Entry
stringlengths 6
10
| Entry Name
stringlengths 5
11
| Sequence
stringlengths 2
35.2k
| EC number
stringlengths 7
118
⌀ | Cofactor
stringlengths 38
1.77k
⌀ | Gene Ontology (biological process)
stringlengths 18
11.3k
⌀ | Gene Ontology (cellular component)
stringlengths 17
1.75k
⌀ | Gene Ontology (molecular function)
stringlengths 24
2.09k
⌀ | Pfam
stringlengths 8
232
⌀ | Gene3D
stringlengths 10
250
⌀ | Protein families
stringlengths 9
237
⌀ | Post-translational modification
stringlengths 16
8.52k
⌀ | Subcellular location [CC]
stringlengths 29
6.18k
⌀ | Catalytic activity
stringlengths 64
35.7k
⌀ | Kinetics
stringlengths 69
11.7k
⌀ | Pathway
stringlengths 27
908
⌀ | pH dependence
stringlengths 64
955
⌀ | Temperature dependence
stringlengths 70
1.16k
⌀ | Function [CC]
stringlengths 17
15.3k
⌀ | Organism
stringlengths 8
196
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
O35728
|
CP4AE_MOUSE
|
MGFFLFSPTRYLDGISGFFQWAFLLSLFLVLFKAVQFYLRRQWLLKTLQHFPCMPSHWLWGHHLKDKELQQILIWVEKFPSACLQCLSGSNIRVLLYDPDYVKVVLGRSDPKASGIYQFFAPWIGYGLLLLNGKKWFQHRRMLTPAFHYDILKPYVKIMADSVNIMLDKWEKLDGQDHPLEIFHCVSLMTLDTVMKCAFSYQGSVQLDENSKLYTKAVEDLNNLTFFRLRNAFYKYNIIYNMSSDGRLSHHACQIAHEHTDGVIKMRKSQLQNEEELQKARKKRHLDFLDILLFARMEDRNSLSDEDLRAEVDTFMFEGHDTTASGISWIFYALATHPEHQQRCREEVQSILGDGTSVTWDHLGQMPYTTMCIKEALRLYPPVISVSRELSSPVTFPDGRSIPKGITATISIYGLHHNPRFWPNPKVFDPSRFAPDSSHHSHAYLPFSGGSRNCIGKQFAMNELKVAVALTLLRFELLPDPTRIPVPIARLVLKSKNGIHLCLKKLR
| null |
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250|UniProtKB:P20817};
|
arachidonic acid metabolic process [GO:0019369]; icosanoid biosynthetic process [GO:0046456]; kidney development [GO:0001822]; lauric acid metabolic process [GO:0048252]; linoleic acid metabolic process [GO:0043651]
|
endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]
|
alkane 1-monooxygenase activity [GO:0018685]; arachidonic acid binding [GO:0050544]; arachidonic acid monooxygenase activity [GO:0008391]; fatty acid binding [GO:0005504]; heme binding [GO:0020037]; iron ion binding [GO:0005506]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
|
CATALYTIC ACTIVITY: Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 12-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38947, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18262, ChEBI:CHEBI:36204, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:17112342}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38948; Evidence={ECO:0000305|PubMed:17112342}; CATALYTIC ACTIVITY: Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 11-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39751, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18262, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76628; Evidence={ECO:0000269|PubMed:17112342}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39752; Evidence={ECO:0000305|PubMed:17112342}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51480, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76625; Evidence={ECO:0000269|PubMed:17112342}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51481; Evidence={ECO:0000305|PubMed:17112342};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=8 uM for dodecanoic acid {ECO:0000269|PubMed:17112342}; Vmax=40 nmol/min/nmol enzyme toward dodecanoic acid {ECO:0000269|PubMed:17112342};
|
PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000305|PubMed:17112342}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:17112342). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:17112342). Catalyzes the hydroxylation of saturated carbon hydrogen bonds of fatty acids (PubMed:17112342). May act as a major omega- and ommega-1 hydroxylase for dodecanoic (lauric) acid in kidney (PubMed:17112342). Catalyzes with low efficiency the epoxidation of 11,12-double bond of arachidonic acid (PubMed:17112342). {ECO:0000269|PubMed:17112342}.
|
Mus musculus (Mouse)
|
O35730
|
RING1_MOUSE
|
MTTPANAQNASKTWELSLYELHRTPQEAIMDGTEIAVSPRSLHSELMCPICLDMLKNTMTTKECLHRFCSDCIVTALRSGNKECPTCRKKLVSKRSLRPDPNFDALISKIYPSREEYEAHQDRVLIRLSRLHNQQALSSSIEEGLRMQAMHRAQRVRRPMPGSDQTATMSGGEGEPGEGEGDGEDVSSDSAPDSAPGPAPKRPRGAGAGASSVGTGGGAAGGACGGAGSEDSGDRGGTLGGGTLGPPSPPGAPSPPEPGGEIELVFRPHPLLVEKGEYCQTRYVKTTGNATVDHLSKYLALRIALERRQQQETTEPGGPGGGASDTGGPDGGGGERGVAGGGEGPEEPALPSLEGVSEKQYTIYIAPGGGAFTTLNGSLTLELVNEKFWKVSRPLELCYAPTKDPK
|
2.3.2.27
| null |
anterior/posterior pattern specification [GO:0009952]; camera-type eye morphogenesis [GO:0048593]; chromatin organization [GO:0006325]; chromatin remodeling [GO:0006338]; negative regulation of DNA-templated transcription [GO:0045892]; protein ubiquitination [GO:0016567]
|
cytosol [GO:0005829]; nuclear body [GO:0016604]; nuclear speck [GO:0016607]; PcG protein complex [GO:0031519]; PRC1 complex [GO:0035102]; sex chromatin [GO:0001739]; ubiquitin ligase complex [GO:0000151]
|
chromatin binding [GO:0003682]; metal ion binding [GO:0046872]; ubiquitin protein ligase activity [GO:0061630]; ubiquitin-protein transferase activator activity [GO:0097027]
|
PF16207;PF13923;
|
3.30.40.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
| null |
PATHWAY: Protein modification; protein ubiquitination.
| null | null |
FUNCTION: Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:15525528, ECO:0000269|PubMed:16710298, ECO:0000269|PubMed:9312051}.
|
Mus musculus (Mouse)
|
O35732
|
CFLAR_MOUSE
|
MAQSPVSAEVIHQVEECLDEDEKEMMLFLCRDVTENLAAPNVRDLLDSLSERGQLSFATLAELLYRVRRFDLLKRILKTDKATVEDHLRRNPHLVSDYRVLLMEIGESLDQNDVSSLVFLTRDYTGRGKIAKDKSFLDLVIELEKLNLIASDQLNLLEKCLKNIHRIDLNTKIQKYTQSSQGARSNMNTLQASLPKLSIKYNSRLQNGRSKEPRFVEYRDSQRTLVKTSIQESGAFLPPHIREETYRMQSKPLGICLIIDCIGNDTKYLQETFTSLGYHIQLFLFPKSHDITQIVRRYASMAQHQDYDSFACVLVSLGGSQSMMGRDQVHSGFSLDHVKNMFTGDTCPSLRGKPKLFFIQNYESLGSQLEDSSLEVDGPSIKNVDSKPLQPRHCTTHPEADIFWSLCTADVSHLEKPSSSSSVYLQKLSQQLKQGRRRPLVDLHVELMDKVYAWNSGVSSKEKYSLSLQHTLRKKLILAPT
| null | null |
apoptotic process [GO:0006915]; cellular response to nitric oxide [GO:0071732]; erythrocyte differentiation [GO:0030218]; execution phase of apoptosis [GO:0097194]; keratinocyte differentiation [GO:0030216]; necroptotic process [GO:0070266]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cardiac muscle cell apoptotic process [GO:0010667]; negative regulation of cellular response to transforming growth factor beta stimulus [GO:1903845]; negative regulation of epithelial cell apoptotic process [GO:1904036]; negative regulation of extrinsic apoptotic signaling pathway [GO:2001237]; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042]; negative regulation of hepatocyte apoptotic process [GO:1903944]; negative regulation of myoblast fusion [GO:1901740]; negative regulation of necroptotic process [GO:0060546]; negative regulation of reactive oxygen species biosynthetic process [GO:1903427]; neuron differentiation [GO:0030182]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of extracellular matrix organization [GO:1903055]; positive regulation of glomerular mesangial cell proliferation [GO:0072126]; positive regulation of hepatocyte proliferation [GO:2000347]; positive regulation of neuron apoptotic process [GO:0043525]; positive regulation of neuron projection development [GO:0010976]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; proteolysis [GO:0006508]; regulation of skeletal muscle satellite cell proliferation [GO:0014842]; response to bacterium [GO:0009617]; response to testosterone [GO:0033574]; skeletal muscle atrophy [GO:0014732]; skeletal muscle tissue development [GO:0007519]; skeletal muscle tissue regeneration [GO:0043403]; skeletal myofibril assembly [GO:0014866]; wound healing [GO:0042060]
|
CD95 death-inducing signaling complex [GO:0031265]; cytoplasm [GO:0005737]; death-inducing signaling complex [GO:0031264]
|
cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:0097199]; cysteine-type endopeptidase activity involved in execution phase of apoptosis [GO:0097200]; death receptor binding [GO:0005123]; enzyme activator activity [GO:0008047]; peptidase activator activity [GO:0016504]; protease binding [GO:0002020]; protein-containing complex binding [GO:0044877]
|
PF01335;PF00656;
|
3.40.50.1460;1.10.533.10;
|
Peptidase C14A family
|
PTM: Proteolytically processed by CASP8 generating subunits p43 and p12. {ECO:0000269|PubMed:31511692}.
| null | null | null | null | null | null |
FUNCTION: Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:10602037, ECO:0000269|PubMed:10894163}.
|
Mus musculus (Mouse)
|
O35734
|
TNFA_MARMO
|
MSTESMIRDVELAEEALPKEAWGPQGSSRCLCLSLFSFLLVAGATTLFCLLHFGVIGPQREEFLNNLPLSPQAQMLTLRSSSQNMNDKPVAHVVAKNEDKEQLVWLSRRANALLANGMELIDNQLVVPANGLYLVYSQVLFKGQGCPSYVLLTHTVSRFAVSYQDKVNLLSAIKSPCPKESLEGAEFKPWYEPIYLGGVFELQKGDRLSAEVNLPSYLDFAESGQVYFGVIAL
| null | null |
extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625]; immune response [GO:0006955]; necroptotic signaling pathway [GO:0097527]; negative regulation of protein-containing complex disassembly [GO:0043242]; positive regulation of apoptotic process [GO:0043065]; positive regulation of JUN kinase activity [GO:0043507]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein-containing complex disassembly [GO:0043243]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of biological quality [GO:0065008]; regulation of developmental process [GO:0050793]; regulation of multicellular organismal process [GO:0051239]; regulation of secretion [GO:0051046]; tumor necrosis factor-mediated signaling pathway [GO:0033209]; vascular endothelial growth factor production [GO:0010573]
|
cell surface [GO:0009986]; extracellular space [GO:0005615]; plasma membrane [GO:0005886]
|
cytokine activity [GO:0005125]; tumor necrosis factor receptor binding [GO:0005164]
|
PF00229;
|
2.60.120.40;
|
Tumor necrosis factor family
|
PTM: The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space (By similarity). {ECO:0000250}.; PTM: The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1 (By similarity). {ECO:0000250}.; PTM: O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid. {ECO:0000250}.; PTM: [Tumor necrosis factor, soluble form]: The soluble form is demyristoylated by SIRT6, promoting its secretion. {ECO:0000250|UniProtKB:P01375}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}.; SUBCELLULAR LOCATION: [Tumor necrosis factor, membrane form]: Membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}.; SUBCELLULAR LOCATION: [Tumor necrosis factor, soluble form]: Secreted {ECO:0000250}.; SUBCELLULAR LOCATION: [C-domain 1]: Secreted {ECO:0000250}.; SUBCELLULAR LOCATION: [C-domain 2]: Secreted {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (By similarity). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity). {ECO:0000250|UniProtKB:P01375, ECO:0000250|UniProtKB:P06804}.; FUNCTION: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. {ECO:0000250|UniProtKB:P01375}.
|
Marmota monax (Woodchuck)
|
O35738
|
KLF12_MOUSE
|
MNIHMKRKTIKNLSALENRMLMLDGMPAVRVKTELVESEQGSPNVHNYPDMEAVPLLLNNVKGEPPEDSLPVDHFQTQTEPVDLSINKARTSPTAASSSPVSMTASASSPSSTSTSSSSSSRPASSPTVITSVSSASSSSTVLSPGPLVASASGVGGQQFLHIIHPVPPSSPMNLQSNKLSHVHRIPVVVQSVPVVYTAVRSPGNVNNTIVVPLLEDGRSHGKAQMEPRGLSPRQSKSDSDDDDLPNVTLDSVNETGSTALSIARAVQEVHPSPVSRVRGNRMNNQKFACSISPFSIESTRRQRRSESPDSRKRRIHRCDFEGCNKVYTKSSHLKAHRRTHTGEKPYKCTWEGCTWKFARSDELTRHYRKHTGVKPFKCADCDRSFSRSDHLALHRRRHMLV
| null | null |
negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]
|
cytosol [GO:0005829]; nucleoplasm [GO:0005654]
|
DNA binding [GO:0003677]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]
|
PF00096;
|
3.30.160.60;
|
Sp1 C2H2-type zinc-finger protein family
| null |
SUBCELLULAR LOCATION: Nucleus.
| null | null | null | null | null |
FUNCTION: Confers strong transcriptional repression to the AP-2-alpha gene. Binds to a regulatory element (A32) in the AP-2-alpha gene promoter.
|
Mus musculus (Mouse)
|
O35739
|
KLF9_MOUSE
|
MSAAAYMDFVAAQCLVSISNRAAVPEHGGAPEAERLRLPEREVTKEHGDPGDTWKDYCTLVTIAKSLLDLNKYRPIQTPSVCSDSLESPDEDIGSDSDVTTESGSSPSHSPEERQDSGSAPSPLSLLHSGVASKGKHASEKRHKCPYSGCGKVYGKSSHLKAHYRVHTGERPFPCTWPDCLKKFSRSDELTRHYRTHTGEKQFRCPLCEKRFMRSDHLTKHARRHTVFHPSMIKRSKKALACPL
| null | null |
cellular response to cortisol stimulus [GO:0071387]; embryo implantation [GO:0007566]; negative regulation of keratinocyte proliferation [GO:0010839]; positive regulation of transcription by RNA polymerase II [GO:0045944]; progesterone receptor signaling pathway [GO:0050847]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; rhythmic process [GO:0048511]
|
nucleus [GO:0005634]
|
DNA binding [GO:0003677]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]
|
PF00096;
|
3.30.160.60;
|
Sp1 C2H2-type zinc-finger protein family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13886}.
| null | null | null | null | null |
FUNCTION: Transcription factor that binds to GC box promoter elements. Selectively activates mRNA synthesis from genes containing tandem repeats of GC boxes but represses genes with a single GC box. Acts as an epidermal circadian transcription factor regulating keratinocyte proliferation. {ECO:0000250|UniProtKB:Q13886}.
|
Mus musculus (Mouse)
|
O35740
|
CITE2_MOUSE
|
MADHMMAMNHGRFPDGTNGLHHHPAHRMGMGQFPSPHHHQQQQPQHAFNALMGEHIHYGAGNMNATSGIRHAMGPGTVNGGHPPSALAPAARFNNSQFMGPPVASQGGSLPASMQLQKLNNQYFNHHPYPHNHYMPDLHPTAGHQMNGTNQHFRDCNPKHSGGSSTPGGAGGSGTPGGSGGTSGGAGGSSAGGSGGGSTMPASVAHVPAAMLPPNVIDTDFIDEEVLMSLVIEMGLDRIKELPELWLGQNEFDFMTDFVCKQQPSRVSC
| null | null |
adrenal cortex formation [GO:0035802]; adrenal gland development [GO:0030325]; blood vessel development [GO:0001568]; bone morphogenesis [GO:0060349]; cardiac neural crest cell development involved in heart development [GO:0061308]; cardiac septum morphogenesis [GO:0060411]; cell population proliferation [GO:0008283]; cellular response to hypoxia [GO:0071456]; cellular senescence [GO:0090398]; central nervous system development [GO:0007417]; cranial nerve morphogenesis [GO:0021602]; decidualization [GO:0046697]; determination of heart left/right asymmetry [GO:0061371]; determination of left/right asymmetry in lateral mesoderm [GO:0003140]; determination of left/right symmetry [GO:0007368]; embryonic camera-type eye morphogenesis [GO:0048596]; embryonic heart tube left/right pattern formation [GO:0060971]; embryonic placenta development [GO:0001892]; embryonic process involved in female pregnancy [GO:0060136]; endocardial cushion development [GO:0003197]; erythrocyte development [GO:0048821]; granulocyte differentiation [GO:0030851]; heart development [GO:0007507]; heart looping [GO:0001947]; hematopoietic progenitor cell differentiation [GO:0002244]; in utero embryonic development [GO:0001701]; left/right axis specification [GO:0070986]; left/right pattern formation [GO:0060972]; lens morphogenesis in camera-type eye [GO:0002089]; leukocyte differentiation [GO:0002521]; liver development [GO:0001889]; male gonad development [GO:0008584]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cardiac muscle cell proliferation [GO:0060044]; negative regulation of cell migration [GO:0030336]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of gene expression [GO:0010629]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neural tube closure [GO:0001843]; neural tube formation [GO:0001841]; nodal signaling pathway [GO:0038092]; outflow tract morphogenesis [GO:0003151]; peripheral nervous system development [GO:0007422]; positive regulation of cell cycle [GO:0045787]; positive regulation of cell-cell adhesion [GO:0022409]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of gene expression [GO:0010628]; positive regulation of male gonad development [GO:2000020]; positive regulation of peroxisome proliferator activated receptor signaling pathway [GO:0035360]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transforming growth factor beta receptor signaling pathway [GO:0030511]; pulmonary artery morphogenesis [GO:0061156]; regulation of animal organ formation [GO:0003156]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; response to estrogen [GO:0043627]; response to fluid shear stress [GO:0034405]; response to hypoxia [GO:0001666]; response to mechanical stimulus [GO:0009612]; sex determination [GO:0007530]; skeletal muscle cell differentiation [GO:0035914]; spleen development [GO:0048536]; thymus development [GO:0048538]; transforming growth factor beta receptor signaling pathway [GO:0007179]; trophectodermal cell differentiation [GO:0001829]; uterus development [GO:0060065]; vasculature development [GO:0001944]; vasculogenesis [GO:0001570]; ventricular septum development [GO:0003281]; ventricular septum morphogenesis [GO:0060412]
|
chromatin [GO:0000785]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
chromatin binding [GO:0003682]; histone acetyltransferase binding [GO:0035035]; LBD domain binding [GO:0050693]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; SMAD binding [GO:0046332]; transcription coactivator activity [GO:0003713]; transcription coregulator activity [GO:0003712]; transcription corepressor activity [GO:0003714]
|
PF04487;
|
6.10.140.2200;
|
CITED family
| null |
SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with EP300 in dot-like structures. {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Transcriptional coactivator of the p300/CBP-mediated transcription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region. {ECO:0000269|PubMed:10593900, ECO:0000269|PubMed:15475956, ECO:0000269|PubMed:15750185, ECO:0000269|PubMed:16619037, ECO:0000269|PubMed:17537799, ECO:0000269|PubMed:19457926, ECO:0000269|PubMed:21224256}.
|
Mus musculus (Mouse)
|
O35744
|
CHIL3_MOUSE
|
MAKLILVTGLAILLNVQLGSSYQLMCYYTSWAKDRPIEGSFKPGNIDPCLCTHLIYAFAGMQNNEITYTHEQDLRDYEALNGLKDKNTELKTLLAIGGWKFGPAPFSAMVSTPQNRQIFIQSVIRFLRQYNFDGLNLDWQYPGSRGSPPKDKHLFSVLVKEMRKAFEEESVEKDIPRLLLTSTGAGIIDVIKSGYKIPELSQSLDYIQVMTYDLHDPKDGYTGENSPLYKSPYDIGKSADLNVDSIISYWKDHGAASEKLIVGFPAYGHTFILSDPSKTGIGAPTISTGPPGKYTDESGLLAYYEVCTFLNEGATEVWDAPQEVPYAYQGNEWVGYDNVRSFKLKAQWLKDNNLGGAVVWPLDMDDFSGSFCHQRHFPLTSTLKGDLNIHSASCKGPY
|
3.2.1.52
| null |
chitin catabolic process [GO:0006032]; inflammatory response [GO:0006954]; polysaccharide catabolic process [GO:0000272]
|
cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; extracellular region [GO:0005576]; nuclear envelope [GO:0005635]; rough endoplasmic reticulum lumen [GO:0048237]
|
beta-N-acetylhexosaminidase activity [GO:0004563]; carbohydrate binding [GO:0030246]; chitin binding [GO:0008061]; N-acetyl-beta-D-galactosaminidase activity [GO:0102148]
|
PF00704;
|
3.10.50.10;3.20.20.80;
|
Glycosyl hydrolase 18 family, Chitinase class II subfamily
| null |
SUBCELLULAR LOCATION: Secreted. Rough endoplasmic reticulum lumen. Nucleus envelope. Cytoplasm. Cytoplasmic granule. Note=Predominantly localizes to the lumen of rough endoplasmic reticulum (rER) and nuclear envelope in alveolar macrophages. Localizes to the dilated lumen of rER in immature neutrophils in spleen and in cytoplasmic granules in peritoneal neutrophils. Detected in needle-shaped crystals present in the cytoplasm of bone marrow macrophages.
|
CATALYTIC ACTIVITY: Reaction=Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides.; EC=3.2.1.52; Evidence={ECO:0000269|PubMed:11733538};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=120.8 uM for 4-methylumbelliferone-N-acetylglucosamine (at pH 4-4.5) {ECO:0000269|PubMed:11733538}; Vmax=0.023 umol/min/mg enzyme {ECO:0000269|PubMed:11733538}; Note=4-methylumbelliferone-N-acetylglucosamine (MU-(GlcNAc)1) is a GlcNAc2 analog.;
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 4.5-5.0. {ECO:0000269|PubMed:11733538};
| null |
FUNCTION: Lectin that binds saccharides with a free amino group, such as glucosamine or galactosamine. Binding to oligomeric saccharides is much stronger than binding to mono- or disaccharides. Also binds chitin and heparin. Has weak hexosaminidase activity but no chitinase activity. Has chemotactic activity for T-lymphocytes, bone marrow cells and eosinophils. May play a role in inflammation and allergy. {ECO:0000269|PubMed:10625674, ECO:0000269|PubMed:11297523, ECO:0000269|PubMed:11733538}.
|
Mus musculus (Mouse)
|
O35750
|
SHOX2_RAT
|
RELDMGAAERSREPGSPRLTEVSPELKDRKEDAKGMEDEGQTKIKQRRSRTNFTLEQLNELERLFDETHYPDAFMREELSQRLGLSEARVQVWFQNRRAKCRKQENQLHKGVLIGAASQFEACRVAPYVNVGALRMPFQQDSHCNVTPLSFQVQAHVQLDSAVRAAHHHLHPHLAAHGPYMMFPAPPFGLPLATLAADSASAASVVAAAAAAKTTSKNSSIADLRLKAKKHAAALGL
| null | null |
cardiac atrium morphogenesis [GO:0003209]; cardiac pacemaker cell differentiation [GO:0060920]; cardiac right atrium morphogenesis [GO:0003213]; cartilage development involved in endochondral bone morphogenesis [GO:0060351]; chondrocyte development [GO:0002063]; chondrocyte differentiation [GO:0002062]; embryonic digestive tract morphogenesis [GO:0048557]; embryonic forelimb morphogenesis [GO:0035115]; embryonic limb morphogenesis [GO:0030326]; embryonic morphogenesis [GO:0048598]; embryonic skeletal joint morphogenesis [GO:0060272]; heart valve development [GO:0003170]; mesenchymal cell proliferation [GO:0010463]; muscle tissue morphogenesis [GO:0060415]; negative regulation of transcription by RNA polymerase II [GO:0000122]; osteoblast differentiation [GO:0001649]; positive regulation of axonogenesis [GO:0050772]; positive regulation of mesenchymal cell proliferation [GO:0002053]; positive regulation of skeletal muscle fiber development [GO:0048743]; positive regulation of smoothened signaling pathway [GO:0045880]; positive regulation of stem cell proliferation [GO:2000648]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of branching morphogenesis of a nerve [GO:2000172]; regulation of chondrocyte differentiation [GO:0032330]; regulation of heart rate [GO:0002027]; regulation of transcription by RNA polymerase II [GO:0006357]; sinoatrial node cell development [GO:0060931]; sinoatrial node development [GO:0003163]; sinoatrial valve development [GO:0003172]; smoothened signaling pathway [GO:0007224]; stem cell proliferation [GO:0072089]
|
nucleus [GO:0005634]
|
DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; sequence-specific DNA binding [GO:0043565]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF00046;PF03826;
|
1.10.10.60;
|
Paired homeobox family, Bicoid subfamily
| null |
SUBCELLULAR LOCATION: Nucleus.
| null | null | null | null | null |
FUNCTION: May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation.
|
Rattus norvegicus (Rat)
|
O35757
|
VEGFC_RAT
|
MHLLCFLSLACSLLAAALIPGPREAPATVAAFESGLGFSEAEPDGGEVKGFEGKDLEEQLRSVSSVDELMSVLYPDYWKMYKCQLRKGGWQQPSLNMRTGDTVKLAAAHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGAATNTFFKPPCVSVYRCGGCCNSEGLQCMNTSTGYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHSIIRRSLPATLPQCQAANKTCPANYVWNNYMCQCLAQQDFIFYSNVEDDSSNGFHDVCGPNKELDEDTCQCVCKGGLRPSSCGPHKELDRDSCQCVCKNKLFLNSCGANREFDENTCQCVCKRTCPRNQPLNPGKCACECTENTQKCFLKGKKFHHQTCSCYRRPCTNRLKHCDPGLSFSEEVCRCVPSYWKRPHLN
| null | null |
angiogenesis [GO:0001525]; animal organ morphogenesis [GO:0009887]; cell population proliferation [GO:0008283]; cellular response to leukemia inhibitory factor [GO:1990830]; glial cell proliferation [GO:0014009]; induction of positive chemotaxis [GO:0050930]; morphogenesis of embryonic epithelium [GO:0016331]; negative regulation of blood pressure [GO:0045776]; negative regulation of osteoblast differentiation [GO:0045668]; positive regulation of angiogenesis [GO:0045766]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of cell division [GO:0051781]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of epithelial cell proliferation [GO:0050679]; positive regulation of glial cell proliferation [GO:0060252]; positive regulation of lymphangiogenesis [GO:1901492]; positive regulation of mast cell chemotaxis [GO:0060754]; positive regulation of mesenchymal stem cell proliferation [GO:1902462]; positive regulation of neuroblast proliferation [GO:0002052]; positive regulation of protein autophosphorylation [GO:0031954]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein secretion [GO:0050714]; regulation of angiogenesis [GO:0045765]; regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030947]; response to hypoxia [GO:0001666]; response to xenobiotic stimulus [GO:0009410]; sprouting angiogenesis [GO:0002040]; vascular endothelial growth factor receptor signaling pathway [GO:0048010]; vascular endothelial growth factor signaling pathway [GO:0038084]
|
extracellular space [GO:0005615]; membrane [GO:0016020]
|
chemoattractant activity [GO:0042056]; growth factor activity [GO:0008083]; vascular endothelial growth factor receptor 3 binding [GO:0043185]
|
PF03128;PF00341;
|
2.10.90.10;
|
PDGF/VEGF growth factor family
|
PTM: Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed form could activate VEGFR-2. VEGF-C first form an antiparallel homodimer linked by disulfide bonds. Before secretion, a cleavage occurs between Arg-223 and Ser-224 producing a heterotetramer. The next extracellular step of the processing removes the N-terminal propeptide. Finally the mature VEGF-C is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors. {ECO:0000250|UniProtKB:P49767}.
|
Rattus norvegicus (Rat)
|
O35762
|
NKX61_RAT
|
MLAVGAMEGPRQSAFLLSSPPLAALHSMAEMKTPLYPAAYPPLPTGPPSSSSSSSSSSSPSPPLGAHNPGGLKPPAAGGLSSLGSPPQQLSAATPHGINDILSRPSMPVASGAALPSASPSGSSSSSSSSASATSASAAAAAAAAAAAAAASSPAGLLAGLPRFSSLSPPPPPPGLYFSPSAAAVAAVGRYPKPLAELPGRTPIFWPGVMQSPPWRDARLACTPHQGSILLDKDGKRKHTRPTFSGQQIFALEKTFEQTKYLAGPERARLAYSLGMTESQVKVWFQNRRTKWRKKHAAEMATAKKKQDSETERLKGTSENEEDDDDYNKPLDPNSDDEKITQLLKKHKSSGGSLLLHASEAEGSS
| null | null |
cell differentiation [GO:0030154]; cellular response to cytokine stimulus [GO:0071345]; cellular response to peptide hormone stimulus [GO:0071375]; central nervous system neuron differentiation [GO:0021953]; endocrine pancreas development [GO:0031018]; negative regulation of oligodendrocyte differentiation [GO:0048715]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neurogenesis [GO:0022008]; neuron differentiation [GO:0030182]; oligodendrocyte differentiation [GO:0048709]; pancreatic A cell differentiation [GO:0003310]; positive regulation of insulin secretion [GO:0032024]; positive regulation of neuron differentiation [GO:0045666]; positive regulation of oligodendrocyte differentiation [GO:0048714]; regulation of axon extension [GO:0030516]; regulation of neuron migration [GO:2001222]; regulation of transcription by RNA polymerase II [GO:0006357]; response to nicotine [GO:0035094]; response to xenobiotic stimulus [GO:0009410]; smoothened signaling pathway [GO:0007224]; transcription by RNA polymerase II [GO:0006366]; type B pancreatic cell development [GO:0003323]; type B pancreatic cell differentiation [GO:0003309]; type B pancreatic cell proliferation [GO:0044342]
|
nucleus [GO:0005634]
|
chromatin binding [GO:0003682]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]
|
PF00046;
|
1.10.10.60;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99MA9}.
| null | null | null | null | null |
FUNCTION: Transcription factor which binds to specific A/T-rich DNA sequences in the promoter regions of a number of genes. Involved in the development of insulin-producing beta cells in the islets of Langerhans at the secondary transition (By similarity). Together with NKX2-2 and IRX3 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class II proteins of neuronal progenitor factors, which are induced by SHH signals (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q99MA9}.
|
Rattus norvegicus (Rat)
|
O35763
|
MOES_RAT
|
MPKTISVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWFFGLQYQDTKAFSTWLKLNKKVTAQDVRKESPLLFKFRAKFYPEDVSEELIQDITQRLFFLQVKEGILNDDIYCPPETAVLLASYAVQSKYGDFNKEVHKSGYLAGDKLLPQRVLEQHKLNKDQWEERIQVWHEEHRGMLREDAVLEYLKIAQDLEMYGVNYFSIKNKKGSELWLGVDALGLNIYEQNDRLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKRILALCMGNHELYMRRRKPDTIEVQQMKAQAREEKHQKQMERALLENEKKKRELAEKEKEKIEREKEELMEKLKQIEEQTKKAQQELEEQTRRALELEQERKRAQSEAEKLAKERQEAEEAKEALLQASRDQKKTQEQLASEMAELTARVSQLEMARKKKESEAEECHQKAQMVQEDLEKTRAELKTAMSTPHVAEPAENEHDEQDENGAEASAELRADAMAKDRSEEERTTEAEKNERVQKHLKALTSELANARDESKKTTNDMIHAENMRLGRDKYKTLRQIRQGNTKQRIDEFESM
| null | null |
cellular response to testosterone stimulus [GO:0071394]; establishment of endothelial barrier [GO:0061028]; establishment of epithelial cell apical/basal polarity [GO:0045198]; gland morphogenesis [GO:0022612]; immunological synapse formation [GO:0001771]; leukocyte cell-cell adhesion [GO:0007159]; leukocyte migration [GO:0050900]; membrane to membrane docking [GO:0022614]; positive regulation of early endosome to late endosome transport [GO:2000643]; positive regulation of gene expression [GO:0010628]; positive regulation of podosome assembly [GO:0071803]; positive regulation of protein catabolic process [GO:0045732]; positive regulation of protein localization to early endosome [GO:1902966]; regulation of cell shape [GO:0008360]; regulation of cell size [GO:0008361]; regulation of lymphocyte migration [GO:2000401]; regulation of organelle assembly [GO:1902115]; T cell aggregation [GO:0070489]; T cell migration [GO:0072678]; T cell proliferation [GO:0042098]
|
adherens junction [GO:0005912]; apical part of cell [GO:0045177]; apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; cell periphery [GO:0071944]; cell surface [GO:0009986]; cell tip [GO:0051286]; cytoplasmic side of plasma membrane [GO:0009898]; cytoskeleton [GO:0005856]; filopodium [GO:0030175]; filopodium membrane [GO:0031527]; microvillus [GO:0005902]; microvillus membrane [GO:0031528]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; pseudopodium [GO:0031143]; T-tubule [GO:0030315]; uropod [GO:0001931]
|
actin binding [GO:0003779]; cell adhesion molecule binding [GO:0050839]; double-stranded RNA binding [GO:0003725]; enzyme binding [GO:0019899]; protein kinase binding [GO:0019901]; protein-macromolecule adaptor activity [GO:0030674]; signaling receptor binding [GO:0005102]
|
PF00769;PF20492;PF09380;PF00373;PF09379;
|
1.20.5.450;1.20.80.10;6.10.360.10;2.30.29.30;
| null |
PTM: Phosphorylation on Thr-558 is crucial for the formation of microvilli-like structures. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding. Phosphorylation on Thr-558 by STK10 negatively regulates lymphocyte migration and polarization (By similarity). {ECO:0000250}.; PTM: S-nitrosylation of Cys-117 is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) implicating the iNOS-S100A8/9 transnitrosylase complex. {ECO:0000250|UniProtKB:P26038}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P26038}; Peripheral membrane protein {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250|UniProtKB:P26041}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P26041}. Apical cell membrane {ECO:0000250|UniProtKB:P26041}; Peripheral membrane protein {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250|UniProtKB:P26041}. Cell projection, microvillus membrane {ECO:0000250|UniProtKB:P26041}; Peripheral membrane protein {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250|UniProtKB:P26041}. Cell projection, microvillus {ECO:0000250|UniProtKB:P26041}. Note=Phosphorylated form is enriched in microvilli-like structures at apical membrane. Increased cell membrane localization of both phosphorylated and non-phosphorylated forms seen after thrombin treatment (By similarity). Localizes at the uropods of T lymphoblasts (By similarity). {ECO:0000250|UniProtKB:P26038, ECO:0000250|UniProtKB:P26041}.
| null | null | null | null | null |
FUNCTION: Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton. Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement. These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction. The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (By similarity). Modulates phagolysosomal biogenesis in macrophages (By similarity). Participates also in immunologic synapse formation (By similarity). {ECO:0000250|UniProtKB:P26038, ECO:0000250|UniProtKB:P26041}.
|
Rattus norvegicus (Rat)
|
O35764
|
NPTXR_RAT
|
MKFLAVLLAAGMLAFLGAVICIIASVPLAASPARALPGGTDNASAASAAGAPGPQRSLSALQGAGGSAGPSVLPGEPAASVFPPPPGPLLSRFLCTPLAAACPSGAEQGDAAGERAELLLLQSTAEQLRQTALQQEARIRADRDTIRELTGKLGRCESGLPRGLQDAGPRRDTMADGAWDSPALLVELENAVRALRDRIERIEQELPARGNLSSSAPAPAVPTALHSKMDELEGQLLAKVLALEKERAALSHGSHQQRQEVEKELDALQGRVAELEHGSSAYSPPDAFKVSIPIRNNYMYARVRKAVPELYAFTACMWLRSRSGGSGQGTPFSYSVPGQANEIVLLEAGLEPMELLINDKVAQLPLSLKDSNWHHICIAWTTRDGLWSAYQDGELRGSGENLAAWHPIKPHGILILGQEQDTLGGRFDATQAFVGDIAQFNLWDHALTPAQVLGIANCTGPLMGNVLPWEDKLVEAFGGAKKAAFDVCKRRAKA
| null |
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; Note=Binds 2 calcium ions per subunit. {ECO:0000250};
|
neuron projection development [GO:0031175]; neurotransmitter receptor localization to postsynaptic specialization membrane [GO:0099645]; regulation of postsynaptic specialization assembly [GO:0099150]; response to hydrogen peroxide [GO:0042542]
|
extracellular space [GO:0005615]; glutamatergic synapse [GO:0098978]; plasma membrane [GO:0005886]
|
metal ion binding [GO:0046872]; pentraxin receptor activity [GO:0008029]; protein phosphatase binding [GO:0019903]; protein-containing complex binding [GO:0044877]
|
PF00354;
|
2.60.120.200;
| null |
PTM: N-glycosylated.; PTM: Ubiquitinated by a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing KLHL2. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II membrane protein {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses. {ECO:0000269|PubMed:10748068}.
|
Rattus norvegicus (Rat)
|
O35767
|
NKX25_RAT
|
MFPSPALTHTPFSVKDILNLEQQQRSLAAGDLSARLEATLAPASCMLAAFKPDGYSGPEAAAPGLAELRAELGPAPSPPKCSPAFPTAPTFYPRAYGDPDPAKDPRADKKELCALQKAVELDKAETDGAERRRPRRRRKPRVLFSQAQVYELERRFKQQRYLSPAERDQLASVLKLTSTQVKIWFQNRRYKCKRQRQDQTLELLGPPPPPARRIAVPVLVRDGKPCLGDSAAYAPAYGLGLNAYGYNAYPYPGYGGAACSPAYSCAAYPAAPPAAHAPAASANSNFVNFGVGDLNTVQSPGMPQGNSGVSTLHGIRAW
| null | null |
adult heart development [GO:0007512]; apoptotic process [GO:0006915]; apoptotic process involved in heart morphogenesis [GO:0003278]; atrial cardiac muscle tissue development [GO:0003228]; atrial septum morphogenesis [GO:0060413]; atrioventricular node cell development [GO:0060928]; atrioventricular node cell fate commitment [GO:0060929]; atrioventricular node development [GO:0003162]; bundle of His development [GO:0003166]; cardiac conduction system development [GO:0003161]; cardiac muscle cell development [GO:0055013]; cardiac muscle cell differentiation [GO:0055007]; cardiac muscle cell proliferation [GO:0060038]; cardiac muscle contraction [GO:0060048]; cardiac muscle tissue development [GO:0048738]; cardiac muscle tissue morphogenesis [GO:0055008]; cardiac septum morphogenesis [GO:0060411]; cardiac ventricle formation [GO:0003211]; cardiac ventricle morphogenesis [GO:0003208]; cell differentiation [GO:0030154]; cell population proliferation [GO:0008283]; cellular response to growth factor stimulus [GO:0071363]; cellular response to hydrogen peroxide [GO:0070301]; embryonic heart tube development [GO:0035050]; embryonic heart tube left/right pattern formation [GO:0060971]; epithelial cell apoptotic process [GO:1904019]; epithelial cell differentiation [GO:0030855]; epithelial cell proliferation [GO:0050673]; heart contraction [GO:0060047]; heart development [GO:0007507]; heart looping [GO:0001947]; heart morphogenesis [GO:0003007]; heart trabecula formation [GO:0060347]; hemopoiesis [GO:0030097]; negative regulation of canonical Wnt signaling pathway [GO:0090090]; negative regulation of cardiac muscle cell apoptotic process [GO:0010667]; negative regulation of epithelial cell apoptotic process [GO:1904036]; negative regulation of myotube differentiation [GO:0010832]; negative regulation of transcription by RNA polymerase II [GO:0000122]; outflow tract morphogenesis [GO:0003151]; outflow tract septum morphogenesis [GO:0003148]; pharyngeal system development [GO:0060037]; positive regulation of cardioblast differentiation [GO:0051891]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of epithelial cell proliferation [GO:0050679]; positive regulation of gene expression [GO:0010628]; positive regulation of heart contraction [GO:0045823]; positive regulation of neuron differentiation [GO:0045666]; positive regulation of sodium ion transport [GO:0010765]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transcription initiation by RNA polymerase II [GO:0060261]; proepicardium development [GO:0003342]; pulmonary myocardium development [GO:0003350]; Purkinje myocyte differentiation [GO:0003168]; regulation of cardiac conduction [GO:1903779]; regulation of cardiac muscle cell proliferation [GO:0060043]; regulation of cardiac muscle contraction [GO:0055117]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; response to estradiol [GO:0032355]; right ventricular cardiac muscle tissue morphogenesis [GO:0003221]; septum secundum development [GO:0003285]; spleen development [GO:0048536]; thyroid gland development [GO:0030878]; transcription by RNA polymerase II [GO:0006366]; vasculogenesis [GO:0001570]; ventricular cardiac myofibril assembly [GO:0055005]; ventricular septum morphogenesis [GO:0060412]; ventricular trabecula myocardium morphogenesis [GO:0003222]
|
cytoplasm [GO:0005737]; Nkx-2.5 complex [GO:1990664]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; protein-DNA complex [GO:0032993]; RNA polymerase II transcription regulator complex [GO:0090575]; transcription regulator complex [GO:0005667]
|
chromatin binding [GO:0003682]; DNA binding [GO:0003677]; DNA-binding transcription activator activity [GO:0001216]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; histone deacetylase binding [GO:0042826]; identical protein binding [GO:0042802]; protein homodimerization activity [GO:0042803]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; sequence-specific DNA binding [GO:0043565]; sequence-specific double-stranded DNA binding [GO:1990837]; transcription cis-regulatory region binding [GO:0000976]
|
PF00046;
|
1.10.10.60;
|
NK-2 homeobox family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P42582}.
| null | null | null | null | null |
FUNCTION: Transcription factor required for the development of the heart and the spleen (By similarity). During heart development, acts as a transcriptional activator of NPPA/ANF in cooperation with GATA4 (By similarity). May cooperate with TBX2 to negatively modulate expression of NPPA/ANF in the atrioventricular canal (By similarity). Binds to the core DNA motif of NPPA promoter. Together with PBX1, required for spleen development through a mechanism that involves CDKN2B repression (By similarity). Positively regulates transcription of genes such as COL3A1 and MMP2, resulting in increased pulmonary endothelial fibrosis in response to hypoxia (By similarity). {ECO:0000250|UniProtKB:P42582, ECO:0000250|UniProtKB:P52952}.
|
Rattus norvegicus (Rat)
|
O35776
|
HYAS2_RAT
|
MHCERFLCVLRIIGTTLFGVSLLLGITAAYIVGYQFIQTDNYYFSFGLYGAFLASHLIIQSLFAFLEHRKMKKSLETPIKLNKTVALCIAAYQEDPDYLRKCLQSVKRLTYPGIKVVMVIDGNSDDDLYMMDIFSEVMGRDKSVTYIWKNNFHERGPGETEESHKESSQHVTQLVLSNKSICIMQKWGGKREVMYTAFRALGRSVDYVQVCDSDTMLDPASSVEMVKVLEEDPMVGGVGGDVQILNKYDSWISFLSSVRYWMAFNIERACQSYFGCVQCISGPLGMYRNSLLHEFVEDWYNQEFMGNQCSFGDDRHLTNRVLSLGYATKYTARSKCLTETPIEYLRWLNQQTRWSKSYFREWLYNAMWFHKHHLWMTYEAVITGFFPFFLIATVIQLFYRGKIWNILLFLLTVQLVGLIKSSFASCLRGNIVMVFMSLYSVLYMSSLLPAKMFAIATINKAGWGTSGRKTIVVNFIGLIPVSVWFTILLGGVIFTIYKESKKPFSESKQTVLIVGTLIYACYWVVLLTLYVVLINKCGRRKKGQQYDMVLDV
|
2.4.1.212
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
|
atrioventricular canal development [GO:0036302]; bone morphogenesis [GO:0060349]; cellular response to fluid shear stress [GO:0071498]; cellular response to interleukin-1 [GO:0071347]; cellular response to platelet-derived growth factor stimulus [GO:0036120]; cellular response to tumor necrosis factor [GO:0071356]; endocardial cushion to mesenchymal transition [GO:0090500]; estrous cycle [GO:0044849]; extracellular matrix assembly [GO:0085029]; extracellular polysaccharide biosynthetic process [GO:0045226]; hyaluronan biosynthetic process [GO:0030213]; hyaluronan metabolic process [GO:0030212]; kidney development [GO:0001822]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of hyaluronan biosynthetic process [GO:1900127]; positive regulation of keratinocyte migration [GO:0051549]; positive regulation of keratinocyte proliferation [GO:0010838]; positive regulation of monocyte aggregation [GO:1900625]; positive regulation of smooth muscle cell migration [GO:0014911]; positive regulation of substrate adhesion-dependent cell spreading [GO:1900026]; positive regulation of urine volume [GO:0035810]; regulation of extracellular matrix assembly [GO:1901201]; renal water absorption [GO:0070295]; vasculogenesis [GO:0001570]
|
cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; endoplasmic reticulum membrane [GO:0005789]; extracellular vesicle [GO:1903561]; Golgi apparatus [GO:0005794]; Golgi membrane [GO:0000139]; lysosome [GO:0005764]; plasma membrane [GO:0005886]; plasma membrane raft [GO:0044853]
|
hyaluronan synthase activity [GO:0050501]; identical protein binding [GO:0042802]
|
PF03142;PF00535;
| null |
NodC/HAS family
|
PTM: Phosphorylation at Thr-328 is essential for hyaluronan synthase activity. {ECO:0000250|UniProtKB:Q92819}.; PTM: O-GlcNAcylation at Ser-221 increases the stability of HAS2 and plasma membrane localization. {ECO:0000250|UniProtKB:Q92819}.; PTM: Ubiquitination at Lys-190; this ubiquitination is essential for hyaluronan synthase activity and homo- or hetero-oligomerization. Can also be poly-ubiquitinated. Deubiquitinated by USP17L22/USP17 and USP4. USP17L22/USP17 efficiently removes 'Lys-63'- and 'Lys-48'-linked polyubiquitin chains, whereas USP4 preferentially removes monoubiquitination and, partially, both 'Lys-63'- and 'Lys-48'-linked polyubiquitin chain. {ECO:0000250|UniProtKB:Q92819}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q92819}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q92819}; Multi-pass membrane protein {ECO:0000255}. Vesicle {ECO:0000250|UniProtKB:Q92819}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q92819}; Multi-pass membrane protein {ECO:0000255}. Lysosome {ECO:0000250|UniProtKB:Q92819}. Note=Travels from endoplasmic reticulum (ER), Golgi to plasma membrane and either back to endosomes and lysosomes, or out into extracellular vesicles. Post-translational modifications control HAS2 trafficking. {ECO:0000250|UniProtKB:Q92819}.
|
CATALYTIC ACTIVITY: Reaction=[hyaluronan](n) + UDP-N-acetyl-alpha-D-glucosamine = H(+) + N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP; Xref=Rhea:RHEA:20465, Rhea:RHEA-COMP:12583, Rhea:RHEA-COMP:12585, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:132153, ChEBI:CHEBI:132154; EC=2.4.1.212; Evidence={ECO:0000250|UniProtKB:Q92819}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20466; Evidence={ECO:0000250|UniProtKB:Q92819}; CATALYTIC ACTIVITY: Reaction=N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP-alpha-D-glucuronate = [hyaluronan](n+1) + H(+) + UDP; Xref=Rhea:RHEA:12528, Rhea:RHEA-COMP:12585, Rhea:RHEA-COMP:12587, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:132153, ChEBI:CHEBI:132154; EC=2.4.1.212; Evidence={ECO:0000250|UniProtKB:Q92819}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12529; Evidence={ECO:0000250|UniProtKB:Q92819};
| null |
PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis. {ECO:0000250|UniProtKB:Q92819}.
| null | null |
FUNCTION: Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation (By similarity). This is one of three isoenzymes responsible for cellular hyaluronan synthesis and it is particularly responsible for the synthesis of high molecular mass hyaluronan (By similarity). {ECO:0000250|UniProtKB:P70312, ECO:0000250|UniProtKB:Q92819}.
|
Rattus norvegicus (Rat)
|
O35779
|
BHE41_RAT
|
MDEGIPHLQERQLLEHRDFIGLDYSSLYMCKPKRSLKRDDTKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKIIALQNGERSLKSPVQADLDAFHSGFQTCAKEVLQYLARFESWTPREPRCAQLVSHLHAVATQLLTPQVTPGRGPGRAPCSAGAAAASGSERVARCVPVIQRTQPGTEPEHDTDTDSGYGGEAEQGRAAVKQEPPGDPSAAPKRLKLEARGALLGPEPALLGSLVALGGGAPFAQPAAAPFCLPFYLLSPSAAAYVQPWLDKSGLDKYLYPAAAAPFPLLYPGIPAAAAAAAAAAFPCLSSVLSPPPEKAGSAAGAPFLAHEVAPPGSLRPQHAHSRTHLPHAVNPESSQEDATQPAKDAP
| null | null |
anterior/posterior pattern specification [GO:0009952]; circadian regulation of gene expression [GO:0032922]; circadian rhythm [GO:0007623]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of myotube differentiation [GO:0010832]; negative regulation of transcription by competitive promoter binding [GO:0010944]; negative regulation of transcription by RNA polymerase II [GO:0000122]; nervous system development [GO:0007399]; regulation of neurogenesis [GO:0050767]; regulation of neuronal synaptic plasticity [GO:0048168]; regulation of transcription by RNA polymerase II [GO:0006357]
|
nucleus [GO:0005634]
|
bHLH transcription factor binding [GO:0043425]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; E-box binding [GO:0070888]; histone deacetylase binding [GO:0042826]; MRF binding [GO:0043426]; protein heterodimerization activity [GO:0046982]; protein homodimerization activity [GO:0042803]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF07527;PF00010;
|
6.10.250.980;4.10.280.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380, ECO:0000255|PROSITE-ProRule:PRU00981}.
| null | null | null | null | null |
FUNCTION: Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes. Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity (By similarity). Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 and CYP3A11 (By similarity). {ECO:0000250|UniProtKB:Q99PV5}.
|
Rattus norvegicus (Rat)
|
O35780
|
BHE40_RAT
|
MERIPSAQPPPTCLPKTPGLEHGDLSGMDFAHMYQVYKSRRGIKRSEDSKETYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKALTNLIDQQQQKIMALQSGLQAGDLSGKNIEAGQEMFCSGFQTCAREVLQYLAKHENTRDLKSSQLVTHLHRVVSELLQGSASRKPLDSAPKPVDFKEKPSFLAKGSEGPGKNCVPVIQRTFAPSGGEQSGSDTDTDSGYGGELEKGDLRSEQPYFKSDHGRRFTVGERVSTIKQESEEPPTKKSRMQLSDEEGHFVGSDLMGSPFLGPHPHQPPFCLPFYLIPPSATAYLPMLEKCWYPTSVPLLYPGLNTSAAALSSFMNPDKIPTPLLLPQRLPSPLAHSSLDSSALLQALKQIPPLNLETKD
| null | null |
anterior/posterior pattern specification [GO:0009952]; circadian regulation of gene expression [GO:0032922]; circadian rhythm [GO:0007623]; entrainment of circadian clock by photoperiod [GO:0043153]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; nervous system development [GO:0007399]; regulation of circadian rhythm [GO:0042752]; regulation of neurogenesis [GO:0050767]; regulation of neuronal synaptic plasticity [GO:0048168]; regulation of transcription by RNA polymerase II [GO:0006357]; response to light stimulus [GO:0009416]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
bHLH transcription factor binding [GO:0043425]; DNA binding [GO:0003677]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; E-box binding [GO:0070888]; MRF binding [GO:0043426]; protein domain specific binding [GO:0019904]; protein heterodimerization activity [GO:0046982]; protein homodimerization activity [GO:0042803]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF07527;PF00010;
|
6.10.250.980;4.10.280.10;
| null |
PTM: Ubiquitinated; which may lead to proteasomal degradation. {ECO:0000250}.; PTM: Sumoylation inhibits its ubiquitination and promotes its negative regulation of the CLOCK-BMAL1 heterodimer transcriptional activator activity. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14503}. Nucleus {ECO:0000250|UniProtKB:O14503}. Note=Predominantly localized in the nucleus (By similarity). {ECO:0000250|UniProtKB:O14503}.
| null | null | null | null | null |
FUNCTION: Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1/2 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1|BMAL2 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes. Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA and NR1H3/LXRA transactivation activity. May be involved in the regulation of chondrocyte differentiation via the cAMP pathway (By similarity). Represses the transcription of NR0B2 and attentuates the transactivation of NR0B2 by the CLOCK-BMAL1 complex (By similarity). Drives the circadian rhythm of blood pressure through transcriptional repression of ATP1B1 in the cardiovascular system (By similarity). {ECO:0000250|UniProtKB:O14503, ECO:0000250|UniProtKB:O35185}.
|
Rattus norvegicus (Rat)
|
O35783
|
CALU_RAT
|
MDLRQFLMCLSLCTAFALSKPTEKKDRVHHEPQLSDKVHNDAQNFDYDHDAFLGAEEAKSFGQLTPEESKEKLGMIVDKIDTDKDGFVTEGELKSRIKHAQKKYIYDNVENQWQEFDMNQDGLISWDEYRNVTYGTYLDDPDPDDGFNYKPIMVRDERRFKMADQDGDLIATKEEFTAFLHPEEYDYMKDIVLQETMEDIDQNADGFIDLEEYIGDMYSHDGNADEPQWVKTEREQFVEFRDKNRDGKMDKEETKDWILPSDYDHAEAEARHLVYESDQDKDGKLTKEEIVDKYDLFVGSQATDFGEALVRHDEF
| null | null |
peripheral nervous system axon regeneration [GO:0014012]; response to organic cyclic compound [GO:0014070]
|
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum lumen [GO:0005788]; endoplasmic reticulum membrane [GO:0005789]; extracellular region [GO:0005576]; Golgi apparatus [GO:0005794]; melanosome [GO:0042470]; sarcoplasmic reticulum lumen [GO:0033018]
|
calcium ion binding [GO:0005509]; enzyme binding [GO:0019899]; enzyme inhibitor activity [GO:0004857]
|
PF13202;PF13499;PF13833;
|
1.10.238.10;
|
CREC family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:O43852}. Golgi apparatus {ECO:0000250|UniProtKB:O43852}. Secreted {ECO:0000250|UniProtKB:O43852}. Melanosome {ECO:0000250|UniProtKB:O43852}. Sarcoplasmic reticulum lumen {ECO:0000250|UniProtKB:O43852}.
| null | null | null | null | null |
FUNCTION: Involved in regulation of vitamin K-dependent carboxylation of multiple N-terminal glutamate residues. Seems to inhibit gamma-carboxylase GGCX. Binds 7 calcium ions with a low affinity (By similarity). {ECO:0000250, ECO:0000269|PubMed:15075329}.
|
Rattus norvegicus (Rat)
|
O35786
|
CML1_RAT
|
MEYEGYNDSSIYGEEYSDGSDYIVDLEEAGPLEAKVAEVFLVVIYSLVCFLGILGNGLVIVIATFKMKKTVNTVWFVNLAVADFLFNIFLPIHITYAAMDYHWVFGKAMCKISSFLLSHNMYTSVFLLTVISFDRCISVLLPVWSQNHRSVRLAYMTCVVVWVLAFFLSSPSLVFRDTVSTSHGKITCFNNFSLAAPEPFSHSTHPRTDPVGYSRHVAVTVTRFLCGFLIPVFIITACYLTIVFKLQRNRLAKTKKPFKIIITIIITFFLCWCPYHTLYLLELHHTAVPASVFSLGLPLATAVAIANSCMNPILYVFMGHDFKKFKVALFSRLVNALSEDTGPSSYPSHRSFTKMSSLIEKASVNEKETSTL
| null | null |
chemotaxis [GO:0006935]; complement receptor mediated signaling pathway [GO:0002430]; G protein-coupled receptor signaling pathway [GO:0007186]; inflammatory response [GO:0006954]; negative regulation of interleukin-12 production [GO:0032695]; negative regulation of NF-kappaB transcription factor activity [GO:0032088]; phospholipase C-activating G protein-coupled receptor signaling pathway [GO:0007200]; positive regulation of cold-induced thermogenesis [GO:0120162]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of fat cell differentiation [GO:0045600]; positive regulation of macrophage chemotaxis [GO:0010759]; regulation of calcium-mediated signaling [GO:0050848]
|
plasma membrane [GO:0005886]
|
adipokinetic hormone binding [GO:0097004]; adipokinetic hormone receptor activity [GO:0097003]; complement receptor activity [GO:0004875]; G protein-coupled chemoattractant receptor activity [GO:0001637]; G protein-coupled receptor activity [GO:0004930]
|
PF00001;
|
1.20.1070.10;
|
Chemokine-like receptor (CMKLR) family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q99788}; Multi-pass membrane protein {ECO:0000255}.
| null | null | null | null | null |
FUNCTION: Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with RARRES2 initiates activation of G proteins G(i)/G(o) and beta-arrestin pathways inducing cellular responses via second messenger pathways such as intracellular calcium mobilization, phosphorylation of MAP kinases MAPK1/MAPK3 (ERK1/2), TYRO3, MAPK14/P38MAPK and PI3K leading to multifunctional effects, like, reduction of immune responses, enhancing of adipogenesis and angionesis. Resolvin E1 down-regulates cytokine production in macrophages by reducing the activation of MAPK1/3 (ERK1/2) and NF-kappa-B. Positively regulates adipogenesis and adipocyte metabolism (By similarity). {ECO:0000250|UniProtKB:Q99788}.
|
Rattus norvegicus (Rat)
|
O35787
|
KIF1C_RAT
|
MAGASVKVAVRVRPFNARETSQDAKCVVSMQGNTTSIINPKQSRMFLKASFDYSYWSHTSVEDPQFASQQQVYRDIGEEMLLHAFEGYNVCIFAYGQTGAGKSYTMMGRQEPGQQGIVPQLCEDLFSRVNVNQSAQLSYSVEVSYMEIYCERVRDLLNPKSRGSLRVREHPILGPYVQDLSKLAVTSYADIADLMDCGNKARTVAATNMNETSSRSHAVFTIVFTQRSHDQLTGLDSEKVSKISLVNLAGSERADSSGARGMRLKEGANINKSLTTLGKVISALADLQSKKRKSDFIPYRDSVLTWLLKENLGGNSRTAMIAALSPADINYEETLSTLRYADRTKQIRCNAVINEDPNARLIRELQEEVARLRELLMAQGLSASALGGLKVEEGSPGGVLPAASSPPAPASPSSPPPHNGELEPSFSPSAEPQIGPEEAMERLQETEKIIAELNETWEEKLRKTEALRMEREALLAEMGSPGGWRTVGVFSPKKTPHLVNLNEDPLMSECLLYHIKDGVTRVGQVDVDIKLTGQFIREQHCLFRSIPQPDGEVMVTLEPCEGAETYVNGKLVTEPLVLKSGNRIVMGKNHVFRFNHPEQARLERERGVPPPPGPPSEPVDWNFAQKDWLEQQGIDIKLEMEKRLQDLENQYRKEKEEADLLLEQQRLYADSDSGEDSDKRSCEESWRLISSLRDELPPNTVQTIVKRCGLPSSGKRRAPRRVYQIPQRRRLQGKDPRWATMADLKMQAVKEICYEVALADFRHGRAEIEALAALKMRELCRTYGKPEGPGDAWRAVARDVWDTVGEEEGCGGGGGGGEEGARGAEVEDLRAHIDKLTGILQEVKLQNSSKDRELQALRDRMLRMERVIPLTQDLEDDNEESGLVTWAPPEGSEAVEEAVSNDHSPAVRPSSPPQSSWERVSRLMEEDPAFRRGRLRWLKQEQLRLQGLQGSGGRGGGLRRPPARFVPPHDCKLRFPFKSNPQHRESWPGMGSGEAPGPQPPEEVTAPPPPPNRRPPSPRRPHRPRRNSLDGGSRSRGGGSTQPEPQHLRPQKHNSYPQQPQPYPAQRPGPRYPPYTTPPRMRRQRSAPDLKESGAAV
| null | null |
anterograde neuronal dense core vesicle transport [GO:1990048]; cytoskeleton-dependent intracellular transport [GO:0030705]; microtubule-based movement [GO:0007018]; microtubule-based process [GO:0007017]; retrograde neuronal dense core vesicle transport [GO:1990049]; retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum [GO:0006890]; vesicle-mediated transport [GO:0016192]
|
axon [GO:0030424]; axon cytoplasm [GO:1904115]; dendrite [GO:0030425]; Golgi apparatus [GO:0005794]; kinesin complex [GO:0005871]; microtubule [GO:0005874]; microtubule associated complex [GO:0005875]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cytoskeletal motor activity [GO:0003774]; microtubule binding [GO:0008017]; plus-end-directed microtubule motor activity [GO:0008574]
|
PF00498;PF00225;PF16183;
|
2.60.200.20;6.10.250.2520;3.40.850.10;
|
TRAFAC class myosin-kinesin ATPase superfamily, Kinesin family, Unc-104 subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Probable motor protein.
|
Rattus norvegicus (Rat)
|
O35789
|
B3GA1_RAT
|
MPKRRDILAIVLIVLPWTLLITVWHQSSLAPLLAVHKDEGSDPRHEAPPGADPREYCMSDRDIVEVVRTEYVYTRPPPWSDTLPTIHVVTPTYSRPVQKAELTRMANTLLHVPNLHWLVVEDAPRRTPLTARLLRDTGLNYTHLHVETPRNYKLRGDARDPRIPRGTMQRNLALRWLRETFPRNSTQPGVVYFADDDNTYSLELFEEMRSTRRVSVWPVAFVGGLRYEAPRVNGAGKVVGWKTVFDPHRPFAIDMAGFAVNLRLILQRSQAYFKLRGVKGGYQESSLLRELVTLNDLEPKAANCTKILVWHTRTEKPVLVNEGKKGFTDPSVEI
|
2.4.1.135
|
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:9804790};
|
carbohydrate metabolic process [GO:0005975]; cellular response to hypoxia [GO:0071456]; chondroitin sulfate proteoglycan biosynthetic process [GO:0050650]; glycosaminoglycan biosynthetic process [GO:0006024]; protein glycosylation [GO:0006486]; visual learning [GO:0008542]
|
endoplasmic reticulum membrane [GO:0005789]; extracellular region [GO:0005576]; Golgi lumen [GO:0005796]; Golgi membrane [GO:0000139]
|
galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity [GO:0015018]; metal ion binding [GO:0046872]
|
PF03360;
| null |
Glycosyltransferase 43 family
|
PTM: The soluble form derives from the membrane form by proteolytic processing. {ECO:0000269|PubMed:19181664}.
|
SUBCELLULAR LOCATION: [Isoform 1]: Golgi apparatus membrane {ECO:0000269|PubMed:19181664}; Single-pass type II membrane protein. Secreted {ECO:0000269|PubMed:19181664}.; SUBCELLULAR LOCATION: [Isoform 2]: Golgi apparatus membrane {ECO:0000269|PubMed:19181664}; Single-pass type II membrane protein. Endoplasmic reticulum membrane {ECO:0000269|PubMed:19181664}. Secreted {ECO:0000269|PubMed:19181664}.
|
CATALYTIC ACTIVITY: Reaction=3-O-(beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:24168, Rhea:RHEA-COMP:12571, Rhea:RHEA-COMP:12573, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:132090, ChEBI:CHEBI:132093; EC=2.4.1.135; Evidence={ECO:0000269|PubMed:19181664, ECO:0000269|PubMed:9804790};
| null |
PATHWAY: Protein modification; protein glycosylation.
| null | null |
FUNCTION: Involved in the biosynthesis of L2/HNK-1 carbohydrate epitope on glycoproteins. Can also play a role in glycosaminoglycan biosynthesis. Substrates include asialo-orosomucoid (ASOR), asialo-fetuin, and asialo-neural cell adhesion molecule. Requires sphingomyelin for activity: stearoyl-sphingomyelin was the most effective, followed by palmitoyl-sphingomyelin and lignoceroyl-sphingomyelin. Activity was demonstrated only for sphingomyelin with a saturated fatty acid and not for that with an unsaturated fatty acid, regardless of the length of the acyl group. {ECO:0000269|PubMed:19181664, ECO:0000269|PubMed:9804790}.
|
Rattus norvegicus (Rat)
|
O35793
|
GREM1_RAT
|
MNRTAYTVGALLLLLGTLLPAAEGKKKGSQGAIPPPDKAQHNDSEQTQSPPQPGSRTRGRGQGRGTAMPGEEVLESSQEALHVTERKYLKRDWCKTQPLKQTIHEEGCNSRTIINRFCYGQCNSFYIPRHIRKEEGSFQSCSFCKPKKFTTMMVTLNCPELQPPTKKKRVTRVKQCRCISIDLD
| null | null |
angiogenesis [GO:0001525]; animal organ morphogenesis [GO:0009887]; cardiac muscle cell differentiation [GO:0055007]; cardiac muscle cell myoblast differentiation [GO:0060379]; cell migration involved in sprouting angiogenesis [GO:0002042]; cell morphogenesis [GO:0000902]; cell-cell signaling [GO:0007267]; collagen fibril organization [GO:0030199]; determination of dorsal identity [GO:0048263]; embryonic limb morphogenesis [GO:0030326]; endothelial cell migration [GO:0043542]; limb development [GO:0060173]; mesenchymal to epithelial transition involved in metanephros morphogenesis [GO:0003337]; negative regulation of apoptotic process [GO:0043066]; negative regulation of BMP signaling pathway [GO:0030514]; negative regulation of bone mineralization [GO:0030502]; negative regulation of bone mineralization involved in bone maturation [GO:1900158]; negative regulation of bone remodeling [GO:0046851]; negative regulation of bone trabecula formation [GO:1900155]; negative regulation of canonical Wnt signaling pathway [GO:0090090]; negative regulation of cell growth [GO:0030308]; negative regulation of chondrocyte differentiation [GO:0032331]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of leukocyte chemotaxis [GO:0002689]; negative regulation of monocyte chemotaxis [GO:0090027]; negative regulation of osteoblast differentiation [GO:0045668]; negative regulation of osteoblast proliferation [GO:0033689]; negative regulation of osteoclast proliferation [GO:0090291]; negative regulation of SMAD protein signal transduction [GO:0060392]; positive regulation of angiogenesis [GO:0045766]; positive regulation of branching involved in ureteric bud morphogenesis [GO:0090190]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of non-canonical NF-kappaB signal transduction [GO:1901224]; positive regulation of peptidyl-tyrosine autophosphorylation [GO:1900086]; positive regulation of receptor internalization [GO:0002092]; positive regulation of transcription by RNA polymerase II [GO:0045944]; proximal/distal pattern formation [GO:0009954]; regulation of epithelial to mesenchymal transition [GO:0010717]; regulation of focal adhesion assembly [GO:0051893]; sequestering of BMP from receptor via BMP binding [GO:0038098]; signal transduction [GO:0007165]; ureteric bud formation [GO:0060676]
|
cell surface [GO:0009986]; extracellular region [GO:0005576]; extracellular space [GO:0005615]
|
BMP binding [GO:0036122]; cytokine activity [GO:0005125]; protein homodimerization activity [GO:0042803]; receptor ligand activity [GO:0048018]; transmembrane receptor protein tyrosine kinase activator activity [GO:0030297]; vascular endothelial growth factor receptor 2 binding [GO:0043184]
|
PF03045;
|
2.10.90.10;
|
DAN family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner (By similarity). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (By similarity). Acts as inhibitor of monocyte chemotaxis (PubMed:15528323). Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed. {ECO:0000250|UniProtKB:O60565, ECO:0000250|UniProtKB:O70326, ECO:0000269|PubMed:15528323, ECO:0000269|PubMed:9234736}.
|
Rattus norvegicus (Rat)
|
O35795
|
ENTP2_RAT
|
MAGKLVSLVPPLLLAAAGLTGLLLLCVPTQDVREPPALKYGIVLDAGSSHTSMFVYKWPADKENDTGIVGQHSSCDVQGGGISSYANDPSKAGQSLVRCLEQALRDVPRDRHASTPLYLGATAGMRPFNLTSPEATARVLEAVTQTLTQYPFDFRGARILSGQDEGVFGWVTANYLLENFIKYGWVGRWIRPRKGTLGAMDLGGASTQITFETTSPSEDPGNEVHLRLYGQHYRVYTHSFLCYGRDQILLRLLASALQIHRFHPCWPKGYSTQVLLQEVYQSPCTMGQRPRAFNGSAIVSLSGTSNATLCRDLVSRLFNISSCPFSQCSFNGVFQPPVAGNFIAFSAFYYTVDFLTTVMGLPVGTLKQLEEATEITCNQTWTELQARVPGQKTRLADYCAVAMFIHQLLSRGYHFDERSFREVVFQKKAADTAVGWALGYMLNLTNLIPADLPGLRKGTHFSSWVALLLLFTVLILAALVLLLRQVRSAKSPGAL
|
3.6.1.-
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
|
cellular response to interferon-alpha [GO:0035457]; cellular response to interleukin-6 [GO:0071354]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to tumor necrosis factor [GO:0071356]; G protein-coupled receptor signaling pathway [GO:0007186]; nucleoside diphosphate catabolic process [GO:0009134]; platelet activation [GO:0030168]; purine ribonucleoside diphosphate catabolic process [GO:0009181]; response to auditory stimulus [GO:0010996]
|
basement membrane [GO:0005604]; cell body [GO:0044297]; cell projection membrane [GO:0031253]; cell surface [GO:0009986]; plasma membrane [GO:0005886]
|
ADP phosphatase activity [GO:0043262]; ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; GDP phosphatase activity [GO:0004382]; identical protein binding [GO:0042802]; nucleoside diphosphate phosphatase activity [GO:0017110]; ribonucleoside triphosphate phosphatase activity [GO:0017111]; UDP phosphatase activity [GO:0045134]
|
PF01150;
|
3.30.420.40;3.30.420.150;
|
GDA1/CD39 NTPase family
| null |
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Hydrolyzes ADP only to a marginal extent.
|
Rattus norvegicus (Rat)
|
O35796
|
C1QBP_RAT
|
MLPLLRCVPRALGAAATGLRASIPAPPLRHLLQPAPRPCLRPFGLLSVRAGSARRSGLLQPPVPCACGCGALHTEGDKAFVEFLTDEIKEEKKIQKHKSLPKMSGDWELEVNGTEAKLLRKVAGEKITVTFNINNSIPPTFDGEEEPSQGQKAEEQEPELTSTPNFVVEVTKTDGKKTLVLDCHYPEDEIGHEDEAESDIFSIKEVSFQTTGDSEWRDTNYTLNTDSLDWALYDHLMDFLADRGVDNTFADELVELSTALEHQEYITFLEDLKSFVKSQ
| null | null |
apoptotic process [GO:0006915]; complement activation, classical pathway [GO:0006958]; cytosolic ribosome assembly [GO:0042256]; immune response [GO:0006955]; innate immune response [GO:0045087]; mRNA processing [GO:0006397]; negative regulation of defense response to virus [GO:0050687]; negative regulation of double-strand break repair via homologous recombination [GO:2000042]; negative regulation of interleukin-12 production [GO:0032695]; negative regulation of MDA-5 signaling pathway [GO:0039534]; negative regulation of mRNA splicing, via spliceosome [GO:0048025]; negative regulation of RIG-I signaling pathway [GO:0039536]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of type II interferon production [GO:0032689]; phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0043491]; positive regulation of apoptotic process [GO:0043065]; positive regulation of cell adhesion [GO:0045785]; positive regulation of dendritic cell chemotaxis [GO:2000510]; positive regulation of mitochondrial translation [GO:0070131]; positive regulation of neutrophil chemotaxis [GO:0090023]; positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0051897]; positive regulation of substrate adhesion-dependent cell spreading [GO:1900026]; positive regulation of trophoblast cell migration [GO:1901165]; regulation of complement activation [GO:0030449]; RNA splicing [GO:0008380]
|
cell surface [GO:0009986]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular space [GO:0005615]; GABA-ergic synapse [GO:0098982]; glutamatergic synapse [GO:0098978]; membrane [GO:0016020]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]; nucleolus [GO:0005730]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; presynaptic active zone [GO:0048786]
|
adrenergic receptor binding [GO:0031690]; complement component C1q complex binding [GO:0001849]; enzyme inhibitor activity [GO:0004857]; hyaluronic acid binding [GO:0005540]; kininogen binding [GO:0030984]; mitochondrial ribosome binding [GO:0097177]; mRNA binding [GO:0003729]; protein kinase C binding [GO:0005080]; transcription corepressor activity [GO:0003714]
|
PF02330;
|
3.10.280.10;
|
MAM33 family
| null |
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250|UniProtKB:Q07021}. Nucleus {ECO:0000250|UniProtKB:Q07021}. Cell membrane {ECO:0000250|UniProtKB:Q07021}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q07021}; Extracellular side {ECO:0000250|UniProtKB:Q07021}. Secreted {ECO:0000250|UniProtKB:Q07021}. Cytoplasm {ECO:0000250|UniProtKB:Q07021}. Nucleus, nucleolus {ECO:0000250|UniProtKB:Q07021}. Note=Seems to be predominantly localized to mitochondria. Secreted by activated lymphocytes. {ECO:0000250|UniProtKB:Q07021}.
| null | null | null | null | null |
FUNCTION: Multifunctional and multicompartmental protein involved in inflammation and infection processes, ribosome biogenesis, protein synthesis in mitochondria, regulation of apoptosis, transcriptional regulation and pre-mRNA splicing. At the cell surface is thought to act as an endothelial receptor for plasma proteins of the complement and kallikrein-kinin cascades. Putative receptor for C1q; specifically binds to the globular 'heads' of C1q thus inhibiting C1; may perform the receptor function through a complex with C1qR/CD93. In complex with cytokeratin-1/KRT1 is a high affinity receptor for kininogen-1/HMWK. Can also bind other plasma proteins, such as coagulation factor XII leading to its autoactivation. May function to bind initially fluid kininogen-1 to the cell membrane. The secreted form may enhance both extrinsic and intrinsic coagulation pathways. It is postulated that the cell surface form requires docking with transmembrane proteins for downstream signaling which might be specific for a cell-type or response. By acting as C1q receptor is involved in chemotaxis of immature dendritic cells and neutrophils and is proposed to signal through CD209/DC-SIGN on immature dendritic cells, through integrin alpha-4/beta-1 during trophoblast invasion of the decidua, and through integrin beta-1 during endothelial cell adhesion and spreading. Signaling involved in inhibition of innate immune response is implicating the PI3K-AKT/PKB pathway. Required for protein synthesis in mitochondria (By similarity). In mitochondrial translation may be involved in formation of functional 55S mitoribosomes; the function seems to involve its RNA-binding activity. May be involved in the nucleolar ribosome maturation process; the function may involve the exchange of FBL for RRP1 in the association with pre-ribosome particles (By similarity). Involved in regulation of RNA splicing by inhibiting the RNA-binding capacity of SRSF1 and its phosphorylation (By similarity). Is required for the nuclear translocation of splicing factor U2AF1L4 (By similarity). Involved in regulation of CDKN2A- and HRK-mediated apoptosis. Stabilizes mitochondrial CDKN2A isoform smARF. May be involved in regulation of FOXC1 transcriptional activity and NFY/CCAAT-binding factor complex-mediated transcription. May play a role in antibacterial defense as it can bind to cell surface hyaluronan and inhibit Streptococcus pneumoniae hyaluronate lyase. May be involved in modulation of the immune response; ligation by HCV core protein is resulting in suppression of interleukin-12 production in monocyte-derived dendritic cells. Involved in regulation of antiviral response by inhibiting RIGI- and IFIH1-mediated signaling pathways probably involving its association with MAVS after viral infection. Acts as a regulator of DNA repair via homologous recombination by inhibiting the activity of MRE11: interacts with unphosphorylated MRE11 and RAD50 in absence of DNA damage, preventing formation and activity of the MRN complex. Following DNA damage, dissociates from phosphorylated MRE11, allowing formation of the MRN complex (By similarity). {ECO:0000250|UniProtKB:O35658, ECO:0000250|UniProtKB:Q07021}.
|
Rattus norvegicus (Rat)
|
O35799
|
HFE_RAT
|
MDRSAGLPVRLLLLLLLLLLWSVAPQALRPGSHSLRYLFMGASKPDLGLPFFEALGYVDDQLFVSYNHESRRAEPRAPWILGQTSSQLWLQLSQSLKGWDYMFIVDFWTIMGNYNHSKVTKLRVVPESHILQVILGCEVHEDNSTSGFWKYGYDGQDHLEFCPKTLNWSAAEPRAWATKMEWEEHRIRARQSRDYLQRDCPQQLKQVLELQRGVLGQQVPTLVKVTRHWASTGTSLRCQALNFFPQNITMRWLKDSQPLDAKDVNPENVLPNGDGTYQGWLTLAVAPGEETRFSCQVEHPGLDQPLTATWEPSRSQDMIIGIISGITICAIFFVGILILVLRKRKVSGGTMGDYVLTECE
| null | null |
acute-phase response [GO:0006953]; antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent [GO:0002486]; antigen processing and presentation of endogenous peptide antigen via MHC class Ib [GO:0002476]; BMP signaling pathway [GO:0030509]; cellular response to iron ion [GO:0071281]; cellular response to iron ion starvation [GO:0010106]; female pregnancy [GO:0007565]; hormone biosynthetic process [GO:0042446]; intracellular iron ion homeostasis [GO:0006879]; iron ion transport [GO:0006826]; liver regeneration [GO:0097421]; multicellular organismal-level iron ion homeostasis [GO:0060586]; negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I [GO:1904283]; negative regulation of CD8-positive, alpha-beta T cell activation [GO:2001186]; negative regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032435]; negative regulation of T cell cytokine production [GO:0002725]; negative regulation of ubiquitin-dependent protein catabolic process [GO:2000059]; positive regulation of gene expression [GO:0010628]; positive regulation of peptide hormone secretion [GO:0090277]; positive regulation of receptor-mediated endocytosis [GO:0048260]; positive regulation of SMAD protein signal transduction [GO:0060391]; positive regulation of T cell mediated cytotoxicity [GO:0001916]; regulation of iron ion transport [GO:0034756]; regulation of protein localization to cell surface [GO:2000008]; response to iron ion [GO:0010039]; response to iron ion starvation [GO:1990641]
|
apical part of cell [GO:0045177]; basal part of cell [GO:0045178]; cytoplasmic vesicle [GO:0031410]; early endosome [GO:0005769]; external side of plasma membrane [GO:0009897]; extracellular space [GO:0005615]; HFE-transferrin receptor complex [GO:1990712]; perinuclear region of cytoplasm [GO:0048471]; recycling endosome [GO:0055037]; terminal web [GO:1990357]
|
beta-2-microglobulin binding [GO:0030881]; co-receptor binding [GO:0039706]; signaling receptor binding [GO:0005102]; transferrin receptor binding [GO:1990459]
|
PF07654;PF00129;
|
2.60.40.10;3.30.500.10;
|
MHC class I family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q30201}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q30201}.
| null | null | null | null | null |
FUNCTION: Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. {ECO:0000250|UniProtKB:Q30201}.
|
Rattus norvegicus (Rat)
|
O35800
|
HIF1A_RAT
|
MEGAGGENEKKKMSSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDEMKAQMNCFYLKAPDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGPVRKGKEQNTQRSFFLRMKCTLTSRGRTMNIKSATWKVLHCTGHIHVYDTSSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKDSQPQCIVCVNYVVSGIIQHDLIFSLQQTESVLKPVESSDMKMTQLFTKVESEDTSCLFDKLKKEPDALTLLAPAAGDTIISLDFGSDDTETEDQQLEDVPLYNDVMFPSSNEKLNINLAMSPLPASETPKPLRSSADPALNQEVALKLESSPESLGLSFTMPQIQDQPASPSDGSTRQSSPEPNSPSEYCFDVDSDMVNVFKLELVEKLFAEDTEAKNPFSAQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESNSPSPPSVSTVTGFQQTQLQKPTITVTAATATTATTTDESKAVTKDNIEDIKILIASPPSTQVPQEMTTAKASAYSGTHSRTASPDRAGKRVIEKTDKAHPRSLNLSVTLNQRNTVPEEELNPRTIALQNAQRKRKMEHDGSLFQAAGIGTLLQQPGDRAPTMSLSWKRVKGYISSEQDGMEQKTIFLIPSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
| null | null |
acute-phase response [GO:0006953]; angiogenesis [GO:0001525]; apoptotic process [GO:0006915]; axonal transport of mitochondrion [GO:0019896]; B-1 B cell homeostasis [GO:0001922]; blood vessel development [GO:0001568]; blood vessel morphogenesis [GO:0048514]; bone mineralization [GO:0030282]; camera-type eye morphogenesis [GO:0048593]; cardiac ventricle morphogenesis [GO:0003208]; cartilage development [GO:0051216]; cell differentiation [GO:0030154]; cellular response to anoxia [GO:0071454]; cellular response to carbon monoxide [GO:0071245]; cellular response to cobalt ion [GO:0071279]; cellular response to cyanide [GO:1903928]; cellular response to electrical stimulus [GO:0071257]; cellular response to estrogen stimulus [GO:0071391]; cellular response to glucose stimulus [GO:0071333]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to hypoxia [GO:0071456]; cellular response to insulin stimulus [GO:0032869]; cellular response to interleukin-1 [GO:0071347]; cellular response to light stimulus [GO:0071482]; cellular response to lipid [GO:0071396]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to mechanical stimulus [GO:0071260]; cellular response to nitrite [GO:0071250]; cellular response to organic cyclic compound [GO:0071407]; cellular response to oxidative stress [GO:0034599]; cellular response to toxic substance [GO:0097237]; cellular response to wortmannin [GO:1904568]; cellular response to xenobiotic stimulus [GO:0071466]; cerebral cortex development [GO:0021987]; chondrocyte differentiation [GO:0002062]; collagen metabolic process [GO:0032963]; connective tissue replacement involved in inflammatory response wound healing [GO:0002248]; digestive tract morphogenesis [GO:0048546]; dopaminergic neuron differentiation [GO:0071542]; elastin metabolic process [GO:0051541]; embryonic hemopoiesis [GO:0035162]; embryonic placenta development [GO:0001892]; epithelial cell differentiation involved in mammary gland alveolus development [GO:0061030]; epithelial to mesenchymal transition [GO:0001837]; glandular epithelial cell differentiation [GO:0002067]; glandular epithelial cell maturation [GO:0002071]; glucose homeostasis [GO:0042593]; heart looping [GO:0001947]; hemoglobin biosynthetic process [GO:0042541]; hypoxia-inducible factor-1alpha signaling pathway [GO:0097411]; insulin secretion involved in cellular response to glucose stimulus [GO:0035773]; intestinal epithelial cell maturation [GO:0060574]; intracellular glucose homeostasis [GO:0001678]; intracellular iron ion homeostasis [GO:0006879]; intracellular oxygen homeostasis [GO:0032364]; iris morphogenesis [GO:0061072]; iron import into the mitochondrion [GO:0048250]; lactate metabolic process [GO:0006089]; lactation [GO:0007595]; maternal process involved in female pregnancy [GO:0060135]; mesenchymal cell apoptotic process [GO:0097152]; muscle cell cellular homeostasis [GO:0046716]; negative regulation of apoptotic process [GO:0043066]; negative regulation of bone mineralization [GO:0030502]; negative regulation of gene expression [GO:0010629]; negative regulation of growth [GO:0045926]; negative regulation of mesenchymal cell apoptotic process [GO:2001054]; negative regulation of miRNA transcription [GO:1902894]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of ossification [GO:0030279]; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway [GO:1903377]; negative regulation of reactive oxygen species biosynthetic process [GO:1903427]; negative regulation of reactive oxygen species metabolic process [GO:2000378]; negative regulation of thymocyte apoptotic process [GO:0070244]; negative regulation of TOR signaling [GO:0032007]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of vasoconstriction [GO:0045906]; neural crest cell migration [GO:0001755]; neural fold elevation formation [GO:0021502]; neuroblast proliferation [GO:0007405]; neuron apoptotic process [GO:0051402]; outflow tract morphogenesis [GO:0003151]; positive regulation of angiogenesis [GO:0045766]; positive regulation of apoptotic process [GO:0043065]; positive regulation of autophagy [GO:0010508]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cell size [GO:0045793]; positive regulation of chemokine-mediated signaling pathway [GO:0070101]; positive regulation of cytokine production involved in inflammatory response [GO:1900017]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of epithelial cell migration [GO:0010634]; positive regulation of erythrocyte differentiation [GO:0045648]; positive regulation of gene expression [GO:0010628]; positive regulation of gluconeogenesis [GO:0045722]; positive regulation of hormone biosynthetic process [GO:0046886]; positive regulation of insulin secretion involved in cellular response to glucose stimulus [GO:0035774]; positive regulation of macroautophagy [GO:0016239]; positive regulation of miRNA transcription [GO:1902895]; positive regulation of mitophagy [GO:1901526]; positive regulation of neuroblast proliferation [GO:0002052]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of sprouting angiogenesis [GO:1903672]; positive regulation of stress granule assembly [GO:0062029]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of vascular endothelial growth factor production [GO:0010575]; positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949]; positive regulation of vascular wound healing [GO:0035470]; regulation of aerobic respiration [GO:1903715]; regulation of cell population proliferation [GO:0042127]; regulation of cellular response to hypoxia [GO:1900037]; regulation of DNA-templated transcription [GO:0006355]; regulation of gene expression [GO:0010468]; regulation of glycolytic process [GO:0006110]; regulation of protein neddylation [GO:2000434]; regulation of thymocyte apoptotic process [GO:0070243]; regulation of transcription by RNA polymerase II [GO:0006357]; regulation of transforming growth factor beta2 production [GO:0032909]; response to activity [GO:0014823]; response to alkaloid [GO:0043279]; response to anesthetic [GO:0072347]; response to auditory stimulus [GO:0010996]; response to cobalt ion [GO:0032025]; response to estradiol [GO:0032355]; response to estrogen [GO:0043627]; response to fungicide [GO:0060992]; response to glucocorticoid [GO:0051384]; response to glucose [GO:0009749]; response to hypoxia [GO:0001666]; response to iron ion [GO:0010039]; response to mechanical stimulus [GO:0009612]; response to muscle activity [GO:0014850]; response to purine-containing compound [GO:0014074]; response to reactive oxygen species [GO:0000302]; response to salt stress [GO:0009651]; response to X-ray [GO:0010165]; response to xenobiotic stimulus [GO:0009410]; retina vasculature development in camera-type eye [GO:0061298]; signal transduction [GO:0007165]; tissue remodeling [GO:0048771]; TOR signaling [GO:0031929]; vascular endothelial growth factor production [GO:0010573]; vasculature development [GO:0001944]; visual learning [GO:0008542]
|
axon cytoplasm [GO:1904115]; chromatin [GO:0000785]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; euchromatin [GO:0000791]; motile cilium [GO:0031514]; nuclear speck [GO:0016607]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; RNA polymerase II transcription regulator complex [GO:0090575]
|
cis-regulatory region sequence-specific DNA binding [GO:0000987]; DNA binding [GO:0003677]; DNA-binding transcription activator activity [GO:0001216]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity [GO:0001217]; E-box binding [GO:0070888]; enzyme binding [GO:0019899]; histone deacetylase binding [GO:0042826]; Hsp90 protein binding [GO:0051879]; nuclear receptor binding [GO:0016922]; p53 binding [GO:0002039]; protein domain specific binding [GO:0019904]; protein heterodimerization activity [GO:0046982]; protein kinase binding [GO:0019901]; protein-containing complex binding [GO:0044877]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; sequence-specific DNA binding [GO:0043565]; transcription coactivator binding [GO:0001223]; transcription regulator activator activity [GO:0140537]; ubiquitin protein ligase binding [GO:0031625]
|
PF11413;PF08778;PF08447;PF13426;
|
4.10.280.10;3.30.450.20;
| null |
PTM: S-nitrosylation of Cys-799 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex. {ECO:0000250|UniProtKB:Q16665}.; PTM: Acetylation of Lys-531 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation. Deacetylated by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:Q16665}.; PTM: Ubiquitinated; in normoxia, following hydroxylation and interaction with VHL. Lys-531 appears to be the principal site of ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-802. Ubiquitinated by E3 ligase VHL. Deubiquitinated by UCHL1 (By similarity). {ECO:0000250|UniProtKB:Q16665}.; PTM: Requires phosphorylation for DNA-binding. Phosphorylation at Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding. Phosphorylation by GSK3-beta and PLK3 promote degradation by the proteasome (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.; PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. {ECO:0000250|UniProtKB:Q16665}.; PTM: Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Both sumoylation and desumoylation seem to be involved in the regulation of its stability during hypoxia. Sumoylation can promote either its stabilization or its VHL-dependent degradation by promoting hydroxyproline-independent HIF1A-VHL complex binding, thus leading to HIF1A ubiquitination and proteasomal degradation. Desumoylation by SENP1 increases its stability amd transcriptional activity. There is a disaccord between various publications on the effect of sumoylation and desumoylation on its stability and transcriptional activity (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.; PTM: In normoxia, is hydroxylated on Pro-402 and Pro-563 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1. EGLN3/PHD3 has also been shown to hydroxylate Pro-563. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity). In normoxia, is hydroxylated on Asn-802 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. Repressed by iron ion, via Fe(2+) prolyl hydroxylase (PHD) enzymes-mediated hydroxylation and subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q16665}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16665}. Nucleus. Nucleus speckle {ECO:0000250|UniProtKB:Q61221}. Note=Colocalizes with HIF3A in the nucleus and speckles (By similarity). Cytoplasmic in normoxia, nuclear translocation in response to hypoxia (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.
| null | null | null | null | null |
FUNCTION: Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (By similarity). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with NCOA1 and/or NCOA2. Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.
|
Rattus norvegicus (Rat)
|
O35806
|
LTBP2_RAT
|
MRAPTTVRCSGRIQRARWRGFLPLVLALLMGTSHAQRDSVGRYEPASRDANRLWRPVGNHPAAAAAKVYSLFREPDAPVPGLSPSEWNQPGQGIPGRLAEAEARRPSRAQQLRRVQSPVQTRRSNPRGQQPPAARTAHSVVRLATPQRPAAARRGRLTGRNVCGGQCCPGWTTSNSTNHCIKPVCQPPCQNRGSCSRPQLCICRSGFRGARCEEVIPEEEFDPQNARPVPRRSVEGAPGPHRSSEARGSLVTRIQPLLPPLPPPPSRTLSQTRPLQQHAGLSRTVRRYPATGTNGQLMSNALPSGPGPELRDSSQQAAHMNHLSHPWGLNLTEKIKKIKVVFTPTICKQTCARGRCANTCEKGDTTTLYSQGGHGHDPKSGFRIYFCQIPCLNGGRCIGRDECWCPANSTGKFCHLPVPQPDREPPGRGSQHRALLEGPLKQSTFTLPLSNQLASVNPSLVKVQMQHPPEASVQIHQVARVRGEVDPVPEDNSVETRASHRPHGSSGHSHWASNSIPARAGEAPRPPPVPSRHYGLLGQCYLSTVNGQCANPLGELTSQEDCCGSVGTSWGVTSCAPCPPRPAFPVIENGQLECPQGYKRLNLSHCQDINECLTLGLCKDSECVNTRGSYLCTCRPGLMLDPSRSRCVSDKAVSMKQGLCYRSMVSGTCTLPLVQRITKQICCCSRVGKAWGSKCEHCPLPGTEAFREICPAGHGYAYSSSDIRLSMRKAEEEELASPVREQRQQSSGPPPGAAERQPLRAATATWIEAETLPDKGDSRAIQITTSAPHLPARVPGDATGRPTPSLPGQGIPEGPAEEQVIPSSDVLVTHGPPGFDPCFAGASNICGPGTCVKLPNGYRCVCSPGYQLHPSQDYCTDDNECLRNPCEGRGRCVNSVGSYSCLCYPGYTLATLGDTQECQDVDECEQPGVCSGGRCSNTEGSYHCECDQGYVMVRRGHCQDINECRHPGTCPDGRCVNSPGSYTCLACEEGYIGQSGNCVDMNECLTPGICAHGRCINMEGSFRCSCEPGYELTPDKKGCRDVDECASRASCPTGLCLNTEGSFTCSACQSGYWVNEDGTACEDLDECAFPGVCPTGVCTNTVGSFSCKDCDRGFRPSPLGNSCEDVDECEGPQNSCLGGECKNTDGSYQCLCPQGFQLANGTVCEDVDECVGEEHCAPHGECLNSPGSFFCLCAPGFASAEGGTRCQDVDECATTEPCLGGHCVNTEGSFNCLCETGFQPAPDSGECVDIDECANDTVCGNHGFCDNTDGSFRCLCDQGFETSPSGWECVDVNECELMLAVCGDALCENVEGSFLCLCASDLEEYDAEEGHCRPRVAGAQRIPEVPTEEQAAGLTGMECYAEHNGGPPCSQILGQNSTQAECCSTQGARWGETCDPCPSEDSVEFSELCPSGQGYIPVEGAWTFGQAMYTDADECILFGPALCQNGRCLNTVPGYICLCNPGYHYDAVSRKCQDHNECQDLACENGECVNTEGSFHCFCSPPLILDLSGQRCVNSTSSSEDFPDHDIHMDICWKKVTNDVCSQPLRGHHTTYTECCCQDGEAWSQQCALCPPRSSEVYAQLCNVARIEAEREAGIHFRPGYEYGPGPDDLPETLYGPDGAPFYNYLGPEDTVPEPPFSNTASHLGDNTPILEPPLQPSELQPPAIQNPLASFEGLQAEECGILNGCENGRCVRVREGYTCDCFEGFQLDTALMACVDVNECEDLNGAARLCAHGHCENTEGSYRCHCSPGYVAEPGPPHCAAKE
| null | null |
Golgi to vacuole transport [GO:0006896]; protein targeting to vacuole [GO:0006623]; response to alkaloid [GO:0043279]; supramolecular fiber organization [GO:0097435]; transforming growth factor beta receptor signaling pathway [GO:0007179]
|
endosome [GO:0005768]; extracellular region [GO:0005576]; Golgi transport complex [GO:0017119]; membrane [GO:0016020]; trans-Golgi network [GO:0005802]
|
calcium ion binding [GO:0005509]; growth factor binding [GO:0019838]; heparin binding [GO:0008201]; microfibril binding [GO:0050436]
|
PF00008;PF07645;PF12661;PF00683;
|
2.10.25.10;3.90.290.10;
|
LTBP family
|
PTM: N-Glycosylated. {ECO:0000250|UniProtKB:Q14767}.; PTM: Contains hydroxylated asparagine residues. {ECO:0000250|UniProtKB:Q14766}.
|
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:Q14767}.
| null | null | null | null | null |
FUNCTION: May play an integral structural role in elastic-fiber architectural organization and/or assembly. {ECO:0000250|UniProtKB:Q14767}.
|
Rattus norvegicus (Rat)
|
O35811
|
P2RY4_RAT
|
MTSAESLLFTSLGPSPSSGDGDCRFNEEFKFILLPMSYAVVFVLGLALNAPTLWLFLFRLRPWDATATYMFHLALSDTLYVLSLPTLVYYYAARNHWPFGTGLCKFVRFLFYWNLYCSVLFLTCISVHRYLGICHPLRAIRWGRPRFASLLCLGVWLVVAGCLVPNLFFVTTNANGTTILCHDTTLPEEFDHYVYFSSAVMVLLFGLPFLITLVCYGLMARRLYRPLPGAGQSSSRLRSLRTIAVVLTVFAVCFVPFHITRTIYYQARLLQADCHVLNIVNVVYKVTRPLASANSCLDPVLYLFTGDKYRNQLQQLCRGSKPKPRTAASSLALVTLHEESISRWADTHQDSTFSAYEGDRL
| null | null |
cellular response to prostaglandin E stimulus [GO:0071380]; G protein-coupled receptor signaling pathway [GO:0007186]; regulation of presynaptic cytosolic calcium ion concentration [GO:0099509]; regulation of synaptic vesicle exocytosis [GO:2000300]; transepithelial chloride transport [GO:0030321]
|
apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; glutamatergic synapse [GO:0098978]; plasma membrane [GO:0005886]; presynaptic active zone membrane [GO:0048787]
|
ATP binding [GO:0005524]; G protein-coupled purinergic nucleotide receptor activity [GO:0045028]; G protein-coupled UTP receptor activity [GO:0045030]
|
PF00001;
|
1.20.1070.10;
|
G-protein coupled receptor 1 family
|
PTM: Phosphorylation of Ser-329 and Ser-330 is a key step in agonist-dependent desensitization and loss of surface P2RY4. This phosphorylation does not involve PKC, nor other calcium-activated kinases (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
| null | null | null | null | null |
FUNCTION: Receptor for ATP and UTP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. Not activated by ADP or UDP.
|
Rattus norvegicus (Rat)
|
O35814
|
STIP1_RAT
|
MEQVNELKEKGNKALSAGNIDDALQCYSEAIKLDPQNHVLYSNRSAAYAKKGDYQKAYEDGCKTVDLKPDWGKGYSRKAAALEFLNRFEEAKRTYEEGLKHEANNLQLKEGLQNMEARLAERKFMNPFNLPNLYQKLENDPRTRTLLSDPTYRELIEQLQNKPSDLGTKLQDPRVMTTLSVLLGVDLGSMDEEEEAATPPPPPPPKKEAKPEPMEEDLPENKKQALKEKELGNDAYKKKDFDKALKHYDKAKELDPTNMTYITNQAAVHFEKGDYNKCRELCEKAIEVGRENREDYRQIAKAYARIGNSYFKEERYKDAIHFYNKSLAEHRTPDVLKKCQQAEKILKEQERLAYINPDLALEEKNKGNECFQKGDYPQAMKHYTEAIKRNPRDAKLYSNRAACYTKLLEFQLALKDCEECIQLEPTFIKGYTRKAAALEAMKDYTKAMDVYQKALDLDSSCKEAADGYQRCMMAQYNRHDSPEDVKRRAMADPEVQQIMSDPAMRLILEQMQKDPQALSEHLKNPVIAQKIQKLMDVGLIAIR
| null | null |
cellular response to interleukin-7 [GO:0098761]
|
dynein axonemal particle [GO:0120293]; nucleus [GO:0005634]; protein folding chaperone complex [GO:0101031]; protein-containing complex [GO:0032991]
|
Hsp70 protein binding [GO:0030544]; Hsp90 protein binding [GO:0051879]; protein-folding chaperone binding [GO:0051087]
|
PF17830;PF00515;PF13414;PF13424;PF13181;
|
1.10.260.100;1.25.40.10;
| null | null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q60864}. Nucleus {ECO:0000250|UniProtKB:Q60864}. Dynein axonemal particle {ECO:0000250|UniProtKB:Q7ZWU1}.
| null | null | null | null | null |
FUNCTION: Acts as a co-chaperone for HSP90AA1 (By similarity). Mediates the association of the molecular chaperones HSPA8/HSC70 and HSP90 (PubMed:9528774). {ECO:0000250|UniProtKB:P31948, ECO:0000269|PubMed:9528774}.
|
Rattus norvegicus (Rat)
|
O35815
|
ATX3_RAT
|
MESIFHEKQEGSLCAQHCLNNLLQGEYFSPVELSSIAHQLDEEERLRMAEGGVTSEDYRTFLQQPSGNMDDSGFFSIQVISNALKVWGLELILFNSPEYQRLRIDPINERSFICNYKEHWFTVRKLGKQWFNLNSLLTGPELISDTYLALFLAQLQQEGYSIFVVKGDLPDCEADQLLQMIKVQQMHRPKLIGEELAHLKEQSALKADLERVLEAADGPGMFDDDEDDLQRALAMSRQEIDMEDEEADLRRAIQLSMQGSSRGMCEDSPQTSSTDLSSEELRKRREAYFEKQQHQQQEADRPGYLSYPCERPTTSSGGLRSNQAGNAMSEEDVLRATVTVSLETAKDSLKAERKK
|
3.4.19.12
| null |
actin cytoskeleton organization [GO:0030036]; cellular response to amino acid starvation [GO:0034198]; cellular response to heat [GO:0034605]; cellular response to misfolded protein [GO:0071218]; chromatin remodeling [GO:0006338]; exploration behavior [GO:0035640]; intermediate filament cytoskeleton organization [GO:0045104]; microtubule cytoskeleton organization [GO:0000226]; monoubiquitinated protein deubiquitination [GO:0035520]; negative regulation of TORC1 signaling [GO:1904262]; positive regulation of ERAD pathway [GO:1904294]; positive regulation of ubiquitin-dependent protein catabolic process [GO:2000060]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; protein K48-linked deubiquitination [GO:0071108]; protein K63-linked deubiquitination [GO:0070536]; protein localization to cytosolic proteasome complex [GO:1904327]; protein modification process [GO:0036211]; protein quality control for misfolded or incompletely synthesized proteins [GO:0006515]; regulation of cell-substrate adhesion [GO:0010810]; ubiquitin-dependent protein catabolic process [GO:0006511]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; lysosomal membrane [GO:0005765]; mitochondrial matrix [GO:0005759]; mitochondrial membrane [GO:0031966]; nuclear inclusion body [GO:0042405]; nuclear matrix [GO:0016363]; nucleus [GO:0005634]
|
ATPase binding [GO:0051117]; cysteine-type deubiquitinase activity [GO:0004843]; histone deacetylase binding [GO:0042826]; identical protein binding [GO:0042802]; K48-linked deubiquitinase activity [GO:1990380]; K63-linked deubiquitinase activity [GO:0061578]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]; transcription corepressor binding [GO:0001222]; ubiquitin protein ligase binding [GO:0031625]
|
PF02099;PF16619;PF02809;
|
3.90.70.40;1.10.287.10;
| null |
PTM: Monoubiquitinated by UBE2W, possibly leading to activate the deubiquitinating enzyme activity (By similarity). {ECO:0000250|UniProtKB:P54252}.
|
SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000250|UniProtKB:P54252}. Nucleus {ECO:0000250|UniProtKB:P54252}. Lysosome membrane {ECO:0000250|UniProtKB:P54252}; Peripheral membrane protein {ECO:0000250|UniProtKB:P54252}. Note=Predominantly nuclear, but not exclusively, inner nuclear matrix. Recruited to lysosomal membrane in response to amino acid deprivation by the RagA/RRAGA-RagB/RRAGB complex. {ECO:0000250|UniProtKB:P54252}.
|
CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:17696782};
| null | null | null | null |
FUNCTION: Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:17696782). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (By similarity). Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (By similarity). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (By similarity). Acts as a negative regulator of mTORC1 signaling in response to amino acid deprivation by mediating deubiquitination of RHEB, thereby promoting RHEB inactivation by the TSC-TBC complex (By similarity). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (By similarity). {ECO:0000250|UniProtKB:P54252, ECO:0000250|UniProtKB:Q9CVD2, ECO:0000269|PubMed:17696782}.
|
Rattus norvegicus (Rat)
|
O35819
|
KLF6_RAT
|
MDVLPMCSIFQELQIVHETGYFSALPSLEEYWQQTCLELERYLQSEPCYVSASEIKFDNQEDLWTKIILARERKEESELKISSSPPEDSLISSGFNYNLETNSLNSDVSSESSDSSEELSPTTKFTSDPIGEVLVNSGNLSSSVISTPPSSPEVNRESSQLWGCGPGDLPSPGKVRSGTSGKSGDKGSGDASPDGRRRVHRCHFNGCRKVYTKSSHLKAHQRTHTGEKPYRCSWEGCEWRFARSDELTRHFRKHTGAKPFKCSHCDRCFSRSDHLALHMKRHL
| null | null |
cellular response to cycloheximide [GO:0071409]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to organic cyclic compound [GO:0071407]; cellular response to peptide [GO:1901653]; cytokine-mediated signaling pathway [GO:0019221]; positive regulation of connective tissue replacement [GO:1905205]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of transcription by RNA polymerase II [GO:0006357]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; double-stranded DNA binding [GO:0003690]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF00096;
|
3.30.160.60;
|
Krueppel C2H2-type zinc-finger protein family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator. Binds a GC box motif. Could play a role in B-cell growth and development (By similarity). {ECO:0000250}.
|
Rattus norvegicus (Rat)
|
O35820
|
DNPH1_RAT
|
MAASGEQAPCSVYFCGSIRGGREDQALYARIVSRLRRYGKVLTEHVADAELEPLGEEAAGGDQFIHEQDLNWLQQADVVVAEVTQPSLGVGYELGRAVALGKPILCLFRPQSGRVLSAMIRGAADGSRFQVWDYAEGEVETMLDRYFEAYLPQKTASSSHPSA
|
3.2.2.-
| null |
allantoin metabolic process [GO:0000255]; deoxyribonucleoside monophosphate catabolic process [GO:0009159]; dGMP catabolic process [GO:0046055]; epithelial cell differentiation [GO:0030855]; nucleoside salvage [GO:0043174]; positive regulation of cell growth [GO:0030307]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
deoxyribonucleoside 5'-monophosphate N-glycosidase activity [GO:0070694]; identical protein binding [GO:0042802]; protein homodimerization activity [GO:0042803]
|
PF05014;
|
3.40.50.450;
|
2'-deoxynucleoside 5'-phosphate N-hydrolase 1 family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O43598}. Nucleus {ECO:0000269|PubMed:9271375}.
|
CATALYTIC ACTIVITY: Reaction=5-hydroxymethyl-dUMP + H2O = 2-deoxy-D-ribose 5-phosphate + 5-hydroxymethyluracil; Xref=Rhea:RHEA:77099, ChEBI:CHEBI:15377, ChEBI:CHEBI:16964, ChEBI:CHEBI:62877, ChEBI:CHEBI:90409; Evidence={ECO:0000250|UniProtKB:O43598}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77100; Evidence={ECO:0000250|UniProtKB:O43598};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=48 uM for dGMP {ECO:0000269|PubMed:17234634}; KM=250 uM for dAMP {ECO:0000269|PubMed:17234634}; KM=450 uM for dIMP {ECO:0000269|PubMed:17234634}; KM=4 mM for dCMP {ECO:0000269|PubMed:17234634}; KM=15.6 mM for dUMP {ECO:0000269|PubMed:17234634}; Vmax=0.09 umol/min/mg enzyme toward dGMP {ECO:0000269|PubMed:17234634};
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 6.0 with dGMP or dCMP as substrate. {ECO:0000269|PubMed:17234634};
| null |
FUNCTION: Part of a nucleotide salvage pathway that eliminates epigenetically modified 5-hydroxymethyl-dCMP (hmdCMP) in a two-step process entailing deamination to cytotoxic 5-hydroxymethyl-dUMP (hmdUMP), followed by its hydrolysis into 5-hydroxymethyluracil (hmU) and 2-deoxy-D-ribose 5-phosphate (deoxyribosephosphate). Catalyzes the second step in that pathway, the hydrolysis of the N-glycosidic bond in hmdUMP, degrading this cytotoxic nucleotide to avoid its genomic integration. {ECO:0000250|UniProtKB:O43598}.
|
Rattus norvegicus (Rat)
|
O35821
|
MBB1A_RAT
|
MAEMKSPTKAEPASPAEAPQGDRRSLLEHSREFLDFFWDIAKPDQETRLRATEKLLEYLRTRPSDSEMKYALKRLITGLGVGREAARPCYSLALAQLLQSFEDIQLCDILGQIQEKYNLQAMNKAMMRPTLFANLFGVLALFQSGRLVKDKEALMKCVRLLKILSHHYNHLQGQPVKALVDILSEVPESMFQEILPKVLKGDMKVILSSPKYLELFLLARQRVPAELESLVGSVDLFSEDNIPSLVNILKVAANSVKKEQKLPDVALNLLRLALQENKFERFWKEVLEEGLLKKPSYTSSYMCFRLLGASLPLLSDEQLQLVMRGDLIRHFGEHMVVSKSQNPLRFIPEISAYVGTFLEGCQDDPKRQFTVMVAFTAITNQGLPVMPTFWRVTRFLNTEALQNYVTWLRDMFLQPDLDSLVDFSTANQKRVQVASLNVPERTVFRLRKWIIHRLVSLVDHLHLEKDEAVVEQIARFCLFHAFFKTKKATPQIPETKQHFSFPLEDGNRGVIVSAFFSLLQTLSVKFRQTPDLAENGKPWTYRLVQLADMLLKHNRNVANVTPLTAQQRQAWDQMMSTLKELEAQSSETRAIAFQHLLLLVGLHLFKSPAESCDVLGDIQTCIKKSMEQNLRRSRSRAKASQEPVWVEVMVEILLSLLAQPSNLMRQVVRSVFGHVCSHLTPRGLQLILAVLNPETNEDEEDNVVVTDTDEKQLKHGEDADSDSEDSKNSESDVDSEDGEESEEEDRDKDVDPGFRQQLMEVLQAGNALGGEEEEEEELGDEAMMALDQNLASLFAEQKMRIQARHEEKNKLQKEKQLRRDFQIRALDLIEVLVTKQPEHPLILELLEPLLNIIQRSMRSRGSTKQEQDLLHKTARIFMHHLCRARHYCHEVEPGAEALHAQVERLVQQAGNQADASVALYYFNASLYLLRVLKGNTTKRYQDGQKLEGADIKSEPKDSEVQTTSCLDLDFVTRVYSASLESLLTKRNSPLTIPMFLDLFSRYPVICKNLLPIVVQHVAGSSRPRHQAQACLLLQKALSARELRVCFEDPEWEQLISQVLGKTTQTLQTLGEAQSKGEHQRELSILELLNTVFRIVNHEKLSVDLTAFLGMLQGKQQKLQQNLQQGNHSSGSSRLYDLYWQAMNLLGVQRPKSEKKNVKDIPSDSQSPISTKRKKKGFLPETKKRKKLKSEGTTSEKKAASQQDAVTEGAMPAATGKDQPPSTGKKRRKRVKANTPSQVNGVTVAKSPAPNNPTLSPSTPPAKTPKVQKKKEKLSQVNGSTPVSPVEPESKKHQKALSTKEVKRRSSQSALPKKRARLSLVSRSPSLLQSGIRKRRVARRRVQTP
| null | null |
cellular response to glucose starvation [GO:0042149]; circadian regulation of gene expression [GO:0032922]; intrinsic apoptotic signaling pathway by p53 class mediator [GO:0072332]; negative regulation of DNA-templated transcription [GO:0045892]; positive regulation of anoikis [GO:2000210]; positive regulation of transcription by RNA polymerase III [GO:0045945]; regulation of G1 to G0 transition [GO:1903450]; respiratory electron transport chain [GO:0022904]; ribosome biogenesis [GO:0042254]
|
B-WICH complex [GO:0110016]; cytoplasm [GO:0005737]; NLS-dependent protein nuclear import complex [GO:0042564]; nucleolus [GO:0005730]; nucleus [GO:0005634]
|
E-box binding [GO:0070888]; rDNA binding [GO:0000182]; RNA binding [GO:0003723]; sequence-specific DNA binding [GO:0043565]; transcription corepressor activity [GO:0003714]
|
PF04931;
| null |
MYBBP1A family
|
PTM: Citrullinated by PADI4. {ECO:0000250|UniProtKB:Q7TPV4}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q7TPV4}. Nucleus, nucleolus {ECO:0000250|UniProtKB:Q7TPV4}. Cytoplasm {ECO:0000250|UniProtKB:Q7TPV4}. Note=Predominantly nucleolar. Also shuttles between the nucleus and cytoplasm. Nuclear import may be mediated by KPNA2, while export appears to depend partially on XPO1/CRM1. {ECO:0000250|UniProtKB:Q7TPV4}.
| null | null | null | null | null |
FUNCTION: May activate or repress transcription via interactions with sequence specific DNA-binding proteins (By similarity). Repression may be mediated at least in part by histone deacetylase activity (HDAC activity) (By similarity). Acts as a corepressor and in concert with CRY1, represses the transcription of the core circadian clock component PER2 (By similarity). Preferentially binds to dimethylated histone H3 'Lys-9' (H3K9me2) on the PER2 promoter (By similarity). Has a role in rRNA biogenesis together with PWP1 (By similarity). {ECO:0000250|UniProtKB:Q7TPV4, ECO:0000250|UniProtKB:Q9BQG0}.
|
Rattus norvegicus (Rat)
|
O35826
|
GLCNE_RAT
|
MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPAFFELDVVVLGSHLIDDYGNTYRMIEQDDFDINTRLHTIVRGEDEAAMVESVGLALVKLPDVLNRLKPDIMIVHGDRFDALALATSAALMNIRILHIEGGEVSGTIDDSIRHAITKLAHYHVCCTRSAEQHLISMCEDHDRILLAGCPSYDKLLSAKNKDYMSIIRMWLGDDVKCKDYIVALQHPVTTDIKHSIKMFELTLDALISFNKRTLVLFPNIDAGSKEMVRVMRKKGIEHHPNFRAVKHVPFDQFIQLVAHAGCMIGNSSCGVREVGAFGTPVINLGTRQIGRETGENVLHVRDADTQDKILQALHLQFGKQYPCSKIYGDGNAVPRILKFLKSIDLQEPLQKKFCFPPVKENISQDIDHILETLSALAVDLGGTNLRVAIVSMKGEIVKKYTQFNPKTYEERISLILQMCVEAAAEAVKLNCRILGVGISTGGRVNPQEGVVLHSTKLIQEWNSVDLRTPLSDTLHLPVWVDNDGNCAAMAERKFGQGKGQENFVTLITGTGIGGGIIHQHELIHGSSFCAAELGHLVVSLDGPDCSCGSHGCIEAYASGMALQREAKKLHDEDLLLVEGMSVPKDEAVGALHLIQAAKLGNVKAQSILRTAGTALGLGVVNILHTMNPSLVILSGVLASHYIHIVRDVIRQQALSSVQDVDVVVSDLVDPALLGAASMVLDYTTRRIH
|
2.7.1.60; 3.2.1.183
| null |
N-acetylglucosamine biosynthetic process [GO:0006045]; N-acetylneuraminate biosynthetic process [GO:0046380]; UDP-N-acetylglucosamine metabolic process [GO:0006047]
|
cytosol [GO:0005829]
|
ATP binding [GO:0005524]; hexokinase activity [GO:0004396]; hydrolase activity, hydrolyzing O-glycosyl compounds [GO:0004553]; metal ion binding [GO:0046872]; N-acylmannosamine kinase activity [GO:0009384]; UDP-N-acetylglucosamine 2-epimerase activity [GO:0008761]
|
PF02350;PF00480;
|
3.30.420.40;3.40.50.2000;
|
UDP-N-acetylglucosamine 2-epimerase family; ROK (NagC/XylR) family
|
PTM: Phosphorylated. Phosphorylation by PKC activates the UDP-N-acetylglucosamine 2-epimerase activity. {ECO:0000250|UniProtKB:Q91WG8}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:9305887, ECO:0000269|PubMed:9305888}.
|
CATALYTIC ACTIVITY: Reaction=H2O + UDP-N-acetyl-alpha-D-glucosamine = H(+) + N-acetyl-D-mannosamine + UDP; Xref=Rhea:RHEA:30683, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17122, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223; EC=3.2.1.183; Evidence={ECO:0000269|PubMed:10334995, ECO:0000269|PubMed:10497249, ECO:0000269|PubMed:9305887, ECO:0000269|PubMed:9305888}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30684; Evidence={ECO:0000269|PubMed:10497249}; CATALYTIC ACTIVITY: Reaction=an N-acyl-D-mannosamine + ATP = ADP + an N-acyl-D-mannosamine 6-phosphate + H(+); Xref=Rhea:RHEA:23832, ChEBI:CHEBI:15378, ChEBI:CHEBI:16062, ChEBI:CHEBI:30616, ChEBI:CHEBI:57666, ChEBI:CHEBI:456216; EC=2.7.1.60; Evidence={ECO:0000269|PubMed:10497249, ECO:0000269|PubMed:9305887, ECO:0000269|PubMed:9305888}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23833; Evidence={ECO:0000269|PubMed:10497249};
| null |
PATHWAY: Amino-sugar metabolism; N-acetylneuraminate biosynthesis. {ECO:0000269|PubMed:10497249, ECO:0000269|PubMed:9305887, ECO:0000269|PubMed:9305888}.
| null | null |
FUNCTION: Bifunctional enzyme that possesses both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities, and serves as the initiator of the biosynthetic pathway leading to the production of N-acetylneuraminic acid (NeuAc), a critical precursor in the synthesis of sialic acids. By catalyzing this pivotal and rate-limiting step in sialic acid biosynthesis, this enzyme assumes a pivotal role in governing the regulation of cell surface sialylation (PubMed:10497249, PubMed:9305887, PubMed:9305888). Sialic acids represent a category of negatively charged sugars that reside on the surface of cells as terminal components of glycoconjugates and mediate important functions in various cellular processes, including cell adhesion, signal transduction, and cellular recognition (PubMed:10334995). {ECO:0000269|PubMed:10334995, ECO:0000269|PubMed:10497249, ECO:0000269|PubMed:9305887, ECO:0000269|PubMed:9305888}.
|
Rattus norvegicus (Rat)
|
O35831
|
CDK17_RAT
|
MKKFKRRLSLTLRGSQTIDESLSELAEQMTIEESSSKDNEPIVKNGRPPTSHSMHSFLHQYTGSFKKPPLRRPHSVIGGSLGSFMAMPRNGSRLDIVHENLKMGSDGESDQASGTSSDEVQSPTGVCLRNRIHRRISMEDLNKRLSLPADIRIPDGYLEKLQISSPPFDQPMSRRSRRASLSEIGFGKMETYIKLEKLGEGTYATVYKGRSKLTENLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLDKDLKQYMDDCGSIMSMHNVKLFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSVPTKTYSNEVVTLWYRPPDVLLGSSEYSTQIDMWGVGCIFFEMASGRPLFPGSTVEDELHLIFRLLGTPSQETWPGVSSNDEFKNYNFPKYKPQPLINHAPRLDSEGIELITKFLQYESKKRAPAEEAMKHVYFRSLGPRIHALPESVSIFSLKEIQLQKDPGFRNSSYPETGVFVINHFTCRS
|
2.7.11.22
| null |
phosphorylation [GO:0016310]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
ATP binding [GO:0005524]; cyclin-dependent protein serine/threonine kinase activity [GO:0004693]; protein serine kinase activity [GO:0106310]
|
PF12330;PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily
| null | null |
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.22;
| null | null | null | null |
FUNCTION: May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1.
|
Rattus norvegicus (Rat)
|
O35854
|
BCAT2_RAT
|
MSAAILGQVWTRKLLPIPWRLCVPGRCVSSNFKAADLQVQVTREPQKKPAPSQPLLFGKTFTDHMLMVEWNSKTGWGPPRIQPFQNLTLHPACSGLHYSLQLFEGLKAYKGRDKQVRLFRPWLNMDRMLRSARRLCLPDFDKQELLECIRQLIEVDKDWVPDGNGTSLYVRPVLIGNEPSLGVGMVTQALLFVILCPVGSYFPGDSMTPVSLLADPSFVRAWIGGVGDCKLGGNYGPTVAVQQEAQKKGCEQVLWLYGPDHQLTEVGTMNIFVYWTHEDGELELATPPLDGIILPGVVRQSLLDLARTWGEFRVAERKVTMKELKRALEEGRVREVFGSGTACQVCPVHQILYEGKQLHIPTMENGPELILRFQKELKAIQYGTSAHDWMLRV
|
2.6.1.42
|
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000250|UniProtKB:O15382};
|
amino acid biosynthetic process [GO:0008652]; branched-chain amino acid catabolic process [GO:0009083]; branched-chain amino acid metabolic process [GO:0009081]; cellular response to leukemia inhibitory factor [GO:1990830]; isoleucine catabolic process [GO:0006550]; isoleucine metabolic process [GO:0006549]; lactation [GO:0007595]; leucine biosynthetic process [GO:0009098]; leucine metabolic process [GO:0006551]; lipid metabolic process [GO:0006629]; regulation of hormone levels [GO:0010817]; valine biosynthetic process [GO:0009099]; valine metabolic process [GO:0006573]
|
mitochondrion [GO:0005739]
|
branched-chain-amino-acid transaminase activity [GO:0004084]; L-isoleucine transaminase activity [GO:0052656]; L-leucine transaminase activity [GO:0052654]; L-leucine:2-oxoglutarate aminotransferase activity [GO:0050048]; L-valine transaminase activity [GO:0052655]
|
PF01063;
|
3.30.470.10;3.20.10.10;
|
Class-IV pyridoxal-phosphate-dependent aminotransferase family
| null |
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:9165094}.
|
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-leucine = 4-methyl-2-oxopentanoate + L-glutamate; Xref=Rhea:RHEA:18321, ChEBI:CHEBI:16810, ChEBI:CHEBI:17865, ChEBI:CHEBI:29985, ChEBI:CHEBI:57427; EC=2.6.1.42; Evidence={ECO:0000269|PubMed:9165094}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-isoleucine = (S)-3-methyl-2-oxopentanoate + L-glutamate; Xref=Rhea:RHEA:24801, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:35146, ChEBI:CHEBI:58045; EC=2.6.1.42; Evidence={ECO:0000269|PubMed:9165094}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-valine = 3-methyl-2-oxobutanoate + L-glutamate; Xref=Rhea:RHEA:24813, ChEBI:CHEBI:11851, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:57762; EC=2.6.1.42; Evidence={ECO:0000269|PubMed:9165094};
| null | null | null | null |
FUNCTION: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine (PubMed:9165094). May also function as a transporter of branched chain alpha-keto acids (PubMed:8428987). {ECO:0000269|PubMed:8428987, ECO:0000269|PubMed:9165094}.
|
Rattus norvegicus (Rat)
|
O35855
|
BCAT2_MOUSE
|
MAAATLGQVWARKLLPVPWLLCGSKRCVSSIFKAADLQIQMTKEPQKKPAPSQALLFGKTFTDHMLMVEWNNKAGWGPPRIQPFQNLTLHPACSGLHYSLQLFEGLKAYKGGDQQVRLFRPWLNMDRMLRSARRLCLPDFDKQELLECIRQLIEVDKDWVPDGNGTSLYVRPVLIGNEPSLGVGMVTQALLYVILCPVGSYFPGDSMTPVSLLADPSFVRAWIGGVGDCKLGGNYGPTVAVQREAQKRGCEQVLWLYGPDHQLTEVGTMNIFVYWTHEDGVLELVTPPLNGVILPGVVRQSLLDLARTWGEFRVAERKVTMKELKRALEEGRVREVFGSGTACQVCPVHQILYEGKQLHIPTMENGPELILRFQKELKAIQYGASAHDWMFRV
|
2.6.1.42
|
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000250|UniProtKB:O15382};
|
amino acid biosynthetic process [GO:0008652]; branched-chain amino acid catabolic process [GO:0009083]; branched-chain amino acid metabolic process [GO:0009081]; cellular response to leukemia inhibitory factor [GO:1990830]; isoleucine catabolic process [GO:0006550]; isoleucine metabolic process [GO:0006549]; leucine biosynthetic process [GO:0009098]; leucine metabolic process [GO:0006551]; lipid metabolic process [GO:0006629]; regulation of hormone levels [GO:0010817]; valine biosynthetic process [GO:0009099]; valine metabolic process [GO:0006573]
|
mitochondrion [GO:0005739]; nucleoplasm [GO:0005654]
|
branched-chain-amino-acid transaminase activity [GO:0004084]; L-isoleucine transaminase activity [GO:0052656]; L-leucine transaminase activity [GO:0052654]; L-leucine:2-oxoglutarate aminotransferase activity [GO:0050048]; L-valine transaminase activity [GO:0052655]
|
PF01063;
|
3.30.470.10;3.20.10.10;
|
Class-IV pyridoxal-phosphate-dependent aminotransferase family
| null |
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:O35854}.
|
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-leucine = 4-methyl-2-oxopentanoate + L-glutamate; Xref=Rhea:RHEA:18321, ChEBI:CHEBI:16810, ChEBI:CHEBI:17865, ChEBI:CHEBI:29985, ChEBI:CHEBI:57427; EC=2.6.1.42; Evidence={ECO:0000250|UniProtKB:O15382}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-isoleucine = (S)-3-methyl-2-oxopentanoate + L-glutamate; Xref=Rhea:RHEA:24801, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:35146, ChEBI:CHEBI:58045; EC=2.6.1.42; Evidence={ECO:0000250|UniProtKB:O15382}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-valine = 3-methyl-2-oxobutanoate + L-glutamate; Xref=Rhea:RHEA:24813, ChEBI:CHEBI:11851, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:57762; EC=2.6.1.42; Evidence={ECO:0000250|UniProtKB:O15382};
| null | null | null | null |
FUNCTION: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine (By similarity). May also function as a transporter of branched chain alpha-keto acids (By similarity). {ECO:0000250|UniProtKB:O15382, ECO:0000250|UniProtKB:O35854}.
|
Mus musculus (Mouse)
|
O35864
|
CSN5_MOUSE
|
MAASGSGMAQKTWELANNMQEAQSIDEIYKYDKKQQQEILAAKPWTKDHHYFKYCKISALALLKMVMHARSGGNLEVMGLMLGKVDGETMIIMDSFALPVEGTETRVNAQAAAYEYMAAYIENAKQVGRLENAIGWYHSHPGYGCWLSGIDVSTQMLNQQFQEPFVAVVIDPTRTISAGKVNLGAFRTYPKGYKPPDEGPSEYQTIPLNKIEDFGVHCKQYYALEVSYFKSSLDRKLLELLWNKYWVNTLSSSSLLTNADYTTGQVFDLSEKLEQSEAQLGRGSFMLGLETHDRKSEDKLAKATRDSCKTTIEAIHGLMSQVIKDKLFNQINVA
|
3.4.-.-
|
COFACTOR: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000250};
|
exosomal secretion [GO:1990182]; negative regulation of apoptotic process [GO:0043066]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein deneddylation [GO:0000338]; proteolysis [GO:0006508]; regulation of cell cycle [GO:0051726]; regulation of DNA-templated transcription [GO:0006355]; regulation of IRE1-mediated unfolded protein response [GO:1903894]; regulation of JNK cascade [GO:0046328]
|
chromatin [GO:0000785]; COP9 signalosome [GO:0008180]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleoplasm [GO:0005654]; perinuclear region of cytoplasm [GO:0048471]; synaptic vesicle [GO:0008021]; transcription regulator complex [GO:0005667]
|
deNEDDylase activity [GO:0019784]; enzyme binding [GO:0019899]; macrophage migration inhibitory factor binding [GO:0035718]; metal ion binding [GO:0046872]; metal-dependent deubiquitinase activity [GO:0140492]; metallopeptidase activity [GO:0008237]; transcription coactivator activity [GO:0003713]
|
PF18323;PF01398;
|
3.40.140.10;
|
Peptidase M67A family, CSN5 subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10721695}. Nucleus {ECO:0000269|PubMed:10721695}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q92905}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle {ECO:0000250|UniProtKB:Q92905}. Note=Nuclear localization is diminished in the presence of IFIT3. {ECO:0000250|UniProtKB:Q92905}.
| null | null | null | null | null |
FUNCTION: Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Promotes the proteasomal degradation of BRSK2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. {ECO:0000250|UniProtKB:Q92905}.
|
Mus musculus (Mouse)
|
O35867
|
NEB1_RAT
|
MLKAESSGERTTLRSASPHRNAYRTEFQALKSTFDKPKPDGEQKTKEGEGSQQSRGRKYGSNVNRIKNLFMQMGMEPNENAAIIAKTRGKGRPSSPQKRMKPKEFVEKTDGSVVKLESSVSERISRFDTMHDGPSYAKFTETRKMFERSGHESGQNNRHSPKKEKAGEAEPQDEWGGSKSNRGSSDSLDSLSPRTEAVSPTVSQLSAVFENSESPGAITPGKAENSNYSVTGHYPLNLPSVTVTNLDTFGRLKDSNSRPSSNKQATDTEEPEKSEAVPVPEVAQKGTSLASLPSEERQLSTEAEDVTAQPDTPDSTDKDSPGEPSAESQAMPKSNTLSRPKEPLEDAEANVVGSEAEQPQRRDLTGGGDLTSPDASASSCGKEVPEDSNSFEGSHVYMHSDYNVYRVRSRYNSDWGETGTEQDEGDDSDENNYYQPDMEYSEIVGLPQEEEIPANRKIKFSCAPIKVFNTYSNEDYDRRNDDVDPVAASAEYELEKRVEKLELFPVELEKDEDGLGISIIGMGVGADAGLEKLGIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQNFAATVLRNTKGNVRFVIGREKPGQVSEVAQLISQTLEQERRQRELLERHYAQYDADDDETGEYATDEEEDEVGPILPGGDMAIEVFELPENEDMFSPSDLDTSKLSHKFKELQIKHAVTEAEIQKLKTKLQAAENEKVRWELEKNQLQQNIEENKERMVKLESYWIEAQTLCHTVNEHLKETQSQYQALEKKYNKAKKLIKDFQQKELDFIRRQEVERKKLEEVEKAHLVEVQGLQVRIRDLEAEVFRLLKQNGTQVNNNNNIFERRPSPGEVSKGDTMENVEVKQTSCQDGLSQDLNEAVPETERLDSKALKTRAQLSVKNRRQRPTRTRLYDSVSSTDGEDSLERKNFTFNDDFSPSSTSSADLSGLGAEPKTPGLSQSLALSSDESLDMIDDEILDDGQSPKHTQSQSRAVHEWSVQQVSHWLVGLSLDQYVSEFSAQNISGEQLLQLDGNKLKALGMTSSQDRALVKKKLKEMKMSLEKARKAQEKMEKQREKLRRKEQEQMQRKSKKSEKMTSTTEQP
| null | null |
actin filament organization [GO:0007015]; calcium-mediated signaling [GO:0019722]; cellular response to toxic substance [GO:0097237]; excitatory postsynaptic potential [GO:0060079]; modulation of chemical synaptic transmission [GO:0050804]; negative regulation of long-term synaptic potentiation [GO:1900272]; negative regulation of spontaneous neurotransmitter secretion [GO:1904049]; negative regulation of stress fiber assembly [GO:0051497]; neuron development [GO:0048666]; neuron projection development [GO:0031175]; positive regulation of dendritic spine development [GO:0060999]; positive regulation of long-term synaptic depression [GO:1900454]; positive regulation of neuron projection development [GO:0010976]; postsynaptic actin cytoskeleton organization [GO:0098974]; regulation of actin filament polymerization [GO:0030833]; regulation of dendritic spine morphogenesis [GO:0061001]; regulation of filopodium assembly [GO:0051489]; regulation of synapse assembly [GO:0051963]; regulation of synapse structural plasticity [GO:0051823]
|
actin cytoskeleton [GO:0015629]; cortical actin cytoskeleton [GO:0030864]; cytoplasm [GO:0005737]; cytoskeleton [GO:0005856]; dendrite [GO:0030425]; dendritic spine [GO:0043197]; dendritic spine neck [GO:0044326]; filopodium [GO:0030175]; glutamatergic synapse [GO:0098978]; growth cone [GO:0030426]; growth cone lamellipodium [GO:1990761]; lamellipodium [GO:0030027]; neuromuscular junction [GO:0031594]; neuronal cell body [GO:0043025]; postsynaptic actin cytoskeleton [GO:0098871]; postsynaptic density [GO:0014069]
|
actin filament binding [GO:0051015]; GTPase binding [GO:0051020]; identical protein binding [GO:0042802]; protein domain specific binding [GO:0019904]; protein kinase binding [GO:0019901]; protein phosphatase 1 binding [GO:0008157]; protein-containing complex binding [GO:0044877]; transmembrane transporter binding [GO:0044325]
|
PF00595;PF17817;PF07647;
|
2.30.42.10;1.10.150.50;
| null | null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Synapse, synaptosome.
| null | null | null | null | null |
FUNCTION: Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May be involved in neurite formation. Inhibits protein phosphatase 1-alpha activity. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction.
|
Rattus norvegicus (Rat)
|
O35874
|
SATT_MOUSE
|
MEKSGETNGYLDGTQAEPAAGPRTPETAMGKSQRCASFFRRHALVLLTVSGVLVGAGMGAALRGLQLTRTQITYLAFPGEMLLRMLRMIILPLVVCSLVSGAASLDASSLGRLGGIAVAYFGLTTLSASALAVALAFIIKPGAGAQTLQSSSLGLENSGPPPVSKETVDSFLDLLRNLFPSNLVVAAFTTSATDYTVVTHNTSSGNVTKEKIPVVTDVEGMNILGLVLFALVLGVALKKLGPEGEDLIRFFNSFNEATMVLVSWIMWYVPIGIMFLIGSKIVEMKDIVMLVTSLGKYIFASMLGHVIHGGIVLPLVYFAFTRKNPFTFLLGLLTPFATAFATCSSSATLPSMMKCIEENNGVDKRISRFILPIGATVNMDGAAIFQCVAAVFIAQLNNVDLNAGQIFTILVTATASSVGAAGVPAGGVLTIAIILEAIGLPTHDLSLILAVDWIVDRTTTVVNVEGDALGAGILNHLNQKVVKKGEQELQEVKVEAIPNSKSEEETSPLVTHQNPAGPVAIAPELESKESVL
| null | null |
cognition [GO:0050890]; L-alanine import across plasma membrane [GO:1904273]; L-aspartate import across plasma membrane [GO:0140009]; L-glutamate transmembrane transport [GO:0015813]; L-serine import across plasma membrane [GO:1903812]; L-serine transport [GO:0015825]; proline transport [GO:0015824]; serine import across plasma membrane [GO:0098718]
|
centrosome [GO:0005813]; dendrite [GO:0030425]; intermediate filament [GO:0005882]; melanosome [GO:0042470]; neuronal cell body [GO:0043025]; plasma membrane [GO:0005886]
|
chloride channel activity [GO:0005254]; L-alanine transmembrane transporter activity [GO:0015180]; L-aspartate transmembrane transporter activity [GO:0015183]; L-cystine transmembrane transporter activity [GO:0015184]; L-hydroxyproline transmembrane transporter activity [GO:0034590]; L-proline transmembrane transporter activity [GO:0015193]; L-serine transmembrane transporter activity [GO:0015194]; L-threonine transmembrane transporter activity [GO:0015195]; neutral L-amino acid transmembrane transporter activity [GO:0015175]; symporter activity [GO:0015293]
|
PF00375;
|
1.10.3860.10;
|
Dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family, SLC1A4 subfamily
| null |
SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P43007}; Multi-pass membrane protein {ECO:0000255}. Melanosome {ECO:0000250|UniProtKB:P43007}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000250|UniProtKB:P43007}.
|
CATALYTIC ACTIVITY: Reaction=L-threonine(in) + Na(+)(in) = L-threonine(out) + Na(+)(out); Xref=Rhea:RHEA:69999, ChEBI:CHEBI:29101, ChEBI:CHEBI:57926; Evidence={ECO:0000250|UniProtKB:P43007}; CATALYTIC ACTIVITY: Reaction=L-serine(in) + Na(+)(in) = L-serine(out) + Na(+)(out); Xref=Rhea:RHEA:29575, ChEBI:CHEBI:29101, ChEBI:CHEBI:33384; Evidence={ECO:0000250|UniProtKB:P43007}; CATALYTIC ACTIVITY: Reaction=L-cysteine(in) + Na(+)(in) = L-cysteine(out) + Na(+)(out); Xref=Rhea:RHEA:68232, ChEBI:CHEBI:29101, ChEBI:CHEBI:35235; Evidence={ECO:0000250|UniProtKB:P43007}; CATALYTIC ACTIVITY: Reaction=L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out); Xref=Rhea:RHEA:29283, ChEBI:CHEBI:29101, ChEBI:CHEBI:57972; Evidence={ECO:0000250|UniProtKB:P43007}; CATALYTIC ACTIVITY: Reaction=L-proline(in) + Na(+)(in) = L-proline(out) + Na(+)(out); Xref=Rhea:RHEA:28967, ChEBI:CHEBI:29101, ChEBI:CHEBI:60039; Evidence={ECO:0000250|UniProtKB:P43007}; CATALYTIC ACTIVITY: Reaction=4-hydroxy-L-proline(in) + Na(+)(in) = 4-hydroxy-L-proline(out) + Na(+)(out); Xref=Rhea:RHEA:70023, ChEBI:CHEBI:29101, ChEBI:CHEBI:58419; Evidence={ECO:0000250|UniProtKB:P43007};
| null | null | null | null |
FUNCTION: Sodium-dependent neutral amino-acid transporter that mediates transport of alanine, serine, cysteine, proline, hydroxyproline and threonine. {ECO:0000250|UniProtKB:P43007}.
|
Mus musculus (Mouse)
|
O35876
|
SMN_RAT
|
MAMGSGGGAGSEQEDTVLFRRGTGQSDDSDIWDDTALIKAYDKAVASFKHALKNGDMCETSDKPKGTARRKPAKKNKNQKKNATAPLKQWKAGDKCSAVWSEDGCVYPATITSVDLKRETCVVVYTGYGNKEEQNLSDLLSPTCEVANNTEQNTQENESQVSTDDSEHSSRSLRSKAHSKSKAAPWTSFLPPPPPVPGAGLGPGKPGLRFSGPPPPPPPPPPFLPCWMPPFPSGPPIIPPPPPISPDCLDDTDALGSMLISWYMSGYHTGYYMGFRQNKKEGKKCSHTN
| null | null |
axonogenesis [GO:0007409]; chemical synaptic transmission [GO:0007268]; DNA-templated transcription termination [GO:0006353]; microtubule depolymerization [GO:0007019]; positive regulation of RNA splicing [GO:0033120]; regulation of neuron projection development [GO:0010975]; spliceosomal complex assembly [GO:0000245]; spliceosomal snRNP assembly [GO:0000387]
|
Cajal body [GO:0015030]; COPI-coated vesicle [GO:0030137]; cytoplasm [GO:0005737]; cytoplasmic ribonucleoprotein granule [GO:0036464]; cytosol [GO:0005829]; Gemini of coiled bodies [GO:0097504]; Golgi apparatus [GO:0005794]; growth cone [GO:0030426]; neuron projection [GO:0043005]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; perikaryon [GO:0043204]; SMN complex [GO:0032797]; SMN-Sm protein complex [GO:0034719]; Z disc [GO:0030018]
|
fibroblast growth factor binding [GO:0017134]; identical protein binding [GO:0042802]; RNA binding [GO:0003723]
|
PF20636;PF06003;PF20635;
|
2.30.30.140;3.40.190.10;
|
SMN family
| null |
SUBCELLULAR LOCATION: Nucleus, gem {ECO:0000250|UniProtKB:Q16637}. Nucleus, Cajal body {ECO:0000250|UniProtKB:Q16637}. Cytoplasm {ECO:0000250|UniProtKB:Q16637}. Cytoplasmic granule {ECO:0000250|UniProtKB:Q16637}. Perikaryon {ECO:0000250|UniProtKB:Q16637}. Cell projection, neuron projection {ECO:0000250|UniProtKB:Q16637}. Cell projection, axon {ECO:0000250|UniProtKB:P97801}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:P97801}. Note=Colocalizes with actin and at the Z-line of skeletal muscle (By similarity). Under stress conditions colocalizes with RPP20/POP7 in punctuated cytoplasmic granules. Colocalized and redistributed with ZPR1 from the cytoplasm to nuclear gems (Gemini of coiled bodies) and Cajal bodies. Colocalizes with FMR1 in cytoplasmic granules in the soma and neurite cell processes (By similarity). {ECO:0000250|UniProtKB:P97801, ECO:0000250|UniProtKB:Q16637}.
| null | null | null | null | null |
FUNCTION: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Within the SMN complex, SMN1 acts as a structural backbone and together with GEMIN2 it gathers the Sm complex subunits. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000250|UniProtKB:Q16637}.
|
Rattus norvegicus (Rat)
|
O35885
|
ASCL2_MOUSE
|
MEAHLDWYGVPGLQEASDACPRESCSSALPEAREGANVHFPPHPVPREHFSCAAPELVAGAQGLNASLMDGGALPRLMPTSSGVAGACAARRRQASPELLRCSRRRRSGATEASSSSAAVARRNERERNRVKLVNLGFQALRQHVPHGGANKKLSKVETLRSAVEYIRALQRLLAEHDAVRAALAGGLLTPATPPSDECAQPSASPASASLSCASTSPSPDRLGCSEPTSPRSAYSSEESSCEGELSPMEQELLDFSSWLGGY
| null | null |
axon development [GO:0061564]; cell differentiation [GO:0030154]; chorionic trophoblast cell development [GO:0060719]; forebrain development [GO:0030900]; in utero embryonic development [GO:0001701]; negative regulation of Schwann cell proliferation [GO:0010626]; negative regulation of T-helper 1 cell differentiation [GO:0045626]; negative regulation of T-helper 17 cell differentiation [GO:2000320]; negative regulation of T-helper 2 cell differentiation [GO:0045629]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neuron differentiation [GO:0030182]; placenta development [GO:0001890]; positive regulation of T cell migration [GO:2000406]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of neurogenesis [GO:0050767]; regulation of transcription by RNA polymerase II [GO:0006357]; response to hypoxia [GO:0001666]; sensory organ development [GO:0007423]; somatic stem cell population maintenance [GO:0035019]; spongiotrophoblast differentiation [GO:0060708]; stem cell population maintenance [GO:0019827]; T follicular helper cell differentiation [GO:0061470]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]; RNA polymerase II transcription regulator complex [GO:0090575]
|
bHLH transcription factor binding [GO:0043425]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; E-box binding [GO:0070888]; protein dimerization activity [GO:0046983]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]; sequence-specific DNA binding [GO:0043565]
|
PF00010;
|
4.10.280.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P19360}.
| null | null | null | null | null |
FUNCTION: Transcription factor (PubMed:10611232, PubMed:29500235). Binds to E-box motifs 5'-CANNTG-3' in the regulatory elements of target genes, probably as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3 (PubMed:10611232, PubMed:29500235). May bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes (PubMed:29500235). Required during post-implantation development for the generation of some differentiated trophoblast cell types (PubMed:8090202). Transcriptional activity of ASCL2 may be antagonised in a subset of trophoblast cells by bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins (PubMed:10611232). Involved in differentiation and function of follicular T-helper (Tfh) cells, thereby playing a role in germinal center responses; probably modulates expression of genes involved in Tfh cell function, such as BCL6 (PubMed:24463518). May also act as a suppressor of Th1-, Th2- and Th17-cell differentiation (PubMed:24463518). Induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin (PubMed:25620640). May form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R-spondin signaling, and thereby maintaining stem cell characteristics (PubMed:25620640). Modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up-regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells (By similarity). May play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C (By similarity). May be dispensable for blastocyst formation and later embryonic function (PubMed:8090202, PubMed:9622625). May be involved in the determination of neuronal precursors (By similarity). {ECO:0000250|UniProtKB:P19360, ECO:0000269|PubMed:10611232, ECO:0000269|PubMed:24463518, ECO:0000269|PubMed:25620640, ECO:0000269|PubMed:29500235, ECO:0000269|PubMed:8090202, ECO:0000269|PubMed:9622625}.
|
Mus musculus (Mouse)
|
O35889
|
AFAD_RAT
|
MSAGGRDEERRKLADIIHHWNANRLDLFEISQPTEDLEFHGVMRFYFQDKAAGNFATKCIRVSSTATTQDVIETLAEKFRPDMRMLSSPKYSLYEVHVSGERRLDIDEKPLVVQLNWNKDDREGRFVLKNENDAIPAKKAQSNGPEKQEKEGVIQNFKRTLSKKEKKEKKKREKEALRQASDKEERPSQGDDSENSRLAAEVYKDMPETSFTRTISNPEVVMKRRRQQKLEKRMQEFRSSDGRPDSGGTLRIYADSLKPNIPYKTILLSTTDPADFAVAESLEKYGLEKENPKDYCIARVMLPPGAQHSDERGAKEIILDDDECPLQIFREWPSDKGILVFQLKRRPPDYIPKKMKKHVEGKPLKGKDRADGSGYGSALPPEKLPYLVELSPGRRNHFAYYSYHTYEDGSDSRDKPKLYRLQLSVTEVGTEKFDDNSIQLFGPGIQPHHCDLTNMDGVVTVTPRSMDAETYVDGQRISETTMLQSGMRLQFGTSHVFKFVDPIQDHVLSKRSVDGGLMVKGPRHKPGAVQETTFELGGDIHSGTALPASRSTTRLDSDRVSSASSTAERGMVKPMIRLDQEQDYRRRESRTQDAAGPELMLPASIEFRESSEDSFLSAIINYTNSSTVHFKLSPTYVLYMACRYVLSSQHRPDISPTERTHKAIAVVNKMVSMMEGVIQEVDQVDQKQKNIAGALAFWMANASELLNFIKQDRDLSRITLDAQDVLAHLVQMAFKYLVHCLQSELNNYMPAFLDDPEENSLQRPKIDDVLHTLTGAMSLLRRCRVNAALTIQLFSQLFHFINMWLFNRLVTDPDSGLCSHYWGAIIRQQLGHIEAWAEKQGLELAADCHLSRIVQATTLLTMDKYVPDDIPNINSTCFKLNSLQLQALLQNYHCAPDEPFIPTDLIENVVAVAENTADELARSDGRDVQLEEDPDLQLPFLLPEDGYSCDVVRNIPNGLQEFLDPLCQRGFCRLVPHTRSPGTWTIYFEGADYESHLMRENTELTQPLRKEPEVITVTLKKQNGMGLSIVAAKGAGQDKLGIYVKSVVKGGAADVDGRLAAGDQLLSVDGRSLVGLSQERAAELMTRTSSVVTLEVAKQGAIYHGLATLLNQPSPMMQRISDRRGSGKPRPKSEGFELYNNSAQNGSPESPQMPWTEYSEPKKLPGDDRLMKNRADHRSSPNVANQPPSPGGKSPYTSGTAAKITSVSTGNLCTEEQTPPPRPEAYPIPTQTYTREYFTFPASKSQDRMAPVQNQWPNYEEKPHMHTESDHASIAIQRVTRSQEELREEKVYQLERHRVESGMDRKCDSDMWINQSSSVESSTSSQEHLNHSSKSVTPASTLTKSGPGRWKTPAAVLPTPVAVSQPIRTDLPPPPPPPPAHYTSDFDGISMDLPLPPPPANQAAPQSAQVAAAERKKREEHQRWYEKEKARLEEERERKRREQERKLGQMRTQSLNPASFSPLATQAKPEKPSTLQRPQETVIRELQPQQQPRTIERRDLQYITISKEELSSGDSLSPDPWKRDAREKLEKQQQMHIVDMLSKEIHELQNKGDRTAEESDRLRKLMLEWQFQKRLQESKQKDEDDDEEEDDDVDTMLIMQRLEAERRARLQDEERRRQQQLEEMRKREVEDRVRQEEDGRHQEEERVKRDAEEKRRQEEGYYSRLEAERRRQHEEAARRLLEPEEPGLSRPPLPQDYEPPSQSSAPSAPPPPPQRNASYLKTQVLSPDSLFTAKFVAYDDDDEEENYVPAGPNSYSGSAGTTAGTYDAPRDTREKLSRSQDADLPGSSGAPENLTFRERQRLFSQGQDVSDKVKASRKLTELENELNTK
| null | null |
adherens junction maintenance [GO:0034334]; bicellular tight junction assembly [GO:0070830]; brain morphogenesis [GO:0048854]; cell-cell adhesion mediated by cadherin [GO:0044331]; cerebral cortex development [GO:0021987]; dendrite arborization [GO:0140059]; establishment of endothelial intestinal barrier [GO:0090557]; establishment of protein localization to plasma membrane [GO:0061951]; homeostasis of number of cells [GO:0048872]; negative regulation of cell migration [GO:0030336]; neuroepithelial cell differentiation [GO:0060563]; pore complex assembly [GO:0046931]; positive regulation of cell-cell adhesion [GO:0022409]; positive regulation of cell-cell adhesion mediated by cadherin [GO:2000049]; positive regulation of dendrite extension [GO:1903861]; positive regulation of dendrite morphogenesis [GO:0050775]; positive regulation of dendritic spine morphogenesis [GO:0061003]; positive regulation of gene expression [GO:0010628]; positive regulation of mini excitatory postsynaptic potential [GO:0061885]; protein localization to cell junction [GO:1902414]; radial glial cell differentiation [GO:0060019]; regulation of oligodendrocyte progenitor proliferation [GO:0070445]; regulation of protein localization [GO:0032880]; signal transduction [GO:0007165]; telencephalon development [GO:0021537]
|
adherens junction [GO:0005912]; apical junction complex [GO:0043296]; apical part of cell [GO:0045177]; axon [GO:0030424]; cell junction [GO:0030054]; cell-cell contact zone [GO:0044291]; cell-cell junction [GO:0005911]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; pore complex [GO:0046930]; somatodendritic compartment [GO:0036477]; tight junction [GO:0070160]
|
actin filament binding [GO:0051015]; cell adhesion molecule binding [GO:0050839]; LIM domain binding [GO:0030274]; small GTPase binding [GO:0031267]
|
PF01843;PF00498;PF00595;PF00788;
|
2.30.42.10;2.60.200.20;
| null | null |
SUBCELLULAR LOCATION: Cell junction, adherens junction {ECO:0000269|PubMed:9334353}. Note=Not found at cell-matrix AJs. {ECO:0000269|PubMed:9334353}.
| null | null | null | null | null |
FUNCTION: Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (PubMed:9334353). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:9334353). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (By similarity). {ECO:0000250|UniProtKB:P55196, ECO:0000250|UniProtKB:Q9QZQ1, ECO:0000269|PubMed:9334353}.
|
Rattus norvegicus (Rat)
|
O35893
|
SP100_MUSCR
|
MEDSNASPRMSTEHENTEMHPFEYMFKHFKTQKVAISNAIRSTFPFLESLRDREFITGKMYEDLIDSCRSLVPVDKVIYKALDELEKKFDVTVLWELFNEVNMEKYPDLNPIRRSFECVFPNELSFQGIDRGNPNSQLSLEQGPSASYSQGSLNGSSLDLSSSEGWRSNDRRNSNLMQANQTENHQLAESPGHLDSCELQVQLNNGDATPESYSLLPQHEERAVQLNNEFQINPCFVQLIDVKKENSSFSLAGNQQTRARTNQNEDSEVIELSSGDSDDGENFSEATTTIPSQPAPAYSRTPPTLRTDRRGDTSDTESSIIIRRRKRTGRKKRERLGSYLIRNIKIPMKTSWKTAVLARSANTSSQRRRKRGPRIPREENADFGGAELPAVCGNVQGFLNKEKFKQGIYVRSIRSETGRLFTPMDFEIEGNCEKAKNWRQTIRCKGWTLRELIQKGVLQDPPRKKKENPRNPRQMKRQVNAL
| null | null |
negative regulation of endothelial cell migration [GO:0010596]; negative regulation of protein export from nucleus [GO:0046826]; regulation of angiogenesis [GO:0045765]; regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902041]; regulation of Fas signaling pathway [GO:1902044]; regulation of transcription by RNA polymerase II [GO:0006357]; telomere maintenance [GO:0000723]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]; PML body [GO:0016605]
|
DNA binding [GO:0003677]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]
|
PF03172;PF01342;
|
3.10.390.10;
| null |
PTM: Sumoylated. Sumoylated with SUMO1. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting. Sumoylation may stabilize the interaction with CBX5 (By similarity). {ECO:0000250}.; PTM: Phosphorylated. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P23497}. Nucleus, PML body {ECO:0000250|UniProtKB:P23497}. Nucleus, nuclear body {ECO:0000250|UniProtKB:P23497}. Cytoplasm {ECO:0000250|UniProtKB:P23497}. Note=Accumulates in the cytoplasm upon FAS activation. {ECO:0000250|UniProtKB:P23497}.
| null | null | null | null | null |
FUNCTION: Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. May also play a role in infection by viruses through mechanisms that may involve chromatin and/or transcriptional regulation (By similarity). {ECO:0000250|UniProtKB:P23497}.
|
Mus caroli (Ryukyu mouse) (Ricefield mouse)
|
O35899
|
SC6A4_CAVPO
|
METTALNSQKAPSVCKDREDCQENSILQKSGPTSAGGVESGQIFNGYSSVPSTGMGDDAEHSVPTATTTLVAEVHHGERETWGKKVDFLLSVIGYAVDLGNIWRFPYVCYQNGGGAFLLPYIIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYTICIIAFYIASYYNTIIAWALYYLISSFTDRLPWTSCRNSWNTANCTNYFSEDNITWTLHSTSPAEEFYIRHILQIHRSKGLQDVGGVSWQLTLCIMLIFTIIYFSIWKGVKTSGKVVWVTATFPYIVLSVLLVRGATLPGAWKGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSAVNCMTSFVSGFVIFTVLGYMAEMRSEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHIWAKHREWFVLAVVITCFFGSLTTLTFGGAYVVKLLEEYATGPAVLTVVFIEAIAVSWFYGVTQFCSDVKEMLGFSPGWFWRICWVAVSPVFLLFIICSFLMSPPQLRLFQYSYPHWSVILGYCIGTSSVICIPTYITYRLVTTPGTLKERIIKSITPETPTEIPCGDICLNAV
| null | null |
membrane depolarization [GO:0051899]; platelet aggregation [GO:0070527]; regulation of thalamus size [GO:0090067]; serotonin uptake [GO:0051610]
|
endomembrane system [GO:0012505]; endosome membrane [GO:0010008]; focal adhesion [GO:0005925]; neuron projection [GO:0043005]; plasma membrane [GO:0005886]; presynapse [GO:0098793]; synapse [GO:0045202]
|
actin filament binding [GO:0051015]; antiporter activity [GO:0015297]; identical protein binding [GO:0042802]; integrin binding [GO:0005178]; monoatomic cation channel activity [GO:0005261]; serotonin binding [GO:0051378]; serotonin:sodium:chloride symporter activity [GO:0005335]; sodium ion binding [GO:0031402]
|
PF03491;PF00209;
| null |
Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family, SLC6A4 subfamily
|
PTM: Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation. {ECO:0000250|UniProtKB:P31645}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P31645}; Multi-pass membrane protein {ECO:0000255}. Endomembrane system {ECO:0000250|UniProtKB:P31652}; Multi-pass membrane protein {ECO:0000255}. Endosome membrane {ECO:0000250|UniProtKB:P31652}; Multi-pass membrane protein {ECO:0000255}. Synapse {ECO:0000250|UniProtKB:Q60857}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:Q60857}. Cell projection, neuron projection {ECO:0000250|UniProtKB:Q60857}. Note=Could be part of recycling endosomes. Density of transporter molecules on the plasma membrane is itself regulated by STX1A. Density of transporter molecules on the plasma membrane is also regulated by serotonin (By similarity). Density of transporter molecules seems to be modulated by ITGAV:ITGB3 (By similarity). {ECO:0000250|UniProtKB:P31645, ECO:0000250|UniProtKB:P31652, ECO:0000250|UniProtKB:Q60857}.
|
CATALYTIC ACTIVITY: Reaction=H(+)(in) + K(+)(in) + Na(+)(out) + serotonin(out) = H(+)(out) + K(+)(out) + Na(+)(in) + serotonin(in); Xref=Rhea:RHEA:75839, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103, ChEBI:CHEBI:350546; Evidence={ECO:0000250|UniProtKB:P31645, ECO:0000269|PubMed:8601815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75840; Evidence={ECO:0000250|UniProtKB:P31645, ECO:0000305|PubMed:8601815};
| null | null | null | null |
FUNCTION: Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (By similarity) (PubMed:8601815). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation. Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (By similarity) (PubMed:8601815). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity). {ECO:0000250|UniProtKB:P31645, ECO:0000250|UniProtKB:P31652, ECO:0000250|UniProtKB:Q60857, ECO:0000269|PubMed:8601815}.
|
Cavia porcellus (Guinea pig)
|
O35902
|
DSG3_MOUSE
|
MTCLFPRALGSLALLMVVLLVQGELHVKPGGQHREDGTALQLAKRRYKREWVKFAKPCREREDNSRRNPIAKITSDFQKNQKITYRISGVGIDQPPFGIFVVDPNNGDINITAIVDREETPSFLITCRALNALGQDVERPLILTVKILDVNDNPPIFSQTIFKGEIEENSASNSLVMILNATDADEPNHMNSKIAFKIVSQEPAGMSMFLISRNTGEVRTLTSSLDREQISSYHLVVSGADNDGTGLSTQCECSIKIKDVNDNFPVLRESQYSARIEENTLNAELLRFQVTDWDEEYTDNWLAVYFFTSGNEGNWFEIETDPRTNEGILKVVKALDYEQVQSMQFSIAVRNKAEFHQSVISQYRVQSTPVTIQVIDVREGISFRPPSKTFTVQRGVSTNKLVGYILGTYQATDEDTGKAASSVRYVLGRNDGGLLVIDSKTAQIKFVKNIDRDSTFIVNKTISAEVLAIDENTGKTSTGTIYVEVPSFNENCPSVVLEKKDICTSSPSVTLSVRTLDRGKYTGPYTVSLEEQPLKLPVMWTITTLNATSALLQAQQQVSPGVYNVPVIVKDNQDGLCDTPESLTLTVCQCDDRSMCRAPIPSREPNTYGESSWRLGPAAIGLILLGLLMLLLAPLLLLTCDCGSGPIGGAATGGFIPVPDGSEGTIHQWGIEGAQPEDKEITNICVPPVTTNGADFMESSEVCTNTYAGGTMVEGASGMEMITKLGGATGATAALGPCSLGYSGTMRTRHSTGGTLKDYAAPVNMTFLGSYFSQKSLAYAEEEDEREVNDCLLIYDDEGEDAAPHSPTLSSCSIFGDDLDDNFLDSLGPKFKKLAEICLGIDDEAKQAKPGPKDSGSGADTCARSMEVPQSGSNRYQTLPGSLEVTQTGSKICHTLSGNQETSVMSTSGSVHPAVAIPDPLQLGNYLLTETYSTSGSFAQPTTVTFDPHVTQNVTVTERVICPLPSASSSIVAPTELRGSYNMLYTKETCSHL
| null | null |
cell adhesion [GO:0007155]; cell-cell adhesion [GO:0098609]; homophilic cell adhesion via plasma membrane adhesion molecules [GO:0007156]
|
desmosome [GO:0030057]; plasma membrane [GO:0005886]; spot adherens junction [GO:0005914]
|
calcium ion binding [GO:0005509]
|
PF00028;
|
2.60.40.60;4.10.900.10;
| null | null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Cell junction, desmosome {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
|
Mus musculus (Mouse)
|
O35903
|
CCL25_MOUSE
|
MKLWLFACLVACFVGAWMPVVHAQGAFEDCCLGYQHRIKWNVLRHARNYHQQEVSGSCNLRAVRFYFRQKVVCGNPEDMNVKRAMRILTARKRLVHWKSASDSQTERKKSNHMKSKVENPNSTSVRSATLGHPRMVMMPRKTNN
| null | null |
cellular response to interleukin-1 [GO:0071347]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to type II interferon [GO:0071346]; chemokine-mediated signaling pathway [GO:0070098]; chemotaxis [GO:0006935]; eosinophil chemotaxis [GO:0048245]; G protein-coupled receptor signaling pathway [GO:0007186]; inflammatory response [GO:0006954]; leukocyte migration [GO:0050900]; lymphocyte chemotaxis [GO:0048247]; lymphoid lineage cell migration [GO:0097534]; monocyte chemotaxis [GO:0002548]; neutrophil chemotaxis [GO:0030593]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]
|
extracellular space [GO:0005615]
|
CCR chemokine receptor binding [GO:0048020]; chemokine activity [GO:0008009]; chemokine receptor binding [GO:0042379]
|
PF00048;
|
2.40.50.40;
|
Intercrine beta (chemokine CC) family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Potentially involved in T-cell development. Recombinant protein shows chemotactic activity on thymocytes, macrophages, THP-1 cells, and dendritics cells but is inactive on peripheral blood lymphocytes and neutrophils. Binds to CCR9. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.
|
Mus musculus (Mouse)
|
O35904
|
PK3CD_MOUSE
|
MPPGVDCPMEFWTKEESQSVVVDFLLPTGVYLNFPVSRNANLSTIKQVLWHRAQYEPLFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGDRVKKLINSQISLLIGKGLHEFDSLRDPEVNDFRTKMRQFCEEAAAHRQQLGWVEWLQYSFPLQLEPSARGWRAGLLRVSNRALLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVEQPEEYALQVNGRHEYLYGNYPLCHFQYICSCLHSGLTPHLTMVHSSSILAMRDEQSNPAPQVQKPRAKPPPIPAKKPSSVSLWSLEQPFSIELIEGRKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTKKKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVAPHPVYFPALEKILELGRHGERGRITEEELQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRFGLIMEAYCRGSTHHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCVEQCTFMDSKMKPLWIMYSSEEAGSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDNRQ
|
2.7.1.137; 2.7.1.153
| null |
adaptive immune response [GO:0002250]; B cell activation [GO:0042113]; B cell homeostasis [GO:0001782]; cell differentiation [GO:0030154]; cell migration [GO:0016477]; cell surface receptor signaling pathway [GO:0007166]; chemotaxis [GO:0006935]; defense response to fungus [GO:0050832]; homeostasis of number of cells [GO:0048872]; inflammatory response [GO:0006954]; innate immune response [GO:0045087]; negative regulation of gene expression [GO:0010629]; phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0043491]; phosphatidylinositol-3-phosphate biosynthetic process [GO:0036092]; phosphatidylinositol-mediated signaling [GO:0048015]; phosphorylation [GO:0016310]; positive regulation of angiogenesis [GO:0045766]; positive regulation of gene expression [GO:0010628]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; phosphatidylinositol 3-kinase complex [GO:0005942]; plasma membrane [GO:0005886]
|
1-phosphatidylinositol-3-kinase activity [GO:0016303]; 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934]; 1-phosphatidylinositol-4-phosphate 3-kinase activity [GO:0035005]; ATP binding [GO:0005524]; kinase activity [GO:0016301]
|
PF00454;PF00792;PF02192;PF00794;PF00613;
|
3.10.20.770;2.60.40.150;1.10.1070.11;1.25.40.70;
|
PI3/PI4-kinase family
|
PTM: Autophosphorylation on Ser-1038 results in the almost complete inactivation of the lipid kinase activity. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836, ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153; Evidence={ECO:0000250|UniProtKB:O00329}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293; Evidence={ECO:0000250|UniProtKB:O00329}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; EC=2.7.1.137; Evidence={ECO:0000250|UniProtKB:O00329}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710; Evidence={ECO:0000250|UniProtKB:O00329}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137, ChEBI:CHEBI:83243, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O00329}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397; Evidence={ECO:0000250|UniProtKB:O00329};
| null |
PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis. {ECO:0000305|PubMed:9235916}.
| null | null |
FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:9235916). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. {ECO:0000269|PubMed:12130661, ECO:0000269|PubMed:12235209, ECO:0000269|PubMed:15496927, ECO:0000269|PubMed:16116162, ECO:0000269|PubMed:18259608, ECO:0000269|PubMed:18809712, ECO:0000269|PubMed:19297623, ECO:0000269|PubMed:9235916}.
|
Mus musculus (Mouse)
|
O35906
|
SPIB_MOUSE
|
MLALEAAQLDGPHLSCLYPEGVFYDLDSCKPFSYPDSDGGLDSTWGWTEAPPAPAIAPYEAFDPATAAFSHSQTVQLCYSHGPNPSTYSPMGTLDPAPSLEAPGPGLQVYPPEDFTSQTLGSLAYAPYPSPVLSEEEDIMLDSPALEVSDSESDEALLAGSEGRGSEAGARKKLRLYQFLLGLLLRGDMRECVWWVEPGAGVFQFSSKHKELLARRWGQQKGNRKRMTYQKLARALRNYAKTGEIRKVKRKLTYQFDSALLPASRHV
| null | null |
immature B cell differentiation [GO:0002327]; macrophage differentiation [GO:0030225]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]
|
nucleus [GO:0005634]; transcription regulator complex [GO:0005667]
|
DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; sequence-specific DNA binding [GO:0043565]
|
PF00178;
|
1.10.10.10;
|
ETS family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q01892}.
| null | null | null | null | null |
FUNCTION: Sequence specific transcriptional activator which binds to the PU-box, a purine-rich DNA sequence (5'-GAGGAA-3') that can act as a lymphoid-specific enhancer. Promotes development of plasmacytoid dendritic cells (pDCs), also known as type 2 DC precursors (pre-DC2) or natural interferon (IFN)-producing cells. These cells have the capacity to produce large amounts of interferon and block viral replication. Required for B-cell receptor (BCR) signaling, which is necessary for normal B-cell development and antigenic stimulation. {ECO:0000269|PubMed:10229183, ECO:0000269|PubMed:11313289, ECO:0000269|PubMed:11672537, ECO:0000269|PubMed:11980719, ECO:0000269|PubMed:12431391, ECO:0000269|PubMed:8691135, ECO:0000269|PubMed:9384589}.
|
Mus musculus (Mouse)
|
O35910
|
MOT4_RAT
|
MGGAVVDEGPTGIKAPDGGWGWAVLFGCFIITGFSYAFPKAVSVFFKELMHEFGIGYSDTAWISSILLAMLYGTGPLCSMCVNRFGCRPVMLVGGLFASLGMVAASFCRSIIQIYLTTGVITGLGLALNFQPSLIMLNRYFNKRRPMANGLAAAGSPVFLCALSPLGQLLQDHYGWRGGFLILGGLLLNCCVCAALMRPLVAPQASGGAEPHGPQRPSPRLLDLSVFRDRGFLIYAVAASIMVLGLFVPPVFVVSYAKDMGVPDTKAAFLLTILGFIDIFARPTAGFITGLKKVRPYSVYLFSFAMFFNGFTDLTGSTASDYGGLVVFCIFFGISYGMVGALQFEVLMAIVGTQKFSSAIGLVLLLEAVAVLIGPPSGGKLLDATKVYKYVFILAGAEVLTSSLVLLLGNFFCIGKRKRPEVTKPEEVASEEEKLHKPPVDVRVDSREVEHFLKAEPEKNGEVVHTPETSV
| null | null |
lactate transmembrane transport [GO:0035873]; monocarboxylic acid transport [GO:0015718]; plasma membrane lactate transport [GO:0035879]; protein catabolic process [GO:0030163]; pyruvate catabolic process [GO:0042867]; pyruvate transmembrane transport [GO:1901475]
|
apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; lateral plasma membrane [GO:0016328]; parallel fiber to Purkinje cell synapse [GO:0098688]; plasma membrane [GO:0005886]; postsynaptic density membrane [GO:0098839]; synapse [GO:0045202]
|
lactate transmembrane transporter activity [GO:0015129]; lactate:proton symporter activity [GO:0015650]; pyruvate transmembrane transporter activity [GO:0050833]
|
PF07690;
|
1.20.1250.20;
|
Major facilitator superfamily, Monocarboxylate porter (TC 2.A.1.13) family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O15427}; Multi-pass membrane protein {ECO:0000250|UniProtKB:O15427}. Basolateral cell membrane {ECO:0000250|UniProtKB:O15427}; Multi-pass membrane protein {ECO:0000255}. Note=Plasma membrane localization is dependent upon the BSG/MCT4 interaction. Basolateral sorting signals (BLSS) in C-terminal cytoplasmic tail ensure its basolateral expression in polarised epithelial cells. {ECO:0000250|UniProtKB:O15427}.
|
CATALYTIC ACTIVITY: Reaction=(S)-lactate(in) + H(+)(in) = (S)-lactate(out) + H(+)(out); Xref=Rhea:RHEA:29415, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651; Evidence={ECO:0000269|PubMed:10926847, ECO:0000269|PubMed:9632638}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29416; Evidence={ECO:0000305|PubMed:10926847}; CATALYTIC ACTIVITY: Reaction=H(+)(out) + pyruvate(out) = H(+)(in) + pyruvate(in); Xref=Rhea:RHEA:64720, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378; Evidence={ECO:0000250|UniProtKB:O15427};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=10.1 mM for (S)-lactate {ECO:0000269|PubMed:9632638}; KM=33.7 mM for (S)-lactate {ECO:0000269|PubMed:10926847};
| null | null | null |
FUNCTION: Proton-dependent transporter of monocarboxylates such as L-lactate and pyruvate (By similarity) (PubMed:10926847, PubMed:9632638). Plays a predominant role in the L-lactate efflux from highly glycolytic cells (PubMed:10926847, PubMed:9632638). {ECO:0000250|UniProtKB:O15427, ECO:0000269|PubMed:10926847, ECO:0000269|PubMed:9632638}.
|
Rattus norvegicus (Rat)
|
O35913
|
SO1A4_RAT
|
MGKSEKRVATHGVRCFAKIKMFLLALTCAYVSKSLSGTYMNSMLTQIERQFGIPTSIVGLINGSFEIGNLLLIIFVSYFGTKLHRPIMIGVGCAVMGLGCFLISLPHFLMGQYEYETILPTSNVSSNSFFCVENRSQTLNPTQDPSECVKEMKSLMWIYVLVGNIIRGIGETPIMPLGISYIEDFAKSENSPLYIGILETGMTIGPLIGLLLASSCANIYVDIESVNTDDLTITPTDTRWVGAWWIGFLVCAGVNILTSFPFFFFPKTLPKEGLQENVDGTENAKEKKHRKKAKEEKRGITKDFFVFMKSLSCNPIYMLFILISVLQFNAFINSFTFMPKYLEQQYGKSTAEVVFLMGLYMLPPICLGYLIGGLIMKKFKVTVKKAAHLAFWLCLSEYLLSFLSYVMTCDNFPVAGLTTSYEGVQHQLYVENKVLADCNTRCNCSTNTWDPVCGDNGLAYMSACLAGCEKSVGTGTNMVFQNCSCIQSSGNSSAVLGLCNKGPDCANKLQYFLIIAIFGCFIYSLAGIPGYMVLLRCIKSEEKSLGVGLHAFCIRILAGIPAPIYFGALIDRTCLHWGTLKCGEPGACRMYDINSFRRLYLGLPAALRGASFVPAFFILRLTRTFQFPGDIESSKTDHAEMKLTLKESECTEVLRSKVTED
| null | null |
bile acid and bile salt transport [GO:0015721]; bile acid signaling pathway [GO:0038183]; cellular response to xenobiotic stimulus [GO:0071466]; monoatomic anion transport [GO:0006820]; regulation of bile acid secretion [GO:0120188]; response to estrogen [GO:0043627]; sodium-independent organic anion transport [GO:0043252]
|
basal plasma membrane [GO:0009925]; basolateral plasma membrane [GO:0016323]; membrane [GO:0016020]; plasma membrane [GO:0005886]
|
bile acid transmembrane transporter activity [GO:0015125]; organic anion transmembrane transporter activity [GO:0008514]; sodium-independent organic anion transmembrane transporter activity [GO:0015347]; transmembrane transporter activity [GO:0022857]
|
PF07648;PF03137;
|
1.20.1250.20;
|
Organo anion transporter (TC 2.A.60) family
| null |
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
|
CATALYTIC ACTIVITY: Reaction=estrone 3-sulfate(out) = estrone 3-sulfate(in); Xref=Rhea:RHEA:71835, ChEBI:CHEBI:60050; Evidence={ECO:0000305|PubMed:19129463}; CATALYTIC ACTIVITY: Reaction=taurocholate(out) = taurocholate(in); Xref=Rhea:RHEA:71703, ChEBI:CHEBI:36257; Evidence={ECO:0000305|PubMed:19129463}; CATALYTIC ACTIVITY: Reaction=prostaglandin E2(out) = prostaglandin E2(in); Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564; Evidence={ECO:0000305|PubMed:19129463}; CATALYTIC ACTIVITY: Reaction=L-thyroxine(out) = L-thyroxine(in); Xref=Rhea:RHEA:71819, ChEBI:CHEBI:58448; Evidence={ECO:0000305|PubMed:19129463};
| null | null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 6.5 with estrone 3-sulfate, taurocholate, prostaglandin E2 and L-thyroxine (T4) as substrates. {ECO:0000269|PubMed:19129463};
| null |
FUNCTION: Mediates the Na(+)-independent transport of organic anions such as taurocholate, cholate, 17-beta-glucuronosyl estradiol, prostaglandin E2, estrone 3-sulfate, L-thyroxine (T4), the cardiac glycosides ouabain and digoxin and thyroid hormones (PubMed:19129463). May play an especially important role in the brain accumulation and toxicity of digoxin and in the hepatobiliary and renal excretion of cardiac glycosides. Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). {ECO:0000269|PubMed:19129463}.
|
Rattus norvegicus (Rat)
|
O35914
|
BNC1_MOUSE
|
MAEAIGCTLNCSCQCFKPGKINHRQCEQCRHGWVAHALSKLRIPPVYPTSQVEIVQSNVVFDISSLMLYGTQAIPVRLKILLDRLFSVLKQDEVLQILHALDWTLQDYIRGYVLQDASGKVLDHWSIMTSEEEVATLQQFLRFGETKSIVELMAIQEKEEQSVIVPPTTANVDIRAFIESCGHRSASLPTPVDKGSPGGMHPFENLISNMTFMLPFQFFNPLPPALIGSLPEQYMLEQGQDQSQEPKQELHGPFSDSSFLTSTPFQVEKEQCLNCPETVPQKEDSAHLSDSSSYSIASKLERTQLSPEAKVKPERNSLSAKKGRVFCTACEKTFYDKGTLKIHYNAVHLKIKHKCTIEGCNMVFSSLRSRNRHSANPNPRLHMPMNRNNRDKDLRNSLNLASSETYKRPGFTVVSPDCGPLPGYTGSVEDSKGQPAFSSIGQNGVLFPNLKTVQPVLPFYRSPATPAELANTPGMLPSLPLLSSSIPEQLVSTDMPFDALPKKKSRKSSMPIKIEKEAVEIAEEKRHSLSSDDEVPLQVVSEDEPEDSSPRSDRVPEEQHTQLSLEEPLPQGERACHLESVIESHGALSRTLEQTTLTEREAEQKVALSSVMPREVEDGGHERHFTAGLVPQIPFPDYMELQQRLLAGGLFGALSNRGMAFPFLEESKELEHLGEHALVRQKEEARFQCDICKKTFKNACSMKTHEKNTHARETHACTVEGCGAAFPSRRSRDRHSSNLSLHQKVLNEEALETSEDHFRAAYLLQDVAKEAYQDVAFTPQASQTSVIFKGTSGMGSLVYPISQVHSASLESYNSGPPSEGTILDLSTTSSMKSESSSHSSWDSDGVSEEGTALMEDSDGNCEGQSLVSGEDEYPLCVLMEKADQSLASLPSGLPITCHLCQKIYSNKGTFRAHYKTVHLRQLHKCKVPGCNTMFSSVRSRNRHSQNPNLHKSLASSPSHLQ
| null | null |
cell differentiation [GO:0030154]; chromosome organization [GO:0051276]; epithelial cell proliferation [GO:0050673]; positive regulation of epithelial cell proliferation [GO:0050679]; regulation of transcription by RNA polymerase I [GO:0006356]; regulation of transcription by RNA polymerase II [GO:0006357]; spermatogenesis [GO:0007283]; wound healing [GO:0042060]
|
cytoplasm [GO:0005737]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
DNA binding [GO:0003677]; metal ion binding [GO:0046872]
|
PF00096;PF12874;
|
3.30.160.60;
| null |
PTM: Phosphorylation on Ser-505 and Ser-509 leads to cytoplasmic localization. {ECO:0000250|UniProtKB:Q01954}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23707421, ECO:0000269|PubMed:9687312}. Cytoplasm {ECO:0000269|PubMed:23707421, ECO:0000269|PubMed:9687312}. Nucleus, nucleoplasm {ECO:0000269|PubMed:23707421}. Note=Relocates to the midpiece of the flagellum during late spermiogenesis in spermatids. {ECO:0000269|PubMed:9687312}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator (PubMed:23707421, PubMed:9687312). It is likely involved in the regulation of keratinocytes terminal differentiation in squamous epithelia and hair follicles (By similarity). Required for the maintenance of spermatogenesis (PubMed:22266914). It is involved in the positive regulation of oocyte maturation, probably acting through the control of BMP15 levels and regulation of AKT signaling cascade (By similarity). May also play a role in the early development of embryos (PubMed:9687312). {ECO:0000250|UniProtKB:Q01954, ECO:0000269|PubMed:22266914, ECO:0000269|PubMed:23707421, ECO:0000269|PubMed:9687312}.
|
Mus musculus (Mouse)
|
O35921
|
EAA4_RAT
|
MSSHGNSLFLRESGAGGGCLQGLQDSLQQRALRTRLRLQTMTREHVRRFLRRNAFILLTVSAVIIGVSLAFALRPYQLTYRQIKYFSFPGELLMRMLQMLVLPLIVSSRVTGMASLDNKATGRMGMRAAVYYMVTTVIAVFIGILMVTIIHPGKGSKEGLHREGRIETVPTADAFMDLVRNMFPPNLVEACFKQFKTQYSTRVVTRTIVRTDNGSELGASISPPSSAENETSILENVTRALGTLQEVISFEETVPVPGSANGINALGLVVFSVAFGLVIGGMKHKGRVLRDFFDSLNEAIMRLVGIIIWYAPVGILFLIAGKILEMEDMAVLGGQLGMYTLTVIVGLFLHAGGVLPLIYFLVTHRNPFPFIGGILQALITAMGTSSSSATLPITFRCLEEGLGVDRRITRFVLPVGATVNMDGTALYEALAAIFIAQVNNYELNLGQITTISITATAASVGAAGIPQAGLVTMVIVLTSVGLPTEDITLIIAVDWFLDRLRTMTNVLGDSIGAAVIEHLSQRELELQEAELTLPSLGKPYKSLMAQAKGASRGRGGNESVM
| null | null |
establishment of localization in cell [GO:0051649]; L-aspartate import across plasma membrane [GO:0140009]; L-glutamate import across plasma membrane [GO:0098712]; L-glutamate transmembrane transport [GO:0015813]; neurotransmitter uptake [GO:0001504]; regulation of membrane potential [GO:0042391]
|
glutamatergic synapse [GO:0098978]; Golgi apparatus [GO:0005794]; membrane [GO:0016020]; membrane protein complex [GO:0098796]; parallel fiber to Purkinje cell synapse [GO:0098688]; plasma membrane [GO:0005886]; postsynaptic membrane [GO:0045211]; presynaptic membrane [GO:0042734]
|
glutamate:sodium symporter activity [GO:0015501]; high-affinity L-glutamate transmembrane transporter activity [GO:0005314]; L-aspartate transmembrane transporter activity [GO:0015183]; L-glutamate transmembrane transporter activity [GO:0005313]; metal ion binding [GO:0046872]; monoatomic anion transmembrane transporter activity [GO:0008509]; neutral L-amino acid transmembrane transporter activity [GO:0015175]
|
PF00375;
|
1.10.3860.10;
|
Dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family, SLC1A6 subfamily
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26690923}; Multi-pass membrane protein {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=H(+)(out) + K(+)(in) + L-glutamate(out) + 3 Na(+)(out) = H(+)(in) + K(+)(out) + L-glutamate(in) + 3 Na(+)(in); Xref=Rhea:RHEA:70699, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103, ChEBI:CHEBI:29985; Evidence={ECO:0000250|UniProtKB:P48664}; CATALYTIC ACTIVITY: Reaction=H(+)(out) + K(+)(in) + L-aspartate(out) + 3 Na(+)(out) = H(+)(in) + K(+)(out) + L-aspartate(in) + 3 Na(+)(in); Xref=Rhea:RHEA:70851, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103, ChEBI:CHEBI:29991; Evidence={ECO:0000250|UniProtKB:P48664}; CATALYTIC ACTIVITY: Reaction=D-aspartate(out) + H(+)(out) + K(+)(in) + 3 Na(+)(out) = D-aspartate(in) + H(+)(in) + K(+)(out) + 3 Na(+)(in); Xref=Rhea:RHEA:71379, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103, ChEBI:CHEBI:29990; Evidence={ECO:0000250|UniProtKB:P48664};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=328 uM for L-glutamate {ECO:0000269|PubMed:26690923};
| null | null | null |
FUNCTION: Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:14506254, PubMed:26690923). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:14506254). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:14506254). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (Probable). {ECO:0000269|PubMed:14506254, ECO:0000269|PubMed:26690923, ECO:0000305}.
|
Rattus norvegicus (Rat)
|
O35923
|
BRCA2_RAT
|
MTVEYKRRPTFWEIFKARCSTADLGPISLNWFEELFSEAPPYNTEHPEESEYKPQGHEPQLFKTPQRNPSYHQFASTPIMFKEQSQTLPLDQSPFKELGNVVANSKRKHHSKKKARKDPVVDVASLPLKACPSESPCTPRCTQVAPQRRKPVVSGSLFYTPKLEETPKHISESLGVEVDPDMSWTSSLATPPTLSSTVLIARDEEAHRNAFPADSPASLKSYFSNHNESLKKNDRFIPSVSDSENKSQQEAFSQGLEKMLGDSSSKINRFRDCLRKPIPNVLEDGETAVDTSGEDSFSLCFPKRRTRNLQKTRMGKMKKKIFSETRTDGLSEEARGQADDKNSFALEIEPRDSEPLDPSVTNQKPLYSQSGDISSEAGQCSDSIWSQPDPSGLNGTQTRKIPLLHISFHKQSILEDFIDMKKEGTGSITFPHISSLPEPEKMFSEETLVDKEHEGQHLESLEDSISGKQMVSGTSQTACLSPSIRKSIVKMREPLEETLDTVFSDSMTSSAFTEELDASAGGLEIHTACSQREDSLCPSSVDTGSWPTTLTDTSATVKNAGLITTLKNKRRKFIYSVSDDASHQGKKLQTQRQSELTNLSAPFEASAFEVPFPFTNVDSGIPDSSIKRSNLPNDPEEPSLSLTNSFVTAASKEISYIHALISQDLNDKEAILSEEKPQPYTALEADFLSCLPERSCENDQKSPKVSDRKEKVLVSACRPSGRLAAAVQLSSISFDSQENPLGSHNVTSTLKLTPSPKTPLSKPVVVSRGKMCKMPEKLQCKSCKDNIELSKNIPLGVNEMCVLSENSETPELLPPLEYITEVSSSVKSQFNQNTKIAVVQKDQKDSTFISEVTVHMNSEELFPEKENNFAFQVTNESNKPNIGSTVEFQEEDLSHAKGHSLKNSPMTVDRDLDDEQAGQVLITEDSDSLAVVHDCTKKSRNTIEQHQKGTADKDFKSNSSLYLKSDGNNDYLDKWSEFLDPLMNHKLGGSFRTASNKEIKLSEDNVKKSKMFFKDIEEQYPTSLDCIDTVSTLQLANKKRLSEPHTFDLKSGTTVSTQCHSQSSVSHEDTHTAPQMLSSKQDFHSSHNLTPSQKAEITELSTILEESGSQFEFTQFKNPSHIAQNNTSAVLGNQMAVVRTASEEWKDVDLHLPLNPSSVGQIDHNKKFECLVGVKQSSSHLLEDTCNQNTSCFLPIKEMEFGGFCSALGTKLSVSNEALRKAMKLFSDIENISEEPSTKVGPRGFSSCAHHDSVASVFKIKKQNTDKSFDEKSSKCQVTVQNNKEMTTCILVDENPENYVKNIKQDNNYTGSQRNAYKLENSDVSKSSTSGTVYINKGDSDLPFAAEKGNKYPESCTQYVREENAQIKESVSDLTCLEVMKAEETCHMKSSDKEQLPSDKMEQNMKEFNISFQTASGKNIRVSKESLNKSVNILDQETEDLTVTSDSLNSKILCGINKDKMHISCHKKSINIKKVFEEHFPIGTVSQLPALQQYPEYEIESIKEPTLLSFHTASGKKVKIMQESLDKVKNLFDETQYVRKTTNFGHQESKPLKDREDYKERLTLAYEKIEVTASKCEEMQNFVSKQTEMLPQQNDHMYRQTENLTSNGSSPKVHGNIENKIEKNPRICCICQSSYFVTEDSALACYTGDSRKTCVGESSLSKGKKWLREQSDKLGTRNTIEIQCVKEHTEDFAGNALYEHSLVIIRTEIDTSHVSENQASTLFSDPNVCHSYLSHSSFCHHDDMHNDSGYFLKDKIDSDVQPDMKNTEGNAIFPKISATKEIKLHPQTVNEECVQKLETNASPYANKNIAIDSAMLDLRNCKVGSPVFITTHSQETVRMKEIFTDNCSKIVEQNRESKPDTCQTSCHKALDNSEDFICPSSSGDVCINSPMAIFYPQSEQILQHNQSVSGLKKAATPPVSLETWDTCKSIRGSPQEVHPSRTYGFFSTASGKAVQVSDASLEKARQVFSEIDGDAKQLASMVSLEGNEKSHHSVKRESSVVHNTHGVLSLRKTLPGNVSSFVFSGFSTAGGKLVTVSESALHKVKGMLEEFDLIRTEHTLQHSPTPEDVSKIPPQPCLESRTPEYSVSSKLQKTYNDKSRSPSNYKESGSSGNTQSLEVSPQLSQMERKQETQSVLGTKVSQRKTNILEKKQNLPQNIKIESNKMETFSDVSMKTNVGEYYSKEPENYFETEAVEIAKAFMEDDELTDSEQTHAKCSLFACPQNEALLNSRTRKRGGMAGVAVGQPPIKRSLLNEFDRIIESKGKSLTPSKSTPDGTIKDRRLFTHHMSLEPVTCGPFCSSKERQETQSPHVTSPAQGLQSKEHPSRHSAVGKSSSNPTVSALRSERTRHSVSDKSTKVFVPPFKVKSRFHRDEHFDSKNVNLEGKNQKSADGVSEDGNDSDFPQFNKDLMSSLQNARDLQDIRIKNKERHHLCPQPGSLYLTKSSTLPRISLQAAVGDSVPSACSPKQLYMYGVSKACISVNSKNAEYFQFAIEDHFGKEALCAGKGFRLADGGWLIPSDDGKAGKEEFYRALCDTPGVDPKLISSVWVSNHYRWIVWKLAAMEFAFPKEFANRCLNPERVLLQLKYRYDVEIDNSSRSALKKILERDDTAAKTLVLCVSDIISLSTNVSETSGSKASSEDSNKVDTIELTDGWYAVKAQLDPPLLALVKSGRLTVGQKIITQGAELVGSPDACAPLEAPDSLRLKISANSTRPARWHSKLGFFHDPRPFPLPLSSLFSDGGNVGCVDVIVQRVYPLQWVEKTVSGSYIFRNEREEEKEALRFAEAQQKKLEALFTKVHTELKEHEEDIAQRRVLSRALTRQQVHALQDGAELYAAVQDASDPEHLETCFSEEQLRALNNYRQMLSDKKQARIQSEFRKALEAAEKEEGLSRDVSTVWKLRVTSYKKREKSALLSIWRPSSDLPSLLTEGQRYRIYHLSVSKSKNKFEWPSIQLTATKRTQYQQLPVSSETLLQLYQPRELLPFSKLSDPAFQPPCSEVDVVGVVVSVVKPIGLAPLVYLSDECLHLLVVKFGIDLNEDIKPRVLIAASNLQWRPESTSRVPTLFAGNFSVFSASPKEAHFQERVTNMKHAIENIDTFYKEAEKKLIQVLKGDSPKWSTPNKDPTREPYPASTCSASDLASGGQLPRSSPTDQQSYRSPLSCCTPTGKSTPLAHSAWMAAKSCSGENEIEDPKTCRKKRALDLLSRLPLPPPLSPVCTFVSPAAQKAFQPPRSCGTKYPTPLKKEGPSSPWSRAPFQKASGVSLLDCDSVADEELALLSTQALVPHSVGGSEQVFPSDSTRTEGPSASTEARPANRSKRESLRDCRDDSDGKLAAETVPDYS
| null | null |
brain development [GO:0007420]; cell population proliferation [GO:0008283]; cellular response to ionizing radiation [GO:0071479]; cellular senescence [GO:0090398]; centrosome duplication [GO:0051298]; chordate embryonic development [GO:0043009]; chromosome organization [GO:0051276]; DNA damage response [GO:0006974]; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator [GO:0006978]; DNA recombination [GO:0006310]; double-strand break repair [GO:0006302]; double-strand break repair via homologous recombination [GO:0000724]; establishment of protein localization to telomere [GO:0070200]; female gonad development [GO:0008585]; hematopoietic stem cell proliferation [GO:0071425]; hemopoiesis [GO:0030097]; homologous chromosome orientation in meiotic metaphase I [GO:0031619]; inner cell mass cell proliferation [GO:0001833]; intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630]; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771]; male meiosis I [GO:0007141]; mammary gland development [GO:0030879]; mitotic recombination-dependent replication fork processing [GO:1990426]; multicellular organism growth [GO:0035264]; negative regulation of mammary gland epithelial cell proliferation [GO:0033600]; nucleotide-excision repair [GO:0006289]; oocyte maturation [GO:0001556]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of mitotic cell cycle [GO:0045931]; regulation of cytokinesis [GO:0032465]; regulation of DNA-templated transcription [GO:0006355]; replication fork processing [GO:0031297]; response to estradiol [GO:0032355]; response to gamma radiation [GO:0010332]; response to nutrient [GO:0007584]; response to UV-C [GO:0010225]; response to X-ray [GO:0010165]; spermatogenesis [GO:0007283]; stem cell proliferation [GO:0072089]; telomere maintenance via recombination [GO:0000722]
|
BRCA2-MAGE-D1 complex [GO:0033593]; centrosome [GO:0005813]; chromosome [GO:0005694]; chromosome, telomeric region [GO:0000781]; cytoplasm [GO:0005737]; DNA repair complex [GO:1990391]; lateral element [GO:0000800]; nuclear ubiquitin ligase complex [GO:0000152]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; secretory granule [GO:0030141]
|
gamma-tubulin binding [GO:0043015]; histone H3 acetyltransferase activity [GO:0010484]; histone H4 acetyltransferase activity [GO:0010485]; identical protein binding [GO:0042802]; protease binding [GO:0002020]; single-stranded DNA binding [GO:0003697]
|
PF09169;PF09103;PF09104;PF00634;PF21318;PF09121;
|
6.10.70.10;2.40.50.140;
| null |
PTM: Phosphorylated by ATM upon irradiation-induced DNA damage. Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. Phosphorylation at Ser-3222 by CDK1 and CDK2 is low in S phase when recombination is active, but increases as cells progress towards mitosis; this phosphorylation prevents homologous recombination-dependent repair during S phase and G2 by inhibiting RAD51 binding. {ECO:0000250|UniProtKB:P51587}.; PTM: Ubiquitinated in the absence of DNA damage; this does not lead to proteasomal degradation. In contrast, ubiquitination in response to DNA damage leads to proteasomal degradation. {ECO:0000250|UniProtKB:P51587}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P51587}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:P51587}.
| null | null | null | null | null |
FUNCTION: Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability, independently of its known role in homologous recombination (By similarity). {ECO:0000250|UniProtKB:P51587, ECO:0000250|UniProtKB:P97929}.
|
Rattus norvegicus (Rat)
|
O35926
|
CD5R2_MOUSE
|
MGTVLSLSPASSAKGRRPGGLPEEKKKAPPAGDEALGGYGAPPAGKGGKGESRLKRPSVLISALTWKRLVAASAKKKKGSKKVTPKPASTGPDPLVQQRNRENLLRKGRDGPDGGGTAKPLAVPVPTVPTTAATCEPPSGGSAAAPPPGSGGGKPPPPPPPAPQAAPPAPGGSPRRVIVQASTGELLRCLGDFVCRRCYRLKELSPGELVGWFRGVDRSLLLQGWQDQAFITPANLVFVYLLCRESLRGDELASAAELQAAFLTCLYLAYSYMGNEISYPLKPFLVEPDKERFWQRCLRLIQRLSPQMLRLNADPHFFTQVFQDLKNEGEAAASTGGPPSGSSASTTSSSSARDSCATGAKHWTMNLDR
| null | null |
axon guidance [GO:0007411]; brain development [GO:0007420]; cerebellum development [GO:0021549]; hippocampus development [GO:0021766]; layer formation in cerebral cortex [GO:0021819]; neuron migration [GO:0001764]; positive regulation of calcium ion-dependent exocytosis [GO:0045956]; superior olivary nucleus maturation [GO:0021722]
|
cytoplasm [GO:0005737]; growth cone [GO:0030426]; membrane [GO:0016020]; neuron projection [GO:0043005]; plasma membrane [GO:0005886]; protein kinase 5 complex [GO:0016533]
|
actin binding [GO:0003779]; cyclin-dependent protein serine/threonine kinase activator activity [GO:0061575]; cytoskeletal protein binding [GO:0008092]; lipid binding [GO:0008289]; protein kinase binding [GO:0019901]
|
PF03261;
|
1.10.472.10;
|
Cyclin-dependent kinase 5 activator family
|
PTM: Myristoylated. The Gly-2-Ala mutant is absent of the cell periphery, suggesting that a proper myristoylation signal is essential for the proper distribution of CDK5R2 (p39) (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Activator of CDK5/TPKII.
|
Mus musculus (Mouse)
|
O35927
|
CTND2_MOUSE
|
MFARKQSGAAPFGAMPVPDQPPSASEKNSSLSPGLNTSNGDGSETETTSAILASVKEQELQFERLTRELEAERQIVASQLERCKLGSETGSMSSISSAGEQFHWQTQDGQKDIEDELTTGLELVDSCIRSLQESGILDPQDYSTSERPSLLSQSALQLNSKPEGSFQYPASYHSNQTLALGDTAPSQLPARSTQARAAGQSFSQGTTGRAGHLAGSEPAPPPPPPREPFAPSLGSAFHLPDAPPAAAALYYSSSTLPAPPRGGSPLTTTQGGSPTKLQRGGSAPEGAAYAAPRGSSPKQSPSRLAKSYSTSSPINIVVSSAGLSPIRVTSPPTVQSTISSSPIHQLSSTIGTYATLSPTKRLVHASEQYSKHSQELYATATLQRPGSLAAGSRASYSSQHGHLAPELRALQSPEHHIDPIYEDRVYQKPPMRSLSQSQGDPLPPAHTGTFRTSTAPSSPGVDSVPLQRTGSQHGPQNAAAATFQRASYAAGPASNYADPYRQLQYCASVDSPYSKSGPALPPEGTLARSPSIDSIQKDPREFGWRDPELPEVIQMLQHQFPSVQSNAAAYLQHLCFGDNKIKAEIRRQGGIQLLVDLLDHRMTEVHRSACGALRNLVYGKANDDNKIALKNCGGIPALVRLLRKTTDLEIRELVTGVLWNLSSCDALKMPIIQDALAVLTNAVIIPHSGWENSPLQDDRKIQLHSSQVLRNATGCLRNVSSAGEEARRRMRECDGLTDALLYVIQSALGSSEIDSKTVENCVCILRNLSYRLAAETSQGQHMGTDELDGLLCGETNGKDTESSGCWGKKKKKKKSQDQWDGVGPLPDCAEPPKGIQMLWHPSIVKPYLTLLSECSNPDTLEGAAGALQNLAAGSWKGWAEDVAGMAYALRSLPEGAPCLPQWSVYIRAAVRKEKGLPILVELLRIDNDRVVCAVATALRNMALDVRNKELIGKYAMRDLVHRLPGGNNSNNSGSKAMSDDTVTAVCCTLHEVITKNMENAKALRDAGGIEKLVGISKSKGDKHSPKVVKAASQVLNSMWQYRDLRSLYKKDGWSQYHFVASSSTIERDRQRPYSSSRTPSISPVRVSPNNRSASAPASPREMISLKERKTDYESAGNNATYHGTKGEHTSRKDTMTAQNTGVSTLYRNSYGAPAEDIKQNQVSTQPVPQEPSRKDYETYQPFPNSTRNYDESFFEDQVHHRPPASEYTMHLGLKSTGNYVDFYSAARPYSELNYETSHYPASPDSWV
| null | null |
cell-cell adhesion [GO:0098609]; cell-cell junction assembly [GO:0007043]; dendritic spine morphogenesis [GO:0060997]; learning [GO:0007612]; morphogenesis of a branching structure [GO:0001763]; regulation of postsynaptic membrane neurotransmitter receptor levels [GO:0099072]; regulation of synaptic plasticity [GO:0048167]
|
adherens junction [GO:0005912]; cytoplasm [GO:0005737]; dendrite [GO:0030425]; glutamatergic synapse [GO:0098978]; nucleus [GO:0005634]; perikaryon [GO:0043204]; plasma membrane [GO:0005886]; postsynaptic density [GO:0014069]
|
cadherin binding [GO:0045296]; structural constituent of postsynaptic density [GO:0098919]
|
PF00514;
|
1.25.10.10;
|
Beta-catenin family
|
PTM: O-glycosylated. {ECO:0000269|PubMed:16452088}.; PTM: Phosphorylated by CDK5 (By similarity). Phosphorylated by GSK3B (PubMed:19706605). {ECO:0000250|UniProtKB:O35116, ECO:0000269|PubMed:19706605}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15282317}. Cell junction, adherens junction {ECO:0000269|PubMed:10753311}. Cell projection, dendrite {ECO:0000250|UniProtKB:O35116}. Perikaryon {ECO:0000250|UniProtKB:O35116}.
| null | null | null | null | null |
FUNCTION: Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:17993462, PubMed:25807484). Involved in the regulation of canonical Wnt signaling (By similarity). It probably acts on beta-catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (PubMed:20623542). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules. Functions as a transcriptional activator when bound to ZBTB33 (PubMed:15282317). {ECO:0000250|UniProtKB:Q9UQB3, ECO:0000269|PubMed:15282317, ECO:0000269|PubMed:17993462, ECO:0000269|PubMed:20623542, ECO:0000269|PubMed:25807484, ECO:0000269|PubMed:9971746}.
|
Mus musculus (Mouse)
|
O35929
|
REM1_MOUSE
|
MTLNTQQEAKTTLRRRASTPLPLSSRGHQPGRLCTAPSAPSQHPRLGQSVSLNPPVRKPSPAQDGWSSESSDSEGSWEALYRVVLLGDPGVGKTSLASLFAEKQDRDPHEQLGGVYERTLSVDGEDTTLVVMDTWEAEKLDESWCQESCLQAGSAYVIVYSIADRSSFESASELRIQLRRTHQANHVPIILVGNKADLARCREVSVEEGRACAVVFDCKFIETSATLQHNVTELFEGVVRQLRLRRQDNAAPETPSPRRRASLGQRARRFLARLTARSARRRALKARSKSCHNLAVL
| null | null |
negative regulation of calcium ion transmembrane transport via high voltage-gated calcium channel [GO:1904878]; regulation of skeletal muscle contraction by calcium ion signaling [GO:0014722]
|
I band [GO:0031674]; plasma membrane [GO:0005886]; T-tubule [GO:0030315]
|
calcium channel regulator activity [GO:0005246]; calmodulin binding [GO:0005516]; GTP binding [GO:0005525]; GTPase activity [GO:0003924]; transmembrane transporter binding [GO:0044325]
|
PF00071;
|
3.40.50.300;
|
Small GTPase superfamily, RGK family
| null | null | null | null | null | null | null |
FUNCTION: Promotes endothelial cell sprouting and actin cytoskeletal reorganization (By similarity). May be involved in angiogenesis. May function in Ca(2+) signaling. {ECO:0000250}.
|
Mus musculus (Mouse)
|
O35930
|
GP1BA_MOUSE
|
MALLILLFLLPSPLHSQHTCSISKVTSLLEVNCENKKLTALPADLPADTGILHLGENQLGTFSTASLVHFTHLTYLYLDRCELTSLQTNGKLIKLENLDLSHNNLKSLPSLGWALPALTTLDVSFNKLGSLSPGVLDGLSQLQELYLQNNDLKSLPPGLLLPTTKLKKLNLANNKLRELPSGLLDGLEDLDTLYLQRNWLRTIPKGFFGTLLLPFVFLHANSWYCDCEILYFRHWLQENANNVYLWKQGVDVKDTTPNVASVRCANLDNAPVYSYPGKGCPTSSGDTDYDDYDDIPDVPATRTEVKFSTNTKVHTTHWSLLAAAPSTSQDSQMISLPPTHKPTKKQSTFIHTQSPGFTTLPETMESNPTFYSLKLNTVLIPSPTTLEPTSTQATPEPNIQPMLTTSTLTTPEHSTTPVPTTTILTTPEHSTIPVPTTAILTTPKPSTIPVPTTATLTTLEPSTTPVPTTATLTTPEPSTTLVPTTATLTTPEHSTTPVPTTATLTTPEHSTTPVPTTATLTTPEPSTTLTNLVSTISPVLTTTLTTPESTPIETILEQFFTTELTLLPTLESTTTIIPEQNSFLNLPEVALVSSDTSESSPFLNSDFCCFLPLGFYVLGLLWLLFASVVLILLLTWTWHVTPHSLDMEQSAALATSTHTTSLEVQRARQVTMPRAWLLFLQGSLPTFRSSLFLWVRPNGRVGPLVAGRRPSALSQGRGQDLLGTVGIRYSGHSL
| null | null |
blood coagulation [GO:0007596]; blood coagulation, intrinsic pathway [GO:0007597]; cell adhesion [GO:0007155]; cell morphogenesis [GO:0000902]; fibrinolysis [GO:0042730]; hemostasis [GO:0007599]; megakaryocyte development [GO:0035855]; positive regulation of leukocyte tethering or rolling [GO:1903238]; positive regulation of platelet activation [GO:0010572]; release of sequestered calcium ion into cytosol [GO:0051209]
|
cell surface [GO:0009986]; external side of plasma membrane [GO:0009897]; extracellular matrix [GO:0031012]; extracellular space [GO:0005615]; glycoprotein Ib-IX-V complex [GO:1990779]; membrane [GO:0016020]; plasma membrane [GO:0005886]
| null |
PF13855;
|
3.80.10.10;
| null |
PTM: O-glycosylated. {ECO:0000250}.; PTM: Glycocalicin is the product of a proteolytic cleavage/shedding, catalyzed by ADAM17, which releases most of the extracellular domain. Binding sites for vWF and thrombin are in this part of the protein. {ECO:0000269|PubMed:12907434}.
|
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
| null | null | null | null | null |
FUNCTION: GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. {ECO:0000250}.
|
Mus musculus (Mouse)
|
O35936
|
ALOX8_MOUSE
|
MAKCRVRVSTGEACGAGTWDKVSVSIVGTHGESPLVPLDHLGKEFSAGAEEDFEVTLPQDVGTVLMLRVHKAPPEVSLPLMSFRSDAWFCRWFELEWLPGAALHFPCYQWLEGAGELVLREGAAKVSWQDHHPTLQDQRQKELESRQKMYSWKTYIEGWPRCLDHETVKDLDLNIKYSAMKNAKLFFKAHSAYTELKVKGLLDRTGLWRSLREMRRLFNFRKTPAAEYVFAHWQEDAFFASQFLNGINPVLIRRCHSLPNNFPVTDEMVAPVLGPGTSLQAELEKGSLFLVDHGILSGVHTNILNGKPQFSAAPMTLLHQSSGSGPLLPIAIQLKQTPGPDNPIFLPSDDTWDWLLAKTWVRNSEFYIHEAVTHLLHAHLIPEVFALATLRQLPRCHPLFKLLIPHIRYTLHINTLARELLVAPGKLIDKSTGLGTGGFSDLIKRNMEQLNYSVLCLPEDIRARGVEDIPGYYYRDDGMQIWGAIKSFVSEIVSIYYPSDTSVQDDQELQAWVREIFSEGFLGRESSGMPSLLDTREALVQYITMVIFTCSAKHAAVSSGQFDSCVWMPNLPPTMQLPPPTSKGQARPESFIATLPAVNSSSYHIIALWLLSAEPGDQRPLGHYPDEHFTEDAPRRSVAAFQRKLIQISKGIRERNRGLALPYTYLDPPLIENSVSI
|
1.13.11.-; 1.13.11.58
|
COFACTOR: Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250|UniProtKB:O15296, ECO:0000255|PROSITE-ProRule:PRU00726}; Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:O15296, ECO:0000255|PROSITE-ProRule:PRU00726};
|
arachidonic acid metabolic process [GO:0019369]; cannabinoid biosynthetic process [GO:1901696]; endocannabinoid signaling pathway [GO:0071926]; hepoxilin biosynthetic process [GO:0051122]; linoleic acid metabolic process [GO:0043651]; lipid oxidation [GO:0034440]; lipoxin A4 biosynthetic process [GO:2001303]; lipoxygenase pathway [GO:0019372]; negative regulation of cell cycle [GO:0045786]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of growth [GO:0045926]; phospholipid metabolic process [GO:0006644]; positive regulation of chemokine production [GO:0032722]; positive regulation of keratinocyte differentiation [GO:0045618]; positive regulation of macrophage derived foam cell differentiation [GO:0010744]; positive regulation of peroxisome proliferator activated receptor signaling pathway [GO:0035360]
|
adherens junction [GO:0005912]; cytoskeleton [GO:0005856]; cytosol [GO:0005829]; focal adhesion [GO:0005925]; plasma membrane [GO:0005886]
|
arachidonate 15-lipoxygenase activity [GO:0050473]; arachidonate 8(S)-lipoxygenase activity [GO:0036403]; calcium ion binding [GO:0005509]; iron ion binding [GO:0005506]; linoleate 13S-lipoxygenase activity [GO:0016165]; linoleate 9S-lipoxygenase activity [GO:1990136]; lipid binding [GO:0008289]
|
PF00305;PF01477;
|
3.10.450.60;2.60.60.20;
|
Lipoxygenase family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:O15296}. Membrane {ECO:0000250|UniProtKB:O15296}; Peripheral membrane protein {ECO:0000250|UniProtKB:O15296}. Note=Predominantly cytosolic; becomes enriched at membranes upon calcium binding. {ECO:0000250|UniProtKB:O15296}.
|
CATALYTIC ACTIVITY: Reaction=(9Z,12Z)-octadecadienoate + O2 = (9S)-hydroperoxy-(10E,12Z)-octadecadienoate; Xref=Rhea:RHEA:30291, ChEBI:CHEBI:15379, ChEBI:CHEBI:30245, ChEBI:CHEBI:60955; EC=1.13.11.58; Evidence={ECO:0000269|PubMed:15558016, ECO:0000269|PubMed:9305900, ECO:0000305|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30292; Evidence={ECO:0000305|PubMed:9305900}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:38675, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:75322; Evidence={ECO:0000269|PubMed:10625675, ECO:0000269|PubMed:10965849, ECO:0000269|PubMed:15558016, ECO:0000269|PubMed:16112079, ECO:0000269|PubMed:16143298, ECO:0000269|PubMed:9305900, ECO:0000305|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38676; Evidence={ECO:0000305|PubMed:16112079}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + O2 = (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:50972, ChEBI:CHEBI:15379, ChEBI:CHEBI:57446, ChEBI:CHEBI:133899; Evidence={ECO:0000269|PubMed:16112079}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50973; Evidence={ECO:0000305|PubMed:16112079}; CATALYTIC ACTIVITY: Reaction=(8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + O2 = (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:50932, ChEBI:CHEBI:15379, ChEBI:CHEBI:75322, ChEBI:CHEBI:133899; Evidence={ECO:0000269|PubMed:16112079, ECO:0000269|PubMed:16143298}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50933; Evidence={ECO:0000305|PubMed:16112079}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + O2 = 1-octadecanoyl-2-(15-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:63264, ChEBI:CHEBI:15379, ChEBI:CHEBI:74965, ChEBI:CHEBI:146283; Evidence={ECO:0000269|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63265; Evidence={ECO:0000305|PubMed:27435673}; CATALYTIC ACTIVITY: Reaction=a 1-acyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol); Xref=Rhea:RHEA:63276, ChEBI:CHEBI:15379, ChEBI:CHEBI:75243, ChEBI:CHEBI:146285; Evidence={ECO:0000269|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63277; Evidence={ECO:0000305|PubMed:27435673}; CATALYTIC ACTIVITY: Reaction=a 1-acyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-8Z,11Z,13E-eicosatrienoyl)-sn-glycero-3-phospho-(1D-myo-inositol); Xref=Rhea:RHEA:63280, ChEBI:CHEBI:15379, ChEBI:CHEBI:146286, ChEBI:CHEBI:146287; Evidence={ECO:0000269|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63281; Evidence={ECO:0000305|PubMed:27435673}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 9-hydroperoxy-(5Z,7E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:63288, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:146289; Evidence={ECO:0000269|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63289; Evidence={ECO:0000269|PubMed:27435673}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 11-hydroperoxy-(5Z,8Z,12E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:63308, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:146291; Evidence={ECO:0000269|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63309; Evidence={ECO:0000269|PubMed:27435673}; CATALYTIC ACTIVITY: Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = 15-hydroperoxy-(8Z,11Z,13E)-eicosatrienoate; Xref=Rhea:RHEA:63312, ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:146292; Evidence={ECO:0000269|PubMed:27435673}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63313; Evidence={ECO:0000269|PubMed:27435673};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.2 uM for arachidonate (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:16112079}; KM=2.1 uM for (8S)-HPETE (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:16112079}; KM=5.7 uM for (8S)-HETE (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:16112079}; KM=39 uM for (15S)-HPETE (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:16112079}; KM=15 uM for (15S)-HETE (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:16112079}; KM=2.86 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate {ECO:0000269|PubMed:27435673}; KM=0.964 uM for (8Z,11Z,14Z)-eicosatrienoate {ECO:0000269|PubMed:27435673}; Note=The highest catalytic efficiency is observed with arachidonate followed by (8S)-HPETE and(15S)-HPETE with similar efficiencies (PubMed:16112079). kcat is 0.22 sec(-1) for (5Z,8Z,11Z,14Z)-eicosatetraenoate. kcat is 0.045 sec(-1) for (8Z,11Z,14Z)-eicosatrienoate (PubMed:27435673). {ECO:0000269|PubMed:16112079, ECO:0000269|PubMed:27435673};
|
PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. {ECO:0000269|PubMed:9305900}.
| null | null |
FUNCTION: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators (PubMed:10625675, PubMed:10965849, PubMed:15558016, PubMed:16112079, PubMed:16143298, PubMed:27435673, PubMed:9305900). Catalyzes the peroxidation of arachidonate and linoleate into (8S)-HPETE and (9S)-HPODE respectively (PubMed:10625675, PubMed:10965849, PubMed:15558016, PubMed:16112079, PubMed:16143298, PubMed:27435673, PubMed:9305900). In addition to generate (8S)-HPETE from free arachidonic acid (AA), may produce other HETE isomers from phospholipid-esterified polyunsaturated fatty acids and minor products derived from (8S)-HPETE itself that may include leukotriene A4 and 8,15-diHPETE (PubMed:16112079, PubMed:16143298, PubMed:27435673). With free arachidonate as substrate, has no detectable 15S-lipoxygenase activity and only displays a 8S-lipoxygenase activity (PubMed:10625675, PubMed:10965849, PubMed:15558016, PubMed:16112079, PubMed:16143298, PubMed:9305900). However may have a 15S-lipoxygenase activity with (8S)-HPETE to produce (8S,15S)-diHPETE and when oxidizes directly arachidonic acid esterified to membrane-bound phospholipids to produce a phospholipid-esterified 15-HpETE (PubMed:16112079, PubMed:16143298, PubMed:27435673). May also catalyze (15S)-HPETE peroxidation to produce 8,15-diHPETE (PubMed:16112079). May play a role in keratinocyte differentiation through activation of the peroxisome proliferator activated receptor signaling pathway (PubMed:10965849). {ECO:0000269|PubMed:10625675, ECO:0000269|PubMed:10965849, ECO:0000269|PubMed:15558016, ECO:0000269|PubMed:16112079, ECO:0000269|PubMed:16143298, ECO:0000269|PubMed:27435673, ECO:0000269|PubMed:9305900}.
|
Mus musculus (Mouse)
|
O35942
|
NEK2_MOUSE
|
MPSRVEDYEVLHSIGTGSYGRCQKIRRKSDGKILVWKELDYGSMTEVEKQMLVSEVNLLRELKHPNIVSYYDRIIDRTNTTLYIVMEYCEGGDLASVISKGTKDRQYLEEEFVLRVMTQLTLALKECHRRSDGGHTVLHRDLKPANVFLDSKHNVKLGDFGLARILNHDTSFAKTFVGTPYYMSPEQMSCLSYNEKSDIWSLGCLLYELCALMPPFTAFNQKELAGKIREGRFRRIPYRYSDGLNDLITRMLNLKDYHRPSVEEILESPLIADLVAEEQRRNLERRGRRSGEPSKLPDSSPVLSELKLKERQLQDREQALRAREDILEQKERELCIRERLAEDKLARAESLMKNYSLLKEHRLLCLAGGPELDLPSSAMKKKVHFHGESKENTARSENSESYLAKSKCRDLKKRLHAAQLRAQALADIEKNYQLKSRQILGMR
|
2.7.11.1
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
|
blastocyst development [GO:0001824]; cell division [GO:0051301]; centrosome separation [GO:0051299]; chromosome segregation [GO:0007059]; meiotic cell cycle [GO:0051321]; mitotic sister chromatid segregation [GO:0000070]; mitotic spindle assembly [GO:0090307]; negative regulation of centriole-centriole cohesion [GO:1903126]; positive regulation of telomere capping [GO:1904355]; positive regulation of telomere maintenance via telomerase [GO:0032212]; protein autophosphorylation [GO:0046777]; regulation of attachment of spindle microtubules to kinetochore [GO:0051988]; regulation of mitotic centrosome separation [GO:0046602]
|
centrosome [GO:0005813]; condensed nuclear chromosome [GO:0000794]; cytoplasm [GO:0005737]; kinetochore [GO:0000776]; microtubule [GO:0005874]; midbody [GO:0030496]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; spindle pole [GO:0000922]
|
ATP binding [GO:0005524]; metal ion binding [GO:0046872]; protein kinase activity [GO:0004672]; protein phosphatase binding [GO:0019903]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]
|
PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, NEK Ser/Thr protein kinase family, NIMA subfamily
|
PTM: Activated by autophosphorylation. Protein phosphatase 1 represses autophosphorylation and activation of isoform 1 by dephosphorylation. Phosphorylation by STK3/MST2 is necessary for its localization to the centrosome. {ECO:0000250|UniProtKB:P51955}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9187143}. Nucleus, nucleolus {ECO:0000250|UniProtKB:P51955}. Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:P51955}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250}. Chromosome, centromere, kinetochore {ECO:0000250}. Chromosome, centromere {ECO:0000269|PubMed:9187143}. Note=STK3/MST2 and SAV1 are required for its targeting to the centrosome. Colocalizes with SGO1 and MAD1L1 at the kinetochore. Not associated with kinetochore in the interphase but becomes associated with it upon the breakdown of the nuclear envelope. Has a nucleolar targeting/ retention activity via a coiled-coil domain at the C-terminal end (By similarity). {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
| null | null | null | null |
FUNCTION: Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (By similarity). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (By similarity). Phosphorylates and activates NEK11 in G1/S-arrested cells. Involved in the regulation of centrosome disjunction (By similarity). {ECO:0000250|UniProtKB:P51955, ECO:0000269|PubMed:14668482, ECO:0000269|PubMed:14697346}.
|
Mus musculus (Mouse)
|
O35943
|
FRDA_MOUSE
|
MWAFGGRAAVGLLPRTASRASAWVGNPRWREPIVTCGRRGLHVTVNAGATRHAHLNLHYLQILNIKKQSVCVVHLRNLGTLDNPSSLDETAYERLAEETLDSLAEFFEDLADKPYTLEDYDVSFGDGVLTIKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDWTGKNWVYSHDGVSLHELLARELTKALNTKLDLSSLAYSGKGT
|
1.16.3.1
| null |
[2Fe-2S] cluster assembly [GO:0044571]; [4Fe-4S] cluster assembly [GO:0044572]; adult walking behavior [GO:0007628]; aerobic respiration [GO:0009060]; cellular response to hydrogen peroxide [GO:0070301]; embryo development ending in birth or egg hatching [GO:0009792]; heme biosynthetic process [GO:0006783]; intracellular iron ion homeostasis [GO:0006879]; iron import into the mitochondrion [GO:0048250]; iron-sulfur cluster assembly [GO:0016226]; mitochondrion organization [GO:0007005]; muscle cell cellular homeostasis [GO:0046716]; negative regulation of lipid storage [GO:0010888]; negative regulation of multicellular organism growth [GO:0040015]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of organ growth [GO:0046621]; negative regulation of release of cytochrome c from mitochondria [GO:0090201]; organ growth [GO:0035265]; oxidative phosphorylation [GO:0006119]; positive regulation of axon extension [GO:0045773]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of mitochondrial membrane permeability [GO:0035794]; proprioception [GO:0019230]; protein autoprocessing [GO:0016540]; regulation of cytosolic calcium ion concentration [GO:0051480]; response to iron ion [GO:0010039]
|
iron-sulfur cluster assembly complex [GO:1990229]; L-cysteine desulfurase complex [GO:1990221]; mitochondrial iron-sulfur cluster assembly complex [GO:0099128]; mitochondrion [GO:0005739]
|
2 iron, 2 sulfur cluster binding [GO:0051537]; enzyme binding [GO:0019899]; ferric iron binding [GO:0008199]; ferrous iron binding [GO:0008198]; ferroxidase activity [GO:0004322]; iron chaperone activity [GO:0034986]
|
PF01491;
|
3.30.920.10;
|
Frataxin family
|
PTM: [Frataxin mature form]: Processed in two steps by mitochondrial processing peptidase (MPP). MPP first cleaves the precursor to intermediate form and subsequently converts the intermediate to yield frataxin mature form (frataxin(81-210)) which is the predominant form. The additional forms, frataxin(56-210) and frataxin(78-210), seem to be produced when the normal maturation process is impaired; their physiological relevance is unsure. {ECO:0000250|UniProtKB:Q16595}.
|
SUBCELLULAR LOCATION: [Frataxin mature form]: Mitochondrion {ECO:0000269|PubMed:17597094, ECO:0000269|PubMed:9241270}.; SUBCELLULAR LOCATION: [Extramitochondrial frataxin]: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q16595}.
|
CATALYTIC ACTIVITY: [Frataxin mature form]: Reaction=4 Fe(2+) + 4 H(+) + O2 = 4 Fe(3+) + 2 H2O; Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1; Evidence={ECO:0000250|UniProtKB:Q16595};
| null | null | null | null |
FUNCTION: [Frataxin mature form]: Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly (PubMed:19805308, PubMed:25597503). Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release (PubMed:25597503). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity. May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems. May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation. May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis (By similarity). {ECO:0000250|UniProtKB:Q16595, ECO:0000250|UniProtKB:Q9H1K1, ECO:0000269|PubMed:19805308, ECO:0000269|PubMed:25597503}.; FUNCTION: [Extramitochondrial frataxin]: Modulates the RNA-binding activity of ACO1. May be involved in the cytoplasmic iron-sulfur protein biogenesis. May contribute to oxidative stress resistance and overall cell survival. {ECO:0000250|UniProtKB:Q16595}.
|
Mus musculus (Mouse)
|
O35945
|
AL1A7_MOUSE
|
MSSPAQPAVPAPLANLKIQHTKIFINNEWHDSVSSKKFPVLNPATEEVICHVEEGDKADVDKAVKAARQAFQIGSPWRTMDASERGRLLNKLADLMERDRLLLATMESMNAGKVFAHAYLLDVEISIKALQYFAGWADKIHGQTIPSDGNIFTYTRREPIGVCGQIIPWNGPLIIFTWKLGPALSCGNTVVVKPAEQTPLTALHMASLIKEAGFPPGVVNIVPGYGPTAGGAISSHMDIDKVSFTGSTEVGKLIKEAAGKSNLKRVTLELGGKSPCIVFADADLDSAVEFAHQGVFFHQGQICVAASRLFVEESIYDEFVRRSVERAKKYILGNPLNSGINQGPQIDKEQHNKILGLIESGKKEGAKLECGGGRWGNKGFFVQPTVFSNVTDEMRIAKEEIFGPVQQIMKFKSMDDVIKRANNTTYGLAAGVFTKDLDKAITVSSALQAGMVWVNCYLAVPVQCPFGGFKMSGNGRELGEHGLYEYTELKTVAMQISQKNS
|
1.2.1.3
| null |
ethanol catabolic process [GO:0006068]; fructose catabolic process [GO:0006001]
|
cytoplasm [GO:0005737]
|
3-chloroallyl aldehyde dehydrogenase activity [GO:0004028]; aldehyde dehydrogenase (NAD+) activity [GO:0004029]; benzaldehyde dehydrogenase (NAD+) activity [GO:0018479]; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity [GO:0043878]; identical protein binding [GO:0042802]
|
PF00171;
| null |
Aldehyde dehydrogenase family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P13601}.
|
CATALYTIC ACTIVITY: Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH; Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.3;
| null |
PATHWAY: Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2.
| null | null |
FUNCTION: Can oxidize benzaldehyde, propionaldehyde and acetaldehyde (By similarity). No detectable activity with retinal. {ECO:0000250, ECO:0000269|PubMed:10191271}.
|
Mus musculus (Mouse)
|
O35949
|
ELOV3_MOUSE
|
MDTSMNFSRGLKMDLMQPYDFETFQDLRPFLEEYWVSSFLIVVVYLLLIVVGQTYMRTRKSFSLQRPLILWSFFLAIFSILGTLRMWKFMATVMFTVGLKQTVCFAIYTDDAVVRFWSFLFLLSKVVELGDTAFIILRKRPLIFVHWYHHSTVLLFTSFGYKNKVPSGGWFMTMNFGVHSVMYTYYTMKAAKLKHPNLLPMVITSLQILQMVLGTIFGILNYIWRQEKGCHTTTEHFFWSFMLYGTYFILFAHFFHRAYLRPKGKVASKSQ
|
2.3.1.199
| null |
fatty acid elongation, monounsaturated fatty acid [GO:0034625]; fatty acid elongation, polyunsaturated fatty acid [GO:0034626]; fatty acid elongation, saturated fatty acid [GO:0019367]; long-chain fatty-acyl-CoA biosynthetic process [GO:0035338]; positive regulation of cold-induced thermogenesis [GO:0120162]; sphingolipid biosynthetic process [GO:0030148]; unsaturated fatty acid biosynthetic process [GO:0006636]; very long-chain fatty acid biosynthetic process [GO:0042761]
|
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]
|
fatty acid elongase activity [GO:0009922]
|
PF01151;
| null |
ELO family, ELOVL3 subfamily
|
PTM: N-Glycosylated. {ECO:0000255|HAMAP-Rule:MF_03203, ECO:0000269|PubMed:10429212}.
|
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000255|HAMAP-Rule:MF_03203, ECO:0000269|PubMed:10429212}; Multi-pass membrane protein {ECO:0000255|HAMAP-Rule:MF_03203}.
|
CATALYTIC ACTIVITY: Reaction=a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:32727, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:90725, ChEBI:CHEBI:90736; EC=2.3.1.199; Evidence={ECO:0000255|HAMAP-Rule:MF_03203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32728; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=eicosanoyl-CoA + H(+) + malonyl-CoA = 3-oxodocosanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:35327, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57380, ChEBI:CHEBI:57384, ChEBI:CHEBI:71451; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35328; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=H(+) + hexadecanoyl-CoA + malonyl-CoA = 3-oxooctadecanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:35315, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57384, ChEBI:CHEBI:71407; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35316; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=H(+) + malonyl-CoA + octadecanoyl-CoA = 3-oxoeicosanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:35319, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57394, ChEBI:CHEBI:65115; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35320; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=(9Z)-octadecenoyl-CoA + H(+) + malonyl-CoA = (11Z)-3-oxoicosenoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36511, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57387, ChEBI:CHEBI:74011; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36512; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z)-octadecadienoyl-CoA + H(+) + malonyl-CoA = (11Z,14Z)-3-oxoicosa-11,14-dienoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36503, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57383, ChEBI:CHEBI:57384, ChEBI:CHEBI:74012; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36504; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z,15Z)-octadecatrienoyl-CoA + H(+) + malonyl-CoA = (11Z,14Z,17Z)-3-oxoeicosatrienoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36523, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74034, ChEBI:CHEBI:74054; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36524; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=docosanoyl-CoA + H(+) + malonyl-CoA = 3-oxotetracosanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36507, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:65059, ChEBI:CHEBI:73977; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36508; Evidence={ECO:0000250|UniProtKB:Q9HB03}; CATALYTIC ACTIVITY: Reaction=H(+) + malonyl-CoA + tetradecanoyl-CoA = 3-oxohexadecanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:39167, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57349, ChEBI:CHEBI:57384, ChEBI:CHEBI:57385; Evidence={ECO:0000250|UniProtKB:Q9HB03}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39168; Evidence={ECO:0000250|UniProtKB:Q9HB03};
| null |
PATHWAY: Lipid metabolism; polyunsaturated fatty acid biosynthesis. {ECO:0000255|HAMAP-Rule:MF_03203}.
| null | null |
FUNCTION: Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that exhibits activity toward saturated and unsaturated acyl-CoA substrates with higher activity toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Participates in the formation of certain VLCFA and triglycerides in certain cells of the hair follicles and the sebaceous glands, required for skin barrier function. Critical enzyme for lipid accumulation and metabolic activity in brown adipocytes during the early phase of the tissue recruitment. Plays a role in lipid storage and in resistance to diet-induced obesity. {ECO:0000255|HAMAP-Rule:MF_03203, ECO:0000269|PubMed:10791983, ECO:0000269|PubMed:14581464, ECO:0000269|PubMed:16326704, ECO:0000269|PubMed:20605947}.
|
Mus musculus (Mouse)
|
O35952
|
GLO2_RAT
|
MVLGRGSLCLRSLSVLGAACARRGLGQALLGLSLCHTDFRKNLTVQQDMMKIELLPALTDNYMYLIIDEDTQEAAVVDPVQPQKVIETVKKHRVKLTTVLTTHHHWDHAGGNEKLVKLEPGLKVYGGDDRIGALTHKVTHLSTLEVGSLSVKCLSTPCHTSGHICYFVSKPGSSEPSAVFTGDTLFVAGCGKFYEGTADEMYKALLEVLGRLPPDTKVICGHEYTVNNLKFARHVEPGNTAVQEKLAWAKEKNAIGEPTVPSTLAEEFTYNPFMRVKEKTVQQHAGETDPVTTMRAIRREKDQFKVPRD
|
3.1.2.6
|
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q16775}; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q16775};
|
glutathione biosynthetic process [GO:0006750]; glutathione metabolic process [GO:0006749]; methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione [GO:0019243]; spermatogenesis [GO:0007283]
|
mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
|
hydroxyacylglutathione hydrolase activity [GO:0004416]; metal ion binding [GO:0046872]
|
PF16123;PF00753;
|
3.60.15.10;
|
Metallo-beta-lactamase superfamily, Glyoxalase II family
| null |
SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion matrix {ECO:0000250|UniProtKB:Q16775}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000250|UniProtKB:Q16775}.
|
CATALYTIC ACTIVITY: Reaction=an S-(2-hydroxyacyl)glutathione + H2O = a 2-hydroxy carboxylate + glutathione + H(+); Xref=Rhea:RHEA:21864, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57925, ChEBI:CHEBI:58896, ChEBI:CHEBI:71261; EC=3.1.2.6; Evidence={ECO:0000269|PubMed:8719777}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21865; Evidence={ECO:0000269|PubMed:8719777}; CATALYTIC ACTIVITY: Reaction=(R)-S-lactoylglutathione + H2O = (R)-lactate + glutathione + H(+); Xref=Rhea:RHEA:25245, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16004, ChEBI:CHEBI:57474, ChEBI:CHEBI:57925; EC=3.1.2.6; Evidence={ECO:0000269|PubMed:8719777}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25246; Evidence={ECO:0000305|PubMed:8719777};
| null |
PATHWAY: Secondary metabolite metabolism; methylglyoxal degradation; (R)-lactate from methylglyoxal: step 2/2.
| null | null |
FUNCTION: Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid. {ECO:0000269|PubMed:8719777}.
|
Rattus norvegicus (Rat)
|
O35954
|
PITM1_MOUSE
|
MLIKEYHILLPMSLDEYQVAQLYMIQKKSREESSGEGSGVEILANRPYTDGPGGNGQYTHKVYHVGSHIPGWFRALLPKAALQVEEESWNAYPYTRTRYTCPFVEKFSIEIETYYLPDGGQQPNVFNLSGAERRQRIVDTIDIVRDAVAPGEYKAEEDPRLYRSAKTGRGPLADDWARTAAQTGPLMCAYKLCKVEFRYWGMQAKIEQFIHDVGLRRVMLRAHRQAWCWQDEWIELSMADIRALEEETARMLAQRMAKCNTGSEGPEAQTPGKSSTEARPGTSTAGTPDGPEAPPGPDASPDASFGKQWSSSSRSSYSSQHGGGVSPQSLSEWRMQNIARDSENSSEEEFFDAHEGFSDSDEVFPKEMTKWNSNDFIDAFASPTEVEGVPDPTVMATKGIEDGARAPRDSEGLDGAGDLVVEACSVHALFLILHSGSILDSGPGDTNSKQADVQTLSTAFEAVTRVHFPEALGHVALRLVPCPPICAAAYALVSNLSPYSHDGDSLSRSQDHIPLAALPLLATSSSRYQGAVATVIARTNQAYAAFLRSSEGTGFCGQVVLIGDGVGGILGFDALCHSASAGPGSRGSSRRGSMNNEMLSPEVGPVRDPLADGVEVLGRASPEPSALPAQRTFSDMANPDPDGSQNSLQVASTATSSGEPRRASTASCPPASSEAPDGPTNAARLDFKVSGFFLFGSPLGLVLALRKTVMPALEVAQLRPACEQIYNLFHAADPCASRLEPLLAPKFQAIAPLAVPRYQKFPLGDGSSLLLADTLQTHSSLFLEELEMMVPSTPTSASGAFWKGSELGNEPASQTAAPSTTSEVVKILDRWWGNKRIDYSLYCPEALTAFPTVTLPHLFHASYWESADVVAFILRQVIEKERPQLTECEEPSIYSPAFPREKWQRKRTQVKIRNVTSNHRASDTVVCEGRPQVLNGRFMYGPLDVVTLTGEKVDVYVMTQPLSGKWIHFGTEVTNSSGRLTFPVPSERALGIGVYPVRMVVRGDHTYAECCLTVVSRGTEAVVFSIDGSFTASVSIMGSDPKVRAGAVDVVRHWQDSGYLIVYVTGRPDMQKHRVVAWLSQHNFPHGVVSFCDGLTHDPLRQKAMFLQSLVQEVELNIVAGYGSPKDVAVYAALGLSPSQTYIVGRAVRKLQAQCQFLSDGYVAHLGQLEAGSHSHAPSGPPRAALAKSSYAVAAPVDFLRKQSQLLRSRGPSQVDREGPGTPPTTLARGKTRSISLKLDSEE
| null | null |
protein transport [GO:0015031]
|
cell body [GO:0044297]; cleavage furrow [GO:0032154]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]; Golgi cisterna membrane [GO:0032580]; lipid droplet [GO:0005811]; midbody [GO:0030496]
|
calcium ion binding [GO:0005509]; phosphatidic acid binding [GO:0070300]; phosphatidylcholine binding [GO:0031210]; phosphatidylcholine transporter activity [GO:0008525]; phosphatidylinositol binding [GO:0035091]; phosphatidylinositol transfer activity [GO:0008526]; phospholipid binding [GO:0005543]; receptor tyrosine kinase binding [GO:0030971]
|
PF02862;PF02121;
|
3.30.530.20;3.40.50.1000;
|
PtdIns transfer protein family, PI transfer class IIA subfamily
|
PTM: Phosphorylated on multiple sites by CDK1 at the onset of mitosis. Phosphorylation facilitates dissociation from the Golgi complex and is required for interaction with PLK1 (By similarity). {ECO:0000250}.; PTM: Phosphorylated on threonine residues upon treatment with oleic acid. {ECO:0000250}.; PTM: Phosphorylated on tyrosine residues by PTK2B. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O00562}. Golgi apparatus, Golgi stack membrane {ECO:0000250|UniProtKB:O00562}; Peripheral membrane protein {ECO:0000250|UniProtKB:O00562}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:O00562}; Peripheral membrane protein {ECO:0000250|UniProtKB:O00562}. Lipid droplet {ECO:0000250|UniProtKB:O00562}. Cleavage furrow {ECO:0000250|UniProtKB:O00562}. Midbody {ECO:0000250|UniProtKB:O00562}. Note=Peripheral membrane protein associated with Golgi stacks in interphase cells. A minor proportion is associated with the endoplasmic reticulum. Associated with lipid droplets. Dissociates from the Golgi early on in mitosis and localizes to the cleavage furrow and midbody during cytokinesis. {ECO:0000250|UniProtKB:O00562}.
|
CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(in) = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(out); Xref=Rhea:RHEA:38691, ChEBI:CHEBI:57880; Evidence={ECO:0000250|UniProtKB:O00562}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38692; Evidence={ECO:0000250|UniProtKB:O00562};
| null | null | null | null |
FUNCTION: Catalyzes the transfer of phosphatidylinositol (PI) between membranes (By similarity). Binds PI (PubMed:10400687). Also binds phosphatidylcholine (PC) and phosphatidic acid (PA) with the binding affinity order of PI > PA > PC (By similarity). Regulates RHOA activity, and plays a role in cytoskeleton remodeling (By similarity). Necessary for normal completion of cytokinesis (By similarity). Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus (By similarity). Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus (By similarity). Required for protein export from the endoplasmic reticulum and the Golgi (By similarity). Binds calcium ions (By similarity). {ECO:0000250|UniProtKB:O00562, ECO:0000269|PubMed:10400687}.
|
Mus musculus (Mouse)
|
O35955
|
PSB10_MOUSE
|
MLKQAVEPTGGFSFENCQRNASLEHVLPGLRVPHARKTGTTIAGLVFRDGVILGADTRATNDSVVADKSCEKIHFIAPKIYCCGAGVAADTEMTTRMAASKMELHALSTGREPRVATVTRILRQTLFRYQGHVGASLVVGGVDLNGPQLYEVHPHGSYSRLPFTALGSGQGAAVALLEDRFQPNMTLEAAQELLVEAITAGILSDLGSGGNVDACVITAGGAKLQRALSTPTEPVQRAGRYRFAPGTTPVLTREVRPLTLELLEETVQAMEVE
|
3.4.25.1
| null |
cell morphogenesis [GO:0000902]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; T cell proliferation [GO:0042098]
|
cytosol [GO:0005829]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; proteasome core complex [GO:0005839]; proteasome core complex, beta-subunit complex [GO:0019774]; spermatoproteasome complex [GO:1990111]
|
endopeptidase activity [GO:0004175]; threonine-type endopeptidase activity [GO:0004298]
|
PF12465;PF00227;
|
3.60.20.10;
|
Peptidase T1B family
|
PTM: Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity. {ECO:0000305|PubMed:10413086}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00809}. Nucleus {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=Cleavage of peptide bonds with very broad specificity.; EC=3.4.25.1;
| null | null | null | null |
FUNCTION: The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Plays a role in determining the T-cell repertoire for an antiviral T-cell response. {ECO:0000269|PubMed:22341445}.
|
Mus musculus (Mouse)
|
O35956
|
S22A6_RAT
|
MAFNDLLKQVGGVGRFQLIQVTMVVAPLLLMASHNTLQNFTAAIPPHHCRPPANANLSKDGGLEAWLPLDKQGQPESCLRFTSPQWGPPFYNGTEANGTRVTEPCIDGWVYDNSTFPSTIVTEWNLVCSHRAFRQLAQSLYMVGVLLGAMVFGYLADRLGRRKVLILNYLQTAVSGTCAAYAPNYTVYCVFRLLSGMSLASIAINCMTLNVEWMPIHTRAYVGTLIGYVYSLGQFLLAGIAYAVPHWRHLQLVVSVPFFIAFIYSWFFIESARWYSSSGRLDLTLRALQRVARINGKQEEGAKLSIEVLRTSLQKELTLSKGQASAMELLRCPTLRHLFLCLSMLWFATSFAYYGLVMDLQGFGVSMYLIQVIFGAVDLPAKFVCFLVINSMGRRPAQMASLLLAGICILVNGIIPKSHTIIRTSLAVLGKGCLASSFNCIFLYTGELYPTVIRQTGLGMGSTMARVGSIVSPLVSMTAEFYPSMPLFIFGAVPVVASAVTALLPETLGQPLPDTVQDLKSRSRGKQNQQQQEQQKQMMPLQASTQEKNGL
| null | null |
alpha-ketoglutarate transport [GO:0015742]; metanephric proximal tubule development [GO:0072237]; monoatomic anion transport [GO:0006820]; organic anion transport [GO:0015711]; prostaglandin transport [GO:0015732]; renal tubular secretion [GO:0097254]; response to organic cyclic compound [GO:0014070]; sodium-independent organic anion transport [GO:0043252]; transmembrane transport [GO:0055085]
|
basal plasma membrane [GO:0009925]; basolateral plasma membrane [GO:0016323]; caveola [GO:0005901]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]
|
alpha-ketoglutarate transmembrane transporter activity [GO:0015139]; antiporter activity [GO:0015297]; chloride ion binding [GO:0031404]; identical protein binding [GO:0042802]; organic anion transmembrane transporter activity [GO:0008514]; prostaglandin transmembrane transporter activity [GO:0015132]; sodium-independent organic anion transmembrane transporter activity [GO:0015347]; solute:inorganic anion antiporter activity [GO:0005452]; transmembrane transporter activity [GO:0022857]; xenobiotic transmembrane transporter activity [GO:0042910]
|
PF00083;
|
1.20.1250.20;
|
Major facilitator (TC 2.A.1) superfamily, Organic cation transporter (TC 2.A.1.19) family
|
PTM: Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane. {ECO:0000250|UniProtKB:Q4U2R8}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8VC69}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8VC69}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q4U2R8}; Multi-pass membrane protein {ECO:0000305}. Basal cell membrane {ECO:0000250|UniProtKB:Q4U2R8}; Multi-pass membrane protein {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin(out) + a dicarboxylate(in) = (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin(in) + a dicarboxylate(out); Xref=Rhea:RHEA:76071, ChEBI:CHEBI:28965, ChEBI:CHEBI:59560; Evidence={ECO:0000250|UniProtKB:Q4U2R8}; CATALYTIC ACTIVITY: Reaction=a dicarboxylate(in) + L-erythro-7,8-dihydrobiopterin(out) = a dicarboxylate(out) + L-erythro-7,8-dihydrobiopterin(in); Xref=Rhea:RHEA:76075, ChEBI:CHEBI:28965, ChEBI:CHEBI:43029; Evidence={ECO:0000250|UniProtKB:Q4U2R8}; CATALYTIC ACTIVITY: Reaction=a dicarboxylate(in) + L-sepiapterin(out) = a dicarboxylate(out) + L-sepiapterin(in); Xref=Rhea:RHEA:76079, ChEBI:CHEBI:28965, ChEBI:CHEBI:194527; Evidence={ECO:0000250|UniProtKB:Q4U2R8}; CATALYTIC ACTIVITY: Reaction=a dicarboxylate(in) + prostaglandin F2alpha(out) = a dicarboxylate(out) + prostaglandin F2alpha(in); Xref=Rhea:RHEA:76119, ChEBI:CHEBI:28965, ChEBI:CHEBI:57404; Evidence={ECO:0000250|UniProtKB:Q4U2R8}; CATALYTIC ACTIVITY: Reaction=a dicarboxylate(in) + prostaglandin E2(out) = a dicarboxylate(out) + prostaglandin E2(in); Xref=Rhea:RHEA:76123, ChEBI:CHEBI:28965, ChEBI:CHEBI:606564; Evidence={ECO:0000269|PubMed:9228014}; CATALYTIC ACTIVITY: Reaction=3',5'-cyclic AMP(out) + a dicarboxylate(in) = 3',5'-cyclic AMP(in) + a dicarboxylate(out); Xref=Rhea:RHEA:76127, ChEBI:CHEBI:28965, ChEBI:CHEBI:58165; Evidence={ECO:0000269|PubMed:9228014}; CATALYTIC ACTIVITY: Reaction=3',5'-cyclic GMP(out) + a dicarboxylate(in) = 3',5'-cyclic GMP(in) + a dicarboxylate(out); Xref=Rhea:RHEA:76131, ChEBI:CHEBI:28965, ChEBI:CHEBI:57746; Evidence={ECO:0000269|PubMed:9228014}; CATALYTIC ACTIVITY: Reaction=a dicarboxylate(in) + urate(out) = a dicarboxylate(out) + urate(in); Xref=Rhea:RHEA:76135, ChEBI:CHEBI:17775, ChEBI:CHEBI:28965; Evidence={ECO:0000269|PubMed:9228014}; CATALYTIC ACTIVITY: Reaction=glutarate(in) + kynurenate(out) = glutarate(out) + kynurenate(in); Xref=Rhea:RHEA:75999, ChEBI:CHEBI:30921, ChEBI:CHEBI:58454; Evidence={ECO:0000269|PubMed:23832370}; CATALYTIC ACTIVITY: Reaction=(indol-3-yl)acetate(out) + a dicarboxylate(in) = (indol-3-yl)acetate(in) + a dicarboxylate(out); Xref=Rhea:RHEA:75983, ChEBI:CHEBI:28965, ChEBI:CHEBI:30854; Evidence={ECO:0000269|PubMed:14675047}; CATALYTIC ACTIVITY: Reaction=a dicarboxylate(in) + indoxyl sulfate(out) = a dicarboxylate(out) + indoxyl sulfate(in); Xref=Rhea:RHEA:75987, ChEBI:CHEBI:28965, ChEBI:CHEBI:144643; Evidence={ECO:0000269|PubMed:14675047}; CATALYTIC ACTIVITY: Reaction=a dicarboxylate(in) + N-benzoylglycine(out) = a dicarboxylate(out) + N-benzoylglycine(in); Xref=Rhea:RHEA:75991, ChEBI:CHEBI:28965, ChEBI:CHEBI:606565; Evidence={ECO:0000269|PubMed:14675047}; CATALYTIC ACTIVITY: Reaction=3-carboxy-4-methyl-5-propyl-2-furanpropanoate(out) + a dicarboxylate(in) = 3-carboxy-4-methyl-5-propyl-2-furanpropanoate(in) + a dicarboxylate(out); Xref=Rhea:RHEA:75995, ChEBI:CHEBI:28965, ChEBI:CHEBI:194524; Evidence={ECO:0000269|PubMed:14675047};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=27.5 uM for hippurate/N-benzoylglycine {ECO:0000269|PubMed:14675047}; KM=47.1 uM for indole acetate {ECO:0000269|PubMed:14675047}; KM=17.7 uM for indoxyl sulfate {ECO:0000269|PubMed:14675047}; KM=154 uM for 3-carboxy-4- methyl-5-propyl-2-furanpropionate {ECO:0000269|PubMed:14675047}; Vmax=519 pmol/min/mg enzyme for hippurate/N-benzoylglycine uptake {ECO:0000269|PubMed:14675047}; Vmax=387 pmol/min/mg enzyme for indole acetate uptake {ECO:0000269|PubMed:14675047}; Vmax=350 pmol/min/mg enzyme for indoxyl sulfate uptake {ECO:0000269|PubMed:14675047}; Vmax=1669 pmol/min/mg enzyme for 3-carboxy-4- methyl-5-propyl-2-furanpropionate uptake {ECO:0000269|PubMed:14675047};
| null | null | null |
FUNCTION: Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as alpha-ketoglutarate or glutarate (PubMed:14675047, PubMed:23832370, PubMed:9228014, PubMed:9374486). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (By similarity). Function as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4) dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (By similarity). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:9228014). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:9228014). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:23832370). May transport glutamate (By similarity). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:14675047, PubMed:9228014). Uremic toxins include the indoxyl sulfate (IS), hippurate, indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate(CMPF) and urate (PubMed:14675047, PubMed:9228014). Xenobiotics include the mycotoxin ochratoxin (OTA) (By similarity). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (By similarity). May also work as a bidirectional OA/dicarboxylate exchanger (PubMed:9228014). {ECO:0000250|UniProtKB:Q4U2R8, ECO:0000269|PubMed:14675047, ECO:0000269|PubMed:23832370, ECO:0000269|PubMed:9228014, ECO:0000269|PubMed:9374486}.
|
Rattus norvegicus (Rat)
|
O35963
|
RB33B_MOUSE
|
MTSEMESSLEVSFSSSCAVSGASGCLPPARSRIFKIIVIGDSNVGKTCLTYRFCAGRFPDRTEATIGVDFRERAVDIDGERIKIQLWDTAGQERFRKSMVQHYYRNVHAVVFVYDMTNMASFHSLPAWIEECKQHLLANDIPRILVGNKCDLRSAIQVPTDLAQKFADTHSMPLFETSAKNPNDNDHVEAIFMTLAHKLKSHKPLMLSQLPDNRISLKPETKPAVTCWC
| null | null |
autophagosome assembly [GO:0000045]; intra-Golgi vesicle-mediated transport [GO:0006891]; negative regulation of constitutive secretory pathway [GO:1903434]; protein localization to Golgi apparatus [GO:0034067]; protein transport [GO:0015031]; Rab protein signal transduction [GO:0032482]; regulation of exocytosis [GO:0017157]; regulation of Golgi organization [GO:1903358]; regulation of retrograde vesicle-mediated transport, Golgi to ER [GO:2000156]; skeletal system morphogenesis [GO:0048705]
|
endosome [GO:0005768]; Golgi apparatus [GO:0005794]; Golgi lumen [GO:0005796]; Golgi membrane [GO:0000139]; presynapse [GO:0098793]
|
GTP binding [GO:0005525]; GTPase activity [GO:0003924]
|
PF00071;
|
3.40.50.300;
|
Small GTPase superfamily, Rab family
| null |
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:18448665, ECO:0000269|PubMed:9512502}; Lipid-anchor {ECO:0000305}. Golgi apparatus, cis-Golgi network {ECO:0000269|PubMed:18448665}. Note=Under starvation conditions punctate RAB33B-positive structures are often observed in the cytoplasm (PubMed:18448665). {ECO:0000269|PubMed:18448665}.
| null | null | null | null | null |
FUNCTION: Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking (By similarity). It is involved in autophagy, acting as a modulator of autophagosome formation. {ECO:0000250, ECO:0000269|PubMed:18448665}.
|
Mus musculus (Mouse)
|
O35964
|
SH3G1_RAT
|
MSVAGLKKQFYKASQLVSEKVGGAEGTKLDDDFREMEKKVDITSKAVAEVLVRTIEYLQPNPASRAKLTMLNTVSKIRGQVKNPGYPQSEGLLGECMVRHGKELGGESNFGDALLDAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCDKDLKEIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFEESKEVAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILEELADKLKRRVREASSRPRREFKPRPQEPFELGELEQPNGGFPCASAPKITASSSFRSGDKPTRTPSKSMPPLDQPSCKALYDFEPENDGELGFREGDLITLTNQIDENWYEGMLHGQSGFFPLSYVQVLVPLPQ
| null | null |
modulation of excitatory postsynaptic potential [GO:0098815]; positive regulation of synaptic vesicle endocytosis [GO:1900244]; regulation of synaptic vesicle endocytosis [GO:1900242]; synaptic vesicle uncoating [GO:0016191]
|
anchoring junction [GO:0070161]; cell projection [GO:0042995]; cytoplasm [GO:0005737]; early endosome membrane [GO:0031901]; glutamatergic synapse [GO:0098978]; hippocampal mossy fiber to CA3 synapse [GO:0098686]; podosome [GO:0002102]; postsynaptic density, intracellular component [GO:0099092]; presynapse [GO:0098793]; Schaffer collateral - CA1 synapse [GO:0098685]; synapse [GO:0045202]
|
beta-1 adrenergic receptor binding [GO:0031697]; GTPase binding [GO:0051020]; identical protein binding [GO:0042802]; lipid binding [GO:0008289]; phosphatase binding [GO:0019902]; SH3 domain binding [GO:0017124]; transmembrane transporter binding [GO:0044325]
|
PF03114;PF00018;
|
1.20.1270.60;2.30.30.40;
|
Endophilin family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17088211}. Early endosome membrane {ECO:0000269|PubMed:17088211}; Peripheral membrane protein {ECO:0000269|PubMed:17088211}. Cell projection, podosome {ECO:0000250}. Note=Associated with postsynaptic endosomes in hippocampal neurons.
| null | null | null | null | null |
FUNCTION: Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity). {ECO:0000250}.
|
Rattus norvegicus (Rat)
|
O35969
|
GAMT_MOUSE
|
MSSSAASPLFAPGEDCGPAWRAAPAAYDASDTHLQILGKPVMERWETPYMHALAAAAASRGGRVLEVGFGMAIAASRVQQAPIEEHWIIECNDGVFQRLQDWALRQPHKVVPLKGLWEEVAPTLPDGHFDGILYDTYPLSEEAWHTHQFNFIKNHAFRLLKTGGVLTYCNLTSWGELMKSKYTDITTMFEETQVPALQEAGFLKENICTEVMALVPPADCRYYAFPQMITPLVTKH
|
2.1.1.2
| null |
animal organ morphogenesis [GO:0009887]; creatine biosynthetic process [GO:0006601]; methylation [GO:0032259]; regulation of multicellular organism growth [GO:0040014]; S-adenosylhomocysteine metabolic process [GO:0046498]; S-adenosylmethionine metabolic process [GO:0046500]; spermatogenesis [GO:0007283]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; microvillus [GO:0005902]; nucleus [GO:0005634]
|
guanidinoacetate N-methyltransferase activity [GO:0030731]; identical protein binding [GO:0042802]; protein arginine N5-methyltransferase activity [GO:0019702]; S-adenosylmethionine-dependent methyltransferase activity [GO:0008757]
| null |
3.40.50.150;
|
Class I-like SAM-binding methyltransferase superfamily, RMT2 methyltransferase family
| null |
SUBCELLULAR LOCATION: Cell projection, microvillus {ECO:0000269|PubMed:8312439}. Note=Detected in microvilli of the epithelial cells lining the caput epididymis.
|
CATALYTIC ACTIVITY: Reaction=guanidinoacetate + S-adenosyl-L-methionine = creatine + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:10656, ChEBI:CHEBI:15378, ChEBI:CHEBI:57742, ChEBI:CHEBI:57856, ChEBI:CHEBI:57947, ChEBI:CHEBI:59789; EC=2.1.1.2; Evidence={ECO:0000255|PROSITE-ProRule:PRU00892};
| null |
PATHWAY: Amine and polyamine biosynthesis; creatine biosynthesis; creatine from L-arginine and glycine: step 2/2.
| null | null |
FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor. Important in nervous system development. {ECO:0000250|UniProtKB:Q14353}.
|
Mus musculus (Mouse)
|
O35973
|
PER1_MOUSE
|
MSGPLEGADGGGDPRPGEPFCPGGVPSPGAPQHRPCPGPSLADDTDANSNGSSGNESNGPESRGASQRSSHSSSSGNGKDSALLETTESSKSTNSQSPSPPSSSIAYSLLSASSEQDNPSTSGCSSEQSARARTQKELMTALRELKLRLPPERRGKGRSGTLATLQYALACVKQVQANQEYYQQWSLEEGEPCAMDMSTYTLEELEHITSEYTLRNQDTFSVAVSFLTGRIVYISEQAGVLLRCKRDVFRGARFSELLAPQDVGVFYGSTTPSRLPTWGTGTSAGSGLKDFTQEKSVFCRIRGGPDRDPGPRYQPFRLTPYVTKIRVSDGAPAQPCCLLIAERIHSGYEAPRIPPDKRIFTTRHTPSCLFQDVDERAAPLLGYLPQDLLGAPVLLFLHPEDRPLMLAIHKKILQLAGQPFDHSPIRFCARNGEYVTMDTSWAGFVHPWSRKVAFVLGRHKVRTAPLNEDVFTPPAPSPAPSLDSDIQELSEQIHRLLLQPVHSSSPTGLCGVGPLMSPGPLHSPGSSSDSNGGDAEGPGPPAPVTFQQICKDVHLVKHQGQQLFIESRAKPPPRPRLLATGTFKAKVLPCQSPNPELEVAPVPDQASLALAPEEPERKETSGCSYQQINCLDSILRYLESCNIPSTTKRKCASSSSYTASSASDDDKQRAGPVPVGAKKDPSSAMLSGEGATPRKEPVVGGTLSPLALANKAESVVSVTSQCSFSSTIVHVGDKKPPESDIIMMEDLPGLAPGPAPSPAPSPTVAPDPTPDAYRPVGLTKAVLSLHTQKEEQAFLNRFRDLGRLRGLDTSSVAPSAPGCHHGPIPPGRRHHCRSKAKRSRHHHHQTPRPETPCYVSHPSPVPSSGPWPPPPATTPFPAMVQPYPLPVFSPRGGPQPLPPAPTSVSPATFPSPLVTPMVALVLPNYLFPTPPSYPYGVSQAPVEGPPTPASHSPSPSLPPPPLSPPHRPDSPLFNSRCSSPLQLNLLQLEESPRTEGGAAAGGPGSSAGPLPPSEETAEPEARLVEVTESSNQDALSGSSDLLELLLQEDSRSGTGSAASGSLGSGLGSGSGSGSHEGGSTSASITRSSQSSHTSKYFGSIDSSEAEAGAARARTEPGDQVIKCVLQDPIWLLMANADQRVMMTYQVPSRDAASVLKQDRERLRAMQKQQPRFSEDQRRELGAVHSWVRKGQLPRALDVTACVDCGSSVQDPGHSDDPLFSELDGLGLEPMEEGGGEGGGCGVGGGGGDGGEEAQTQIGAKGSSSQDSAMEEEEQGGGSSSPALPAEENSTS
| null | null |
chromatin remodeling [GO:0006338]; circadian regulation of gene expression [GO:0032922]; circadian regulation of translation [GO:0097167]; circadian rhythm [GO:0007623]; entrainment of circadian clock by photoperiod [GO:0043153]; negative regulation of canonical NF-kappaB signal transduction [GO:0043124]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of glucocorticoid receptor signaling pathway [GO:2000323]; negative regulation of JNK cascade [GO:0046329]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of transcription by RNA polymerase II [GO:0045944]; post-transcriptional regulation of gene expression [GO:0010608]; regulation of circadian rhythm [GO:0042752]; regulation of cytokine production involved in inflammatory response [GO:1900015]; regulation of hair cycle [GO:0042634]; regulation of p38MAPK cascade [GO:1900744]; regulation of sodium ion transport [GO:0002028]; response to cAMP [GO:0051591]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
chromatin DNA binding [GO:0031490]; DNA-binding transcription factor binding [GO:0140297]; E-box binding [GO:0070888]; kinase binding [GO:0019900]; transcription cis-regulatory region binding [GO:0000976]; transcription corepressor binding [GO:0001222]; ubiquitin protein ligase binding [GO:0031625]
|
PF08447;PF21353;PF12114;
|
3.30.450.20;
| null |
PTM: Phosphorylated on serine residues by CSNK1D, CSNK1E and probably also by CSNK1G2. Phosphorylation by CSNK1D or CSNK1E promotes nuclear location of PER proteins as well as ubiquitination and subsequent degradation. May be dephosphorylated by PP1. {ECO:0000269|PubMed:11865049}.; PTM: Ubiquitinated; requires phosphorylation by CSNK1E and interaction with BTRC and FBXW11. Deubiquitinated by USP2. {ECO:0000269|PubMed:11865049, ECO:0000269|PubMed:23213472}.
|
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nucleocytoplasmic shuttling is effected by interaction with other circadian core oscillator proteins and/or by phosphorylation. Retention of PER1 in the cytoplasm occurs through PER1-PER2 heterodimer formation. Translocate to the nucleus after phosphorylation by CSNK1D or CSNK1E. Also translocated to the nucleus by CRY1 or CRY2.
| null | null | null | null | null |
FUNCTION: Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/BMAL1 target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by BMAL1:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1. {ECO:0000269|PubMed:11395012, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:15888647, ECO:0000269|PubMed:21930935, ECO:0000269|PubMed:22331899, ECO:0000269|PubMed:24154698, ECO:0000269|PubMed:24378737, ECO:0000269|PubMed:24610784, ECO:0000269|PubMed:9856465}.
|
Mus musculus (Mouse)
|
O35975
|
NAR2B_MOUSE
|
MTSKIFKFFLTWWLTQQVTGLAVPFMLDMAPNAFDDQYESCVEDMEKKAPQLLQEDFNMNEELKLEWEKAEINWKEIKNSTSYPAGFHDFHGTALVAYTGNLAIDFNRAVRDFKKSPDNFHYKAFHYYLTRAVQLLNDQGCSLVYRGTKVMFEYTGKGSVRFGQFSSSSLTKRVALSSNFFSNHGTLFIIRTCLGVNIKEFSSFPREEEVLIPGYEVYHKVTAQNDNGYNEIFLDSPERKKSNFNCFYNGSAQTVNIDFSISGSRESCVSLFLVVLLGLLVQQLTLAEL
|
2.4.2.31; 3.2.2.5
| null |
NAD catabolic process [GO:0019677]
|
external side of plasma membrane [GO:0009897]; extrinsic component of plasma membrane [GO:0019897]; membrane [GO:0016020]
|
hydrolase activity, acting on glycosyl bonds [GO:0016798]; NAD+ ADP-ribosyltransferase activity [GO:0003950]; NAD+ nucleosidase activity [GO:0003953]; NAD+ nucleotidase, cyclic ADP-ribose generating [GO:0061809]; NAD+-protein-arginine ADP-ribosyltransferase activity [GO:0106274]; nucleotidyltransferase activity [GO:0016779]
|
PF01129;
| null |
Arg-specific ADP-ribosyltransferase family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-anchor {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=L-arginyl-[protein] + NAD(+) = H(+) + N(omega)-(ADP-D-ribosyl)-L-arginyl-[protein] + nicotinamide; Xref=Rhea:RHEA:19149, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540, ChEBI:CHEBI:142554; EC=2.4.2.31; Evidence={ECO:0000269|PubMed:11011142, ECO:0000269|PubMed:9300695}; CATALYTIC ACTIVITY: Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.5; Evidence={ECO:0000269|PubMed:11011142};
| null | null | null | null |
FUNCTION: Has both NAD(+) glycohydrolase and ADP-ribosyltransferase activity. {ECO:0000269|PubMed:17928361, ECO:0000269|PubMed:9300695}.
|
Mus musculus (Mouse)
|
O35980
|
NTH_MOUSE
|
MNSGVRMVTRSRSRATRIASEGCREELAPREAAAEGRKSHRPVRHPRRTQKTHVAYEAANGEEGEDAEPLKVPVWEPQNWQQQLANIRIMRSKKDAPVDQLGAEHCYDASASPKVRRYQVLLSLMLSSQTKDQVTAGAMQRLRARGLTVESILQTDDDTLGRLIYPVGFWRNKVKYIKQTTAILQQRYEGDIPASVAELVALPGVGPKMAHLAMAVAWGTISGIAVDTHVHRIANRLRWTKKMTKTPEETRKNLEEWLPRVLWSEVNGLLVGFGQQICLPVHPRCQACLNKALCPAAQDL
|
3.2.2.-; 4.2.99.18
|
COFACTOR: Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000255|HAMAP-Rule:MF_03183}; Note=Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a role in catalysis, but is probably involved in the proper positioning of the enzyme along the DNA strand. {ECO:0000255|HAMAP-Rule:MF_03183};
|
base-excision repair, AP site formation [GO:0006285]; DNA repair [GO:0006281]; nucleotide-excision repair [GO:0006289]
|
mitochondrion [GO:0005739]; nucleus [GO:0005634]
|
4 iron, 4 sulfur cluster binding [GO:0051539]; class I DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0140078]; damaged DNA binding [GO:0003684]; DNA N-glycosylase activity [GO:0019104]; DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0003906]; double-stranded DNA binding [GO:0003690]; metal ion binding [GO:0046872]; oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity [GO:0000703]
|
PF00633;PF00730;
|
1.10.1670.10;
|
Nth/MutY family
|
PTM: Ubiquitinated by TRIM26; leading to proteasomal degradation. {ECO:0000250|UniProtKB:P78549}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03183}. Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03183, ECO:0000269|PubMed:12531031}.
|
CATALYTIC ACTIVITY: Reaction=2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho-2'-deoxyribonucleoside-DNA + H(+); Xref=Rhea:RHEA:66592, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067, ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695, ChEBI:CHEBI:167181; EC=4.2.99.18; Evidence={ECO:0000250|UniProtKB:P20625, ECO:0000255|HAMAP-Rule:MF_03183};
| null | null | null | null |
FUNCTION: Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines. {ECO:0000255|HAMAP-Rule:MF_03183, ECO:0000269|PubMed:9743625}.
|
Mus musculus (Mouse)
|
O35984
|
PBX2_MOUSE
|
MDERLLGPPPPGGGRGGLGLVGAEPGGPGEPPGGGDPGGGSGGVPGGRGKQDIGDILQQIMTITDQSLDEAQAKKHALNCHRMKPALFSVLCEIKEKTGLSIRSSQEEEPVDPQLMRLDNMLLAEGVAGPEKGGGSAAAAAAAAASGGGVSPDNSIEHSDYRSKLAQIRHIYHSELEKYEQACNEFTTHVMNLLREQSRTRPVAPKEMERMVSIIHRKFSAIQMQLKQSTCEAVMILRSRFLDARRKRRNFSKQATEVLNEYFYSHLSNPYPSEEAKEELAKKCGITVSQVSNWFGNKRIRYKKNIGKFQEEANIYAVKTAVSVAQGGHSRTSSPTPPSSAGSGGSFNLSGSGDMFLGMPGLNGDSYPASQVESLRHSMGPGSYGDNIGGGQIYSPREIRANGGWQEAVTPSSVTSPTEGPGSVHSDTSN
| null | null |
animal organ morphogenesis [GO:0009887]; brain development [GO:0007420]; embryonic limb morphogenesis [GO:0030326]; embryonic organ development [GO:0048568]; eye development [GO:0001654]; neuron development [GO:0048666]; positive regulation of transcription by RNA polymerase II [GO:0045944]; proximal/distal pattern formation [GO:0009954]; regulation of transcription by RNA polymerase II [GO:0006357]
|
nucleus [GO:0005634]; transcription regulator complex [GO:0005667]
|
chromatin binding [GO:0003682]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription factor binding [GO:0140297]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]
|
PF05920;PF03792;
|
1.10.10.60;
|
TALE/PBX homeobox family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'. Activates transcription of PF4 in complex with MEIS1 (By similarity). {ECO:0000250}.
|
Mus musculus (Mouse)
|
O35987
|
NSF1C_RAT
|
MAEERQDALREFVAVTGAEEDRARFFLESAGWDLQIALASFYEDGGDEDIVTISQATPSSVSRGTAPSDNRVTSFRDLIHDQDEEEEEEEGQRFYAGGSERSGQQIVGPPRKKSPNELVDDLFKGAKEHGAVAVERVTKSPGETSKPRPFAGGGYRLGAAPEEESAYVAGERRRHSGQDVHVVLKLWKTGFSLDNGDLRSYQDPSNAQFLESIRRGEVPAELRRLAHGGQVNLDMEDHRDEDFVKPKGAFKAFTGEGQKLGSTAPQVLNTSSPAQQAENEAKASSSILINEAEPTTNIQIRLADGGRLVQKFNHSHRISDIRLFIVDARPAMAATSFVLMTTFPNKELADENQTLKEANLLNAVIVQRLT
| null | null |
autophagosome assembly [GO:0000045]; establishment of mitotic spindle orientation [GO:0000132]; Golgi organization [GO:0007030]; membrane fusion [GO:0061025]; negative regulation of protein localization to centrosome [GO:1904780]; nuclear membrane reassembly [GO:0031468]; positive regulation of mitotic centrosome separation [GO:0046604]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]
|
chromosome [GO:0005694]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; Golgi stack [GO:0005795]; nucleus [GO:0005634]; spindle pole centrosome [GO:0031616]; VCP-NSFL1C complex [GO:1990730]
|
ATPase binding [GO:0051117]; lipid binding [GO:0008289]; ubiquitin binding [GO:0043130]
|
PF08059;PF14555;PF00789;
|
1.10.8.10;3.30.420.210;
|
NSFL1C family
|
PTM: Phosphorylated during mitosis. Phosphorylation inhibits interaction with Golgi membranes and is required for the fragmentation of the Golgi stacks during mitosis. {ECO:0000269|PubMed:12810701}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12810701}. Golgi apparatus, Golgi stack {ECO:0000269|PubMed:12810701, ECO:0000269|PubMed:9214505}. Chromosome {ECO:0000269|PubMed:1495983}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:23649807}. Note=Predominantly nuclear in interphase cells (PubMed:12810701). Bound to the axial elements of sex chromosomes in pachytene spermatocytes (PubMed:1495983). A small proportion of the protein is cytoplasmic, associated with Golgi stacks (PubMed:12810701). Localizes to centrosome during mitotic prophase and metaphase (PubMed:23649807). {ECO:0000269|PubMed:12810701, ECO:0000269|PubMed:1495983, ECO:0000269|PubMed:23649807}.
| null | null | null | null | null |
FUNCTION: Reduces the ATPase activity of VCP (PubMed:9214505, PubMed:9824302). Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis (PubMed:12411482). May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (PubMed:10930451). Inhibits the activity of CTSL (in vitro) (By similarity). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase (By similarity). Also, regulates spindle orientation during mitosis (By similarity). {ECO:0000250|UniProtKB:Q9UNZ2, ECO:0000269|PubMed:10930451, ECO:0000269|PubMed:12411482, ECO:0000269|PubMed:9214505, ECO:0000269|PubMed:9824302}.
|
Rattus norvegicus (Rat)
|
O35988
|
SDC4_MOUSE
|
MAPACLLAPLLLLLLGGFPLVPGESIRETEVIDPQDLLEGRYFSGALPDDEDAGGSDDFELSGSGDLDDTEEPRPFPEVIEPLVPLDNHIPENAQPGIRVPSEPKELEENEVIPKRAPSDVGDDMSNKVSMSSTAQGSNIFERTEVLAALIVGGVVGILFAVFLILLLVYRMKKKDEGSYDLGKKPIYKKAPTNEFYA
| null | null |
cell migration [GO:0016477]; inner ear receptor cell stereocilium organization [GO:0060122]; negative regulation of T cell proliferation [GO:0042130]; neural tube closure [GO:0001843]; positive regulation of exosomal secretion [GO:1903543]; positive regulation of extracellular exosome assembly [GO:1903553]; positive regulation of focal adhesion assembly [GO:0051894]; positive regulation of stress fiber assembly [GO:0051496]; regulation of fibroblast migration [GO:0010762]; ureteric bud development [GO:0001657]; wound healing [GO:0042060]
|
cell surface [GO:0009986]; costamere [GO:0043034]; extracellular region [GO:0005576]; focal adhesion [GO:0005925]; Golgi lumen [GO:0005796]; membrane [GO:0016020]
|
fibronectin binding [GO:0001968]; identical protein binding [GO:0042802]; protein kinase C binding [GO:0005080]; thrombospondin receptor activity [GO:0070053]
|
PF01034;
| null |
Syndecan proteoglycan family
|
PTM: Shedding is enhanced by a number of factors such as heparanase, thrombin or EGF. Also by stress and wound healing. PMA-mediated shedding is inhibited by TIMP3. {ECO:0000269|PubMed:10684261}.; PTM: O-glycosylated; contains both chondroitin sulfate and heparan sulfate. Ser-44, Ser-62 and Ser-64 can all be modified by either chondroitin sulfate or heparan sulfate, and the protein exists in forms that contain only chondroitin sulfate, only heparan sulfate and both chondroitin sulfate and heparan sulfate. {ECO:0000250|UniProtKB:P34901}.
|
SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type I membrane protein {ECO:0000255}. Secreted {ECO:0000269|PubMed:10684261}. Note=Shedding of the ectodomain produces a soluble form. {ECO:0000269|PubMed:10684261}.
| null | null | null | null | null |
FUNCTION: Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP. {ECO:0000250|UniProtKB:P31431}.
|
Mus musculus (Mouse)
|
O36006
|
P53_MARMO
|
MEEAQSDLSIEPPLSQETFSDLWNLLPENNVLSPVLSPPMDDLLLSSEDVENWFDKGPDEALQMSAAPAPKAPTPAASTLAAPSPATSWPLSSSVPSQNTYPGVYGFRLGFLHSGTAKSVTCTYSPSLNKLFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKKSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRAEYLDDRNTFRHSVVVPYEPPEVGSECTTIHYNYMCNSSCMGGMNRRPILTIITLEGSSGNLLGRNSFEVRVCACPGRDRRTEEENFRKRGEPCPEPPPRSTKRALPNGTSSSPQPKKKPLDGEYFTLKIRGRARFEMFQELNEALELKDAQAEKEPGESRPHPSYLKSKKGQSTSRHKKIIFKREGPDSD
| null |
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};
|
cell cycle [GO:0007049]; cellular senescence [GO:0090398]; circadian behavior [GO:0048512]; DNA damage response [GO:0006974]; entrainment of circadian clock by photoperiod [GO:0043153]; negative regulation of cell growth [GO:0030308]; negative regulation of DNA-templated transcription [GO:0045892]; nucleotide-excision repair [GO:0006289]; oligodendrocyte apoptotic process [GO:0097252]; positive regulation of apoptotic process [GO:0043065]; positive regulation of intrinsic apoptotic signaling pathway [GO:2001244]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein tetramerization [GO:0051262]
|
centrosome [GO:0005813]; cytoplasm [GO:0005737]; endoplasmic reticulum [GO:0005783]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]; nucleolus [GO:0005730]; nucleus [GO:0005634]; PML body [GO:0016605]
|
ATP-dependent DNA/DNA annealing activity [GO:0036310]; copper ion binding [GO:0005507]; DNA binding [GO:0003677]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; promoter-specific chromatin binding [GO:1990841]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]
|
PF00870;PF08563;PF07710;
|
2.60.40.720;6.10.50.20;4.10.170.10;
|
P53 family
|
PTM: Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter (By similarity). Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2. Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Phosphorylated on Ser-33 by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required for acetylation by CREBBP. Phosphorylated by CK2 following UV but not gamma irradiation. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, Ser-33 and Ser-46, leading to accumulation of p53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated by DYRK2 at Ser-46 in response to genotoxic stress. Phosphorylated at Ser-313 and Ser-390 by CDK2 in response to DNA-damage (By similarity). {ECO:0000250}.; PTM: Monomethylated at Lys-370 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-368 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-370 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-368. Dimethylated at Lys-371 by EHMT1 and EHMT2. Monomethylated at Lys-380 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-368 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity). Monomethylated at Arg-331 and dimethylated at Arg-333 and Arg-335 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity). {ECO:0000250|UniProtKB:P04637}.; PTM: Sumoylated with SUMO1. Sumoylated at Lys-384 by UBC9 (By similarity). {ECO:0000250}.; PTM: Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation. Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. Ubiquitinated by MKRN1, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it. Ubiquitinated by COP1, which leads to proteasomal degradation (By similarity). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (By similarity). Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic, leading to TP53 stabilization (By similarity). Deubiquitinated by USP3, leading to stabilization (By similarity). Ubiquitinated by MSL2, promoting its cytoplasmic localization (By similarity). {ECO:0000250|UniProtKB:P02340, ECO:0000250|UniProtKB:P04637}.; PTM: Acetylation of Lys-380 by CREBBP enhances transcriptional activity. Acetylation of Lys-380 by EP300. Deacetylation of Lys-380 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner. Acetylation at Lys-379 increases stability. Deacetylation at Lys-379 by SIRT6 decreases its stability, thereby regulating cell senescence. Acetylated at Lys-118 by KAT5, KAT6A and KAT8; regulating its ability to induce proapoptotic program. {ECO:0000250|UniProtKB:P04637}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus {ECO:0000250|UniProtKB:P04637}. Nucleus, PML body {ECO:0000250|UniProtKB:P04637}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P04637}. Mitochondrion matrix {ECO:0000250|UniProtKB:P04637}. Note=Interaction with BANP promotes nuclear localization. Recruited into PML bodies together with CHEK2. Translocates to mitochondria upon oxidative stress. Translocates to mitochondria in response to mitomycin C treatment (By similarity). Competitive inhibition of TP53 interaction with HSPA9/MOT-2 by UBXN2A results in increased protein abundance and subsequent translocation of TP53 to the nucleus (By similarity). {ECO:0000250|UniProtKB:P04637}.
| null | null | null | null | null |
FUNCTION: Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (By similarity). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (By similarity). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2. {ECO:0000250|UniProtKB:P02340, ECO:0000250|UniProtKB:P04637}.
|
Marmota monax (Woodchuck)
|
O36015
|
TRM7_SCHPO
|
MGRSSKDKRDAYYRLAKEQGWRARSAFKLLQLNEQFNLFEGAKRVVDLCAAPGSWSQVLSRELLKNIDTSIAADEKPMIVAVDLQPMAPIDGVCTLQLDITHPNTLSIILSHFGNEPADLVVSDGAPDVTGLHDLDEYIQAQILLAAFNLAVCVLKPGGKFVAKIFRGRDVSLLYSQLRLMFRKVSCAKPRSSRASSIESFVVCEDFNPPSNFQPDLTKPLCVIDPTNAHEIAPFIACGDLDGYDADATYPVEINMKKATLDVIQPPTAPPYKRAIELKHSKMMS
|
2.1.1.205
| null |
cytoplasmic translation [GO:0002181]; tRNA methylation [GO:0030488]; wobble position ribose methylation [GO:0002130]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleus [GO:0005634]
|
S-adenosyl-L-methionine binding [GO:1904047]; tRNA (cytidine(32)-2'-O)-methyltransferase activity [GO:0106339]; tRNA (guanine(34)-2'-O)-methyltransferase activity [GO:0106340]; tRNA (guanine) methyltransferase activity [GO:0016423]; tRNA 2'-O-methyltransferase activity [GO:0106050]; tRNA methyltransferase activity [GO:0008175]
|
PF01728;
|
3.40.50.150;
|
Class I-like SAM-binding methyltransferase superfamily, RNA methyltransferase RlmE family, TRM7 subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03162}.
|
CATALYTIC ACTIVITY: Reaction=cytidine(32)/guanosine(34) in tRNA + 2 S-adenosyl-L-methionine = 2'-O-methylcytidine(32)/2'-O-methylguanosine(34) in tRNA + 2 H(+) + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:42396, Rhea:RHEA-COMP:10246, Rhea:RHEA-COMP:10247, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74269, ChEBI:CHEBI:74445, ChEBI:CHEBI:74495, ChEBI:CHEBI:82748; EC=2.1.1.205; Evidence={ECO:0000255|HAMAP-Rule:MF_03162, ECO:0000305|PubMed:25404562};
| null | null | null | null |
FUNCTION: Methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs (PubMed:25404562). Requires trm732 for methylation of the cytidine at position 32 of the anticodon loop of substrate tRNAs (PubMed:25404562). Requires trm734 for methylation of the nucleotide at position 34 of the anticodon loop of substrate tRNAs (PubMed:25404562). Methylates tRNA(Phe) (PubMed:25404562). {ECO:0000269|PubMed:25404562}.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
O36019
|
ATG13_SCHPO
|
MPRLNTQLPRMYSAPPGHSKAVSTELNKDLSSVGGRSAKLGQVIHHCFYKTGLIILESRLNVFGTSRPRESSKNNKWFNLEIVETELYAEQFKIWKNIELSPSRKIPPMVLHTYLDISDLSKNQTLSVSDGTHSHAINFNNMSTMKIVLERWIVNLDGEALSTPLELAVLYKKLVVLFRSLYTYTHLMPLWKLKSKIHKLRAHGTSLKVGCALSTDDVLSNDFLPISAPISSSLGSSIATFSFSPVGTPAGDFRISVQYRKNCHFEVHDSDALLSNQLLSADKHQLAASNNSQDFEDGKQYDQPPPSFATRLAKQSDPNSLLQSEIQHLASIESITAQAAPLVTIHPFKSPSLSASPGSNFDNMSISPKVAVNRYIHRGPSATSLNKFSMISDAASKSRAKLPPLTSGSLKLNTLDISNTPNLRRFSSSFGPRERKESFSSRNRLPLVNHPIRSIFKHNVSENPITDHSEHAVYDSEFASKDDLSGFIQLLDSHAHHLNASEGSKSSGSFPGKVQTLTSGISPVAHPHNSLGSSNEIFDIDTYNHSIDNSGSRFTEAVKHNLGNSSHSIMRHHTLGTLRSRPSFSEKSTFPAPLTSISQASTFQGDNRSPSTVIPHTQTEVPSANDTSKQLASLHDMRKSQSPICARSATSAGLPRFEYHTSLSKSLEHSSTPASLQATKTPSPSFVLEPGIPQEYKKHFDNLSEERRQCLTPSTPTYEYYNEHNPNYDDDLLFTMTDMTLEPHDVSAIRLGSPKSDD
| null | null |
autophagosome assembly [GO:0000045]; macroautophagy [GO:0016236]; meiotic cell cycle [GO:0051321]; mitophagy [GO:0000423]; piecemeal microautophagy of the nucleus [GO:0034727]; protein localization to phagophore assembly site [GO:0034497]; protein transport [GO:0015031]; sporulation resulting in formation of a cellular spore [GO:0030435]
|
Atg1/ULK1 kinase complex [GO:1990316]; autophagosome [GO:0005776]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; phagophore assembly site [GO:0000407]
|
protein kinase regulator activity [GO:0019887]
|
PF10033;
|
3.30.900.10;
|
ATG13 family, Fungi subfamily
|
PTM: Phosphorylated (PubMed:17295836). Dephosphorylated under depletion of nitrogen (PubMed:17295836). {ECO:0000269|PubMed:17295836}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Preautophagosomal structure {ECO:0000269|PubMed:23950735}.
| null | null | null | null | null |
FUNCTION: Component of the atg1 kinase complex that activates the atg1 kinase in a nutritional condition dependent manner through the TOR pathway, leading to autophagy (PubMed:23950735, PubMed:26030876). Autophagy functions to supply nitrogen and is activated when cells cannot access exogenous nitrogen, thus ensuring that they can adapt and subsequently propagate (PubMed:17295836). Finally, atg13 is also required for glycogen storage during stationary phase and has a role in meiosis and sporulation (PubMed:16303567, PubMed:19778961). {ECO:0000269|PubMed:16303567, ECO:0000269|PubMed:17295836, ECO:0000269|PubMed:19778961, ECO:0000269|PubMed:23950735, ECO:0000269|PubMed:26030876}.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
O36023
|
SPN1_SCHPO
|
MASMVLADGMPTVKDDSTRSRGSDVDSFTSTDNVTQINVEAAISENKNEEKPIQDNSEQEFNPHVSIIQRQLNGYVGFASLPNQWHRRCVRQGFNFNVLVLGESGSGKSTLVNTLLNRDVYPPTQKSLTGDFGVNPEPTVMINSSAVEIVENGISLQLNVIDTPGFGDFIDNTDCWQPVLTDIEGRYDQYLELEKHNPRSTIQDPRVHACIFFIQPTGHAISAMELRVMLALHEKVNIIPIIAKADTLTDDELNFTKEMILRDIQYHNIRIFFPPTYETDDPESVAENADIMSRIPFAIIASNTFVVNNEGKRVRGRRYPWGVVEVDNEEHSDFPKLREMLIRTHLEELKEQTNKLYEAYRTERLLSSGISQDHSVFREVNPSAKLEEERALHEEKLMKMEAEMKTIFSQKVQEKEDRLKQSENELRTRHREMKAALEKQKADLIDHKNRLMQAKAAAENEKSKRKFFK
| null | null |
cytoskeleton-dependent cytokinesis [GO:0061640]; mitotic cytokinesis [GO:0000281]
|
cell division site [GO:0032153]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; medial cortex [GO:0031097]; medial cortex septin ring [GO:0036391]; microtubule cytoskeleton [GO:0015630]; mitotic actomyosin contractile ring, proximal layer [GO:0120104]; mitotic septin complex [GO:0032151]; nucleus [GO:0005634]; septin complex [GO:0031105]; septin ring [GO:0005940]
|
GTP binding [GO:0005525]; GTPase activity [GO:0003924]; molecular adaptor activity [GO:0060090]
|
PF00735;
|
3.40.50.300;
|
TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily, Septin GTPase family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cell cortex {ECO:0000269|PubMed:15385632}. Note=Localizes to the medial ring at the cell cortex of dividing cells.
| null | null | null | null | null |
FUNCTION: Plays a role in the cell cycle. Involved in a late stage of septum formation leading to the separation of the daughter cells. {ECO:0000269|PubMed:15385632}.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
O36027
|
WSP1_SCHPO
|
MPPSSSITQEDKATIRKYIPKSTNKIIAAAVVKLYVAYPDPNKWNYTGLCGALVLSYDTTAKCCWFKLVDVVNNSGIIWDQELYQNMDYRQDRTFFHSFELDKCLAGFSFANETDAQKFYKKVLDKGCHPESIENPVLSFITRKGSSRHAPNNSNIQPPSAAPPVPGKENYNAVGSKSPNEPELLNSLDPSLIDSLMKMGISQDQIAENADFVKAYLNESAGTPTSTSAPPIPPSIPSSRPPERVPSLSAPAPPPIPPPSNGTVSSPPNSPPRPIAPVSMNPAINSTSKPPLPPPSSRVSAAALAANKKRPPPPPPPSRRNRGKPPIGNGSSNSSLPPPPPPPRSNAAGSIPLPPQGRSAPPPPPPRSAPSTGRQPPPLSSSRAVSNPPAPPPAIPGRSAPALPPLGNASRTSTPPVPTPPSLPPSAPPSLPPSAPPSLPMGAPAAPPLPPSAPIAPPLPAGMPAAPPLPPAAPAPPPAPAPAPAAPVASIAELPQQDGRANLMASIRASGGMDLLKSRKVSASPSVASTKTSNPPVEAPPSNNLMDALASALNQRKTKVAQSDEEDEDDDEWD
| null | null |
actin cortical patch assembly [GO:0000147]; actin filament branching [GO:0090135]; Arp2/3 complex-mediated actin nucleation [GO:0034314]; endocytosis [GO:0006897]; establishment or maintenance of cell polarity [GO:0007163]; mitotic actomyosin contractile ring assembly [GO:1903475]; mitotic cytokinesis [GO:0000281]
|
actin cortical patch [GO:0030479]; mating projection tip [GO:0043332]; medial cortex [GO:0031097]
|
actin monomer binding [GO:0003785]; Arp2/3 complex binding [GO:0071933]
|
PF00568;
|
2.30.29.30;
| null | null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Has a role in regulating actin assembly, so regulating polarized growth. {ECO:0000269|PubMed:11076964}.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
O36028
|
ATCZ_SCHPO
|
MPSLINFDAISSLKSSLHGLSICAFNHLHHVPQHNGSLAHEGPTNQTDYSSRHHESQFSQEAHAEQRSRDDEEANSFEGSCNNSDQSWTSRVTSKKNEAGTESGDASVRRIYVTSIPEEHRHLPSQWFPSNKIRTTKYTPVSFIPKNLWNQFKNIANAFFLFVTLLQCIPLFCPEHLGLSFIPLSVILLTTAIKDGIEDYRRCVLDKKFNNTLTWKLVGFNNANALGEHIGLWRKLKKFISHTVADMSYCLKNSGISSGLATLTVDNISHRHSLESDSAFTLSSVSQDSLEIHEIGNSGPSNSFSVIQEQSTGSSNAKFERVCRKSLLVGDIVKVLADEAIPADLLILSTENSNGVCYVETKNLDGETNLKDKYALCSTKCCKSEYRCSAASFWVECEQPHADLYSLNGVVKAPGAVQSPSESTNGRKIHEEPFSISNVLLCGCTLRNSKWVIGLVLYTGSETRIQKNRGLTPSKRSRITRDLNWTIILNFLLLFAMCLFSGVLRSIYSAQNNSARVFELSKNSNTAPAHGIISIFTSLILFQNLVPISLYITMDIVRSIQSYFIFSDREMYDEKLDCPCSPKSWNISDDLGQIEYIFSDKTGTLTQNIMSFKKCSINGIRYGKSHNEDTCIKKRRNLNYNENLSCKVDLDKKKMLETLSLSDSPNPESITFISSKFVDHLQSNENYIQTEACFEFFKALALCHSVVTDVQDETLIYNAQSPDEEALVKVARDFGFTLLNTKNRRYTIRIRGENKNFRVLDIIPFTSTRKRMSVIIRDEDGIIHLICKGADTVIFPRLSSGQNNIIEKTKKHLASFSSEGFRTLCIARRTIDKQDYLEWKVNFNEANSAIHERNEKVSKVSEMIEQELELLGGTAIEDKLQENVPETIALLAIAGIKLWVLTGDKVETAINIGYSCNLLDPNMTIFRIDANSFGALEEVEAFIRNTLCFNFGYMGTDEEFRFLLKDHSPPSPKHAIVIDGDALNFVLSEQVSFLFLMLCKQCKTVLCCRVSPSQKAAVVALVKKSLNVVTLAIGDGANDVSMIQEADVGVGIKGVEGQAASMSADYAIGQFSFLGRLLLVHGRWDYKRMSQMISFFFYKNVIWTFILFWYQFYNEFDGNYIFDYTYVMLFNLLFTSLPVIIAGCFDQDVDASVSMKNPSLYQRGILGLEWNGKRFWSYMLDGIYQSLVCFGVALFVFKFGDFVSWTGRNIECIEDIGLFISSPTIFVINIFILMNQERLNLISLITWMFSIGVFWIWTFIYSEVGPSYAFHKSASRTCQTFGFWCVTVLTIALCLLPRFSYICLQKLFYPRDIDLLRRRLCAKSDDETSSSSSFATDIEMCEQCNDPLSSKKNSGIVTSVSFDDSNK
|
7.6.2.1
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P39524};
|
phospholipid translocation [GO:0045332]
|
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; phospholipid-translocating ATPase complex [GO:1990531]; plasma membrane [GO:0005886]; trans-Golgi network [GO:0005802]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATPase-coupled intramembrane lipid transporter activity [GO:0140326]; glycosylceramide flippase activity [GO:0140351]; magnesium ion binding [GO:0000287]; phosphatidylcholine flippase activity [GO:0140345]; phosphatidylcholine floppase activity [GO:0090554]; phosphatidylethanolamine flippase activity [GO:0090555]; phosphatidylserine floppase activity [GO:0090556]
|
PF13246;PF16212;PF16209;
|
3.40.1110.10;2.70.150.10;3.40.50.1000;
|
Cation transport ATPase (P-type) (TC 3.A.3) family, Type IV subfamily
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P32660}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:16823372}; Multi-pass membrane protein {ECO:0000255}.
|
CATALYTIC ACTIVITY: Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.; EC=7.6.2.1; Evidence={ECO:0000250|UniProtKB:P32660}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:64612, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P32660}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66133; Evidence={ECO:0000250|UniProtKB:P32660}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:38583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P32660}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38584; Evidence={ECO:0000250|UniProtKB:P32660}; CATALYTIC ACTIVITY: Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine(out) + ATP + H2O = a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine(in) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66036, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:22801, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P32660}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66037; Evidence={ECO:0000250|UniProtKB:P32660}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:38567, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57262, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P32660}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568; Evidence={ECO:0000250|UniProtKB:P32660};
| null | null | null | null |
FUNCTION: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide, phosphatidylcholine, phosphatidylethanolamine, and small amounts of phosphatidylserine from the lumenal to the cytosolic leaflet of the cell membrane and ensures the maintenance of asymmetric distribution of phospholipids. {ECO:0000250|UniProtKB:P32660}.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
O36307
|
NCAP_ANDV
|
MSTLQELQENITAHEQQLVTARQKLKDAEKAVEVDPDDVNKSTLQSRRAAVSTLETKLGELKRQLADLVAAQKLATKPVDPTGLEPDDHLKEKSSLRYGNVLDVNSIDLEEPSGQTADWKAIGAYILGFAIPIILKALYMLSTRGRQTVKDNKGTRIRFKDDSSFEEVNGIRKPKHLYVSMPTAQSTMKAEEITPGRFRTIACGLFPAQVKARNIISPVMGVIGFGFFVKDWMDRIEEFLAAECPFLPKPKVASEAFMSTNKMYFLNRQRQVNESKVQDIIDLIDHAETESATLFTEIATPHSVWVFACAPDRCPPTALYVAGVPELGAFFSILQDMRNTIMASKSVGTAEEKLKKKSAFYQSYLRRTQSMGIQLDQKIIILYMLSWGKEAVNHFHLGDDMDPELRQLAQSLIDTKVKEISNQEPLKL
|
3.1.-.-
| null |
virus-mediated perturbation of host defense response [GO:0019049]
|
host cell Golgi apparatus [GO:0044177]; host cell perinuclear region of cytoplasm [GO:0044220]; ribonucleoprotein complex [GO:1990904]; viral nucleocapsid [GO:0019013]
|
endonuclease activity [GO:0004519]; RNA binding [GO:0003723]
|
PF00846;
|
1.20.58.90;
|
Hantavirus nucleocapsid protein family
| null |
SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P05133}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P05133}. Host Golgi apparatus, host cis-Golgi network {ECO:0000250|UniProtKB:P05133}. Note=Internal protein of virus particle. {ECO:0000250|UniProtKB:P05133}.
| null | null | null | null | null |
FUNCTION: Encapsidates the genome protecting it from nucleases (Probable). The encapsidated genomic RNA is termed the nucleocapsid (NC) and serves as template for transcription and replication (Probable). The nucleocapsid has a left-handed helical structure (By similarity). As a trimer, specifically binds and acts as a chaperone to unwind the panhandle structure formed by the viral RNA (vRNA) termini (By similarity). Involved in the transcription and replication initiation of vRNA by mediating primer annealing (By similarity). Plays a role in cap snatching by sequestering capped RNAs in P bodies for use by the viral RdRp during transcription initiation (By similarity). Substitutes for the cellular cap-binding complex (eIF4F) to preferentially facilitate the translation of capped mRNAs (By similarity). Initiates the translation by specifically binding to the cap and 40S ribosomal subunit (By similarity). Prevents the viral glycoprotein N (Gn) from autophagy-dependent breakdown maybe by blocking autophagosome formation (By similarity). Inhibits host EIF2AK2/PKR dimerization to prevent PKR-induced translational shutdown in cells and thus the activation of the antiviral state (PubMed:25410857). Inhibits IFN signaling responses directed by the dsRNA sensors RIGI and IFIH1/MDA5, probably by interacting with host E3 ubiquitin ligase TRIM21 (PubMed:24549848). As a consequence, TBK1-directed IRF3 phosphorylation and TBK1 autophosphorylation are inhibited (PubMed:24549848, PubMed:30867297). Also displays sequence-unspecific DNA endonuclease activity (By similarity). {ECO:0000250|UniProtKB:P05133, ECO:0000250|UniProtKB:Q89462, ECO:0000269|PubMed:24549848, ECO:0000269|PubMed:25410857, ECO:0000269|PubMed:30867297, ECO:0000305}.
|
Andes orthohantavirus (ANDV) (Andes virus)
|
O36634
|
FUS_HRSVB
|
MELLIHRLSAIFLTLAINALYLTSSQNITEEFYQSTCSAVSRGYFSALRTGWYTSVITIELSNIKETKCNGTDTKVKLIKQELDKYKNAVTELQLLMQNTPAANNRARREAPQYMNYTINTTKNLNVSISKKRKRRFLGFLLGVGSAIASGIAVSKVLHLEGEVNKIKNALLSTNKAVVSLSNGVSVLTSKVLDLKNYINNQLLPIVNQQSCRISNIETVIEFQQKNSRLLEINREFSVNAGVTTPLSTYMLTNSELLSLINDMPITNDQKKLMSSNVQIVRQQSYSIMSIIKEEVLAYVVQLPIYGVIDTPCWKLHTSPLCTTNIKEGSNICLTRTDRGWYCDNAGSVSFFPQADTCKVQSNRVFCDTMNSLTLPSEVSLCNTDIFNSKYDCKIMTSKTDISSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKLEGKNLYVKGEPIINYYDPLVFPSDEFDASISQVNEKINQSLAFIRRSDELLHNVNTGKSTTNIMITTIIIVIIVVLLSLIAIGLLLYCKAKNTPVTLSKDQLSGINNIAFSK
| null | null |
entry receptor-mediated virion attachment to host cell [GO:0098670]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of syncytium formation by virus [GO:0060141]; symbiont entry into host cell [GO:0046718]
|
host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
| null |
PF00523;
|
1.10.287.2480;6.10.250.1160;6.20.370.50;
|
Paramyxoviruses fusion glycoprotein family
|
PTM: [Fusion glycoprotein F0]: The F glycoprotein is synthesized as a F0 inactive precursor that is heavily N-glycosylated and processed at two sites by a host furin-like protease probably in the Golgi. The cleavage site between p27 and F1 may occur after endocytosis to yield the mature F1 and F2 proteins. Both cleavages are required for membrane fusion and p27 is released from the processed protein. {ECO:0000250|UniProtKB:P03420}.
|
SUBCELLULAR LOCATION: [Fusion glycoprotein F0]: Host Golgi apparatus membrane {ECO:0000250|UniProtKB:P03420}; Single-pass membrane protein {ECO:0000250|UniProtKB:P03420}.; SUBCELLULAR LOCATION: [Fusion glycoprotein F1]: Virion membrane {ECO:0000250|UniProtKB:P03420}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P03420}. Host cell membrane {ECO:0000250|UniProtKB:P03420}; Single-pass membrane protein {ECO:0000250|UniProtKB:P03420}. Note=Localized at the host apical membrane. {ECO:0000250|UniProtKB:P03420}.; SUBCELLULAR LOCATION: [Fusion glycoprotein F2]: Virion membrane {ECO:0000250|UniProtKB:P03420}. Host cell membrane {ECO:0000250|UniProtKB:P03420}. Note=Localized at the host apical membrane. {ECO:0000250|UniProtKB:P03420}.
| null | null | null | null | null |
FUNCTION: [Fusion glycoprotein F0]: Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins. {ECO:0000250|UniProtKB:P03420}.; FUNCTION: [Fusion glycoprotein F1]: Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the coiled coil regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs at the plasma or endosomal membrane. The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate. F protein is involved in the entry into the host cell through the interaction with host IGF1R. This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1. Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. F protein may trigger p53-dependent apoptosis. {ECO:0000250|UniProtKB:P03420}.; FUNCTION: [Fusion glycoprotein F2]: Major determinant of the species specificity of RSV infection. The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate. F protein is involved in the entry into the host cell through the interaction with host IGF1R. This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1. Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. F protein seems to trigger p53-dependent apoptosis. {ECO:0000250|UniProtKB:P03420}.
|
Human respiratory syncytial virus B (strain B1)
|
O36635
|
L_HRSVB
|
MDPIINGNSANVYLTDSYLKGVISFSECNALGSYLFNGPYLKNDYTNLISRQSPLLEHMNLKKLTITQSLISRYHKGELKLEEPTYFQSLLMTYKSMSSSEQIATTNLLKKIIRRAIEISDVKVYAILNKLGLKEKDRVKPNNNSGDENSVLTTIIKDDILSAVESNQSYTNSDKNHSVNQNITIKTTLLKKLMCSMQHPPSWLIHWFNLYTKLNNILTQYRSNEVKSHGFILIDNQTLSGFQFILNQYGCIVYHKGLKKITTTTYNQFLTWKDISLSRLNVCLITWISNCLNTLNKSLGLRCGFNNVVLSQLFLYGDCILKLFHNEGFYIIKEVEGFIMSLILNITEEDQFRKRFYNSMLNNITDAAIKAQKNLLSRVCHTLLDKTVSDNIINGKWIILLSKFLKLIKLAGDNNLNNLSELYFLFRIFGHPMVDERQAMDAVRINCNETKFYLLSSLSTLRGAFIYRIIKGFVNTYNRWPTLRNAIVLPLRWLNYYKLNTYPSLLEITENDLIILSGLRFYREFHLPKKVDLEMIINDKAISPPKDLIWTSFPRNYMPSHIQNYIEHEKLKFSESDRSRRVLEYYLRDNKFNECDLYNCVVNQSYLNNSNHVVSLTGKERELSVGRMFAMQPGMFRQIQILAEKMIAENILQFFPESLTRYGDLELQKILELKAGISNKSNRYNDNYNNYISKCSIITDLSKFNQAFRYETSCICSDVLDELHGVQSLFSWLHLTIPLVTIICTYRHAPPFIKDHVVNLNEVDEQSGLYRYHMGGIEGWCQKLWTIEAISLLDLISLKGKFSITALINGDNQSIDISKPVRLIEGQTHAQADYLLALNSLKLLYKEYAGIGHKLKGTETYISRDMQFMSKTIQHNGVYYPASIKKVLRVGPWINTILDDFKVSLESIGSLTQELEYRGESLLCSLIFRNIWLYNQIALQLRNHALCNNKLYLDILKVLKHLKTFFNLDSIDMALSLYMNLPMLFGGGDPNLLYRSFYRRTPDFLTEAIVHSVFVLSYYTGHDLQDKLQDLPDDRLNKFLTCVITFDKNPNAEFVTLMRDPQALGSERQAKITSEINRLAVTEVLSIAPNKIFSKSAQHYTTTEIDLNDIMQNIEPTYPHGLRVVYESLPFYKAEKIVNLISGTKSITNILEKTSAIDTTDINRATDMMRKNITLLIRILPLDCNKDKRELLSLENLSITELSKYVRERSWSLSNIVGVTSPSIMFTMDIKYTTSTIASGIIIEKYNVNSLTRGERGPTKPWVGSSTQEKKTMPVYNRQVLTKKQRDQIDLLAKLDWVYASIDNKDEFMEELSTGTLGLSYEKAKKLFPQYLSVNYLHRLTVSSRPCEFPASIPAYRTTNYHFDTSPINHVLTEKYGDEDIDIVFQNCISFGLSLMSVVEQFTNICPNRIILIPKLNEIHLMKPPIFTGDVDIIKLKQVIQKQHMFLPDKISLTQYVELFLSNKALKSGSNINSNLILVHKMSDYFHNAYILSTNLAGHWILIIQLMKDSKGIFEKDWGEGYITDHMFINLNVFFNAYKTYLLCFHKGYGKAKLECDMNTSDLLCVLELIDSSYWKSMSKVFLEQKVIKYIVNQDTSLHRIKGCHSFKLWFLKRLNNAKFTVCPWVVNIDYHPTHMKAILSYIDLVRMGLINVDKLTIKNKNKFNDEFYTSNLFYISYNFSDNTHLLTKQIRIANSELEDNYNKLYHPTPETLENISLIPVKSNNSNKPKFCISGNTESIMMSTFSNKMHIKSSTVTTRFNYSKQDLYNLFPNVVIDRIIDHSGNTAKSNQLYITTSHQTSLVRNSASLYCMLPWHHVNRFNFVFSSTGCKISIEYILKDLKIKDPSCIAFIGEGAGNLLLRTVVELHPDIRYIYRSLKDCNDHSLPIEFLRLYNGHINIDYGENLTIPATDATNNIHWSYLHIKFAEPISIFVCDAELPVTANWSKIIIEWSKHVRKCKYCSSVNRCILIAKYHAQDDIDFKLDNITILKTYVCLGSKLKGSEVYLVLTIGPANILPVFDVVQNAKLIFSRTKNFIMPKKTDKESIDANIKSLIPFLCYPITKKGIKTSLSKLKSVVNGDILSYSIAGRNEVFSNKLINHKHMNILKWLDHVLNFRSAELNYNHLYMIESTYPYLSELLNSLTTNELKKLIKITGSVLYNLPNEQ
|
2.1.1.375; 2.7.7.48; 2.7.7.88; 3.6.1.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P28887}; Note=For RNA-directed RNA polymerase activity. Mn(2+) can stimulate de novo initiation but it is inefficient at supporting elongation of de novo initiated RNA. {ECO:0000250|UniProtKB:P28887};
| null |
host cell cytoplasm [GO:0030430]; virion component [GO:0044423]
|
ATP binding [GO:0005524]; GTPase activity [GO:0003924]; metal ion binding [GO:0046872]; mRNA 5'-cap (guanine-N7-)-methyltransferase activity [GO:0004482]; RNA-dependent RNA polymerase activity [GO:0003968]
|
PF14314;PF14318;PF00946;
| null |
Paramyxovirus L protein family
| null |
SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P28887}. Host cytoplasm {ECO:0000250|UniProtKB:P28887}. Note=Localizes in cytoplasmic inclusion bodies. {ECO:0000250|UniProtKB:P28887}.
|
CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000250|UniProtKB:P28887}; CATALYTIC ACTIVITY: Reaction=a 5'-end triphospho-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + GDP + H(+) = a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + diphosphate; Xref=Rhea:RHEA:65436, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16799, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:58189, ChEBI:CHEBI:156484, ChEBI:CHEBI:156503; EC=2.7.7.88; Evidence={ECO:0000250|UniProtKB:P28887}; CATALYTIC ACTIVITY: Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + 2 S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + H(+) + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:65376, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16798, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156483, ChEBI:CHEBI:156484; EC=2.1.1.375; Evidence={ECO:0000250|UniProtKB:P03523}; CATALYTIC ACTIVITY: Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-methionine = a 5'-end (5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:65380, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16801, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156482, ChEBI:CHEBI:156484; Evidence={ECO:0000250|UniProtKB:P03523}; CATALYTIC ACTIVITY: Reaction=a 5'-end (5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:65440, Rhea:RHEA-COMP:16798, Rhea:RHEA-COMP:16801, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156482, ChEBI:CHEBI:156483; Evidence={ECO:0000250|UniProtKB:P03523};
| null | null | null | null |
FUNCTION: Responsible for RNA synthesis (replicase and transcriptase), cap addition, and cap methylation. Performs also the polyadenylation of subgenomic mRNAs by a stuttering mechanism at a slipery stop site present at the end of viral genes. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at two different sites in the 3' leader promoter thereby initiating either genome replication or mRNA transcription. In the transcription mode, the polymerase performs the sequential transcription of all mRNAs using a termination-reinitiation mechanism responding to gene start and gene end signals. Some polymerase disengage from the template at each gene junction, resulting in a decreasing abundance of transcripts from the 3' to the 5' end of the genome. The first gene is the most transcribed, and the last the least transcribed. Needs as cofactors the phosphoprotein for processivity and the M2-1 anti-termination protein. Polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides (By similarity). Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation (By similarity). In the replication mode, the polymerase replicates the whole viral genome without recognizing the gene end transcriptional signals. The ability of the polymerase to override the gene end signals as it is producing the antigenome is probably due to replicative RNA becoming encapsidated with nucleoprotein as it is synthesized (By similarity). {ECO:0000250|UniProtKB:P03523, ECO:0000250|UniProtKB:P28887}.
|
Human respiratory syncytial virus B (strain B1)
|
O36966
|
POLN_DCVEB
|
MESDKSMACLNRILMNKMMFVEDKISTLKMVADYYQKEVKYDFDAVESPREAPVFRCTCRFLGYTIMTQGIGKKNPKQEAARQMLLLLSGDVETNPGPVQSRPVYYRYNDPRYTRLEKAIERRDDKIKTLIKELRRQIKNRKIYSQGMFDKLTKQISDGIKDGVGSEQMNGNLTRICDFLENTLPGLQANIQATVIDTTDKYVSLKEDIMKIVLVILLVRLLMVWKKYRASLCVILIFIFKFYGFDQKLIDLIMDLKNKIFSQGALEDTVEEVVYHPWFHTCGKIIFAVMAFLTIKKIPGKQDWDSYITRLDRIPKSIEGAKKITDYCSEYFNIANDQIKMMVLGKTKEELQRANGLYGEIQAWAQEVRQYLELDQRNKIDLDTETANRVEQLWIKGLKFKSEPLLSKEMSALVHTTLLPAKQLYEYVSCSPVKGGGPRMRPICLWLVGESGVGKTEMVYPLCIDVLREMGMIKKDDFHHQVYGRQVETEFWDGYKGQKIVIYDDAFQKKDDKTAANPEIFEVIRSCNTFPQHLHMAALHDKNTFSAAELLLYTTNDYNVKLESITFPDAFFNRMGDMAYKVSPKKEYGIETEKGNSGKTYLKLDKSKLDKTKAIDLSVYEFQKIVRDEKSDAGWIDSGSPLDYEDFAKLVCSKWKEAKQSSMNKLKFLEEYAIRAQVGSEENSEYGDCIDFVDDIAKRLQKGETLEEIEFDYASDPEMFTQYYHFKSTIKPASRWQKYKDRMDICLSDCKTYLAKKYEEIKKILAEHPILTILGMIGVALSALAMYYWFSKSLDPVEAEVAPSGDAKTVRLPRKLVEIGASGDVKTQKIVKPVVETEWHRNNKGEIEISCDECGMHRMSAFNNMTDEEFDNCTYEDLNKDQKRELAQWSTKDSWLGRFFLSRDRKNKVGIWAEVGQSGDVKTNKAQIKRVEAGAEELVTVALTQGCSDDAAHNLMIDVFQKNTYRMSYFRGDKRYQLGNCTFVRGWSFIMPYHFVQAVFARRLPPNTIISLSQQMSEDLMQIPLSHFFSAGVDNFYLTDNCVRLPFKNGDFRDCVMVNLHSRMCTPHRDLVRHFILTSDQGKLKGSFSGAMATFHVNNMGLYRVYNWLNAVRPCDKKIEIFHPEDGFEYPEESYIQRDCYEYNAPTRTGDCGSIIGLYNKYLERKIIGMHIAGNDAEEHGYACPLTQECLETAFSALVNKNKKNISSQFYYEIPNMVDPLGDSSVPEGKFYALGKSSIRVGQAVNSSIIPSRIYGKLSVPTMKPALLKPTILNNKVHNPLLSGLKKCGVDTAVLSDDEVLSASQDVCRVMLNQYNKNLNKTKYQRILTYEEAIRGTQDDEFMCAINRTTSPGFPYAQMKRNAPGKQQWMGFGEEFDFTSNYALALRKDVEQLIEDCASGKISNVIFVDTLKDERRDIAKVNVGKTRVFSAGPQHFVVAFRQYFLPFAAWLMHNRISNEVAVGTNVYSSDWERIAKRLKTKGSHVIAGDFGNFDGSLVAQILWAIFWEIFVVWLKQFIDIENSEGKRILCICLGLWSHLVHSVHIYEDNVYMWTHSQPSGNPFTVIINCLYNSIIMRLSWIRVMEKFQPRLKSMKWFNEYVALITYGDDNVLNIDAKVVEWFNQINISEVMTEMRHEYTDEAKTGDIVKSRKLEDIFFLKRKFRFSPELQRHVAPLKIEVIYEMLNWSRRSIDPDEILMSNIETAFREVVYHGKEEYDKLRSAVLALKVPQELPENPQILTYNQYLHDIEYLADPLYDF
|
2.7.7.48; 3.4.22.-
| null |
DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; viral RNA genome replication [GO:0039694]; virus-mediated perturbation of host defense response [GO:0019049]
| null |
ATP binding [GO:0005524]; cysteine-type endopeptidase activity [GO:0004197]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]
|
PF12381;PF00680;PF00910;
|
3.30.160.20;3.30.70.270;2.40.10.10;
| null |
PTM: Protein 1A might be expressed through a ribosomal skip from one codon to the next without formation of a peptide bond.
| null |
CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
| null | null | null | null |
FUNCTION: Protein 1A functions as a suppressor of RNA-mediated gene silencing, an antiviral defense mechanism of insect cells. Binds to long dsRNA and to a lesser extent, to siRNA.; FUNCTION: RNA-directed RNA polymerase replicates genomic and antigenomic RNA.
|
Drosophila C virus (strain EB) (DCV)
|
O36979
|
POLG_ZYMVS
|
MAAIMIGSISVPIIGSAQCATAPIGNRVNIVAPGHMAICKPQMRSHAYYKHASQKLSEQSSRGIEVLNSFFNNDPEDAFRLTRNGMSKVKKGPNGRIILRKPKARHVFERINLEKSEKEQKGKFFNGEYDTTVTSIKGVTTSKENDLGAFSLRSPFYKRTCKKEKRRITRENIVCVDDVNNLCERILKITRDKNIPVEIIGKRRNHHTLTFKKFKGSFVGKVSLAPERSQMKHVEMSYGQFDYILQAICRITSTKHVRDEDIKPGCSGWVFSTDHALTQKYSRLPYLVIRGRDDDGIVNALEPVLFYSDVEHYSFQNEVQFFNGWRKMFDKLKPHSDHTCKVDHNNEECGEMAAVLSQAIFPVLKLSCQVCREKLSRVSFEEFKDFLSRNFMTHESEWSTLRDGVHCDNVLKLIKGAVQTTQNLKLSSDIMKLVQNHTSTHMKQIQDINKALMKGSLVTQDELDLALKQLLEMTQWFKNHMHLTGEEALKTFRNKRSNKAMINPSLLCDNQLDKNGNFIWGERGYHSKRLFKNFFEEVIPSEGYTKYIVRNFPNGTRKLAIGSLIVPLNLDRARTALLGESIEKEPLTSACISQQNENYIHSCCCVTMDDGTPMYSELKSPTKRHLVIGASGDPKYIDLPASEAERMYIAKEGYCYLNIFLAMLVNVNENEAKDFTKMIRDVLIPMLGQWPSLMDVATAAYILGVFHPETRCAELPRILVDHATQTMHVIDSYGSLTVGYHVLKAGTVNHLIQFASNDLQSEMKHYRVGGTPTQRIRLEEQLIKGIFKPKIMMQLLHDDPYILLLGMISPTILVHMYRMRHFERGIEIWIKRDHEIGKIFVILEQLTRKVALAEILVDQLDLISEASPHLLEIMNGCQDNQRAYAPALDLLTIQVEREFSNKELKTNGYPDLHQTLHDMREKMYAKQLHNSWQELSLLEKSCVTVRLKQFSIFTERNLTQRAKERKHASSLQFVHECFITTRVHAKSIRDAGVRKLNEALVGTCKFFFSCGFRIFARCYSDIIYFVNVCLVFSLVLQMSNTVRNMIAATREEKERAMANKADENERTLMHMYHIFCKKQDDAPIYNDFLEHVRSVRPDLEETLLYMAGGEVVTAQAKSAVQIQFEKIIAVLALLTMCFDAERSDAIFKILTKLKIVFGTVGETVRLQGLEDIENLEDDKRLTIDFDINTNEAQSSTTFDVHFEDWWNRQLQQNRTVPHYRTTGKFLEFTRSTAAYVANEIASSSEGEFLVRGAVGSGKSTSLPAHLAKKGKVLLLEPTRPLAENVSRQLAGDPFFQNVTLRMRGLSCFGSSNITVMTSGFAFHYYVNNPHQLMEFDFVIIDECHVTDSATIAFNCALKEYSFAGKLIKVSATPPGRECDFDTQFAVKVKTEDHLSFNAFVGAQKTGSNADMVQHGNNILVYVASYNEVDMLSKLLTERQFSVTKVDGRTMQLGKTTIETHGTSQKPHFIVATNIIENGVTLDVECVVDFGLKVVAELDSEKRCVRYSKKPVSYGERIQRLGRVGRSKPGTALRIGHTEKGIENIPEFIATEAAALSFAYGLSVTTHGVSTNNLGKCTVKQMKCALNFELTPFFTTHLIRHDGSMHPLIHEELKQFKLRDSEMVLNKVALPHQFVSQWMDQSEYERIGVHIQCHESTRIPFYTNGIPDKVYERIWKCIQENKNDALFGKLSSAFPSKVSYTLSTDPAALPRTIAIIDHLLAEEMMKRNHFDMISSAVTGYSFSLAGIADSFRKRYMRDHTAHHIAILQQARAQLLEFNSKNVNINNLSDLEGIGVIKSVVLQSKQEVSSFLGLRGKWDGRKFANDVILAVMTLFGGGWFMWEYFTKKVNEPVRVESKKRRSQKLKFRDAYDRKVGREIFGDNDTIGRTFGEAYTKRGKVKGNNSTKGMGRKTRNFVHLYGVEPEIYSFIRFVDPLTGHTLDESTHTDISLVQEEFGNIREKFLENDLISRQSIINKPGIQAYFMGKGTEEALKVDLTPHVPLLLCRNTNAIAGYPERENELRQTGTPIKVSFKEVPEKNEHVELESKSIYKGVRDYNGISTIVCQLTNDSDGLKETMYGIGYGPIIITNGHLFRKNNGTLLVRSWHGEFTVKNTTTLKVHFIEGKDVVLVRMPKDFPPFRSNASFRAPKREERACLVGTNFQEKSLRSTVSESSMTIPEGTGSYWIHWISTNEGDCGLPMVSTTDGKIIGIHGLASTVSSKNYFVPFTDDLLTTHLSKLDDLTWTQHWLWQPSKIAWGSLNLVDEQPGPEFRISNLVKDLLTSGVETQSKRERWVYESCEGNLRAVGSAQSALVTKHVVKGKCPFFEEYLQTHAEANTYFRPLMGEYQPSKLNKEAFKKDFFKYNKPVVVNQLDHDKFLGAVNGVIRMMCDFEFNECRFITDPEEIYDSLNMKAAIGAQYRGKKKEYFEGLDNFDRERLLFQSCERLFNGHKGLWNGSLKAELRPLEKVQANKTRTFTAAPIDTLLGAKVCVDDFNNEFYSKNLKCPWTVGMTKFYGGWDKLMRELPDGWLYCHADGSQFDSSLTPALLNAVLIIRSFYMEDWWVGQEMLENLYAEIVYTPILAPDGTIFKKFRGNNSGQPSTVVDNTLMVVISIYYACMKFGWSYEEIENKLVFFANGDDLILAVKDEDSGLLDNMSASFSELGLNYDFSERTHKREDLWFMSHQAMLVDGMYIPKLEKERIVSILEWDRSKEIMHRTEAICAAMIEAWGHTDLLREIRKFYLWFVEKEEVRELATLGKAPYIAETALRKLYTDKGAETGELARYLQALHQDIFFEQGDTVMLQSDTQTREAGAGASKKDKDEDKDKKKDVASSSASEKAVATATKDKDVNAGSHGKIVPRLSKITKKMSLPRVKGSVILDIDHLLEYKPDQIELYNTRASHQQFASWFNQVKAEYDLNEQQMGVVMNGFMVWCIENGTSPDINGVWVMMDGNEQVEYPLKPIVENAKPTLRQIMHHFSDAAEAYIEMRNAEAPYMPRYGLLRNLRDRSLARYAFDFYEVNSKTPDRAREAVAQMKAAALSNVSSRLFGLDGNVATTSEDTERHTARDVNRNMHTLLGVNTMQ
|
2.7.7.48; 3.4.-.-; 3.4.22.44; 3.4.22.45; 3.6.4.-
| null |
DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; viral RNA genome replication [GO:0039694]; virus-mediated perturbation of host defense response [GO:0019049]
|
helical viral capsid [GO:0019029]; host cell cytoplasmic vesicle [GO:0044161]; host cell nucleus [GO:0042025]
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ATP binding [GO:0005524]; cysteine-type endopeptidase activity [GO:0004197]; helicase activity [GO:0004386]; hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides [GO:0016818]; RNA binding [GO:0003723]; RNA-dependent RNA polymerase activity [GO:0003968]; structural molecule activity [GO:0005198]
|
PF00270;PF00271;PF00863;PF00851;PF01577;PF00767;PF08440;PF13608;PF00680;
|
3.30.70.270;3.90.70.150;3.40.50.300;2.40.10.10;
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Potyviridae genome polyprotein family
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PTM: [Viral genome-linked protein]: VPg is uridylylated by the polymerase and is covalently attached to the 5'-end of the genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase (By similarity). {ECO:0000250|UniProtKB:P09814}.; PTM: [Genome polyprotein]: Potyviral RNA is expressed as two polyproteins which undergo post-translational proteolytic processing. Genome polyprotein is processed by NIa-pro, P1 and HC-pro proteinases resulting in the production of at least ten individual proteins. P3N-PIPO polyprotein is cleaved by P1 and HC-pro proteinases resulting in the production of three individual proteins. The P1 proteinase and the HC-pro cleave only their respective C-termini autocatalytically. 6K1 is essential for proper proteolytic separation of P3 from CI (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: [6 kDa protein 1]: Host cytoplasmic vesicle. Note=Probably colocalizes with 6K2-induced vesicles associated with host chloroplasts. {ECO:0000250|UniProtKB:P13529}.; SUBCELLULAR LOCATION: [6 kDa protein 2]: Host cytoplasmic vesicle {ECO:0000250|UniProtKB:P09814}. Note=6K-induced vesicles associate with host chloroplasts. {ECO:0000250|UniProtKB:P09814}.; SUBCELLULAR LOCATION: [Viral genome-linked protein]: Host nucleus {ECO:0000250|UniProtKB:P21231}. Note=Binds to host plant eIF4E proteins in the host nucleus. {ECO:0000250|UniProtKB:P21231}.; SUBCELLULAR LOCATION: [Capsid protein]: Virion {ECO:0000305}.
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CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes glutaminyl bonds, and activity is further restricted by preferences for the amino acids in P6 - P1' that vary with the species of potyvirus, e.g. Glu-Xaa-Xaa-Tyr-Xaa-Gln-|-(Ser or Gly) for the enzyme from tobacco etch virus. The natural substrate is the viral polyprotein, but other proteins and oligopeptides containing the appropriate consensus sequence are also cleaved.; EC=3.4.22.44; Evidence={ECO:0000250|UniProtKB:P04517}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes a Gly-|-Gly bond at its own C-terminus, commonly in the sequence -Tyr-Xaa-Val-Gly-|-Gly, in the processing of the potyviral polyprotein.; EC=3.4.22.45; Evidence={ECO:0000250|UniProtKB:P04517};
| null | null | null | null |
FUNCTION: [Helper component proteinase]: Required for aphid transmission and also has proteolytic activity. Only cleaves a Gly-Gly dipeptide at its own C-terminus. Interacts with virions and aphid stylets. Acts as a suppressor of RNA-mediated gene silencing, also known as post-transcriptional gene silencing (PTGS), a mechanism of plant viral defense that limits the accumulation of viral RNAs. May have RNA-binding activity. {ECO:0000250|UniProtKB:P04517}.; FUNCTION: [Cytoplasmic inclusion protein]: Has helicase activity. It may be involved in replication.; FUNCTION: [6 kDa protein 1]: Indispensable for virus replication. {ECO:0000250|UniProtKB:P13529}.; FUNCTION: [6 kDa protein 2]: Indispensable for virus replication. {ECO:0000250|UniProtKB:P09814}.; FUNCTION: [Viral genome-linked protein]: Mediates the cap-independent, EIF4E-dependent translation of viral genomic RNAs (By similarity). Binds to the cap-binding site of host EIF4E and thus interferes with the host EIF4E-dependent mRNA export and translation (By similarity). VPg-RNA directly binds EIF4E and is a template for transcription (By similarity). Also forms trimeric complexes with EIF4E-EIF4G, which are templates for translation (By similarity). {ECO:0000250|UniProtKB:P18247}.; FUNCTION: [Nuclear inclusion protein A]: Has RNA-binding and proteolytic activities. {ECO:0000250|UniProtKB:P04517}.; FUNCTION: [Nuclear inclusion protein B]: An RNA-dependent RNA polymerase that plays an essential role in the virus replication.; FUNCTION: [Capsid protein]: Involved in aphid transmission, cell-to-cell and systemis movement, encapsidation of the viral RNA and in the regulation of viral RNA amplification. {ECO:0000250|UniProtKB:P04517}.
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Zucchini yellow mosaic virus (strain Singapore) (ZYMV)
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O39521
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REPA_BEYDV
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MPSASKNFRLQSKYVFLTYPKCSSQRDDLFQFLWEKLTPFLIFFLGVASELHQDGTTHYHALIQLDKKPCIRDPSFFDFEGNHPNIQPARNSKQVLDYISKDGDIKTRGDFRDHKVSPRKSDARWRTIIQTATSKEEYLDMIKEEFPHEWATKLQWLEYSANKLFPPQPEQYVSPFTESDLRCHEDLHNWRETHLYHVSIDAYTFIHPVSYDQAQSDLEWMADLTRMREGLGSDTPASTSADQLVPERPPGLEVSGDTTTGTGPSTSPTTMNTPPIISSTTSPSSSSHCGSN
|
3.1.21.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|PROSITE-ProRule:PRU01364}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|PROSITE-ProRule:PRU01364}; Note=Divalent metal cations, possibly Mg(2+) or Mn(2+). {ECO:0000255|PROSITE-ProRule:PRU01364};
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DNA replication [GO:0006260]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]
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host cell cytoplasm [GO:0030430]; host cell nucleus [GO:0042025]
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DNA binding [GO:0003677]; endodeoxyribonuclease activity, producing 5'-phosphomonoesters [GO:0016888]; metal ion binding [GO:0046872]; nucleotide binding [GO:0000166]; nucleotidyltransferase activity [GO:0016779]; structural molecule activity [GO:0005198]
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PF00799;PF08283;
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3.40.1310.20;
|
Geminiviridae Rep protein family
| null |
SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:16972938}. Host cytoplasm {ECO:0000269|PubMed:16972938}. Note=distributed equally throughout both the nucleus and the cytoplasm.
| null | null | null | null | null |
FUNCTION: Implicated in enhancement of V-sense gene expression. Acts a an inhibitor of C-sense gene transcription. {ECO:0000269|PubMed:14645928, ECO:0000269|PubMed:16972938}.
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Bean yellow dwarf virus (BeYDV)
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O39522
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REP_BEYDV
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MPSASKNFRLQSKYVFLTYPKCSSQRDDLFQFLWEKLTPFLIFFLGVASELHQDGTTHYHALIQLDKKPCIRDPSFFDFEGNHPNIQPARNSKQVLDYISKDGDIKTRGDFRDHKVSPRKSDARWRTIIQTATSKEEYLDMIKEEFPHEWATKLQWLEYSANKLFPPQPEQYVSPFTESDLRCHEDLHNWRETHLYHDEGRTGVRHPSLYICGPTRTGKTTWARSLGRHNYWNGTIDFTNYDEHATYNIIDDIPFKFVPLWKQLIGCQSDFTVNPKYGKKKKIKGGIPSIILCNPDEDWMLSMTSQQKDYFEDNCVTHYMCDGETFFARESSSH
|
2.7.7.-; 3.1.21.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|PROSITE-ProRule:PRU01364}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|PROSITE-ProRule:PRU01364}; Note=Divalent metal cations, possibly Mg(2+) or Mn(2+). {ECO:0000255|PROSITE-ProRule:PRU01364};
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DNA replication [GO:0006260]
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host cell nucleus [GO:0042025]
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ATP binding [GO:0005524]; DNA binding [GO:0003677]; endodeoxyribonuclease activity, producing 5'-phosphomonoesters [GO:0016888]; helicase activity [GO:0004386]; metal ion binding [GO:0046872]; nucleotidyltransferase activity [GO:0016779]; structural molecule activity [GO:0005198]
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PF00799;PF08283;
|
3.40.1310.20;
|
Geminiviridae Rep protein family
| null |
SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:16972938}.
| null | null | null | null | null |
FUNCTION: Essential for the replication of viral ssDNA. The closed circular ssDNA genome is first converted to a superhelical dsDNA. Rep binds a specific region at the genome origin of replication. It introduces an endonucleolytic nick within the conserved sequence 5'-TAATATTAC-3' in the intergenic region of the genome present in all geminiviruses, thereby initiating the rolling circle replication (RCR). Following cleavage, binds covalently to the 5'-phosphate of DNA as a tyrosyl ester. The cleavage gives rise to a free 3'-OH that serves as a primer for the cellular DNA polymerase. The polymerase synthesizes the (+) strand DNA by rolling circle mechanism. After one round of replication, a Rep-catalyzed nucleotidyl transfer reaction releases a circular single-stranded virus genome, thereby terminating the replication. Displays origin-specific DNA cleavage, nucleotidyl transferase, ATPase and helicase activities (By similarity). Acts a an inhibitor of C-sense gene transcription. {ECO:0000250, ECO:0000269|PubMed:14645928, ECO:0000269|PubMed:16972938}.
|
Bean yellow dwarf virus (BeYDV)
|
O39828
|
MREP_FBNY2
|
MARQVICWCFTLNNPLSPLSLHDSMKYLVYQTEQGEAGNIHFQGYIEMKKRTSLAGMKKLIPGAHFEKRRGTQGEARAYSMKEDTRLEGPWEYGEFVPTIEDKLREVMNDMKITGKRPIEYIEECCNTYDKSASTLREFRGELKKKKAISSWELQRKPWMGEVDALLQERDGRRIIWVYGPQGGEGKTSYAKHLVKTRDAFYSTGGKTADIAFAWDHQELVLFDFPRSFEEYVNYGVIEQLKNGIIQSGKYQSVIKYSDYVEVIVFANFTPRSGMFSEDRIVYVYA
|
2.7.7.-; 3.1.21.-; 3.6.1.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305|PubMed:17472345}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000305|PubMed:17472345}; Note=Divalent metal cations, possibly Mg(2+) or Mn(2+). {ECO:0000305|PubMed:17472345};
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DNA replication [GO:0006260]
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host cell nucleus [GO:0042025]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; DNA binding [GO:0003677]; endodeoxyribonuclease activity, producing 5'-phosphomonoesters [GO:0016888]; metal ion binding [GO:0046872]; nucleotidyltransferase activity [GO:0016779]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]
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PF00910;PF02407;
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3.40.1310.20;
|
Nanoviridea/circoviridae replication-associated protein family
| null |
SUBCELLULAR LOCATION: Host nucleus {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
| null | null | null | null |
FUNCTION: Essential for the replication of all genomic viral ssDNA (trans-replication). The closed circular ssDNA genome is first converted to a superhelical dsDNA. Rep binds a specific hairpin at the genome origin of replication. Introduces an endonucleolytic nick within the conserved sequence 5'-A[GT]TATTAC-3' in the intergenic region of the genome, thereby initiating the rolling circle replication (RCR). Following cleavage, binds covalently to the 5'-phosphate of DNA as a tyrosyl ester. The cleavage gives rise to a free 3'-OH that serves as a primer for the cellular DNA polymerase. The polymerase synthesizes the (+) strand DNA by rolling circle mechanism. After one round of replication, a Rep-catalyzed nucleotidyl transfer reaction releases a circular single-stranded virus genome, thereby terminating the replication. Displays origin-specific DNA cleavage, nucleotidyl transferase, ATPase and helicase activities.
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Faba bean necrotic yellows virus (isolate SV292-88) (FBNYV)
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O39927
|
POLG_HCVEU
|
MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRKGPRLGVRATRKTSERSQPRGRRQPIPKARQPQGRHWAQPGYPWPLYGSEGCGWAGWLLSPRGSRPHWGPNDPRRRSRNLGKVIDTLTCGFADLMWYIPVVGAPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIFLLALLSCLTTPASALTYGNSSGLYHLTNDCSNSSIVLEADAMILHLPGCLPCVRVGNQSTCWHAVSPTLATPNASTPATGFRRHVDLLAGAAVVCSSLYIGDLCGSLFLAGQLFAFQPRRHWTVQDCNCSIYTGHVTGHKMAWDMMMNWSPTTTLVLSSILRVPEICASVIFGGHWGILLAVAYFGMAGNWLKVLAVLFLFAGVEAQTMIAHGVSQTTSGFASLLTPGAKQNIQLINTNGSWHINRTALNCNDSLQTGFLASLFYTHKFNSSGCPERMAACKPLAEFRQGWGQITHKNVSGPSDDRPYCWHYAPRPCEVVPARSVCGPVYCFTPSPVVVGTTDKRGNPTYTWGENETDVFMLESLRPPTGGWFGCTWMNSTGFTKTCGAPPCQIVPGNYNSSANELLCPTDCFRKHPEATYQRCGSGPWVTPRCLVDYAYRLWHYPCTVNFTLHKVRMFVGGTEHRFDVACNWTRGERCELHDRNRIEMSPLLFSTTQLSILPCSFSTMPALSTGLIHLHQNIVDVQYLYGVSTNVTSWVVKWEYIVLMFLVLADARICTCLWLMLLISTVEAAVERLVVLNAASAAGTAGWWWAVLFLCCVWYVKGRLVPACTYMALGMWPLLLTILALPPRAYAMDNEQAASLGAVGLLVITIFSITPMYKKLLNCFIWWNQYFLARAEAMVHEWVPDLRVRGGRDSIILLTCLLHPQLGFEVTKILLAVLAPLYILQYSLLKVPYFVRAHILLRACLLVRRLAGGKYVQACLLRLGAWTGTFVYDHLAPLSDWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILSGLPVSARLGNLVLLGPADDMQRGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEVQVVSTDTQSFVATSINGVMWTVYHGPGFKTLAGPKGPVCQMYTNVDLDLVGWPSPPGARSLTPCNCGSSDLYLVTREADVIPARRRGDSRAALLSPRPISTLKGSSGGPIMCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMRSPSFTDNSTPPAVPQTYQVGYLHAPTGSGKSTRVPAAYASQGYKVLVLNPSVAATLSFGSYMRQAYGVEPNIRTGVRTVTTGGAITYSTYGEFLADGGCSGGAYDIIICDECHSTDPTTVLGVGTVLDQAETAGVRLTVLPTATPPGSVTVPHPNITETALPTTGEIPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAGKLKSLGLNAVAFYRGVDVSVIPTSGDVVVCATDALMTGYTGDFDSVIDCNVAVTQVVDFSLDPTFSIETTTVPQDAVSRSQRRGRTGRGKPGVYRFVSQGERPSGMFDTVVLCEAYDTGCAWYELTPSETTVRLRAYMNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSHTKQAGENFAYLVAYQATVCARAKAPPPSWDMMWKCLIRLKPTLTGPTPLLYRLGAVQNGVITTHPITKYIMTCMSADLEVITSTWVLVGGVLAALAAYCLSVGCVVICGRITLTGKPAVVPDREILYQQFDEMEECSRHIPYLAEGQQIAEQFRQKVLGLLQASAKQAEELKPAVHSAWPRVEDFWRKHMWNFVSGIQYLAGLSTLPGNPAVASLMSFTASLTSPLRTSQTLLLNILGGWIAAQVAPPPASTAFVVSGLAGAAVGSIRLGRVLVDVLAGYGAGVSGALVAFKIMSGECPSTEDMVNLLPALLSPGVALVGVVCAAILRRHVGPAEGANQWMNRLIAFASRGNHVSPTHYVPETDASKNVTQILTSLTITSLLRRLHQWVNEDTATPCATSWLRDVWDWVCTVLSDFKVWLQAKLFPRLPGIPFLSCQAGYRGVWAGDGVCHTTCTCGAVIAGHVKNGTMKITGPKTCSNTWHGTFPINATTTGPSTPRPAPNYQRALWRVSAEDYVEVRRLGDCHYVVGVTAEGLKCPCQVPAPEFFTEVDGVRIHRYAPPCKPLLRDEVTFSVGLSNYAVGSQLPCEPEPDVTVVTSMLTDPTHITAETAARRLKKGSPPSLASSSANQLSAPSLRATCTTSQKHPEMELLQANLLWKHEMGSHIPRVQSENKVVVLDSFELYPLEYEEREISVSVECHRQPRCKFPPVFPVWARPDNNPPFIQAWQMPGYEPPVVSGCAVAPPKPAPVPPPRRKRLVHLDESTVSHALAQLADKVFVESSNDPGPSSDSGLSITSPVPPDPTTPEDAGSEAESYSSMPPLEGEPGDPDLSSGSWSTVSDEDDVVCCSMSYSWTGALITPCAAEEEKLPINPLSNSLVRHHNMVYSTTSRSASLRQKKVTFDRVQVFDQHYQDVLKEIKLRASTVQAKLLSIEEACDLTPSHSARSKYGYGAQDVRSRASKAVDHIPSVWEGLLEDSDTPIPTTIMAKNEVFCVDPSKGGRKPARLIVYPDLGVRVCEKMALYDVTQKLPQAVMGPAYGFQYSPNQRVEYLLKMWRSKKVPMGFSYDTRCFDSTVTERDIRTENDIYQSCQLDPVARRVVSSLTERLYVGGPMANSKGQSCGYRRCRASGVLPTSMGNTLTCYLKAQAACRAANIKDCDMLVCGDDLVVICESAGVQEDTASLRAFTDAMTRYSAPPGDAPQPTYDLELITSCSSNVSVAHEGNGKKYYYLTRDCTTPLARAAWETARHTPVNSWLGNIIMFAPTIWVRMVLMNHFFSILQSQEQLEKAFDFDIYGVTYSVSPLDLPAIIQRLHGMAAFSLHGYSPVELNRVGACLRKLGVLPSRAWRHRARAVRAKLIAQGGKAAICGKYLFNWAVKTKLKLTPLVSASKLDLSGWFVAGYDGGDIYHSVSQARPRFLLLGLLLLTVGVGIFLLPAR
|
2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
|
COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
|
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF07652;PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
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FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 6a (isolate EUHK2) (HCV)
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O39928
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POLG_HCVEV
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MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPKLGVRATRKNSERSQPRGRRQPIPKARRPTGRSWGQPGYPWPLYANEGLGWAGWLLSPRSSRPNWGPNDPRRKSPNLGRVIHTLTCGFPHLMGYIPLVGGPVGGVSRALAHGVKVLEDGINYATGNLPGCPFSIFVLALLWCLTVPASAVPYRNASGVYHVTNDCPNSSIVYEADNLILHAPGCVPCVLEDNVSRCWVQITPTLSAPSFGAVTALLRRAVDYLAGGAAFCSALYVGDACGALSLVGQMFTYKPRQHTTVQDCNCSIYSGHITGHRMAWDMMMKWSPTTALLMAQLLRIPQVVIDIIAGGHWGVLLAAAYFASTANWAKVILVLFLFAGVDGRTHTVGGTVGQGLKSLTSFFNPGPQRQLQFVNTNGSWHINSTALNCNDSLQTGFIAGLMYAHKFNSSGCPERMSSCRPLAAFDQGWGTISYATISGPSDDKPYCWHYPPRPCGVVPARDVCGPVYCFTPSPVVVGTTDRRGCPTYNWGSNETDILLLNNIRPPAGNWFGCTWMNSTGFVKNCGAPPCNLGPTGNNSLKCPTDCFRKHPDATYTRCGSGPWLTPRCLVHYPYRLWHYPCTVNYTIFKVRMFIGGLEHRLEAACNWTYGERCDLEDRDRAELSPLLHTTTQWAILPCSFTPTPALSTGLIHLHQNIVDTQYLYGLSSSIVSWAVKWEYIMLVFLLLADARICTCLLILLLICQAEATCKNVIVLNAAAAAGNHGFFWGLLVVCLAWHVKGRLVPGATYLCLGVWPLLLVRLLRPHRALALDSSDGGTVGCLVLIVLTIFTLTPGYKKKVVLVMWWLQYFIARVEAIIHVWVPPLQVKGGRDAVIMLTCLFHPALGFEITKILFGILGPLYLLQHSLTKVPYFLRARALLRLCLLAKHLVYGKYVQAALLHLGRLTGTYIYDHLAPMKDWAASGLRELTVATEPIVFSAMETKVITWGADTAACGNILAVLPVSARRGREIFLGPADDIKTSGWRLLAPITAYAQQTRGVLGAIVLSLTGRDKNEAEGEVQFLSTATQTFLGICINGVMWTLFHGAGSKTLAGPKGPVVQMYTNVDKDLVGWPSPPGKGSLTRCTCGSADLYLVTRHADVIPARRRGDTRASLLSPRPISYLKGSSGGPIMCPSGHVVGVFRAAVCTRGVAKALEFVPVENLETTMRSPVFTDNSTPPAVPHEFQVGHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATFGFGAYMSRAYGVDPNIRTGVRTVTTGAGITYSTYGKFFADGGCSGGAYDVIICDECHSQDATTILGIGTVLDQAETAGARLVVLATAIPPGSVTTPHPNIEEVALPSEGEIPFYGRAIPLVLIKGGRHLIFCHSKKKCDELAKQLTSLGVNAVAYYRGLDVAVIPATGDVVVCSTDALMTGFTGDFDSVIDCNSAVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRHGIYRYVSSGERPSGIFDSVVLCECYDAGCAWYDLTPAETTVRLRAYLNTPGLPVCQEHLEFWEGVFTGLTNIDAHMLSQAKQGGENFPYLVAYQATVCVRAKAPPPSWDTMWKCMICLKPTLTGPTPLLYRLGAVQNEITLTHPITKYIMACMSADLEVITSTWVLVGGVVAALAAYCLTVGSVAIVGRIILSGRPAITPDREVLYQQFDEMEECSASLPYVDEARAIAGQFKEKVLGLIGTAGQKAETLKPAATSMWSKAEQFWAKHMWNFVSGIQYLAGLSTLPGNPAVATLMSFTAAVTSPLTTHQTLLFNILGGWVASQIAPPTAATAFVVSGMAGAAVGNIGLGRVLIDILAGYGTGVAGALVAFKIMCGERPTAEELVNLLPSILCPGALVVGVICAAVLRRHIGPGEGAVQWMNRLIAFASRGNHGSPTHYVPETDASAKVTQLLSSLTVTSLLKRLHTWIGEDYSTPCDGTWLRAIWDWVCTALTDFKAWLQAKLLPQLPGVPFFSCQKGYKGVWRGDGVNSTKCPCGATISGHVKNGTMRIVGPKLCSNTWQGTFPINATTTGPSVPAPAPNYKFALWRVGAADYAEVRRVGDYHYITGVTQDNLKCPCQVPSPEFFTELDGVRIHRFAPPCNPLLREEVTFSVGLHSYVVGSQLPCEPEPDVTVLTSMLSDPAHITAETAKRRLNRGSPPSLANSSASQLSAPSLKATCTIQGHHPDADLIKANLLWRQCMGGNITRVEAENKVEILDCFKPLKEEEDDREISVSADCFKKGPAFPPALPVWARPGYDPPLLETWKRPDYDPPQVWGCPIPPAGPPPVPLPRRKRKPMELSDSTVSQVMADLADARFKVDTPSIEGQDSALGTSSQHDSGPEEKRDDNSDAASYSSMPPLEGEPGDPDLSSGSWSTVSGEDNVVCCSMSYTWTGALITPCSAEEEKLPINPLSNTLLRHHNLVYSTSSRSAGLRQKKVTFDRLQVLDDHYREVVDEMKRLASKVKARLLPLEEACGLTPPHSARSKYGYGAKEVRSLDKKALKHIEGVWQDLLDDSDTPLPTTIMAKNEVFAVEPSKGGKKPARLIVYPDLGVRVCEKRALYDVAQKLPTALMGPSYGFQYSPAQRVDFLLKAWKSKKIPMAFSYDTRCFDSTITEHDIMTEESIYQSCDLQPEARVAIRSLTQRLYCGGPMYNSKGQQCGYRRCRASGVFTTSMGNTMTCYIKALASCRAAKLRDCTLLVCGDDLVAICESQGTHEDEASLRAFTEAMTRYSAPPGDPPVPAYDLELVTSCSSNVSVARDASGNRIYYLTRDPQVPLAKAAWETAKHSPVNSWLGNIIMYAPTLWARIVLMTHFFSVLQSQEQLEKTLAFEMYGSVYSVTPLDLPAIIQRLHGLSAFSLHSYSPSEINRVASCLRKLGVPPLRAWRHRARAVRAKLIAQGGRAAICGIYLFNWAVKTKRKLTPLADADRLDLSSWFTVGAGGGDIYHSMSRARPRNLLLCLLLLSVGVGIFLLPAR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
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FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 5a (isolate EUH1480) (HCV)
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O39929
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POLG_HCVED
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MSTNPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRSWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPNDPRGRSRNLGKVIDTLTCGFADLMGYIPLVGAPVGSVARALAHGVRALEDGINYATGNLPGCSFSIFLLALLSCLTVPASAVNYRNVSGIYHVTNDCPNSSIVYEADHHIMHLPGCVPCVREGNQSRCWVALTPTVAAPYIGAPLESLRSHVDLMVGAATVCSGLYIGDLCGGLFLVGQMFSFRPRRHWTTQDCNCSIYTGHITGHRMAWDMMMNWSPTTTLVLAQVMRIPTTLVDLLSGGHWGVLVGVAYFSMQANWAKVILVLFLFAGVDAETHVSGAAVGRSTAGLANLFSSGSKQNLQLINSNGSWHINRTALNCNDSLNTGFLASLFYTHKFNSSGCSERLACCKSLDSYGQGWGPLGVANISGSSDDRPYCWHYAPRPCGIVPASSVCGPVYCFTPSPVVVGTTDHVGVPTYTWGENETDVFLLNSTRPPHGAWFGCVWMNSTGFTKTCGAPPCEVNTNNGTWHCPTDCFRKHPETTYAKCGSGPWITPRCLIDYPYRLWHFPCTANFSVFNIRTFVGGIEHRMQAACNWTRGEVCGLEHRDRVELSPLLLTTTAWQILPCSFTTLPALSTGLIHLHQNIVDVQYLYGVGSAVVSWALKWEYVVLAFLLLADARVSAYLWMMFMVSQVEAALSNLININAASAAGAQGFWYAILFICIVWHVKGRFPAAAAYAACGLWPCFLLLLMLPERAYAYDQEVAGSLGGAIVVMLTILTLSPHYKLWLARGLWWIQYFIARTEAVLHVYIPSFNVRGPRDSVIVLAVLVCPDLVFDITKYLLAILGPLHILQASLLRIPYFVRAQALVKICSLLRGVVYGKYFQMVVLKSRGLTGTYIYDHLTPMSDWPPYGLRDLAVALEPVVFTPMEKKVIVWGADTAACGDIIRGLPVSARLGNEILLGPADTETSKGWRLLAPITAYAQQTRGLFSTIVTSLTGRDTNENCGEVQVLSTATQSFLGTAVNGVMWTVYHGAGAKTISGPKGPVNQMYTNVDQDLVGWPAPPGVRSLAPCTCGSADLYLVTRHADVIPVRRRGDTRGALLSPRPISILKGSSGGPLLCPMGHRAGIFRAAVCTRGVAKAVDFVPVESLETTMRSPVFTDNSTPPAVPQTYQVAHLHAPTGSGKSTKVPAAHAAQGYKVLVLNPSVAATLGFGVYMSKAYGIDPNIRSGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECYSTDSTTILGIGTVLDQAETAGVRLTVLATATPPGSVTTPHSNIEEVALPTTGEIPFYGKAIPLELIKGGRHLIFCHSKKKCDELARQLTSLGLNAVAYYRGLDVSVIPTSGDVVVCATDALMTGFTGDFDSVIDCNTSVIQTVDFSLDPTFSIEITTVPQDAVSRSQRRGRTGRGRLGTYRYVTPGERPSGMFDTAELCECYDAGCAWYELTPAETTTRLKAYFDTPGLPVCQDHLEFWESVFTGLTHIDGHFLSQTKQSGENFPYLVAYQATVSAKVWLAPPSWDTMWKCLIRLKPTLHGPTPLLYRLGSVQNEVVLTHPITKYIMACMSADLEVVTSTWVLVGGVLAALAAYCLSVGSVVIVGRVVLSGQPAVIPDREVLYQQFDEMEECSKHLPLVEHGLQLAEQFKQKALGLLNFAGKQAQEATPVIQSNFAKLEQFWANDMWNFISGIQYLAGLSTLPGNPAIASLMSFTAAVTSPLTTQQTLLFNILGGWVASQIRDSDASTAFVVSGLAGAAVGSVGLGKILVDILPGYGAGVRGAVVTFKIMSGEMPSTEDLVNLLPAILSPGALVVEVVCPAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAARRVTTILSSLTVTSLLRRLHKWINEDCSTPCAESWLWEVWDWVLHVLSDFKTCLKAKFVPLMPGIPLLSWPRGYKGEWRGDGVMHTTCPCGADLAGHIKNGSMRITGPKTCSNTWHGTFPINAYTTGPGVPIPAPNYKFALWRVSAEDYVEVRRVGDFHYVTGVTQDNIKFPCQVPAPELFTEVDGIRIHRHAPKCKPLLRDEVSFSVGLNSFVVGSQLPCEPEPDVAVLTSMLTDPSHITAESARRRLARGSRPSLASSSASQLSPRLLQATCTAPHDSPGTDLLEANLLWGSTATRVETDEKVIILDSFESCVAEQNDDREVSVAAEILRPTKKFPPALPIWARPDYNPPLTETWKQQDYQAPTVHGCALPPAKQPPVPSPRRKRTVQLTESVVSTALAELAAKTFGQSEPSSDRDTDLTTPTETTDSGPIVVDDASDDGSYSSMPPLEGEPGDPDLTSDSWSTVSGSEDVVCCSMSYSWTGALVTPCAAEESKLPISPLSNSLLRHHNMVYATTTRSAVTRQKKVTFDRLQVVDSTYNEVLKEIKARASRVKPRLLTTEEACDLTPPHSARSKFGYGKKDVRSHSRKAINHISSVWKDLLDDNNTPIPTTIMAKNEVFAVNPAKGGRKPARLIVYPDLGSRVCEKRALHDVIKKTALAVMGAAYGFQYSPAQRVEFLLTAWKSKNDPMGFSYDTRCFDSTVTEKDIRVEEEVYQCCDLEPEARKVITALTDRLYVGGPMHNSKGDLCGYRRCRATGVYTTSFGNTLTCYLKATAAIRAAALRDCTMLVCGDDLVVIAESDGVEEDNRALRAFTEAMTRYSAPPGDAPQPAYDLELITSCSSNVSVAHDVTGKKVYYLTRDPETPLARAVWETVRHTPVNSWLGNIIVYAPTIWVRMILMTHFFSILQSQEALEKALDFDMYGVTYSITPLDLPAIIQRLHGLSAFTLHGYSPHELNRVAGALRKLGVPPLRAWRHRARAVRAKLIAQGGRAKICGIYLFNWAVKTKLKLTPLPAAAKLDLSGWFTVGAGGGDIYHSMSHARPRYLLLCLLILTVGVGIFLLPAR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
| null | null | null | null |
FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 4a (isolate ED43) (HCV)
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O40955
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POLN_RUBVR
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MERLLDEVLAPGGPYNLTVGSWVRDHVRSIVEGAWEVRDVVSAAQKRAIVAVIPRPVFTQMQVSDHPALHAISRYTRRHWIEWGPKEALHVLIDPSPGLLREVARVERRWVALCLHRTARKLATALAETASEAWHADYVCALRGAPSGPFYVHPEDVPHGGRAVADRCLLYYTPMQMCELMRTIDATLLVAVDLWPVALAAHVGDDWDDLGIAWHLDHDGGCPADCRGAGAGPTPGYTRPCTTRIYQVLPDTAHPGRLYRCGPRLWTRDCAVAELSWEVAQHCGHQARVRAVRCTLPIRHVRSLQPSARVRLPDLVHLAEVGRWRWFSLPRPVFQRMLSYCKTLSPDAYYSERVFKFKNALSHSITLAGNVLQEGWKGTCAEEDALCAYVAFRAWQSNARLAGIMKSAKRCAADSLSVAGWLDTIWGAIKRFFGSVPLAERMEEWEQDAAVAAFDRGPLEDGGRHLDTVQPPKSPPRPEIAATWIVHAASADRHCACAPRCDVPRERPSAPAGPPDDEALIPPWLFAEHRALRCREWDFEVLRARADTAAAPAPLAPRPARYPTVLYRHPAHHGPWLTLDEPGEADAALVLCDPLGQPLRGPERHFAAGAHMCAQARGLQAFVRVVPPPERPWADGGARAWAKFFRGCAWAQRLLGEPAVMHLPYTDGDVPQLIALALRTLAQQGAALALSVRDLPGGAAFDANAVTAAVRAGPGQSAATSSPPGDPPPPRCARRSQRHSDARGTPPPAPARDPPPPAPSPPAPPRAGDPVPPTSAGPADRARDAELEVAYEPSGPPTSTKADPDSDIVESYARAAGPVHLRVRDIMDPPPGCKVVVNAANEGLLAGSGVCGAIFANATAALAADCRRLAPCPTGEAVATPGHGCGYTHIIHAVAPRRPRDPAALEEGEALLERAYRSIVALAAARRWARVACPLLGAGVYGWSAAESLRAALAATRTEPAERVSLHICHPDRATLTHASVLVGAGLAARRVSPPPTEPLASCPAGDPGRPAQRSASPPATPLGDATAPEPRGCQGCELCRYTRVTNDRAYVNLWLERDRGATSWAMRIPEVVVYGPEHLATHFPLNHYSVLKPAEVRPPRGMCGSDMWRCRGWQGVPQVRCTPSNAHAALCRTGVPPRVSTRGGELDPNTCWLRAAANVAQAARACGAYTSAGCPRCAYGRALSEARTHKDFAALSQRWSASHADASSDGTGDPLDPLMETVGCACSRVWVGSEHEAPPDHLLVSLHRAPNGPWGVVLEVRARPEGGNPTGHFVCAVGGGPRRVSDRPHLWLAVPLSRGGGTCAATDEGLAQAYYDDLEVRRLGDDAMARAALASVQRPRKGPYNIRVWNMAAGAGKTTRILAAFTREDLYVCPTNALLHEIQAKLRARDIEIKNAATYERALTKPLAAYRRIYIDEAFTLGGEYCAFVASQTTAEVICVGDRDQCGPHYANNCRTPVPDRWPTERSRHTWRFPDCWAARLRAGLDYDIEGERTGTFACNLWDGRQVDLHLAFSRETVRRLHEAGIRAYTVREAQGMSVGTACIHVGRDGTDVALALTRDLAIVSLTRASDALYLHELEDGSLRAAGLSAFLDAGALAELKEVPAGIDRVVAVEQAPPPLPPADGIPEAQDVPPFCPRTLEELVFGRAGHPHYADLNRVTEGEREVRYMRISRHLLNKNHTEMPGTERVLSAVCAVRRYRAGEDGSTLRTAVARQHPRPFRQIPPPRVTAGVAQEWRMTYLRERIDLTDVYTQMGVAARELTDRYARRYPEIFAGMCTAQSLSVPAFLKATLKCVDAALGPRDTEDCHAAQGKAGLEIRAWAKEWVQVMSPHFRAIQKIIMRALRPQFLVAAGHTEPEVDAWWQAHYTTNAIEVDFTEFDMNQTLATRDVELEISAALLGLPCAEDYRALRAGSYCTLRELGSTETGCERTSGEPATLLHNTTVAMCMAMRMVPKGVRWAGIFQGDDMVIFLPEGARSAALKWTPAEVGLFGFHIPVKHVSTPTPSFCGHVGTAAGLFHDVMHQAIKVLCRRFDPDVLEEQQVALLDRLRGVYAALPDTVAANAAYYDYSAERVLAIVRELTAYARGRGLDHPATIGALEEIQTPYARANLHDAD
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2.7.7.48; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|PROSITE-ProRule:PRU01237}; Note=Zn(2+) is necessary for the protease activity. The protease can also function efficiently with Cd(2+) and Co(2+). {ECO:0000255|PROSITE-ProRule:PRU01237};
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DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; RNA processing [GO:0006396]; viral RNA genome replication [GO:0039694]
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host cell membrane [GO:0033644]; host cell perinuclear region of cytoplasm [GO:0044220]; membrane [GO:0016020]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; metal ion binding [GO:0046872]; mRNA methyltransferase activity [GO:0008174]; O-acetyl-ADP-ribose deacetylase activity [GO:0061463]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]
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PF01661;PF05407;PF00978;PF12601;PF01443;
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3.40.220.10;3.40.50.300;
| null |
PTM: [Non-structural polyprotein p200]: Specific enzymatic cleavage by its own cysteine protease yield mature proteins p150 and p90. {ECO:0000250|UniProtKB:Q86500}.
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SUBCELLULAR LOCATION: [Non-structural polyprotein p200]: Host membrane {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm {ECO:0000250|UniProtKB:Q86500}. Note=Localizes to cytoplasmic foci at 24 hpi. {ECO:0000250|UniProtKB:Q86500}.; SUBCELLULAR LOCATION: [Protease/methyltransferase p150]: Host membrane {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm {ECO:0000250|UniProtKB:Q86500}. Note=At 36 hpi, localizes to the host cytoplasm, probably in vesicles inside host vacuoles of endosomal and lysosomal origin (By similarity). At 72 hpi, localizes to filamentous structures in the host cytoplasm (By similarity). {ECO:0000250|UniProtKB:P13889, ECO:0000250|UniProtKB:Q86500}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase p90]: Host membrane {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm {ECO:0000250|UniProtKB:Q86500}. Note=Localizes to the cytoplasm and to the cytoplasmic fibers formed by protease/methyltransferase p150. {ECO:0000250|UniProtKB:Q86500}.
|
CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000250|UniProtKB:Q86500, ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:Q86500}; CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:Q86500};
| null | null | null | null |
FUNCTION: [Non-structural polyprotein p200]: Probable principal replicase for the negative-strand DNA, which replicates the 40S (+) genomic RNA into (-) antigenomic RNA. It cannot replicate the (-) into (+) until cleaved into p150 and p90 mature proteins. {ECO:0000250|UniProtKB:Q86500}.; FUNCTION: [Protease/methyltransferase p150]: Protease that cleaves the precursor polyprotein into two mature products. Together with RNA-directed RNA polymerase p90, replicates the 40S genomic and antigenomic RNA by recognizing replications specific signals. The heterodimer P150/p90 is probably the principal replicase for positive-strand genomic RNA and the 24S subgenomic RNA, which codes for structural proteins. Responsible for the mRNA-capping of the viral mRNAs. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. Forms fibers late in the infection that may be involved in cell-to-cell spread of the virus RNA in the absence of virus particle formation. {ECO:0000250|UniProtKB:Q86500}.; FUNCTION: [RNA-directed RNA polymerase p90]: Together with protease/methyltransferase p150, replicates the 40S genomic and antigenomic RNA by recognizing replications specific signals. The heterodimer P150/p90 is probably the principal replicase for positive-strand genomic RNA and the 24S subgenomic RNA, which codes for structural proteins. A helicase activity is probably also present. {ECO:0000250|UniProtKB:Q86500}.
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Rubella virus (strain RA27/3 vaccine) (RUBV)
|
O41174
|
POLG_PEV9U
|
MGMQMSKNTAGSHTTVTQASGGSHINYTNINYYSHSASASQNKQDITQDPSKFTQPMVDIMKESAVPLKSPSAEACGYSDRVAQLTLGNSTITTQEAANITVAYGEWPSYLSDLDATAVDKTTKPGVSCDRFYTLPGKKWEATTKGWEWKLPDALTELGVFGQNCQFHFLYRCGWSIHVQCNATKFHQGTLLVVAVPDHQLGTTYQPEFDNVMPGKAGREVKYPYNFEDGTSLANSLIYPHQWINLRTNNSATLVLPYANAIPMDSPIRHSSWSLLVIPVVPLACATGTTPFVGITITLAPMFSEFSGLRRAIAQGIPTTNTPGSYQFLTTDEDSSACILPDFTPTQEIHIPGEVKNLQALCQVESLLEINNVDGKTGIERLRLEVSTQSELDRQLFALKVSFTEGEIMSKTLCGVMCSYYTQWSGSLEITFMFTGSFMTTGKLLLAYTPPGGSAPASREDAMLGTHVIWDFGLQSSITLVVPWICGGYYRDVNRANNYYAAGYVTGWFQTNMVIPPDFPSTAYILCFLAAQPNFSLRILKDRPDITQTAALQAPVETALNSAISSVIAGITAQDTQPSSHNISTSETPALQAAETGASSNASDEGMMETRHVVNTNTVSETSIESFYGRCGLVSIKEIADNKQVEKWLVNFNEFVQLRAKIELFTYMRFDIEFTLVATFTKGNSASQHPVQVQVMYLPPEQLLQLQQDSYAWQSAANPSAIFSANTVPARFSVPFVGTANAYTIMYDGYNVFGSNRPSADYGMINSSHMGSMAFRAISQLQATEKVKFMDLCQVKDVRAWCPRAPRMAPYKYIRNPVFETQDRIVPNRNNITTTGAFGQQSGAIYVGNYKIMNRHLATHEDWENVEWEDYNRDILVARTTAHGADKLARCHCNTGVYYCKSRNKHYPVTSRVQASIGSRLVSTTQLDTRPICSLPSGISEPGDCGGILRCQHGVIGIVTAGGQGVVGFADVRDLFWVEHEAMEQGLTDYIQQLGNSFGQGFTAEITNYASQLSEMLIGADGMVERCLQTFVKVISAVVIATRSQGDVPTILATLALIGCDGSPWRWLKRQFCGIFKIPYVEKQGDDWLKKFTSYVNAFKGLDWVAEKIMKFIDWMKNKLIPQARERQEFTTNLKTLPLLEAQVATLEHSCPTTEQQETIFGNIQYLAHHCRRYAPLYAAEARRVYALEKRILGYIQFKSKQRIEPVCLLIHGTAGTGKSLATSIIGRKLAEYEHSEVYAIPPDSDHFDGYQQQAVVVMDDLNQNPDGKDMVAFCQMVSTVPYHVPMAAIEEKGMLFTSSYVLASTNSGSIHPPTVSNSKALSRRFAFDVDIEVSEHYKTHNGTLDVVNATQRCEDCCPANFKTCMPLICGEAYQLVDRRNGMRYSIDTMISAMRAEWKRRNQVGLCYVRLFQGPPQFKPLKISVDPEIPAPPAIADLLASVDSEEVREYCKKKGWIVEVPVTATTLERNVSIATTILSSLVLLTSVITLVYLVYRLFAGYQGPYTGLPNAKPKPPVLREVRAQGPLMDFGVGMMKKNIVTVRTGAGEFTGLGVHDHVLVLPKHSHPAEIVVVDGKETPVEDAYNLTDEQGVSLELTLVTLKRNEKFRDIRAMIPENPCGTNEAVVCVNTSNFPNAFLPVGKVEYYGYLNLAGSPTHRTMMYNFPTKAGQCGGVVLSTGKVLGIHIGGNGAQGFCAALKRSYFTKPQGKIDWVEPSKKHGFPVINAPSKTKLEPSVFFDVFEGVKEPAALHPKDPRLEVNLEEALFSKYTGNVDIEMPEEMKEAVDHYANQLLALDIPTEPLSMEEAIYGTEGLEALDLTTSAGYPYVTMGIKKRDILNKETRDVKKMQECIDKYGLNLPMVTYIKDELRSKEKVKKGKSRLIEASSLNDSVAMRCYFGNLYKAFHQNPGTLTGCAVGCDPDTFWSKIPVMMDGELFGFDYTAYDASLSPLMFQALQMVLEKIGFGEGKHFIDNLCYSHHLFRDKYYFVKGGMPSGCSGTSIFNSMINNIIIRTVVLQTYKGIELDQLKIIAYGDDVIASYPYRIDPAELAKAGAKLGLHMTPPDKSETYVDLDWTNVTFLKRNFVPDEKYPFLVHPVMPMKEIYESIRWTRDARNTQDHVRSLCLLAWHNGRKEYEEFCRKIRSVPVGRALHLPSYSSLLREWYEKF
|
2.7.7.48; 3.4.22.28; 3.4.22.29; 3.6.1.15
|
COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P03300}; Note=Binds 2 magnesium ions that constitute a dinuclear catalytic metal center (By similarity). The magnesium ions are not prebound but only present for catalysis (By similarity). Requires the presence of 3CDpro or 3CPro (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03313};
|
DNA replication [GO:0006260]; DNA-templated transcription [GO:0006351]; endocytosis involved in viral entry into host cell [GO:0075509]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; suppression by virus of host mRNA export from nucleus [GO:0039522]; symbiont genome entry into host cell via pore formation in plasma membrane [GO:0044694]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity [GO:0039540]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell cytoplasmic vesicle membrane [GO:0044162]; host cell nucleus [GO:0042025]; membrane [GO:0016020]; T=pseudo3 icosahedral viral capsid [GO:0039618]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; metal ion binding [GO:0046872]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; structural molecule activity [GO:0005198]
|
PF08727;PF00548;PF02226;PF00947;PF01552;PF00680;PF00073;PF00910;
|
1.20.960.20;2.60.120.20;3.30.70.270;6.10.20.20;4.10.880.10;2.40.10.10;
|
Picornaviruses polyprotein family
|
PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo by the viral proteases yield processing intermediates and the mature proteins. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP0]: Myristoylation is required for the formation of pentamers during virus assembly. Further assembly of 12 pentamers and a molecule of genomic RNA generates the provirion. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP0]: During virion maturation, immature virions are rendered infectious following cleavage of VP0 into VP4 and VP2. This maturation seems to be an autocatalytic event triggered by the presence of RNA in the capsid and it is followed by a conformational change infectious virion. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP4]: Myristoylation is required during RNA encapsidation and formation of the mature virus particle. {ECO:0000250|UniProtKB:P03300}.; PTM: [Viral protein genome-linked]: VPg is uridylylated by the polymerase into VPg-pUpU. This acts as a nucleotide-peptide primer for the genomic RNA replication. {ECO:0000250|UniProtKB:P03300}.
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SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion.; SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 3AB]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Viral protein genome-linked]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000250|UniProtKB:Q66478}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm.; SUBCELLULAR LOCATION: [Protein 3CD]: Host nucleus {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000250|UniProtKB:P03300}. Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.
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CATALYTIC ACTIVITY: [Protein 2C]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P03300}; CATALYTIC ACTIVITY: [Protease 2A]: Reaction=Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein.; EC=3.4.22.29; Evidence={ECO:0000250|UniProtKB:P03300}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: [Protease 3C]: Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.; EC=3.4.22.28; Evidence={ECO:0000255|PROSITE-ProRule:PRU01222};
| null | null | null | null |
FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP1 mainly forms the vertices of the capsid (By similarity). Capsid protein VP1 interacts with host cell receptor to provide virion attachment to target host cells (By similarity). This attachment induces virion internalization (By similarity). Tyrosine kinases are probably involved in the entry process (By similarity). After binding to its receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity). Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid shell (By similarity). After binding to the host receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP0]: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protease 2A]: Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity). It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity). Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity). Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity). Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03301}.; FUNCTION: [Protein 2B]: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 2C]: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3AB]: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3A]: Localizes the viral replication complex to the surface of membranous vesicles (By similarity). It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity). This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity). Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03313}.; FUNCTION: [Viral protein genome-linked]: Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3CD]: Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [RNA-directed RNA polymerase]: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protease 3C]: Major viral protease that mediates proteolytic processing of the polyprotein (By similarity). Cleaves host EIF5B, contributing to host translation shutoff (By similarity). Cleaves also host PABPC1, contributing to host translation shutoff (By similarity). Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03303}.
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Porcine enterovirus 9 (strain UKG/410/73)
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O41515
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MLP3B_BOVIN
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MPSEKTFKQRRTFEQRVEDVRLIREQHPTKIPVIIERYKGEKQLPVLDKTKFLVPDHVNMSELIKIIRRRLQLNANQAFFLLVNGHSMVSVSTPICEVYESEKDEDGFLYMVYASQETFGMKLSV
| null | null |
autophagosome assembly [GO:0000045]; autophagosome maturation [GO:0097352]; cellular response to nitrogen starvation [GO:0006995]; cellular response to starvation [GO:0009267]; mitophagy [GO:0000423]
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autophagosome [GO:0005776]; autophagosome membrane [GO:0000421]; axoneme [GO:0005930]; cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; cytosol [GO:0005829]; endomembrane system [GO:0012505]; microtubule [GO:0005874]; mitochondrial membrane [GO:0031966]; organelle membrane [GO:0031090]
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microtubule binding [GO:0008017]; phosphatidylethanolamine binding [GO:0008429]; ubiquitin protein ligase binding [GO:0031625]
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PF02991;
| null |
ATG8 family
|
PTM: The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, LC3-I. The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, LC3-II. During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid. ATG4 proteins also mediate the delipidation of PE-conjugated forms. In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy. ATG4B constitutes the major protein for proteolytic activation (By similarity). ATG4D is the main enzyme for delipidation activity (By similarity). {ECO:0000250|UniProtKB:Q9CQV6, ECO:0000250|UniProtKB:Q9GZQ8}.; PTM: Phosphorylation by PKA inhibits conjugation of phosphatidylethanolamine (PE). Interaction with MAPK15 reduces the inhibitory phosphorylation and increases autophagy activity. {ECO:0000250|UniProtKB:Q9GZQ8}.
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SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome membrane {ECO:0000250|UniProtKB:Q9CQV6}; Lipid-anchor {ECO:0000250|UniProtKB:Q9GZQ8}. Endomembrane system {ECO:0000250|UniProtKB:Q9CQV6}; Lipid-anchor {ECO:0000250|UniProtKB:Q9GZQ8}. Mitochondrion membrane {ECO:0000250|UniProtKB:Q9GZQ8}; Lipid-anchor {ECO:0000250|UniProtKB:Q9GZQ8}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9CQV6}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q9GZQ8}. Note=LC3-II binds to the autophagic membranes. LC3-II localizes with the mitochondrial inner membrane during Parkin-mediated mitophagy (By similarity). Localizes also to discrete punctae along the ciliary axoneme (By similarity). {ECO:0000250|UniProtKB:Q9GZQ8}.
| null | null | null | null | null |
FUNCTION: Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. In response to cellular stress and upon mitochondria fission, binds C-18 ceramides and anchors autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria. While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover. Upon nutrient stress, directly recruits cofactor JMY to the phagophore membrane surfaces and promotes JMY's actin nucleation activity and autophagosome biogenesis during autophagy. {ECO:0000250|UniProtKB:Q9GZQ8}.
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Bos taurus (Bovine)
|
O41798
|
POL_HV19N
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MGARASVLSGGKLDSWEKIRLRPGGRKKYKLKHIVWASRELGRFALNRDLLETAEGCVQIMKQLQPALTGTEELRSLFNTVATLYCVHQKIEVKDTKEAPEEVEKIQKNSQQEIQQAAKNEGNSNPVSQNYPIVQNAQGQMIHQAISPWTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKDTINDEAAEWDRIHPQQAGPIPPGQIREPSGSDIAGTTSTLQEQIRWMTSNPPIPVGEIYKRWIILGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFFKTLRAEQATQEVKGWMTDTLLVQNANPDCKTILRALGPGATLEEMMTACQGVGGPSHKARVLAEAMSQASGAAAAAIMMQKSNFKGPRRIIKCFNCGKEGHLARNCRAPRKKGCWKCGKEGHQMKECTERQANFLRENLAFQQGEARKLSPEQDRANSPTSRELRIRRGDSPLPEAGAKGEGAISLNFPQITLWQRPLVTVKIGGQLIEALLDTGADDTVLEGINLPGKWKPKMIGGIGGFIKVRQYDQILIEIGGKKAIGTVLVGPTPINIIGRNMLTQIGCTLNFPISPIETVPVKLKPGMDGPRVKQWPLTEEKIKALTEICKDMEKEGKISKIGPENPYNTPIFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKRSVTVLDVGDAYFSVPLDKDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPSRTKNPEMVIYQYMDDLYVGSDLEIGQHRAKIEELREHLLKWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIQLPEKEDWTVNDIQKLVGKLNWASQIYPGIKVKHLCRLLRGAKALTDIVPLTAEAEMELAENREILKEPVHGVYHDPSKELIAEVQKQGPDQWTYQIYQEPYKNLKTGKYAKRGSAHTNDVKQLTEVVQKIATEGIVIWGKIPKFKLPIRKETWEVWWTEYWQAAWIPEWEFVNTPPLVKLWYQLETEPIPGAETYYVDGAANRETKLGKAGHVTDKGKQKIITLTETTNQKAELHAIQLALQDSRPEVNIVTDSQYALGIIQAQPDRSGSELVNQIIEQLIKKEKVYLSWVPAHKGIGGNEQVDKLVSSGIRKVLFLDGIDKAQEEHERYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKIIIVAVHVASGYIEAEVIPAETGQETAYFILKLAGRWPVKVIHTDNGPNFISAAVKAACWWANITQEFGIPYNPQSQGVVESMNKELKKIIGQVGDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIIDIIASDIQTKELQKQIIKIQNFRVYYRDSRDPIWKGPAKLLWKGEGAVVIQDNNEIKVVPRRKAKILKDYGKQMAGGDCVAGRQDED
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2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
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host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
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1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
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PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
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SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
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CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
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FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
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Human immunodeficiency virus type 1 group M subtype G (isolate 92NG083) (HIV-1)
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O41801
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TAT_HV19N
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MDPVDPKLEPWNHPGSQPTTPCNKCYCKVCCWHCQVCFLNKGLGISYGRKKRRPRRGTPQGSKDHQNPVPKQPLPITSGNPTGSEKPKKEVASKTETDPLD
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DNA-templated transcription [GO:0006351]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; virus-mediated perturbation of host defense response [GO:0019049]
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extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
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actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
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PF00539;
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4.10.20.10;
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Lentiviruses Tat family
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PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
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SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
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FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
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Human immunodeficiency virus type 1 group M subtype G (isolate 92NG083) (HIV-1)
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O41803
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ENV_HV19N
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MRVKGIQRNWQHLWKWGTLILGLVIICSASDNLWVTVYYGVPVWEDADTPLFCASDAKSYSSEKHNVWATHACVPTDPNPQEIAIENVTENFNMWKNNMVEQMQEDIISLWEESLKPCVKLTPLCITLNCTNVNSANHTEANNTVENKEEIKNCSFKITTERGGKKKEEYALFYKLDVVPISNGNKTSYRLIHCNVSTIKQACPKVNFDPIPIHYCAPAGFAILKCRDKEYNGTGPCKNVSTVQCTHGIKPVVSTQLLLNGSLAEEDIRIRSENFTDNTKVIIVQLNNSIEINCIRPNNNTRKSIPIGPGQAFYATGDIIGDIRQAHCNVSRIKWREMLKNVTAQLRKIYNNKNITFNSSAGGDLEITTHSFNCRGEFFYCNTSGLFNNNISNINNETITLPCKIKQIVRMWQKVGQAMYALPIAGNLVCKSNITGLILTRDGGNNNDSTEETFRPGGGDMRDNWRSELYKYKTVKIKSLGVAPTRARRRVVEREKRAVGLGAVFLGFLGAAGSTMGAASITLTAQVRQLLSGIVQQQSNLLRAIEAQQHLLQLTVWGIKQLQSRVLAIERYLKDQQLLGIWGCSGKLICTTNVPWNTSWSNKSYNEIWDNMTWLEWEREIHNYTQHIYSLIEESQNQQEKNEQDLLALDKWASLWNWFDISNWLWYIRIFIMIVGGLIGLRIVFAVLSIVNRVRQGYSPLSFQTLTHHQREPDRLGKTEEGGGEQDRDRSTRLVSGFLALAWDDLRSLCLFSYHRLRDLVLIAARTVELLGRSSLKGLRLGWEGLKYLWNLLLYWGRELKNSAINLLDTIAIATANGTDRVIEVAQRAYRAILNVPTRIRQGLERALL
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
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structural molecule activity [GO:0005198]
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PF00516;PF00517;
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1.10.287.210;2.170.40.20;1.20.5.490;
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HIV-1 env protein family
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PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
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SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
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FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
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Human immunodeficiency virus type 1 group M subtype G (isolate 92NG083) (HIV-1)
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O41804
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NEF_HV19N
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MGGKWSKSSIVGWPQIRERIRQTPVAAEGVGAVSQDLARHGAITSSNTATNNPDCAWLEAQEEDSDVGFPVRPQVPLRPMTYKAAFDLSFFLKEKGGLDGLIYSKRRQDILDLWVYNTQGFFPDWQNYTPGPGTRLPLTFGWCFKLVPMDPAEIEEANKGENISLLHPICQHGMEDEDREVLVWRFNSSLARRHLARELHPEYYKDC
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suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
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extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
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GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
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PF00469;
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4.10.890.10;3.30.62.10;
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Lentivirus primate group Nef protein family
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PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
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SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078}.
| null | null | null | null | null |
FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of host BAD. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
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Human immunodeficiency virus type 1 group M subtype G (isolate 92NG083) (HIV-1)
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