HUMAN:IRS1

Species (Taxon ID)	Homo sapiens (Human). (9606)
Gene Name(s)	IRS1
Protein Name(s)	Insulin receptor substrate 1 IRS-1
External Links
UniProt	P35568
EMBL	S85963 S62539 BC053895
CCDS	CCDS2463.1
PIR	I53160
RefSeq	NP_005535.1
UniGene	Hs.471508
PDB	1IRS 1K3A 1QQG 2Z8C
PDBsum	1IRS 1K3A 1QQG 2Z8C
ProteinModelPortal	P35568
SMR	P35568
BioGrid	109874
DIP	DIP-523N
IntAct	P35568
MINT	MINT-149537
STRING	9606.ENSP00000304895
PhosphoSite	P35568
BioMuta	IRS1
DMDM	547738
MaxQB	P35568
PaxDb	P35568
PRIDE	P35568
DNASU	3667
Ensembl	ENST00000305123
GeneID	3667
KEGG	hsa:3667
UCSC	uc002voh.4
CTD	3667
GeneCards	GC02M227563
HGNC	HGNC:6125
HPA	CAB005261 HPA046433 HPA050221
MIM	125853 147545
neXtProt	NX_P35568
PharmGKB	PA203
eggNOG	NOG81285
GeneTree	ENSGT00530000063420
HOGENOM	HOG000113103
HOVERGEN	HBG000542
InParanoid	P35568
KO	K16172
OMA	HALPHPK
OrthoDB	EOG7XM2X6
PhylomeDB	P35568
TreeFam	TF325994
Reactome	REACT_111133 REACT_12464 REACT_147727 REACT_150203 REACT_169118 REACT_508 REACT_524 REACT_570 REACT_75829 REACT_976
SignaLink	P35568
ChiTaRS	IRS1
EvolutionaryTrace	P35568
GeneWiki	IRS1
GenomeRNAi	3667
NextBio	14355
PMAP-CutDB	P35568
PRO	PR:P35568
Proteomes	UP000005640
Bgee	P35568
CleanEx	HS_IRS1
ExpressionAtlas	P35568
Genevisible	P35568
GO	GO:0005901 GO:0036064 GO:0005737 GO:0005829 GO:0005899 GO:0043231 GO:0005634 GO:0005886 GO:0005158 GO:0005159 GO:0043548 GO:0005080 GO:0042169 GO:0004871 GO:0005068 GO:0032869 GO:0007173 GO:0038095 GO:0008543 GO:0042593 GO:0045087 GO:0008286 GO:0048009 GO:0060397 GO:0016042 GO:0030879 GO:0046627 GO:0046676 GO:0048011 GO:0014065 GO:0048015 GO:0030335 GO:0008284 GO:0032000 GO:0046326 GO:2001275 GO:0010907 GO:0045725 GO:0046628 GO:0002053 GO:0043552 GO:0043491 GO:0034504 GO:0010468 GO:0032868 GO:0043434 GO:0007165
Gene3D	2.30.29.30
InterPro	IPR002404 IPR011993 IPR001849
Pfam	PF02174 PF00169
PRINTS	PR00628
SMART	SM00233 SM00310
PROSITE	PS51064 PS50003

Annotations

Qualifier	GO ID	GO term name	Reference	ECO ID	ECO term name	with/from	Aspect	Extension	Notes	Status
	GO:0005069	transmembrane receptor protein tyrosine kin...		ECO:0000304			F		Source: ProtInc	Missing: reference
involved_in	GO:0046326	positive regulation of glucose import	PMID:7493946^[1]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0005070	SH3/SH2 adaptor activity	PMID:7493946^[1]	ECO:0000314	direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0071398	cellular response to fatty acid	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35569	P	occurs_in:(CL:0000182)	Seeded From UniProt	complete
involved_in	GO:0008286	insulin receptor signaling pathway	PMID:7559478^[2]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P06213	P		Seeded From UniProt	complete
enables	GO:0001784	phosphotyrosine residue binding	PMID:20624904^[3]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:Q6GX35	F		Seeded From UniProt	complete
involved_in	GO:0046628	positive regulation of insulin receptor signaling pathway	PMID:7493946^[1]	ECO:0000314	direct assay evidence used in manual assertion		P	positively_regulates:(GO:0046326)	Seeded From UniProt	complete
involved_in	GO:0046676	negative regulation of insulin secretion	PMID:15572028^[4]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0046628	positive regulation of insulin receptor signaling pathway	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	P		Seeded From UniProt	complete
involved_in	GO:0046627	negative regulation of insulin receptor signaling pathway	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	P		Seeded From UniProt	complete
involved_in	GO:0046326	positive regulation of glucose import	PMID:16814735^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0045725	positive regulation of glycogen biosynthetic process	PMID:16814735^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0045725	positive regulation of glycogen biosynthetic process	PMID:17925406^[6]	ECO:0000303	author statement without traceable support used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	P		Seeded From UniProt	complete
enables	GO:0043548	phosphatidylinositol 3-kinase binding	PMID:7782332^[7]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P27986	F		Seeded From UniProt	complete
involved_in	GO:0043434	response to peptide hormone	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	P		Seeded From UniProt	complete
involved_in	GO:0032869	cellular response to insulin stimulus	PMID:16814735^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0032868	response to insulin	PMID:16516141^[8]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0032000	positive regulation of fatty acid beta-oxidation	PMID:16814735^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0014065	phosphatidylinositol 3-kinase signaling	PMID:7782332^[7]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0010907	positive regulation of glucose metabolic process	PMID:16814735^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0008286	insulin receptor signaling pathway	PMID:16814735^[5]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0008286	insulin receptor signaling pathway	PMID:16516141^[8]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0008284	positive regulation of cell population proliferation	PMID:17925406^[6]	ECO:0000303	author statement without traceable support used in manual assertion		P		Seeded From UniProt	complete
part_of	GO:0005901	caveola	PMID:15182363^[9]	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005899	insulin receptor complex	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	C		Seeded From UniProt	complete
enables	GO:0005158	insulin receptor binding	PMID:7493946^[1]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P06213	F		Seeded From UniProt	complete
enables	GO:0005080	protein kinase C binding	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	F		Seeded From UniProt	complete
enables	GO:0005068	transmembrane receptor protein tyrosine kinase adaptor activity	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	F		Seeded From UniProt	complete
involved_in	GO:0048009	insulin-like growth factor receptor signaling pathway	PMID:7541045^[10]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P08069	P		Seeded From UniProt	complete
enables	GO:0043548	phosphatidylinositol 3-kinase binding	PMID:16043515^[11]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P26450	F		Seeded From UniProt	complete
enables	GO:0043548	phosphatidylinositol 3-kinase binding	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	F		Seeded From UniProt	complete
part_of	GO:0043231	intracellular membrane-bounded organelle	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35569	C		Seeded From UniProt	complete
enables	GO:0042169	SH2 domain binding	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35570	F		Seeded From UniProt	complete
involved_in	GO:0008286	insulin receptor signaling pathway	PMID:7537849^[12]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P06213	P		Seeded From UniProt	complete
part_of	GO:0005737	cytoplasm	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35569	C		Seeded From UniProt	complete
part_of	GO:0005634	nucleus	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P35569	C		Seeded From UniProt	complete
enables	GO:0005159	insulin-like growth factor receptor binding	PMID:7541045^[10]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P08069	F		Seeded From UniProt	complete
enables	GO:0005158	insulin receptor binding	PMID:7537849^[12]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P06213	F		Seeded From UniProt	complete
enables	GO:0043548	phosphatidylinositol 3-kinase binding	PMID:21873635^[13]	ECO:0000318	biological aspect of ancestor evidence used in manual assertion	MGI:MGI:109334 MGI:MGI:1194882 MGI:MGI:99454 PANTHER:PTN000064809 RGD:2922 RGD:69316 UniProtKB:P35568	F		Seeded From UniProt	complete
involved_in	GO:0008286	insulin receptor signaling pathway	PMID:21873635^[13]	ECO:0000318	biological aspect of ancestor evidence used in manual assertion	FB:FBgn0024248 MGI:MGI:109334 PANTHER:PTN000064809 RGD:2922 RGD:69316 UniProtKB:P35568	P		Seeded From UniProt	complete
part_of	GO:0005886	plasma membrane	PMID:21873635^[13]	ECO:0000318	biological aspect of ancestor evidence used in manual assertion	MGI:MGI:109334 MGI:MGI:1194882 MGI:MGI:99454 PANTHER:PTN000064809 RGD:2922 RGD:69317 UniProtKB:P35568	C		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	PMID:21873635^[13]	ECO:0000318	biological aspect of ancestor evidence used in manual assertion	FB:FBgn0024248 MGI:MGI:109334 PANTHER:PTN000064809 RGD:2922 RGD:69317 UniProtKB:P35568	C		Seeded From UniProt	complete
enables	GO:0005158	insulin receptor binding	PMID:21873635^[13]	ECO:0000318	biological aspect of ancestor evidence used in manual assertion	FB:FBgn0024248 PANTHER:PTN000064809 RGD:2922 RGD:69316 UniProtKB:P35568	F		Seeded From UniProt	complete
part_of	GO:0005886	plasma membrane	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005634	nucleus	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
enables	GO:0005158	insulin receptor binding	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR039011	F		Seeded From UniProt	complete
involved_in	GO:0008286	insulin receptor signaling pathway	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR039011	P		Seeded From UniProt	complete
involved_in	GO:0007165	signal transduction	PMID:1311924^[14]	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
part_of	GO:0005737	cytoplasm	PMID:1648180^[15]	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
enables	GO:0005068	transmembrane receptor protein tyrosine kinase adaptor activity	PMID:1648180^[15]	ECO:0000304	author statement supported by traceable reference used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0042593	glucose homeostasis	PMID:16814735^[5]	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0051897	positive regulation of protein kinase B signaling	Reactome:R-HSA-2316434	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0048015	phosphatidylinositol-mediated signaling	Reactome:R-HSA-198203	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0038111	interleukin-7-mediated signaling pathway	Reactome:R-HSA-1266695	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
part_of	GO:0005886	plasma membrane	Reactome:R-HSA-2428930 Reactome:R-HSA-2428926 Reactome:R-HSA-2400009 Reactome:R-HSA-2316434 Reactome:R-HSA-198266	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	Reactome:R-HSA-8983003 Reactome:R-HSA-74747 Reactome:R-HSA-74737 Reactome:R-HSA-74736 Reactome:R-HSA-74712 Reactome:R-HSA-74711 Reactome:R-HSA-74707 Reactome:R-HSA-5686315 Reactome:R-HSA-5672965 Reactome:R-HSA-198315 Reactome:R-HSA-109823 Reactome:R-HSA-109699	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
involved_in	GO:0000165	MAPK cascade	Reactome:R-HSA-5673001	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0007165	signal transduction	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0807	P		Seeded From UniProt	complete
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Notes

References

See Help:References for how to manage references in GONUTS.

↑ ^1.0 ^1.1 ^1.2 ^1.3 Kharitonenkov, A et al. (1995) Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction. J. Biol. Chem. 270 29189-93 PubMed GONUTS page
↑ He, W et al. (1995) Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. J. Biol. Chem. 270 23258-62 PubMed GONUTS page
↑ Mehlitz, A et al. (2010) Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1. J. Cell Biol. 190 143-57 PubMed GONUTS page
↑ Mohanty, S et al. (2005) Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human beta-cells from hyperglycemia-induced apoptosis. Exp. Cell Res. 303 68-78 PubMed GONUTS page
↑ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 ^5.6 Bouzakri, K et al. (2006) siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle. Cell Metab. 4 89-96 PubMed GONUTS page
↑ ^6.0 ^6.1 Jensen, M et al. (2007) Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses. J. Biol. Chem. 282 35179-86 PubMed GONUTS page
↑ ^7.0 ^7.1 Argetsinger, LS et al. (1995) Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1. J. Biol. Chem. 270 14685-92 PubMed GONUTS page
↑ ^8.0 ^8.1 Danielsson, A et al. (2006) Phosphorylation of IRS1 at serine 307 and serine 312 in response to insulin in human adipocytes. Biochem. Biophys. Res. Commun. 342 1183-7 PubMed GONUTS page
↑ Karlsson, M et al. (2004) Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes. Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control. Eur. J. Biochem. 271 2471-9 PubMed GONUTS page
↑ ^10.0 ^10.1 Craparo, A et al. (1995) Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J. Biol. Chem. 270 15639-43 PubMed GONUTS page
↑ Luo, J et al. (2005) The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. J. Cell Biol. 170 455-64 PubMed GONUTS page
↑ ^12.0 ^12.1 Gustafson, TA et al. (1995) Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol. Cell. Biol. 15 2500-8 PubMed GONUTS page
↑ ^13.0 ^13.1 ^13.2 ^13.3 ^13.4 Gaudet, P et al. (2011) Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief. Bioinformatics 12 449-62 PubMed GONUTS page
↑ Nishiyama, M & Wands, JR (1992) Cloning and increased expression of an insulin receptor substrate-1-like gene in human hepatocellular carcinoma. Biochem. Biophys. Res. Commun. 183 280-5 PubMed GONUTS page
↑ ^15.0 ^15.1 Sun, XJ et al. (1991) Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352 73-7 PubMed GONUTS page

[PMID:7493946-1] 1.0 ^1.1 ^1.2 ^1.3 Kharitonenkov, A et al. (1995) Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction. J. Biol. Chem. 270 29189-93 PubMed GONUTS page

[PMID:7559478-2] He, W et al. (1995) Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. J. Biol. Chem. 270 23258-62 PubMed GONUTS page

[PMID:20624904-3] Mehlitz, A et al. (2010) Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1. J. Cell Biol. 190 143-57 PubMed GONUTS page

[PMID:15572028-4] Mohanty, S et al. (2005) Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human beta-cells from hyperglycemia-induced apoptosis. Exp. Cell Res. 303 68-78 PubMed GONUTS page

[PMID:16814735-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 ^5.6 Bouzakri, K et al. (2006) siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle. Cell Metab. 4 89-96 PubMed GONUTS page

[PMID:17925406-6] 6.0 ^6.1 Jensen, M et al. (2007) Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses. J. Biol. Chem. 282 35179-86 PubMed GONUTS page

[PMID:7782332-7] 7.0 ^7.1 Argetsinger, LS et al. (1995) Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1. J. Biol. Chem. 270 14685-92 PubMed GONUTS page

[PMID:16516141-8] 8.0 ^8.1 Danielsson, A et al. (2006) Phosphorylation of IRS1 at serine 307 and serine 312 in response to insulin in human adipocytes. Biochem. Biophys. Res. Commun. 342 1183-7 PubMed GONUTS page

[PMID:15182363-9] Karlsson, M et al. (2004) Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes. Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control. Eur. J. Biochem. 271 2471-9 PubMed GONUTS page

[PMID:7541045-10] 10.0 ^10.1 Craparo, A et al. (1995) Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J. Biol. Chem. 270 15639-43 PubMed GONUTS page

[PMID:16043515-11] Luo, J et al. (2005) The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. J. Cell Biol. 170 455-64 PubMed GONUTS page

[PMID:7537849-12] 12.0 ^12.1 Gustafson, TA et al. (1995) Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol. Cell. Biol. 15 2500-8 PubMed GONUTS page

[PMID:21873635-13] 13.0 ^13.1 ^13.2 ^13.3 ^13.4 Gaudet, P et al. (2011) Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief. Bioinformatics 12 449-62 PubMed GONUTS page

[PMID:1311924-14] Nishiyama, M & Wands, JR (1992) Cloning and increased expression of an insulin receptor substrate-1-like gene in human hepatocellular carcinoma. Biochem. Biophys. Res. Commun. 183 280-5 PubMed GONUTS page

[PMID:1648180-15] 15.0 ^15.1 Sun, XJ et al. (1991) Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352 73-7 PubMed GONUTS page

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HUMAN:IRS1

Contents

Annotations

Notes

References

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