Protein: Hepatocyte growth factor-regulated tyrosine kinase substrate (Q99LI8)
Organism: Mus musculus (Mouse)
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. Note=Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments. {ECO:0000250|UniProtKB:O14964}.
Sequence: MGRGSGTFERLLDKATSQLLLETDWESILQICDLIRQGDTQAKYAVNSIKKKVNDKNPHVALYALEVMESVVKNCGQTVHDEVANKQTMEELKELLKRQVEVNVRNKILYLIQAWAHAFRNEPKYKVVQDTYQIMKVEGHVFPEFKESDAMFAAERAPDWVDAEECHRCRVQFGVVTRKHHCRACGQIFCGKCSSKYSTIPKFGIEKEVRVCEPCYEQLNKKAEGKASSTTELPPEYLTSPLSQQSQLPPKRDETALQEEEELQLALALSQSEAEEKERMRQKTTYTAHPKAEPTPLASSAPPAGSLYSSPVNSSAPLAEDIDPELARYLNRNYWEKKQEEARKSPTPSAPVPLTEPAAQPGEGHTAPNSMAEAPLPETDSQPITPCSGPFSEYQNGESEESHEQFLKALQNAVSTFVNRMKSNHMRGRSITNDSAVLSLFQSINTMHPQLLELLNQLDERRLYYEGLQDKLAQIRDARGALSALREEHREKLRRAAEEAERQRQIQLAQKLEIMRQKKQEYLEVQRQLAIQRLQEQEKERQMRLEQQKQTVQMRAQMPAFPLPYAQLQAMPTAGGVLYQPSGPTSFPATFSPAGSVEGSPMHGVYMSQPAPATGPYPSMPGTTADPSMVSAYMYPTGAPGAQAAPQAQAGPTTSPAYSSYQPTPTPGYQSVASQAPQSLPAISQPPQTSNIGYMGSQPMSMGYQPYNMQNLMTALPGQDASLPAQQPYIPGQQPLYQQMAPSTGPPQQQPPVAQPAPTQGPPAQGSEAQLISFD
InterPro domains: - IPR003903: Ubiquitin interacting motif (conserved_site) [258-277]
- IPR011011: Zinc finger, FYVE/PHD-type (homologous_superfamily) [159-221]
- IPR024641: Hepatocyte growth factor-regulated tyrosine kinase substrate, helical domain (domain) [404-499]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [155-225]
- IPR002014: VHS domain (domain) [7-143]
- IPR017073: Hepatocyte growth factor-regulated tyrosine kinase substrate/VPS27 (family) [1-775]
- IPR017455: Zinc finger, FYVE-related (domain) [160-220]
- IPR000306: FYVE zinc finger (domain) [155-221]
- IPR008942: ENTH/VHS (homologous_superfamily) [1-154]
Interaction partners: - Signal transducing adapter molecule 2
- Signal transducing adapter molecule 1
- Tumor susceptibility gene 101 protein
- Epidermal growth factor receptor substrate 15
- Polyubiquitin-C
- Vacuolar protein sorting-associated protein 28 homolog
- Charged multivesicular body protein 3
- Charged multivesicular body protein 2a
- Vacuolar protein-sorting-associated protein 25
- Ubiquitin-ribosomal protein eS31 fusion protein
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019904 (protein domain specific binding)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0002376 (immune system process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0023057 (negative regulation of signaling), GO:0009653 (anatomical structure morphogenesis), GO:0042221 (response to chemical), GO:0045321 (leukocyte activation), GO:0006955 (immune response), GO:0002684 (positive regulation of immune system process), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0051050 (positive regulation of transport), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0009719 (response to endogenous stimulus), GO:0008219 (cell death), GO:0040017 (positive regulation of locomotion), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0021700 (developmental maturation), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0007165 (signal transduction), GO:0040012 (regulation of locomotion), GO:0048869 (cellular developmental process), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0001775 (cell activation), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0051234 (establishment of localization), GO:0002682 (regulation of immune system process), GO:0009056 (catabolic process), GO:0044237 (cellular metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0002252 (immune effector process), GO:0065009 (regulation of molecular function), GO:0140352 (export from cell), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0048522 (positive regulation of cellular process), GO:0009968 (negative regulation of signal transduction), GO:0032103 (positive regulation of response to external stimulus), GO:0012501 (programmed cell death), GO:2000145 (regulation of cell motility), GO:0002685 (regulation of leukocyte migration), GO:0002366 (leukocyte activation involved in immune response), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0080134 (regulation of response to stress), GO:0044248 (cellular catabolic process), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0030155 (regulation of cell adhesion), GO:0060255 (regulation of macromolecule metabolic process), GO:0032101 (regulation of response to external stimulus), GO:0060627 (regulation of vesicle-mediated transport), GO:0002694 (regulation of leukocyte activation), GO:1903706 (regulation of hemopoiesis), GO:0001817 (regulation of cytokine production), GO:0046649 (lymphocyte activation), GO:0006914 (autophagy), GO:0071695 (anatomical structure maturation), GO:0035295 (tube development), GO:0009894 (regulation of catabolic process), GO:0010632 (regulation of epithelial cell migration), GO:0046907 (intracellular transport), GO:0007162 (negative regulation of cell adhesion), GO:0002697 (regulation of immune effector process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0050778 (positive regulation of immune response), GO:0045595 (regulation of cell differentiation), GO:0032940 (secretion by cell), GO:0002443 (leukocyte mediated immunity), GO:0002698 (negative regulation of immune effector process), GO:0031349 (positive regulation of defense response), GO:0051128 (regulation of cellular component organization), GO:0050865 (regulation of cell activation), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0035239 (tube morphogenesis), GO:0009967 (positive regulation of signal transduction), GO:0010648 (negative regulation of cell communication), GO:1903530 (regulation of secretion by cell), GO:1902742 (apoptotic process involved in development), GO:0051049 (regulation of transport), GO:0044093 (positive regulation of molecular function), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0050920 (regulation of chemotaxis), GO:0080135 (regulation of cellular response to stress), GO:0031343 (positive regulation of cell killing), GO:0051649 (establishment of localization in cell), GO:1901700 (response to oxygen-containing compound), GO:0051130 (positive regulation of cellular component organization), GO:0045785 (positive regulation of cell adhesion), GO:0030522 (intracellular receptor signaling pathway), GO:0030641 (regulation of cellular pH), GO:0031324 (negative regulation of cellular metabolic process), GO:0010033 (response to organic substance), GO:2000147 (positive regulation of cell motility), GO:0009891 (positive regulation of biosynthetic process), GO:0002687 (positive regulation of leukocyte migration), GO:0046883 (regulation of hormone secretion), GO:0002831 (regulation of response to biotic stimulus), GO:2000026 (regulation of multicellular organismal development), GO:0050776 (regulation of immune response), GO:0042127 (regulation of cell population proliferation), GO:0002757 (immune response-activating signaling pathway), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0045596 (negative regulation of cell differentiation), GO:0006810 (transport), GO:0002263 (cell activation involved in immune response), GO:0009889 (regulation of biosynthetic process), GO:0062012 (regulation of small molecule metabolic process), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0002274 (myeloid leukocyte activation), GO:0002699 (positive regulation of immune effector process), GO:0080090 (regulation of primary metabolic process), GO:0045807 (positive regulation of endocytosis), GO:0009896 (positive regulation of catabolic process), GO:1903532 (positive regulation of secretion by cell), GO:0043300 (regulation of leukocyte degranulation), GO:0031347 (regulation of defense response), GO:1901532 (regulation of hematopoietic progenitor cell differentiation), GO:0045089 (positive regulation of innate immune response), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0010810 (regulation of cell-substrate adhesion), GO:0022407 (regulation of cell-cell adhesion), GO:0002704 (negative regulation of leukocyte mediated immunity), GO:0070302 (regulation of stress-activated protein kinase signaling cascade), GO:0008406 (gonad development), GO:0030334 (regulation of cell migration), GO:1900424 (regulation of defense response to bacterium), GO:0051250 (negative regulation of lymphocyte activation), GO:0010468 (regulation of gene expression), GO:0030098 (lymphocyte differentiation), GO:0006140 (regulation of nucleotide metabolic process), GO:1902903 (regulation of supramolecular fiber organization), GO:0045639 (positive regulation of myeloid cell differentiation), GO:0043412 (macromolecule modification), GO:0051251 (positive regulation of lymphocyte activation), GO:0007399 (nervous system development), GO:0010594 (regulation of endothelial cell migration), GO:0010508 (positive regulation of autophagy), GO:0032231 (regulation of actin filament bundle assembly), GO:0050729 (positive regulation of inflammatory response), GO:1902905 (positive regulation of supramolecular fiber organization), GO:0010563 (negative regulation of phosphorus metabolic process), GO:0030335 (positive regulation of cell migration), GO:1902533 (positive regulation of intracellular signal transduction), GO:0051252 (regulation of RNA metabolic process), GO:0071675 (regulation of mononuclear cell migration), GO:0022408 (negative regulation of cell-cell adhesion), GO:1901701 (cellular response to oxygen-containing compound), GO:0010629 (negative regulation of gene expression), GO:0045920 (negative regulation of exocytosis), GO:0051249 (regulation of lymphocyte activation), GO:0007507 (heart development), GO:0030100 (regulation of endocytosis), GO:0030097 (hemopoiesis), GO:0071559 (response to transforming growth factor beta), GO:0034097 (response to cytokine), GO:0050728 (negative regulation of inflammatory response), GO:1902106 (negative regulation of leukocyte differentiation), GO:0002521 (leukocyte differentiation), GO:0045088 (regulation of innate immune response), GO:0071310 (cellular response to organic substance), GO:0072594 (establishment of protein localization to organelle), GO:0060284 (regulation of cell development), GO:0051248 (negative regulation of protein metabolic process), GO:0002718 (regulation of cytokine production involved in immune response), GO:0017157 (regulation of exocytosis), GO:0062207 (regulation of pattern recognition receptor signaling pathway), GO:0036230 (granulocyte activation), GO:0030099 (myeloid cell differentiation), GO:0045921 (positive regulation of exocytosis), GO:0016236 (macroautophagy), GO:0036211 (protein modification process), GO:0016236 (macroautophagy), GO:0050764 (regulation of phagocytosis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0036452 (ESCRT complex), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043227 (membrane-bounded organelle), GO:0005769 (early endosome), GO:0043231 (intracellular membrane-bounded organelle), GO:0010008 (endosome membrane), GO:0098588 (bounding membrane of organelle), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0012506 (vesicle membrane), GO:0097708 (intracellular vesicle)