IRS4

IRS4
Identifiers
Aliases	IRS4 , IRS-4, PY160, insulin receptor substrate 4, CHNG9
External IDs	OMIM: 300904; MGI: 1338009; HomoloGene: 136777; GeneCards: IRS4; OMA:IRS4 - orthologs
Gene location (Human) Chr. X chromosome (human) [1] Band Xq22.3 Start 108,719,946 bp [1] End 108,736,563 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X F2|X 62.43 cM Start 140,493,994 bp [2] End 140,508,259 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pituitary gland anterior pituitary ovary left ovary right ovary gastric mucosa hypothalamus body of uterus right lobe of thyroid gland cervix Top expressed in median eminence arcuate nucleus ventromedial nucleus dorsomedial hypothalamic nucleus substantia nigra gastrula mammillary body lateral hypothalamus nucleus of stria terminalis paraventricular nucleus of hypothalamus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphatidylinositol 3-kinase binding protein binding signal transducer activity insulin receptor binding Cellular component cytosol membrane plasma 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 16370 Ensembl ENSG00000133124 ENSMUSG00000054667 UniProt O14654 Q9Z0Y7 RefSeq (mRNA) NM_003604 NM_001379150 NM_010572 RefSeq (protein) NP_003595 NP_001366079 NP_034702 Location (UCSC) Chr X: 108.72 – 108.74 Mb Chr X: 140.49 – 140.51 Mb PubMed search [3] [4]
Wikidata
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Insulin receptor substrate 4 is a protein that in humans is encoded by the IRS4 gene. ^{[5] [6] [7]}

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. ^[7]

Interactions

IRS4 has been shown to interact with CRK ^{[8] [9]} and NISCH. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000133124 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000054667 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: IRS4 insulin receptor substrate 4".
8. 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 . 142 (5). United States: 1835–40. doi: 10.1210/endo.142.5.8135 . ISSN   0013-7227. PMID   11316748.
9. Koval AP, 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. 273 (24). UNITED STATES: 14780–7. doi: 10.1074/jbc.273.24.14780 . ISSN   0021-9258. PMID   9614078.
10. Sano H, 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. 277 (22). United States: 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. S2CID   32623861.
• 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. S2CID   20484894.
• 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. Bibcode:2004CBio...14.1436J. doi: 10.1016/j.cub.2004.07.051 . PMID   15324660. S2CID   2371325.
• 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.