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{{Infobox_gene}}
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'''Insulin receptor substrate 4''' is a [[protein]] that in humans is encoded by the ''IRS4'' [[gene]].<ref name="pmid9261155">{{cite journal |vauthors=Lavan BE, Fantin VR, Chang ET, Lane WS, Keller SR, Lienhard GE | title = A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family | journal = J Biol Chem | volume = 272 | issue = 34 | pages = 21403–7 |date=Sep 1997 | pmid = 9261155 | pmc =  | doi =10.1074/jbc.272.34.21403 }}</ref><ref name="pmid9553137">{{cite journal |vauthors=Fantin VR, Sparling JD, Slot JW, Keller SR, Lienhard GE, Lavan BE | title = Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells | journal = J Biol Chem | volume = 273 | issue = 17 | pages = 10726–32 |date=May 1998 | pmid = 9553137 | pmc =  | doi =10.1074/jbc.273.17.10726 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: IRS4 insulin receptor substrate 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8471| accessdate = }}</ref>
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{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Insulin receptor substrate 4
| HGNCid = 6128
| Symbol = IRS4
| AltSymbols =; IRS-4; PY160
| OMIM = 603510
| ECnumber =
| Homologene = 2673
| MGIid = 1338009
  | GeneAtlas_image1 = PBB_GE_IRS4_207403_at_tn.png
  | Function = {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005070 |text = SH3/SH2 adaptor activity}} {{GNF_GO|id=GO:0005158 |text = insulin receptor binding}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 8471
    | Hs_Ensembl = ENSG00000133124
    | Hs_RefseqProtein = NP_003595
    | Hs_RefseqmRNA = NM_003604
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 107862368
    | Hs_GenLoc_end = 107866295
    | Hs_Uniprot = 
    | Mm_EntrezGene = 16370
    | Mm_Ensembl = 
    | Mm_RefseqmRNA = XM_980033
    | Mm_RefseqProtein = XP_985127
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
'''Insulin receptor substrate 4''', also known as '''IRS4''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: IRS4 insulin receptor substrate 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8471| accessdate = }}</ref>


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{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =  
| summary_text = 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..<ref name="entrez">{{cite web | title = Entrez Gene: IRS4 insulin receptor substrate 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8471| accessdate = }}</ref>
| summary_text = 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.<ref name="entrez"/>
}}
}}
==Interactions==
IRS4 has been shown to [[Protein-protein interaction|interact]] with [[CRK (gene)|CRK]]<ref name=pmid11316748>{{cite journal |last=Karas |first=M |authorlink= |author2=Koval A P |author3=Zick Y |author4=LeRoith D  |date=May 2001 |title=The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II |journal=[[Endocrinology (journal)|Endocrinology]] |volume=142 |issue=5 |pages=1835–40 |publisher= |location = United States| issn = 0013-7227| pmid = 11316748 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1210/en.142.5.1835 }}</ref><ref name=pmid9614078>{{cite journal |last=Koval |first=A P |authorlink= |author2=Karas M |author3=Zick Y |author4=LeRoith D  |date=Jun 1998 |title=Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction |journal=J. Biol. Chem. |volume=273 |issue=24 |pages=14780–7 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 9614078 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1074/jbc.273.24.14780 }}</ref> and [[NISCH]].<ref name=pmid11912194>{{cite journal |last=Sano |first=Hiroyuki |authorlink= |author2=Liu Simon C H |author3=Lane William S |author4=Piletz John E |author5=Lienhard Gustav E  |date=May 2002 |title=Insulin receptor substrate 4 associates with the protein IRAS |journal=J. Biol. Chem. |volume=277 |issue=22 |pages=19439–47 |publisher= |location = United States| issn = 0021-9258| pmid = 11912194 |doi = 10.1074/jbc.M111838200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=White MF |title=The IRS-signalling system: a network of docking proteins that mediate insulin action. |journal=Mol. Cell. Biochem. |volume=182 |issue= 1-2 |pages= 3-11 |year= 1999 |pmid= 9609109 |doi= }}
*{{cite journal  | author=White MF |title=The IRS-signalling system: a network of docking proteins that mediate insulin action. |journal=Mol. Cell. Biochem. |volume=182 |issue= 1–2 |pages= 3–11 |year= 1999 |pmid= 9609109 |doi=10.1023/A:1006806722619 }}
*{{cite journal  | author=Lavan BE, Fantin VR, Chang ET, ''et al.'' |title=A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family. |journal=J. Biol. Chem. |volume=272 |issue= 34 |pages= 21403-7 |year= 1997 |pmid= 9261155 |doi=  }}
*{{cite journal  |vauthors=Koval AP, Karas M, Zick Y, LeRoith D |title=Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. |journal=J. Biol. Chem. |volume=273 |issue= 24 |pages= 14780–7 |year= 1998 |pmid= 9614078 |doi=10.1074/jbc.273.24.14780 }}
*{{cite journal  | author=Fantin VR, Sparling JD, Slot JW, ''et al.'' |title=Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells. |journal=J. Biol. Chem. |volume=273 |issue= 17 |pages= 10726-32 |year= 1998 |pmid= 9553137 |doi= }}
*{{cite journal  |vauthors=Uchida T, Myers MG, White MF |title=IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis. |journal=Mol. Cell. Biol. |volume=20 |issue= 1 |pages= 126–38 |year= 2000 |pmid= 10594015 |doi=10.1128/MCB.20.1.126-138.2000  | pmc=85068 }}
*{{cite journal  | author=Koval AP, Karas M, Zick Y, LeRoith D |title=Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. |journal=J. Biol. Chem. |volume=273 |issue= 24 |pages= 14780-7 |year= 1998 |pmid= 9614078 |doi=  }}
*{{cite journal  |vauthors=Karas M, Koval AP, Zick Y, LeRoith D |title=The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II. |journal=Endocrinology |volume=142 |issue= 5 |pages= 1835–40 |year= 2001 |pmid= 11316748 |doi=10.1210/en.142.5.1835 }}
*{{cite journal  | author=Uchida T, Myers MG, White MF |title=IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis. |journal=Mol. Cell. Biol. |volume=20 |issue= 1 |pages= 126-38 |year= 2000 |pmid= 10594015 |doi=  }}
*{{cite journal   |vauthors=Sano H, Liu SC, Lane WS, etal |title=Insulin receptor substrate 4 associates with the protein IRAS. |journal=J. Biol. Chem. |volume=277 |issue= 22 |pages= 19439–47 |year= 2002 |pmid= 11912194 |doi= 10.1074/jbc.M111838200 }}
*{{cite journal  | author=Karas M, Koval AP, Zick Y, LeRoith D |title=The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II. |journal=Endocrinology |volume=142 |issue= 5 |pages= 1835-40 |year= 2001 |pmid= 11316748 |doi=  }}
*{{cite journal   |vauthors=Krebs DL, Uren RT, Metcalf D, etal |title=SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. |journal=Mol. Cell. Biol. |volume=22 |issue= 13 |pages= 4567–78 |year= 2002 |pmid= 12052866 |doi=10.1128/MCB.22.13.4567-4578.2002  | pmc=133908 }}
*{{cite journal | author=Sano H, Liu SC, Lane WS, ''et al.'' |title=Insulin receptor substrate 4 associates with the protein IRAS. |journal=J. Biol. Chem. |volume=277 |issue= 22 |pages= 19439-47 |year= 2002 |pmid= 11912194 |doi= 10.1074/jbc.M111838200 }}
*{{cite journal   |vauthors=Schreyer S, Ledwig D, Rakatzi I, etal |title=Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor. |journal=Endocrinology |volume=144 |issue= 4 |pages= 1211–8 |year= 2003 |pmid= 12639902 |doi=10.1210/en.2002-220723 }}
*{{cite journal | author=Krebs DL, Uren RT, Metcalf D, ''et al.'' |title=SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. |journal=Mol. Cell. Biol. |volume=22 |issue= 13 |pages= 4567-78 |year= 2002 |pmid= 12052866 |doi=  }}
*{{cite journal   |vauthors=Escribano O, Fernández-Moreno MD, Zueco JA, etal |title=Insulin receptor substrate-4 signaling in quiescent rat hepatocytes and in regenerating rat liver. |journal=Hepatology |volume=37 |issue= 6 |pages= 1461–9 |year= 2003 |pmid= 12774026 |doi= 10.1053/jhep.2003.50245 }}
*{{cite journal | author=Schreyer S, Ledwig D, Rakatzi I, ''et al.'' |title=Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor. |journal=Endocrinology |volume=144 |issue= 4 |pages= 1211-8 |year= 2003 |pmid= 12639902 |doi=  }}
*{{cite journal  |vauthors=Yen HW, Jakimiuk AJ, Munir I, Magoffin DA |title=Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries. |journal=Mol. Hum. Reprod. |volume=10 |issue= 7 |pages= 473–9 |year= 2005 |pmid= 15155816 |doi= 10.1093/molehr/gah066 }}
*{{cite journal | author=Escribano O, Fernández-Moreno MD, Zueco JA, ''et al.'' |title=Insulin receptor substrate-4 signaling in quiescent rat hepatocytes and in regenerating rat liver. |journal=Hepatology |volume=37 |issue= 6 |pages= 1461-9 |year= 2003 |pmid= 12774026 |doi= 10.1053/jhep.2003.50245 }}
*{{cite journal  |vauthors=Hinsby AM, Olsen JV, Mann M |title=Tyrosine phosphoproteomics of fibroblast growth factor signaling: a role for insulin receptor substrate-4. |journal=J. Biol. Chem. |volume=279 |issue= 45 |pages= 46438–47 |year= 2004 |pmid= 15316024 |doi= 10.1074/jbc.M404537200 }}
*{{cite journal  | author=Yen HW, Jakimiuk AJ, Munir I, Magoffin DA |title=Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries. |journal=Mol. Hum. Reprod. |volume=10 |issue= 7 |pages= 473-9 |year= 2005 |pmid= 15155816 |doi= 10.1093/molehr/gah066 }}
*{{cite journal   |vauthors=Jin J, Smith FD, Stark C, etal |title=Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. |journal=Curr. Biol. |volume=14 |issue= 16 |pages= 1436–50 |year= 2004 |pmid= 15324660 |doi= 10.1016/j.cub.2004.07.051 }}
*{{cite journal  | author=Hinsby AM, Olsen JV, Mann M |title=Tyrosine phosphoproteomics of fibroblast growth factor signaling: a role for insulin receptor substrate-4. |journal=J. Biol. Chem. |volume=279 |issue= 45 |pages= 46438-47 |year= 2004 |pmid= 15316024 |doi= 10.1074/jbc.M404537200 }}
*{{cite journal  |vauthors=Mihindukulasuriya KA, Zhou G, Qin J, Tan TH |title=Protein phosphatase 4 interacts with and down-regulates insulin receptor substrate 4 following tumor necrosis factor-alpha stimulation. |journal=J. Biol. Chem. |volume=279 |issue= 45 |pages= 46588–94 |year= 2004 |pmid= 15331607 |doi= 10.1074/jbc.M408067200 }}
*{{cite journal | author=Jin J, Smith FD, Stark C, ''et al.'' |title=Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. |journal=Curr. Biol. |volume=14 |issue= 16 |pages= 1436-50 |year= 2004 |pmid= 15324660 |doi= 10.1016/j.cub.2004.07.051 }}
*{{cite journal   |vauthors=Qiu H, Zappacosta F, Su W, etal |title=Interaction between Brk kinase and insulin receptor substrate-4. |journal=Oncogene |volume=24 |issue= 36 |pages= 5656–64 |year= 2005 |pmid= 15870689 |doi= 10.1038/sj.onc.1208721 }}
*{{cite journal  | author=Mihindukulasuriya KA, Zhou G, Qin J, Tan TH |title=Protein phosphatase 4 interacts with and down-regulates insulin receptor substrate 4 following tumor necrosis factor-alpha stimulation. |journal=J. Biol. Chem. |volume=279 |issue= 45 |pages= 46588-94 |year= 2004 |pmid= 15331607 |doi= 10.1074/jbc.M408067200 }}
*{{cite journal   |vauthors=Cuevas EP, Escribano O, Chiloeches A, etal |title=Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation. |journal=J. Hepatol. |volume=46 |issue= 6 |pages= 1089–98 |year= 2007 |pmid= 17408801 |doi= 10.1016/j.jhep.2007.01.031 }}
*{{cite journal | author=Qiu H, Zappacosta F, Su W, ''et al.'' |title=Interaction between Brk kinase and insulin receptor substrate-4. |journal=Oncogene |volume=24 |issue= 36 |pages= 5656-64 |year= 2005 |pmid= 15870689 |doi= 10.1038/sj.onc.1208721 }}
*{{cite journal | author=Cuevas EP, Escribano O, Chiloeches A, ''et al.'' |title=Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation. |journal=J. Hepatol. |volume=46 |issue= 6 |pages= 1089-98 |year= 2007 |pmid= 17408801 |doi= 10.1016/j.jhep.2007.01.031 }}
}}
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Latest revision as of 00:05, 1 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Insulin receptor substrate 4 is a protein that in humans is encoded by the IRS4 gene.[1][2][3]

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.[3]

Interactions

IRS4 has been shown to interact with CRK[4][5] and NISCH.[6]

References

  1. 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.
  2. 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.
  3. 3.0 3.1 "Entrez Gene: IRS4 insulin receptor substrate 4".
  4. 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.
  5. 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.
  6. 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