Gene Symbol: Hgs
Description: hepatocyte growth factor-regulated tyrosine kinase substrate
Alias: Hrs, hepatocyte growth factor-regulated tyrosine kinase substrate, HGF-regulated tyrosine kinase substrate, SNAP-25-interacting protein Hrs-2
Species: rat
Products:     Hgs

Top Publications

  1. Bean A, Seifert R, Chen Y, Sacks R, Scheller R. Hrs-2 is an ATPase implicated in calcium-regulated secretion. Nature. 1997;385:826-9 pubmed
    ..We have now characterized a protein, Hrs-2, that interacts with SNAP-25...
  2. Malerød L, Stuffers S, Brech A, Stenmark H. Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation. Traffic. 2007;8:1617-29 pubmed
    The ubiquitin-binding protein Hrs and endosomal sorting complex required for transport (ESCRT)-I and ESCRT-III are involved in sorting endocytosed and ubiquitinated receptors to lysosomes for degradation and efficient termination of ..
  3. Bean A, Davanger S, Chou M, Gerhardt B, Tsujimoto S, Chang Y. Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15. J Biol Chem. 2000;275:15271-8 pubmed
    b>Hrs-2, via interactions with SNAP-25, plays a regulatory role on the exocytic machinery. We now show that Hrs-2 physically interacts with Eps15, a protein required for receptor-mediated endocytosis...
  4. Bishop N, Horman A, Woodman P. Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol. 2002;157:91-101 pubmed
    ..Both tumor susceptibility gene 101 (TSG101)/human VPS (hVPS)28 and hepatocyte growth factor receptor substrate (Hrs) cytosolic complexes bind ubiquitin-agarose...
  5. Komada M, Kitamura N. Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain. Mol Cell Biol. 1995;15:6213-21 pubmed
    ..To clarify the structure and possible function of the 115-kDa protein (designated Hrs for hepatocyte growth factor-regulated tyrosine kinase substrate), we purified this protein from B16-F1 mouse ..
  6. Tsujimoto S, Pelto Huikko M, Aitola M, Meister B, Vik Mo E, Davanger S, et al. The cellular and developmental expression of hrs-2 in rat. Eur J Neurosci. 1999;11:3047-63 pubmed
    ..We have previously characterized a protein, hrs-2, that interacts with SNAP-25 and inhibits secretion from permeabilized PC12 cells...
  7. Chin L, Raynor M, Wei X, Chen H, Li L. Hrs interacts with sorting nexin 1 and regulates degradation of epidermal growth factor receptor. J Biol Chem. 2001;276:7069-78 pubmed
    Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a mammalian homologue of yeast vacuolar protein sorting (Vps) protein Vps27p; however, the role of Hrs in lysosomal trafficking is unclear...
  8. Holleman J, Marchese A. The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein-coupled receptor CXCR4. Mol Biol Cell. 2014;25:1892-904 pubmed publisher
    ..Therefore we define a novel role for DTX3L in GPCR endosomal sorting and reveal an unprecedented link between two distinct E3 ubiquitin ligases to control the activity of the ESCRT machinery. ..
  9. Pons V, Luyet P, Morel E, Abrami L, van der Goot F, Parton R, et al. Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. PLoS Biol. 2008;6:e214 pubmed publisher
    ..Receptor sorting is achieved by Hrs--an adaptor--like protein that binds membrane PtdIns3P via a FYVE motif-and then by ESCRT complexes, which ..

More Information


  1. Kirk E, Chin L, Li L. GRIF1 binds Hrs and is a new regulator of endosomal trafficking. J Cell Sci. 2006;119:4689-701 pubmed
    ..analysis reveal that GRIF1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting machinery...
  2. Puertollano R. Interactions of TOM1L1 with the multivesicular body sorting machinery. J Biol Chem. 2005;280:9258-64 pubmed
    ..of Myb1) and Tom1L2 (Tom1-like2) constitute a new protein family characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain...
  3. Kwong J, Roundabush F, Hutton Moore P, Montague M, Oldham W, Li Y, et al. Hrs interacts with SNAP-25 and regulates Ca(2+)-dependent exocytosis. J Cell Sci. 2000;113 ( Pt 12):2273-84 pubmed
    ..protein that is the rat homologue of mouse hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs). Hrs specifically interacts with SNAP-25, but not SNAP-23/syndet...
  4. Scoles D, Nguyen V, Qin Y, Sun C, Morrison H, Gutmann D, et al. Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling. Hum Mol Genet. 2002;11:3179-89 pubmed
    ..Previously we demonstrated that the hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) strongly interacts with schwannomin...
  5. Sun W, Yan Q, Vida T, Bean A. Hrs regulates early endosome fusion by inhibiting formation of an endosomal SNARE complex. J Cell Biol. 2003;162:125-37 pubmed
    ..We found that the endosome-associated hepatocyte responsive serum phosphoprotein (Hrs) inhibited the homotypic fusion of early endosomes...
  6. Scoles D, Qin Y, Nguyen V, Gutmann D, Pulst S. HRS inhibits EGF receptor signaling in the RT4 rat schwannoma cell line. Biochem Biophys Res Commun. 2005;335:385-92 pubmed
    Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) is required for trafficking of cell surface receptors to the lysosome...
  7. Pullan L, Mullapudi S, Huang Z, Baldwin P, Chin C, Sun W, et al. The endosome-associated protein Hrs is hexameric and controls cargo sorting as a "master molecule". Structure. 2006;14:661-71 pubmed
    The structure of the endosomal-associated protein, Hrs, has been determined with cryo-electron microscopy. Hrs interacts with a number of proteins, including SNAP-25 and STAM1, forming a complex that binds ubiquitin moieties...
  8. Scoles D, Huynh D, Chen M, Burke S, Gutmann D, Pulst S. The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate. Hum Mol Genet. 2000;9:1567-74 pubmed
    ..Using yeast two-hybrid interaction cloning, we identified the HGF-regulated tyrosine kinase substrate (HRS) as a schwannomin interactor...
  9. Stephens D, Banting G. Direct interaction of the trans-Golgi network membrane protein, TGN38, with the F-actin binding protein, neurabin. J Biol Chem. 1999;274:30080-6 pubmed
    ..These data suggest that neurabin provides a direct physical link between TGN38-containing membranes and the actin cytoskeleton. ..
  10. Leithe E, Kjenseth A, Sirnes S, Stenmark H, Brech A, Rivedal E. Ubiquitylation of the gap junction protein connexin-43 signals its trafficking from early endosomes to lysosomes in a process mediated by Hrs and Tsg101. J Cell Sci. 2009;122:3883-93 pubmed publisher
    ..the ubiquitin-binding proteins Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate; also known as Hgs) and Tsg101 (tumor susceptibility gene 101)...
  11. Li Y, Chin L, Levey A, Li L. Huntingtin-associated protein 1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate and functions in endosomal trafficking. J Biol Chem. 2002;277:28212-21 pubmed
    ..Here we report that HAP1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a mammalian homologue of yeast vacuolar protein sorting protein Vps27p involved in the endosome-to-lysosome ..
  12. Wurdinger T, Tannous B, Saydam O, Skog J, Grau S, Soutschek J, et al. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008;14:382-93 pubmed publisher
    ..to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) mRNA, leading to decreased levels of HGS and thereby reducing HGS-mediated degradation of the growth factor ..
  13. Huang S, Zhao L, Sun Z, Li X, Geng Z, Zhang K, et al. Essential role of Hrs in endocytic recycling of full-length TrkB receptor but not its isoform TrkB.T1. J Biol Chem. 2009;284:15126-36 pubmed publisher
    ..TrkB-FL receptors recycle to a lesser extent in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner which relies on its tyrosine kinase activity...
  14. Rusten T, Stenmark H. How do ESCRT proteins control autophagy?. J Cell Sci. 2009;122:2179-83 pubmed publisher
    ..We propose that the involvement of ESCRT proteins in the fusion of autophagosomes with the endolysosomal system is the most plausible model. ..
  15. Zhou R, Kabra R, Olson D, Piper R, Snyder P. Hrs controls sorting of the epithelial Na+ channel between endosomal degradation and recycling pathways. J Biol Chem. 2010;285:30523-30 pubmed publisher
    ..targets ENaC to lysosomes, we tested the role of hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a component of the endosomal sorting complexes required for transport (ESCRT)-0 complex...
  16. Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013;126:5553-65 pubmed publisher
    ..Silencing of HRS, STAM1 or TSG101 reduced the secretion of EV-associated CD63 and MHC II but each gene altered differently the size ..
  17. Ogura K, Kohno K, Tai T. Molecular cloning of a rat brain cDNA, with homology to a tyrosine kinase substrate, that induces galactosylceramide expression in COS-7 cells. J Neurochem. 1998;71:1827-36 pubmed
    ..Taking these results together, it is suggested that GEF-1 may play an important role in regulating GalCer expression in the brain. ..