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Hgs  -  HGF-regulated tyrosine kinase substrate

Mus musculus

Synonyms: Hepatocyte growth factor-regulated tyrosine kinase substrate, Hgr, Hrs, ZFYVE8
 
 
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Disease relevance of Hgs

 

High impact information on Hgs

  • Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis [4].
  • Hrs has a FYVE double zinc finger domain, which specifically binds phosphatidylinositol(3)-phosphate and is conserved in several proteins involved in vesicular traffic [4].
  • Hrs homozygous mutant embryos developed with their ventral region outside of the yolk sac, had two independent bilateral heart tubes (cardia bifida), lacked a foregut, and died around embryonic day 11 (E11) [4].
  • Met/Hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation [5].
  • Although Met Y1003F undergoes endosomal trafficking and localizes with the cargo-sorting protein Hrs, it is unable to induce phosphorylation of Hrs [5].
 

Biological context of Hgs

  • Hrs is thought to play a regulatory role in the endocytosis of growth factor/receptor complexes through early endosomes [6].
  • Deletion mutants of Hbp lacking either the SH3 domain or the Hrs binding domain showed dominantly negative effects on the intracellular degradation of a growth factor and its receptor, but not on the internalization of growth factor/receptor complexes [6].
  • These results suggest that the STAMs and Hrs play important roles in the mammalian endosomal/vacuolar protein sorting pathway [7].
  • Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation [7].
  • In addition, this rescues Hrs tyrosine phosphorylation and decreases transformation in a focus-forming assay [5].
 

Anatomical context of Hgs

 

Associations of Hgs with chemical compounds

 

Physical interactions of Hgs

  • Hbp was co-immunoprecipitated with Hrs, and its intracellular localization was similar to that of Hrs [6].
 

Regulatory relationships of Hgs

 

Other interactions of Hgs

  • These findings suggest that the two FYVE domain proteins, Hgs and SARA, are prerequisites for receptor-mediated activation of Smad2 [11].
  • CONCLUSIONS: Hbp is thought to be closely associated with Hrs on early endosomes [6].
 

Analytical, diagnostic and therapeutic context of Hgs

References

  1. Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain. Komada, M., Kitamura, N. Mol. Cell. Biol. (1995) [Pubmed]
  2. Acquisition of Hrs, an essential component of phagosomal maturation, is impaired by mycobacteria. Vieira, O.V., Harrison, R.E., Scott, C.C., Stenmark, H., Alexander, D., Liu, J., Gruenberg, J., Schreiber, A.D., Grinstein, S. Mol. Cell. Biol. (2004) [Pubmed]
  3. Mercury-resistant plasmids in bacteria from a mercury and antimony deposit area. Khesin, R.B., Karasyova, E.V. Mol. Gen. Genet. (1984) [Pubmed]
  4. Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis. Komada, M., Soriano, P. Genes Dev. (1999) [Pubmed]
  5. Met/Hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation. Abella, J.V., Peschard, P., Naujokas, M.A., Lin, T., Saucier, C., Urbé, S., Park, M. Mol. Cell. Biol. (2005) [Pubmed]
  6. A hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors. Takata, H., Kato, M., Denda, K., Kitamura, N. Genes Cells (2000) [Pubmed]
  7. Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation. Kanazawa, C., Morita, E., Yamada, M., Ishii, N., Miura, S., Asao, H., Yoshimori, T., Sugamura, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. Galactosylceramide expression factor-1 induces myogenesis in MDCK and C3H10T1/2 cells. Ogura, K., Niino, Y.S., Tai, T. Arch. Biochem. Biophys. (2004) [Pubmed]
  9. Involvement of Hgs/Hrs in signaling for cytokine-mediated c-fos induction through interaction with TAK1 and Pak1. Sasaki, Y., Sugamura, K. J. Biol. Chem. (2001) [Pubmed]
  10. Molecular cloning and characterization of galactosylceramide expression factor-1 (GEF-1). Ogura, K., Tai, T. Neurochem. Res. (2002) [Pubmed]
  11. Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA. Miura, S., Takeshita, T., Asao, H., Kimura, Y., Murata, K., Sasaki, Y., Hanai, J.I., Beppu, H., Tsukazaki, T., Wrana, J.L., Miyazono, K., Sugamura, K. Mol. Cell. Biol. (2000) [Pubmed]
  12. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Raiborg, C., Bache, K.G., Gillooly, D.J., Madshus, I.H., Stang, E., Stenmark, H. Nat. Cell Biol. (2002) [Pubmed]
 
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