IRS4

Insulin receptor substrate 4 is a protein that in humans is encoded by the IRS4 gene.[2][3][4]

IRS4
Identifiers
Aliases	IRS4, IRS-4, PY160, insulin receptor substrate 4, CHNG9
External IDs	OMIM: 300904 HomoloGene: 136777 GeneCards: IRS4
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphatidylinositol 3-kinase binding • GO:0001948 protein binding • signal transducer activity • insulin receptor binding Cellular component • cytosol • membrane • cell membrane Biological process • insulin receptor signaling pathway • regulation of lipid metabolic process • signal transduction • positive regulation of signal transduction Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8471	n/a
Ensembl	n/a	n/a
UniProt	O14654	n/a
RefSeq (mRNA)	NM_003604 NM_001379150	n/a
RefSeq (protein)	NP_003595 NP_001366079	n/a
Location (UCSC)	n/a	n/a
PubMed search	[1]	n/a
Wikidata
View/Edit Human

IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.[4]

Interactions

IRS4 has been shown to interact with CRK[5][6] and NISCH.[7]

References

1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
2. Lavan BE, Fantin VR, Chang ET, Lane WS, Keller SR, Lienhard GE (Sep 1997). "A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family". J Biol Chem. 272 (34): 21403–7. doi:10.1074/jbc.272.34.21403. PMID 9261155.
3. Fantin VR, Sparling JD, Slot JW, Keller SR, Lienhard GE, Lavan BE (May 1998). "Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells". J Biol Chem. 273 (17): 10726–32. doi:10.1074/jbc.273.17.10726. PMID 9553137.
4. "Entrez Gene: IRS4 insulin receptor substrate 4".
5. Karas, M; Koval A P; Zick Y; LeRoith D (May 2001). "The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II". Endocrinology. United States. 142 (5): 1835–40. doi:10.1210/en.142.5.1835. ISSN 0013-7227. PMID 11316748.
6. Koval, A P; Karas M; Zick Y; LeRoith D (Jun 1998). "Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction". J. Biol. Chem. UNITED STATES. 273 (24): 14780–7. doi:10.1074/jbc.273.24.14780. ISSN 0021-9258. PMID 9614078.
7. Sano, Hiroyuki; Liu Simon C H; Lane William S; Piletz John E; Lienhard Gustav E (May 2002). "Insulin receptor substrate 4 associates with the protein IRAS". J. Biol. Chem. United States. 277 (22): 19439–47. doi:10.1074/jbc.M111838200. ISSN 0021-9258. PMID 11912194.

Further reading

• White MF (1999). "The IRS-signalling system: a network of docking proteins that mediate insulin action". Mol. Cell. Biochem. 182 (1–2): 3–11. doi:10.1023/A:1006806722619. PMID 9609109.
• Koval AP, Karas M, Zick Y, LeRoith D (1998). "Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction". J. Biol. Chem. 273 (24): 14780–7. doi:10.1074/jbc.273.24.14780. PMID 9614078.
• Uchida T, Myers MG, White MF (2000). "IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis". Mol. Cell. Biol. 20 (1): 126–38. doi:10.1128/MCB.20.1.126-138.2000. PMC 85068. PMID 10594015.
• Karas M, Koval AP, Zick Y, LeRoith D (2001). "The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II". Endocrinology. 142 (5): 1835–40. doi:10.1210/en.142.5.1835. PMID 11316748.
• Sano H, Liu SC, Lane WS, et al. (2002). "Insulin receptor substrate 4 associates with the protein IRAS". J. Biol. Chem. 277 (22): 19439–47. doi:10.1074/jbc.M111838200. PMID 11912194.
• Krebs DL, Uren RT, Metcalf D, et al. (2002). "SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation". Mol. Cell. Biol. 22 (13): 4567–78. doi:10.1128/MCB.22.13.4567-4578.2002. PMC 133908. PMID 12052866.
• Schreyer S, Ledwig D, Rakatzi I, et al. (2003). "Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor". Endocrinology. 144 (4): 1211–8. doi:10.1210/en.2002-220723. PMID 12639902.
• Escribano O, Fernández-Moreno MD, Zueco JA, et al. (2003). "Insulin receptor substrate-4 signaling in quiescent rat hepatocytes and in regenerating rat liver". Hepatology. 37 (6): 1461–9. doi:10.1053/jhep.2003.50245. PMID 12774026.
• Yen HW, Jakimiuk AJ, Munir I, Magoffin DA (2005). "Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries". Mol. Hum. Reprod. 10 (7): 473–9. doi:10.1093/molehr/gah066. PMID 15155816.
• Hinsby AM, Olsen JV, Mann M (2004). "Tyrosine phosphoproteomics of fibroblast growth factor signaling: a role for insulin receptor substrate-4". J. Biol. Chem. 279 (45): 46438–47. doi:10.1074/jbc.M404537200. PMID 15316024.
• Jin J, Smith FD, Stark C, et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
• Mihindukulasuriya KA, Zhou G, Qin J, Tan TH (2004). "Protein phosphatase 4 interacts with and down-regulates insulin receptor substrate 4 following tumor necrosis factor-alpha stimulation". J. Biol. Chem. 279 (45): 46588–94. doi:10.1074/jbc.M408067200. PMID 15331607.
• Qiu H, Zappacosta F, Su W, et al. (2005). "Interaction between Brk kinase and insulin receptor substrate-4". Oncogene. 24 (36): 5656–64. doi:10.1038/sj.onc.1208721. PMID 15870689.
• Cuevas EP, Escribano O, Chiloeches A, et al. (2007). "Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation". J. Hepatol. 46 (6): 1089–98. doi:10.1016/j.jhep.2007.01.031. PMID 17408801.