HGS (gene)

Hepatocyte growth factor-regulated tyrosine kinase substrate
Rendering of HGS from PDB 2D3G​
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2D3G​, 3F1I​, 3OBQ​, 3ZYQ​, 4AVX​
Identifiers
Symbols	HGS ; HRS
External IDs	OMIM: 604375 MGI: 104681 HomoloGene: 37954 GeneCards: HGS Gene
Gene ontology Molecular function • protein binding • protein domain specific binding • metal ion binding Cellular component • cytoplasm • endosome • early endosome • cytosol • secretory granule • early endosome membrane • multivesicular body membrane • intracellular membrane-bounded organelle • extracellular exosome Biological process • protein targeting to lysosome • post-Golgi vesicle-mediated transport • signal transduction • epidermal growth factor receptor signaling pathway • negative regulation of cell proliferation • endosome to lysosome transport • membrane invagination • positive regulation of gene expression • endosomal transport • negative regulation of epidermal growth factor receptor signaling pathway • regulation of protein catabolic process • regulation of MAP kinase activity • negative regulation of JAK-STAT cascade • membrane organization • protein localization to membrane • positive regulation of exosomal secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9146	15239
Ensembl	ENSG00000185359	ENSMUSG00000025793
UniProt	O14964	Q99LI8
RefSeq (mRNA)	NM_004712	NM_001159328
RefSeq (protein)	NP_004703	NP_001152800
Location (UCSC)	Chr 17: 81.68 – 81.7 Mb	Chr 11: 120.47 – 120.48 Mb
PubMed search

Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene.^{[1] [2][3]}

Interactions

HGS (gene) has been shown to interact with:

• CLTC^[4]
• DLG4,^[5]
• EPS15,^[6][7]
• IL2RB,^[8]
• Merlin,^[9][10]
• STAM2,^[6][11]
• Signal transducing adaptor molecule,^[1][6][11] and
• TSG101.^[11][12]

References

1. Asao, H.; Sasaki, Y.; Arita, T.; Tanaka, N.; Endo, K.; Kasai, H.; Takeshita, T.; Endo, Y.; Fujita, T.; Sugamura, K. (1997). "Hrs Is Associated with STAM, a Signal-transducing Adaptor Molecule: Its suppressive effect on cytokine-induced cell growth". Journal of Biological Chemistry 272 (52): 32785–32791. doi:10.1074/jbc.272.52.32785. ISSN 0021-9258. PMID 9407053.
2. Lu L, Komada M, Kitamura N (August 1998). "Human Hrs, a tyrosine kinase substrate in growth factor-stimulated cells: cDNA cloning and mapping of the gene to chromosome 17". Gene 213 (1-2): 125–32. doi:10.1016/S0378-1119(98)00184-X. PMID 9630564.
3. "Entrez Gene: HGS hepatocyte growth factor-regulated tyrosine kinase substrate".
4. Raiborg C, Bache KG, Mehlum A, Stang E, Stenmark H (September 2001). "Hrs recruits clathrin to early endosomes". EMBO J. 20 (17): 5008–21. doi:10.1093/emboj/20.17.5008. PMC 125612. PMID 11532964.
5. Chetkovich DM, Bunn RC, Kuo SH, Kawasaki Y, Kohwi M, Bredt DS (August 2002). "Postsynaptic targeting of alternative postsynaptic density-95 isoforms by distinct mechanisms". J. Neurosci. 22 (15): 6415–25. PMID 12151521.
6. Bache KG, Raiborg C, Mehlum A, Stenmark H (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". J. Biol. Chem. 278 (14): 12513–21. doi:10.1074/jbc.M210843200. PMID 12551915.
7. Bean AJ, Davanger S, Chou MF, Gerhardt B, Tsujimoto S, Chang Y (May 2000). "Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15". J. Biol. Chem. 275 (20): 15271–8. doi:10.1074/jbc.275.20.15271. PMID 10809762.
8. Yamashita Y, Kojima K, Tsukahara T, Agawa H, Yamada K, Amano Y, Kurotori N, Tanaka N, Sugamura K, Takeshita T (May 2008). "Ubiquitin-independent binding of Hrs mediates endosomal sorting of the interleukin-2 receptor beta-chain". J. Cell. Sci. 121 (Pt 10): 1727–38. doi:10.1242/jcs.024455. PMID 18445679.
9. Gutmann DH, Haipek CA, Burke SP, Sun CX, Scoles DR, Pulst SM (April 2001). "The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the "open" conformation and suppresses cell growth and motility". Hum. Mol. Genet. 10 (8): 825–34. doi:10.1093/hmg/10.8.825. PMID 11285248.
10. Scoles DR, Huynh DP, Chen MS, Burke SP, Gutmann DH, Pulst SM (July 2000). "The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate". Hum. Mol. Genet. 9 (11): 1567–74. doi:10.1093/hmg/9.11.1567. PMID 10861283.
11. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
12. Lu Q, Hope LW, Brasch M, Reinhard C, Cohen SN (June 2003). "TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation". Proc. Natl. Acad. Sci. U.S.A. 100 (13): 7626–31. doi:10.1073/pnas.0932599100. PMC 164637. PMID 12802020.

Further reading

• Comoglio PM (1993). "Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells". EXS 65: 131–65. PMID 8380735.
• Komada M, Masaki R, Yamamoto A, Kitamura N (1997). "Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain, is localized to the cytoplasmic surface of early endosomes". J. Biol. Chem. 272 (33): 20538–44. doi:10.1074/jbc.272.33.20538. PMID 9252367.
• Stephens DJ, Banting G (1999). "Direct interaction of the trans-Golgi network membrane protein, TGN38, with the F-actin binding protein, neurabin". J. Biol. Chem. 274 (42): 30080–6. doi:10.1074/jbc.274.42.30080. PMID 10514494.
• Bean AJ, Davanger S, Chou MF, Gerhardt B, Tsujimoto S, Chang Y (2000). "Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15". J. Biol. Chem. 275 (20): 15271–8. doi:10.1074/jbc.275.20.15271. PMID 10809762.
• Kwong J, Roundabush FL, Hutton Moore P, Montague M, Oldham W, Li Y, Chin LS, Li L (2000). "Hrs interacts with SNAP-25 and regulates Ca(2+)-dependent exocytosis". J. Cell. Sci. 113 (12): 2273–84. PMID 10825299.
• Scoles DR, Huynh DP, Chen MS, Burke SP, Gutmann DH, Pulst SM (2000). "The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate". Hum. Mol. Genet. 9 (11): 1567–74. doi:10.1093/hmg/9.11.1567. PMID 10861283.
• Gillooly DJ, Morrow IC, Lindsay M, Gould R, Bryant NJ, Gaullier JM, Parton RG, Stenmark H (2000). "Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells". EMBO J. 19 (17): 4577–88. doi:10.1093/emboj/19.17.4577. PMC 302054. PMID 10970851.
• Miura S, Takeshita T, Asao H, Kimura Y, Murata K, Sasaki Y, Hanai JI, Beppu H, Tsukazaki T, Wrana JL, Miyazono K, Sugamura K (2000). "Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA". Mol. Cell. Biol. 20 (24): 9346–55. doi:10.1128/MCB.20.24.9346-9355.2000. PMC 102191. PMID 11094085.
• Chin LS, Raynor MC, Wei X, Chen HQ, Li L (2001). "Hrs interacts with sorting nexin 1 and regulates degradation of epidermal growth factor receptor". J. Biol. Chem. 276 (10): 7069–78. doi:10.1074/jbc.M004129200. PMID 11110793.
• Gutmann DH, Haipek CA, Burke SP, Sun CX, Scoles DR, Pulst SM (2001). "The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the "open" conformation and suppresses cell growth and motility". Hum. Mol. Genet. 10 (8): 825–34. doi:10.1093/hmg/10.8.825. PMID 11285248.
• Sasaki Y, Sugamura K (2001). "Involvement of Hgs/Hrs in signaling for cytokine-mediated c-fos induction through interaction with TAK1 and Pak1". J. Biol. Chem. 276 (32): 29943–52. doi:10.1074/jbc.M104230200. PMID 11397816.
• Raiborg C, Bremnes B, Mehlum A, Gillooly DJ, D'Arrigo A, Stang E, Stenmark H (2001). "FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes". J. Cell. Sci. 114 (Pt 12): 2255–63. PMID 11493665.
• Raiborg C, Bache KG, Mehlum A, Stang E, Stenmark H (2001). "Hrs recruits clathrin to early endosomes". EMBO J. 20 (17): 5008–21. doi:10.1093/emboj/20.17.5008. PMC 125612. PMID 11532964.
• Steen H, Kuster B, Fernandez M, Pandey A, Mann M (2002). "Tyrosine phosphorylation mapping of the epidermal growth factor receptor signaling pathway". J. Biol. Chem. 277 (2): 1031–9. doi:10.1074/jbc.M109992200. PMID 11687594.
• Bishop N, Horman A, Woodman P (2002). "Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates". J. Cell Biol. 157 (1): 91–101. doi:10.1083/jcb.200112080. PMC 2173266. PMID 11916981.
• Tchernev VT, Mansfield TA, Giot L, Kumar AM, Nandabalan K, Li Y, Mishra VS, Detter JC, Rothberg JM, Wallace MR, Southwick FS, Kingsmore SF (2002). "The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins". Mol. Med. 8 (1): 56–64. PMC 2039936. PMID 11984006.
• Li Y, Chin LS, Levey AI, Li L (2002). "Huntingtin-associated protein 1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate and functions in endosomal trafficking". J. Biol. Chem. 277 (31): 28212–21. doi:10.1074/jbc.M111612200. PMID 12021262.