Protein: Hepatocyte growth factor-regulated tyrosine kinase substrate (A0A7I2V5A3)
Organism: Homo sapiens (Human)
Function: Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin- coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. May contribute to the efficient recruitment of SMADs to the activin receptor complex. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation
Subcellular location: Cytoplasm. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Endosome, multivesicular body membrane; Peripheral membrane protein
InterPro domains:
- IPR017455: Zinc finger, FYVE-related (domain) [160-220]
- IPR024641: Hepatocyte growth factor-regulated tyrosine kinase substrate, helical domain (domain) [406-501]
- IPR002014: VHS domain (domain) [7-143]
- IPR000306: FYVE zinc finger (domain) [155-221]
- IPR008942: ENTH/VHS (homologous_superfamily) [1-154]
- IPR003903: Ubiquitin interacting motif (conserved_site) [258-277]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [155-225]
- IPR017073: Hepatocyte growth factor-regulated tyrosine kinase substrate/VPS27 (family) [1-745]
- IPR011011: Zinc finger, FYVE/PHD-type (homologous_superfamily) [159-221]
Sequence:
MGRGSGTFERLLDKATSQLLLETDWESILQICDLIRQGDTQAKYAVNSIKKKVNDKNPHVALYALEVMESVVKNCGQTVHDEVANKQTMEELKDLLKRQVEVNVRNKILYLIQAWAHAFRNEPKYKVVQDTYQIMKVEGHVFPEFKESDAMFAAERAPDWVDAEECHRCRVQFGVMTRKHHCRACGQIFCGKCSSKYSTIPKFGIEKEVRVCEPCYEQLNRKAEGKATSTTELPPEYLTSPLSQQSQLPPKRDETALQEEEELQLALALSQSEAEEKERLRQKSTYTSYPKAEPMPSASSAPPASSLYSSPVNSSAPLAEDIDPELARYLNRNYWEKKQEEARKSPTPSAPVPLTEPAAQPGEGHAAPTNVVENPLPETDSQPIPPSGGPFSEPQFHNGESEESHEQFLKALQNAVTTFVNRMKSNHMRGRSITNDSAVLSLFQSINGMHPQLLELLNQLDERRLYYEGLQDKLAQIRDARGALSALREEHREKLRRAAEEAERQRQIQLAQKLEIMRQKKQEYLEVQRQLAIQRLQEQEKERQMRLEQQKQTVQMRAQMPAFPLPYAQLQAMPAAGGVLYQPSGPASFPSTFSPAGSVEGSPMHGVYMSQPAPAAGPYPSMPSTAADPSMVSAYMYPAGATGAQAAPQAQAGPTASPAYSSYQPTPTAGYQNVASQAPQSLPAISQPPQSSTMGYMGSQSVSMGYQPYNMQNLMTTLPSQDASLPPQQPYIAGQQPMYQQAMLTSGVTLHTVHLKRLVSNCRRPASLSSTAGSVPSLRVRGGLHPKPTSLVLSLLQSLS
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019904 (protein domain specific binding), GO:0019899 (enzyme binding), GO:0044389 (ubiquitin-like protein ligase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0023057 (negative regulation of signaling), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0051050 (positive regulation of transport), GO:0009056 (catabolic process), GO:0033036 (macromolecule localization), GO:0050793 (regulation of developmental process), GO:0044237 (cellular metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0065009 (regulation of molecular function), GO:0061919 (process utilizing autophagic mechanism), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0090287 (regulation of cellular response to growth factor stimulus), GO:0050790 (regulation of catalytic activity), GO:0009968 (negative regulation of signal transduction), GO:0010648 (negative regulation of cell communication), GO:1903530 (regulation of secretion by cell), GO:0051049 (regulation of transport), GO:0051047 (positive regulation of secretion), GO:0044085 (cellular component biogenesis), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0044248 (cellular catabolic process), GO:0008285 (negative regulation of cell population proliferation), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0051649 (establishment of localization in cell), GO:0060627 (regulation of vesicle-mediated transport), GO:0090288 (negative regulation of cellular response to growth factor stimulus), GO:0051668 (localization within membrane), GO:0044089 (positive regulation of cellular component biogenesis), GO:1901343 (negative regulation of vasculature development), GO:0045184 (establishment of protein localization), GO:0006914 (autophagy), GO:0044087 (regulation of cellular component biogenesis), GO:0009894 (regulation of catabolic process), GO:2000026 (regulation of multicellular organismal development), GO:0042127 (regulation of cell population proliferation), GO:0046907 (intracellular transport), GO:0010646 (regulation of cell communication), GO:1903532 (positive regulation of secretion by cell), GO:0006810 (transport), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0070727 (cellular macromolecule localization), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0071705 (nitrogen compound transport), GO:0042176 (regulation of protein catabolic process), GO:0051246 (regulation of protein metabolic process), GO:0010256 (endomembrane system organization), GO:0072594 (establishment of protein localization to organelle), GO:1901342 (regulation of vasculature development), GO:0017157 (regulation of exocytosis), GO:0071702 (organic substance transport), GO:0010628 (positive regulation of gene expression), GO:1904892 (regulation of receptor signaling pathway via STAT), GO:0045921 (positive regulation of exocytosis), GO:0010468 (regulation of gene expression), GO:0022607 (cellular component assembly), GO:0016236 (macroautophagy), GO:0010640 (regulation of platelet-derived growth factor receptor signaling pathway), GO:0006886 (intracellular protein transport), GO:1904893 (negative regulation of receptor signaling pathway via STAT), GO:0015031 (protein transport), GO:0030948 (negative regulation of vascular endothelial growth factor receptor signaling pathway), GO:0051046 (regulation of secretion), GO:0045765 (regulation of angiogenesis), GO:0008104 (protein localization), GO:0051338 (regulation of transferase activity), GO:0030947 (regulation of vascular endothelial growth factor receptor signaling pathway), GO:0007034 (vacuolar transport), GO:0006996 (organelle organization), GO:0051174 (regulation of phosphorus metabolic process), GO:2000181 (negative regulation of blood vessel morphogenesis), GO:0061024 (membrane organization), GO:0072657 (protein localization to membrane), GO:0016525 (negative regulation of angiogenesis), GO:0070925 (organelle assembly), GO:0033365 (protein localization to organelle), GO:0072666 (establishment of protein localization to vacuole), GO:0031399 (regulation of protein modification process), GO:0046425 (regulation of receptor signaling pathway via JAK-STAT), GO:0016050 (vesicle organization), GO:0046426 (negative regulation of receptor signaling pathway via JAK-STAT), GO:0019220 (regulation of phosphate metabolic process), GO:0043549 (regulation of kinase activity), GO:0006605 (protein targeting), GO:0010324 (membrane invagination), GO:0007032 (endosome organization), GO:0007041 (lysosomal transport), GO:0006623 (protein targeting to vacuole), GO:0042325 (regulation of phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0036258 (multivesicular body assembly), GO:0006622 (protein targeting to lysosome), GO:0036257 (multivesicular body organization), GO:0045859 (regulation of protein kinase activity), GO:0072665 (protein localization to vacuole), GO:0071900 (regulation of protein serine/threonine kinase activity), GO:0061462 (protein localization to lysosome), GO:0043405 (regulation of MAP kinase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005773 (vacuole), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043227 (membrane-bounded organelle), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0005764 (lysosome), GO:0097708 (intracellular vesicle)