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
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
O15353
|
FOXN1_HUMAN
|
MVSLPPPQSDVTLPGPTRLEGERQGDLMQAPGLPGSPAPQSKHAGFSCSSFVSDGPPERTPSLPPHSPRIASPGPEQVQGHCPAGPGPGPFRLSPSDKYPGFGFEEAAASSPGRFLKGSHAPFHPYKRPFHEDVFPEAETTLALKGHSFKTPGPLEAFEEIPVDVAEAEAFLPGFSAEAWCNGLPYPSQEHGPQVLGSEVKVKPPVLESGAGMFCYQPPLQHMYCSSQPPFHQYSPGGGSYPIPYLGSSHYQYQRMAPQASTDGHQPLFPKPIYSYSILIFMALKNSKTGSLPVSEIYNFMTEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVENKSGSSSRKGCLWALNPAKIDKMQEELQKWKRKDPIAVRKSMAKPEELDSLIGDKREKLGSPLLGCPPPGLSGSGPIRPLAPPAGLSPPLHSLHPAPGPIPGKNPLQDLLMGHTPSCYGQTYLHLSPGLAPPGPPQPLFPQPDGHLELRAQPGTPQDSPLPAHTPPSHSAKLLAEPSPARTMHDTLLPDGDLGTDLDAINPSLTDFDFQGNLWEQLKDDSLALDPLVLVTSSPTSSSMPPPQPPPHCFPPGPCLTETGSGAGDLAAPGSGGSGALGDLHLTTLYSAFMELEPTPPTAPAGPSVYLSPSSKPVALA
| null | null |
animal organ morphogenesis [GO:0009887]; blood vessel morphogenesis [GO:0048514]; defense response [GO:0006952]; epidermis development [GO:0008544]; hair follicle development [GO:0001942]; keratinocyte differentiation [GO:0030216]; lymphoid lineage cell migration into thymus [GO:0097535]; nail development [GO:0035878]; positive regulation of epithelial cell differentiation [GO:0030858]; positive regulation of hair follicle development [GO:0051798]; regulation of positive thymic T cell selection [GO:1902232]; regulation of transcription by RNA polymerase II [GO:0006357]; T cell homeostasis [GO:0043029]; T cell lineage commitment [GO:0002360]; thymus epithelium morphogenesis [GO:0097536]
|
chromatin [GO:0000785]; nucleus [GO:0005634]
|
DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; transcription cis-regulatory region binding [GO:0000976]
|
PF00250;
|
1.10.10.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus.
| null | null | null | null | null |
FUNCTION: Transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs) both in the prenatal and postnatal thymus. Acts as a master regulator of the TECs lineage development and is required from the onset of differentiation in progenitor TECs in the developing fetus to the final differentiation steps through which TECs mature to acquire their full functionality. Regulates, either directly or indirectly the expression of a variety of genes that mediate diverse aspects of thymus development and function, including MHC Class II, DLL4, CCL25, CTSL, CD40 and PAX1. Regulates the differentiation of the immature TECs into functional cortical TECs (cTECs) and medullary TECs (mTECs). Essential for maintenance of mTECs population in the postnatal thymus. Involved in the morphogenesis and maintenance of the three-dimensional thymic microstructure which is necessary for a fully functional thymus. Plays an important role in the maintenance of hematopoiesis and particularly T lineage progenitors within the bone marrow niche with age. Essential for the vascularization of the thymus anlage. Promotes the terminal differentiation of epithelial cells in the epidermis and hair follicles, partly by negatively regulating the activity of protein kinase C (By similarity). Plays a crucial role in the early prenatal stages of T-cell ontogeny (PubMed:21507891). {ECO:0000250|UniProtKB:Q61575, ECO:0000269|PubMed:21507891}.
|
Homo sapiens (Human)
|
O15354
|
GPR37_HUMAN
|
MRAPGALLARMSRLLLLLLLKVSASSALGVAPASRNETCLGESCAPTVIQRRGRDAWGPGNSARDVLRARAPREEQGAAFLAGPSWDLPAAPGRDPAAGRGAEASAAGPPGPPTRPPGPWRWKGARGQEPSETLGRGNPTALQLFLQISEEEEKGPRGAGISGRSQEQSVKTVPGASDLFYWPRRAGKLQGSHHKPLSKTANGLAGHEGWTIALPGRALAQNGSLGEGIHEPGGPRRGNSTNRRVRLKNPFYPLTQESYGAYAVMCLSVVIFGTGIIGNLAVMCIVCHNYYMRSISNSLLANLAFWDFLIIFFCLPLVIFHELTKKWLLEDFSCKIVPYIEVASLGVTTFTLCALCIDRFRAATNVQMYYEMIENCSSTTAKLAVIWVGALLLALPEVVLRQLSKEDLGFSGRAPAERCIIKISPDLPDTIYVLALTYDSARLWWYFGCYFCLPTLFTITCSLVTARKIRKAEKACTRGNKRQIQLESQMNCTVVALTILYGFCIIPENICNIVTAYMATGVSQQTMDLLNIISQFLLFFKSCVTPVLLFCLCKPFSRAFMECCCCCCEECIQKSSTVTSDDNDNEYTTELELSPFSTIRREMSTFASVGTHC
| null | null |
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway [GO:0007193]; cellular response to reactive oxygen species [GO:0034614]; dendrite development [GO:0016358]; dopamine biosynthetic process [GO:0042416]; G protein-coupled receptor signaling pathway [GO:0007186]; locomotion involved in locomotory behavior [GO:0031987]; neuropeptide signaling pathway [GO:0007218]; positive regulation of dopamine metabolic process [GO:0045964]; positive regulation of MAPK cascade [GO:0043410]
|
cell surface [GO:0009986]; cytoplasm [GO:0005737]; dendrite [GO:0030425]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; plasma membrane [GO:0005886]; receptor complex [GO:0043235]; synapse [GO:0045202]; ubiquitin ligase complex [GO:0000151]
|
G protein-coupled peptide receptor activity [GO:0008528]; G protein-coupled receptor activity [GO:0004930]; heat shock protein binding [GO:0031072]; Hsp70 protein binding [GO:0030544]; neuropeptide binding [GO:0042923]; neuropeptide receptor activity [GO:0008188]; PDZ domain binding [GO:0030165]; peptide binding [GO:0042277]; prosaposin receptor activity [GO:0036505]; ubiquitin protein ligase binding [GO:0031625]
|
PF00001;
|
1.20.1070.10;
|
G-protein coupled receptor 1 family
|
PTM: The N-terminus is cleaved by ADAM10 metalloproteinase; mediating limited proteolysis leading to the release of receptor ectodomain by shedding (PubMed:26869225, PubMed:34042202). In addition, cleaved by FURIN between Arg-54 and Asp-55 (PubMed:34042202). {ECO:0000269|PubMed:26869225, ECO:0000269|PubMed:34042202}.; PTM: Ubiquitinated by PRKN in the presence of UBE2E1 and UBE2L3 in the endoplasmic reticulum. The unfolded form is specifically ubiquitinated by SYVN1, which promotes its proteasomal degradation and prevents neuronal cell death. {ECO:0000269|PubMed:17059562}.
|
SUBCELLULAR LOCATION: Cell projection, dendrite {ECO:0000269|PubMed:25977097}. Synapse {ECO:0000269|PubMed:25977097}. Cell membrane {ECO:0000269|PubMed:17059562, ECO:0000269|PubMed:25977097, ECO:0000269|PubMed:26869225}; Multi-pass membrane protein {ECO:0000269|PubMed:17059562}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:17059562}; Multi-pass membrane protein {ECO:0000269|PubMed:17059562}.
| null | null | null | null | null |
FUNCTION: G-protein-coupled receptor that plays a role in several physiological pathways such as resolution of inflammatory pain and oligodendrocyte differentiation (By similarity). Acts as a receptor for several ligands including prosaposin, osteocalcin or neuroprotectin D1. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade (PubMed:11439185, PubMed:23690594). Acts as a receptor for osteocalcin (OCN) to regulate oligodendrocyte differentiation and central nervous system myelination. Mechanistically, plays a negative role in oligodendrocyte differentiation and myelination during development via activation of the ERK1/2 signaling pathway. Therefore, regulates the stability of myelin or resistance of myelin itself to demyelination. Upon activation by neuroprotectin D1 (NPD1), promotes the activation of phagocytosis in macrophages as well as the shift in cytokine release toward an anti-inflammatory profile, and thus helps to reverse inflammatory pain. In addition, the increased macrophage phagocytosis mediates protection against sepsis upon pathogen infection. Additionally, extracellular vesicles derived from efferocyte express prosaposin, which binds to macrophage GPR37 to increase expression of the efferocytosis receptor TIM4 via an ERK-AP1-dependent signaling axis, leading to increased macrophage efferocytosis efficiency and accelerated resolution of inflammation (By similarity). May also act as a maturation factor of LRP6, protecting LRP6 from the endoplasmic reticulum (ER)-associated protein degradation (ERAD) and thereby promoting the Wnt/beta-catenin signaling pathway (PubMed:28341812). {ECO:0000250|UniProtKB:Q9QY42, ECO:0000269|PubMed:11439185, ECO:0000269|PubMed:23690594, ECO:0000269|PubMed:25977097, ECO:0000269|PubMed:28341812, ECO:0000269|PubMed:9526070}.
|
Homo sapiens (Human)
|
O15355
|
PPM1G_HUMAN
|
MGAYLSQPNTVKCSGDGVGAPRLPLPYGFSAMQGWRVSMEDAHNCIPELDSETAMFSVYDGHGGEEVALYCAKYLPDIIKDQKAYKEGKLQKALEDAFLAIDAKLTTEEVIKELAQIAGRPTEDEDEKEKVADEDDVDNEEAALLHEEATMTIEELLTRYGQNCHKGPPHSKSGGGTGEEPGSQGLNGEAGPEDSTRETPSQENGPTAKAYTGFSSNSERGTEAGQVGEPGIPTGEAGPSCSSASDKLPRVAKSKFFEDSEDESDEAEEEEEDSEECSEEEDGYSSEEAENEEDEDDTEEAEEDDEEEEEEMMVPGMEGKEEPGSDSGTTAVVALIRGKQLIVANAGDSRCVVSEAGKALDMSYDHKPEDEVELARIKNAGGKVTMDGRVNGGLNLSRAIGDHFYKRNKNLPPEEQMISALPDIKVLTLTDDHEFMVIACDGIWNVMSSQEVVDFIQSKISQRDENGELRLLSSIVEELLDQCLAPDTSGDGTGCDNMTCIIICFKPRNTAELQPESGKRKLEEVLSTEGAEENGNSDKKKKAKRD
|
3.1.3.16
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};
|
peptidyl-threonine dephosphorylation [GO:0035970]; protein dephosphorylation [GO:0006470]; regulation of cell cycle [GO:0051726]
|
cytoplasm [GO:0005737]; membrane [GO:0016020]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
metal ion binding [GO:0046872]; myosin phosphatase activity [GO:0017018]; protein serine/threonine phosphatase activity [GO:0004722]
|
PF00481;
|
3.60.40.10;
|
PP2C family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16; CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16;
| null | null | null | null | null |
Homo sapiens (Human)
|
O15357
|
SHIP2_HUMAN
|
MASACGAPGPGGALGSQAPSWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEGEREPDPPDDRDASDGEDEKPPLPPRSGSTSISAPTGPSSPLPAPETPTAPAAESAPNGLSTVSHDYLKGSYGLDLEAVRGGASHLPHLTRTLATSCRRLHSEVDKVLSGLEILSKVFDQQSSPMVTRLLQQQNLPQTGEQELESLVLKLSVLKDFLSGIQKKALKALQDMSSTAPPAPQPSTRKAKTIPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNKHSKQDEPDMISVFIGTWNMGSVPPPKNVTSWFTSKGLGKTLDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTARRNQNYLDILRLLSLGDRQLNAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRKEFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDEAGAKSKAPSVSRGSQEPRSGSRKPAFTEASCPLSRLFEEPEKPPPTGRPPAPPRAAPREEPLTPRLKPEGAPEPEGVAAPPPKNSFNNPAYYVLEGVPHQLLPPEPPSPARAPVPSATKNKVAITVPAPQLGHHRHPRVGEGSSSDEESGGTLPPPDFPPPPLPDSAIFLPPSLDPLPGPVVRGRGGAEARGPPPPKAHPRPPLPPGPSPASTFLGEVASGDDRSCSVLQMAKTLSEVDYAPAGPARSALLPGPLELQPPRGLPSDYGRPLSFPPPRIRESIQEDLAEEAPCLQGGRASGLGEAGMSAWLRAIGLERYEEGLVHNGWDDLEFLSDITEEDLEEAGVQDPAHKRLLLDTLQLSK
|
3.1.3.86
| null |
actin filament organization [GO:0007015]; apoptotic process [GO:0006915]; cell adhesion [GO:0007155]; endochondral ossification [GO:0001958]; endocytosis [GO:0006897]; ERK1 and ERK2 cascade [GO:0070371]; establishment of mitotic spindle orientation [GO:0000132]; gene expression [GO:0010467]; glucose metabolic process [GO:0006006]; immune system process [GO:0002376]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of gene expression [GO:0010629]; negative regulation of insulin-like growth factor receptor signaling pathway [GO:0043569]; phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0043491]; phosphatidylinositol biosynthetic process [GO:0006661]; phosphatidylinositol dephosphorylation [GO:0046856]; post-embryonic development [GO:0009791]; regulation of actin filament organization [GO:0110053]; regulation of immune response [GO:0050776]; regulation of protein localization [GO:0032880]; response to insulin [GO:0032868]; ruffle assembly [GO:0097178]
|
basal plasma membrane [GO:0009925]; cytosol [GO:0005829]; filopodium [GO:0030175]; Golgi apparatus [GO:0005794]; lamellipodium [GO:0030027]; nuclear speck [GO:0016607]; nucleus [GO:0005634]; spindle pole [GO:0000922]
|
actin binding [GO:0003779]; inositol-polyphosphate 5-phosphatase activity [GO:0004445]; phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity [GO:0034485]; SH2 domain binding [GO:0042169]; SH3 domain binding [GO:0017124]
|
PF00536;PF00017;
|
3.60.10.10;3.30.505.10;1.10.150.50;
|
Inositol 1,4,5-trisphosphate 5-phosphatase family
|
PTM: Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as insulin, growth factors such as EGF or PDGF, chemokines, integrin ligands and hypertonic and oxidative stress. May be phosphorylated upon IgG receptor FCGR2B-binding. Phosphorylated at Tyr-986 following cell attachment and spreading. Phosphorylated at Tyr-1162 following EGF signaling pathway stimulation. Phosphorylated at Thr-958 in response to PDGF. {ECO:0000269|PubMed:10194451, ECO:0000269|PubMed:11158326, ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11687594, ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:17219406, ECO:0000269|PubMed:9660833}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11349134}. Cytoplasm, cytoskeleton. Membrane {ECO:0000269|PubMed:11739414}; Peripheral membrane protein. Cell projection, filopodium {ECO:0000269|PubMed:12676785}. Cell projection, lamellipodium {ECO:0000269|PubMed:12676785}. Basal cell membrane {ECO:0000250|UniProtKB:F1PNY0}. Nucleus {ECO:0000250|UniProtKB:D7PF45}. Nucleus speckle {ECO:0000250|UniProtKB:D7PF45}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:F1PNY0}. Note=Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type (PubMed:11739414). Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B). Tyrosine phosphorylation may also participate in membrane localization. Insulin specifically stimulates its redistribution from the cytosol to the plasma membrane. Recruited to the membrane following M-CSF stimulation. In activated spreading platelets, localizes with actin at filopodia, lamellipodia and the central actin ring. {ECO:0000269|PubMed:11739414}.
|
CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:25528, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658, ChEBI:CHEBI:57836; EC=3.1.3.86; Evidence={ECO:0000269|PubMed:10194451, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:9660833}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529; Evidence={ECO:0000305|PubMed:10194451}; CATALYTIC ACTIVITY: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43548, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83416, ChEBI:CHEBI:83417; Evidence={ECO:0000269|PubMed:16824732}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43549; Evidence={ECO:0000305|PubMed:16824732}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43556, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83420, ChEBI:CHEBI:83422; Evidence={ECO:0000269|PubMed:16824732}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43557; Evidence={ECO:0000305|PubMed:16824732};
| null | null | null | null |
FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (PubMed:16824732). Required for correct mitotic spindle orientation and therefore progression of mitosis (By similarity). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (PubMed:9660833). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (By similarity). Confers resistance to dietary obesity (By similarity). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane (By similarity). Part of a signaling pathway that regulates actin cytoskeleton remodeling (PubMed:11739414, PubMed:12676785). Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation (PubMed:15668240). Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956). Regulates cell adhesion and cell spreading (PubMed:12235291). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (PubMed:15735664). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (PubMed:17135240). Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (PubMed:12690104). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (PubMed:11016922). Involved in EGF signaling pathway (PubMed:11349134). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (PubMed:11349134). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (PubMed:11349134). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (By similarity). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (By similarity). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (By similarity). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (By similarity). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (By similarity). May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (PubMed:23273569). {ECO:0000250|UniProtKB:F1PNY0, ECO:0000250|UniProtKB:Q6P549, ECO:0000250|UniProtKB:Q9WVR3, ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11739414, ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12676785, ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:15668240, ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:17135240, ECO:0000269|PubMed:21624956, ECO:0000269|PubMed:23273569, ECO:0000269|PubMed:9660833}.
|
Homo sapiens (Human)
|
O15360
|
FANCA_HUMAN
|
MSDSWVPNSASGQDPGGRRRAWAELLAGRVKREKYNPERAQKLKESAVRLLRSHQDLNALLLEVEGPLCKKLSLSKVIDCDSSEAYANHSSSFIGSALQDQASRLGVPVGILSAGMVASSVGQICTAPAETSHPVLLTVEQRKKLSSLLEFAQYLLAHSMFSRLSFCQELWKIQSSLLLEAVWHLHVQGIVSLQELLESHPDMHAVGSWLFRNLCCLCEQMEASCQHADVARAMLSDFVQMFVLRGFQKNSDLRRTVEPEKMPQVTVDVLQRMLIFALDALAAGVQEESSTHKIVRCWFGVFSGHTLGSVISTDPLKRFFSHTLTQILTHSPVLKASDAVQMQREWSFARTHPLLTSLYRRLFVMLSAEELVGHLQEVLETQEVHWQRVLSFVSALVVCFPEAQQLLEDWVARLMAQAFESCQLDSMVTAFLVVRQAALEGPSAFLSYADWFKASFGSTRGYHGCSKKALVFLFTFLSELVPFESPRYLQVHILHPPLVPGKYRSLLTDYISLAKTRLADLKVSIENMGLYEDLSSAGDITEPHSQALQDVEKAIMVFEHTGNIPVTVMEASIFRRPYYVSHFLPALLTPRVLPKVPDSRVAFIESLKRADKIPPSLYSTYCQACSAAEEKPEDAALGVRAEPNSAEEPLGQLTAALGELRASMTDPSQRDVISAQVAVISERLRAVLGHNEDDSSVEISKIQLSINTPRLEPREHMAVDLLLTSFCQNLMAASSVAPPERQGPWAALFVRTMCGRVLPAVLTRLCQLLRHQGPSLSAPHVLGLAALAVHLGESRSALPEVDVGPPAPGAGLPVPALFDSLLTCRTRDSLFFCLKFCTAAISYSLCKFSSQSRDTLCSCLSPGLIKKFQFLMFRLFSEARQPLSEEDVASLSWRPLHLPSADWQRAALSLWTHRTFREVLKEEDVHLTYQDWLHLELEIQPEADALSDTERQDFHQWAIHEHFLPESSASGGCDGDLQAACTILVNALMDFHQSSRSYDHSENSDLVFGGRTGNEDIISRLQEMVADLELQQDLIVPLGHTPSQEHFLFEIFRRRLQALTSGWSVAASLQRQRELLMYKRILLRLPSSVLCGSSFQAEQPITARCEQFFHLVNSEMRNFCSHGGALTQDITAHFFRGLLNACLRSRDPSLMVDFILAKCQTKCPLILTSALVWWPSLEPVLLCRWRRHCQSPLPRELQKLQEGRQFASDFLSPEAASPAPNPDWLSAAALHFAIQQVREENIRKQLKKLDCEREELLVFLFFFSLMGLLSSHLTSNSTTDLPKAFHVCAAILECLEKRKISWLALFQLTESDLRLGRLLLRVAPDQHTRLLPFAFYSLLSYFHEDAAIREEAFLHVAVDMYLKLVQLFVAGDTSTVSPPAGRSLELKGQGNPVELITKARLFLLQLIPRCPKKSFSHVAELLADRGDCDPEVSAALQSRQQAAPDADLSQEPHLF
| null | null |
DNA repair [GO:0006281]; female gonad development [GO:0008585]; interstrand cross-link repair [GO:0036297]; male gonad development [GO:0008584]; male meiotic nuclear division [GO:0007140]; protein-containing complex assembly [GO:0065003]; regulation of CD40 signaling pathway [GO:2000348]; regulation of germ cell proliferation [GO:1905936]; regulation of inflammatory response [GO:0050727]; regulation of regulatory T cell differentiation [GO:0045589]
|
chromatin [GO:0000785]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; Fanconi anaemia nuclear complex [GO:0043240]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
| null |
PF03511;PF15865;
| null | null |
PTM: Phosphorylation is required for the formation of the nuclear complex. Not phosphorylated in cells derived from groups A, B, C, E, F, G, and H. {ECO:0000269|PubMed:9789045}.
|
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The major form is nuclear. The minor form is cytoplasmic.
| null | null | null | null | null |
FUNCTION: DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be involved in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.
|
Homo sapiens (Human)
|
O15370
|
SOX12_HUMAN
|
MVQQRGARAKRDGGPPPPGPGPAEEGAREPGWCKTPSGHIKRPMNAFMVWSQHERRKIMDQWPDMHNAEISKRLGRRWQLLQDSEKIPFVREAERLRLKHMADYPDYKYRPRKKSKGAPAKARPRPPGGSGGGSRLKPGPQLPGRGGRRAAGGPLGGGAAAPEDDDEDDDEELLEVRLVETPGRELWRMVPAGRAARGQAERAQGPSGEGAAAAAAASPTPSEDEEPEEEEEEAAAAEEGEEETVASGEESLGFLSRLPPGPAGLDCSALDRDPDLQPPSGTSHFEFPDYCTPEVTEMIAGDWRPSSIADLVFTY
| null | null |
anatomical structure morphogenesis [GO:0009653]; brain development [GO:0007420]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neuron differentiation [GO:0030182]; positive regulation of regulatory T cell differentiation [GO:0045591]; positive regulation of transcription by RNA polymerase II [GO:0045944]; spinal cord development [GO:0021510]
|
chromatin [GO:0000785]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
DNA binding [GO:0003677]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific double-stranded DNA binding [GO:1990837]; transcription cis-regulatory region binding [GO:0000976]
|
PF00505;
|
1.10.30.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267, ECO:0000269|PubMed:9215677}.
| null | null | null | null | null |
FUNCTION: Transcription factor that binds to DNA at the consensus sequence 5'-ACCAAAG-3' (By similarity). Acts as a transcriptional activator (By similarity). Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation (By similarity). Involved in the differentiation of naive CD4-positive T-cells into peripherally induced regulatory T (pT reg) cells under inflammatory conditions (By similarity). Binds to the promoter region of the FOXP3 gene and promotes its transcription, and might thereby contribute to pT reg cell differentiation in the spleen and lymph nodes during inflammation (By similarity). Plays a redundant role with SOX4 and SOX11 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis (By similarity). {ECO:0000250|UniProtKB:Q04890}.
|
Homo sapiens (Human)
|
O15371
|
EIF3D_HUMAN
|
MAKFMTPVIQDNPSGWGPCAVPEQFRDMPYQPFSKGDRLGKVADWTGATYQDKRYTNKYSSQFGGGSQYAYFHEEDESSFQLVDTARTQKTAYQRNRMRFAQRNLRRDKDRRNMLQFNLQILPKSAKQKERERIRLQKKFQKQFGVRQKWDQKSQKPRDSSVEVRSDWEVKEEMDFPQLMKMRYLEVSEPQDIECCGALEYYDKAFDRITTRSEKPLRSIKRIFHTVTTTDDPVIRKLAKTQGNVFATDAILATLMSCTRSVYSWDIVVQRVGSKLFFDKRDNSDFDLLTVSETANEPPQDEGNSFNSPRNLAMEATYINHNFSQQCLRMGKERYNFPNPNPFVEDDMDKNEIASVAYRYRRWKLGDDIDLIVRCEHDGVMTGANGEVSFINIKTLNEWDSRHCNGVDWRQKLDSQRGAVIATELKNNSYKLARWTCCALLAGSEYLKLGYVSRYHVKDSSRHVILGTQQFKPNEFASQINLSVENAWGILRCVIDICMKLEEGKYLILKDPNKQVIRVYSLPDGTFSSDEDEEEEEEEEEEEEEEET
| null | null |
cap-dependent translational initiation [GO:0002191]; formation of cytoplasmic translation initiation complex [GO:0001732]; IRES-dependent viral translational initiation [GO:0075522]; positive regulation of mRNA binding [GO:1902416]; positive regulation of translation [GO:0045727]; translational initiation [GO:0006413]; viral translational termination-reinitiation [GO:0075525]
|
cytosol [GO:0005829]; eukaryotic 43S preinitiation complex [GO:0016282]; eukaryotic 48S preinitiation complex [GO:0033290]; eukaryotic translation initiation factor 3 complex [GO:0005852]; eukaryotic translation initiation factor 3 complex, eIF3m [GO:0071541]; membrane [GO:0016020]; synapse [GO:0045202]
|
mRNA cap binding [GO:0098808]; RNA binding [GO:0003723]; translation initiation factor activity [GO:0003743]
|
PF05091;
| null |
EIF-3 subunit D family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03003}.
| null | null | null | null | null |
FUNCTION: mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815). {ECO:0000269|PubMed:18599441, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}.
|
Homo sapiens (Human)
|
O15372
|
EIF3H_HUMAN
|
MASRKEGTGSTATSSSSTAGAAGKGKGKGGSGDSAVKQVQIDGLVVLKIIKHYQEEGQGTEVVQGVLLGLVVEDRLEITNCFPFPQHTEDDADFDEVQYQMEMMRSLRHVNIDHLHVGWYQSTYYGSFVTRALLDSQFSYQHAIEESVVLIYDPIKTAQGSLSLKAYRLTPKLMEVCKEKDFSPEALKKANITFEYMFEEVPIVIKNSHLINVLMWELEKKSAVADKHELLSLASSNHLGKNLQLLMDRVDEMSQDIVKYNTYMRNTSKQQQQKHQYQQRRQQENMQRQSRGEPPLPEEDLSKLFKPPQPPARMDSLLIAGQINTYCQNIKEFTAQNLGKLFMAQALQEYNN
| null | null |
formation of cytoplasmic translation initiation complex [GO:0001732]; negative regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032435]; regulation of translational initiation [GO:0006446]; translational initiation [GO:0006413]
|
cytosol [GO:0005829]; eukaryotic 43S preinitiation complex [GO:0016282]; eukaryotic 48S preinitiation complex [GO:0033290]; eukaryotic translation initiation factor 3 complex [GO:0005852]; eukaryotic translation initiation factor 3 complex, eIF3m [GO:0071541]; extracellular exosome [GO:0070062]; membrane [GO:0016020]
|
metal-dependent deubiquitinase activity [GO:0140492]; metallopeptidase activity [GO:0008237]; RNA binding [GO:0003723]; translation initiation factor activity [GO:0003743]
|
PF19445;PF01398;
|
3.40.140.10;
|
EIF-3 subunit H family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03007}.
| null | null | null | null | null |
FUNCTION: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03007, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.
|
Homo sapiens (Human)
|
O15374
|
MOT5_HUMAN
|
MLKREGKVQPYTKTLDGGWGWMIVIHFFLVNVFVMGMTKTFAIFFVVFQEEFEGTSEQIGWIGSIMSSLRFCAGPLVAIICDILGEKTTSILGAFVVTGGYLISSWATSIPFLCVTMGLLPGLGSAFLYQVAAVVTTKYFKKRLALSTAIARSGMGLTFLLAPFTKFLIDLYDWTGALILFGAIALNLVPSSMLLRPIHIKSENNSGIKDKGSSLSAHGPEAHATETHCHETEESTIKDSTTQKAGLPSKNLTVSQNQSEEFYNGPNRNRLLLKSDEESDKVISWSCKQLFDISLFRNPFFYIFTWSFLLSQLAYFIPTFHLVARAKTLGIDIMDASYLVSVAGILETVSQIISGWVADQNWIKKYHYHKSYLILCGITNLLAPLATTFPLLMTYTICFAIFAGGYLALILPVLVDLCRNSTVNRFLGLASFFAGMAVLSGPPIAGWLYDYTQTYNGSFYFSGICYLLSSVSFFFVPLAERWKNSLT
| null | null |
monocarboxylic acid transport [GO:0015718]
|
membrane [GO:0016020]; plasma membrane [GO:0005886]
|
monocarboxylic acid transmembrane transporter activity [GO:0008028]; symporter activity [GO:0015293]
|
PF07690;
|
1.20.1250.20;
|
Major facilitator superfamily, Monocarboxylate porter (TC 2.A.1.13) family
| null |
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
| null | null | null | null | null |
FUNCTION: Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate (By similarity). {ECO:0000250}.
|
Homo sapiens (Human)
|
O15379
|
HDAC3_HUMAN
|
MAKTVAYFYDPDVGNFHYGAGHPMKPHRLALTHSLVLHYGLYKKMIVFKPYQASQHDMCRFHSEDYIDFLQRVSPTNMQGFTKSLNAFNVGDDCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFCYVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHLFQPVINQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPYSEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYDGDHDNDKESDVEI
|
3.5.1.-; 3.5.1.98
| null |
cellular response to fluid shear stress [GO:0071498]; chromatin organization [GO:0006325]; circadian regulation of gene expression [GO:0032922]; cornified envelope assembly [GO:1903575]; DNA repair-dependent chromatin remodeling [GO:0140861]; establishment of mitotic spindle orientation [GO:0000132]; establishment of skin barrier [GO:0061436]; in utero embryonic development [GO:0001701]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cardiac muscle cell differentiation [GO:2000726]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of JNK cascade [GO:0046329]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of cold-induced thermogenesis [GO:0120162]; positive regulation of protein import into nucleus [GO:0042307]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein ubiquitination [GO:0031398]; positive regulation of TOR signaling [GO:0032008]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein deacetylation [GO:0006476]; regulation of circadian rhythm [GO:0042752]; regulation of mitotic cell cycle [GO:0007346]; regulation of multicellular organism growth [GO:0040014]; regulation of protein stability [GO:0031647]; spindle assembly [GO:0051225]; transcription by RNA polymerase II [GO:0006366]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; Golgi apparatus [GO:0005794]; histone deacetylase complex [GO:0000118]; mitotic spindle [GO:0072686]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; Rpd3L-Expanded complex [GO:0070210]; transcription repressor complex [GO:0017053]
|
chromatin binding [GO:0003682]; chromatin DNA binding [GO:0031490]; cyclin binding [GO:0030332]; DNA-binding transcription factor binding [GO:0140297]; enzyme binding [GO:0019899]; histone deacetylase activity [GO:0004407]; histone deacetylase binding [GO:0042826]; histone decrotonylase activity [GO:0160009]; NF-kappaB binding [GO:0051059]; protein de-2-hydroxyisobutyrylase activity [GO:0160010]; protein decrotonylase activity [GO:0160008]; protein lysine deacetylase activity [GO:0033558]; transcription corepressor activity [GO:0003714]; transcription corepressor binding [GO:0001222]
|
PF00850;
|
3.40.800.20;
|
Histone deacetylase family, HD type 1 subfamily
|
PTM: Sumoylated in vitro. {ECO:0000269|PubMed:12032081}.; PTM: Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38; leading to a decreased level of histone acetylation. {ECO:0000269|PubMed:32404892}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21030595}. Cytoplasm {ECO:0000269|PubMed:25190803}. Cytoplasm, cytosol {ECO:0000269|PubMed:21030595}. Note=Colocalizes with XBP1 and AKT1 in the cytoplasm (PubMed:25190803). Predominantly expressed in the nucleus in the presence of CCAR2 (PubMed:21030595). {ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:25190803}.
|
CATALYTIC ACTIVITY: Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-[histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089, ChEBI:CHEBI:61930; EC=3.5.1.98; Evidence={ECO:0000269|PubMed:28497810, ECO:0000305|PubMed:23911289}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197; Evidence={ECO:0000269|PubMed:28497810, ECO:0000305|PubMed:23911289}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] = acetate + L-lysyl-[protein]; Xref=Rhea:RHEA:58108, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089, ChEBI:CHEBI:61930; Evidence={ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:25301942, ECO:0000305|PubMed:21030595, ECO:0000305|PubMed:21444723}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58109; Evidence={ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:25301942, ECO:0000305|PubMed:21030595, ECO:0000305|PubMed:21444723}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] = (2E)-2-butenoate + L-lysyl-[protein]; Xref=Rhea:RHEA:69172, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13707, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:35899, ChEBI:CHEBI:137954; Evidence={ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:34608293}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69173; Evidence={ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:34608293}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] = 2-hydroxy-2-methylpropanoate + L-lysyl-[protein]; Xref=Rhea:RHEA:69176, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:15921, ChEBI:CHEBI:15377, ChEBI:CHEBI:19641, ChEBI:CHEBI:29969, ChEBI:CHEBI:144968; Evidence={ECO:0000269|PubMed:29192674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69177; Evidence={ECO:0000269|PubMed:29192674};
| null | null | null | null |
FUNCTION: Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:21030595, PubMed:21444723, PubMed:23911289, PubMed:25301942, PubMed:28167758, PubMed:28497810, PubMed:32404892). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:23911289). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as a deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3 (PubMed:15653507, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293). {ECO:0000250|UniProtKB:O88895, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21444723, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:32404892, ECO:0000269|PubMed:34608293}.
|
Homo sapiens (Human)
|
O15381
|
NVL_HUMAN
|
MKPRPAGFVDNKLKQRVIQYLTSNKCGKYVDIGVLASDLQRVYSIDYGRRKRNAFRIQVEKVFSIISSEKELKNLTELEDEHLAKRARQGEEDNEYTESYSDDDSSMEDYPDPQSANHMNSSLLSLYRKGNPDSVSNTPEMEQRETTSSTPRISSKTGSIPLKTPAKDSEGGWFIDKTPSVKKDSFFLDLSCEKSNPKKPITEIQDSKDSSLLESDMKRKGKLKNKGSKRKKEDLQEVDGEIEAVLQKKAKARGLEFQISNVKFEDVGGNDMTLKEVCKMLIHMRHPEVYHHLGVVPPRGVLLHGPPGCGKTLLAHAIAGELDLPILKVAAPEIVSGVSGESEQKLRELFEQAVSNAPCIIFIDEIDAITPKREVASKDMERRIVAQLLTCMDDLNNVAATARVLVIGATNRPDSLDPALRRAGRFDREICLGIPDEASRERILQTLCRKLRLPQAFDFCHLAHLTPGFVGADLMALCREAAMCAVNRVLMKLQEQQKKNPEMEDLPSKGVQEERLGTEPTSETQDELQRLLGLLRDQDPLSEEQMQGLCIELNDFIVALSSVQPSAKREGFVTVPNVTWADIGALEDIREELTMAILAPVRNPDQFKALGLVTPAGVLLAGPPGCGKTLLAKAVANESGLNFISVKGPELLNMYVGESERAVRQVFQRAKNSAPCVIFFDEVDALCPRRSDRETGASVRVVNQLLTEMDGLEARQQVFIMAATNRPDIIDPAILRPGRLDKTLFVGLPPPADRLAILKTITKNGTKPPLDADVNLEAIAGDLRCDCYTGADLSALVREASICALRQEMARQKSGNEKGELKVSHKHFEEAFKKVRSSISKKDQIMYERLQESLSR
| null | null |
positive regulation of protein binding [GO:0032092]; positive regulation of telomerase activity [GO:0051973]; regulation of protein localization to nucleolus [GO:1904749]; ribosomal large subunit biogenesis [GO:0042273]; ribosome biogenesis [GO:0042254]; rRNA processing [GO:0006364]
|
membrane [GO:0016020]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; telomerase holoenzyme complex [GO:0005697]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; preribosome binding [GO:1990275]; RNA binding [GO:0003723]
|
PF00004;PF17862;PF16725;
|
1.10.10.2010;1.10.8.60;3.40.50.300;
|
AAA ATPase family
| null |
SUBCELLULAR LOCATION: [Isoform 2]: Nucleus, nucleoplasm {ECO:0000269|PubMed:15469983}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus {ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:15469983, ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:9286697}. Nucleus, nucleoplasm {ECO:0000269|PubMed:15469983}. Note=Expressed predominantly in the nucleolus. Associates with pre-ribosomal particles in the nucleus. {ECO:0000269|PubMed:16782053}.
| null | null | null | null | null |
FUNCTION: Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT (PubMed:22226966). Involved in both early and late stages of the pre-rRNA processing pathways (PubMed:26166824). Spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus (PubMed:15469983, PubMed:16782053, PubMed:26456651, PubMed:29107693). Catalyzes the release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles through the ATPase activity (PubMed:26456651, PubMed:28416111, PubMed:29107693). {ECO:0000269|PubMed:15469983, ECO:0000269|PubMed:16782053, ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:26166824, ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:28416111, ECO:0000269|PubMed:29107693}.
|
Homo sapiens (Human)
|
O15382
|
BCAT2_HUMAN
|
MAAAALGQIWARKLLSVPWLLCGPRRYASSSFKAADLQLEMTQKPHKKPGPGEPLVFGKTFTDHMLMVEWNDKGWGQPRIQPFQNLTLHPASSSLHYSLQLFEGMKAFKGKDQQVRLFRPWLNMDRMLRSAMRLCLPSFDKLELLECIRRLIEVDKDWVPDAAGTSLYVRPVLIGNEPSLGVSQPTRALLFVILCPVGAYFPGGSVTPVSLLADPAFIRAWVGGVGNYKLGGNYGPTVLVQQEALKRGCEQVLWLYGPDHQLTEVGTMNIFVYWTHEDGVLELVTPPLNGVILPGVVRQSLLDMAQTWGEFRVVERTITMKQLLRALEEGRVREVFGSGTACQVCPVHRILYKDRNLHIPTMENGPELILRFQKELKEIQYGIRAHEWMFPV
|
2.6.1.42
|
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:12269802, ECO:0000269|PubMed:16141215, ECO:0000269|PubMed:17050531};
|
amino acid biosynthetic process [GO:0008652]; branched-chain amino acid biosynthetic process [GO:0009082]; cellular response to leukemia inhibitory factor [GO:1990830]; isoleucine catabolic process [GO:0006550]; leucine biosynthetic process [GO:0009098]; lipid metabolic process [GO:0006629]; regulation of hormone levels [GO:0010817]; valine biosynthetic process [GO:0009099]
|
mitochondrial matrix [GO:0005759]; 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:0000269|PubMed:8702755}; 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:8702755}; 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:8702755};
| null | null | null | null |
FUNCTION: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine (PubMed:17050531, PubMed:25653144, PubMed:8702755). May also function as a transporter of branched chain alpha-keto acids (By similarity). {ECO:0000250|UniProtKB:O35854, ECO:0000269|PubMed:17050531, ECO:0000269|PubMed:25653144, ECO:0000269|PubMed:8702755}.
|
Homo sapiens (Human)
|
O15389
|
SIGL5_HUMAN
|
MLPLLLLPLLWGGSLQEKPVYELQVQKSVTVQEGLCVLVPCSFSYPWRSWYSSPPLYVYWFRDGEIPYYAEVVATNNPDRRVKPETQGRFRLLGDVQKKNCSLSIGDARMEDTGSYFFRVERGRDVKYSYQQNKLNLEVTALIEKPDIHFLEPLESGRPTRLSCSLPGSCEAGPPLTFSWTGNALSPLDPETTRSSELTLTPRPEDHGTNLTCQMKRQGAQVTTERTVQLNVSYAPQTITIFRNGIALEILQNTSYLPVLEGQALRLLCDAPSNPPAHLSWFQGSPALNATPISNTGILELRRVRSAEEGGFTCRAQHPLGFLQIFLNLSVYSLPQLLGPSCSWEAEGLHCRCSFRARPAPSLCWRLEEKPLEGNSSQGSFKVNSSSAGPWANSSLILHGGLSSDLKVSCKAWNIYGSQSGSVLLLQGRSNLGTGVVPAALGGAGVMALLCICLCLIFFLIVKARRKQAAGRPEKMDDEDPIMGTITSGSRKKPWPDSPGDQASPPGDAPPLEEQKELHYASLSFSEMKSREPKDQEAPSTTEYSEIKTSK
| null | null |
cell adhesion [GO:0007155]
|
ficolin-1-rich granule membrane [GO:0101003]; plasma membrane [GO:0005886]; secretory granule membrane [GO:0030667]; tertiary granule membrane [GO:0070821]
|
carbohydrate binding [GO:0030246]; sialic acid binding [GO:0033691]
|
PF13927;PF07686;
|
2.60.40.10;
|
Immunoglobulin superfamily, SIGLEC (sialic acid binding Ig-like lectin) family
| null |
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
| null | null | null | null | null |
FUNCTION: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Binds equally to alpha-2,3-linked and alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.
|
Homo sapiens (Human)
|
O15391
|
TYY2_HUMAN
|
MASNEDFSITQDLEIPADIVELHDINVEPLPMEDIPTESVQYEDVDGNWIYGGHNHPPLMVLQPLFTNTGYGDHDQEMLMLQTQEEVVGYCDSDNQLGNDLEDQLALPDSIEDEHFQMTLASLSASAASTSTSTQSRSKKPSKKPSGKSATSTEANPAGSSSSLGTRKWEQKQMQVKTLEGEFSVTMWSPNDNNDQGAVGEGQAENPPDYSEYLKGKKLPPGGLPGIDLSDPKQLAEFTKVKPKRSKGEPPKTVPCSYSGCEKMFRDYAAMRKHLHIHGPRVHVCAECGKAFLESSKLRRHQLVHTGEKPFQCTFEGCGKRFSLDFNLRTHLRIHTGDKPFVCPFDVCNRKFAQSTNLKTHILTHVKTKNNP
| null | null |
positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of transcription by RNA polymerase II [GO:0006357]
|
nucleus [GO:0005634]; PcG protein complex [GO:0031519]; transcription regulator complex [GO:0005667]
|
cis-regulatory region sequence-specific DNA binding [GO:0000987]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; 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]; sequence-specific DNA binding [GO:0043565]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF00096;
|
3.30.160.60;
|
YY transcription factor family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Functions as a multifunctional transcription factor that may exhibit positive and negative control on a large number of genes. May antagonize YY1 and function in development and differentiation. {ECO:0000269|PubMed:16260628}.
|
Homo sapiens (Human)
|
O15392
|
BIRC5_HUMAN
|
MGAPTLPPAWQPFLKDHRISTFKNWPFLEGCACTPERMAEAGFIHCPTENEPDLAQCFFCFKELEGWEPDDDPIEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIAKETNNKKKEFEETAKKVRRAIEQLAAMD
| null | null |
apoptotic process [GO:0006915]; cell division [GO:0051301]; establishment of chromosome localization [GO:0051303]; G2/M transition of mitotic cell cycle [GO:0000086]; mitotic cell cycle [GO:0000278]; mitotic cytokinesis [GO:0000281]; mitotic spindle assembly [GO:0090307]; mitotic spindle assembly checkpoint signaling [GO:0007094]; mitotic spindle midzone assembly [GO:0051256]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154]; negative regulation of DNA-templated transcription [GO:0045892]; positive regulation of attachment of mitotic spindle microtubules to kinetochore [GO:1902425]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of exit from mitosis [GO:0031536]; positive regulation of mitotic cell cycle [GO:0045931]; positive regulation of mitotic cell cycle spindle assembly checkpoint [GO:0090267]; positive regulation of mitotic cytokinesis [GO:1903490]; positive regulation of mitotic sister chromatid separation [GO:1901970]; protein phosphorylation [GO:0006468]; protein-containing complex localization [GO:0031503]; sensory perception of sound [GO:0007605]
|
centriole [GO:0005814]; chromosome passenger complex [GO:0032133]; chromosome, centromeric region [GO:0000775]; cytoplasm [GO:0005737]; cytoplasmic microtubule [GO:0005881]; cytosol [GO:0005829]; interphase microtubule organizing center [GO:0031021]; kinetochore [GO:0000776]; microtubule [GO:0005874]; microtubule cytoskeleton [GO:0015630]; midbody [GO:0030496]; nuclear chromosome [GO:0000228]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; spindle [GO:0005819]; spindle microtubule [GO:0005876]; survivin complex [GO:1990713]
|
cobalt ion binding [GO:0050897]; cysteine-type endopeptidase inhibitor activity [GO:0004869]; cysteine-type endopeptidase inhibitor activity involved in apoptotic process [GO:0043027]; enzyme binding [GO:0019899]; identical protein binding [GO:0042802]; metal ion binding [GO:0046872]; microtubule binding [GO:0008017]; protein heterodimerization activity [GO:0046982]; protein homodimerization activity [GO:0042803]; protein-folding chaperone binding [GO:0051087]; small GTPase binding [GO:0031267]; tubulin binding [GO:0015631]; zinc ion binding [GO:0008270]
|
PF00653;
| null |
IAP family
|
PTM: Ubiquitinated by the Cul9-RING ubiquitin-protein ligase complex, leading to its degradation. Ubiquitination is required for centrosomal targeting. Deubiquitinated by USP35 or USP38; leading to stabilization (PubMed:34438346). {ECO:0000269|PubMed:16322459, ECO:0000269|PubMed:24793696, ECO:0000269|PubMed:34438346}.; PTM: In vitro phosphorylation at Thr-117 by AURKB prevents interaction with INCENP and localization to mitotic chromosomes (PubMed:14610074). Phosphorylation at Thr-48 by CK2 is critical for its mitotic and anti-apoptotic activities (PubMed:21252625). Phosphorylation at Thr-34 by CDK15 is critical for its anti-apoptotic activity (PubMed:24866247). Phosphorylation at Ser-20 by AURKC is critical for regulation of proper chromosome alignment and segregation, and possibly cytokinesis. {ECO:0000269|PubMed:11069302, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:21252625, ECO:0000269|PubMed:24866247, ECO:0000269|PubMed:27332895}.; PTM: Acetylation at Lys-129 by CBP results in its homodimerization, while deacetylation promotes the formation of monomers which heterodimerize with XPO1/CRM1 which facilitates its nuclear export. The acetylated form represses STAT3 transactivation. The dynamic equilibrium between its acetylation and deacetylation at Lys-129 determines its interaction with XPO1/CRM1, its subsequent subcellular localization, and its ability to inhibit STAT3 transactivation. {ECO:0000269|PubMed:20826784}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:21364656}. Nucleus {ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:21364656}. Chromosome {ECO:0000269|PubMed:14610074}. Chromosome, centromere {ECO:0000269|PubMed:11084331, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:16322459}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:11084331}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:11084331}. Midbody {ECO:0000269|PubMed:15665297}. Note=Localizes at the centromeres from prophase to metaphase, at the spindle midzone during anaphase and a the midbody during telophase and cytokinesis. Accumulates in the nucleus upon treatment with leptomycin B (LMB), a XPO1/CRM1 nuclear export inhibitor (By similarity). Localizes on chromosome arms and inner centromeres from prophase through metaphase. Localizes to kinetochores in metaphase, distributes to the midzone microtubules in anaphase and at telophase, localizes exclusively to the midbody (PubMed:11084331). Colocalizes with AURKB at mitotic chromosomes (PubMed:14610074). Acetylation at Lys-129 directs its localization to the nucleus by enhancing homodimerization and thereby inhibiting XPO1/CRM1-mediated nuclear export (PubMed:20826784). {ECO:0000250|UniProtKB:E3SCZ8, ECO:0000269|PubMed:11084331, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:20826784}.
| null | null | null | null | null |
FUNCTION: Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:20627126, PubMed:21364656, PubMed:25778398, PubMed:28218735, PubMed:9859993). Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis (PubMed:16322459). Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules (PubMed:20826784). Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (PubMed:20929775). The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). May counteract a default induction of apoptosis in G2/M phase (PubMed:9859993). The acetylated form represses STAT3 transactivation of target gene promoters (PubMed:20826784). May play a role in neoplasia (PubMed:10626797). Inhibitor of CASP3 and CASP7 (PubMed:21536684). Essential for the maintenance of mitochondrial integrity and function (PubMed:25778398). Isoform 2 and isoform 3 do not appear to play vital roles in mitosis (PubMed:12773388, PubMed:16291752). Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform (PubMed:10626797). {ECO:0000269|PubMed:10626797, ECO:0000269|PubMed:12773388, ECO:0000269|PubMed:16291752, ECO:0000269|PubMed:16322459, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:20929775, ECO:0000269|PubMed:21364656, ECO:0000269|PubMed:21536684, ECO:0000269|PubMed:25778398, ECO:0000269|PubMed:28218735, ECO:0000269|PubMed:9859993}.
|
Homo sapiens (Human)
|
O15393
|
TMPS2_HUMAN
|
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG
|
3.4.21.122
| null |
positive regulation of viral entry into host cell [GO:0046598]; protein autoprocessing [GO:0016540]; proteolysis [GO:0006508]; viral translation [GO:0019081]
|
extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; nucleoplasm [GO:0005654]; plasma membrane [GO:0005886]
|
serine-type endopeptidase activity [GO:0004252]; serine-type peptidase activity [GO:0008236]
|
PF15494;PF00089;
|
4.10.400.10;3.10.250.10;2.40.10.10;
|
Peptidase S1 family
|
PTM: Proteolytically processed; by an autocatalytic mechanism.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20382709, ECO:0000269|PubMed:21068237}; Single-pass type II membrane protein {ECO:0000269|PubMed:20382709, ECO:0000269|PubMed:21068237}.; SUBCELLULAR LOCATION: [Transmembrane protease serine 2 catalytic chain]: Secreted {ECO:0000269|PubMed:20382709}. Note=Activated by cleavage and secreted. {ECO:0000269|PubMed:11245484, ECO:0000269|PubMed:20382709}.
|
CATALYTIC ACTIVITY: Reaction=The enzyme cleaves angiotensin-converting enzyme 2 (EC 3.4.17.23) and cleaves influenzea A and B virus and coronavirus spike glycoproteins at arginine residues.; EC=3.4.21.122; Evidence={ECO:0000269|PubMed:32703818};
| null | null | null | null |
FUNCTION: Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818). Participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:25122198, PubMed:26018085). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity). {ECO:0000250|UniProtKB:Q9JIQ8, ECO:0000269|PubMed:15537383, ECO:0000269|PubMed:25122198, ECO:0000269|PubMed:26018085, ECO:0000269|PubMed:32703818}.; FUNCTION: (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436, PubMed:33051876, PubMed:34159616). The cleavage of SARS-COV2 spike glycoprotein occurs between the S2 and S2' site (PubMed:32703818). Upon SARS-CoV-2 infection, increases syncytia formation by accelerating the fusion process (PubMed:33051876, PubMed:34159616). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity. {ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:32703818, ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:34159616}.
|
Homo sapiens (Human)
|
O15394
|
NCAM2_HUMAN
|
MSLLLSFYLLGLLVSSGQALLQVTISLSKVELSVGESKFFTCTAIGEPESIDWYNPQGEKIISTQRVVVQKEGVRSRLTIYNANIEDAGIYRCQATDAKGQTQEATVVLEIYQKLTFREVVSPQEFKQGEDAEVVCRVSSSPAPAVSWLYHNEEVTTISDNRFAMLANNNLQILNINKSDEGIYRCEGRVEARGEIDFRDIIVIVNVPPAISMPQKSFNATAERGEEMTFSCRASGSPEPAISWFRNGKLIEENEKYILKGSNTELTVRNIINSDGGPYVCRATNKAGEDEKQAFLQVFVQPHIIQLKNETTYENGQVTLVCDAEGEPIPEITWKRAVDGFTFTEGDKSLDGRIEVKGQHGSSSLHIKDVKLSDSGRYDCEAASRIGGHQKSMYLDIEYAPKFISNQTIYYSWEGNPINISCDVKSNPPASIHWRRDKLVLPAKNTTNLKTYSTGRKMILEIAPTSDNDFGRYNCTATNHIGTRFQEYILALADVPSSPYGVKIIELSQTTAKVSFNKPDSHGGVPIHHYQVDVKEVASEIWKIVRSHGVQTMVVLNNLEPNTTYEIRVAAVNGKGQGDYSKIEIFQTLPVREPSPPSIHGQPSSGKSFKLSITKQDDGGAPILEYIVKYRSKDKEDQWLEKKVQGNKDHIILEHLQWTMGYEVQITAANRLGYSEPTVYEFSMPPKPNIIKDTLFNGLGLGAVIGLGVAALLLILVVTDVSCFFIRQCGLLMCITRRMCGKKSGSSGKSKELEEGKAAYLKDGSKEPIVEMRTEDERVTNHEDGSPVNEPNETTPLTEPEKLPLKEEDGKEALNPETIEIKVSNDIIQSKEDDSKA
| null | null |
axonal fasciculation [GO:0007413]; neuron cell-cell adhesion [GO:0007158]
|
axon [GO:0030424]; membrane [GO:0016020]; nuclear body [GO:0016604]; plasma membrane [GO:0005886]
|
identical protein binding [GO:0042802]
|
PF00041;PF07679;PF13927;
|
2.60.40.10;
| null | null |
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.
| null | null | null | null | null |
FUNCTION: May play important roles in selective fasciculation and zone-to-zone projection of the primary olfactory axons.
|
Homo sapiens (Human)
|
O15397
|
IPO8_HUMAN
|
MDLNRIIQALKGTIDPKLRIAAENELNQSYKIINFAPSLLRIIVSDHVEFPVRQAAAIYLKNMVTQYWPDREPPPGEAIFPFNIHENDRQQIRDNIVEGIIRSPDLVRVQLTMCLRAIIKHDFPGHWPGVVDKIDYYLQSQSSASWLGSLLCLYQLVKTYEYKKAEEREPLIIAMQIFLPRIQQQIVQLLPDSSYYSVLLQKQILKIFYALVQYALPLQLVNNQTMTTWMEIFRTIIDRTVPPETLHIDEDDRPELVWWKCKKWALHIVARLFERYGSPGNVTKEYFEFSEFFLKTYAVGIQQVLLKILDQYRQKEYVAPRVLQQAFNYLNQGVVHSITWKQMKPHIQNISEDVIFSVMCYKDEDEELWQEDPYEYIRMKFDIFEDYASPTTAAQTLLYTAAKKRKEVLPKMMAFCYQILTDPNFDPRKKDGALHVIGSLAEILLKKSLFKDQMELFLQNHVFPLLLSNLGYLRARSCWVLHAFSSLKFHNELNLRNAVELAKKSLIEDKEMPVKVEAALALQSLISNQIQAKEYMKPHVRPIMQELLHIVRETENDDVTNVIQKMICEYSQEVASIAVDMTQHLAEIFGKVLQSDEYEEVEDKTVMAMGILHTIDTILTVVEDHKEITQQLENICLRIIDLVLQKHVIEFYEEILSLAYSLTCHSISPQMWQLLGILYEVFQQDCFEYFTDMMPLLHNYVTIDTDTLLSNAKHLEILFTMCRKVLCGDAGEDAECHAAKLLEVIILQCKGRGIDQCIPLFVQLVLERLTRGVKTSELRTMCLQVAIAALYYNPDLLLHTLERIQLPHNPGPITVQFINQWMNDTDCFLGHHDRKMCIIGLSILLELQNRPPAVDAVVGQIVPSILFLFLGLKQVCATRQLVNREDRSKAEKADMEENEEISSDEEETNVTAQAMQSNNGRGEDEEEEDDDWDEEVLEETALEGFSTPLDLDNSVDEYQFFTQALITVQSRDAAWYQLLMAPLSEDQRTALQEVYTLAEHRRTVAEAKKKIEQQGGFTFENKGVLSAFNFGTVPSNN
| null | null |
protein import into nucleus [GO:0006606]; signal transduction [GO:0007165]
|
cytosol [GO:0005829]; nuclear envelope [GO:0005635]; nucleoplasm [GO:0005654]
|
small GTPase binding [GO:0031267]
|
PF08506;PF03810;
|
1.25.10.10;
|
Importin beta family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Involved in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously, may serve as receptor for nuclear localization signals (NLS) and promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (PubMed:9214382). In vitro mediates the nuclear import of the signal recognition particle protein SRP19 (PubMed:11682607). May also be involved in cytoplasm-to-nucleus shuttling of a broad spectrum of other cargos, including Argonaute-microRNAs complexes, the JUN protein, RELA/NF-kappa-B p65 subunit, the translation initiation factor EIF4E and a set of receptor-activated mothers against decapentaplegic homolog (SMAD) transcription factors that play a critical role downstream of the large family of transforming growth factor beta and bone morphogenetic protein (BMP) cytokines (Probable). {ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9214382, ECO:0000305|PubMed:34010604}.
|
Homo sapiens (Human)
|
O15399
|
NMDE4_HUMAN
|
MRGAGGPRGPRGPAKMLLLLALACASPFPEEAPGPGGAGGPGGGLGGARPLNVALVFSGPAYAAEAARLGPAVAAAVRSPGLDVRPVALVLNGSDPRSLVLQLCDLLSGLRVHGVVFEDDSRAPAVAPILDFLSAQTSLPIVAVHGGAALVLTPKEKGSTFLQLGSSTEQQLQVIFEVLEEYDWTSFVAVTTRAPGHRAFLSYIEVLTDGSLVGWEHRGALTLDPGAGEAVLSAQLRSVSAQIRLLFCAREEAEPVFRAAEEAGLTGSGYVWFMVGPQLAGGGGSGAPGEPPLLPGGAPLPAGLFAVRSAGWRDDLARRVAAGVAVVARGAQALLRDYGFLPELGHDCRAQNRTHRGESLHRYFMNITWDNRDYSFNEDGFLVNPSLVVISLTRDRTWEVVGSWEQQTLRLKYPLWSRYGRFLQPVDDTQHLTVATLEERPFVIVEPADPISGTCIRDSVPCRSQLNRTHSPPPDAPRPEKRCCKGFCIDILKRLAHTIGFSYDLYLVTNGKHGKKIDGVWNGMIGEVFYQRADMAIGSLTINEERSEIVDFSVPFVETGISVMVARSNGTVSPSAFLEPYSPAVWVMMFVMCLTVVAVTVFIFEYLSPVGYNRSLATGKRPGGSTFTIGKSIWLLWALVFNNSVPVENPRGTTSKIMVLVWAFFAVIFLASYTANLAAFMIQEEYVDTVSGLSDRKFQRPQEQYPPLKFGTVPNGSTEKNIRSNYPDMHSYMVRYNQPRVEEALTQLKAGKLDAFIYDAAVLNYMARKDEGCKLVTIGSGKVFATTGYGIALHKGSRWKRPIDLALLQFLGDDEIEMLERLWLSGICHNDKIEVMSSKLDIDNMAGVFYMLLVAMGLSLLVFAWEHLVYWRLRHCLGPTHRMDFLLAFSRGMYSCCSAEAAPPPAKPPPPPQPLPSPAYPAPRPAPGPAPFVPRERASVDRWRRTKGAGPPGGAGLADGFHRYYGPIEPQGLGLGLGEARAAPRGAAGRPLSPPAAQPPQKPPPSYFAIVRDKEPAEPPAGAFPGFPSPPAPPAAAATAVGPPLCRLAFEDESPPAPARWPRSDPESQPLLGPGAGGAGGTGGAGGGAPAAPPPCRAAPPPCPYLDLEPSPSDSEDSESLGGASLGGLEPWWFADFPYPYAERLGPPPGRYWSVDKLGGWRAGSWDYLPPRSGPAAWHCRHCASLELLPPPRHLSCSHDGLDGGWWAPPPPPWAAGPLPRRRARCGCPRSHPHRPRASHRTPAAAAPHHHRHRRAAGGWDLPPPAPTSRSLEDLSSCPRAAPARRLTGPSRHARRCPHAAHWGPPLPTASHRRHRGGDLGTRRGSAHFSSLESEV
| null | null |
adult locomotory behavior [GO:0008344]; brain development [GO:0007420]; calcium ion transmembrane import into cytosol [GO:0097553]; cellular response to L-glutamate [GO:1905232]; excitatory chemical synaptic transmission [GO:0098976]; excitatory postsynaptic potential [GO:0060079]; ionotropic glutamate receptor signaling pathway [GO:0035235]; long-term synaptic potentiation [GO:0060291]; monoatomic cation transmembrane transport [GO:0098655]; positive regulation of excitatory postsynaptic potential [GO:2000463]; positive regulation of synaptic transmission, glutamatergic [GO:0051968]; regulation of monoatomic cation transmembrane transport [GO:1904062]; regulation of neuronal synaptic plasticity [GO:0048168]; regulation of sensory perception of pain [GO:0051930]; regulation of synaptic plasticity [GO:0048167]; startle response [GO:0001964]; synaptic transmission, glutamatergic [GO:0035249]
|
endoplasmic reticulum membrane [GO:0005789]; glutamatergic synapse [GO:0098978]; hippocampal mossy fiber to CA3 synapse [GO:0098686]; NMDA selective glutamate receptor complex [GO:0017146]; plasma membrane [GO:0005886]; postsynaptic density membrane [GO:0098839]; postsynaptic membrane [GO:0045211]; presynaptic active zone membrane [GO:0048787]
|
glutamate binding [GO:0016595]; glutamate-gated calcium ion channel activity [GO:0022849]; glutamate-gated receptor activity [GO:0004970]; ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential [GO:0099507]; NMDA glutamate receptor activity [GO:0004972]; transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential [GO:1904315]; voltage-gated monoatomic cation channel activity [GO:0022843]
|
PF01094;PF00060;PF10613;PF00497;
|
3.40.50.2300;3.40.190.10;
|
Glutamate-gated ion channel (TC 1.A.10.1) family, NR2D/GRIN2D subfamily
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:9489750}; Multi-pass membrane protein. Postsynaptic cell membrane; Multi-pass membrane protein.
| null | null | null | null | null |
FUNCTION: Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:27616483, PubMed:28126851, PubMed:9489750). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:9489750). {ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:27616483, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:9489750}.
|
Homo sapiens (Human)
|
O15400
|
STX7_HUMAN
|
MSYTPGVGGDPAQLAQRISSNIQKITQCSVEIQRTLNQLGTPQDSPELRQQLQQKQQYTNQLAKETDKYIKEFGSLPTTPSEQRQRKIQKDRLVAEFTTSLTNFQKVQRQAAEREKEFVARVRASSRVSGSFPEDSSKERNLVSWESQTQPQVQVQDEEITEDDLRLIHERESSIRQLEADIMDINEIFKDLGMMIHEQGDVIDSIEANVENAEVHVQQANQQLSRAADYQRKSRKTLCIIILILVIGVAIISLIIWGLNH
| null | null |
intracellular protein transport [GO:0006886]; organelle assembly [GO:0070925]; organelle localization [GO:0051640]; positive regulation of receptor localization to synapse [GO:1902685]; positive regulation of T cell mediated cytotoxicity [GO:0001916]; regulation of protein localization to plasma membrane [GO:1903076]; vesicle docking [GO:0048278]; vesicle fusion [GO:0006906]
|
azurophil granule [GO:0042582]; early endosome [GO:0005769]; early endosome membrane [GO:0031901]; endocytic vesicle [GO:0030139]; endomembrane system [GO:0012505]; endosome [GO:0005768]; extracellular exosome [GO:0070062]; immunological synapse [GO:0001772]; late endosome [GO:0005770]; lysosomal membrane [GO:0005765]; lysosome [GO:0005764]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; recycling endosome [GO:0055037]; SNARE complex [GO:0031201]; synaptic vesicle [GO:0008021]; tertiary granule [GO:0070820]; vesicle [GO:0031982]
|
chloride channel inhibitor activity [GO:0019869]; SNAP receptor activity [GO:0005484]; SNARE binding [GO:0000149]; syntaxin binding [GO:0019905]
|
PF05739;PF14523;
|
1.20.5.110;1.20.58.70;
|
Syntaxin family
| null |
SUBCELLULAR LOCATION: Early endosome membrane {ECO:0000250}; Single-pass type IV membrane protein {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: May be involved in protein trafficking from the plasma membrane to the early endosome (EE) as well as in homotypic fusion of endocytic organelles. Mediates the endocytic trafficking from early endosomes to late endosomes and lysosomes.
|
Homo sapiens (Human)
|
O15405
|
TOX3_HUMAN
|
MDVRFYPAAAGDPASLDFAQCLGYYGYSKFGNNNNYMNMAEANNAFFAASEQTFHTPSLGDEEFEIPPITPPPESDPALGMPDVLLPFQALSDPLPSQGSEFTPQFPPQSLDLPSITISRNLVEQDGVLHSSGLHMDQSHTQVSQYRQDPSLIMRSIVHMTDAARSGVMPPAQLTTINQSQLSAQLGLNLGGASMPHTSPSPPASKSATPSPSSSINEEDADEANRAIGEKRAAPDSGKKPKTPKKKKKKDPNEPQKPVSAYALFFRDTQAAIKGQNPNATFGEVSKIVASMWDSLGEEQKQVYKRKTEAAKKEYLKALAAYRASLVSKAAAESAEAQTIRSVQQTLASTNLTSSLLLNTPLSQHGTVSASPQTLQQSLPRSIAPKPLTMRLPMNQIVTSVTIAANMPSNIGAPLISSMGTTMVGSAPSTQVSPSVQTQQHQMQLQQQQQQQQQQMQQMQQQQLQQHQMHQQIQQQMQQQHFQHHMQQHLQQQQQHLQQQINQQQLQQQLQQRLQLQQLQHMQHQSQPSPRQHSPVASQITSPIPAIGSPQPASQQHQSQIQSQTQTQVLSQVSIF
| null | null |
apoptotic process [GO:0006915]; negative regulation of neuron apoptotic process [GO:0043524]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of apoptotic process [GO:0042981]; regulation of transcription by RNA polymerase II [GO:0006357]
|
cytosol [GO:0005829]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
chromatin binding [GO:0003682]; chromatin DNA binding [GO:0031490]; phosphoprotein binding [GO:0051219]; protein homodimerization activity [GO:0042803]; transcription coactivator activity [GO:0003713]
|
PF00505;
|
1.10.30.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Transcriptional coactivator of the p300/CBP-mediated transcription complex. Activates transactivation through cAMP response element (CRE) sites. Protects against cell death by inducing antiapoptotic and repressing pro-apoptotic transcripts. Stimulates transcription from the estrogen-responsive or BCL-2 promoters. Required for depolarization-induced transcription activation of the C-FOS promoter in neurons. Associates with chromatin to the estrogen-responsive C3 promoter region. {ECO:0000269|PubMed:21172805}.
|
Homo sapiens (Human)
|
O15409
|
FOXP2_HUMAN
|
MMQESATETISNSSMNQNGMSTLSSQLDAGSRDGRSSGDTSSEVSTVELLHLQQQQALQAARQLLLQQQTSGLKSPKSSDKQRPLQVPVSVAMMTPQVITPQQMQQILQQQVLSPQQLQALLQQQQAVMLQQQQLQEFYKKQQEQLHLQLLQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQHPGKQAKEQQQQQQQQQQLAAQQLVFQQQLLQMQQLQQQQHLLSLQRQGLISIPPGQAALPVQSLPQAGLSPAEIQQLWKEVTGVHSMEDNGIKHGGLDLTTNNSSSTTSSNTSKASPPITHHSIVNGQSSVLSARRDSSSHEETGASHTLYGHGVCKWPGCESICEDFGQFLKHLNNEHALDDRSTAQCRVQMQVVQQLEIQLSKERERLQAMMTHLHMRPSEPKPSPKPLNLVSSVTMSKNMLETSPQSLPQTPTTPTAPVTPITQGPSVITPASVPNVGAIRRRHSDKYNIPMSSEIAPNYEFYKNADVRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQKRRSQKITGSPTLVKNIPTSLGYGAALNASLQAALAESSLPLLSNPGLINNASSGLLQAVHEDLNGSLDHIDSNGNSSPGCSPQPHIHSIHVKEEPVIAEDEDCPMSLVTTANHSPELEDDREIEEEPLSEDLE
| null | null |
caudate nucleus development [GO:0021757]; cerebral cortex development [GO:0021987]; negative regulation of DNA-templated transcription [GO:0045892]; putamen development [GO:0021758]; regulation of transcription by RNA polymerase II [GO:0006357]
|
chromatin [GO:0000785]; nucleus [GO:0005634]
|
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]; identical protein binding [GO:0042802]; metal ion binding [GO:0046872]; protein homodimerization activity [GO:0042803]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]
|
PF00250;PF16159;
|
1.20.5.340;1.10.10.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Plays a role in synapse formation by regulating SRPX2 levels. Involved in neural mechanisms mediating the development of speech and language.
|
Homo sapiens (Human)
|
O15427
|
MOT4_HUMAN
|
MGGAVVDEGPTGVKAPDGGWGWAVLFGCFVITGFSYAFPKAVSVFFKELIQEFGIGYSDTAWISSILLAMLYGTGPLCSVCVNRFGCRPVMLVGGLFASLGMVAASFCRSIIQVYLTTGVITGLGLALNFQPSLIMLNRYFSKRRPMANGLAAAGSPVFLCALSPLGQLLQDRYGWRGGFLILGGLLLNCCVCAALMRPLVVTAQPGSGPPRPSRRLLDLSVFRDRGFVLYAVAASVMVLGLFVPPVFVVSYAKDLGVPDTKAAFLLTILGFIDIFARPAAGFVAGLGKVRPYSVYLFSFSMFFNGLADLAGSTAGDYGGLVVFCIFFGISYGMVGALQFEVLMAIVGTHKFSSAIGLVLLMEAVAVLVGPPSGGKLLDATHVYMYVFILAGAEVLTSSLILLLGNFFCIRKKPKEPQPEVAAAEEEKLHKPPADSGVDLREVEHFLKAEPEKNGEVVHTPETSV
| null | null |
lactate transmembrane transport [GO:0035873]; monocarboxylic acid transport [GO:0015718]; 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]; membrane [GO:0016020]; nuclear membrane [GO:0031965]; plasma membrane [GO:0005886]; synapse [GO:0045202]
|
lactate:proton symporter activity [GO:0015650]; monocarboxylic acid transmembrane transporter activity [GO:0008028]; pyruvate transmembrane transporter activity [GO:0050833]; RNA binding [GO:0003723]
|
PF07690;
|
1.20.1250.20;
|
Major facilitator superfamily, Monocarboxylate porter (TC 2.A.1.13) family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10921872, ECO:0000269|PubMed:11101640, ECO:0000269|PubMed:15505343, ECO:0000269|PubMed:23935841}; Multi-pass membrane protein. Basolateral cell membrane {ECO:0000269|PubMed:21199217}; Multi-pass membrane protein {ECO:0000255}. Note=Plasma membrane localization is dependent upon the BSG/MCT4 interaction (PubMed:10921872). Basolateral sorting signals (BLSS) in C-terminal cytoplasmic tail ensure its basolateral expression in polarised epithelial cells (PubMed:21199217). {ECO:0000269|PubMed:10921872, ECO:0000269|PubMed:21199217}.
|
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:11101640, ECO:0000269|PubMed:23935841, ECO:0000269|PubMed:31719150}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29416; Evidence={ECO:0000269|PubMed:31719150}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29417; Evidence={ECO:0000269|PubMed:31719150}; CATALYTIC ACTIVITY: Reaction=H(+)(out) + pyruvate(out) = H(+)(in) + pyruvate(in); Xref=Rhea:RHEA:64720, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378; Evidence={ECO:0000269|PubMed:31719150};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=3.4 mM for (S)-lactate (pH 5.5) {ECO:0000269|PubMed:23935841}; KM=37.6 mM for (S)-lactate (pH 7.5) {ECO:0000269|PubMed:23935841}; KM=28 mM for (S)-lactate {ECO:0000269|PubMed:11101640}; KM=519 mM for D-lactate {ECO:0000269|PubMed:11101640}; KM=153 mM for pyruvate {ECO:0000269|PubMed:11101640}; KM=1.7 mM for (S)-lactate {ECO:0000269|PubMed:31719150}; KM=4.2 mM for pyruvate {ECO:0000269|PubMed:31719150};
| null | null | null |
FUNCTION: Proton-dependent transporter of monocarboxylates such as L-lactate and pyruvate (PubMed:11101640, PubMed:23935841, PubMed:31719150). Plays a predominant role in L-lactate efflux from highly glycolytic cells (By similarity). {ECO:0000250|UniProtKB:O35910, ECO:0000269|PubMed:11101640, ECO:0000269|PubMed:23935841, ECO:0000269|PubMed:31719150}.
|
Homo sapiens (Human)
|
O15431
|
COPT1_HUMAN
|
MDHSHHMGMSYMDSNSTMQPSHHHPTTSASHSHGGGDSSMMMMPMTFYFGFKNVELLFSGLVINTAGEMAGAFVAVFLLAMFYEGLKIARESLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKAVVVDITEHCH
| null | null |
angiogenesis [GO:0001525]; copper ion import [GO:0015677]; copper ion transport [GO:0006825]; establishment of localization in cell [GO:0051649]; intracellular copper ion homeostasis [GO:0006878]; plasma membrane copper ion transport [GO:0015679]; protein complex oligomerization [GO:0051259]; silver ion transmembrane transport [GO:1902601]; vascular endothelial growth factor receptor-2 signaling pathway [GO:0036324]; xenobiotic transport [GO:0042908]
|
apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; early endosome membrane [GO:0031901]; intercalated disc [GO:0014704]; late endosome membrane [GO:0031902]; plasma membrane [GO:0005886]; recycling endosome membrane [GO:0055038]
|
copper ion binding [GO:0005507]; copper ion transmembrane transporter activity [GO:0005375]; identical protein binding [GO:0042802]; silver ion transmembrane transporter activity [GO:0015080]; xenobiotic transmembrane transporter activity [GO:0042910]
|
PF04145;
| null |
Copper transporter (Ctr) (TC 1.A.56) family, SLC31A subfamily
|
PTM: O-Glycosylation at Thr-27 protects from proteolytic cleavage in the N-terminal extracellular domain. {ECO:0000269|PubMed:17525160}.; PTM: Proteolytic cleavage, leading to a truncated form, is facilitated by SLC31A2 (PubMed:24167251) and initiated preferentially by CTSL and to a minor extend by CTSB in endolysosomal compartments (PubMed:24167251, PubMed:27143361). In vitro, is cleaved by CTSL/cathepsin L between residues 8 and 9 from the amino terminus (PubMed:27143361). A post-CTSL/cathepsin L processing occurs to yield to the fully truncated form (PubMed:27143361). {ECO:0000269|PubMed:24167251, ECO:0000269|PubMed:27143361}.; PTM: Sulfenylated at Cys-189 after stimulation with VEGFA, which induces SLC31A1-KDR disulfide bond formation and their co-internalization to early endosomes, driving to a sustained VEGFR2 signaling. {ECO:0000269|PubMed:35027734}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:12023893, ECO:0000269|PubMed:15326162, ECO:0000269|PubMed:17525160, ECO:0000269|PubMed:20451502, ECO:0000269|PubMed:26205368, ECO:0000269|PubMed:26945057, ECO:0000269|PubMed:35913762}; Multi-pass membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:26945057}; Multi-pass membrane protein {ECO:0000255}. Recycling endosome membrane {ECO:0000269|PubMed:26945057}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q8K211}; Multi-pass membrane protein {ECO:0000255}. Note=The localization is controlled by the intra and extra-cellular copper concentration (PubMed:15326162, PubMed:19740744, PubMed:23658018, PubMed:26205368, PubMed:26945057). Under conditions of elevated extracellular copper concentrations, it is rapidly internalized by endocytosis from the plasma membrane by a clathrin- and dynamin-mediated process and degradated in order to prevent intracellular copper accumulation and to reduce the transport of the copper across the membrane (PubMed:15326162, PubMed:19740744, PubMed:23658018, PubMed:26205368, PubMed:26945057). The internalized SLC31A1 is then localized in early endosomes, and, upon a low extracellular copper concentrations, it is transported back to the plasma membrane in a RAB11A-dependent recycling pathway (PubMed:26945057). Localizes to the apical membrane in intestinal epithelial cells (By similarity). Mainly localized on the basolateral side of renal tubular cells (By similarity). Localizes to the neuronal cell body plasma membranes (By similarity). {ECO:0000250|UniProtKB:Q8K211, ECO:0000250|UniProtKB:Q9JK41, ECO:0000269|PubMed:15326162, ECO:0000269|PubMed:19740744, ECO:0000269|PubMed:23658018, ECO:0000269|PubMed:26205368, ECO:0000269|PubMed:26945057}.
|
CATALYTIC ACTIVITY: Reaction=Ag(+)(out) = Ag(+)(in); Xref=Rhea:RHEA:75207, ChEBI:CHEBI:49468; Evidence={ECO:0000269|PubMed:20569931}; CATALYTIC ACTIVITY: Reaction=Cu(+)(out) = Cu(+)(in); Xref=Rhea:RHEA:75211, ChEBI:CHEBI:49552; Evidence={ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:17525160, ECO:0000269|PubMed:19740744, ECO:0000269|PubMed:20451502, ECO:0000269|PubMed:20569931, ECO:0000269|PubMed:23658018};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.71 uM for copper(1+) {ECO:0000269|PubMed:11734551}; KM=8.9 uM for copper(1+) {ECO:0000269|PubMed:16135512}; KM=9.2 uM for copper(1+) (in Sf9 cells expressing SLC31A1) {ECO:0000269|PubMed:16135512}; KM=4.4 uM for copper(1+) {ECO:0000269|PubMed:23658018}; Vmax=6.76 pmol/min/mg protein toward copper(1+) {ECO:0000269|PubMed:11734551}; Vmax=75.7 pmol/min/mg protein toward copper(1+) {ECO:0000269|PubMed:16135512}; Vmax=59.5 pmol/min/mg protein toward copper(1+) (in Sf9 cells expressing SLC31A1) {ECO:0000269|PubMed:16135512};
| null | null | null |
FUNCTION: [High affinity copper uptake protein 1]: Uniporter that mediates the transport of copper(1+) from the extracellular space to the cytoplasm, across the plasma membrane (PubMed:11734551, PubMed:16135512, PubMed:17525160, PubMed:19740744, PubMed:20451502, PubMed:20569931, PubMed:23658018) and delivers directly copper(1+) to specific chaperone such as ATOX1, via a copper(1+)- mediated transient interaction between the C-terminal domain and a copper(1+) chaperone, thus controlling intracellular copper(1+) levels (PubMed:11734551, PubMed:16135512, PubMed:17525160, PubMed:19740744, PubMed:20451502, PubMed:20569931, PubMed:23658018, PubMed:26745413). May function in copper(1+) import from the apical membrane thus may drive intestinal copper absorption (By similarity). The copper(1+) transport mechanism is sodium-independent, saturable and of high-affinity (PubMed:11734551). Also mediates the uptake of silver(1+) (PubMed:20569931). May function in the influx of the platinum-containing chemotherapeutic agents (PubMed:20451502, PubMed:20569931). The platinum-containing chemotherapeutic agents uptake is saturable (By similarity). In vitro, mediates the transport of cadmium(2+) into cells (PubMed:33294387). Also participates in the first step of copper(2+) acquisition by cells through a direct transfer of copper(2+) from copper(2+) carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper(2+) reduction and probably followed by copper(1+) stabilization (PubMed:30489586). In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper(1+) transport independent manner, by transmitting the VEGF-induced ROS signal through a sulfenylation at Cys-189 leadin g to a subsequent disulfide bond formation between SLC31A1 and KDR (PubMed:35027734). The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling (PubMed:35027734). {ECO:0000250|UniProtKB:Q8K211, ECO:0000250|UniProtKB:Q9JK41, ECO:0000269|PubMed:11734551, ECO:0000269|PubMed:16135512, ECO:0000269|PubMed:17525160, ECO:0000269|PubMed:19740744, ECO:0000269|PubMed:20451502, ECO:0000269|PubMed:20569931, ECO:0000269|PubMed:23658018, ECO:0000269|PubMed:26745413, ECO:0000269|PubMed:30489586, ECO:0000269|PubMed:33294387, ECO:0000269|PubMed:35027734}.; FUNCTION: [Truncated CTR1 form]: Mobilizes copper(1+) out of the endosomal compartment, making copper(1+) available for export out of the cells. {ECO:0000250|UniProtKB:Q8K211}.
|
Homo sapiens (Human)
|
O15432
|
COPT2_HUMAN
|
MAMHFIFSDTAVLLFDFWSVHSPAGMALSVLVLLLLAVLYEGIKVGKAKLLNQVLVNLPTSISQQTIAETDGDSAGSDSFPVGRTHHRWYLCHFGQSLIHVIQVVIGYFIMLAVMSYNTWIFLGVVLGSAVGYYLAYPLLSTA
| null | null |
copper ion import [GO:0015677]; copper ion transport [GO:0006825]; intracellular copper ion homeostasis [GO:0006878]; regulation of copper ion transmembrane transport [GO:1902311]
|
late endosome membrane [GO:0031902]; lysosomal membrane [GO:0005765]; plasma membrane [GO:0005886]; recycling endosome [GO:0055037]
|
copper ion transmembrane transporter activity [GO:0005375]
|
PF04145;
| null |
Copper transporter (Ctr) (TC 1.A.56) family, SLC31A subfamily
|
PTM: Ubiquitinated; ubiquitination and the subsequent proteasomal degradation are prevent by SLC31A1 that stabilizes it. {ECO:0000269|PubMed:26205368}.
|
SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:17944601}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:17944601}; Multi-pass membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:17617060}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:17617060}; Multi-pass membrane protein {ECO:0000255}. Note=Plasma membrane localization is partial. {ECO:0000269|PubMed:17944601}.
| null |
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=11 uM for copper (in COS-7 cells transfected with human SLC31A1) {ECO:0000269|PubMed:17944601}; Vmax=10.2 pmol/min/mg protein for copper (in COS-7 cells transfected with human SLC31A1) {ECO:0000269|PubMed:17944601};
| null | null | null |
FUNCTION: Does not function as a copper(1+) importer in vivo (By similarity). However, in vitro functions as a low-affinity copper(1+) importer (PubMed:17617060, PubMed:17944601). Regulator of SLC31A1 which facilitates the cleavage of the SLC31A1 ecto-domain or which stabilizes the truncated form of SLC31A1 (Truncated CTR1 form), thereby drives the SLC31A1 truncated form-dependent endosomal copper export and modulates the copper and cisplatin accumulation via SLC31A1 (By similarity). {ECO:0000250|UniProtKB:Q9CPU9, ECO:0000269|PubMed:17617060, ECO:0000269|PubMed:17944601}.
|
Homo sapiens (Human)
|
O15438
|
MRP3_HUMAN
|
MDALCGSGELGSKFWDSNLSVHTENPDLTPCFQNSLLAWVPCIYLWVALPCYLLYLRHHCRGYIILSHLSKLKMVLGVLLWCVSWADLFYSFHGLVHGRAPAPVFFVTPLVVGVTMLLATLLIQYERLQGVQSSGVLIIFWFLCVVCAIVPFRSKILLAKAEGEISDPFRFTTFYIHFALVLSALILACFREKPPFFSAKNVDPNPYPETSAGFLSRLFFWWFTKMAIYGYRHPLEEKDLWSLKEEDRSQMVVQQLLEAWRKQEKQTARHKASAAPGKNASGEDEVLLGARPRPRKPSFLKALLATFGSSFLISACFKLIQDLLSFINPQLLSILIRFISNPMAPSWWGFLVAGLMFLCSMMQSLILQHYYHYIFVTGVKFRTGIMGVIYRKALVITNSVKRASTVGEIVNLMSVDAQRFMDLAPFLNLLWSAPLQIILAIYFLWQNLGPSVLAGVAFMVLLIPLNGAVAVKMRAFQVKQMKLKDSRIKLMSEILNGIKVLKLYAWEPSFLKQVEGIRQGELQLLRTAAYLHTTTTFTWMCSPFLVTLITLWVYVYVDPNNVLDAEKAFVSVSLFNILRLPLNMLPQLISNLTQASVSLKRIQQFLSQEELDPQSVERKTISPGYAITIHSGTFTWAQDLPPTLHSLDIQVPKGALVAVVGPVGCGKSSLVSALLGEMEKLEGKVHMKGSVAYVPQQAWIQNCTLQENVLFGKALNPKRYQQTLEACALLADLEMLPGGDQTEIGEKGINLSGGQRQRVSLARAVYSDADIFLLDDPLSAVDSHVAKHIFDHVIGPEGVLAGKTRVLVTHGISFLPQTDFIIVLADGQVSEMGPYPALLQRNGSFANFLCNYAPDEDQGHLEDSWTALEGAEDKEALLIEDTLSNHTDLTDNDPVTYVVQKQFMRQLSALSSDGEGQGRPVPRRHLGPSEKVQVTEAKADGALTQEEKAAIGTVELSVFWDYAKAVGLCTTLAICLLYVGQSAAAIGANVWLSAWTNDAMADSRQNNTSLRLGVYAALGILQGFLVMLAAMAMAAGGIQAARVLHQALLHNKIRSPQSFFDTTPSGRILNCFSKDIYVVDEVLAPVILMLLNSFFNAISTLVVIMASTPLFTVVILPLAVLYTLVQRFYAATSRQLKRLESVSRSPIYSHFSETVTGASVIRAYNRSRDFEIISDTKVDANQRSCYPYIISNRWLSIGVEFVGNCVVLFAALFAVIGRSSLNPGLVGLSVSYSLQVTFALNWMIRMMSDLESNIVAVERVKEYSKTETEAPWVVEGSRPPEGWPPRGEVEFRNYSVRYRPGLDLVLRDLSLHVHGGEKVGIVGRTGAGKSSMTLCLFRILEAAKGEIRIDGLNVADIGLHDLRSQLTIIPQDPILFSGTLRMNLDPFGSYSEEDIWWALELSHLHTFVSSQPAGLDFQCSEGGENLSVGQRQLVCLARALLRKSRILVLDEATAAIDLETDNLIQATIRTQFDTCTVLTIAHRLNTIMDYTRVLVLDKGVVAEFDSPANLIAARGIFYGMARDAGLA
|
7.6.2.-; 7.6.2.2; 7.6.2.3
| null |
bile acid and bile salt transport [GO:0015721]; leukotriene transport [GO:0071716]; transmembrane transport [GO:0055085]; transport across blood-brain barrier [GO:0150104]; xenobiotic metabolic process [GO:0006805]; xenobiotic transmembrane transport [GO:0006855]; xenobiotic transport [GO:0042908]
|
basal plasma membrane [GO:0009925]; basolateral plasma membrane [GO:0016323]; membrane [GO:0016020]; plasma membrane [GO:0005886]
|
ABC-type bile acid transporter activity [GO:0015432]; ABC-type glutathione S-conjugate transporter activity [GO:0015431]; ABC-type transporter activity [GO:0140359]; ABC-type xenobiotic transporter activity [GO:0008559]; ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATPase-coupled inorganic anion transmembrane transporter activity [GO:0043225]; ATPase-coupled transmembrane transporter activity [GO:0042626]; glucuronoside transmembrane transporter activity [GO:0015164]; icosanoid transmembrane transporter activity [GO:0071714]; xenobiotic transmembrane transporter activity [GO:0042910]
|
PF00664;PF00005;
|
1.20.1560.10;3.40.50.300;
|
ABC transporter superfamily, ABCC family, Conjugate transporter (TC 3.A.1.208) subfamily
| null |
SUBCELLULAR LOCATION: Basolateral cell membrane {ECO:0000269|PubMed:10094960, ECO:0000269|PubMed:10359813, ECO:0000269|PubMed:15083066, ECO:0000269|PubMed:28408210}; Multi-pass membrane protein {ECO:0000255}. Basal cell membrane {ECO:0000269|PubMed:35307651}; Multi-pass membrane protein {ECO:0000255}. Note=Localized to the basolateral membrane of enterocytes (PubMed:28408210). Localized to the basal membrane of Sertoli cells (PubMed:35307651). {ECO:0000269|PubMed:28408210, ECO:0000269|PubMed:35307651}.
|
CATALYTIC ACTIVITY: Reaction=ATP + H2O + taurocholate(in) = ADP + H(+) + phosphate + taurocholate(out); Xref=Rhea:RHEA:50052, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:36257, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O88563}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50053; Evidence={ECO:0000250|UniProtKB:O88563}; CATALYTIC ACTIVITY: Reaction=ATP + glycocholate(in) + H2O = ADP + glycocholate(out) + H(+) + phosphate; Xref=Rhea:RHEA:50056, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29746, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O88563}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50057; Evidence={ECO:0000250|UniProtKB:O88563}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + taurolithocholate 3-sulfate(in) = ADP + H(+) + phosphate + taurolithocholate 3-sulfate(out); Xref=Rhea:RHEA:50084, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58301, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O88563}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + taurochenodeoxycholate 3-sulfate(in) = ADP + H(+) + phosphate + taurochenodeoxycholate 3-sulfate(out); Xref=Rhea:RHEA:66176, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:166912, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:O88563}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66177; Evidence={ECO:0000250|UniProtKB:O88563}; CATALYTIC ACTIVITY: Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-substituted glutathione(out) + H(+) + phosphate; Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779, ChEBI:CHEBI:456216; EC=7.6.2.3; Evidence={ECO:0000269|PubMed:11581266, ECO:0000269|PubMed:15083066, ECO:0000269|PubMed:9827529}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122; Evidence={ECO:0000305|PubMed:11581266, ECO:0000305|PubMed:15083066}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:10359813, ECO:0000269|PubMed:11581266, ECO:0000269|PubMed:9827529}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:60128, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:82961, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:11581266, ECO:0000269|PubMed:15083066}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129; Evidence={ECO:0000305|PubMed:15083066}; CATALYTIC ACTIVITY: Reaction=ATP + dehydroepiandrosterone 3-sulfate(in) + H2O = ADP + dehydroepiandrosterone 3-sulfate(out) + H(+) + phosphate; Xref=Rhea:RHEA:61364, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57905, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15083066}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61365; Evidence={ECO:0000305|PubMed:15083066}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57973, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:11581266, ECO:0000269|PubMed:15083066}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964; Evidence={ECO:0000305|PubMed:15083066}; CATALYTIC ACTIVITY: Reaction=(4Z,15Z)-bilirubin IXalpha C8-beta-D-glucuronoside(in) + ATP + H2O = (4Z,15Z)-bilirubin IXalpha C8-beta-D-glucuronoside(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66180, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:229704, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15083066}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66181; Evidence={ECO:0000305|PubMed:15083066}; CATALYTIC ACTIVITY: Reaction=(4Z,15Z)-bilirubin IXalpha C8,C12-beta-D-bisglucuronoside(in) + ATP + H2O = (4Z,15Z)-bilirubin IXalpha C8,C12-beta-D-bisglucuronoside(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66192, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:229706, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15083066}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66193; Evidence={ECO:0000305|PubMed:15083066};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=17.7 uM for oestradiol-17-(beta-D-glucuronide) {ECO:0000269|PubMed:11581266}; KM=24.2 uM for oestradiol-17-(beta-D-glucuronide) {ECO:0000269|PubMed:15083066}; KM=46.3 uM for dehydroepiandrosterone- 3-sulfate {ECO:0000269|PubMed:15083066}; Vmax=281 pmol/min/mg enzyme for dehydroepiandrosterone- 3-sulfate transport {ECO:0000269|PubMed:15083066}; Vmax=474 pmol/min/mg enzyme for oestradiol-17-(beta-D-glucuronide) transport {ECO:0000269|PubMed:11581266}; Vmax=71.5 pmol/min/mg enzyme for oestradiol-17-(beta-D-glucuronide) transport {ECO:0000269|PubMed:15083066};
| null | null | null |
FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266). {ECO:0000250|UniProtKB:O88563, ECO:0000269|PubMed:10359813, ECO:0000269|PubMed:11581266, ECO:0000269|PubMed:15083066, ECO:0000305|PubMed:35307651}.
|
Homo sapiens (Human)
|
O15439
|
MRP4_HUMAN
|
MLPVYQEVKPNPLQDANLCSRVFFWWLNPLFKIGHKRRLEEDDMYSVLPEDRSQHLGEELQGFWDKEVLRAENDAQKPSLTRAIIKCYWKSYLVLGIFTLIEESAKVIQPIFLGKIINYFENYDPMDSVALNTAYAYATVLTFCTLILAILHHLYFYHVQCAGMRLRVAMCHMIYRKALRLSNMAMGKTTTGQIVNLLSNDVNKFDQVTVFLHFLWAGPLQAIAVTALLWMEIGISCLAGMAVLIILLPLQSCFGKLFSSLRSKTATFTDARIRTMNEVITGIRIIKMYAWEKSFSNLITNLRKKEISKILRSSCLRGMNLASFFSASKIIVFVTFTTYVLLGSVITASRVFVAVTLYGAVRLTVTLFFPSAIERVSEAIVSIRRIQTFLLLDEISQRNRQLPSDGKKMVHVQDFTAFWDKASETPTLQGLSFTVRPGELLAVVGPVGAGKSSLLSAVLGELAPSHGLVSVHGRIAYVSQQPWVFSGTLRSNILFGKKYEKERYEKVIKACALKKDLQLLEDGDLTVIGDRGTTLSGGQKARVNLARAVYQDADIYLLDDPLSAVDAEVSRHLFELCICQILHEKITILVTHQLQYLKAASQILILKDGKMVQKGTYTEFLKSGIDFGSLLKKDNEESEQPPVPGTPTLRNRTFSESSVWSQQSSRPSLKDGALESQDTENVPVTLSEENRSEGKVGFQAYKNYFRAGAHWIVFIFLILLNTAAQVAYVLQDWWLSYWANKQSMLNVTVNGGGNVTEKLDLNWYLGIYSGLTVATVLFGIARSLLVFYVLVNSSQTLHNKMFESILKAPVLFFDRNPIGRILNRFSKDIGHLDDLLPLTFLDFIQTLLQVVGVVSVAVAVIPWIAIPLVPLGIIFIFLRRYFLETSRDVKRLESTTRSPVFSHLSSSLQGLWTIRAYKAEERCQELFDAHQDLHSEAWFLFLTTSRWFAVRLDAICAMFVIIVAFGSLILAKTLDAGQVGLALSYALTLMGMFQWCVRQSAEVENMMISVERVIEYTDLEKEAPWEYQKRPPPAWPHEGVIIFDNVNFMYSPGGPLVLKHLTALIKSQEKVGIVGRTGAGKSSLISALFRLSEPEGKIWIDKILTTEIGLHDLRKKMSIIPQEPVLFTGTMRKNLDPFNEHTDEELWNALQEVQLKETIEDLPGKMDTELAESGSNFSVGQRQLVCLARAILRKNQILIIDEATANVDPRTDELIQKKIREKFAHCTVLTIAHRLNTIIDSDKIMVLDSGRLKEYDEPYVLLQNKESLFYKMVQQLGKAEAAALTETAKQVYFKRNYPHIGHTDHMVTNTSNGQPSTLTIFETAL
|
7.6.2.-; 7.6.2.2; 7.6.2.3
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:15364914};
|
bile acid and bile salt transport [GO:0015721]; cAMP transport [GO:0070730]; cilium assembly [GO:0060271]; export across plasma membrane [GO:0140115]; leukotriene transport [GO:0071716]; platelet degranulation [GO:0002576]; prostaglandin secretion [GO:0032310]; prostaglandin transport [GO:0015732]; transmembrane transport [GO:0055085]; transport across blood-brain barrier [GO:0150104]; urate transport [GO:0015747]; xenobiotic metabolic process [GO:0006805]; xenobiotic transmembrane transport [GO:0006855]
|
apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; external side of apical plasma membrane [GO:0098591]; Golgi apparatus [GO:0005794]; membrane [GO:0016020]; nucleolus [GO:0005730]; plasma membrane [GO:0005886]; platelet dense granule membrane [GO:0031088]
|
15-hydroxyprostaglandin dehydrogenase (NAD+) activity [GO:0016404]; ABC-type bile acid transporter activity [GO:0015432]; ABC-type glutathione S-conjugate transporter activity [GO:0015431]; ABC-type transporter activity [GO:0140359]; ABC-type xenobiotic transporter activity [GO:0008559]; ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATPase-coupled inorganic anion transmembrane transporter activity [GO:0043225]; ATPase-coupled transmembrane transporter activity [GO:0042626]; efflux transmembrane transporter activity [GO:0015562]; glutathione transmembrane transporter activity [GO:0034634]; guanine nucleotide transmembrane transporter activity [GO:0001409]; prostaglandin transmembrane transporter activity [GO:0015132]; purine nucleotide transmembrane transporter activity [GO:0015216]; urate transmembrane transporter activity [GO:0015143]; xenobiotic transmembrane transporter activity [GO:0042910]
|
PF00664;PF00005;
|
1.20.1560.10;3.40.50.300;
|
ABC transporter superfamily, ABCC family, Conjugate transporter (TC 3.A.1.208) subfamily
|
PTM: N-glycosylated; leading to substrate-selective effects on its transport activity. {ECO:0000269|PubMed:26721430}.
|
SUBCELLULAR LOCATION: Basolateral cell membrane {ECO:0000269|PubMed:11106685, ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:26721430}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:26721430}; Multi-pass membrane protein {ECO:0000255}. Note=Its localization to the basolateral or apical membranes is tissue-dependent. {ECO:0000305|PubMed:26721430}.
|
CATALYTIC ACTIVITY: Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:12105214, ECO:0000269|PubMed:15454390, ECO:0000269|PubMed:17344354, ECO:0000269|PubMed:18300232}; CATALYTIC ACTIVITY: Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-substituted glutathione(out) + H(+) + phosphate; Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779, ChEBI:CHEBI:456216; EC=7.6.2.3; Evidence={ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:17959747, ECO:0000269|PubMed:26721430}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122; Evidence={ECO:0000305|PubMed:17959747}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:60128, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:82961, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:26721430}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129; Evidence={ECO:0000305|PubMed:11856762, ECO:0000305|PubMed:26721430}; CATALYTIC ACTIVITY: Reaction=ATP + dehydroepiandrosterone 3-sulfate(in) + H2O = ADP + dehydroepiandrosterone 3-sulfate(out) + H(+) + phosphate; Xref=Rhea:RHEA:61364, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57905, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:12523936}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61365; Evidence={ECO:0000305|PubMed:12523936}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57973, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:17959747}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964; Evidence={ECO:0000305|PubMed:17959747}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + leukotriene B4(in) = ADP + H(+) + leukotriene B4(out) + phosphate; Xref=Rhea:RHEA:66424, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57461, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:17959747}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + urate(in) = ADP + H(+) + phosphate + urate(out); Xref=Rhea:RHEA:16461, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17775, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15454390}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16462; Evidence={ECO:0000305|PubMed:15454390}; CATALYTIC ACTIVITY: Reaction=3',5'-cyclic GMP(in) + ATP + H2O = 3',5'-cyclic GMP(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66188, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57746, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:15454390}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66189; Evidence={ECO:0000305|PubMed:15454390}; CATALYTIC ACTIVITY: Reaction=3',5'-cyclic AMP(in) + ATP + H2O = 3',5'-cyclic AMP(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66184, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58165, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:11856762}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66185; Evidence={ECO:0000305|PubMed:11856762}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + prostaglandin E2(in) = ADP + H(+) + phosphate + prostaglandin E2(out); Xref=Rhea:RHEA:66388, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216, ChEBI:CHEBI:606564; Evidence={ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:15364914, ECO:0000269|PubMed:26721430}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66389; Evidence={ECO:0000305|PubMed:15364914, ECO:0000305|PubMed:26721430}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + prostaglandin E1(in) = ADP + H(+) + phosphate + prostaglandin E1(out); Xref=Rhea:RHEA:66392, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57397, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:15364914}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66393; Evidence={ECO:0000305|PubMed:15364914}; CATALYTIC ACTIVITY: Reaction=ATP + glutathione(in) + glycodeoxycholate(in) + H2O = ADP + glutathione(out) + glycodeoxycholate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66380, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:82982, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66381; Evidence={ECO:0000305|PubMed:16282361}; CATALYTIC ACTIVITY: Reaction=ATP + cholate(in) + glutathione(in) + H2O = ADP + cholate(out) + glutathione(out) + H(+) + phosphate; Xref=Rhea:RHEA:66396, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66397; Evidence={ECO:0000305|PubMed:16282361}; CATALYTIC ACTIVITY: Reaction=ATP + glutathione(in) + glycocholate(in) + H2O = ADP + glutathione(out) + glycocholate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66400, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29746, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66401; Evidence={ECO:0000305|PubMed:16282361}; CATALYTIC ACTIVITY: Reaction=ATP + glutathione(in) + H2O + taurocholate(in) = ADP + glutathione(out) + H(+) + phosphate + taurocholate(out); Xref=Rhea:RHEA:66404, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:36257, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66405; Evidence={ECO:0000305|PubMed:16282361}; CATALYTIC ACTIVITY: Reaction=ATP + glutathione(in) + glycochenodeoxycholate(in) + H2O = ADP + glutathione(out) + glycochenodeoxycholate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:36252, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66409; Evidence={ECO:0000305|PubMed:16282361}; CATALYTIC ACTIVITY: Reaction=ATP + glutathione(in) + H2O + taurochenodeoxycholate(in) = ADP + glutathione(out) + H(+) + phosphate + taurochenodeoxycholate(out); Xref=Rhea:RHEA:66412, ChEBI:CHEBI:9407, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66413; Evidence={ECO:0000305|PubMed:16282361}; CATALYTIC ACTIVITY: Reaction=ATP + glutathione(in) + glycoursodeoxycholate(in) + H2O = ADP + glutathione(out) + glycoursodeoxycholate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66416, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:132030, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66417; Evidence={ECO:0000305|PubMed:16282361}; CATALYTIC ACTIVITY: Reaction=ATP + glutathione(in) + H2O + tauroursodeoxycholate(in) = ADP + glutathione(out) + H(+) + phosphate + tauroursodeoxycholate(out); Xref=Rhea:RHEA:66420, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57925, ChEBI:CHEBI:132028, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16282361}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66421; Evidence={ECO:0000305|PubMed:16282361};
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BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.1 uM for prostaglandin E1 {ECO:0000269|PubMed:12835412}; KM=3.4 uM for prostaglandin E2 {ECO:0000269|PubMed:12835412}; KM=25.8 uM for cholylglycine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=7.7 uM for cholyltaurine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=6.7 uM for deoxycholylglycine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=5.9 uM for chenodeoxycholylglycine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=3.6 uM for chenodeoxycholyltaurine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=12.5 uM for ursodeoxycholylglycine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=7.8 uM for ursodeoxycholyltaurine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=14.8 uM for cholate (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; KM=1500 uM for urate {ECO:0000269|PubMed:15454390}; KM=180 uM for cGMP {ECO:0000269|PubMed:15454390}; KM=0.62 uM for ATP {ECO:0000269|PubMed:15364914}; KM=0.13 uM for LTC4 {ECO:0000269|PubMed:17959747}; KM=1.3 uM for methotrexate {ECO:0000269|PubMed:11856762}; KM=5.2 uM for LTB4 (in the presence of 5 mM GSH) {ECO:0000269|PubMed:17959747}; KM=2 uM for 3beta-sulfooxy-androst-5-en-17-one {ECO:0000269|PubMed:12523936}; Vmax=430 pmol/min/mg enzyme for methotrexate transport {ECO:0000269|PubMed:11856762}; Vmax=47 pmol/min/mg enzyme for urate transport {ECO:0000269|PubMed:15454390}; Vmax=75 pmol/min/mg enzyme for cholate transport (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; Vmax=175 pmol/min/mg enzyme for cholylglycine transport (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; Vmax=154 pmol/min/mg enzyme for cholyltaurine transport (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; Vmax=93 pmol/min/mg enzyme for chenodeoxycholylglycine transport (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; Vmax=83 pmol/min/mg enzyme for chenodeoxycholyltaurine transport (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; Vmax=130 pmol/min/mg enzyme for ursodeoxycholylglycine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; Vmax=133 pmol/min/mg enzyme for ursodeoxycholyltaurine (in the presence of 5 mM GSH) {ECO:0000269|PubMed:16282361}; Vmax=45 pmol/min/mg enzyme for 3beta-sulfooxy-androst-5-en-17-one transport {ECO:0000269|PubMed:12523936};
| null | null | null |
FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685). {ECO:0000269|PubMed:11106685, ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:12105214, ECO:0000269|PubMed:12523936, ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:15364914, ECO:0000269|PubMed:15454390, ECO:0000269|PubMed:16282361, ECO:0000269|PubMed:17344354, ECO:0000269|PubMed:17959747, ECO:0000269|PubMed:18300232, ECO:0000269|PubMed:26721430}.
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Homo sapiens (Human)
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O15440
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MRP5_HUMAN
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MKDIDIGKEYIIPSPGYRSVRERTSTSGTHRDREDSKFRRTRPLECQDALETAARAEGLSLDASMHSQLRILDEEHPKGKYHHGLSALKPIRTTSKHQHPVDNAGLFSCMTFSWLSSLARVAHKKGELSMEDVWSLSKHESSDVNCRRLERLWQEELNEVGPDAASLRRVVWIFCRTRLILSIVCLMITQLAGFSGPAFMVKHLLEYTQATESNLQYSLLLVLGLLLTEIVRSWSLALTWALNYRTGVRLRGAILTMAFKKILKLKNIKEKSLGELINICSNDGQRMFEAAAVGSLLAGGPVVAILGMIYNVIILGPTGFLGSAVFILFYPAMMFASRLTAYFRRKCVAATDERVQKMNEVLTYIKFIKMYAWVKAFSQSVQKIREEERRILEKAGYFQSITVGVAPIVVVIASVVTFSVHMTLGFDLTAAQAFTVVTVFNSMTFALKVTPFSVKSLSEASVAVDRFKSLFLMEEVHMIKNKPASPHIKIEMKNATLAWDSSHSSIQNSPKLTPKMKKDKRASRGKKEKVRQLQRTEHQAVLAEQKGHLLLDSDERPSPEEEEGKHIHLGHLRLQRTLHSIDLEIQEGKLVGICGSVGSGKTSLISAILGQMTLLEGSIAISGTFAYVAQQAWILNATLRDNILFGKEYDEERYNSVLNSCCLRPDLAILPSSDLTEIGERGANLSGGQRQRISLARALYSDRSIYILDDPLSALDAHVGNHIFNSAIRKHLKSKTVLFVTHQLQYLVDCDEVIFMKEGCITERGTHEELMNLNGDYATIFNNLLLGETPPVEINSKKETSGSQKKSQDKGPKTGSVKKEKAVKPEEGQLVQLEEKGQGSVPWSVYGVYIQAAGGPLAFLVIMALFMLNVGSTAFSTWWLSYWIKQGSGNTTVTRGNETSVSDSMKDNPHMQYYASIYALSMAVMLILKAIRGVVFVKGTLRASSRLHDELFRRILRSPMKFFDTTPTGRILNRFSKDMDEVDVRLPFQAEMFIQNVILVFFCVGMIAGVFPWFLVAVGPLVILFSVLHIVSRVLIRELKRLDNITQSPFLSHITSSIQGLATIHAYNKGQEFLHRYQELLDDNQAPFFLFTCAMRWLAVRLDLISIALITTTGLMIVLMHGQIPPAYAGLAISYAVQLTGLFQFTVRLASETEARFTSVERINHYIKTLSLEAPARIKNKAPSPDWPQEGEVTFENAEMRYRENLPLVLKKVSFTIKPKEKIGIVGRTGSGKSSLGMALFRLVELSGGCIKIDGVRISDIGLADLRSKLSIIPQEPVLFSGTVRSNLDPFNQYTEDQIWDALERTHMKECIAQLPLKLESEVMENGDNFSVGERQLLCIARALLRHCKILILDEATAAMDTETDLLIQETIREAFADCTMLTIAHRLHTVLGSDRIMVLAQGQVVEFDTPSVLLSNDSSRFYAMFAAAENKVAVKG
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7.6.2.-; 7.6.2.2
| null |
cAMP transport [GO:0070730]; cGMP transport [GO:0070731]; export across plasma membrane [GO:0140115]; folate transmembrane transport [GO:0098838]; glutathione transmembrane transport [GO:0034775]; heme transmembrane transport [GO:0035351]; hyaluronan biosynthetic process [GO:0030213]; purine nucleotide transport [GO:0015865]; transmembrane transport [GO:0055085]; transport across blood-brain barrier [GO:0150104]; xenobiotic metabolic process [GO:0006805]; xenobiotic transmembrane transport [GO:0006855]; xenobiotic transport [GO:0042908]
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apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; endosome membrane [GO:0010008]; Golgi lumen [GO:0005796]; membrane [GO:0016020]; plasma membrane [GO:0005886]
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ABC-type xenobiotic transporter activity [GO:0008559]; ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATPase-coupled inorganic anion transmembrane transporter activity [GO:0043225]; ATPase-coupled transmembrane transporter activity [GO:0042626]; carbohydrate derivative transmembrane transporter activity [GO:1901505]; efflux transmembrane transporter activity [GO:0015562]; glutathione transmembrane transporter activity [GO:0034634]; heme transmembrane transporter activity [GO:0015232]; macromolecule transmembrane transporter activity [GO:0022884]; organic anion transmembrane transporter activity [GO:0008514]; purine nucleotide transmembrane transporter activity [GO:0015216]; xenobiotic transmembrane transporter activity [GO:0042910]
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PF00664;PF00005;
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1.20.1560.10;3.40.50.300;
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ABC transporter superfamily, ABCC family, Conjugate transporter (TC 3.A.1.208) subfamily
| null |
SUBCELLULAR LOCATION: Basolateral cell membrane {ECO:0000269|PubMed:24836561}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus lumen {ECO:0000269|PubMed:24836561}. Endosome membrane {ECO:0000269|PubMed:24836561}. Cytoplasmic granule {ECO:0000250|UniProtKB:Q9R1X5}. Apical cell membrane {ECO:0000269|PubMed:15501592}; Multi-pass membrane protein {ECO:0000255}. Note=In most cells, routes to the basolateral plasma membrane, but in the brain capillary endothelial cells that form the blood-brain barrier, resides in the apical membrane. {ECO:0000269|PubMed:15501592, ECO:0000269|PubMed:24836561}.
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CATALYTIC ACTIVITY: Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:10840050, ECO:0000269|PubMed:12435799, ECO:0000269|PubMed:12695538, ECO:0000269|PubMed:15899835}; CATALYTIC ACTIVITY: Reaction=3',5'-cyclic GMP(in) + ATP + H2O = 3',5'-cyclic GMP(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66188, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57746, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:10893247, ECO:0000269|PubMed:12637526, ECO:0000269|PubMed:12695538}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66189; Evidence={ECO:0000305|PubMed:10893247}; CATALYTIC ACTIVITY: Reaction=3',5'-cyclic AMP(in) + ATP + H2O = 3',5'-cyclic AMP(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66184, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58165, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:10893247, ECO:0000269|PubMed:12637526, ECO:0000269|PubMed:12695538}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66185; Evidence={ECO:0000305|PubMed:10893247}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + N-acetyl-L-aspartyl-L-glutamate(in) = ADP + H(+) + N-acetyl-L-aspartyl-L-glutamate(out) + phosphate; Xref=Rhea:RHEA:66728, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:76931, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66729; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + N-acetyl-L-aspartyl-L-glutamyl-L-glutamate(in) = ADP + H(+) + N-acetyl-L-aspartyl-L-glutamyl-L-glutamate(out) + phosphate; Xref=Rhea:RHEA:66732, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:76935, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66733; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + N-acetyl-L-glutamate(in) = ADP + H(+) + N-acetyl-L-glutamate(out) + phosphate; Xref=Rhea:RHEA:66740, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:44337, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66741; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + N-acetyl-L-aspartate(in) = ADP + H(+) + N-acetyl-L-aspartate(out) + phosphate; Xref=Rhea:RHEA:66744, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16953, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66745; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=(2S)-2-[5-amino-1-(beta-D-ribosyl)imidazole-4-carboxamido]succinate(in) + ATP + H2O = (2S)-2-[5-amino-1-(beta-D-ribosyl)imidazole-4-carboxamido]succinate(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:66752, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167466, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66753; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=ATP + domoate(in) + H2O = ADP + domoate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66756, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167470, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66757; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=ATP + beta-citrylglutamate(in) + H2O = ADP + beta-citrylglutamate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66736, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:76942, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66737; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + kainate(in) = ADP + H(+) + kainate(out) + phosphate; Xref=Rhea:RHEA:66760, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:156548, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66761; Evidence={ECO:0000305|PubMed:26515061}; CATALYTIC ACTIVITY: Reaction=ATP + H2O + N-[(S)-lactoyl]-L-phenylalanine(in) = ADP + H(+) + N-[(S)-lactoyl]-L-phenylalanine(out) + phosphate; Xref=Rhea:RHEA:66720, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167456, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:25964343}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66721; Evidence={ECO:0000305|PubMed:25964343}; CATALYTIC ACTIVITY: Reaction=ATP + folate(in) + H2O = ADP + folate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66764, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:62501, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15899835}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66765; Evidence={ECO:0000305|PubMed:15899835};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=379 uM for cAMP {ECO:0000269|PubMed:10893247}; KM=2.1 uM for cGMP {ECO:0000269|PubMed:10893247}; KM=132 uM for cGMP {ECO:0000269|PubMed:17229149}; KM=1 mM for folate {ECO:0000269|PubMed:15899835}; KM=1 mM for N-[(S)-lactoyl]-L-phenylalanine {ECO:0000269|PubMed:25964343}; KM=1.9 mM for ZJ43 (glutamate analog) {ECO:0000269|PubMed:26515061}; KM=3.5 mM for N-acetylaspartylglutamate (NAAG) {ECO:0000269|PubMed:26515061}; KM=1.3 mM for methotrexate {ECO:0000269|PubMed:15899835}; Vmax=780 pmol/min/mg enzyme for methotrexate transport {ECO:0000269|PubMed:15899835}; Vmax=875 pmol/min/mg enzyme for folate transport {ECO:0000269|PubMed:15899835};
| null | null | null |
FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) (PubMed:10893247, PubMed:12637526, PubMed:12695538, PubMed:15899835, PubMed:17229149, PubMed:25964343). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins (PubMed:26515061). Confers resistance to the antiviral agent PMEA (PubMed:12695538). Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated (PubMed:10840050, PubMed:12435799, PubMed:12695538, PubMed:15899835). Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway (PubMed:24836561). May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity). {ECO:0000250|UniProtKB:Q9R1X5, ECO:0000269|PubMed:10840050, ECO:0000269|PubMed:10893247, ECO:0000269|PubMed:12435799, ECO:0000269|PubMed:12637526, ECO:0000269|PubMed:12695538, ECO:0000269|PubMed:15899835, ECO:0000269|PubMed:17229149, ECO:0000269|PubMed:24836561, ECO:0000269|PubMed:25964343, ECO:0000269|PubMed:26515061}.
|
Homo sapiens (Human)
|
O15444
|
CCL25_HUMAN
|
MNLWLLACLVAGFLGAWAPAVHTQGVFEDCCLAYHYPIGWAVLRRAWTYRIQEVSGSCNLPAAIFYLPKRHRKVCGNPKSREVQRAMKLLDARNKVFAKLHHNTQTFQAGPHAVKKLSSGNSKLSSSKFSNPISSSKRNVSLLISANSGL
| null | null |
cell chemotaxis [GO:0060326]; cell surface receptor signaling pathway [GO:0007166]; 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]; immune response [GO:0006955]; inflammatory response [GO:0006954]; lymphocyte chemotaxis [GO:0048247]; monocyte chemotaxis [GO:0002548]; negative regulation of leukocyte tethering or rolling [GO:1903237]; neutrophil chemotaxis [GO:0030593]; positive regulation of cell-matrix adhesion [GO:0001954]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]
|
extracellular region [GO:0005576]; extracellular space [GO:0005615]
|
CCR chemokine receptor binding [GO:0048020]; CCR10 chemokine receptor binding [GO:0031735]; chemokine activity [GO:0008009]; chemokine receptor binding [GO:0042379]; hormone activity [GO:0005179]
|
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. Isoform 2 is an antagonist of isoform 1. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.
|
Homo sapiens (Human)
|
O15446
|
RPA34_HUMAN
|
MEEPQAGDAARFSCPPNFTAKPPASESPRFSLEALTGPDTELWLIQAPADFAPECFNGRHVPLSGSQIVKGKLAGKRHRYRVLSSCPQAGEATLLAPSTEAGGGLTCASAPQGTLRILEGPQQSLSGSPLQPIPASPPPQIPPGLRPRFCAFGGNPPVTGPRSALAPNLLTSGKKKKEMQVTEAPVTQEAVNGHGALEVDMALGSPEMDVRKKKKKKNQQLKEPEAAGPVGTEPTVETLEPLGVLFPSTTKKRKKPKGKETFEPEDKTVKQEQINTEPLEDTVLSPTKKRKRQKGTEGMEPEEGVTVESQPQVKVEPLEEAIPLPPTKKRKKEKGQMAMMEPGTEAMEPVEPEMKPLESPGGTMAPQQPEGAKPQAQAALAAPKKKTKKEKQQDATVEPETEVVGPELPDDLEPQAAPTSTKKKKKKKERGHTVTEPIQPLEPELPGEGQPEARATPGSTKKRKKQSQESRMPETVPQEEMPGPPLNSESGEEAPTGRDKKRKQQQQQPV
| null | null |
rRNA transcription [GO:0009303]; transcription initiation at RNA polymerase I promoter [GO:0006361]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]
|
chromosome [GO:0005694]; cytosol [GO:0005829]; fibrillar center [GO:0001650]; mitochondrion [GO:0005739]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; RNA polymerase I complex [GO:0005736]; RNA polymerase I transcription regulator complex [GO:0000120]
|
RNA binding [GO:0003723]
|
PF08208;
|
6.20.250.70;
|
Eukaryotic RPA34 RNA polymerase subunit family
|
PTM: [Isoform 2]: Undergoes tyrosine phosphorylation upon T-cell receptor (TCR) stimulation. This phosphorylation has not been confirmed by other groups. {ECO:0000269|PubMed:10373416}.; PTM: [Isoform 1]: Phosphorylated on tyrosine residues in initiation-competent Pol I-beta complexes but not in Pol I-alpha complexes. {ECO:0000269|PubMed:16809778}.
|
SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:9426281}. Chromosome {ECO:0000269|PubMed:9426281}. Note=Found at the fibrillar centers of the nucleolus in interphase and during cell division it is localized to the nucleolus organizer regions of the chromosomes.
| null | null | null | null | null |
FUNCTION: Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Involved in UBTF-activated transcription, presumably at a step following PIC formation. {ECO:0000269|PubMed:34671025, ECO:0000269|PubMed:34887565, ECO:0000269|PubMed:36271492}.; FUNCTION: [Isoform 2]: Has been described as a component of preformed T-cell receptor (TCR) complex. {ECO:0000269|PubMed:10373416}.
|
Homo sapiens (Human)
|
O15455
|
TLR3_HUMAN
|
MRQTLPCIYFWGGLLPFGMLCASSTTKCTVSHEVADCSHLKLTQVPDDLPTNITVLNLTHNQLRRLPAANFTRYSQLTSLDVGFNTISKLEPELCQKLPMLKVLNLQHNELSQLSDKTFAFCTNLTELHLMSNSIQKIKNNPFVKQKNLITLDLSHNGLSSTKLGTQVQLENLQELLLSNNKIQALKSEELDIFANSSLKKLELSSNQIKEFSPGCFHAIGRLFGLFLNNVQLGPSLTEKLCLELANTSIRNLSLSNSQLSTTSNTTFLGLKWTNLTMLDLSYNNLNVVGNDSFAWLPQLEYFFLEYNNIQHLFSHSLHGLFNVRYLNLKRSFTKQSISLASLPKIDDFSFQWLKCLEHLNMEDNDIPGIKSNMFTGLINLKYLSLSNSFTSLRTLTNETFVSLAHSPLHILNLTKNKISKIESDAFSWLGHLEVLDLGLNEIGQELTGQEWRGLENIFEIYLSYNKYLQLTRNSFALVPSLQRLMLRRVALKNVDSSPSPFQPLRNLTILDLSNNNIANINDDMLEGLEKLEILDLQHNNLARLWKHANPGGPIYFLKGLSHLHILNLESNGFDEIPVEVFKDLFELKIIDLGLNNLNTLPASVFNNQVSLKSLNLQKNLITSVEKKVFGPAFRNLTELDMRFNPFDCTCESIAWFVNWINETHTNIPELSSHYLCNTPPHYHGFPVRLFDTSSCKDSAPFELFFMINTSILLIFIFIVLLIHFEGWRISFYWNVSVHRVLGFKEIDRQTEQFEYAAYIIHAYKDKDWVWEHFSSMEKEDQSLKFCLEERDFEAGVFELEAIVNSIKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAIEQNLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKLQVALGSKNSVH
| null | null |
activation of NF-kappaB-inducing kinase activity [GO:0007250]; cellular response to exogenous dsRNA [GO:0071360]; cellular response to interferon-beta [GO:0035458]; cellular response to mechanical stimulus [GO:0071260]; cellular response to type II interferon [GO:0071346]; cellular response to virus [GO:0098586]; cellular response to xenobiotic stimulus [GO:0071466]; defense response to bacterium [GO:0042742]; defense response to virus [GO:0051607]; detection of virus [GO:0009597]; extrinsic apoptotic signaling pathway [GO:0097191]; hyperosmotic response [GO:0006972]; I-kappaB phosphorylation [GO:0007252]; inflammatory response to wounding [GO:0090594]; innate immune response [GO:0045087]; JNK cascade [GO:0007254]; male gonad development [GO:0008584]; microglial cell activation [GO:0001774]; necroptotic signaling pathway [GO:0097527]; negative regulation of osteoclast differentiation [GO:0045671]; positive regulation of angiogenesis [GO:0045766]; positive regulation of apoptotic process [GO:0043065]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of chemokine production [GO:0032722]; positive regulation of cytokine production involved in inflammatory response [GO:1900017]; positive regulation of gene expression [GO:0010628]; positive regulation of inflammatory response [GO:0050729]; positive regulation of interferon-alpha production [GO:0032727]; positive regulation of interferon-beta production [GO:0032728]; positive regulation of interleukin-12 production [GO:0032735]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of JNK cascade [GO:0046330]; positive regulation of macrophage cytokine production [GO:0060907]; positive regulation of non-canonical NF-kappaB signal transduction [GO:1901224]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of tumor necrosis factor production [GO:0032760]; positive regulation of type II interferon production [GO:0032729]; positive regulation of type III interferon production [GO:0034346]; regulation of dendritic cell cytokine production [GO:0002730]; response to dsRNA [GO:0043331]; response to exogenous dsRNA [GO:0043330]; signal transduction [GO:0007165]; toll-like receptor 3 signaling pathway [GO:0034138]; toll-like receptor signaling pathway [GO:0002224]; type III interferon production [GO:0034343]
|
cytoplasm [GO:0005737]; early endosome [GO:0005769]; endolysosome membrane [GO:0036020]; endoplasmic reticulum membrane [GO:0005789]; endosome membrane [GO:0010008]; extracellular matrix [GO:0031012]; extracellular space [GO:0005615]; Golgi membrane [GO:0000139]; lysosomal membrane [GO:0005765]; membrane [GO:0016020]; plasma membrane [GO:0005886]
|
double-stranded RNA binding [GO:0003725]; identical protein binding [GO:0042802]; pattern recognition receptor activity [GO:0038187]; signaling receptor activity [GO:0038023]; transmembrane signaling receptor activity [GO:0004888]
|
PF13516;PF13855;PF01582;PF17968;
|
3.80.10.10;3.40.50.10140;
|
Toll-like receptor family
|
PTM: Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding. {ECO:0000269|PubMed:15961631, ECO:0000269|PubMed:16043704, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22579623}.; PTM: TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes. {ECO:0000269|PubMed:22611194}.; PTM: Ubiquitinated by TRIM3; leading to recognition and sorting of polyubiquitinated TLR3 by the ESCRT complexes (PubMed:32878999). Ubiquitinated by ZNRF1 via 'Lys-63'-linked ubiquitin chains; leading to TLR3 lysosomal trafficking and degradation (PubMed:37158982). Ubiquitinated by RNF170 at Lys-765 via 'Lys-48'-linked ubiquitin chains; leading to TLR3 proteasomal degradation (PubMed:31076723). {ECO:0000269|PubMed:31076723, ECO:0000269|PubMed:32878999, ECO:0000269|PubMed:37158982}.
|
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane. Early endosome {ECO:0000269|PubMed:25736436}.
| null | null | null | null | null |
FUNCTION: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response. {ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:16043704, ECO:0000269|PubMed:16144834, ECO:0000269|PubMed:16720699, ECO:0000269|PubMed:16858407, ECO:0000269|PubMed:17178723, ECO:0000269|PubMed:18172197, ECO:0000269|PubMed:22611194}.
|
Homo sapiens (Human)
|
O15457
|
MSH4_HUMAN
|
MLRPEISSTSPSAPAVSPSSGETRSPQGPRYNFGLQETPQSRPSVQVVSASTCPGTSGAAGDRSSSSSSLPCPAPNSRPAQGSYFGNKRAYAENTVASNFTFGASSSSARDTNYPQTLKTPLSTGNPQRSGYKSWTPQVGYSASSSSAISAHSPSVIVAVVEGRGLARGEIGMASIDLKNPQIILSQFADNTTYAKVITKLKILSPLEIIMSNTACAVGNSTKLFTLITENFKNVNFTTIQRKYFNETKGLEYIEQLCIAEFSTVLMEVQSKYYCLAAVAALLKYVEFIQNSVYAPKSLKICFQGSEQTAMIDSSSAQNLELLINNQDYRNNHTLFGVLNYTKTPGGSRRLRSNILEPLVDIETINMRLDCVQELLQDEELFFGLQSVISRFLDTEQLLSVLVQIPKQDTVNAAESKITNLIYLKHTLELVDPLKIAMKNCNTPLLRAYYGSLEDKRFGIILEKIKTVINDDARYMKGCLNMRTQKCYAVRSNINEFLDIARRTYTEIVDDIAGMISQLGEKYSLPLRTSFSSARGFFIQMTTDCIALPSDQLPSEFIKISKVKNSYSFTSADLIKMNERCQESLREIYHMTYMIVCKLLSEIYEHIHCLYKLSDTVSMLDMLLSFAHACTLSDYVRPEFTDTLAIKQGWHPILEKISAEKPIANNTYVTEGSNFLIITGPNMSGKSTYLKQIALCQIMAQIGSYVPAEYSSFRIAKQIFTRISTDDDIETNSSTFMKEMKEIAYILHNANDKSLILIDELGRGTNTEEGIGICYAVCEYLLSLKAFTLFATHFLELCHIDALYPNVENMHFEVQHVKNTSRNKEAILYTYKLSKGLTEEKNYGLKAAEVSSLPPSIVLDAKEITTQITRQILQNQRSTPEMERQRAVYHLATRLVQTARNSQLDPDSLRIYLSNLKKKYKEDFPRTEQVPEKTEE
| null | null |
female gamete generation [GO:0007292]; homologous chromosome pairing at meiosis [GO:0007129]; mismatch repair [GO:0006298]; ovarian follicle development [GO:0001541]; reciprocal meiotic recombination [GO:0007131]; spermatogenesis [GO:0007283]
|
chromosome [GO:0005694]; nucleus [GO:0005634]; recombination nodule [GO:0005713]; synaptonemal complex [GO:0000795]
|
ATP binding [GO:0005524]; ATP-dependent DNA damage sensor activity [GO:0140664]; DNA binding [GO:0003677]; double-stranded DNA binding [GO:0003690]; mismatched DNA binding [GO:0030983]
|
PF05188;PF05192;PF05190;PF00488;
|
1.10.1420.10;3.30.420.110;3.40.50.300;
|
DNA mismatch repair MutS family
| null |
SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:Q99MT2}.
| null | null | null | null | null |
FUNCTION: Involved in meiotic recombination. Required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis.
|
Homo sapiens (Human)
|
O15460
|
P4HA2_HUMAN
|
MKLWVSALLMAWFGVLSCVQAEFFTSIGHMTDLIYAEKELVQSLKEYILVEEAKLSKIKSWANKMEALTSKSAADAEGYLAHPVNAYKLVKRLNTDWPALEDLVLQDSAAGFIANLSVQRQFFPTDEDEIGAAKALMRLQDTYRLDPGTISRGELPGTKYQAMLSVDDCFGMGRSAYNEGDYYHTVLWMEQVLKQLDAGEEATTTKSQVLDYLSYAVFQLGDLHRALELTRRLLSLDPSHERAGGNLRYFEQLLEEEREKTLTNQTEAELATPEGIYERPVDYLPERDVYESLCRGEGVKLTPRRQKRLFCRYHHGNRAPQLLIAPFKEEDEWDSPHIVRYYDVMSDEEIERIKEIAKPKLARATVRDPKTGVLTVASYRVSKSSWLEEDDDPVVARVNRRMQHITGLTVKTAELLQVANYGVGGQYEPHFDFSRNDERDTFKHLGTGNRVATFLNYMSDVEAGGATVFPDLGAAIWPKKGTAVFWYNLLRSGEGDYRTRHAACPVLVGCKWVSNKWFHERGQEFLRPCGSTEVD
|
1.14.11.2
|
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|PROSITE-ProRule:PRU00805}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-ProRule:PRU00805}; COFACTOR: Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; Evidence={ECO:0000305|PubMed:9211872};
| null |
cytosol [GO:0005829]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum lumen [GO:0005788]; intracellular membrane-bounded organelle [GO:0043231]; nucleoplasm [GO:0005654]
|
electron transfer activity [GO:0009055]; iron ion binding [GO:0005506]; L-ascorbic acid binding [GO:0031418]; procollagen-proline 4-dioxygenase activity [GO:0004656]
|
PF13640;PF08336;
|
6.10.140.1460;2.60.120.620;1.25.40.10;
|
P4HA family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
|
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-prolyl-[collagen] + O2 = CO2 + succinate + trans-4-hydroxy-L-prolyl-[collagen]; Xref=Rhea:RHEA:18945, Rhea:RHEA-COMP:11676, Rhea:RHEA-COMP:11680, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:50342, ChEBI:CHEBI:61965; EC=1.14.11.2; Evidence={ECO:0000269|PubMed:9211872};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=22 uM for 2-oxoglutarate {ECO:0000269|PubMed:9211872};
| null | null | null |
FUNCTION: Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. {ECO:0000269|PubMed:9211872}.
|
Homo sapiens (Human)
|
O15466
|
SIA8E_HUMAN
|
MRYADPSANRDLLGSRTLLFIFICAFALVTLLQQILYGRNYIKRYFEFYEGPFEYNSTRCLELRHEILEVKVLSMVKQSELFDRWKSLQMCKWAMNISEANQFKSTLSRCCNAPAFLFTTQKNTPLGTKLKYEVDTSGIYHINQEIFRMFPKDMPYYRSQFKKCAVVGNGGILKNSRCGREINSADFVFRCNLPPISEKYTMDVGVKTDVVTVNPSIITERFHKLEKWRRPFYRVLQVYENASVLLPAFYNTRNTDVSIRVKYVLDDFESPQAVYYFHPQYLVNVSRYWLSLGVRAKRISTGLILVTAALELCEEVHLFGFWAFPMNPSGLYITHHYYDNVKPRPGFHAMPSEIFNFLHLHSRGILRVHTGTCSCC
|
2.4.99.-
| null |
carbohydrate metabolic process [GO:0005975]; glycosphingolipid biosynthetic process [GO:0006688]; N-glycan processing [GO:0006491]; oligosaccharide metabolic process [GO:0009311]; protein glycosylation [GO:0006486]
|
Golgi membrane [GO:0000139]
|
alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity [GO:0003828]; sialyltransferase activity [GO:0008373]
|
PF00777;
|
3.90.1480.20;
|
Glycosyltransferase 29 family
| null |
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250|UniProtKB:Q6ZXC8}; Single-pass type II membrane protein {ECO:0000255}.
|
CATALYTIC ACTIVITY: [Isoform 1]: Reaction=a ganglioside GT1b (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GQ1b (d18:1(4E)) + CMP + H(+); Xref=Rhea:RHEA:41772, ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377, ChEBI:CHEBI:78452, ChEBI:CHEBI:78455; Evidence={ECO:0000269|PubMed:9199191}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41773; Evidence={ECO:0000269|PubMed:9199191}; CATALYTIC ACTIVITY: [Isoform 1]: Reaction=a ganglioside GD3 (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GT3 (d18:1(4E)) + CMP + H(+); Xref=Rhea:RHEA:41764, ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377, ChEBI:CHEBI:78436, ChEBI:CHEBI:78438; Evidence={ECO:0000269|PubMed:9199191}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41765; Evidence={ECO:0000269|PubMed:9199191}; CATALYTIC ACTIVITY: [Isoform 1]: Reaction=a ganglioside GD1a (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GT1a (d18:1(4E)) + CMP + H(+); Xref=Rhea:RHEA:41768, ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377, ChEBI:CHEBI:78445, ChEBI:CHEBI:78447; Evidence={ECO:0000269|PubMed:9199191}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41769; Evidence={ECO:0000269|PubMed:9199191}; CATALYTIC ACTIVITY: [Isoform 1]: Reaction=a ganglioside GM1b (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GD1c (d18:1(4E)) + CMP + H(+); Xref=Rhea:RHEA:47576, ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377, ChEBI:CHEBI:78568, ChEBI:CHEBI:87787; Evidence={ECO:0000269|PubMed:9199191}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47577; Evidence={ECO:0000269|PubMed:9199191}; CATALYTIC ACTIVITY: Reaction=a ganglioside GQ1c (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GP1c (d18:1(4E)) + CMP + H(+); Xref=Rhea:RHEA:47592, ChEBI:CHEBI:15378, ChEBI:CHEBI:57812, ChEBI:CHEBI:60377, ChEBI:CHEBI:87791, ChEBI:CHEBI:87792; Evidence={ECO:0000250|UniProtKB:Q6ZXC8}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47593; Evidence={ECO:0000250|UniProtKB:Q6ZXC8};
| null |
PATHWAY: Protein modification; protein glycosylation. {ECO:0000269|PubMed:9199191}.
| null | null |
FUNCTION: Involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, GP1c and GT3 from GD1a, GT1b, GM1b and GD3 respectively. {ECO:0000269|PubMed:9199191}.
|
Homo sapiens (Human)
|
O15467
|
CCL16_HUMAN
|
MKVSEAALSLLVLILIITSASRSQPKVPEWVNTPSTCCLKYYEKVLPRRLVVGYRKALNCHLPAIIFVTKRNREVCTNPNDDWVQEYIKDPNLPLLPTRNLSTVKIITAKNGQPQLLNSQ
| null | null |
cell communication [GO:0007154]; cell-cell signaling [GO:0007267]; 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]; lymphocyte chemotaxis [GO:0048247]; monocyte chemotaxis [GO:0002548]; neutrophil chemotaxis [GO:0030593]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]
|
extracellular region [GO:0005576]; extracellular space [GO:0005615]
|
CCR chemokine receptor binding [GO:0048020]; chemoattractant activity [GO:0042056]; chemokine activity [GO:0008009]
|
PF00048;
|
2.40.50.40;
|
Intercrine beta (chemokine CC) family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Shows chemotactic activity for lymphocytes and monocytes but not neutrophils. Also shows potent myelosuppressive activity, suppresses proliferation of myeloid progenitor cells. Recombinant SCYA16 shows chemotactic activity for monocytes and THP-1 monocytes, but not for resting lymphocytes and neutrophils. Induces a calcium flux in THP-1 cells that were desensitized by prior expression to RANTES.
|
Homo sapiens (Human)
|
O15479
|
MAGB2_HUMAN
|
MPRGQKSKLRAREKRRKARDETRGLNVPQVTEAEEEEAPCCSSSVSGGAASSSPAAGIPQEPQRAPTTAAAAAAGVSSTKSKKGAKSHQGEKNASSSQASTSTKSPSEDPLTRKSGSLVQFLLYKYKIKKSVTKGEMLKIVGKRFREHFPEILKKASEGLSVVFGLELNKVNPNGHTYTFIDKVDLTDEESLLSSWDFPRRKLLMPLLGVIFLNGNSATEEEIWEFLNMLGVYDGEEHSVFGEPWKLITKDLVQEKYLEYKQVPSSDPPRFQFLWGPRAYAETSKMKVLEFLAKVNGTTPCAFPTHYEEALKDEEKAGV
| null | null |
negative regulation of transcription by RNA polymerase II [GO:0000122]
|
nucleus [GO:0005634]
| null |
PF01454;PF12440;
|
1.10.10.1200;1.10.10.1210;
| null | null | null | null | null | null | null | null |
FUNCTION: May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. {ECO:0000269|PubMed:20864041}.
|
Homo sapiens (Human)
|
O15481
|
MAGB4_HUMAN
|
MPRGQKSKLRAREKRQRTRGQTQDLKVGQPTAAEKEESPSSSSSVLRDTASSSLAFGIPQEPQREPPTTSAAAAMSCTGSDKGDESQDEENASSSQASTSTERSLKDSLTRKTKMLVQFLLYKYKMKEPTTKAEMLKIISKKYKEHFPEIFRKVSQRTELVFGLALKEVNPTTHSYILVSMLGPNDGNQSSAWTLPRNGLLMPLLSVIFLNGNCAREEEIWEFLNMLGIYDGKRHLIFGEPRKLITQDLVQEKYLEYQQVPNSDPPRYQFLWGPRAHAETSKMKVLEFLAKVNDTTPNNFPLLYEEALRDEEERAGARPRVAARRGTTAMTSAYSRATSSSSSQPM
| null | null |
negative regulation of transcription by RNA polymerase II [GO:0000122]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
| null |
PF01454;PF12440;
|
1.10.10.1200;1.10.10.1210;
| null | null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A2A9R3}.
| null | null | null | null | null | null |
Homo sapiens (Human)
|
O15484
|
CAN5_HUMAN
|
MFSCVKPYEDQNYSALRRDCRRRKVLFEDPLFPATDDSLYYKGTPGPAVRWKRPKGICEDPRLFVDGISSHDLHQGQVGNCWFVAACSSLASRESLWQKVIPDWKEQEWDPEKPNAYAGIFHFHFWRFGEWVDVVIDDRLPTVNNQLIYCHSNSRNEFWCALVEKAYAKLAGCYQALDGGNTADALVDFTGGVSEPIDLTEGDFANDETKRNQLFERMLKVHSRGGLISASIKAVTAADMEARLACGLVKGHAYAVTDVRKVRLGHGLLAFFKSEKLDMIRLRNPWGEREWNGPWSDTSEEWQKVSKSEREKMGVTVQDDGEFWMTFEDVCRYFTDIIKCRVINTSHLSIHKTWEEARLHGAWTLHEDPRQNRGGGCINHKDTFFQNPQYIFEVKKPEDEVLICIQQRPKRSTRREGKGENLAIGFDIYKVEENRQYRMHSLQHKAASSIYINSRSVFLRTDQPEGRYVIIPTTFEPGHTGEFLLRVFTDVPSNCRELRLDEPPHTCWSSLCGYPQLVTQVHVLGAAGLKDSPTGANSYVIIKCEGDKVRSAVQKGTSTPEYNVKGIFYRKKLSQPITVQVWNHRVLKDEFLGQVHLKADPDNLQALHTLHLRDRNSRQPSNLPGTVAVHILSSTSLMAV
|
3.4.22.-
| null |
proteolysis [GO:0006508]; signal transduction [GO:0007165]
|
cell surface [GO:0009986]; cytoplasm [GO:0005737]; extracellular exosome [GO:0070062]; focal adhesion [GO:0005925]; synapse [GO:0045202]
|
calcium-dependent cysteine-type endopeptidase activity [GO:0004198]
|
PF00168;PF01067;PF00648;
|
2.60.120.380;2.60.40.150;3.90.70.10;
|
Peptidase C2 family
| null | null | null | null | null | null | null |
FUNCTION: Calcium-regulated non-lysosomal thiol-protease. {ECO:0000250}.
|
Homo sapiens (Human)
|
O15488
|
GLYG2_HUMAN
|
MSETEFHHGAQAGLELLRSSNSPTSASQSAGMTVTDQAFVTLATNDIYCQGALVLGQSLRRHRLTRKLVVLITPQVSSLLRVILSKVFDEVIEVNLIDSADYIHLAFLKRPELGLTLTKLHCWTLTHYSKCVFLDADTLVLSNVDELFDRGEFSAAPDPGWPDCFNSGVFVFQPSLHTHKLLLQHAMEHGSFDGADQGLLNSFFRNWSTTDIHKHLPFIYNLSSNTMYTYSPAFKQFGSSAKVVHFLGSMKPWNYKYNPQSGSVLEQGSASSSQHQAAFLHLWWTVYQNNVLPLYKSVQAGEARASPGHTLCHSDVGGPCADSASGVGEPCENSTPSAGVPCANSPLGSNQPAQGLPEPTQIVDETLSLPEGRRSEDMIACPETETPAVITCDPLSQPSPQPADFTETETILQPANKVESVSSEETFEPSQELPAEALRDPSLQDALEVDLAVSVSQISIEEKVKELSPEEERRKWEEGRIDYMGKDAFARIQEKLDRFLQ
|
2.4.1.186
|
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:P46976};
|
glycogen biosynthetic process [GO:0005978]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]
|
glycogenin glucosyltransferase activity [GO:0008466]; glycosyltransferase activity [GO:0016757]; metal ion binding [GO:0046872]; UDP-alpha-D-glucose:glucosyl-glycogenin alpha-D-glucosyltransferase activity [GO:0102751]
|
PF01501;
| null |
Glycosyltransferase 8 family, Glycogenin subfamily
|
PTM: Self-glycosylated by the transfer of glucose residues from UDP-glucose to itself, forming an alpha-1,4-glycan of around 10 residues attached to Tyr-228. {ECO:0000269|PubMed:9857012}.
| null |
CATALYTIC ACTIVITY: Reaction=L-tyrosyl-[glycogenin] + UDP-alpha-D-glucose = alpha-D-glucosyl-L-tyrosyl-[glycogenin] + H(+) + UDP; Xref=Rhea:RHEA:23360, Rhea:RHEA-COMP:14604, Rhea:RHEA-COMP:14605, ChEBI:CHEBI:15378, ChEBI:CHEBI:46858, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885, ChEBI:CHEBI:140573; EC=2.4.1.186; Evidence={ECO:0000269|PubMed:9346895, ECO:0000269|PubMed:9857012}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23361; Evidence={ECO:0000269|PubMed:9346895, ECO:0000269|PubMed:9857012}; CATALYTIC ACTIVITY: Reaction=[1,4-alpha-D-glucosyl](n)-L-tyrosyl-[glycogenin] + UDP-alpha-D-glucose = [1,4-alpha-D-glucosyl](n+1)-L-tyrosyl-[glycogenin] + H(+) + UDP; Xref=Rhea:RHEA:56560, Rhea:RHEA-COMP:14606, Rhea:RHEA-COMP:14607, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885, ChEBI:CHEBI:140574; EC=2.4.1.186; Evidence={ECO:0000269|PubMed:9346895, ECO:0000269|PubMed:9857012}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56561; Evidence={ECO:0000269|PubMed:9346895, ECO:0000269|PubMed:9857012};
| null |
PATHWAY: Glycan biosynthesis; glycogen biosynthesis. {ECO:0000269|PubMed:9346895, ECO:0000269|PubMed:9857012}.
| null | null |
FUNCTION: Glycogenin participates in the glycogen biosynthetic process along with glycogen synthase and glycogen branching enzyme. It self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase. {ECO:0000269|PubMed:9346895, ECO:0000269|PubMed:9857012}.
|
Homo sapiens (Human)
|
O15492
|
RGS16_HUMAN
|
MCRTLAAFPTTCLERAKEFKTRLGIFLHKSELGCDTGSTGKFEWGSKHSKENRNFSEDVLGWRESFDLLLSSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKIRSATKLASRAHQIFEEFICSEAPKEVNIDHETHELTRMNLQTATATCFDAAQGKTRTLMEKDSYPRFLKSPAYRDLAAQASAASATLSSCSLDEPSHT
| null | null |
G protein-coupled receptor signaling pathway [GO:0007186]; negative regulation of signal transduction [GO:0009968]; positive regulation of GTPase activity [GO:0043547]; regulation of G protein-coupled receptor signaling pathway [GO:0008277]; visual perception [GO:0007601]
|
cytoplasm [GO:0005737]; membrane [GO:0016020]; plasma membrane [GO:0005886]
|
calmodulin binding [GO:0005516]; GTPase activator activity [GO:0005096]; GTPase activity [GO:0003924]
|
PF00615;
|
1.10.196.10;1.10.167.10;
| null |
PTM: Palmitoylated on Cys-2 and/or Cys-12. {ECO:0000250|UniProtKB:P97428}.; PTM: Phosphorylated. Phosphorylation at Tyr-168 by EGFR enhances GTPase accelerating (GAP) activity toward GNAI1. {ECO:0000269|PubMed:11602604}.
|
SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P97428}; Lipid-anchor {ECO:0000250|UniProtKB:P97428}.
| null | null | null | null | null |
FUNCTION: Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:11602604, PubMed:18434541). Plays an important role in the phototransduction cascade by regulating the lifetime and effective concentration of activated transducin alpha. May regulate extra and intracellular mitogenic signals (By similarity). {ECO:0000250|UniProtKB:P97428, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:18434541}.
|
Homo sapiens (Human)
|
O15496
|
PA2GX_HUMAN
|
MGPLPVCLPIMLLLLLPSLLLLLLLPGPGSGEASRILRVHRRGILELAGTVGCVGPRTPIAYMKYGCFCGLGGHGQPRDAIDWCCHGHDCCYTRAEEAGCSPKTERYSWQCVNQSVLCGPAENKCQELLCKCDQEIANCLAQTEYNLKYLFYPQFLCEPDSPKCD
|
3.1.1.4
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:12161451, ECO:0000269|PubMed:9188469}; Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:12161451};
|
arachidonic acid metabolic process [GO:0019369]; arachidonic acid secretion [GO:0050482]; axon guidance [GO:0007411]; cellular response to leukemia inhibitory factor [GO:1990830]; cholesterol homeostasis [GO:0042632]; defense response to virus [GO:0051607]; erythrocyte maturation [GO:0043249]; fertilization [GO:0009566]; hair follicle morphogenesis [GO:0031069]; intestinal stem cell homeostasis [GO:0036335]; low-density lipoprotein particle remodeling [GO:0034374]; lysophospholipid transport [GO:0051977]; macrophage activation [GO:0042116]; negative regulation of cholesterol efflux [GO:0090370]; negative regulation of cytokine production involved in inflammatory response [GO:1900016]; negative regulation of DNA-binding transcription factor activity [GO:0043433]; negative regulation of inflammatory response [GO:0050728]; phosphatidic acid metabolic process [GO:0046473]; phosphatidylcholine catabolic process [GO:0034638]; phosphatidylcholine metabolic process [GO:0046470]; phosphatidylethanolamine metabolic process [GO:0046337]; phosphatidylglycerol metabolic process [GO:0046471]; phosphatidylserine metabolic process [GO:0006658]; phospholipid metabolic process [GO:0006644]; platelet activating factor catabolic process [GO:0062234]; positive regulation of acrosome reaction [GO:2000344]; positive regulation of arachidonic acid secretion [GO:0090238]; positive regulation of lipid storage [GO:0010884]; positive regulation of macrophage derived foam cell differentiation [GO:0010744]; positive regulation of prostaglandin secretion [GO:0032308]; positive regulation of protein metabolic process [GO:0051247]; production of molecular mediator involved in inflammatory response [GO:0002532]; prostaglandin biosynthetic process [GO:0001516]; regulation of macrophage activation [GO:0043030]
|
acrosomal vesicle [GO:0001669]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; lysosome [GO:0005764]
|
1-alkyl-2-acetylglycerophosphocholine esterase activity [GO:0003847]; calcium ion binding [GO:0005509]; calcium-dependent phospholipase A2 activity [GO:0047498]; phospholipase A2 activity [GO:0004623]; phospholipase activity [GO:0004620]; phospholipid binding [GO:0005543]
|
PF00068;
|
1.20.90.10;
|
Phospholipase A2 family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9188469}. Lysosome {ECO:0000250|UniProtKB:Q9QXX3}. Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250|UniProtKB:Q9QXX3}.
|
CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4; Evidence={ECO:0000255|PROSITE-ProRule:PRU10035, ECO:0000255|PROSITE-ProRule:PRU10036, ECO:0000269|PubMed:12021277}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802; Evidence={ECO:0000305|PubMed:12021277}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:38779, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:72998, ChEBI:CHEBI:73001; Evidence={ECO:0000269|PubMed:12359733, ECO:0000269|PubMed:16962371}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38780; Evidence={ECO:0000305|PubMed:12359733, ECO:0000305|PubMed:16962371}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-octadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40519, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, ChEBI:CHEBI:73858, ChEBI:CHEBI:74965; Evidence={ECO:0000269|PubMed:12359733}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40520; Evidence={ECO:0000305|PubMed:12359733}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) + hexadecanoate; Xref=Rhea:RHEA:41223, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:72998, ChEBI:CHEBI:72999; Evidence={ECO:0000269|PubMed:12359733}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41224; Evidence={ECO:0000305|PubMed:12359733}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoglycerol + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphoglycerol + H(+); Xref=Rhea:RHEA:44524, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:84472, ChEBI:CHEBI:84475; Evidence={ECO:0000269|PubMed:12359733}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44525; Evidence={ECO:0000305|PubMed:12359733}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + H(+) + hexadecanoate; Xref=Rhea:RHEA:45472, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:72829, ChEBI:CHEBI:75158; Evidence={ECO:0000250|UniProtKB:Q9QXX3}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45473; Evidence={ECO:0000250|UniProtKB:Q9QXX3}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H(+); Xref=Rhea:RHEA:41752, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75020, ChEBI:CHEBI:75029; Evidence={ECO:0000269|PubMed:12359733}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41753; Evidence={ECO:0000305|PubMed:12359733}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + H(+); Xref=Rhea:RHEA:40815, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:73004, ChEBI:CHEBI:73008; Evidence={ECO:0000269|PubMed:12359733}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40816; Evidence={ECO:0000305|PubMed:12359733}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphate + H(+); Xref=Rhea:RHEA:63996, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:57518, ChEBI:CHEBI:64839; Evidence={ECO:0000269|PubMed:12359733}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63997; Evidence={ECO:0000305|PubMed:12359733}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:40479, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:44811, ChEBI:CHEBI:64496; Evidence={ECO:0000269|PubMed:16962371}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40480; Evidence={ECO:0000305|PubMed:16962371};
| null | null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.4. {ECO:0000269|PubMed:9188469};
| null |
FUNCTION: Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids (PubMed:12021277, PubMed:9188469). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids with preference for phosphatidylcholines and phosphatidylglycerols over phosphatidylethanolamines. Preferentially releases sn-2 omega-6 and omega-3 polyunsaturated fatty acyl (PUFA) chains over saturated fatty acyls (PubMed:12021277, PubMed:12359733). Contributes to phospholipid remodeling of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (PubMed:12021277). Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells (PubMed:12021277). Efficiently hydrolyzes and inactivates platelet activating factor (PAF), a potent lipid mediator present in oxidized LDL (PubMed:16962371). May act in an autocrine and paracrine manner. Secreted by lung epithelium, targets membrane phospholipids of infiltrating eosinophils, releasing arachidonate and boosting eicosanoid and cysteinyl leukotriene synthesis involved in airway inflammatory response (By similarity). Secreted by gut epithelium, hydrolyzes dietary and biliary phosphatidylcholines in the gastrointestinal lumen (By similarity). Plays a stem cell regulator role in colon epithelium. Within intracellular compartment, mediates Paneth-like cell differentiation and its stem cell supporting functions by inhibiting the Wnt signaling pathway in intestinal stem cell (ISC). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ISCs and tissue regeneration (By similarity). May participate in hair follicle morphogenesis by regulating phosphatidylethanolamines metabolism at the outermost epithelial layer and facilitating melanin synthesis (By similarity). By releasing lysophosphatidylcholines (LPCs) at sperm acrosome, controls sperm cell capacitation, acrosome reaction and overall fertility (By similarity). May promote neurite outgrowth in neuron fibers involved in nociception (By similarity). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria (PubMed:12359733). Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541). In pulmonary epithelium, may contribute to host defense response against adenoviral infection. Prevents adenovirus entry into host cells by hydrolyzing host cell plasma membrane, releasing C16:0 LPCs that inhibit virus-mediated membrane fusion and viral infection. Likely prevents adenoviral entry into the endosomes of host cells (PubMed:16146426). May play a role in maturation and activation of innate immune cells including macrophages, group 2 innate lymphoid cells and mast cells (By similarity). {ECO:0000250|UniProtKB:Q9QXX3, ECO:0000269|PubMed:11694541, ECO:0000269|PubMed:12021277, ECO:0000269|PubMed:12359733, ECO:0000269|PubMed:16146426, ECO:0000269|PubMed:16962371, ECO:0000269|PubMed:9188469}.
|
Homo sapiens (Human)
|
O15498
|
YKT6_HUMAN
|
MKLYSLSVLYKGEAKVVLLKAAYDVSSFSFFQRSSVQEFMTFTSQLIVERSSKGTRASVKEQDYLCHVYVRNDSLAGVVIADNEYPSRVAFTLLEKVLDEFSKQVDRIDWPVGSPATIHYPALDGHLSRYQNPREADPMTKVQAELDETKIILHNTMESLLERGEKLDDLVSKSEVLGTQSKAFYKTARKQNSCCAIM
|
2.3.1.-
| null |
endoplasmic reticulum to Golgi vesicle-mediated transport [GO:0006888]; protein transport [GO:0015031]; retrograde transport, endosome to Golgi [GO:0042147]; vesicle docking involved in exocytosis [GO:0006904]; vesicle targeting [GO:0006903]
|
apical dendrite [GO:0097440]; basal dendrite [GO:0097441]; cytoplasm [GO:0005737]; cytoplasmic vesicle membrane [GO:0030659]; cytosol [GO:0005829]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum-Golgi intermediate compartment membrane [GO:0033116]; endosome [GO:0005768]; Golgi apparatus [GO:0005794]; Golgi membrane [GO:0000139]; mitochondrion [GO:0005739]; neuronal cell body [GO:0043025]; plasma membrane [GO:0005886]; SNARE complex [GO:0031201]; transport vesicle [GO:0030133]
|
cadherin binding [GO:0045296]; protein-cysteine S-palmitoyltransferase activity [GO:0019706]; SNAP receptor activity [GO:0005484]
|
PF13774;PF00957;
|
1.20.5.110;3.30.450.50;
|
Synaptobrevin family
|
PTM: Palmitoylated; catalyzes its own palmitoylation. Palmitoylation is required for Golgi targeting. {ECO:0000269|PubMed:15044687, ECO:0000269|PubMed:15479160}.; PTM: Farnesylation is required for Golgi targeting.
|
SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasmic vesicle membrane; Lipid-anchor; Cytoplasmic side. Golgi apparatus membrane; Lipid-anchor; Cytoplasmic side. Note=Probably cycles through vesicles between Golgi and endosomes.
| null | null | null | null | null |
FUNCTION: Vesicular soluble NSF attachment protein receptor (v-SNARE) mediating vesicle docking and fusion to a specific acceptor cellular compartment. Functions in endoplasmic reticulum to Golgi transport; as part of a SNARE complex composed of GOSR1, GOSR2 and STX5. Functions in early/recycling endosome to TGN transport; as part of a SNARE complex composed of BET1L, GOSR1 and STX5. Has a S-palmitoyl transferase activity. {ECO:0000269|PubMed:15215310, ECO:0000269|PubMed:9211930}.
|
Homo sapiens (Human)
|
O15499
|
GSC2_HUMAN
|
MAAAAGGAASRRGAGRPCPFSIEHILSSLPERSLPARAACPPQPAGRQSPAKPEEPGAPEAAPCACCCCCGPRAAPCGPPEAAAGLGARLAWPLRLGPAVPLSLGAPAGGSGALPGAVGPGSQRRTRRHRTIFSEEQLQALEALFVQNQYPDVSTRERLAGRIRLREERVEVWFKNRRAKWRHQKRASASARLLPGVKKSPKGSC
| null | null |
anatomical structure morphogenesis [GO:0009653]; regulation of transcription by RNA polymerase II [GO:0006357]
|
chromatin [GO:0000785]; nucleus [GO:0005634]
|
DNA binding [GO:0003677]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF00046;
|
1.10.10.60;
|
Paired homeobox family, Bicoid subfamily
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
| null | null | null | null | null |
FUNCTION: May have a role in development. May regulate its own transcription. May bind the bicoid consensus sequence TAATCC.
|
Homo sapiens (Human)
|
O15503
|
INSI1_HUMAN
|
MPRLHDHFWSCSCAHSARRRGPPRASAAGLAAKVGEMINVSVSGPSLLAAHGAPDADPAPRGRSAAMSGPEPGSPYPNTWHHRLLQRSLVLFSVGVVLALVLNLLQIQRNVTLFPEEVIATIFSSAWWVPPCCGTAAAVVGLLYPCIDSHLGEPHKFKREWASVMRCIAVFVGINHASAKLDFANNVQLSLTLAALSLGLWWTFDRSRSGLGLGITIAFLATLITQFLVYNGVYQYTSPDFLYIRSWLPCIFFSGGVTVGNIGRQLAMGVPEKPHSD
| null | null |
cellular response to insulin stimulus [GO:0032869]; cellular response to sterol [GO:0036315]; cholesterol biosynthetic process [GO:0006695]; cholesterol homeostasis [GO:0042632]; cranial suture morphogenesis [GO:0060363]; inner ear morphogenesis [GO:0042472]; middle ear morphogenesis [GO:0042474]; negative regulation of cargo loading into COPII-coated vesicle [GO:1901303]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of fatty acid biosynthetic process [GO:0045717]; negative regulation of protein exit from endoplasmic reticulum [GO:0070862]; negative regulation of steroid biosynthetic process [GO:0010894]; roof of mouth development [GO:0060021]; SREBP signaling pathway [GO:0032933]; SREBP-SCAP complex retention in endoplasmic reticulum [GO:0036316]; triglyceride metabolic process [GO:0006641]
|
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; SREBP-SCAP-Insig complex [GO:0032937]
|
oxysterol binding [GO:0008142]; protein sequestering activity [GO:0140311]
|
PF07281;
| null |
INSIG family
|
PTM: Phosphorylation at Ser-207 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG1 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes. {ECO:0000269|PubMed:32322062}.; PTM: Ubiquitinated by AMFR/gp78 in response to sterol deprivation, leading to its degradation: when the SCAP-SREBP complex becomes dissociated from INSIG1, INSIG1 is then ubiquitinated and degraded in proteasomes (PubMed:16399501, PubMed:17043353). Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex (PubMed:16399501). Ubiquitinated by RNF139 (PubMed:20068067). {ECO:0000269|PubMed:16399501, ECO:0000269|PubMed:17043353, ECO:0000269|PubMed:20068067}.
|
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12202038, ECO:0000269|PubMed:32322062}; Multi-pass membrane protein {ECO:0000269|PubMed:12202038}.
| null | null | null | null | null |
FUNCTION: Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:12202038, PubMed:12535518, PubMed:16168377, PubMed:16399501, PubMed:16606821, PubMed:32322062). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:12202038, PubMed:16399501, PubMed:32322062). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:32322062). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (PubMed:15899885, PubMed:32322062). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG1 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligases AMFR/gp78 and/or RNF139 (PubMed:12535518, PubMed:16168377, PubMed:22143767). Also regulates degradation of SOAT2/ACAT2 when the lipid levels are low: initiates the ubiquitin-mediated degradation of SOAT2/ACAT2 via recruitment of the ubiquitin ligases AMFR/gp78 (PubMed:28604676). {ECO:0000269|PubMed:12202038, ECO:0000269|PubMed:12535518, ECO:0000269|PubMed:15899885, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16399501, ECO:0000269|PubMed:16606821, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:28604676, ECO:0000269|PubMed:32322062}.
|
Homo sapiens (Human)
|
O15504
|
NUP42_HUMAN
|
MAICQFFLQGRCRFGDRCWNEHPGARGAGGGRQQPQQQPSGNNRRGWNTTSQRYSNVIQPSSFSKSTPWGGSRDQEKPYFSSFDSGASTNRKEGFGLSENPFASLSPDEQKDEKKLLEGIVKDMEVWESSGQWMFSVYSPVKKKPNISGFTDISPEELRLEYHNFLTSNNLQSYLNSVQRLINQWRNRVNELKSLNISTKVALLSDVKDGVNQAAPAFGFGSSQAATFMSPGFPVNNSSSDNAQNFSFKTNSGFAAASSGSPAGFGSSPAFGAAASTSSGISTSAPAFGFGKPEVTSAASFSFKSPAASSFGSPGFSGLPASLATGPVRAPVAPAFGGGSSVAGFGSPGSHSHTAFSKPSSDTFGNSSISTSLSASSSIIATDNVLFTPRDKLTVEELEQFQSKKFTLGKIPLKPPPLELLNV
| null | null |
mRNA transport [GO:0051028]; nucleocytoplasmic transport [GO:0006913]; protein export from nucleus [GO:0006611]
|
cytosol [GO:0005829]; nuclear envelope [GO:0005635]; nuclear membrane [GO:0031965]; nuclear pore [GO:0005643]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
metal ion binding [GO:0046872]; nuclear export signal receptor activity [GO:0005049]; RNA binding [GO:0003723]
|
PF18044;
| null | null |
PTM: O-glycosylated. {ECO:0000269|PubMed:10358091}.
|
SUBCELLULAR LOCATION: Nucleus, nuclear pore complex {ECO:0000269|PubMed:12228227, ECO:0000269|PubMed:16000379}. Nucleus membrane {ECO:0000269|PubMed:12228227, ECO:0000269|PubMed:16000379}; Peripheral membrane protein; Cytoplasmic side {ECO:0000269|PubMed:12228227}. Note=Excluded from the nucleolus. {ECO:0000269|PubMed:10358091}.
| null | null | null | null | null |
FUNCTION: Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm. {ECO:0000269|PubMed:10610322, ECO:0000269|PubMed:16000379}.; FUNCTION: (Microbial infection) In case of infection by HIV-1, it may participate in the docking of viral Vpr at the nuclear envelope. {ECO:0000269|PubMed:12228227}.
|
Homo sapiens (Human)
|
O15511
|
ARPC5_HUMAN
|
MSKNTVSSARFRKVDVDEYDENKFVDEEDGGDGQAGPDEGEVDSCLRQGNMTAALQAALKNPPINTKSQAVKDRAGSIVLKVLISFKANDIEKAVQSLDKNGVDLLMKYIYKGFESPSDNSSAMLLQWHEKALAAGGVGSIVRVLTARKTV
| null | null |
actin cytoskeleton organization [GO:0030036]; Arp2/3 complex-mediated actin nucleation [GO:0034314]; cell migration [GO:0016477]; regulation of actin filament polymerization [GO:0030833]
|
actin cytoskeleton [GO:0015629]; Arp2/3 protein complex [GO:0005885]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; ficolin-1-rich granule lumen [GO:1904813]; focal adhesion [GO:0005925]; lamellipodium [GO:0030027]; nucleus [GO:0005634]; secretory granule lumen [GO:0034774]; site of double-strand break [GO:0035861]
|
actin filament binding [GO:0051015]; structural constituent of cytoskeleton [GO:0005200]
|
PF04699;
|
1.25.40.190;
|
ARPC5 family
|
PTM: Polyubiquitinated by RNF128 with 'Lys-63'-linked chains, leading to proteasomal degradation. {ECO:0000269|PubMed:22016387}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:9230079}. Cell projection {ECO:0000269|PubMed:9230079}. Nucleus {ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:37349293}.
| null | null | null | null | null |
FUNCTION: Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9230079). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9230079}.
|
Homo sapiens (Human)
|
O15514
|
RPB4_HUMAN
|
MAAGGSDPRAGDVEEDASQLIFPKEFETAETLLNSEVHMLLEHRKQQNESAEDEQELSEVFMKTLNYTARFSRFKNRETIASVRSLLLQKKLHKFELACLANLCPETAEESKALIPSLEGRFEDEELQQILDDIQTKRSFQY
| null | null |
recruitment of 3'-end processing factors to RNA polymerase II holoenzyme complex [GO:0034402]; transcription by RNA polymerase II [GO:0006366]; transcription initiation at RNA polymerase II promoter [GO:0006367]
|
cytosol [GO:0005829]; nuclear speck [GO:0016607]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; RNA polymerase II, core complex [GO:0005665]
|
nucleotide binding [GO:0000166]; translation initiation factor binding [GO:0031369]
|
PF03874;
|
1.20.1250.40;
|
Eukaryotic RPB4 RNA polymerase subunit family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9852112}.
| null | null | null | null | null |
FUNCTION: Core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. POLR2D/RPB4 is part of a subcomplex with POLR2G/RPB7 that binds to a pocket formed by POLR2A/RPB1, POLR2B/RPB2 and POLR2F/RPABC2 at the base of the clamp element. The POLR2D/RPB4-POLR2G/RPB7 subcomplex seems to lock the clamp via POLR2G/RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The POLR2D/RPB4-POLR2G/RPB7 subcomplex binds single-stranded DNA and RNA. {ECO:0000250|UniProtKB:P20433, ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:30190596, ECO:0000269|PubMed:9852112}.
|
Homo sapiens (Human)
|
O15516
|
CLOCK_HUMAN
|
MLFTVSCSKMSSIVDRDDSSIFDGLVEEDDKDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLRKHKEITAQSDASEIRQDWKPTFLSNEEFTQLMLEALDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPEGEHSEVYKILSTHLLESDSLTPEYLKSKNQLEFCCHMLRGTIDPKEPSTYEYVKFIGNFKSLNSVSSSAHNGFEGTIQRTHRPSYEDRVCFVATVRLATPQFIKEMCTVEEPNEEFTSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYDYYHVDDLENLAKCHEHLMQYGKGKSCYYRFLTKGQQWIWLQTHYYITYHQWNSRPEFIVCTHTVVSYAEVRAERRRELGIEESLPETAADKSQDSGSDNRINTVSLKEALERFDHSPTPSASSRSSRKSSHTAVSDPSSTPTKIPTDTSTPPRQHLPAHEKMVQRRSSFSSQSINSQSVGSSLTQPVMSQATNLPIPQGMSQFQFSAQLGAMQHLKDQLEQRTRMIEANIHRQQEELRKIQEQLQMVHGQGLQMFLQQSNPGLNFGSVQLSSGNSSNIQQLAPINMQGQVVPTNQIQSGMNTGHIGTTQHMIQQQTLQSTSTQSQQNVLSGHSQQTSLPSQTQSTLTAPLYNTMVISQPAAGSMVQIPSSMPQNSTQSAAVTTFTQDRQIRFSQGQQLVTKLVTAPVACGAVMVPSTMLMGQVVTAYPTFATQQQQSQTLSVTQQQQQQSSQEQQLTSVQQPSQAQLTQPPQQFLQTSRLLHGNPSTQLILSAAFPLQQSTFPQSHHQQHQSQQQQQLSRHRTDSLPDPSKVQPQ
|
2.3.1.48
| null |
cellular response to ionizing radiation [GO:0071479]; circadian regulation of gene expression [GO:0032922]; circadian rhythm [GO:0007623]; DNA damage checkpoint signaling [GO:0000077]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of glucocorticoid receptor signaling pathway [GO:2000323]; photoperiodism [GO:0009648]; positive regulation of circadian rhythm [GO:0042753]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of inflammatory response [GO:0050729]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; protein acetylation [GO:0006473]; regulation of circadian rhythm [GO:0042752]; regulation of DNA-templated transcription [GO:0006355]; regulation of hair cycle [GO:0042634]; regulation of insulin secretion [GO:0050796]; regulation of transcription by RNA polymerase II [GO:0006357]; regulation of type B pancreatic cell development [GO:2000074]; response to redox state [GO:0051775]; signal transduction [GO:0007165]; spermatogenesis [GO:0007283]
|
chromatin [GO:0000785]; chromatoid body [GO:0033391]; chromosome [GO:0005694]; CLOCK-BMAL transcription complex [GO:1990513]; cytosol [GO:0005829]; intracellular membrane-bounded organelle [GO:0043231]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
chromatin DNA binding [GO:0031490]; 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]; E-box binding [GO:0070888]; histone acetyltransferase activity [GO:0004402]; protein dimerization activity [GO:0046983]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF00010;PF00989;PF14598;
|
4.10.280.10;3.30.450.20;
| null |
PTM: Ubiquitinated, leading to its proteasomal degradation. {ECO:0000250|UniProtKB:O08785}.; PTM: O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-BMAL1 heterodimer thereby increasing CLOCK-BMAL1-mediated transcriptional activation of PER1/2/3 and CRY1/2. {ECO:0000250|UniProtKB:O08785}.; PTM: Phosphorylation is dependent on the CLOCK-BMAL1 heterodimer formation. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver. May be phosphorylated by CSNK1D and CKSN1E. {ECO:0000269|PubMed:24235147}.; PTM: Sumoylation enhances its transcriptional activity and interaction with ESR1, resulting in up-regulation of ESR1 activity. Estrogen stimulates sumoylation. Desumoylation by SENP1 negatively regulates its transcriptional activity. Sumoylation stimulates cell proliferation and increases the proportion of S phase cells in breast cancer cell lines. {ECO:0000269|PubMed:23160374}.; PTM: Undergoes lysosome-mediated degradation in a time-dependent manner in the liver. {ECO:0000250|UniProtKB:O08785}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:23160374, ECO:0000269|PubMed:28985504}. Cytoplasm {ECO:0000250|UniProtKB:O08785}. Cytoplasm, cytosol {ECO:0000269|PubMed:28985504}. Note=Shuttling between the cytoplasm and the nucleus is under circadian regulation and is BMAL1-dependent. Phosphorylated form located in the nucleus while the nonphosphorylated form found only in the cytoplasm. Sequestered to the cytoplasm in the presence of ID2 (By similarity). Localizes to sites of DNA damage in a H2AX-independent manner. {ECO:0000250|UniProtKB:O08785, ECO:0000269|PubMed:21659603}.
|
CATALYTIC ACTIVITY: Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48;
| null | null | null | null |
FUNCTION: Transcriptional activator 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 the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region (PubMed:21980503). The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (By similarity). {ECO:0000250|UniProtKB:O08785, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503, ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}.
|
Homo sapiens (Human)
|
O15519
|
CFLAR_HUMAN
|
MSAEVIHQVEEALDTDEKEMLLFLCRDVAIDVVPPNVRDLLDILRERGKLSVGDLAELLYRVRRFDLLKRILKMDRKAVETHLLRNPHLVSDYRVLMAEIGEDLDKSDVSSLIFLMKDYMGRGKISKEKSFLDLVVELEKLNLVAPDQLDLLEKCLKNIHRIDLKTKIQKYKQSVQGAGTSYRNVLQAAIQKSLKDPSNNFRLHNGRSKEQRLKEQLGAQQEPVKKSIQESEAFLPQSIPEERYKMKSKPLGICLIIDCIGNETELLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMPEHRDYDSFVCVLVSRGGSQSVYGVDQTHSGLPLHHIRRMFMGDSCPYLAGKPKMFFIQNYVVSEGQLEDSSLLEVDGPAMKNVEFKAQKRGLCTVHREADFFWSLCTADMSLLEQSHSSPSLYLQCLSQKLRQERKRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT
| null | null |
apoptotic process [GO:0006915]; cellular response to dexamethasone stimulus [GO:0071549]; cellular response to epidermal growth factor stimulus [GO:0071364]; cellular response to estradiol stimulus [GO:0071392]; cellular response to hypoxia [GO:0071456]; cellular response to insulin stimulus [GO:0032869]; cellular response to nitric oxide [GO:0071732]; erythrocyte differentiation [GO:0030218]; execution phase of apoptosis [GO:0097194]; keratinocyte differentiation [GO:0030216]; 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 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 reactive oxygen species biosynthetic process [GO:1903427]; neuron differentiation [GO:0030182]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; 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 necroptotic process [GO:0060544]; regulation of skeletal muscle satellite cell proliferation [GO:0014842]; 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]; cytosol [GO:0005829]; death-inducing signaling complex [GO:0031264]; ripoptosome [GO:0097342]
|
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]; 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 subunit p43 and p12. {ECO:0000269|PubMed:9228018}.
| 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. {ECO:0000269|PubMed:9880531}.
|
Homo sapiens (Human)
|
O15520
|
FGF10_HUMAN
|
MWKWILTHCASAFPHLPGCCCCCFLLLFLVSSVPVTCQALGQDMVSPEATNSSSSSFSSPSSAGRHVRSYNHLQGDVRWRKLFSFTKYFLKIEKNGKVSGTKKENCPYSILEITSVEIGVVAVKAINSNYYLAMNKKGKLYGSKEFNNDCKLKERIEENGYNTYASFNWQHNGRQMYVALNGKGAPRRGQKTRRKNTSAHFLPMVVHS
| null | null |
actin cytoskeleton organization [GO:0030036]; angiogenesis [GO:0001525]; animal organ morphogenesis [GO:0009887]; blood vessel remodeling [GO:0001974]; branch elongation involved in salivary gland morphogenesis [GO:0060667]; branching morphogenesis of an epithelial tube [GO:0048754]; bronchiole morphogenesis [GO:0060436]; bud elongation involved in lung branching [GO:0060449]; bud outgrowth involved in lung branching [GO:0060447]; cell differentiation [GO:0030154]; determination of left/right symmetry [GO:0007368]; embryonic camera-type eye development [GO:0031076]; embryonic digestive tract morphogenesis [GO:0048557]; embryonic genitalia morphogenesis [GO:0030538]; embryonic pattern specification [GO:0009880]; endothelial cell proliferation [GO:0001935]; epithelial cell proliferation [GO:0050673]; epithelial cell proliferation involved in salivary gland morphogenesis [GO:0060664]; ERK1 and ERK2 cascade [GO:0070371]; establishment of mitotic spindle orientation [GO:0000132]; extrinsic apoptotic signaling pathway in absence of ligand [GO:0097192]; female genitalia morphogenesis [GO:0048807]; fibroblast growth factor receptor apoptotic signaling pathway [GO:1902178]; fibroblast growth factor receptor signaling pathway [GO:0008543]; fibroblast growth factor receptor signaling pathway involved in mammary gland specification [GO:0060595]; fibroblast proliferation [GO:0048144]; hair follicle morphogenesis [GO:0031069]; Harderian gland development [GO:0070384]; induction of positive chemotaxis [GO:0050930]; keratinocyte proliferation [GO:0043616]; lacrimal gland development [GO:0032808]; limb bud formation [GO:0060174]; limb development [GO:0060173]; lung epithelium development [GO:0060428]; lung proximal/distal axis specification [GO:0061115]; lung saccule development [GO:0060430]; male genitalia morphogenesis [GO:0048808]; mammary gland bud formation [GO:0060615]; mesenchymal cell differentiation involved in lung development [GO:0060915]; mesenchymal-epithelial cell signaling involved in lung development [GO:0060496]; mesonephros development [GO:0001823]; metanephros development [GO:0001656]; metanephros morphogenesis [GO:0003338]; muscle cell fate commitment [GO:0042693]; negative regulation of epithelial cell differentiation [GO:0030857]; negative regulation of extrinsic apoptotic signaling pathway in absence of ligand [GO:2001240]; negative regulation of stem cell proliferation [GO:2000647]; odontogenesis of dentin-containing tooth [GO:0042475]; organ induction [GO:0001759]; otic vesicle formation [GO:0030916]; pancreas development [GO:0031016]; pituitary gland development [GO:0021983]; positive chemotaxis [GO:0050918]; positive regulation of ATP-dependent activity [GO:0032781]; positive regulation of canonical Wnt signaling pathway [GO:0090263]; positive regulation of DNA repair [GO:0045739]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of epithelial cell migration [GO:0010634]; positive regulation of epithelial cell proliferation [GO:0050679]; positive regulation of epithelial cell proliferation involved in wound healing [GO:0060054]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of G1/S transition of mitotic cell cycle [GO:1900087]; positive regulation of gene expression [GO:0010628]; positive regulation of hair follicle cell proliferation [GO:0071338]; positive regulation of keratinocyte migration [GO:0051549]; positive regulation of keratinocyte proliferation [GO:0010838]; positive regulation of lymphocyte proliferation [GO:0050671]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of Notch signaling pathway [GO:0045747]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of Ras protein signal transduction [GO:0046579]; positive regulation of stem cell proliferation [GO:2000648]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of urothelial cell proliferation [GO:0050677]; positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949]; positive regulation of white fat cell proliferation [GO:0070352]; prostatic bud formation [GO:0060513]; protein localization to cell surface [GO:0034394]; radial glial cell differentiation [GO:0060019]; regulation of activin receptor signaling pathway [GO:0032925]; regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling [GO:0060665]; regulation of saliva secretion [GO:0046877]; regulation of smoothened signaling pathway [GO:0008589]; response to estradiol [GO:0032355]; response to lipopolysaccharide [GO:0032496]; salivary gland development [GO:0007431]; secretion by lung epithelial cell involved in lung growth [GO:0061033]; semicircular canal fusion [GO:0060879]; smooth muscle cell differentiation [GO:0051145]; somatic stem cell population maintenance [GO:0035019]; spleen development [GO:0048536]; stem cell proliferation [GO:0072089]; submandibular salivary gland formation [GO:0060661]; tear secretion [GO:0070075]; thymus development [GO:0048538]; thyroid gland development [GO:0030878]; tissue regeneration [GO:0042246]; type II pneumocyte differentiation [GO:0060510]; urothelial cell proliferation [GO:0050674]; vascular endothelial growth factor receptor signaling pathway [GO:0048010]; white fat cell differentiation [GO:0050872]; white fat cell proliferation [GO:0070343]; Wnt signaling pathway [GO:0016055]; wound healing [GO:0042060]
|
cell surface [GO:0009986]; cytoplasm [GO:0005737]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
|
chemoattractant activity [GO:0042056]; fibroblast growth factor receptor binding [GO:0005104]; growth factor activity [GO:0008083]; heparin binding [GO:0008201]; type 2 fibroblast growth factor receptor binding [GO:0005111]
|
PF00167;
|
2.80.10.50;
|
Heparin-binding growth factors family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. May play a role in wound healing. {ECO:0000269|PubMed:16597617}.
|
Homo sapiens (Human)
|
O15522
|
NKX28_HUMAN
|
MATSGRLSFTVRSLLDLPEQDAQHLPRREPEPRAPQPDPCAAWLDSERGHYPSSDESSLETSPPDSSQRPSARPASPGSDAEKRKKRRVLFSKAQTLELERRFRQQRYLSAPEREQLASLLRLTPTQVKIWFQNHRYKLKRARAPGAAESPDLAASAELHAAPGLLRRVVVPVLVRDGQPCGGGGGGEVGTAAAQEKCGAPPAAACPLPGYPAFGPGSALGLFPAYQHLASPALVSWNW
| null | null |
axonogenesis [GO:0007409]; cell differentiation [GO:0030154]; DNA-templated transcription [GO:0006351]; epithelial cell proliferation [GO:0050673]; liver development [GO:0001889]; lung development [GO:0030324]; negative regulation of epithelial cell proliferation [GO:0050680]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of transcription by RNA polymerase II [GO:0006357]; transcription by RNA polymerase II [GO:0006366]
|
chromatin [GO:0000785]; 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]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF00046;
|
1.10.10.60;
|
NK-2 homeobox family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
| null | null | null | null | null | null |
Homo sapiens (Human)
|
O15523
|
DDX3Y_HUMAN
|
MSHVVVKNDPELDQQLANLDLNSEKQSGGASTASKGRYIPPHLRNREASKGFHDKDSSGWSCSKDKDAYSSFGSRDSRGKPGYFSERGSGSRGRFDDRGRSDYDGIGNRERPGFGRFERSGHSRWCDKSVEDDWSKPLPPSERLEQELFSGGNTGINFEKYDDIPVEATGSNCPPHIENFSDIDMGEIIMGNIELTRYTRPTPVQKHAIPIIKGKRDLMACAQTGSGKTAAFLLPILSQIYTDGPGEALKAVKENGRYGRRKQYPISLVLAPTRELAVQIYEEARKFSYRSRVRPCVVYGGADIGQQIRDLERGCHLLVATPGRLVDMMERGKIGLDFCKYLVLDEADRMLDMGFEPQIRRIVEQDTMPPKGVRHTMMFSATFPKEIQMLARDFLDEYIFLAVGRVGSTSENITQKVVWVEDLDKRSFLLDILGATGSDSLTLVFVETKKGADSLEDFLYHEGYACTSIHGDRSQRDREEALHQFRSGKSPILVATAVAARGLDISNVRHVINFDLPSDIEEYVHRIGRTGRVGNLGLATSFFNEKNMNITKDLLDLLVEAKQEVPSWLENMAYEHHYKGGSRGRSKSNRFSGGFGARDYRQSSGSSSSGFGASRGSSSRSGGGGYGNSRGFGGGGYGGFYNSDGYGGNYNSQGVDWWGN
|
3.6.4.13
| null |
cell differentiation [GO:0030154]; gamete generation [GO:0007276]; negative regulation of gene expression [GO:0010629]
|
cytosol [GO:0005829]; membrane [GO:0016020]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; P granule [GO:0043186]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; DNA binding [GO:0003677]; mRNA binding [GO:0003729]; RNA helicase activity [GO:0003724]
|
PF00270;PF00271;
|
3.40.50.300;
|
DEAD box helicase family, DDX3/DED1 subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15294876, ECO:0000269|PubMed:15383328}. Nucleus {ECO:0000269|PubMed:15383328}. Note=Shuttles between the nucleus and the cytoplasm in an XPO1-dependent manner.
|
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;
| null | null | null | null |
FUNCTION: Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway (By similarity). {ECO:0000250|UniProtKB:Q62095}.
|
Homo sapiens (Human)
|
O15524
|
SOCS1_HUMAN
|
MVAHNQVAADNAVSTAAEPRRRPEPSSSSSSSPAAPARPRPCPAVPAPAPGDTHFRTFRSHADYRRITRASALLDACGFYWGPLSVHGAHERLRAEPVGTFLVRDSRQRNCFFALSVKMASGPTSIRVHFQAGRFHLDGSRESFDCLFELLEHYVAAPRRMLGAPLRQRRVRPLQELCRQRIVATVGRENLARIPLNPVLRDYLSSFPFQI
| null | null |
cellular response to amino acid stimulus [GO:0071230]; cytokine-mediated signaling pathway [GO:0019221]; fat cell differentiation [GO:0045444]; intracellular signal transduction [GO:0035556]; macrophage differentiation [GO:0030225]; negative regulation of CD8-positive, alpha-beta T cell differentiation [GO:0043377]; negative regulation of insulin receptor signaling pathway [GO:0046627]; negative regulation of receptor signaling pathway via JAK-STAT [GO:0046426]; negative regulation of tyrosine phosphorylation of STAT protein [GO:0042532]; phosphatidylinositol phosphate biosynthetic process [GO:0046854]; positive regulation of CD4-positive, alpha-beta T cell differentiation [GO:0043372]; positive regulation of regulatory T cell differentiation [GO:0045591]; protein ubiquitination [GO:0016567]; receptor signaling pathway via JAK-STAT [GO:0007259]; regulation of cytokine production [GO:0001817]; regulation of protein phosphorylation [GO:0001932]
|
cytoplasm [GO:0005737]; cytoplasmic ribonucleoprotein granule [GO:0036464]; cytoplasmic vesicle [GO:0031410]; cytosol [GO:0005829]; nucleoplasm [GO:0005654]; phosphatidylinositol 3-kinase complex [GO:0005942]
|
1-phosphatidylinositol-3-kinase regulator activity [GO:0046935]; insulin-like growth factor receptor binding [GO:0005159]; kinase inhibitor activity [GO:0019210]; protein kinase binding [GO:0019901]; protein kinase inhibitor activity [GO:0004860]
|
PF00017;PF07525;
|
3.30.505.10;1.10.750.20;
|
SOCS1 family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16410555}. Cytoplasmic vesicle {ECO:0000269|PubMed:16410555}. Note=Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3.
| null | null |
PATHWAY: Protein modification; protein ubiquitination.
| null | null |
FUNCTION: Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF) (PubMed:32499645, PubMed:33087723). Downregulates cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding to JAK proteins and to IFNGR1 and inhibiting their kinase activity. In vitro, suppresses Tec protein-tyrosine activity (PubMed:9341160). Regulates IFN-gamma (IFNG)-mediated sensory neuron survival (By similarity). Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11278610, PubMed:11313480). {ECO:0000250|UniProtKB:O35716, ECO:0000269|PubMed:11278610, ECO:0000269|PubMed:11313480, ECO:0000269|PubMed:32499645, ECO:0000269|PubMed:33087723, ECO:0000269|PubMed:9341160}.
|
Homo sapiens (Human)
|
O15525
|
MAFG_HUMAN
|
MTTPNKGNKALKVKREPGENGTSLTDEELVTMSVRELNQHLRGLSKEEIVQLKQRRRTLKNRGYAASCRVKRVTQKEELEKQKAELQQEVEKLASENASMKLELDALRSKYEALQTFARTVARSPVAPARGPLAAGLGPLVPGKVAATSVITIVKSKTDARS
| null | null |
adult behavior [GO:0030534]; in utero embryonic development [GO:0001701]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of gene expression [GO:0010628]; regulation of cell population proliferation [GO:0042127]; regulation of epidermal cell differentiation [GO:0045604]; regulation of transcription by RNA polymerase II [GO:0006357]
|
nucleoplasm [GO:0005654]; nucleus [GO:0005634]; RNA polymerase II transcription regulator complex [GO:0090575]
|
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]; identical protein binding [GO:0042802]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF03131;
|
1.20.5.170;
|
BZIP family, Maf subfamily
|
PTM: Acetylated in erythroid cells by CREB-binding protein (CBP). Acetylation augments the DNA-binding activity of NFE2, but has no effect on binding NFE2. {ECO:0000269|PubMed:11154691}.; PTM: Sumoylation at Lys-14 is required for active transcriptional repression. {ECO:0000250|UniProtKB:O54790}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:11154691}.
| null | null | null | null | null |
FUNCTION: Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves (PubMed:11154691). However, they seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1 and NFE2L2, and recruiting them to specific DNA-binding sites (PubMed:11154691, PubMed:8932385, PubMed:9421508). Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NFE2L2 transcription factor (PubMed:11154691). Transcription factor, component of erythroid-specific transcription factor NFE2L2 (PubMed:11154691). Activates globin gene expression when associated with NFE2L2 (PubMed:11154691). May be involved in signal transduction of extracellular H(+) (By similarity). {ECO:0000250|UniProtKB:Q76MX4, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:8932385, ECO:0000269|PubMed:9421508}.
|
Homo sapiens (Human)
|
O15527
|
OGG1_HUMAN
|
MPARALLPRRMGHRTLASTPALWASIPCPRSELRLDLVLPSGQSFRWREQSPAHWSGVLADQVWTLTQTEEQLHCTVYRGDKSQASRPTPDELEAVRKYFQLDVTLAQLYHHWGSVDSHFQEVAQKFQGVRLLRQDPIECLFSFICSSNNNIARITGMVERLCQAFGPRLIQLDDVTYHGFPSLQALAGPEVEAHLRKLGLGYRARYVSASARAILEEQGGLAWLQQLRESSYEEAHKALCILPGVGTKVADCICLMALDKPQAVPVDVHMWHIAQRDYSWHPTTSQAKGPSPQTNKELGNFFRSLWGPYAGWAQAVLFSADLRQSRHAQEPPAKRRKGSKGPEG
|
3.2.2.-; 4.2.99.18
| null |
base-excision repair [GO:0006284]; base-excision repair, AP site formation [GO:0006285]; cellular response to cadmium ion [GO:0071276]; cellular response to reactive oxygen species [GO:0034614]; depurination [GO:0045007]; depyrimidination [GO:0045008]; DNA damage response [GO:0006974]; negative regulation of apoptotic process [GO:0043066]; negative regulation of double-strand break repair via single-strand annealing [GO:1901291]; nucleotide-excision repair [GO:0006289]; positive regulation of gene expression via CpG island demethylation [GO:0044029]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of DNA-templated transcription [GO:0006355]; response to estradiol [GO:0032355]; response to ethanol [GO:0045471]; response to folic acid [GO:0051593]; response to light stimulus [GO:0009416]; response to oxidative stress [GO:0006979]; response to radiation [GO:0009314]; response to xenobiotic stimulus [GO:0009410]
|
cytosol [GO:0005829]; mitochondrial matrix [GO:0005759]; nuclear matrix [GO:0016363]; nuclear speck [GO:0016607]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]
|
8-oxo-7,8-dihydroguanine DNA N-glycosylase activity [GO:0034039]; class I DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0140078]; damaged DNA binding [GO:0003684]; endonuclease activity [GO:0004519]; enzyme binding [GO:0019899]; microtubule binding [GO:0008017]; oxidized purine DNA binding [GO:0032357]; oxidized purine nucleobase lesion DNA N-glycosylase activity [GO:0008534]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]
|
PF00730;PF07934;
|
3.30.310.40;1.10.1670.10;
|
Type-1 OGG1 family
| null |
SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000269|PubMed:17148573}. Nucleus speckle {ECO:0000269|PubMed:17148573}. Nucleus matrix {ECO:0000269|PubMed:17148573}. Note=Together with APEX1 is recruited to nuclear speckles in UVA-irradiated cells.; SUBCELLULAR LOCATION: [Isoform 1A]: Nucleus.; SUBCELLULAR LOCATION: [Isoform 2A]: Mitochondrion.
|
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;
| null | null | null | null |
FUNCTION: DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion.
|
Homo sapiens (Human)
|
O15528
|
CP27B_HUMAN
|
MTQTLKYASRVFHRVRWAPELGASLGYREYHSARRSLADIPGPSTPSFLAELFCKGGLSRLHELQVQGAAHFGPVWLASFGTVRTVYVAAPALVEELLRQEGPRPERCSFSPWTEHRRCRQRACGLLTAEGEEWQRLRSLLAPLLLRPQAAARYAGTLNNVVCDLVRRLRRQRGRGTGPPALVRDVAGEFYKFGLEGIAAVLLGSRLGCLEAQVPPDTETFIRAVGSVFVSTLLTMAMPHWLRHLVPGPWGRLCRDWDQMFAFAQRHVERREAEAAMRNGGQPEKDLESGAHLTHFLFREELPAQSILGNVTELLLAGVDTVSNTLSWALYELSRHPEVQTALHSEITAALSPGSSAYPSATVLSQLPLLKAVVKEVLRLYPVVPGNSRVPDKDIHVGDYIIPKNTLVTLCHYATSRDPAQFPEPNSFRPARWLGEGPTPHPFASLPFGFGKRSCMGRRLAELELQMALAQILTHFEVQPEPGAAPVRPKTRTVLVPERSINLQFLDR
|
1.14.15.18
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250|UniProtKB:O35084};
|
bone mineralization [GO:0030282]; C21-steroid hormone biosynthetic process [GO:0006700]; calcitriol biosynthetic process from calciol [GO:0036378]; calcium ion homeostasis [GO:0055074]; calcium ion transport [GO:0006816]; cellular response to peptide hormone stimulus [GO:0071375]; cholesterol metabolic process [GO:0008203]; cortisol metabolic process [GO:0034650]; decidualization [GO:0046697]; G1 to G0 transition [GO:0070314]; glucocorticoid biosynthetic process [GO:0006704]; negative regulation of calcidiol 1-monooxygenase activity [GO:0010956]; negative regulation of cell growth [GO:0030308]; negative regulation of cell population proliferation [GO:0008285]; positive regulation of keratinocyte differentiation [GO:0045618]; positive regulation of vitamin D 24-hydroxylase activity [GO:0010980]; positive regulation of vitamin D receptor signaling pathway [GO:0070564]; regulation of bone mineralization [GO:0030500]; response to estrogen [GO:0043627]; response to lipopolysaccharide [GO:0032496]; response to type II interferon [GO:0034341]; response to vitamin D [GO:0033280]; vitamin D catabolic process [GO:0042369]; vitamin D metabolic process [GO:0042359]; vitamin metabolic process [GO:0006766]
|
cytoplasm [GO:0005737]; mitochondrial inner membrane [GO:0005743]; mitochondrial outer membrane [GO:0005741]; mitochondrion [GO:0005739]
|
calcidiol 1-monooxygenase activity [GO:0004498]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; secalciferol 1-monooxygenase activity [GO:0062185]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Mitochondrion membrane.
|
CATALYTIC ACTIVITY: Reaction=calcidiol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = calcitriol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:20573, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17823, ChEBI:CHEBI:17933, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.14.15.18; Evidence={ECO:0000269|PubMed:10518789, ECO:0000269|PubMed:10566658, ECO:0000269|PubMed:12050193, ECO:0000269|PubMed:22862690, ECO:0000269|PubMed:9486994}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20574; Evidence={ECO:0000305|PubMed:22862690}; CATALYTIC ACTIVITY: Reaction=2 H(+) + O2 + 2 reduced [adrenodoxin] + secalciferol = calcitetrol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:49064, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:28818, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47799; EC=1.14.15.18; Evidence={ECO:0000269|PubMed:10518789}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49065; Evidence={ECO:0000305|PubMed:10518789}; CATALYTIC ACTIVITY: Reaction=25-hydroxy-24-oxocalciol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (1S)-1,25-dihydroxy-24-oxocalciol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:49068, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47805, ChEBI:CHEBI:47812; Evidence={ECO:0000269|PubMed:22862690}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49069; Evidence={ECO:0000305|PubMed:22862690}; CATALYTIC ACTIVITY: Reaction=25-hydroxyvitamin D2 + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 1alpha,25-dihydroxyvitamin D2 + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:49048, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:86319, ChEBI:CHEBI:86320; Evidence={ECO:0000269|PubMed:22862690}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49049; Evidence={ECO:0000305|PubMed:22862690};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.7 uM for 25-hydroxyvitamin D3 {ECO:0000269|PubMed:10518789}; KM=1.1 uM for 24,25-dihydroxyvitamin D3 {ECO:0000269|PubMed:10518789}; KM=0.9 uM for 25-hydroxyvitamin D3 {ECO:0000269|PubMed:22862690}; Vmax=3.9 pmol/min/mg enzyme toward 25-hydroxyvitamin D3 {ECO:0000269|PubMed:10518789}; Vmax=3.2 pmol/min/mg enzyme toward 24,25-dihydroxyvitamin D3 {ECO:0000269|PubMed:10518789}; Vmax=1.3 nmol/min/mg enzyme toward 25-hydroxyvitamin D3 {ECO:0000269|PubMed:22862690};
|
PATHWAY: Hormone biosynthesis; vitamin D biosynthesis. {ECO:0000269|PubMed:9486994}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase involved in vitamin D metabolism and in calcium and phosphorus homeostasis. Catalyzes the rate-limiting step in the activation of vitamin D in the kidney, namely the hydroxylation of 25-hydroxyvitamin D3/calcidiol at the C1alpha-position to form the hormonally active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3/calcitriol that acts via the vitamin D receptor (VDR) (PubMed:10518789, PubMed:10566658, PubMed:12050193, PubMed:22862690, PubMed:9486994). Has 1alpha-hydroxylase activity on vitamin D intermediates of the CYP24A1-mediated inactivation pathway (PubMed:10518789, PubMed:22862690). Converts 24R,25-dihydroxyvitamin D3/secalciferol to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand of VDR. Also active on 25-hydroxyvitamin D2 (PubMed:10518789). 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 FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:22862690). {ECO:0000269|PubMed:10518789, ECO:0000269|PubMed:10566658, ECO:0000269|PubMed:12050193, ECO:0000269|PubMed:22862690, ECO:0000269|PubMed:9486994}.
|
Homo sapiens (Human)
|
O15529
|
GPR42_HUMAN
|
MDTGPDQSYFSGNHWFVFSVYLLTFLVGLPLNLLALVVFVGKLRCRPVAVDVLLLNLTASDLLLLLFLPFRMVEAANGMHWPLPFILCPLSGFIFFTTIYLTALFLAAVSIERFLSVAHPLWYKTRPRLGQAGLVSVACWLLASAHCSVVYVIEFSGDISHSQGTNGTCYLEFRKDQLAILLPVRLEMAVVLFVVPLIITSYCYSRLVWILGRGGSHRRQRRVAGLVAATLLNFLVCFGPYNVSHVVGYICGESPVWRIYVTLLSTLNSCVDPFVYYFSSSGFQADFHELLRRLCGLWGQWQQESSMELKEQKGGEEQRADRPAERKTSEHSQGCGTGGQVACAEN
| null | null |
cellular response to fatty acid [GO:0071398]; G protein-coupled receptor signaling pathway [GO:0007186]
|
plasma membrane [GO:0005886]
|
G protein-coupled receptor activity [GO:0004930]
|
PF00001;
|
1.20.1070.10;
|
G-protein coupled receptor 1 family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: G protein-coupled receptor that is activated by short chain fatty acids (SCFAs), such as propionate. Hence may play a role in the regulation of whole-body energy homeostasis and/or in intestinal immunity. {ECO:0000269|PubMed:19630535}.
|
Homo sapiens (Human)
|
O15530
|
PDPK1_HUMAN
|
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLDSNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQRYQSHPDAAVQ
|
2.7.11.1
| null |
actin cytoskeleton organization [GO:0030036]; activation of protein kinase B activity [GO:0032148]; calcium-mediated signaling [GO:0019722]; cell migration [GO:0016477]; cellular response to epidermal growth factor stimulus [GO:0071364]; cellular response to insulin stimulus [GO:0032869]; epidermal growth factor receptor signaling pathway [GO:0007173]; extrinsic apoptotic signaling pathway [GO:0097191]; hyperosmotic response [GO:0006972]; insulin receptor signaling pathway [GO:0008286]; insulin-like growth factor receptor signaling pathway [GO:0048009]; intracellular signal transduction [GO:0035556]; negative regulation of cardiac muscle cell apoptotic process [GO:0010667]; negative regulation of endothelial cell apoptotic process [GO:2000352]; negative regulation of protein kinase activity [GO:0006469]; negative regulation of toll-like receptor signaling pathway [GO:0034122]; negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512]; peptidyl-threonine phosphorylation [GO:0018107]; positive regulation of angiogenesis [GO:0045766]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0051897]; positive regulation of phospholipase activity [GO:0010518]; positive regulation of protein localization to plasma membrane [GO:1903078]; positive regulation of release of sequestered calcium ion into cytosol [GO:0051281]; positive regulation of sprouting angiogenesis [GO:1903672]; positive regulation of vascular endothelial cell proliferation [GO:1905564]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; regulation of canonical NF-kappaB signal transduction [GO:0043122]; regulation of mast cell degranulation [GO:0043304]; T cell costimulation [GO:0031295]; type B pancreatic cell development [GO:0003323]
|
cell projection [GO:0042995]; cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; cytosol [GO:0005829]; focal adhesion [GO:0005925]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; postsynaptic density [GO:0014069]
|
3-phosphoinositide-dependent protein kinase activity [GO:0004676]; ATP binding [GO:0005524]; phospholipase activator activity [GO:0016004]; phospholipase binding [GO:0043274]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]
|
PF14593;PF00069;
|
2.30.29.30;1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, PDPK1 subfamily
|
PTM: Phosphorylation on Ser-241 in the activation loop is required for full activity. PDPK1 itself can autophosphorylate Ser-241, leading to its own activation. Autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 (By similarity). Tyr-9 phosphorylation is critical for stabilization of both PDPK1 and the PDPK1/SRC complex via HSP90-mediated protection of PDPK1 degradation. Angiotensin II stimulates the tyrosine phosphorylation of PDPK1 in vascular smooth muscle in a calcium- and SRC-dependent manner. Phosphorylated on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin. Palmitate negatively regulates autophosphorylation at Ser-241 and palmitate-induced phosphorylation at Ser-529 and Ser-501 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylation at Thr-354 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-394 and Ser-398 by MAP3K5. {ECO:0000250, ECO:0000269|PubMed:10455013, ECO:0000269|PubMed:11481331, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15743829, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16780920, ECO:0000269|PubMed:22544756, ECO:0000269|Ref.8}.; PTM: Autophosphorylated; autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. {ECO:0000250}.; PTM: Monoubiquitinated in the kinase domain, deubiquitinated by USP4.
|
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Cell junction, focal adhesion. Note=Tyrosine phosphorylation seems to occur only at the cell membrane. Translocates to the cell membrane following insulin stimulation by a mechanism that involves binding to GRB14 and INSR. SRC and HSP90 promote its localization to the cell membrane. Its nuclear localization is dependent on its association with PTPN6 and its phosphorylation at Ser-396. Restricted to the nucleus in neuronal cells while in non-neuronal cells it is found in the cytoplasm. The Ser-241 phosphorylated form is distributed along the perinuclear region in neuronal cells while in non-neuronal cells it is found in both the nucleus and the cytoplasm. IGF1 transiently increases phosphorylation at Ser-241 of neuronal PDPK1, resulting in its translocation to other cellular compartments. The tyrosine-phosphorylated form colocalizes with PTK2B in focal adhesions after angiotensin II stimulation.
|
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: Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive. {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.
|
Homo sapiens (Human)
|
O15533
|
TPSN_HUMAN
|
MKSLSLLLAVALGLATAVSAGPAVIECWFVEDASGKGLAKRPGALLLRQGPGEPPPRPDLDPELYLSVHDPAGALQAAFRRYPRGAPAPHCEMSRFVPLPASAKWASGLTPAQNCPRALDGAWLMVSISSPVLSLSSLLRPQPEPQQEPVLITMATVVLTVLTHTPAPRVRLGQDALLDLSFAYMPPTSEAASSLAPGPPPFGLEWRRQHLGKGHLLLAATPGLNGQMPAAQEGAVAFAAWDDDEPWGPWTGNGTFWLPTVQPFQEGTYLATIHLPYLQGQVTLELAVYKPPKVSLMPATLARAAPGEAPPELLCLVSHFYPSGGLEVEWELRGGPGGRSQKAEGQRWLSALRHHSDGSVSLSGHLQPPPVTTEQHGARYACRIHHPSLPASGRSAEVTLEVAGLSGPSLEDSVGLFLSAFLLLGLFKALGWAAVYLSTCKDSKKKAE
| null | null |
antigen processing and presentation of endogenous peptide antigen via MHC class I [GO:0019885]; MHC class Ib protein complex assembly [GO:0002398]; peptide antigen assembly with MHC class I protein complex [GO:0002502]; peptide antigen stabilization [GO:0050823]; protein-containing complex assembly [GO:0065003]; regulation of gene expression [GO:0010468]; regulation of protein complex stability [GO:0061635]; retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum [GO:0006890]
|
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; endoplasmic reticulum-Golgi intermediate compartment membrane [GO:0033116]; Golgi membrane [GO:0000139]; lumenal side of endoplasmic reticulum membrane [GO:0098553]; MHC class I peptide loading complex [GO:0042824]; phagocytic vesicle membrane [GO:0030670]; Tapasin-ERp57 complex [GO:0061779]
|
MHC class I protein binding [GO:0042288]; MHC class I protein complex binding [GO:0023024]; molecular adaptor activity [GO:0060090]; peptide antigen binding [GO:0042605]; protein folding chaperone [GO:0044183]; TAP complex binding [GO:0062061]; TAP1 binding [GO:0046978]; TAP2 binding [GO:0046979]; unfolded protein binding [GO:0051082]
|
PF07654;
|
2.60.40.10;
| null | null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Involved in the association of MHC class I with transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading). {ECO:0000269|PubMed:10636848, ECO:0000269|PubMed:12582157, ECO:0000269|PubMed:21263072, ECO:0000269|PubMed:26611325}.
|
Homo sapiens (Human)
|
O15534
|
PER1_HUMAN
|
MSGPLEGADGGGDPRPGESFCPGGVPSPGPPQHRPCPGPSLADDTDANSNGSSGNESNGHESRGASQRSSHSSSSGNGKDSALLETTESSKSTNSQSPSPPSSSIAYSLLSASSEQDNPSTSGCSSEQSARARTQKELMTALRELKLRLPPERRGKGRSGTLATLQYALACVKQVQANQEYYQQWSLEEGEPCSMDMSTYTLEELEHITSEYTLQNQDTFSVAVSFLTGRIVYISEQAAVLLRCKRDVFRGTRFSELLAPQDVGVFYGSTAPSRLPTWGTGASAGSGLRDFTQEKSVFCRIRGGPDRDPGPRYQPFRLTPYVTKIRVSDGAPAQPCCLLIAERIHSGYEAPRIPPDKRIFTTRHTPSCLFQDVDERAAPLLGYLPQDLLGAPVLLFLHPEDRPLMLAIHKKILQLAGQPFDHSPIRFCARNGEYVTMDTSWAGFVHPWSRKVAFVLGRHKVRTAPLNEDVFTPPAPSPAPSLDTDIQELSEQIHRLLLQPVHSPSPTGLCGVGAVTSPGPLHSPGSSSDSNGGDAEGPGPPAPVTFQQICKDVHLVKHQGQQLFIESRARPQSRPRLPATGTFKAKALPCQSPDPELEAGSAPVQAPLALVPEEAERKEASSCSYQQINCLDSILRYLESCNLPSTTKRKCASSSSYTTSSASDDDRQRTGPVSVGTKKDPPSAALSGEGATPRKEPVVGGTLSPLALANKAESVVSVTSQCSFSSTIVHVGDKKPPESDIIMMEDLPGLAPGPAPSPAPSPTVAPDPAPDAYRPVGLTKAVLSLHTQKEEQAFLSRFRDLGRLRGLDSSSTAPSALGERGCHHGPAPPSRRHHCRSKAKRSRHHQNPRAEAPCYVSHPSPVPPSTPWPTPPATTPFPAVVQPYPLPVFSPRGGPQPLPPAPTSVPPAAFPAPLVTPMVALVLPNYLFPTPSSYPYGALQTPAEGPPTPASHSPSPSLPALAPSPPHRPDSPLFNSRCSSPLQLNLLQLEELPRAEGAAVAGGPGSSAGPPPPSAEAAEPEARLAEVTESSNQDALSGSSDLLELLLQEDSRSGTGSAASGSLGSGLGSGSGSGSHEGGSTSASITRSSQSSHTSKYFGSIDSSEAEAGAARGGAEPGDQVIKYVLQDPIWLLMANADQRVMMTYQVPSRDMTSVLKQDRERLRAMQKQQPRFSEDQRRELGAVHSWVRKGQLPRALDVMACVDCGSSTQDPGHPDDPLFSELDGLGLEPMEEGGGEQGSSGGGSGEGEGCEEAQGGAKASSSQDLAMEEEEEGRSSSSPALPTAGNCTS
| 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 [GO:0009649]; 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]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; 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:15917222}.; PTM: Ubiquitinated; requires phosphorylation by CSNK1E and interaction with BTRC and FBXW11. Deubiquitinated by USP2 (By similarity). {ECO:0000250|UniProtKB:O35973, ECO:0000269|PubMed:15917222}.
|
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 (By similarity). {ECO:0000250}.
| 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:24005054}.
|
Homo sapiens (Human)
|
O15535
|
ZSC9_HUMAN
|
MNTNSKEVLSLGVQVPEAWEELLTMKVEAKSHLQWQESRLKRSNPLAREIFRRHFRQLCYQETPGPREALTRLQELCYQWLRPHVSTKEQILDLLVLEQFLSILPKELQGWVREHCPESGEEAVILLEDLERELDEPQHEMVAHRHRQEVLCKEMVPLAEQTPLTLQSQPKEPQLTCDSAQKCHSIGETDEVTKTEDRELVLRKDCPKIVEPHGKMFNEQTWEVSQQDPSHGEVGEHKDRIERQWGNLLGEGQHKCDECGKSFTQSSGLIRHQRIHTGERPYECNECGKAFSRSSGLFNHRGIHNIQKRYHCKECGKVFSQSAGLIQHQRIHKGEKPYQCSQCSKSYSRRSFLIEHQRSHTGERPHQCIECGKSFNRHCNLIRHQKIHTVAELV
| null | null |
regulation of transcription by RNA polymerase II [GO:0006357]
|
nucleus [GO:0005634]
|
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]; sequence-specific double-stranded DNA binding [GO:1990837]
|
PF02023;PF00096;
|
3.30.160.60;1.10.4020.10;
|
Krueppel C2H2-type zinc-finger protein family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00187}.
| null | null | null | null | null |
FUNCTION: May be involved in transcriptional regulation.
|
Homo sapiens (Human)
|
O15537
|
XLRS1_HUMAN
|
MSRKIEGFLLLLLFGYEATLGLSSTEDEGEDPWYQKACKCDCQGGPNALWSAGATSLDCIPECPYHKPLGFESGEVTPDQITCSNPEQYVGWYSSWTANKARLNSQGFGCAWLSKFQDSSQWLQIDLKEIKVISGILTQGRCDIDEWMTKYSVQYRTDERLNWIYYKDQTGNNRVFYGNSDRTSTVQNLLRPPIISRFIRLIPLGWHVRIAIRMELLECVSKCA
| null | null |
adaptation of rhodopsin mediated signaling [GO:0016062]; cell adhesion [GO:0007155]; eye development [GO:0001654]; protein homooligomerization [GO:0051260]; retina layer formation [GO:0010842]; visual perception [GO:0007601]
|
external side of plasma membrane [GO:0009897]; extracellular space [GO:0005615]; neuron to neuron synapse [GO:0098984]; photoreceptor inner segment [GO:0001917]; protein-containing complex [GO:0032991]
|
phosphatidylinositol-3,4-bisphosphate binding [GO:0043325]; phosphatidylserine binding [GO:0001786]; protein-containing complex binding [GO:0044877]
|
PF00754;
|
2.60.120.260;
| null | null |
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10915776, ECO:0000269|PubMed:19849666, ECO:0000269|PubMed:26812435}. Cell membrane {ECO:0000250|UniProtKB:Q9Z1L4}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9Z1L4}; Extracellular side {ECO:0000250|UniProtKB:Q9Z1L4}. Note=Binds to phosphatidylserine-containing lipid membranes and embeds itself partially into the lipid bilayer. Lipid-binding requires the presence of Ca(2+) ions. {ECO:0000250|UniProtKB:Q9Z1L4}.
| null | null | null | null | null |
FUNCTION: Binds negatively charged membrane lipids, such as phosphatidylserine and phosphoinositides (By similarity). May play a role in cell-cell adhesion processes in the retina, via homomeric interaction between octamers present on the surface of two neighboring cells (PubMed:27114531). Required for normal structure and function of the retina (PubMed:19093009). {ECO:0000250|UniProtKB:Q9Z1L4, ECO:0000269|PubMed:19093009, ECO:0000305|PubMed:27114531}.
|
Homo sapiens (Human)
|
O15540
|
FABP7_HUMAN
|
MVEAFCATWKLTNSQNFDEYMKALGVGFATRQVGNVTKPTVIISQEGDKVVIRTLSTFKNTEISFQLGEEFDETTADDRNCKSVVSLDGDKLVHIQKWDGKETNFVREIKDGKMVMTLTFGDVVAVRHYEKA
| null | null |
epithelial cell proliferation [GO:0050673]; fatty acid transport [GO:0015908]; negative regulation of cell population proliferation [GO:0008285]; nervous system development [GO:0007399]
|
cytosol [GO:0005829]; nucleus [GO:0005634]
|
fatty acid binding [GO:0005504]; lipid binding [GO:0008289]
|
PF00061;
|
2.40.128.20;
|
Calycin superfamily, Fatty-acid binding protein (FABP) family
| null |
SUBCELLULAR LOCATION: Cytoplasm.
| null | null | null | null | null |
FUNCTION: B-FABP could be involved in the transport of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development. It is required for the establishment of the radial glial fiber system in developing brain, a system that is necessary for the migration of immature neurons to establish cortical layers (By similarity). {ECO:0000250}.
|
Homo sapiens (Human)
|
O15541
|
R113A_HUMAN
|
MAEQLSPGKAVDQVCTFLFKKPGRKGAAGRRKRPACDPEPGESGSSSDEGCTVVRPEKKRVTHNPMIQKTRDSGKQKAAYGDLSSEEEEENEPESLGVVYKSTRSAKPVGPEDMGATAVYELDTEKERDAQAIFERSQKIQEELRGKEDDKIYRGINNYQKYMKPKDTSMGNASSGMVRKGPIRAPEHLRATVRWDYQPDICKDYKETGFCGFGDSCKFLHDRSDYKHGWQIERELDEGRYGVYEDENYEVGSDDEEIPFKCFICRQSFQNPVVTKCRHYFCESCALQHFRTTPRCYVCDQQTNGVFNPAKELIAKLEKHRATGEGGASDLPEDPDEDAIPIT
|
2.3.2.27
| null |
DNA repair [GO:0006281]; mRNA splicing, via spliceosome [GO:0000398]; negative regulation of chemokine-mediated signaling pathway [GO:0070100]; protein ubiquitination [GO:0016567]; snoRNA splicing [GO:0034247]
|
nuclear speck [GO:0016607]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; U2-type precatalytic spliceosome [GO:0071005]; U2-type spliceosomal complex [GO:0005684]
|
metal ion binding [GO:0046872]; ubiquitin protein ligase activity [GO:0061630]
|
PF13920;PF00642;
|
3.30.40.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316}. Nucleus speckle {ECO:0000269|PubMed:29144457}. Note=Colocalizes with ASCC2 in nuclear foci after DNA damage by alkylating agents. In the absence of DNA damage, colocalizes with the spliceosome components SNRNP200/BRR2 and PRPF8 in nuclear speckles. {ECO:0000269|PubMed:29144457}.
|
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; Evidence={ECO:0000269|PubMed:28978524, ECO:0000269|PubMed:29144457};
| null |
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:28978524, ECO:0000269|PubMed:29144457}.
| null | null |
FUNCTION: Required for pre-mRNA splicing as component of the spliceosome (PubMed:29360106, PubMed:29361316). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin onto target proteins (PubMed:28978524, PubMed:29144457). Catalyzes polyubiquitination of SNRNP200/BRR2 with non-canonical 'Lys-63'-linked polyubiquitin chains (PubMed:29144457). Plays a role in DNA repair via its role in the synthesis of 'Lys-63'-linked polyubiquitin chains that recruit ALKBH3 and the ASCC complex to sites of DNA damage by alkylating agents (PubMed:29144457). Ubiquitinates CXCR4, leading to its degradation, and thereby contributes to the termination of CXCR4 signaling (PubMed:28978524). {ECO:0000269|PubMed:28978524, ECO:0000269|PubMed:29144457, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000305|PubMed:33509932}.
|
Homo sapiens (Human)
|
O15547
|
P2RX6_HUMAN
|
MCPQLAGAGSMGSPGATTGWGLLDYKTEKYVMTRNWRVGALQRLLQFGIVVYVVGWALLAKKGYQERDLEPQFSIITKLKGVSVTQIKELGNRLWDVADFVKPPQGENVFFLVTNFLVTPAQVQGRCPEHPSVPLANCWVDEDCPEGEGGTHSHGVKTGQCVVFNGTHRTCEIWSWCPVESGVVPSRPLLAQAQNFTLFIKNTVTFSKFNFSKSNALETWDPTYFKHCRYEPQFSPYCPVFRIGDLVAKAGGTFEDLALLGGSVGIRVHWDCDLDTGDSGCWPHYSFQLQEKSYNFRTATHWWEQPGVEARTLLKLYGIRFDILVTGQAGKFGLIPTAVTLGTGAAWLGVVTFFCDLLLLYVDREAHFYWRTKYEEAKAPKATANSVWRELALASQARLAECLRRSSAPAPTATAAGSQTQTPGWPCPSSDTHLPTHSGSL
| null | null |
calcium ion transmembrane transport [GO:0070588]; muscle contraction [GO:0006936]; response to ATP [GO:0033198]; signal transduction [GO:0007165]
|
cell junction [GO:0030054]; cytoplasm [GO:0005737]; dendritic spine [GO:0043197]; glutamatergic synapse [GO:0098978]; neuronal cell body [GO:0043025]; parallel fiber to Purkinje cell synapse [GO:0098688]; plasma membrane [GO:0005886]; postsynaptic specialization membrane [GO:0099634]; receptor complex [GO:0043235]
|
ATP binding [GO:0005524]; channel activity [GO:0015267]; extracellularly ATP-gated monoatomic cation channel activity [GO:0004931]; protein-containing complex binding [GO:0044877]; purinergic nucleotide receptor activity [GO:0001614]; transmembrane signaling receptor activity [GO:0004888]
|
PF00864;
|
1.10.287.940;2.60.490.10;
|
P2X receptor family
|
PTM: N-glycosylated. {ECO:0000269|PubMed:15657042}.
|
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
| null | null | null | null | null |
FUNCTION: Receptor for ATP that acts as a ligand-gated ion channel. {ECO:0000250}.
|
Homo sapiens (Human)
|
O15550
|
KDM6A_HUMAN
|
MKSCGVSLATAAAAAAAFGDEEKKMAAGKASGESEEASPSLTAEEREALGGLDSRLFGFVRFHEDGARTKALLGKAVRCYESLILKAEGKVESDFFCQLGHFNLLLEDYPKALSAYQRYYSLQSDYWKNAAFLYGLGLVYFHYNAFQWAIKAFQEVLYVDPSFCRAKEIHLRLGLMFKVNTDYESSLKHFQLALVDCNPCTLSNAEIQFHIAHLYETQRKYHSAKEAYEQLLQTENLSAQVKATVLQQLGWMHHTVDLLGDKATKESYAIQYLQKSLEADPNSGQSWYFLGRCYSSIGKVQDAFISYRQSIDKSEASADTWCSIGVLYQQQNQPMDALQAYICAVQLDHGHAAAWMDLGTLYESCNQPQDAIKCYLNATRSKSCSNTSALAARIKYLQAQLCNLPQGSLQNKTKLLPSIEEAWSLPIPAELTSRQGAMNTAQQNTSDNWSGGHAVSHPPVQQQAHSWCLTPQKLQHLEQLRANRNNLNPAQKLMLEQLESQFVLMQQHQMRPTGVAQVRSTGIPNGPTADSSLPTNSVSGQQPQLALTRVPSVSQPGVRPACPGQPLANGPFSAGHVPCSTSRTLGSTDTILIGNNHITGSGSNGNVPYLQRNALTLPHNRTNLTSSAEEPWKNQLSNSTQGLHKGQSSHSAGPNGERPLSSTGPSQHLQAAGSGIQNQNGHPTLPSNSVTQGAALNHLSSHTATSGGQQGITLTKESKPSGNILTVPETSRHTGETPNSTASVEGLPNHVHQMTADAVCSPSHGDSKSPGLLSSDNPQLSALLMGKANNNVGTGTCDKVNNIHPAVHTKTDNSVASSPSSAISTATPSPKSTEQTTTNSVTSLNSPHSGLHTINGEGMEESQSPMKTDLLLVNHKPSPQIIPSMSVSIYPSSAEVLKACRNLGKNGLSNSSILLDKCPPPRPPSSPYPPLPKDKLNPPTPSIYLENKRDAFFPPLHQFCTNPNNPVTVIRGLAGALKLDLGLFSTKTLVEANNEHMVEVRTQLLQPADENWDPTGTKKIWHCESNRSHTTIAKYAQYQASSFQESLREENEKRSHHKDHSDSESTSSDNSGRRRKGPFKTIKFGTNIDLSDDKKWKLQLHELTKLPAFVRVVSAGNLLSHVGHTILGMNTVQLYMKVPGSRTPGHQENNNFCSVNINIGPGDCEWFVVPEGYWGVLNDFCEKNNLNFLMGSWWPNLEDLYEANVPVYRFIQRPGDLVWINAGTVHWVQAIGWCNNIAWNVGPLTACQYKLAVERYEWNKLQSVKSIVPMVHLSWNMARNIKVSDPKLFEMIKYCLLRTLKQCQTLREALIAAGKEIIWHGRTKEEPAHYCSICEVEVFDLLFVTNESNSRKTYIVHCQDCARKTSGNLENFVVLEQYKMEDLMQVYDQFTLAPPLPSASS
|
1.14.11.68
|
COFACTOR: Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; Evidence={ECO:0000269|PubMed:17761849}; COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:17761849};
|
chromatin remodeling [GO:0006338]; heart development [GO:0007507]; regulation of gene expression [GO:0010468]
|
histone methyltransferase complex [GO:0035097]; MLL3/4 complex [GO:0044666]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
chromatin DNA binding [GO:0031490]; histone demethylase activity [GO:0032452]; histone H3K27me2/H3K27me3 demethylase activity [GO:0071558]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]
|
PF02373;PF21322;PF21326;PF13432;PF13181;
|
1.20.58.1370;2.10.110.20;2.60.120.650;1.25.40.10;
|
UTX family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=2 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(27)-[histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + N(6)-methyl-L-lysyl(27)-[histone H3] + 2 succinate; Xref=Rhea:RHEA:60224, Rhea:RHEA-COMP:15535, Rhea:RHEA-COMP:15544, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:61929, ChEBI:CHEBI:61961; EC=1.14.11.68; Evidence={ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914};
| null | null | null | null |
FUNCTION: Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17761849, PubMed:17851529). Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17713478, PubMed:17761849, PubMed:17851529). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (PubMed:17761849). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity). {ECO:0000250|UniProtKB:O70546, ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914}.
|
Homo sapiens (Human)
|
O15551
|
CLD3_HUMAN
|
MSMGLEITGTALAVLGWLGTIVCCALPMWRVSAFIGSNIITSQNIWEGLWMNCVVQSTGQMQCKVYDSLLALPQDLQAARALIVVAILLAAFGLLVALVGAQCTNCVQDDTAKAKITIVAGVLFLLAALLTLVPVSWSANTIIRDFYNPVVPEAQKREMGAGLYVGWAAAALQLLGGALLCCSCPPREKKYTATKVVYSAPRSTGPGASLGTGYDRKDYV
| null | null |
actin cytoskeleton organization [GO:0030036]; bicellular tight junction assembly [GO:0070830]; calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules [GO:0016338]; cell adhesion [GO:0007155]; cell junction maintenance [GO:0034331]; epithelial cell morphogenesis [GO:0003382]; establishment of endothelial blood-brain barrier [GO:0014045]; maintenance of blood-brain barrier [GO:0035633]; negative regulation of cell migration [GO:0030336]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of gene expression [GO:0010629]; negative regulation of wound healing [GO:0061045]; positive regulation of bicellular tight junction assembly [GO:1903348]; positive regulation of cell junction assembly [GO:1901890]; positive regulation of cell migration [GO:0030335]; positive regulation of gene expression [GO:0010628]; positive regulation of metallopeptidase activity [GO:1905050]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of wound healing [GO:0090303]; regulation of cell morphogenesis [GO:0022604]; regulation of membrane permeability [GO:0090559]; regulation of transepithelial transport [GO:0150111]; response to ethanol [GO:0045471]; response to Gram-positive bacterium [GO:0140459]; response to hypoxia [GO:0001666]
|
apical junction complex [GO:0043296]; apicolateral plasma membrane [GO:0016327]; bicellular tight junction [GO:0005923]; cell-cell junction [GO:0005911]; lateral plasma membrane [GO:0016328]; membrane [GO:0016020]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]; tight junction [GO:0070160]
|
identical protein binding [GO:0042802]; structural molecule activity [GO:0005198]; transmembrane signaling receptor activity [GO:0004888]
|
PF00822;
|
1.20.140.150;
|
Claudin family
| null |
SUBCELLULAR LOCATION: Cell junction, tight junction {ECO:0000250|UniProtKB:Q9Z0G9}. Cell membrane {ECO:0000250|UniProtKB:Q9Z0G9}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9Z0G9}.
| null | null | null | null | null |
FUNCTION: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. {ECO:0000250|UniProtKB:Q9Z0G9}.
|
Homo sapiens (Human)
|
O15552
|
FFAR2_HUMAN
|
MLPDWKSSLILMAYIIIFLTGLPANLLALRAFVGRIRQPQPAPVHILLLSLTLADLLLLLLLPFKIIEAASNFRWYLPKVVCALTSFGFYSSIYCSTWLLAGISIERYLGVAFPVQYKLSRRPLYGVIAALVAWVMSFGHCTIVIIVQYLNTTEQVRSGNEITCYENFTDNQLDVVLPVRLELCLVLFFIPMAVTIFCYWRFVWIMLSQPLVGAQRRRRAVGLAVVTLLNFLVCFGPYNVSHLVGYHQRKSPWWRSIAVVFSSLNASLDPLLFYFSSSVVRRAFGRGLQVLRNQGSSLLGRRGKDTAEGTNEDRGVGQGEGMPSSDFTTE
| null | null |
cell surface pattern recognition receptor signaling pathway [GO:0002752]; cellular response to fatty acid [GO:0071398]; fat cell differentiation [GO:0045444]; G protein-coupled receptor signaling pathway [GO:0007186]; glucose homeostasis [GO:0042593]; leukocyte chemotaxis involved in inflammatory response [GO:0002232]; ligand-gated ion channel signaling pathway [GO:1990806]; lipid storage [GO:0019915]; mucosal immune response [GO:0002385]; negative regulation of insulin secretion [GO:0046676]; phospholipase C-activating G protein-coupled receptor signaling pathway [GO:0007200]; positive regulation of acute inflammatory response to non-antigenic stimulus [GO:0002879]; positive regulation of chemokine production [GO:0032722]; positive regulation of cytokine production involved in immune response [GO:0002720]; positive regulation of insulin secretion [GO:0032024]; positive regulation of interleukin-8 production [GO:0032757]; regulation of acute inflammatory response [GO:0002673]; regulation of peptide hormone secretion [GO:0090276]
|
cell projection [GO:0042995]; plasma membrane [GO:0005886]
|
G protein-coupled receptor activity [GO:0004930]; lipid binding [GO:0008289]
|
PF00001;
|
1.20.1070.10;
|
G-protein coupled receptor 1 family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18801738}; Multi-pass membrane protein {ECO:0000269|PubMed:18801738}.
| null | null | null | null | null |
FUNCTION: G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:12496283, PubMed:12711604, PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids accumulating in the intestine. May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake. Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes. In parallel to its role in energy homeostasis, may also mediate the activation of the inflammatory and immune responses by SCFA in the intestine, regulating the rapid production of chemokines and cytokines. May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils. In addition to SCFAs, may also be activated by the extracellular lectin FCN1 in a process leading to activation of monocytes and inducing the secretion of interleukin-8/IL-8 in response to the presence of microbes (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably acetate, propionate and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016). {ECO:0000269|PubMed:12496283, ECO:0000269|PubMed:12684041, ECO:0000269|PubMed:12711604, ECO:0000269|PubMed:18801738, ECO:0000269|PubMed:21037097, ECO:0000269|PubMed:23066016, ECO:0000269|PubMed:23589301}.
|
Homo sapiens (Human)
|
O15553
|
MEFV_HUMAN
|
MAKTPSDHLLSTLEELVPYDFEKFKFKLQNTSVQKEHSRIPRSQIQRARPVKMATLLVTYYGEEYAVQLTLQVLRAINQRLLAEELHRAAIQEYSTQENGTDDSAASSSLGENKPRSLKTPDHPEGNEGNGPRPYGGGAASLRCSQPEAGRGLSRKPLSKRREKASEGLDAQGKPRTRSPALPGGRSPGPCRALEGGQAEVRLRRNASSAGRLQGLAGGAPGQKECRPFEVYLPSGKMRPRSLEVTISTGEKAPANPEILLTLEEKTAANLDSATEPRARPTPDGGASADLKEGPGNPEHSVTGRPPDTAASPRCHAQEGDPVDGTCVRDSCSFPEAVSGHPQASGSRSPGCPRCQDSHERKSPGSLSPQPLPQCKRHLKQVQLLFCEDHDEPICLICSLSQEHQGHRVRPIEEVALEHKKKIQKQLEHLKKLRKSGEEQRSYGEEKAVSFLKQTEALKQRVQRKLEQVYYFLEQQEHFFVASLEDVGQMVGQIRKAYDTRVSQDIALLDALIGELEAKECQSEWELLQDIGDILHRAKTVPVPEKWTTPQEIKQKIQLLHQKSEFVEKSTKYFSETLRSEMEMFNVPELIGAQAHAVNVILDAETAYPNLIFSDDLKSVRLGNKWERLPDGPQRFDSCIIVLGSPSFLSGRRYWEVEVGDKTAWILGACKTSISRKGNMTLSPENGYWVVIMMKENEYQASSVPPTRLLIKEPPKRVGIFVDYRVGSISFYNVTARSHIYTFASCSFSGPLQPIFSPGTRDGGKNTAPLTICPVGGQGPD
| null | null |
inflammatory response [GO:0006954]; innate immune response [GO:0045087]; negative regulation of cytokine production involved in inflammatory response [GO:1900016]; negative regulation of inflammatory response [GO:0050728]; negative regulation of interleukin-1 beta production [GO:0032691]; negative regulation of interleukin-12 production [GO:0032695]; negative regulation of macrophage inflammatory protein 1 alpha production [GO:0071641]; negative regulation of NLRP3 inflammasome complex assembly [GO:1900226]; pattern recognition receptor signaling pathway [GO:0002221]; positive regulation of autophagy [GO:0010508]; positive regulation of cysteine-type endopeptidase activity [GO:2001056]; positive regulation of inflammatory response [GO:0050729]; positive regulation of interleukin-1 beta production [GO:0032731]; protein ubiquitination [GO:0016567]; pyroptosis [GO:0070269]; pyroptosome complex assembly [GO:1904270]; regulation of gene expression [GO:0010468]; regulation of interleukin-1 beta production [GO:0032651]; response to type II interferon [GO:0034341]
|
autophagosome [GO:0005776]; canonical inflammasome complex [GO:0061702]; cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; cytosol [GO:0005829]; lamellipodium [GO:0030027]; microtubule [GO:0005874]; microtubule associated complex [GO:0005875]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; ruffle [GO:0001726]
|
actin binding [GO:0003779]; identical protein binding [GO:0042802]; ubiquitin protein ligase activity [GO:0061630]; zinc ion binding [GO:0008270]
|
PF13765;PF02758;PF00622;PF00643;
|
2.60.120.920;3.30.160.60;1.10.533.10;
| null |
PTM: Cleaved by CASP1 (Probable). The N-terminal cleavage product localizes to the nucleus as a filamentous network and to the cytoplasm, interacts more strongly with RELA and NFKBIA than the full-length protein, enhances the nuclear localization of RELA and induces NFKBIA proteolysis. The C-terminal cleavage product localizes to the cytoplasm (Probable). {ECO:0000305|PubMed:18577712}.; PTM: Phosphorylation at Ser-242 is required for the interaction with 14-3-3 proteins and down-regulation of pyrin pro-inflammatory activity. {ECO:0000269|PubMed:27030597}.; PTM: Degraded along with the delivery of its substrates to autolysosomal compartments (at protein level). {ECO:0000269|PubMed:26347139}.
|
SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11468188, ECO:0000269|PubMed:19109554}. Cell projection, ruffle {ECO:0000269|PubMed:11468188}. Cell projection, lamellipodium {ECO:0000269|PubMed:11468188}. Nucleus {ECO:0000269|PubMed:11115844}. Cytoplasm {ECO:0000269|PubMed:10666224, ECO:0000269|PubMed:11498534, ECO:0000269|PubMed:18577712, ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:26347139}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:26347139}. Note=Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles (PubMed:11468188). In pre-apoptotic cells, colocalizes with PYCARD/ASC in large specks (inflammasomes) (PubMed:11468188). In migrating monocytes, strongly polarized at the leading edge of the cell where it colocalizes with polymerizing actin and PYCARD/ASC (PubMed:11468188). {ECO:0000269|PubMed:11468188}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:11115844}.
| null | null | null | null | null |
FUNCTION: Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma (PubMed:10807793, PubMed:11468188, PubMed:16037825, PubMed:16785446, PubMed:17431422, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923, PubMed:26347139, PubMed:27030597, PubMed:28835462). Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy (PubMed:16785446, PubMed:17431422, PubMed:26347139). Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:16785446, PubMed:17431422, PubMed:26347139). However, it can also have a positive effect in the inflammatory pathway, acting as an innate immune sensor that triggers PYCARD/ASC specks formation, caspase-1 activation, and IL1B and IL18 production (PubMed:16037825, PubMed:27030597, PubMed:28835462). Together with AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (By similarity). It is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923). Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923). {ECO:0000250|UniProtKB:Q9JJ26, ECO:0000269|PubMed:10807793, ECO:0000269|PubMed:11468188, ECO:0000269|PubMed:16037825, ECO:0000269|PubMed:16785446, ECO:0000269|PubMed:17431422, ECO:0000269|PubMed:17964261, ECO:0000269|PubMed:18577712, ECO:0000269|PubMed:19109554, ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:27030597, ECO:0000269|PubMed:28835462}.
|
Homo sapiens (Human)
|
O15554
|
KCNN4_HUMAN
|
MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFLVKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPAPVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYRSIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDTLWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRKLREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLPEPSQQSK
| null | null |
calcium ion transport [GO:0006816]; cell volume homeostasis [GO:0006884]; defense response [GO:0006952]; establishment of localization in cell [GO:0051649]; immune system process [GO:0002376]; phospholipid translocation [GO:0045332]; positive regulation of potassium ion transmembrane transport [GO:1901381]; positive regulation of protein secretion [GO:0050714]; positive regulation of T cell receptor signaling pathway [GO:0050862]; potassium ion transmembrane transport [GO:0071805]; potassium ion transport [GO:0006813]; saliva secretion [GO:0046541]; stabilization of membrane potential [GO:0030322]
|
cytosol [GO:0005829]; neuron projection [GO:0043005]; neuronal cell body [GO:0043025]; plasma membrane [GO:0005886]; vesicle [GO:0031982]; voltage-gated potassium channel complex [GO:0008076]
|
calcium-activated potassium channel activity [GO:0015269]; calmodulin binding [GO:0005516]; intermediate conductance calcium-activated potassium channel activity [GO:0022894]; potassium channel activity [GO:0005267]; protein phosphatase binding [GO:0019903]; small conductance calcium-activated potassium channel activity [GO:0016286]
|
PF02888;PF07885;PF03530;
|
1.10.287.70;
|
Potassium channel KCNN family, KCa3.1/KCNN4 subfamily
|
PTM: Phosphorylation at His-358 by NDKB activates the channel, and conversely it's dephosphorylation by PHPT1 inhibits the channel. {ECO:0000269|PubMed:17157250}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26148990}; Multi-pass membrane protein {ECO:0000255}.
| null | null | null | null | null |
FUNCTION: Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells (PubMed:17157250, PubMed:18796614). Plays a role in the late stages of EGF-induced macropinocytosis (PubMed:24591580). {ECO:0000269|PubMed:17157250, ECO:0000269|PubMed:18796614, ECO:0000269|PubMed:24591580, ECO:0000269|PubMed:26148990}.
|
Homo sapiens (Human)
|
O15648
|
PFKA_TRYBB
|
MAVESRSRVTSKLVKAHRAMLNSVTQEDLKVDRLPGADYPNPSKKYSSRTEFRDKTDYIMYNPRPRDEPSSENPVSVSPLLCELAAARSRIHFNPTETTIGIVTCGGICPGLNDVIRSITLTGINVYNVKRVIGFRFGYWGLSKKGSQTAIELHRGRVTNIHHYGGTILGSSRGPQDPKEMVDTLERLGVNILFTVGGDGTQRGALVISQEAKRRGVDISVFGVPKTIDNDLSFSHRTFGFQTAVEKAVQAIRAAYAEAVSANYGVGVVKLMGRDSGFIAAQAAVASAQANICLVPENPISEQEVMSLLERRFCHSRSCVIIVAEGFGQDWGRGSGGYDASGNKKLIDIGVILTEKVKAFLKANKSRYPDSTVKYIDPSYMIRACPPSANDALFCATLATLAVHEAMAGATGCIIAMRHNNYILVPIKVATSVRRVLDLRGQLWRQVREITVDLGSDVRLARKLEIRRELEAINRNRDRLHEELAKL
|
2.7.1.11
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_03186};
|
fructose 6-phosphate metabolic process [GO:0006002]; glycolytic process [GO:0006096]
|
glycosome [GO:0020015]
|
6-phosphofructokinase activity [GO:0003872]; ATP binding [GO:0005524]; metal ion binding [GO:0046872]; phosphate ion binding [GO:0042301]
|
PF00365;
|
3.40.50.450;
|
Phosphofructokinase type A (PFKA) family, PPi-dependent PFK group II subfamily, Atypical ATP-dependent clade 'X' sub-subfamily
| null |
SUBCELLULAR LOCATION: Glycosome {ECO:0000255|HAMAP-Rule:MF_03186, ECO:0000269|PubMed:2940090}.
|
CATALYTIC ACTIVITY: Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634, ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-Rule:MF_03186, ECO:0000269|PubMed:9461292};
| null |
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4. {ECO:0000255|HAMAP-Rule:MF_03186}.
| null | null |
FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis. {ECO:0000255|HAMAP-Rule:MF_03186}.
|
Trypanosoma brucei brucei
|
O15706
|
VACA_DICDI
|
MIEGSGSKTPKRNSDEISVKSLSIHEANTLSSEHEHESGNEELTLSQIVIRSDFANESSERQSKIILDRFNQGIGKNSAFTDSPALGRGLSRVDVSYFVMGHRNQVAELYDPRGQRFSTVLTPDPTVNIKYVGPVSKTAHYFGAYGKHVLNVPAGHYAKAFSKNRPVLYGEGPHVIIDPTFQFDENNGFVNQQEPFIEHSTINILRIPAGKIAKVWIGTQPHILESRRDPYVFVDAQFKLVSPDGAKKAQLFESSSCTFVEHGSIKRIIPHTGEVAITYNNGILTIIPTPKDGKPVIIDSPTHNFEGFISTSLQTCLFPSKETKQQALADNKSALADEINLKIFQTRDSLRVGVVLVVAFKIVDPELAITKLGKEGIINHIENVSFADMGKAIQLSTLQEIMYFNSIKPGQATNDDSVQTIQDRVKSHLARDLFDYGVELSRLQIETMKVLDTEIAKKLAGQSVTSAEFTTKQATLVKEYDIKTTEARLKAETDNIALEQRNKAIISESQAKLSSAQREAESLLITAEAQKKASELQGELYTKYPILAEIELARIKAEALKNATLYITPQDAGAFMNSPLVYFDKMMNANNTIQQKKN
| null | null |
establishment of protein localization to plasma membrane [GO:0061951]; phagocytosis, recognition [GO:0006910]; phagosome maturation [GO:0090382]; regulation of DNA-templated transcription [GO:0006355]; response to bacterium [GO:0009617]
|
early phagosome [GO:0032009]; endosome membrane [GO:0010008]; late endosome [GO:0005770]; membrane [GO:0016020]; pathogen-containing vacuole [GO:0140220]; phagocytic vesicle [GO:0045335]; phagolysosome [GO:0032010]; vacuole [GO:0005773]
| null |
PF01145;
|
3.30.479.30;
|
Vacuolin family
| null |
SUBCELLULAR LOCATION: Endosome membrane; Peripheral membrane protein. Lysosome. Note=Post-lysosome.
| null | null | null | null | null | null |
Dictyostelium discoideum (Social amoeba)
|
O15726
|
KC1_PLAF4
|
MEIRVANKYALGKKLGSGSFGDIYVAKDIVTMEEFAVKLESTRSKHPQLLYESKLYKILGGGIGVPKVYWYGIEGDFTIMVLDLLGPSLEDLFTLCNRKFSLKTVRMTADQMLNRIEYVHSKNFIHRDIKPDNFLIGRGKKVTLIHIIDFGLAKKYRDSRSHTSYPYKEGKNLTGTARYASINTHLGIEQSRRDDIEALGYVLMYFLRGSLPWQGLKAISKKDKYDKIMEKKISTSVEVLCRNASFEFVTYLNYCRSLRFEDRPDYTYLRRLLKDLFIREGFTYDFLFDWTCVYASEKDKKKMLENKNRFDQTADQEGRDQRNN
|
2.7.11.1
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:9334178};
|
endocytosis [GO:0006897]; non-motile cilium assembly [GO:1905515]; phosphorylation [GO:0016310]; positive regulation of canonical Wnt signaling pathway [GO:0090263]; positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436]; regulation of circadian rhythm [GO:0042752]; signal transduction [GO:0007165]; spindle assembly [GO:0051225]
|
cytoplasmic vesicle [GO:0031410]; extracellular region [GO:0005576]; host cell surface [GO:0044228]; microneme [GO:0020009]; nucleus [GO:0005634]; spindle microtubule [GO:0005876]
|
ATP binding [GO:0005524]; metal ion binding [GO:0046872]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]
|
PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, CK1 Ser/Thr protein kinase family, Casein kinase I subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8IHZ9}. Cytoplasmic vesicle, secretory vesicle, microneme {ECO:0000250|UniProtKB:Q8IHZ9}. Secreted {ECO:0000250|UniProtKB:Q8IHZ9}. Host cell surface {ECO:0000250|UniProtKB:Q8IHZ9}. Note=At the ring and early trophozoite stages, localizes to the host erythrocyte cell surface. In mature trophozoites, localizes to the parasite cytoplasm. At the segmented schizont stage, localizes to a single dot, probably micronemes, in each merozoite. {ECO:0000250|UniProtKB:Q8IHZ9}.
|
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; Evidence={ECO:0000269|PubMed:9334178}; 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; Evidence={ECO:0000305|PubMed:9334178};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=14 uM for ATP (at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:9334178}; Note=kcat is 1550 sec(-1) with ATP as substrate (at pH 7.5 and 37 degrees Celsius). {ECO:0000269|PubMed:9334178};
| null | null | null |
FUNCTION: Serine/threonine-protein kinase likely to be involved in many cellular processes (PubMed:9334178). Phosphorylates rhoptry protein RON3, nucleosome assembly protein NAPL and DNA/RNA-binding protein ALBA4 in vitro (By similarity). {ECO:0000250|UniProtKB:Q8IHZ9, ECO:0000269|PubMed:9334178}.
|
Plasmodium falciparum (isolate Dd2)
|
O15736
|
TIPD_DICDI
|
MFSSQNNSYMMMMGGGGIGNINNNQFYSPIISTSAQSFNSIVEWKRDIIRQLNDRNQNQTNNYSEFMRIYTDLLKRERTLNDRTLLYEKEIVSLRNEKKTQQQPPSGSSKMDSSSSSSSSNRVSGMGSTIEEMEQKLFKLQEDLTNSYKRNADNASSILLLNDKNKDLQNELMSKEIEIERIRSTIQQDLDSIKRLEMVVIEKENVSQIIRDELSSLQTEFLHNESKVVKLEQENSSLVERWLRKKNEEASKMNEANDFYQKMVEQRDSTPAKAAVQLSESISNLVVKLPDANDVPIPIVLERGVFSSEAMLPSKAKKRWTGHNSEIYCMAFNSIGNLLATGGGDKCVKVWDVISGQQKSTLLGASQSIVSVSFSPNDESILGTSNDNSARLWNTELGRSRHTLTGHIGKVYTGKFINSNRVVTGSHDRTIKLWDLQKGYCTRTIFCFSSCNDLVILGGSGTHLASGHVDHSVRFWDSNAGEPTQVLSSIHEGQITSITNSPTNTNQILTNSRDHTLKIIDIRTFDTIRTFKDPEYRNGLNWTKASWSPDGRYIASGSIDGSICIWDATNGKTVKVLTKVHNNGSSVCCCSWSPLANIFISADKDKNIIQWE
| null | null |
autophagosome assembly [GO:0000045]; autophagosome maturation [GO:0097352]; culmination involved in sorocarp development [GO:0031154]; macroautophagy [GO:0016236]; negative stranded viral RNA replication [GO:0039689]; phagocytosis [GO:0006909]; pinocytosis [GO:0006907]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; sorocarp development [GO:0030587]
|
Atg12-Atg5-Atg16 complex [GO:0034274]; autophagosome membrane [GO:0000421]; extracellular matrix [GO:0031012]; phagophore assembly site membrane [GO:0034045]
|
Atg8-family ligase activity [GO:0019776]
|
PF08614;PF00400;
|
1.20.5.170;2.130.10.10;
|
WD repeat tipD family
| null | null | null | null | null | null | null |
FUNCTION: Not known; disruption of the gene for tipD results in morphological defects.
|
Dictyostelium discoideum (Social amoeba)
|
O15743
|
SPNA_DICDI
|
MKKMLFMNKKEKKEEQSPAHSSLAQQHQLAQQQYQLQQQQLQLQYQQHQQQLQLAQQQKQNEQNLAQLSTSTSSNSSVNNTTNTNTNTTNSSSISSNNNNNNNTAVPILKAHDFCGTIMILGHTESGKTTLQRQLEFIYGVTDPTDAKHYQRLIYGNTLATLIRFIENSERLNITLSPDNLARVKRIQSQPVELARNRLPRFPLKLGWDCKCIWEDKVIQSVYNHSKICSEIRTPGRPKYYMDRMFKVFDPSYTPTEMDIISAYDQKDTIQSSAIIHKRFKVDLFGCSGKQSSPKNWVGLHQNYKPNYIFYVVALKDYFSDHLVATQNTDPTIVEMCNNHIHRNLLLESLNSFETLTKSELFDKSLAIYLIFNTSDIFYENIKQYDLKSCFSEYEGGNDPEKAVSFISNKFTKFLQNKDKPYKSHIVNLLDKNNVREEFEGIFDSLKIDAEKRGFTTPYNQSNSSPVSSIGSNSSRNSRLPNTSVSIPGLYSSDNDNTRLKNVNNNNNNNNNTTTYGSSTFPSSVISTTGSISNSIASAMDNDSSYSNESSPTSSMTLLPTTTTTTTTTTTTATTTDSTNNNNNNATVVIGKGKPPKEPKPVKPPKEPKPPKEPKPPKEPKPPKEPKPIKEPKEKPVKESKPPKEPKPIKEPKESKEPKEPKEPKPTKPPKEKKTSKVDGAAESKKNGADSCGNGGVGSKIKLESGFGSLQGRRKNMEDTHVILNNLMGAVTYNGPPKDIPISYYAVYDGHGGTETSTLLEPTVHNCLVNSQSFRDGDYEQAFRDAYAEADDIVIEKCEKSGSTGVSALLVGNKLYTANVGDSEIVLARAQPNANPKGPVTYEPVLLSYKHLASDDQEKKRVTDLGGMIIFNRLFGSLAVSRSFGDKEYKEGEKKFCVSDPYQTTTDLTARDHFFILACDGLWDKVEYDEAVQFVQRNIKLGKSATEISELLAQDSYDRGSGDNITVLVVILNWN
|
3.1.3.16
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};
|
anatomical structure morphogenesis [GO:0009653]; cell differentiation [GO:0030154]; G protein-coupled receptor signaling pathway [GO:0007186]
|
cytosol [GO:0005829]; membrane [GO:0016020]; nucleoplasm [GO:0005654]; plasma membrane [GO:0005886]; ruffle [GO:0001726]
|
G-protein beta/gamma-subunit complex binding [GO:0031683]; GTP binding [GO:0005525]; GTPase activity [GO:0003924]; magnesium ion binding [GO:0000287]; myosin phosphatase activity [GO:0017018]; protein serine/threonine phosphatase activity [GO:0004722]
|
PF00503;PF00481;
|
1.10.400.10;3.40.50.300;3.60.40.10;
|
G-alpha family; PP2C family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:9585512}. Cell membrane {ECO:0000269|PubMed:9585512}.
|
CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16; CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16;
| null | null | null | null |
FUNCTION: Involved in cell-type differentiation and morphogenesis. Dephosphorylates casein; in vitro. May also be involved as modulators or transducers in various transmembrane signaling systems. {ECO:0000269|PubMed:14597204, ECO:0000269|PubMed:9585512}.
|
Dictyostelium discoideum (Social amoeba)
|
O15757
|
PP1_DICDI
|
MEIDLDSIITRLLEPRTTKPGKLVDLAEEEIRYLTVQATEIFINQPILLELEAPIKICGDIHGQYYDLLRLFEYGGFPPQSNYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFILRGNHECASINRIYGFYDECKRRYNSKLWKAFTDCFNCLPVAAIIDEKIFCMHGGLSPDLKNMDQIRRITRPTVVPDFGLLCDLLWADPDKNIQGWEDNDRGVSYTFGADVVESFLKKHDLDLVCRAHQVVEDGYEFFAKRQLVTLFSAPNYFGEFDNAGAMMGVDETLMCSFQILKPADKKKLTNDSNGRPLTPPRNKQQKPKK
|
3.1.3.16
|
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; Note=Binds 2 manganese ions per subunit. {ECO:0000250};
|
chromosome segregation [GO:0007059]; regulation of mitotic cell cycle [GO:0007346]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
metal ion binding [GO:0046872]; myosin phosphatase activity [GO:0017018]; protein serine/threonine phosphatase activity [GO:0004722]
|
PF00149;PF16891;
|
3.60.21.10;
|
PPP phosphatase family
| null | null |
CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16; CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16;
| null | null | null | null |
FUNCTION: Protein phosphatase activity in vitro. {ECO:0000269|PubMed:12737629}.
|
Dictyostelium discoideum (Social amoeba)
|
O15770
|
GSHR_PLAF7
|
MYKHRYFHFFFFFFFFLVSTKIIRSFTFLNNNTNLSNPVYFKKKANMVYDLIVIGGGSGGMAAARRAARHNAKVALVEKSRLGGTCVNVGCVPKKIMFNAASVHDILENSRHYGFDTKFSFNLPLLVERRDKYIQRLNNIYRQNLSKDKVDLYEGTASFLSENRILIKGTKDNNNKDNGPLNEEILEGRNILIAVGNKPVFPPVKGIENTISSDEFFNIKESKKIGIVGSGYIAVELINVIKRLGIDSYIFARGNRILRKFDESVINVLENDMKKNNINIVTFADVVEIKKVSDKNLSIHLSDGRIYEHFDHVIYCVGRSPDTENLNLEKLNVETNNNYIVVDENQRTSVNNIYAVGDCCMVKKSKEIEDLNLLKLYNEETYLNKKENVTEDIFYNVQLTPVAINAGRLLADRLFLKKTRKTNYKLIPTVIFSHPPIGTIGLSEEAAIQIYGKENVKIYESKFTNLFFSVYDIEPELKEKTYLKLVCVGKDELIKGLHIIGLNADEIVQGFAVALKMNATKKDFDETIPIHPTAAEEFLTLQPWMK
|
1.8.1.7
|
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250|UniProtKB:Q94655}; Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:Q94655};
|
cell redox homeostasis [GO:0045454]; cellular response to oxidative stress [GO:0034599]; glutathione metabolic process [GO:0006749]; response to oxidative stress [GO:0006979]
|
apicoplast [GO:0020011]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; mitochondrion [GO:0005739]
|
flavin adenine dinucleotide binding [GO:0050660]; glutathione-disulfide reductase (NADP) activity [GO:0004362]
|
PF07992;PF02852;
|
3.30.390.30;3.50.50.60;
|
Class-I pyridine nucleotide-disulfide oxidoreductase family
| null |
SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:21203490}.; SUBCELLULAR LOCATION: [Isoform 2]: Plastid, apicoplast {ECO:0000269|PubMed:21203490}.
|
CATALYTIC ACTIVITY: Reaction=2 glutathione + NADP(+) = glutathione disulfide + H(+) + NADPH; Xref=Rhea:RHEA:11740, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:58349; EC=1.8.1.7; Evidence={ECO:0000269|PubMed:12729762}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11742; Evidence={ECO:0000269|PubMed:12729762};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=71 uM for glutathione disulfide (GSSG) (at 25 degrees Celsius and pH 6.9) {ECO:0000269|PubMed:12729762};
| null | null | null |
FUNCTION: Maintains high levels of reduced glutathione in the cytosol. {ECO:0000269|PubMed:12729762}.
|
Plasmodium falciparum (isolate 3D7)
|
O15819
|
H33A_DICDI
|
MARTKQTARKSTGAKVPRKHIGSKQAHKQTPVSSSSGGVKKVHRFRPGTVALREIRKYQKSTDLLIRKLPFQRLVREIAQEFKTDLRFQSAAIGALQEASEAYLVGLFEDTNLCAIHAKRVTIMPKDIHLARRIRGERS
| null | null |
chromatin remodeling [GO:0006338]; epigenetic regulation of gene expression [GO:0040029]; response to mercury ion [GO:0046689]
|
nucleolar chromatin [GO:0030874]; nucleosome [GO:0000786]; nucleus [GO:0005634]
|
DNA binding [GO:0003677]; protein heterodimerization activity [GO:0046982]; structural constituent of chromatin [GO:0030527]
|
PF00125;
|
1.10.20.10;
|
Histone H3 family
|
PTM: Acetylation is generally linked to gene activation. {ECO:0000250}.; PTM: Different methylation states of H3K4 mark distinct developmental phases. H3K4me2 is associated with euchromatic regions. H3K4me3 is a mark of active chromatin. set1 is responsible for all mono-, di- and tri-methylation of H3K4. H3K4me facilitates subsequent acetylation of H3 and H4. Methylation at H3K9 and H3K27 are linked to gene repression (By similarity). {ECO:0000250}.; PTM: H3S10ph, which is linked to gene activation, prevents methylation at H3K9 but facilitates acetylation of H3 and H4. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Associated with pericentromeric heterochromatin.
| null | null | null | null | null |
FUNCTION: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. {ECO:0000269|PubMed:16469305}.
|
Dictyostelium discoideum (Social amoeba)
|
O15865
|
CDPK2_PLAFK
|
MGNHLSVNKLKRKKKKKSFLNIYGKNTNENTSKQSNDYKYDINTSCISREGTTTLERKNLILCHSGKLEDKYIIDEKLGQGTYGCVYKGIDKVTNQLYAIKEEKKDRLKNINRFFQEIEIMKKLDHPNIVKLYETYENDNYIYLIMELCSGRELFDSIIENGSFTEKNAATIMKQIFSAIFYLHSLNIVHRDLKPENFLFQSENKDSLLKIIDFGLSKNLGTGEFTTTKAGTPYYVAPQVLDGKYDKKCDIWSSGVIMYTLLCGYPPFYGDTDNEVLKKVKKGEFCFYENDWGSISSDAKNLITKLLTYNPNERCTIEEALNHPWITQMTKSHEHVELSSTLLKNLKNFKKENELKKIALTIIAKHLCDVEINNLRNIFIALDVDNSGTLSSQEILDGLKKIGYQKIPPDIHQVLRDIDSNASGQIHYTDFLAATIDKQTYLKKEVCLIPFKFFDIDGNGKISVEELKRIFGRDDIENPLIDKAIDSLLQEVDLNGDGEIDFHEFMLMMSKKK
|
2.7.11.1
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q8ICR0};
|
intracellular signal transduction [GO:0035556]; phosphorylation [GO:0016310]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
ATP binding [GO:0005524]; calcium ion binding [GO:0005509]; calcium-dependent protein serine/threonine kinase activity [GO:0009931]; calmodulin binding [GO:0005516]; calmodulin-dependent protein kinase activity [GO:0004683]; mitogen-activated protein kinase binding [GO:0051019]; protein serine kinase activity [GO:0106310]
|
PF13499;PF00069;
|
1.10.238.10;1.10.510.10;
|
Protein kinase superfamily, Ser/Thr protein kinase family, CDPK subfamily
|
PTM: Myristoylated; myristoylation may target it to different subcellular compartments. {ECO:0000250|UniProtKB:P62344}.; PTM: Autophosphorylated in vitro. {ECO:0000269|PubMed:9247932}.
| 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=2.7.11.1; Evidence={ECO:0000269|PubMed:9247932}; 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; Evidence={ECO:0000269|PubMed:9247932};
| null | null | null | null |
FUNCTION: Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (PubMed:9247932). During male gametogenesis in the mosquito gut, required for male exflagellation, possibly by regulating male gamete exit from the host erythrocytes. Not required for asexual blood stage proliferation (By similarity). {ECO:0000250|UniProtKB:Q8ICR0, ECO:0000269|PubMed:9247932}.
|
Plasmodium falciparum (isolate K1 / Thailand)
|
O15909
|
RIR1_TRYBB
|
MLETVKLVTKRDGSVEPYDEKVVRSRIVNLMSGIDSYYVDVDDLVRVVGEGVREGMSTSMLDELLAETAAYCVTKHPDYGLLAGRLAVTALHKTTTESVLDSFRVLHEHVSQATKRHAPLISEELWDIANKHSAALQQIINYERDFDFEYFGYKTLERSYLLRVHKGRGVMEVVERPQQMFLRVALGIHGEDLERVKETYDYMSQGFFTHATPTLFNAGTPFPQMSSCFLVAMREDSIDGIYDTLKQCAIISKSAGGIGIHMHNIRAAGSYIAGTNGTSNGLVPMLRVWNNTARYVDQGGGKRKGAFAIYLEPWHADIFGFLLLKKNTGKEDQRARDLFYGLWIPDLFMERVESHGTWTLMDPNTAPFLSDCYGQEFTDLYERYEREGRGVRTIQAQELWFLILESQVETGVPFMLYKDACNFKSNQKNLGTIKCSNLCTEIVEYTSRDEVAVCNLASIALPRFVKDGAFDYVALKEVTKVVTRNLNRVIDRNHYPVCEARYSNLRHRPVGIGVQGLADAFALLSLPFAHPEAKKLNRQIFETIYIAAVEASTELAEKDGPYETFKGSPASEGKLQFDLWDEERRIRGMNEDSVHSHCGLWDWDSLKERVVKVGMRNSLLIAPMPTASTSQILGNNECIEPFTSNIYVRRVLSGEFPVVNKHLVKELIRLRLWNDDMRRKIIALNGSVSGIKEIPERIRELYKVVWEIRQKDLIDMAADRGRYIDQSQSLNLFLATPTSSQLTSMHFYSWKKGLKTGMYYLRSQPAADAIKFTLDPKAMKELPKPDKQSKEEVHGSVGRGKRKRVGEKPTANHSNAGAPNLNGPPDTDGDGGCLNCGS
|
1.17.4.1
| null |
deoxyribonucleotide biosynthetic process [GO:0009263]; DNA replication [GO:0006260]
|
nucleoplasm [GO:0005654]; ribonucleoside-diphosphate reductase complex [GO:0005971]
|
ATP binding [GO:0005524]; ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor [GO:0004748]
|
PF03477;PF02867;PF00317;
|
3.20.70.20;
|
Ribonucleoside diphosphate reductase large chain family
| null | null |
CATALYTIC ACTIVITY: Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-diphosphate; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1; Evidence={ECO:0000269|PubMed:9192674}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23254; Evidence={ECO:0000269|PubMed:9192674}; CATALYTIC ACTIVITY: Reaction=[thioredoxin]-disulfide + dCDP + H2O = [thioredoxin]-dithiol + CDP; Xref=Rhea:RHEA:28038, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:58069, ChEBI:CHEBI:58593; EC=1.17.4.1; Evidence={ECO:0000269|PubMed:9192674}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:28040; Evidence={ECO:0000269|PubMed:9192674};
| null | null | null | null |
FUNCTION: Provides the precursors necessary for DNA synthesis. Catalyzes the rate limiting step in the de novo synthesis of deoxyribonucleotides by directly reducing ribonucleotides to the corresponding deoxyribonucleotides. {ECO:0000269|PubMed:9192674}.
|
Trypanosoma brucei brucei
|
O15943
|
CADN_DROME
|
MAARRCLNQLRQRYITNRFNICTCAIFLISLPFILAIEETTFAGLSAENAARMLAGSPGDVEKSSLSHHSEMSLVLPHDTYPGFSIKKFKTHPVKINGSSHSGAAAYHMLDTDYSKYFTVLEDGVVMTTADISPLVNRPVQLVVVEQTPNATNTHNLQLFVMHRNDMLRFSGSLLDASGEVRENQPAGTRVRGVPLMQAFSGSILDEELATPKKVRYTIIDGNVDDAFALQERKANKNIQISAKSLVINGDDESGVWLVTNRPLDREERAHYDLSVEASDVDGLDRTVSKIQITVLDENDNRPIFKSLDYKFAIAGQKSASMESNSSVTYQRFAIMGKVEATDADGDKIAYRLKSPSNVVIIVPQTGEIMLAGEPTSNELLIEVIAHDLRYPSLVSAKPAKVLLEFLAAEPVSFIMQHLEHDDINNHSHHREKRRVTRAVRPTKRIEFTEADGDTEGKSVFQLEKETDKETFKIRDDNPWVTVETNGAVRVKKKWDYEELGPEKTIDFWVIITNMGHNAGIKYTDNQRVIILVKDVNDEPPYFINRPLPMQAVVQLNAPPNTPVFTLQARDPDTDHNIHYFIVRDRTGGRFEVDERSGVVRTRGTDLFQLDMEYVLYVKAEDQNGKVDDRRFQSTPEERLSIVGGKRAPQFYMPSYEAEIPENQKKDSDIISIKAKSFADREIRYTLKAQGQGAGTFNIGPTSGIVKLAKELDFEDLRQPHVYSLIVTATEDSGGFSTSVDLTIRVTDVNDNAPKFELPDYQAHNVDEDIPLGTSILRVKAMDSDSGSNAEIEYLVSDDHFAVDSNGIIVNNKQLDADNNNAYYEFIVTAKDKGEPPKSGVATVRVYTKNKNDEEPKFSQQVYTPNVDENAGPNTLVTTVVASDKDGDNVRFGFVGGGTSSGQFVIEDITGVIRLHNKAISLDKDKYELNVTAMDDGSCCVNGDQTIHTSTAVVVVFITDVNDNKPVFKDCSTYYPKVEEGAPNGSPVIKVVATDEDKGVNGQVKYSIVQQPNQKGTKFTVDEETGEVSTNKVFDREGDDGKFVSVTVKATDQGDPSLEGVCSFTVEITDVNDNPPLFDRQKYVENVKQDASIGTNILRVSASDEDADNNGAIVYSLTAPFNPNDLEYFEIQAESGWIVLKKPLDRETYKLEAMAQDKGYPPLSRTVEVQIDVVDRANNPPVWDHTVYGPIYVKENMPVGGKVVSIKASSGIEGNPTVFYRLMPGSTAQTNKFHTFYLQQRPDNGDTWADIKVNHPLDYESIKEYNLTIRVENNGAQQLASEATVYIMLEDVNDEIPLFTEREQETVLEGEPIGTKVTQVNAIDKDGTFPNNQVYYYIVDSPRNEGKEFFEINLQSGEIFTKTVFDREKKGAYALEVEARDGAPSARPNSNGPNSVTKFIRIGIADKNDNPPYFDKSLYEAEVDENEDIQHTVLTVTAKDHDESSRIRYEITSGNIGGAFAVKNMTGAIYVAGALDYETRRRYELRLAASDNLKENYTTVIIHVKDVNDNPPVFERPTYRTQITEEDDRNLPKRVLQVTATDGDKDRPQNIVYFLTGQGIDPDNPANSKFDINRTTGEIFVLKPLDRDQPNGRPQWRFTVFAQDEGGEGLVGYADVQVNLKDINDNAPIFPQGVYFGNVTENGTAGMVVMTMTAVDYDDPNEGSNARLVYSIEKNVIEEETGSPIFEIEPDTGVIKTAVCCLDRERTPDYSIQVVAMDGGGLKGTGTASIRVKDINDMPPQFTKDEWFTEVDETDGTALPEMPILTVTVHDEDETNKFQYKVIDNSGYGADKFTMVRNNDGTGSLKIVQPLDYEDQLQSNGFRFRIQVNDKGEDNDNDKYHVAYSWVVVKLRDINDNKPHFERANVEVSVFEDTKVGTELEKFKATDPDQGGKSKVSYSIDRSSDRQRQFAINQNGSVTIQRSLDREVVPRHQVKILAIDDGSPPKTATATLTVIVQDINDNAPKFLKDYRPVLPEHVPPRKVVEILATDDDDRSKSNGPPFQFRLDPSADDIIRASFKVEQDQKGANGDGMAVISSLRSFDREQQKEYMIPIVIKDHGSPAMTGTSTLTVIIGDVNDNKMQPGSKDIFVYNYQGQSPDTPIGRVYVYDLDDWDLPDKKFYWEAMEHPRFKLDEDSGMVTMRAGTREGRYHLRFKVYDRKHTQTDIPANVTVTVREIPHEAVVNSGSVRLSGISDEDFIRVWNYRTQSMSRSKMDRFRDKLADLLNTERENVDIFSVQLKRKHPPLTDVRFSAHGSPYYKPVRLNGIVLMHREEIEKDVGINITMVGIDECLYENQMCEGSCTNSLEISPLPYMVNANKTALVGVRVDTIADCTCGARNFTKPESCRTTPCHNGGRCVDTRFGPHCSCPVGYTGPRCQQTTRSFRGNGWAWYPPLEMCDESHLSLEFITRKPDGLIIYNGPIVPPERDETLISDFIALELERGYPRLLIDFGSGTLELRVKTKKTLDDGEWHRIDLFWDTESIRMVVDFCKSAEIAEMEDGTPPEFDDMSCQARGQIPPFNEYLNVNAPLQVGGLYREQFDQSLYFWHYMPTAKGFDGCIRNLVHNSKLYDLAHPGLSRNSVAGCPQTEEVCAQTETTARCWEHGNCVGSLSEARCHCRPGWTGPACNIPTIPTTFKAQSYVKYALSFEPDRFSTQVQLRFRTREEYGELFRVSDQHNREYGILEIKDGHLHFRYNLNSLRTEEKDLWLNAIVVNDGQWHVVKVNRYGSAATLELDGGEGRRYNETFEFVGHQWLLVDKQEGVYAGGKAEYTGVRTFEVYADYQKSCLDDIRLEGKHLPLPPAMNGTQWGQATMARNLEKGCPSNKPCSNVICPDPFECVDLWNVYECTCGEGRIMSPDSKGCMDRNECLDMPCMNGATCINLEPRLRYRCICPDGFWGENCELVQEGQTLKLSMGALAAILVCLLIILILVLVFVVYNRRREAHIKYPGPDDDVRENIINYDDEGGGEDDMTAFDITPLQIPIGGPMPPELAPMKMPIMYPVMTLMPGQEPNVGMFIEEHKKRADGDPNAPPFDDLRNYAYEGGGSTAGSLSSLASGTDDEQQEYDYLGAWGPRFDKLANMYGPEAPNPHNTELEL
| null | null |
adherens junction organization [GO:0034332]; axon extension [GO:0048675]; axon extension involved in axon guidance [GO:0048846]; axon guidance [GO:0007411]; axon target recognition [GO:0007412]; axonal fasciculation [GO:0007413]; calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules [GO:0016339]; cell-cell adhesion [GO:0098609]; cell-cell adhesion mediated by cadherin [GO:0044331]; cell-cell junction assembly [GO:0007043]; homophilic cell adhesion via plasma membrane adhesion molecules [GO:0007156]; negative regulation of dendrite morphogenesis [GO:0050774]; ommatidial rotation [GO:0016318]; R7 cell development [GO:0045467]; R8 cell development [GO:0045463]; regulation of axon extension involved in axon guidance [GO:0048841]; regulation of dendrite morphogenesis [GO:0048814]; retinal ganglion cell axon guidance [GO:0031290]
|
adherens junction [GO:0005912]; axon [GO:0030424]; catenin complex [GO:0016342]; cell-cell junction [GO:0005911]; dendrite [GO:0030425]; membrane [GO:0016020]; plasma membrane [GO:0005886]
|
cadherin binding [GO:0045296]; calcium ion binding [GO:0005509]; protein homodimerization activity [GO:0042803]
|
PF01049;PF00028;PF00008;PF02210;
|
2.60.120.200;2.60.40.60;2.10.25.10;4.10.900.10;
| null | null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. May associate with arm neural isoform and participate in the transmission of developmental information.
|
Drosophila melanogaster (Fruit fly)
|
O15945
|
ARNT_DROME
|
MDEANIQDKERFASRENHCEIERRRRNKMTAYITELSDMVPTCSALARKPDKLTILRMAVAHMKALRGTGNTSSDGTYKPSFLTDQELKHLILEAADGFLFVVSCDSGRVIYVSDSVTPVLNYTQSDWYGTSLYEHIHPDDREKIREQLSTQESQNAGRILDLKSGTVKKEGHQSSMRLSMGARRGFICRMRVGNVNPESMVSGHLNRLKQRNSLGPSRDGTNYAVVHCTGYIKNWPPTDMFPNMHMERDVDDMSSHCCLVAIGRLQVTSTAANDMSGSNNQSEFITRHAMDGKFTFVDQRVLNILGYTPTELLGKICYDFFHPEDQSHMKESFDQVLKQKGQMFSLLYRARAKNSEYVWLRTQAYAFLNPYTDEVEYIVCTNSSGKTMHGAPLDAAAAHTPEQVQQQQQQEQHVYVQAAPGVDYARRELTPVGSATNDGMYQTHMLAMQAPTPQQQQQQQQRPGSAQTTPVGYTYDTTHSPYSAGGPSPLAKIPKSGTSPTPVAPNSWAALRPQQQQQQQQPVTEGYQYQQTSPARSPSGPTYTQLSAGNGNRQQAQPGAYQAGPPPPPNAPGMWDWQQAGGHPHPPHPTAHPHHPHAHPGGPAGAGQPQGQEFSDMLQMLDHTPTTFEDLNINMFSTPFE
| null | null |
appendage development [GO:0048736]; brain development [GO:0007420]; cellular response to hypoxia [GO:0071456]; cellular response to insulin stimulus [GO:0032869]; central nervous system development [GO:0007417]; glial cell migration [GO:0008347]; imaginal disc-derived leg joint morphogenesis [GO:0016348]; insulin receptor signaling pathway [GO:0008286]; negative regulation of transcription by RNA polymerase II [GO:0000122]; oogenesis [GO:0048477]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of DNA-templated transcription [GO:0006355]; regulation of R7 cell differentiation [GO:0045676]; regulation of transcription by RNA polymerase II [GO:0006357]
|
aryl hydrocarbon receptor complex [GO:0034751]; cytoplasm [GO:0005737]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; RNA polymerase II transcription regulator complex [GO:0090575]
|
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]; myosin binding [GO:0017022]; protein heterodimerization activity [GO:0046982]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]
|
PF00010;PF00989;PF14598;
|
4.10.280.10;3.30.450.20;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
| null | null | null | null | null |
FUNCTION: Heterodimers of tgo/trh are involved in the control of breathless expression. Plays a role in the cellular or tissue response to oxygen deprivation. {ECO:0000269|PubMed:10581393, ECO:0000269|PubMed:9284047, ECO:0000269|PubMed:9374395, ECO:0000269|PubMed:9409674}.
|
Drosophila melanogaster (Fruit fly)
|
O16000
|
STX1A_CAEEL
|
MTKDRLSALKAAQSEDEQDDDMHMDTGNAQYMEEFFEQVEEIRGSVDIIANNVEEVKKKHSAILSNPVNDQKTKEELDELMAVIKRAANKVRGKLKLIENAIDHDEQGAGNADLRIRKTQHSTLSRRFVEVMTDYNKTQTDYRERCKGRIQRQLDIAGKQVGDEDLEEMIESGNPGVFTQGIITDTQQAKQTLADIEARHNDIMKLESSIRELHDMFMDMAMLVESQGEMVDRIEYNVEHAKEFVDRAVADTKKAVQYQSKARRKKICILVTGVILITGLIIFILFYAKVL
| null | null |
calcium-mediated signaling [GO:0019722]; cell differentiation [GO:0030154]; chemical synaptic transmission [GO:0007268]; exocytosis [GO:0006887]; insulin receptor signaling pathway [GO:0008286]; intracellular protein transport [GO:0006886]; locomotion [GO:0040011]; neurotransmitter secretion [GO:0007269]; positive regulation of anterior/posterior axon guidance [GO:1905488]; regulation of multicellular organism growth [GO:0040014]; synaptic transmission, cholinergic [GO:0007271]; synaptic vesicle fusion to presynaptic active zone membrane [GO:0031629]; ventral cord development [GO:0007419]; vesicle docking [GO:0048278]
|
axon [GO:0030424]; basolateral plasma membrane [GO:0016323]; dendrite [GO:0030425]; endomembrane system [GO:0012505]; membrane [GO:0016020]; neuronal cell body [GO:0043025]; perikaryon [GO:0043204]; plasma membrane [GO:0005886]; presynaptic active zone membrane [GO:0048787]; SNARE complex [GO:0031201]; synaptic vesicle [GO:0008021]
|
protein-folding chaperone binding [GO:0051087]; SNAP receptor activity [GO:0005484]; SNARE binding [GO:0000149]; structural constituent of cuticle [GO:0042302]
|
PF05739;PF00804;
|
1.20.5.110;1.20.58.70;
|
Syntaxin family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12973353}; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P32851, ECO:0000255}. Cell projection, axon {ECO:0000269|PubMed:12973353, ECO:0000269|PubMed:18596236}. Cell projection, dendrite {ECO:0000269|PubMed:12973353, ECO:0000269|PubMed:18596236}. Perikaryon {ECO:0000269|PubMed:18596236}.
| null | null | null | null | null |
FUNCTION: Plays a critical role in several secretory processes, including cuticle secretion and neurotransmitter release, and probably assists in neuronal membrane maturation or the final stages of neuronal differentiation (PubMed:1945043, PubMed:9442061). Plays a role in synaptic vesicle docking and tethering through its association with unc-18 (PubMed:21423527). Through binding to unc-18 mediates the release of the neurotransmitter acetylcholine from cholinergic motor neurons, and thereby promotes locomotory behaviors (PubMed:18596236). Essential for embryonic viability and development. Has a role in dauer formation and adult life span (PubMed:10377425). Required for locomotion (PubMed:10377425). Probably by regulating neuronal transmission downstream of lin-3 and receptor lin-23 and phospholipase plc-3 and upstream of innexin unc-7 and egl-4/PKG in ALA neurons, involved in the decrease in pharyngeal pumping during the quiescent state that precedes each larval molt (PubMed:17891142). {ECO:0000269|PubMed:10377425, ECO:0000269|PubMed:17891142, ECO:0000269|PubMed:18596236, ECO:0000269|PubMed:1945043, ECO:0000269|PubMed:21423527, ECO:0000269|PubMed:9442061}.
|
Caenorhabditis elegans
|
O16011
|
MBL_DROME
|
MANVVNMNSLLNGKDSRWLQLEVCREFQRNKCSRQDTECKFAHPPANVEVQNGKVTACYDSIKGRCNRDKPPCKYFHPPQHLKDQLLINGRNHLALKNALMQQMGIAPGQPVISGQVPAVATNPYLTGIPANSYSPYYTTGHLVPALLGPDPVTSQLGPVVPQTVQVAQQKIPRSDRLETSPLAAHHHQQQQQLQHQLNNINNNNNHSTAGAAATSTTATTTTNNAAAAAAAAAAAAAAAVMGHHTLEVGKKRAADTTDMFPLVFFCSFPSPCVFAFLNCSIFGFLRLWFSLFNLRH
| null | null |
apoptotic process [GO:0006915]; compound eye photoreceptor cell differentiation [GO:0001751]; eye development [GO:0001654]; muscle cell cellular homeostasis [GO:0046716]; muscle organ development [GO:0007517]; regulation of alternative mRNA splicing, via spliceosome [GO:0000381]; regulation of female receptivity [GO:0045924]; regulation of gene expression [GO:0010468]; regulation of RNA splicing [GO:0043484]; response to stimulus [GO:0050896]; rhabdomere development [GO:0042052]; visual perception [GO:0007601]
|
cytoplasm [GO:0005737]; H zone [GO:0031673]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; Z disc [GO:0030018]
|
metal ion binding [GO:0046872]; nucleic acid binding [GO:0003676]; RNA binding [GO:0003723]
| null |
3.30.1370.210;
|
Muscleblind family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9334280}.
| null | null | null | null | null |
FUNCTION: Required for terminal differentiation of photoreceptor cells. Vital for embryonic development. {ECO:0000269|PubMed:9334280}.
|
Drosophila melanogaster (Fruit fly)
|
O16025
|
AOSL_PLEHO
|
MTWKNFGFEIFGEKYGQEELEKRIKDEHTPPPDSPVFGGLKLKLKKEKFKTLFTLGTTLKGFRRATHTVGTGGIGEITIVNDPKFPEHEFFTAGRTFPARLRHANLKYPDDAGADARSFSIKFADSDSDGPLDIVMNTGEANIFWNSPSLEDFVPVEEGDAAEEYVYKNPYYYYNLVEALRRAPDTFAHLYYYSQVTMPFKAKDGKVRYCRYRALPGDVDIKEEDESGRLTEEEQRKIWIFSRHENEKRPDDYLRKEYVERLQKGPVNYRLQIQIHEASPDDTATIFHAGILWDKETHPWFDLAKVSIKTPLSPDVLEKTAFNIANQPASLGLLEAKSPEDYNSIGELRVAVYTWVQHLRKLKIGSLVPAGQNAIYNVEVETGDREHAGTDATITIRITGAKGRTDYLKLDKWFHNDFEAGSKEQYTVQGFDVGDIQLIELHSDGGGYWSGDPDWFVNRVIIISSTQDRVYSFPCFRWVIKDMVLFPGEATLPFNEVPAIVSEQRQKELEQRKLTYQWDYVSDDMPGNIKAKTHDDLPRDVQFTDEKSRSYQESRKAALVNLGIGSLFTMFENWDSYDDYHILYRNWILGGTPNMADRWHEDRWFGYQFLNGANPVILTRCDALPSNFPVTNEHVNASLDRGKNLDEEIKDGHIYIVDFKVLVGAKSYGGPVLEDIGYKVPDHLKHDEADIRYCAAPLALFYVNKLGHLMPIAIQINQEPGPENPIWTPHEENEHDWMMAKFWLGVAESNFHQLNTHLLRTHLTTESFALSTWRNLASAHPVFKLLQPHIYGVLAIDTIGRKELIGSGGIVDQSLSLGGGGHVTFMEKCFKEVNLQDYHLPNALKKRGVDDPSKLPGFYYRDDGLALWEAIETFIGEIIAIFYKNDDDVKRDNEIQSWIYDVHKNGWRVNPGHQDHGVPASFESREQLKEVLTSLVFTFSCQHAAVNFSQKDHYGFTPNAPAVLRHPPPKKKGEATLQSILSTLPSKSQAAKAIATVYILTKFSEDERYLGNYSATAWEDKDALDAINRFQDKLEDISKKIKQRNENLEVPYIYLLPERIPNGTAI
|
1.13.11.40; 4.2.1.-
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 2 calcium ions per subunit.; COFACTOR: Name=Fe cation; Xref=ChEBI:CHEBI:24875; Note=Binds 1 Fe cation per subunit.; COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Note=Binds 1 heme group per subunit.;
|
arachidonic acid metabolic process [GO:0019369]; hepoxilin biosynthetic process [GO:0051122]; linoleic acid metabolic process [GO:0043651]; lipid oxidation [GO:0034440]; lipoxygenase pathway [GO:0019372]; oxylipin biosynthetic process [GO:0031408]
|
cytoplasm [GO:0005737]; membrane [GO:0016020]
|
allene oxide synthase activity [GO:0009978]; arachidonate 8(R)-lipoxygenase activity [GO:0047677]; heme binding [GO:0020037]; iron ion binding [GO:0005506]
|
PF00305;PF01477;
|
3.10.450.60;2.40.180.10;
|
Lipoxygenase family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00726, ECO:0000269|PubMed:16162493}. Membrane {ECO:0000269|PubMed:16162493}; Peripheral membrane protein {ECO:0000269|PubMed:16162493}. Note=Calcium binding promotes binding to membranes.
|
CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:14985, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57447; EC=1.13.11.40; Evidence={ECO:0000269|PubMed:10559269, ECO:0000269|PubMed:9302294}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14986; Evidence={ECO:0000269|PubMed:10559269, ECO:0000269|PubMed:9302294}; CATALYTIC ACTIVITY: Reaction=(8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate = 8,9-epoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:51344, ChEBI:CHEBI:15377, ChEBI:CHEBI:57447, ChEBI:CHEBI:134054; Evidence={ECO:0000269|PubMed:10559269, ECO:0000269|PubMed:29909837, ECO:0000269|PubMed:9302294}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51345; Evidence={ECO:0000269|PubMed:10559269, ECO:0000269|PubMed:29909837, ECO:0000269|PubMed:9302294}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = (8R)-hydroperoxy-(5Z,9E,11Z,14Z,17Z)-eicosapentaenoate; Xref=Rhea:RHEA:51412, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562, ChEBI:CHEBI:134079; Evidence={ECO:0000305|PubMed:10559269}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51413; Evidence={ECO:0000305|PubMed:10559269}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = 10-hydroperoxy-(4Z,7Z,11E,13Z,16Z,19Z)-docosahexaenoate; Xref=Rhea:RHEA:51340, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, ChEBI:CHEBI:134057; Evidence={ECO:0000269|PubMed:10559269}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51341; Evidence={ECO:0000269|PubMed:10559269}; CATALYTIC ACTIVITY: Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = (8R)-hydroperoxy-(9E,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:51324, ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:134051; Evidence={ECO:0000305|PubMed:10559269}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51325; Evidence={ECO:0000305|PubMed:10559269}; CATALYTIC ACTIVITY: Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = 10-hydroperoxy-(8Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:51328, ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:134052; Evidence={ECO:0000269|PubMed:10559269}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51329; Evidence={ECO:0000269|PubMed:10559269}; CATALYTIC ACTIVITY: Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = 11-hydroperoxy-(8Z,12E,14Z)-eicosatrienoate; Xref=Rhea:RHEA:51332, ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:134053; Evidence={ECO:0000269|PubMed:10559269}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51333; Evidence={ECO:0000269|PubMed:10559269};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=45.28 uM for arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) {ECO:0000269|PubMed:10559269};
|
PATHWAY: Lipid metabolism; arachidonate metabolism.; PATHWAY: Lipid metabolism; fatty acid metabolism.
|
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0. {ECO:0000269|PubMed:10559269};
| null |
FUNCTION: Bifunctional enzyme which is responsible for allene oxide biosynthesis via a two-step reaction; first the lipoxygenase reaction that converts polyunsaturated fatty acids such as arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) into a (8R)-hydroperoxide intermediate ((8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate) followed by the allene oxide synthase reaction that converts the hydroperoxide intermediate ((8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate) into the allene oxide (8,9-epoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate) (PubMed:10559269, PubMed:9302294). Shows preference for C20 or C22 highly polyunsaturated fatty acids and no activity with C18 fatty acids in vitro (PubMed:10559269). Fatty acid allene oxides are intermediates in the formation of cyclopentenones or hydrolytic products in marine systems, most notably the prostanoid-related clavulones (PubMed:29909837). {ECO:0000269|PubMed:10559269, ECO:0000269|PubMed:9302294, ECO:0000303|PubMed:29909837}.
|
Plexaura homomalla (Black sea rod)
|
O16076
|
HSP83_DROPE
|
MPEEAETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLTDPSKLDSGKELYIKLIPNKTAGTLTIIDTGIGMTKSDLVNNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLIADRVTVTSKNNDDEQYVWESXXXGSFTXKADNXEPLXRGTKIXLYIKEDQTDYLEESKIKEIVNKHSQFIGYPIKLLVEKEREKEVSDDEADDEKKDDEAKKDMDTDEPKIEDVGEDEDADKKDKDGKKKKTIKEKY
| null | null |
cellular response to heat [GO:0034605]; centrosome cycle [GO:0007098]; cold acclimation [GO:0009631]; membrane bending [GO:0097753]; multivesicular body fusion to apical plasma membrane [GO:0098866]; negative regulation of cell population proliferation [GO:0008285]; pole plasm mRNA localization [GO:0019094]; positive regulation of insulin receptor signaling pathway [GO:0046628]; positive regulation of neuroblast proliferation [GO:0002052]; proteasome assembly [GO:0043248]; protein stabilization [GO:0050821]; regulation of circadian sleep/wake cycle, sleep [GO:0045187]; RISC complex assembly [GO:0070922]
|
centrosome [GO:0005813]; cytosol [GO:0005829]; endoplasmic reticulum chaperone complex [GO:0034663]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; polytene chromosome interband [GO:0005705]; protein folding chaperone complex [GO:0101031]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATP-dependent protein folding chaperone [GO:0140662]; disordered domain specific binding [GO:0097718]; insulin receptor binding [GO:0005158]; TPR domain binding [GO:0030911]; unfolded protein binding [GO:0051082]
|
PF13589;PF00183;
|
3.30.565.10;
|
Heat shock protein 90 family
| null |
SUBCELLULAR LOCATION: Cytoplasm.
| null | null | null | null | null |
FUNCTION: Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Required for piRNA biogenesis by facilitating loading of piRNAs into PIWI proteins (By similarity). {ECO:0000250}.
|
Drosophila persimilis (Fruit fly)
|
O16102
|
CHD3_DROME
|
MSSKRGADPDWKTPGKASKDKRPKTNAKKQKFRDEEYCKVCSDGGDLLCCDSCPSVYHRTCLSPPLKSIPKGDWICPRCIPLPGKAEKILSWRWALDRSVELRTSKGEKRREYFIKWHGMSYWHCEWIPEGQMLLHHASMVASFQRRSDMEEPSLEELDDQDGNLHERFYRYGIKPEWLLVQRVINHSEEPNGGTMYLVKWRELSYNDSSWERESDSIPGLNQAIALYKKLRSSNKGRQRDRPAPTIDLNKKYEDQPVFLKEAGLKLHPFQIEGVSWLRYSWGQGIPTILADEMGLGKTIQTVVFLYSLFKEGHCRGPFLISVPLSTLTNWERELELWAPELYCVTYVGGKTARAVIRKHEISFEEVTTKTMRENQTQYKFNVMLTSYEFISVDAAFLGCIDWAALVVDEAHRLRSNQSKFFRILSKYRIGYKLLLTGTPLQNNLEELFHLLNFLSSGKFNDLQTFQAEFTDVSKEEQVKRLHEILEPHMLRRLKADVLKSMPPKSEFIVRVELSSMQKKFYKHILTKNFKALNQKGGGRVCSLLNIMMDLRKCCNHPYLFPSAAEEATISPSGLYEMSSLTKASGKLDLLSKMLKQLKADNHRVLLFSQMTKMLNVLEHFLEGEGYQYDRIDGSIKGDLRQKAIDRFNDPVSEHFVFLLSTRAGGLGINLATADTVIIFDSDWNPHNDVQAFSRAHRMGQKKKVMIYRFVTHNSVEERIMQVAKHKMMLTHLVVRPGMGGMTTNFSKDELEDILRFGTEDLFKDGKSEAIHYDDKAVADLLDRTNRGIEEKESWANEYLSSFKVASYATKEDHEEHDDYNNDAENTDPFYWENLMGKSQPKLPKKQKKQSQQSQVDVESIMGKGKRIRKEIDYSNQYPSPNRATPSSIVLM
|
3.6.4.12
| null |
chromatin organization [GO:0006325]; chromatin remodeling [GO:0006338]; negative regulation of transcription by RNA polymerase II [GO:0000122]; nucleosome organization [GO:0034728]
|
chromatin [GO:0000785]; euchromatin [GO:0000791]; nucleus [GO:0005634]; NuRD complex [GO:0016581]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATP-dependent chromatin remodeler activity [GO:0140658]; chromatin binding [GO:0003682]; DNA binding [GO:0003677]; helicase activity [GO:0004386]; histone binding [GO:0042393]; metal ion binding [GO:0046872]
|
PF00385;PF00271;PF00628;PF00176;
|
2.40.50.40;3.40.50.300;3.40.50.10810;3.30.40.10;
|
SNF2/RAD54 helicase family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18250149}. Chromosome {ECO:0000269|PubMed:18250149}. Note=During embryogenesis, detected in nuclei before and after their migration to the membrane of the preblastoderm embryo (PubMed:18250149). Remains associated with condensed chromosomes in mitotic nuclei. Not detected in nuclei postgastrulation (PubMed:18250149). In polytene chromosomes of third instar larvae, weakly expressed at the chromocenter and fourth chromosome localizing mainly to the interbands (PubMed:18250149). {ECO:0000269|PubMed:18250149}.
|
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=3.6.4.12; Evidence={ECO:0000269|PubMed:18250149};
| null | null | null | null |
FUNCTION: Helicase which acts in nucleosome-remodeling by catalyzing ATP-dependent nucleosome mobilization (PubMed:18250149). Likely to be involved in the regulation of transcription (PubMed:18250149). {ECO:0000269|PubMed:18250149}.
|
Drosophila melanogaster (Fruit fly)
|
O16228
|
DJ12_CAEEL
|
MAAQKSALILLPPEDAEEIEVIVTGDVLVRGGLQVLYAGSSTEPVKCAKGARIVPDVALKDVKNKTFDIIIIPGGPGCSKLAECPVIGELLKTQVKSGGLIGAICAGPTVLLAHGIVAERVTCHYTVKDKMTEGGYKYLDDNVVISDRVITSKGPGTAFEFALKIVETLEGPEKTNSLLKPLCLAK
|
4.2.1.130
| null |
cellular response to glyoxal [GO:0036471]; cellular response to methylglyoxal [GO:0097238]; glycolate biosynthetic process [GO:0046295]; glyoxal metabolic process [GO:1903189]; lactate biosynthetic process [GO:0019249]; methylglyoxal metabolic process [GO:0009438]; negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway [GO:1902176]; response to oxidative stress [GO:0006979]
|
cytoplasm [GO:0005737]; mitochondrion [GO:0005739]; nucleus [GO:0005634]
|
glyoxalase III activity [GO:0019172]
|
PF01965;
|
3.40.50.880;
|
Peptidase C56 family, DJ-1 subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22523093}.
|
CATALYTIC ACTIVITY: Reaction=H2O + methylglyoxal = (R)-lactate + H(+); Xref=Rhea:RHEA:27754, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16004, ChEBI:CHEBI:17158; EC=4.2.1.130; Evidence={ECO:0000269|PubMed:22523093};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.39 mM for methylglyoxal {ECO:0000269|PubMed:22523093}; KM=0.78 mM for glyoxal {ECO:0000269|PubMed:22523093}; Note=kcat is 60.0 min(-1) with methylglyoxal as substrate and 146.4 min(-1) with glyoxal as substrate. {ECO:0000269|PubMed:22523093};
| null | null | null |
FUNCTION: Catalyzes the conversion of methylglyoxal (MG) or glyoxal (GO) to D-lactate or glycolic acid respectively in a single glutathione (GSH)-independent step. May play a role in detoxifying endogenously produced glyoxals. Involved in protection against glyoxal-induced cell death. Protects dopaminergic neurons from glyoxal-dependent neuronal degeneration. {ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23624124}.
|
Caenorhabditis elegans
|
O16259
|
STIP1_CAEEL
|
MTDAAIAEKDLGNAAYKQKDFEKAHVHYDKAIELDPSNITFYNNKAAVYFEEKKFAECVQFCEKAVEVGRETRADYKLIAKAMSRAGNAFQKQNDLSLAVQWFHRSLSEFRDPELVKKVKELEKQLKAAERLAYINPELAQEEKNKGNEYFKKGDYPTAMRHYNEAVKRDPENAILYSNRAACLTKLMEFQRALDDCDTCIRLDSKFIKGYIRKAACLVAMREWSKAQRAYEDALQVDPSNEEAREGVRNCLRSNDEDPEKAKERSLADPEVQEILRDPGMRMILEQMSNDPGAVREHLKNPEIFQKLMKLRDAGVIQMR
| null | null |
determination of adult lifespan [GO:0008340]; protein maturation by protein folding [GO:0022417]; reproduction [GO:0000003]; response to heat [GO:0009408]
|
cytoplasm [GO:0005737]; protein folding chaperone complex [GO:0101031]
|
ATPase inhibitor activity [GO:0042030]; Hsp70 protein binding [GO:0030544]; Hsp90 protein binding [GO:0051879]
|
PF17830;PF13414;
|
1.10.260.100;1.25.40.10;
| null | null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19467242}. Note=Detected in cytoplasm in early-stage embryos. {ECO:0000269|PubMed:19467242}.
| null | null | null | null | null |
FUNCTION: Plays a role in gonad development. Up-regulates longevity and thermotolerance. Binds daf-21/hsp90 and inhibits its ATPase activity. {ECO:0000269|PubMed:19467242, ECO:0000269|PubMed:19559711}.
|
Caenorhabditis elegans
|
O16299
|
FIGL1_CAEEL
|
MYSPKRVKLNVTSGMRKRPETGENNDDLYPPTALARNGISPYFIGKPRRKIVVETPSDSAQQQPPFKSRSQQNGLDDELDGIIIDEDEDRTVDVSFSQKQDTRKLKSRPFLGEKSSFKLGEIPKPKEEKRREEPFTMRGFDFGSDDKVTKIRDKICDIVDPTNARRTDPNFIRQMHENTLKGIEVASNPHFKKTRAPTKNRAAIQNTLGTLYPSFTTAAGQDPQNSKFQVPLDRQSSSQSIGSLAGIPPARRAPDIPKRCSNPLIRKAMGMDTEGGGKDEKMSGLRAEPTLKHFDENIISLIESEIMSVNNEIGWADVAGLEGAKKALREIVVLPFKRPDVFTGIRAPPKGVLLFGPPGTGKTMIGRCVASQCKATFFNISASSLTSKWVGEGEKLVRALFSVARLKLPSVIFIDEIDSLLSSRSESEHESSRRIKTEFLVQLDGVNTAPDERLLVLGATNRPQELDEAARRRFQKRLYIALPEPESRTQIVQNLLVGTRHDITNHNLERIRELTDGYSGADMRQLCTEAAMGPIRDIGDDIETIDKDDIRAVTVMDFAEAARVVRPTVDDSQLDAYAAWDKKFGCLPPPSISR
|
3.6.4.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:15581640};
|
ATP metabolic process [GO:0046034]; cell cycle [GO:0007049]; cell division [GO:0051301]; positive regulation of mitotic cell cycle [GO:0045931]
|
nucleus [GO:0005634]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; hydrolase activity [GO:0016787]; magnesium ion binding [GO:0000287]; microtubule binding [GO:0008017]; microtubule severing ATPase activity [GO:0008568]
|
PF00004;PF17862;PF09336;
|
1.10.8.60;3.40.50.300;
|
AAA ATPase family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17878235}.
|
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; Evidence={ECO:0000269|PubMed:15581640};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.44 mM for ATP {ECO:0000269|PubMed:15581640}; Vmax=225 nmol/min/mg enzyme {ECO:0000269|PubMed:15581640}; Note=At 25 degrees Celsius and pH 8.0.;
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.0-8.8. {ECO:0000269|PubMed:15581640};
|
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 25-30 degrees Celsius. {ECO:0000269|PubMed:15581640};
|
FUNCTION: Has a role in spindle assembly which acts in the progression through mitosis during embryogenesis. Required for fertility. {ECO:0000269|PubMed:17878235}.
|
Caenorhabditis elegans
|
O16305
|
CALM_CAEEL
|
MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVTMMTTK
| null | null |
apoptotic cell clearance [GO:0043277]; cell migration [GO:0016477]; embryo development ending in birth or egg hatching [GO:0009792]; establishment of meiotic spindle orientation [GO:0051296]; negative regulation of gene expression [GO:0010629]; positive chemotaxis [GO:0050918]; regulation of apoptotic process [GO:0042981]; regulation of cell cycle [GO:0051726]; regulation of protein localization [GO:0032880]
|
calcineurin complex [GO:0005955]; cell periphery [GO:0071944]; centrosome [GO:0005813]; mitotic spindle [GO:0072686]; nuclear membrane [GO:0031965]
|
calcium ion binding [GO:0005509]; enzyme regulator activity [GO:0030234]
|
PF13499;
|
1.10.238.10;
|
Calmodulin family
| null | null | null | null | null | null | null |
FUNCTION: Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases.
|
Caenorhabditis elegans
|
O16374
|
GALT1_CAEEL
|
MPRITASKIVLLIALSFCITVIYHFPIATRSSKEYDEYGNEYENVASIESDIKNVRRLLDEVPDPSQNRLQFLKLDEHAFAFSAYTDDRNGNMGYKYVRVLMFITSQDNFSCEINGRKSTDVSLYEFSENHKMKWQMFILNCKLPDGIDFNNVSSVKVIRSTTKQFVDVPIRYRIQDEKIITPDEYDYKMSICVPALFGNGYDAKRIVEFIELNTLQGIEKIYIYTNQKELDGSMKKTLKYYSDNHKITLIDYTLPFREDGVWYHGQLATVTDCLLRNTGITKYTFFNDFDEFFVPVIKSRTLFETISGLFEDPTIGSQRTALKYINAKIKSAPYSLKNIVSEKRIETRFTKCVVRPEMVFEQGIHHTSRVIQDNYKTVSHGGSLLRVYHYKDKKYCCEDESLLKKRHGDQLREKFDSVVGLLDL
|
2.4.1.-
|
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:19858195}; Note=Can also use Fe(2+) and Co(2+). {ECO:0000269|PubMed:19858195};
|
glycosylation [GO:0070085]; N-glycan processing [GO:0006491]; protein galactosylation [GO:0042125]
|
cytoplasm [GO:0005737]; Golgi cisterna membrane [GO:0032580]; intracellular organelle [GO:0043229]
|
beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity [GO:0003831]; glycosyltransferase activity [GO:0016757]; metal ion binding [GO:0046872]; UDP-galactosyltransferase activity [GO:0035250]
|
PF01697;
| null |
Glycosyltransferase 92 family
|
PTM: N-glycosylated. {ECO:0000269|PubMed:19858195}.
|
SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane {ECO:0000303|PubMed:19858195}; Single-pass type II membrane protein {ECO:0000303|PubMed:19858195}. Note=Localizes to vesicles or organelles in coelomocytes. {ECO:0000269|PubMed:19858195}.
| null |
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=84 uM for UDP-galactose {ECO:0000269|PubMed:19858195};
| null | null | null |
FUNCTION: Catalyzes the transfer of beta-galactose from UDP-galactose to position 4 of alpha-1,6-linked fucose at the reducing end GlcNAc in N-glycan cores (PubMed:19858195). Involved in susceptibility to the nematotoxic C.cinerea galectin Cgl2, likely by contributing to the synthesis of core alpha-1,6-fucosylated N-glycans to which Cgl2 binds (PubMed:20062796). {ECO:0000269|PubMed:19858195, ECO:0000269|PubMed:20062796}.
|
Caenorhabditis elegans
|
O16466
|
ATG18_CAEEL
|
MSATTSEENPDSINYIGFNQDSKVICVGHKDGYMFYKTADILENNTLTYEGENLTHLGLNNCLIIERLFSSALMVVISQKDPRVLHVYHFTSRNIICDHRFNKSVLTVRLNRDRIVVCLEDCIYIYNLKDMKMMHNIMDTPTNKLGVLDLTSNPGNALIAYPGSTDTGSVHLFDAINLSSVSTFNAHEGTIACLKFNQEGNMIATASTKGTVIRVYSVPNGHRLFEFRRGVTRCVNIYSLCFSSDSKYLTSSSNTETVHVFKLEKTEGVDNKPEASTEGGGWFDAINKTFSAYMPSQVLQVGELMTTERSFATAKLPGAARSNQVSLVSHKNQQYVMAATSDGFVYAYRLDPEGGELDLIKQHNIGPKSDTSRASPTSTGSGGAAKSAEASNQSVPNMDDPDDFPPMSHTSG
| null | null |
apoptotic cell clearance [GO:0043277]; autophagy [GO:0006914]; cellular response to toxic substance [GO:0097237]; dauer larval development [GO:0040024]; determination of adult lifespan [GO:0008340]; embryo development ending in birth or egg hatching [GO:0009792]; embryonic morphogenesis [GO:0048598]; germ cell proliferation [GO:0036093]; germ-line stem cell division [GO:0042078]; glycophagy [GO:0061723]; nucleophagy [GO:0044804]; plasma membrane repair [GO:0001778]; positive regulation of autophagy [GO:0010508]; programmed cell death [GO:0012501]; protein catabolic process [GO:0030163]; protein localization to phagophore assembly site [GO:0034497]; xenophagy [GO:0098792]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; extrinsic component of membrane [GO:0019898]; phagocytic vesicle [GO:0045335]; phagocytic vesicle membrane [GO:0030670]; phagophore assembly site membrane [GO:0034045]
|
phosphatidylinositol-3,5-bisphosphate binding [GO:0080025]; phosphatidylinositol-3-phosphate binding [GO:0032266]; phosphatidylinositol-4-phosphate binding [GO:0070273]; phosphatidylinositol-5-phosphate binding [GO:0010314]
|
PF21032;
|
2.130.10.10;
|
WD repeat PROPPIN family
| null |
SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome membrane {ECO:0000269|PubMed:22451698}; Peripheral membrane protein {ECO:0000305|PubMed:22451698}; Cytoplasmic side {ECO:0000305|PubMed:22451698}. Cytoplasm {ECO:0000269|PubMed:25124690}. Note=Partially localizes to the phagosome membrane of engulfed apoptotic cells. {ECO:0000269|PubMed:22451698}.
| null | null | null | null | null |
FUNCTION: Component of the autophagy machinery that is recruited to phosphatidylinositols on preautophagosomal structures, which are early autophagic structures, to promote autophagosome formation, and the subsequent degradation and clearance of engulfed apoptotic cells and P-granules in somatic cells (PubMed:12958363, PubMed:19167332, PubMed:21183797, PubMed:21802374, PubMed:22451698, PubMed:25124690, PubMed:28557996). In particular, binds with high affinity to phosphatidylinositols including phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P), and more weakly to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:21802374, PubMed:22451698). Plays a role in mitophagy, which is the autophagic consumption of mitochondria, in response to dietary restriction (PubMed:30133321). Involved in xenophagy, the autophagy-mediated degradation of pathogens and pathogen products, such as toxins (PubMed:27875098). Also plays a role in membrane-pore repair (PubMed:27875098). In a daf-18/PTEN- and daf-16/FOXO-dependent manner, required for the proliferation of germ stem cell progenitors in the gonad during the late phases of larval development (PubMed:28285998). By regulating the release of neurotransmitters and neuropeptides, involved in the control of lifespan in response to dietary restriction and daf-2 signaling (PubMed:28557996). Probably through its involvement in autophagy, required for dauer formation (PubMed:12958363). {ECO:0000269|PubMed:12958363, ECO:0000269|PubMed:19167332, ECO:0000269|PubMed:21183797, ECO:0000269|PubMed:21802374, ECO:0000269|PubMed:22451698, ECO:0000269|PubMed:25124690, ECO:0000269|PubMed:27875098, ECO:0000269|PubMed:28285998, ECO:0000269|PubMed:28557996, ECO:0000269|PubMed:30133321, ECO:0000303|PubMed:22451698}.
|
Caenorhabditis elegans
|
O16658
|
S35A3_CAEEL
|
MNRANDTSSNLKLISLVVLIVQTTALVLTLRYSQTQKSEGPRYLSSTAVVCAEIIKLITCFFVIYRNNGYRFSGMLNELNREIFASPQTRADSLKVAVPAIMYVIQNNLLFFALKKLDAATYQVTYQLKILTTAIFSVTMLGKSLHRYNWMALILLTAGVALVQYPSGDSTTSKSTAAEHDASDNILGLGAVLAACFSSGFAGVYFEKILKTSKVSLWIRNIQLAFFSVFGALLVCWLYDWQAISDDGFLRGYNGVIWIVVLLQAYGGLVIALVVKYADNILKGFAVSLSIILSSFTSWLVLGDLTITTTFAIGATVVIFATFLYGHEPKSTPAEAHNA
| null | null |
UDP-galactose transmembrane import into Golgi lumen [GO:0097624]; UDP-N-acetylgalactosamine transmembrane transport [GO:0015789]; UDP-N-acetylglucosamine transmembrane transport [GO:1990569]
|
Golgi membrane [GO:0000139]
|
UDP-galactose transmembrane transporter activity [GO:0005459]; UDP-N-acetylgalactosamine transmembrane transporter activity [GO:0005463]; UDP-N-acetylglucosamine transmembrane transporter activity [GO:0005462]
|
PF04142;
|
1.10.3730.20;
|
Nucleotide-sugar transporter family, SLC35A subfamily
| null |
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9Y2D2}; Multi-pass membrane protein {ECO:0000255}.
| null |
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=25.2 uM for uridine diphosphate-N-acetylglucosamine as substrate (at 25 degrees Celsius) {ECO:0000269|PubMed:17060606}; KM=24.9 uM for uridine diphosphate-N-acetylgalactosamine as substrate (at 25 degrees Celsius) {ECO:0000269|PubMed:17060606};
| null | null | null |
FUNCTION: Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) transporter in the Golgi apparatus (PubMed:17060606). UDP-N-acetylgalactosamine (UDP-GalNAc) transporter in the Golgi apparatus (PubMed:17060606). Apparently transports UDP-GlcNAc and UDP-GalNAc simultaneously, and independently, by an unknown mechanism (PubMed:17060606). Functions redundantly with nucleotide sugar transporter srf-3 (PubMed:17652078). May be involved in gonadal development (PubMed:17652078). {ECO:0000269|PubMed:17060606, ECO:0000269|PubMed:17652078}.
|
Caenorhabditis elegans
|
O16785
|
PARV_CAEEL
|
MSTLGRSKTPSRDEPKKPGVFEKLSGTLSRKKKAPEDEHGNQGGAHHATDEDEVLELELEGREALDQSLVPVLARNIWLEEGEIRRYLTKETARDQKLAQVVDLLIYWLNEELADQRIVVRHLQEDLFDGQIIQKLLEKLEQIRIEVPEVSQSEEGQRQKLQIVVQTANRILGQPREQEKWSADLIHQKDFTAIIQLLVLLALHYRAPVRFPDNVVANVVVAQKEHGQVKTHRITEQITTVQTELAPKGTRDAFDTLFDYGPDKLAHVKTSLLAFCNKHLNKINLEVSDLDNQFQDGVFLVLLVGLLEGYFVPLYHFNLQVQSHEEKVKNVQFAFKLMEDTGLEKPRSRVQDIANGDVKSTLRLLHLLFTKYKHI
| null | null |
actin cytoskeleton organization [GO:0030036]; cell projection assembly [GO:0030031]; establishment or maintenance of cell polarity [GO:0007163]; mitochondrion organization [GO:0007005]; muscle cell cellular homeostasis [GO:0046716]; positive regulation of locomotion [GO:0040017]; positive regulation of sarcomere organization [GO:0060298]; striated muscle cell development [GO:0055002]; substrate adhesion-dependent cell spreading [GO:0034446]
|
actin cytoskeleton [GO:0015629]; axon [GO:0030424]; basal plasma membrane [GO:0009925]; cytoplasm [GO:0005737]; focal adhesion [GO:0005925]; M band [GO:0031430]; perikaryon [GO:0043204]; striated muscle dense body [GO:0055120]
|
actin binding [GO:0003779]
|
PF00307;
|
1.10.418.10;
|
Parvin family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12781130}. Cytoplasm, myofibril, sarcomere, M line {ECO:0000269|PubMed:23283987}. Perikaryon {ECO:0000269|PubMed:12781130}. Cell projection, axon {ECO:0000269|PubMed:12781130}. Note=Colocalizes with integrins and pat-4/ILK (PubMed:12781130). Colocalizes to M line and dense bodies with cpna-1 (PubMed:23283987). {ECO:0000269|PubMed:12781130, ECO:0000269|PubMed:23283987}.
| null | null | null | null | null |
FUNCTION: Involved in the regulation of cell adhesion and cytoskeleton organization. Component of an integrin containing attachment complex, which is required for muscle development and maintenance (PubMed:22253611). During embryonic development, required to recruit cpna-1, unc-89 and myofilaments to newly forming integrin attachments composed of integrins pat-2/pat-3, pat-4 and unc-112 (PubMed:12781130, PubMed:23283987). Also required to reposition the integrin-based attachments so that they form the highly ordered array of dense body and M-line attachments that are characteristic of mature muscle cells (PubMed:12781130, PubMed:23283987). During the formation of neuromuscular junctions at the larval stage, negatively regulates membrane protrusion from body wall muscles (PubMed:16495308). {ECO:0000269|PubMed:12781130, ECO:0000269|PubMed:16495308, ECO:0000269|PubMed:22253611, ECO:0000269|PubMed:23283987}.
|
Caenorhabditis elegans
|
O16810
|
ORC1_DROME
|
MVNKENARSVGQQVKWIGSQDELPPVKNLEHKNVYFYQKCIYGPLTLSVGDFILVSNADAAEPDTVSGCDVARILHMYELRELTDREPCRAIVQWYSWPKAIPHNKYDDDEVAIDFSLEVIEEHRPYDNDVALGAIYRKCIVLEGTSKTSAEEILKRHANKLKSTACPMFVSRYRFVKVKRSYRLIPLEIHLEQPEDNARPTRSSRKSLTAHRESKRSISARHDDTAGNKGSSVEKRRRASMAASSSVEFIDVNSFICENKVSPIKIVGGRSVVRLSEKKNAPEINANYLPASPLTEKNAKVETPKSRASAARRNLNLSLDRGADTTADSDCLNYSIVQQTPDPKTPSNDMKIKLRLSERRRSVRLASMDVDPLSLEEAVQEPNAQGRKRLGVANGDIYHTPTKKSKEPLESAAATEQTPSTRRKSILKSATSRLAEGTPRRSIHLSNIVEQRVFEDDEIISTPKRGRSKKTVQDNDEDYSPKKSVQKTPTRTRRSSTTTKTATTPSKGITTATATPMTPSQKMKKIRAGELSPSMQQRTDLPAKDSSKSELQLAREQLHVSVVPKSLPCREREFENIYAFLEGKIQDQCGGCMYVSGVPGTGKTATVTGVIRTLQRMAKQNELPAFEYLEINGMRLTEPRQAYVQIYKQLTGKTVSWEQAHALLEKRFTTPAPRRVTTVLLVDELDILCNRRQDVVYNLLDWPTKSAAKLVVVTIANTMDLPERLLMGKVTSRLGLTRLTFQPYSHKQLQEIVTARLGGSETFKGEAVQLVARKVAAVSGDARRALDICRRATEIADTAAVKCVTMLHVQQALAEMIASAKVQAIRNCSRMEQIFLQAIAAEVTRTGVEETTFMGVYQQVETIAAFMGVTFPPPGRALRLCSKLGAERLIISEHSRNDLFQKILLNVSADDIHYALRVEEMVN
| null | null |
DNA amplification [GO:0006277]; DNA replication initiation [GO:0006270]; mitotic DNA replication checkpoint signaling [GO:0033314]
|
nuclear origin of replication recognition complex [GO:0005664]; nucleus [GO:0005634]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; chromatin binding [GO:0003682]; DNA replication origin binding [GO:0003688]; metal ion binding [GO:0046872]
|
PF00004;PF17872;PF01426;PF09079;
|
1.10.8.60;2.30.30.490;3.40.50.300;
|
ORC1 family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. {ECO:0000269|PubMed:9363940}.
|
Drosophila melanogaster (Fruit fly)
|
O16829
|
CECC_DROME
|
MNFYKIFVFVALILAISIGQSEAGWLKKLGKRIERIGQHTRDATIQGLGIAQQAANVAATARG
| null | null |
antibacterial humoral response [GO:0019731]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; humoral immune response [GO:0006959]; innate immune response [GO:0045087]
|
extracellular region [GO:0005576]; extracellular space [GO:0005615]
| null |
PF00272;
| null |
Cecropin family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Cecropins have lytic and antibacterial activity against several Gram-positive and Gram-negative bacteria.
|
Drosophila melanogaster (Fruit fly)
|
O16844
|
COS_DROME
|
MEIPIQVAVRIFPHRELKDLLRSFGPTEPKKDAQAVDEGADSKDSEAQVPAAEKDNPSISETDPNGNAEQDSAADSKTIPDANGNDSGQKDYPDSAYCVQAIPISASALGLPSALPGGDPMDSIAAGLIQVGPHTVPVTHALPSSSSQEQVYHQTVFPLITLFLEGFDASVVTYGQRGQGKSYTLYGNVQDPTLTDSTEGVVQLCVRDIFSHISLHPERTYAINVGFVEICGGDVCDLLGMGNIHCTNVDAVFHWLQVGLSARQSLPAHTLFTLTLEQQWVSKEGLLQHRLSTASFSDLCGTERCGDQPPGRPLDAGLCMLEQVISTLTDPGLMYGVNGNIPYGQTTLTTLLKDSFGGRAQTLVILCVSPLEEHLPETLGNLQFAFKVQCVRNFVIMNTYSDDNTMIVQPAEPVPESNSSAGPLSQAGPGDNFGLQFAASQWSKLVTNAEGLFSKLIDSKLITEVEKEQIEEWLFLKQECEECLSSTEAMRQQKQLVPILEAEEPEDVNSEAANSESPNSDNENDTDNESHRPDLDDKIESLMEEFRDKTDALILEKHAEYLSKHPKAVMQSQDREIEAQPPEENGDDRKVSIGSRRRSVQPGASLSTAELAMLNRVASQQPPPPIDPESVVDPLESSSGEGIRQAALAAAAATAPIEQLQKKLRKLVAEIEGKQRQLREIEETIQVKQNIIAELVKNSDTRSHAKQRFHKKRAKLEAECDKAKKQLGKALVQGRDQSEIERWTTIIGHLERRLEDLSSMKHIAGESGQKVKKLQQSVGESRKQADDLQKKLRKECKLRCQMEAELAKLRESRETGKELVKAQGSPEQQGRQLKAVQARITHLNHILREKSDNLEEQPGPEQQETLRHEIRNLRGTRDLLLEERCHLDRKLKRDKVLTQKEERKLLECDEAIEAIDAAIEFKNEMITGHRSIDTSDRIQREKGEQMLMARLNRLSTEEMRTLLYKYFTKVIDLRDSSRKLELQLVQLERERDAWEWKERVLSNAVRQARLEGERNAVLLQRQHEMKLTLMLRHMAEETSASSASYGERALAPACVAPPVQASSDFDYDHFYKGGGNPSKALIKAPKPMPTGSALDKYKDKEQRSGRNIFAKFHVLTRYASAAAAGSSGSTAEESTALIESTTTATATTTSTTTTGAVGKVKDKALVSFRPEQLKRLMPAPTATKVTRQKNKIIIQDASRRN
| null | null |
cytoplasmic sequestering of protein [GO:0051220]; follicle cell of egg chamber development [GO:0030707]; imaginal disc-derived wing morphogenesis [GO:0007476]; intraciliary transport [GO:0042073]; microtubule-based movement [GO:0007018]; negative regulation of smoothened signaling pathway [GO:0045879]; regulation of apoptotic process [GO:0042981]; smoothened signaling pathway [GO:0007224]
|
cilium [GO:0005929]; cytosol [GO:0005829]; Hedgehog signaling complex [GO:0035301]; 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]; molecular sequestering activity [GO:0140313]; plus-end-directed microtubule motor activity [GO:0008574]; protein kinase binding [GO:0019901]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; signaling adaptor activity [GO:0035591]; smoothened binding [GO:0005119]; ubiquitin protein ligase binding [GO:0031625]
|
PF00225;
|
3.40.850.10;
|
TRAFAC class myosin-kinesin ATPase superfamily, Kinesin family, KIF27 subfamily
|
PTM: Polyubiquitinated by Ubr3, which leads to proteasomal degradation. {ECO:0000269|PubMed:27195754}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:9244298}.
| null | null | null | null | null |
FUNCTION: Regulates cubitus interruptus (ci) processing by recruiting multiple kinases to promote its efficient phosphorylation. Scaffolds multiple kinases and ci into proximity to promote its hyperphosphorylation, which then targets it for SCFSlimb/proteasome-mediated processing to generate its repressor form. Hh signaling inhibits ci phosphorylation by interfering with the cos-ci-kinases complex formation. Negatively regulates hh-signaling pathways during various processes, including photoreceptor differentiation (PubMed:25639794, PubMed:27195754). May negatively regulate a hh-signaling pathway which functions in the intestinal immune response to bacterial uracil by activating the Duox-dependent production of reactive oxygen species (ROS) (PubMed:25639794). {ECO:0000269|PubMed:15691767, ECO:0000269|PubMed:25639794, ECO:0000269|PubMed:9244298}.
|
Drosophila melanogaster (Fruit fly)
|
O16850
|
FOXO_CAEEL
|
MQLEQKSSLHCSKCRNFLQKFSQDMQAWNCRELDSPLPSDITLHNLEPARPDSGMSFSTDFDDDFFNLDLHQQERSASFGGVTQYSQQFLREKCSFSPYFHTSLETVDSGRTSLYGSNEQCGQLGGASSNGSTAMLHTPDGSNSHQTSFPSDFRMSESPDDTVSGKKTTTRRNAWGNMSYAELITTAIMASPEKRLTLAQVYEWMVQNVPYFRDKGDSNSSAGWKNSIRHNLSLHSRFMRIQNEGAGKSSWWVINPDAKPGRNPRRTRERSNTIETTTKAQLEKSRRGAKKRIKERALMGSLHSTLNGNSIAGSIQTISHDLYDDDSMQGAFDNVPSSFRPRTQSNLSIPGSSSRVSPAIGSDIYDDLEFPSWVGESVPAIPSDIVDRTDQMRIDATTHIGGVQIKQESKPIKTEPIAPPPSYHELNSVRGSCAQNPLLRNPIVPSTNFKPMPLPGAYGNYQNGGITPINWLSTSNSSPLPGIQSCGIVAAQHTVASSSALPIDLENLTLPDQPLMDTMDVDALIRHELSQAGGQHIHFDL
| null | null |
cellular response to heat [GO:0034605]; cellular response to oxidative stress [GO:0034599]; cytoplasmic sequestering of protein [GO:0051220]; dauer larval development [GO:0040024]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; determination of adult lifespan [GO:0008340]; DNA damage response [GO:0006974]; heat acclimation [GO:0010286]; innate immune response [GO:0045087]; insulin receptor signaling pathway [GO:0008286]; intracellular signal transduction [GO:0035556]; maintenance of protein location in nucleus [GO:0051457]; muscle tissue development [GO:0060537]; negative regulation of gene expression [GO:0010629]; negative regulation of multicellular organism growth [GO:0040015]; negative regulation of transcription by RNA polymerase II [GO:0000122]; nematode larval development [GO:0002119]; positive regulation of adaptive immune response [GO:0002821]; positive regulation of apoptotic process [GO:0043065]; positive regulation of dauer larval development [GO:0061066]; positive regulation of defense response to bacterium [GO:1900426]; positive regulation of gene expression [GO:0010628]; positive regulation of neuromuscular synaptic transmission [GO:1900075]; positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436]; positive regulation of synaptic assembly at neuromuscular junction [GO:0045887]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of cell cycle process [GO:0010564]; regulation of dauer entry [GO:1905909]; regulation of dauer larval development [GO:0061065]; regulation of DNA-templated transcription [GO:0006355]; regulation of gene expression [GO:0010468]; regulation of lipid biosynthetic process [GO:0046890]; regulation of lipid storage [GO:0010883]; regulation of synaptic assembly at neuromuscular junction [GO:0008582]; regulation of transcription by RNA polymerase II [GO:0006357]; response to oxidative stress [GO:0006979]; response to starvation [GO:0042594]; response to UV [GO:0009411]; short-term memory [GO:0007614]; sleep [GO:0030431]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleus [GO:0005634]
|
14-3-3 protein binding [GO:0071889]; beta-catenin binding [GO:0008013]; DEAD/H-box RNA helicase binding [GO:0017151]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription factor binding [GO:0140297]; enzyme binding [GO:0019899]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]; sequence-specific DNA binding [GO:0043565]; ubiquitin protein ligase binding [GO:0031625]; ubiquitin-specific protease binding [GO:1990381]
|
PF00250;
|
1.10.10.10;
| null |
PTM: Phosphorylated by akt-1 and/or akt-2 (PubMed:18358814, PubMed:21531333). Phosphorylated by sgk-1 (PubMed:18358814). Phosphorylated by unc-43 (PubMed:23805378). Phosphorylated by jnk-1 (PubMed:15767565). Dephosphorylated by tax-6 in vitro (PubMed:23805378). {ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:18358814, ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:23805378}.; PTM: Ubiquitinated. Ubiquitination by rle-1 leads to proteasome-mediated degradation. {ECO:0000269|PubMed:17276341}.; PTM: Methylation by prmt-1 prevents phosphorylation and promotes translocation to the nucleus to allow for daf-16-dependent transcription. {ECO:0000269|PubMed:21531333}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11381260, ECO:0000269|PubMed:11747825, ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:15888317, ECO:0000269|PubMed:17551714, ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:18832074, ECO:0000269|PubMed:19252938, ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:22916022, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:24146615}. Cytoplasm {ECO:0000269|PubMed:11381260, ECO:0000269|PubMed:11747825, ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:15888317, ECO:0000269|PubMed:17551714, ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:18832074, ECO:0000269|PubMed:19252938, ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:22916022, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:24146615}. Note=Shuttles between cytoplasm and nucleus (PubMed:11381260, PubMed:17894411). Nuclear translocation is inhibited by phosphorylation by AKT proteins (PubMed:11381260, PubMed:11747825, PubMed:21531333). Association with ftt-2 sequesters daf-16 in the cytoplasm (PubMed:21531333). Association with prmt-1 allows for translocation to the nucleus (PubMed:21531333). Nuclear translocation is promoted by phosphorylation by unc-43 and inhibited by dephosphorylation by tax-6 (PubMed:23805378). Nuclear translocation is promoted by jnk-1 upon heat stress and by sek-1 upon oxidative stress (PubMed:15767565, PubMed:15888317). Nucleocytoplasmic shuttling is induced by starvation, heat treatment, hypergravity, reactive oxygen species (generated by juglone), exposure to tributyltin or 4-hydroxy-E-globularinin (4-HEG) and the flavonoids kaempferol and fisetin (PubMed:11381260, PubMed:17551714, PubMed:18832074, PubMed:19252938, PubMed:21531333, PubMed:23805378). Nuclear localization induced by nematophagous fungal infection (PubMed:24146615). {ECO:0000269|PubMed:11381260, ECO:0000269|PubMed:11747825, ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:15888317, ECO:0000269|PubMed:17551714, ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:18832074, ECO:0000269|PubMed:19252938, ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:24146615}.; SUBCELLULAR LOCATION: [Isoform a]: Nucleus {ECO:0000269|PubMed:24834345}. Cytoplasm {ECO:0000269|PubMed:24834345}. Note=Ratio of nuclear to cytoplasmic localization is daf-2-dependent. {ECO:0000269|PubMed:24834345}.; SUBCELLULAR LOCATION: [Isoform d]: Nucleus {ECO:0000269|PubMed:24834345}. Cytoplasm {ECO:0000269|PubMed:24834345}. Note=Ratio of nuclear to cytoplasmic localization is daf-2-dependent. {ECO:0000269|PubMed:24834345}.; SUBCELLULAR LOCATION: [Isoform f]: Nucleus {ECO:0000269|PubMed:24834345}. Cytoplasm {ECO:0000269|PubMed:24834345}. Note=Ratio of nuclear to cytoplasmic localization is daf-2-dependent. {ECO:0000269|PubMed:24834345}.
| null | null | null | null | null |
FUNCTION: Forkhead-type transcription factor (PubMed:9360933). Binds to the promoters of genes that contain the daf-16/FOXO binding element (DBE), TTGTTTAC, in their regulatory region (PubMed:10880363, PubMed:23770237, PubMed:26675724). Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway which affects lipogenesis, lifespan, starvation survival, heat shock and oxidative stress responses, sleep, associative memory, and dauer formation (PubMed:11381260, PubMed:11747821, PubMed:11747825, PubMed:12750521, PubMed:14622602, PubMed:17900900, PubMed:18358814, PubMed:18762027, PubMed:18832074, PubMed:19103192, PubMed:21531333, PubMed:22081913, PubMed:26675724, PubMed:29523076, PubMed:8247153, PubMed:9360933). Longevity signaling predominantly arises from expression in the intestine (PubMed:14622602). Transcriptional activity of daf-16/FOXO is negatively regulated by interaction with host cell factor homolog hcf-1; and by cytoplasmic sequestration by association with ftt-2 (PubMed:11381260, PubMed:18828672, PubMed:21531333). Inhibition is required for the carbon dioxide (CO2) avoidance response (PubMed:18524954). Upon loss of inhibition, daf-16 translocates to the nucleus to regulate genes that result in delayed reproduction and growth while increasing stress resistance starvation tolerance and longevity (PubMed:11747825, PubMed:21531333). Association with arginine methyltransferase prmt-1 prevents phosphorylation and allows for translocation to the nucleus and the subsequent transcription of longevity-related genes (PubMed:21531333). Modulation of its activity by cGMP levels in sensory neurons regulates lifespan (PubMed:19489741). Has a protective role against muscle dystrophy (PubMed:18397876). Involved in mediating protection against aberrant protein aggregation proteotoxicity (PubMed:16902091). Influences transcription of genes that code for proteins involved in immunity as part of a general stress response (PubMed:17096597, PubMed:18245330). Targets genes that inhibit and stimulate tumor growth (PubMed:17934462). Targets kinases, phosphatases and transcription factors that are primarily involved in signaling and gene regulation (PubMed:24516399). Thought to regulate ins-7 in FOXO-to-FOXO signaling, which coordinates daf-16 expression (PubMed:18025456). Activity is positively regulated by shc-1-mediated inhibition of daf-2 and activation of JNK pathway (PubMed:18832074, PubMed:22916022). Through the regulation of its activity by shc-1-mediated inhibition of daf-2 and activation of JNK pathway, plays a role in maintaining the integrity of the gonad (PubMed:22916022). Functions by indirect interaction with jnk-1 of the mitogen-activated protein kinase (MAPK) pathway (PubMed:17894411). Involved in increased proteasome activity by activating expression of rpn-6.1 in response to proteotoxic stress, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity (PubMed:22922647). Also regulates proteasome activity in the intestine by preventing expression of deubiquitinase ubh-4 (PubMed:23770237). Represses transcription of natc-1 (PubMed:25330323). Involved in regulation of srh-234 expression (PubMed:25357003). Binds to the promoter of the AMPK-gamma regulatory subunit, aakg-4, and activates its transcription (PubMed:24516399). Also activates transcription of AMPK-gamma regulatory subunit, aakg-1 (PubMed:24516399). Maintains endoplasmic reticulum (ER) function by inducing protein degradation and elimination to remove misfolded secretory proteins from the ER independently of the ire-1/xbp-1 unfolded protein response pathway (PubMed:25448701). Regulates epidermal innate immunity to nematophagous fungal infection and physical wounding which trigger bli-3 induced ROS release, leading to daf-16 activation independently of daf-2 signaling (PubMed:24146615). May negatively regulate resistance to stress caused by oxidized cholesterol adducts by preventing the activation of daf-9 and nuclear hormone receptor daf-12, two members of the steroid signaling pathway (PubMed:24957743). Promotes apoptosis during embryonic development (PubMed:25383666). Probably through the regulation of the autophagy genes atg-18 and atg-16.2, plays a role in regulating stem cell number in the germline during larval development (PubMed:28285998). Plays a role in learning and memory; including associative memory, and aversive gustatory associated learning known as salt avoidance learning (PubMed:26675724, PubMed:30779740). Plays a role in regulating gene transcription in response to white light exposure (PubMed:29500338). Binds to the promoter of dex-1 to positively regulate its expression in seam cells during the dauer phase (PubMed:30409788). Plays a role in transgenerational lipid accumulation in response to a high-fat diet (PubMed:35140229). {ECO:0000269|PubMed:10880363, ECO:0000269|PubMed:11381260, ECO:0000269|PubMed:11747821, ECO:0000269|PubMed:11747825, ECO:0000269|PubMed:12750521, ECO:0000269|PubMed:14622602, ECO:0000269|PubMed:16902091, ECO:0000269|PubMed:17096597, ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:17900900, ECO:0000269|PubMed:17934462, ECO:0000269|PubMed:18025456, ECO:0000269|PubMed:18245330, ECO:0000269|PubMed:18358814, ECO:0000269|PubMed:18397876, ECO:0000269|PubMed:18524954, ECO:0000269|PubMed:18762027, ECO:0000269|PubMed:18832074, ECO:0000269|PubMed:19103192, ECO:0000269|PubMed:19489741, ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:22081913, ECO:0000269|PubMed:22916022, ECO:0000269|PubMed:22922647, ECO:0000269|PubMed:23770237, ECO:0000269|PubMed:24146615, ECO:0000269|PubMed:24516399, ECO:0000269|PubMed:24957743, ECO:0000269|PubMed:25330323, ECO:0000269|PubMed:25357003, ECO:0000269|PubMed:25383666, ECO:0000269|PubMed:25448701, ECO:0000269|PubMed:28285998, ECO:0000269|PubMed:29500338, ECO:0000269|PubMed:30409788, ECO:0000269|PubMed:30779740, ECO:0000269|PubMed:8247153, ECO:0000269|PubMed:9360933}.; FUNCTION: [Isoform a]: Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway (PubMed:24834345). May play a role in lifespan modulation, but less significant than that played by isoforms d and f (PubMed:24834345). {ECO:0000269|PubMed:24834345}.; FUNCTION: [Isoform d]: Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway (PubMed:24834345). Transcript level in the early adult may play a role in lifespan modulation, but effect is more significant than that played by isoform a (PubMed:24834345). {ECO:0000269|PubMed:24834345}.; FUNCTION: [Isoform f]: Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway (PubMed:24834345). Transcript level in the early adult may play a role in lifespan modulation, but effect is more significant than that played by isoform a (PubMed:24834345). {ECO:0000269|PubMed:24834345}.
|
Caenorhabditis elegans
|
O17072
|
NFYC1_CAEEL
|
MSQFPEVLDNNLLHAENNETAEYIQNDGTNQSEVFMEHPYTPNMHPINMPSIVEGAVHPYNNLIHHNDAIPPAKYASMRQMTEDFWREKKQKMTEISEEDMLNKSKNMSVPMARVKKIMRIDDDVRNFMIASDAPIFMAQAAEFFIEEMTAMGWQYVSEARRRILQKADIASAVQKSDQFDFLIDFLPPKTVPTTSTNGPGHMSEDSFQDPNMHSDFHQRTSNSSVNRSHHN
| null | null |
negative regulation of transcription by RNA polymerase II [GO:0000122]; regulation of gene expression [GO:0010468]; regulation of transcription by RNA polymerase II [GO:0006357]; tissue development [GO:0009888]
|
CCAAT-binding factor complex [GO:0016602]; cytoplasm [GO:0005737]; nucleus [GO:0005634]; perikaryon [GO:0043204]
|
DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription repressor activity [GO:0001217]; protein heterodimerization activity [GO:0046982]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]
|
PF00808;
|
1.10.20.10;
|
NFYC/HAP5 subunit family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17574230}. Cytoplasm {ECO:0000269|PubMed:15704008, ECO:0000269|PubMed:17574230}. Perikaryon {ECO:0000269|PubMed:15704008}. Note=Localizes to the cytoplasm of secretory cells and cell bodies of the small ganglia surrounding the pharynx. {ECO:0000269|PubMed:15704008}.
| null | null | null | null | null |
FUNCTION: Component of sequence-specific heterotrimeric transcription factor (nfya-1-NF-Y and nfya-2-NF-Y) complexes which specifically recognize a 5'-CCAAT-3' box motif found in the promoters of its target genes to regulate their expression and control cellular identity in particular tissue types (PubMed:17574230). In association with the components in the NF-Y complexes, represses the expression of the T-box transcription factor tbx-2 throughout larval development, which most likely restricts its expression to certain tissues (PubMed:23933492). May act to repress txb-2 expression in conjunction with tbx-2 itself, which has an autoregulatory role (Probable). In association with the components in the nfya-1-NF-Y complex, negatively regulates the expression of the homeobox protein egl-5 to spatially restrict its expression in tissues such as the head (PubMed:17574230). May regulate egl-5 expression in association with the mes-2-mes-3-mes-6 complex (PubMed:17574230). {ECO:0000269|PubMed:17574230, ECO:0000269|PubMed:23933492, ECO:0000305|PubMed:25873636}.
|
Caenorhabditis elegans
|
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