2k9g

Structural highlights

Function

[SH3K1_HUMAN] Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through a association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Szymkiewicz I, Kowanetz K, Soubeyran P, Dinarina A, Lipkowitz S, Dikic I. CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases. J Biol Chem. 2002 Oct 18;277(42):39666-72. Epub 2002 Aug 12. PMID:12177062 doi:10.1074/jbc.M205535200
2. ↑ Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I. Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature. 2002 Mar 14;416(6877):183-7. PMID:11894095 doi:10.1038/416183a
3. ↑ Petrelli A, Gilestro GF, Lanzardo S, Comoglio PM, Migone N, Giordano S. The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature. 2002 Mar 14;416(6877):187-90. PMID:11894096 doi:10.1038/416187a
4. ↑ Schmidt MH, Chen B, Randazzo LM, Bogler O. SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion. J Cell Sci. 2003 Jul 15;116(Pt 14):2845-55. Epub 2003 May 27. PMID:12771190 doi:10.1242/jcs.00522
5. ↑ Schmidt MH, Furnari FB, Cavenee WK, Bogler O. Epidermal growth factor receptor signaling intensity determines intracellular protein interactions, ubiquitination, and internalization. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6505-10. Epub 2003 May 6. PMID:12734385 doi:10.1073/pnas.1031790100
6. ↑ Kowanetz K, Husnjak K, Holler D, Kowanetz M, Soubeyran P, Hirsch D, Schmidt MH, Pavelic K, De Camilli P, Randazzo PA, Dikic I. CIN85 associates with multiple effectors controlling intracellular trafficking of epidermal growth factor receptors. Mol Biol Cell. 2004 Jul;15(7):3155-66. Epub 2004 Apr 16. PMID:15090612 doi:10.1091/mbc.E03-09-0683
7. ↑ Aissouni Y, Zapart G, Iovanna JL, Dikic I, Soubeyran P. CIN85 regulates the ability of MEKK4 to activate the p38 MAP kinase pathway. Biochem Biophys Res Commun. 2005 Dec 16;338(2):808-14. Epub 2005 Oct 18. PMID:16256071 doi:10.1016/j.bbrc.2005.10.032
8. ↑ Narita T, Nishimura T, Yoshizaki K, Taniyama T. CIN85 associates with TNF receptor 1 via Src and modulates TNF-alpha-induced apoptosis. Exp Cell Res. 2005 Mar 10;304(1):256-64. Epub 2004 Dec 1. PMID:15707590 doi:S0014-4827(04)00682-2
9. ↑ Molfetta R, Belleudi F, Peruzzi G, Morrone S, Leone L, Dikic I, Piccoli M, Frati L, Torrisi MR, Santoni A, Paolini R. CIN85 regulates the ligand-dependent endocytosis of the IgE receptor: a new molecular mechanism to dampen mast cell function. J Immunol. 2005 Oct 1;175(7):4208-16. PMID:16177060
10. ↑ Bai SW, Herrera-Abreu MT, Rohn JL, Racine V, Tajadura V, Suryavanshi N, Bechtel S, Wiemann S, Baum B, Ridley AJ. Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. BMC Biol. 2011 Aug 11;9:54. doi: 10.1186/1741-7007-9-54. PMID:21834987 doi:10.1186/1741-7007-9-54