IRS4

Protein-coding gene in the species Homo sapiens
IRS4
Identifiers
AliasesIRS4, IRS-4, PY160, insulin receptor substrate 4, CHNG9
External IDsOMIM: 300904; MGI: 1338009; HomoloGene: 136777; GeneCards: IRS4; OMA:IRS4 - orthologs
Gene location (Human)
X chromosome (human)
Chr.X chromosome (human)[1]
X chromosome (human)
Genomic location for IRS4
Genomic location for IRS4
BandXq22.3Start108,719,946 bp[1]
End108,736,563 bp[1]
Gene location (Mouse)
X chromosome (mouse)
Chr.X chromosome (mouse)[2]
X chromosome (mouse)
Genomic location for IRS4
Genomic location for IRS4
BandX F2|X 62.43 cMStart140,493,994 bp[2]
End140,508,259 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
SpeciesHumanMouse
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 MbChr X: 140.49 – 140.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000133124 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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.


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