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IRS1 (human)

Overview IRS1 an adaptor protein that is one of the major substrates of the insulin receptor kinase. Contains multiple tyrosine phosphorylation motifs that serve as docking sites for SH2-domain-containing proteins including phosphatidylinositol 3-kinase p85 subunit and GRB-2. Phosphorylated on ser/thr residues by kinases including JNK and IKK. Note: This description may include information from UniProtKB. Protein type: Motility/polarity/chemotaxis; Adaptor/scaffold Cellular Component: intracellular membrane-bound organelle; cytoplasm; plasma membrane; caveola; cytosol; nucleus Molecular Function: insulin-like growth factor receptor binding; signal transducer activity; protein binding; protein kinase C binding; phosphoinositide 3-kinase binding; phospholipid binding; SH2 domain binding; transmembrane receptor protein tyrosine kinase adaptor protein activity; insulin-like growth factor receptor activity; insulin receptor binding Biological Process: response to peptide hormone stimulus; phosphoinositide 3-kinase cascade; nerve growth factor receptor signaling pathway; protein heterooligomerization; positive regulation of glycogen biosynthetic process; negative regulation of insulin receptor signaling pathway; signal transduction; glucose homeostasis; negative regulation of insulin secretion; response to insulin stimulus; positive regulation of glucose import; mammary gland development; positive regulation of cell proliferation; positive regulation of mesenchymal cell proliferation; protein kinase B signaling cascade; phosphoinositide-mediated signaling; positive regulation of phosphoinositide 3-kinase activity; positive regulation of fatty acid beta-oxidation; insulin-like growth factor receptor signaling pathway; cellular response to insulin stimulus; regulation of gene expression; insulin receptor signaling pathway; positive regulation of insulin receptor signaling pathway; positive regulation of phosphorylation; lipid catabolic process; positive regulation of cell migration Reference #:  P35568 (UniProtKB) Alt. Names/Synonyms: HIRS-1; Insulin receptor substrate 1; IRS-1; IRS1 Gene Symbols: IRS1 Molecular weight: 131,591 Da Basal Isoelectric point: 8.83  Predict pI for various phosphorylation states CST Pathways:  Insulin Receptor Signaling  |  MAPK/Erk in Growth and Differentiation  |  mTOR Signaling  |  PI3K/Akt Signaling  |  SAPK/JNK Signaling Cascades  |  Translation: eIF4E and p70S6K Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below IRS1 1IRS - A=157-267 (human) 1K3A - B=891-902 (human) 1QQG - A/B=4-267 (human) 2Z8C - B=731-736 (human) 1AYB - P=887-898 (mouse)

STRING  |  Scansite  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 1IRS 1K3A 1QQG 2Z8C  |  Phospho3D  |  DISEASE 125853 147545  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene

	Sites Implicated In
apoptosis, altered: S312‑p apoptosis, induced: S794‑p cell cycle regulation: Y896‑p cell growth, altered: S794‑p inhibition: S616‑p, S1101‑p, S1223‑p intracellular localization: S307‑p, S312‑p, S527‑p, S616‑p, S636‑p, S639‑p molecular association, regulation: S24‑p, S270‑p, S307‑p, S312‑p, Y612‑p, S629‑p, Y632‑p, S794‑p, Y896‑p phosphorylation: S307‑p, S323‑p, Y896‑p protein degradation: S312‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	5		S3	_____MASPPESDGF
2	1		S24-p	GYLRKPKsMHKRFFV
0	27		Y46-p	GGPARLEyyENEKkW
0	4		Y47-p	GPARLEyyENEKkWR
0	1		K52-a	EyyENEKkWRHKSSA
0	1		K61-a	RHKSSAPkRSIPLES
0	7		Y87-p	NKHLVALyTRDEHFA
1	0		S99	HFAIAADSEAEQDSW
0	1		Y151	EAGEDLSYGDVPPGP
0	3		K169-u	EVWQVILkPKGLGQT
0	1		Y183-p	TKNLIGIyRLCLTSK
0	2		S268-p	SDEFRPRsKsQSssN
3	29		S270-p	EFRPRsKsQSssNCS
1	0		S272	RPRsKsQSssNCSNP
0	1		S273-p	PRsKsQSssNCSNPI
0	1		S274-p	RsKsQSssNCSNPIS
2	2		S303-p	QVGLTRRsRtEsItA
0	2		T305-p	GLTRRsRtEsItAts
31	3		S307-p	TRRsRtEsItAtsPA
0	2		T309-p	RsRtEsItAtsPAsM
0	1		T311-p	RtEsItAtsPAsMVG
62	5		S312-p	tEsItAtsPAsMVGG
0	1		S315-p	ItAtsPAsMVGGKPG
10	6		S323-p	MVGGKPGsFRVRAss
0	1		S329-p	GsFRVRAssDGEGTM
3	8		S330-p	sFRVRAssDGEGTMS
1	0		S337	sDGEGTMSRPAsVDG
2	7		S341-p	GTMSRPAsVDGSPVs
2	21		S348-p	sVDGSPVsPstNRTH
0	1		S350-p	DGSPVsPstNRTHAH
0	2		T351-p	GSPVsPstNRTHAHR
2	0		S362-p	HAHRHRGsARLHPPL
3	0		A363	AHRHRGsARLHPPLN
0	1		S372-p	LHPPLNHsRsIPMPA
1	3		S374-p	PPLNHsRsIPMPASR
1	0		S412	DCLFPRRSSASVSGS
2	0		S413	CLFPRRSSASVSGSP
0	1		S417	RRSSASVSGSPSDGG
0	1		S419	SSASVSGSPSDGGFI
0	1		S428	SDGGFISSDEYGSSP
1	0		S441-p	SPCDFRSsFRSVtPD
0	1		S444	DFRSsFRSVtPDsLG
1	7		T446-p	RSsFRSVtPDsLGHt
0	2		S449-p	FRSVtPDsLGHtPPA
0	8		T453-p	tPDsLGHtPPARGEE
0	1		S463-p	ARGEEELsNyICMGG
1	8		Y465-p	GEEELsNyICMGGKG
0	2		Y483-p	LTAPNGHyILsRGGN
0	2		S486-p	PNGHyILsRGGNGHR
1	2		T495-p	GGNGHRCtPGTGLGT
1	0		S503	PGTGLGTSPALAGDE
1	0		A507	LGTSPALAGDEAASA
0	1		T525	DNRFRKRTHsAGtsP
4	6		S527-p	RFRKRTHsAGtsPTI
0	1		T530-p	KRTHsAGtsPTITHQ
2	5		S531-p	RTHsAGtsPTITHQK
0	1		T535	AGtsPTITHQKTPSQ
4	3		S574-p	RLPGHRHsAFVPTRS
0	21		S603-p	GGHHRPDsstLHtDD
0	10		S604-p	GHHRPDsstLHtDDG
0	20		T605-p	HHRPDsstLHtDDGy
0	21		T608-p	PDsstLHtDDGyMPM
17	301		Y612-p	tLHtDDGyMPMsPGV
30	7		S616-p	DDGyMPMsPGVAPVP
3	39		S629-p	VPSGRKGsGDyMPMs
6	286		Y632-p	GRKGsGDyMPMsPKs
31	11		S636-p	sGDyMPMsPKsVSAP
26	3		S639-p	yMPMsPKsVSAPQQI
0	92		Y662-p	QRVDPNGyMMMsPsG
1	6		S666-p	PNGyMMMsPsGGCsP
0	7		S668-p	GyMMMsPsGGCsPDI
0	3		S672-p	MsPsGGCsPDIGGGP
0	1		S680-p	PDIGGGPsSSSSSSN
0	1		S694-p	NAVPSGTsyGKLWTN
0	2		Y695-p	AVPSGTsyGKLWTNG
0	1		Y732-p	LLPCTGDyMNMSPVG
1	0		S736	TGDyMNMSPVGDSNT
0	3		S766-p	KPVLSYYsLPRSFKH
7	0		S794-p	QHLRLSTsSGRLLYA
0	1		T847-p	HLPRKVDtAAQTNSR
0	1		T859-p	NSRLARPtRLSLGDP
4	7		S892-p	LHPPEPKsPGEyVNI
8	1		Y896-p	EPKsPGEyVNIEFGS
1	0		F915	YLSGPVAFHSSPSVR
0	1		T936-p	PAPREEEtGtEEyMK
0	2		T938-p	PREEEtGtEEyMKMD
2	48		Y941-p	EEtGtEEyMKMDLGP
1	0		S984-g	RPTRAVPssRGDyMT
1	0		S985-g	PTRAVPssRGDyMTM
2	18		Y989-p	VPssRGDyMTMQMSC
3	4		S1005-p	RQSYVDTsPAAPVsy
1	0		S1011-g	TsPAAPVsyADMRTG
0	1		Y1012-p	sPAAPVsyADMRTGI
2	1		S1038	MAAASSSSAAsAsPT
1	0		S1041-p	ASSSSAAsAsPTGPQ
1	0		S1043-p	SSSAAsAsPTGPQGA
1	0		S1043	SSSAAsASPTGPQGA
1	1		G1046	AAsAsPTGPQGAAEL
2	10		S1078-p	AFTRVNLsPNRNQSA
2	86		S1100-p	QGCRRRHssEtFSSt
7	110		S1101-p	GCRRRHssEtFSStP
0	7		T1103-p	RRRHssEtFSStPsA
0	2		T1107-p	ssEtFSStPsAtRVG
0	1		S1109-p	EtFSStPsAtRVGNT
0	4		T1111-p	FSStPsAtRVGNTVP
2	3		S1142-p	SEDVKRHssAsFENV
1	1		S1143-p	EDVKRHssAsFENVW
2	4		S1145-p	VKRHssAsFENVWLR
0	1		G1176	AAGGLENGLNyIDLD
3	25		Y1179-p	GLENGLNyIDLDLVK
2	3		S1222-p	ESSSTRRssEDLSAY
3	10		S1223-p	SSSTRRssEDLSAYA
0	1		S1227	RRssEDLSAYASISF
2	1		Y1229	ssEDLSAYASISFQK

	mouse
S3-p	_____MAsPPDTDGF
S24	GYLRKPKSMHKRFFV
Y46-p	GGPARLEyyENEKKW
Y47-p	GPARLEyyENEKKWR
K52	EyyENEKKWRHKSSA
K61	RHKSSAPKRSIPLES
Y87	NKHLVALYTRDEHFA
S99	HFAIAADSEAEQDSW
Y147-p	EAGEDLSyDTGPGPA
K164	EVWQVILKPKGLGQT
Y178	TKNLIGIYRLCLTSK
S263	SDEFRPRSKsQsSSS
S265-p	EFRPRSKsQsSSSCS
S267-p	RPRSKsQsSSSCSNP
S268	PRSKsQsSSSCSNPI
S269	RSKsQsSSSCSNPIS
S298	QVGLTRRSRTEsITA
T300	GLTRRSRTEsITATs
S302-p	TRRSRTEsITATsPA
T304	RSRTEsITATsPASM
T306	RTEsITATsPASMVG
S307-p	TEsITATsPASMVGG
S310	ITATsPASMVGGKPG
S318-p	MVGGKPGsFRVRAss
S324-p	GsFRVRAssDGEGTM
S325-p	sFRVRAssDGEGTMS
S332	sDGEGTMSRPASVDG
S336	GTMSRPASVDGSPVs
S343-p	SVDGSPVsPStNRTH
S345	DGSPVsPStNRTHAH
T346-p	GSPVsPStNRTHAHR
S357	HAHRHRGSSRLHPPL
S358	AHRHRGSSRLHPPLN
S367	LHPPLNHSRsIPMPS
S369-p	PPLNHSRsIPMPSSR
S407	DCLFPRRSsASVsGs
S408-p	CLFPRRSsASVsGsP
S412-p	RRSsASVsGsPSDGG
S414-p	SsASVsGsPSDGGFI
S423-p	SDGGFISsDEYGSSP
S436	SPCDFRSSFRsVtPD
S439-p	DFRSSFRsVtPDsLG
T441-p	RSSFRsVtPDsLGHt
S444-p	FRsVtPDsLGHtPPA
T448-p	tPDsLGHtPPARGEE
S458	ARGEEELSNyICMGG
Y460-p	GEEELSNyICMGGKG
Y478	LAAPNGHYILSRGGN
S481	PNGHYILSRGGNGHR
I490	GGNGHRYIPGANLGT
S498	PGANLGTSPALPGDE
P502	LGTSPALPGDEAAGA
T520-p	DNRFRKRtHsAGTSP
S522-p	RFRKRtHsAGTSPTI
T525	KRtHsAGTSPTIsHQ
S526	RtHsAGTSPTIsHQK
S530-p	AGTSPTIsHQKTPSQ
S570	RLPGYRHSAFVPTHS
T599-p	GGHHRPDtsNLHTDD
S600-p	GHHRPDtsNLHTDDG
N601	HHRPDtsNLHTDDGy
T604	PDtsNLHTDDGyMPM
Y608-p	NLHTDDGyMPMsPGV
S612-p	DDGyMPMsPGVAPVP
N625	VPSNRKGNGDyMPMs
Y628-p	NRKGNGDyMPMsPKs
S632-p	NGDyMPMsPKsVSAP
S635-p	yMPMsPKsVSAPQQI
Y658	QRVDPNGYMMMsPSG
S662-p	PNGYMMMsPSGSCSP
S664	GYMMMsPSGSCSPDI
S668	MsPSGSCSPDIGGGS
S675	SPDIGGGSSSSSSIS
S689	SAAPSGSSYGKPWTN
Y690	AAPSGSSYGKPWTNG
Y727	LLPCTGDYMNMsPVG
S731-p	TGDYMNMsPVGDSNT
S761	KPVLSYYSLPRSFKH
S789-p	QHLRLSSsSGRLRYT
T842	HLPRKVDTAAQTNSR
T854	NSRLARPTRLSLGDP
S887-p	LHPPEPKsPGEyVNI
Y891-p	EPKsPGEyVNIEFGS
S910	YLAGPATSRSSPSVR
T930	HPAPREETGSEEyMN
S932	APREETGSEEyMNMD
Y935-p	EETGSEEyMNMDLGP
N978	RPTRSVPNSRGDyMT
S979	PTRSVPNSRGDyMTM
Y983-p	VPNSRGDyMTMQIGC
S999-p	RQSYVDTsPVAPVSY
S1005	TsPVAPVSYADMRTG
Y1006	sPVAPVSYADMRTGI
S1032	GAAPPPSSTASSSAS
S1035	PPPSSTASSSASVTP
S1037	PSSTASSSASVTPQG
S1037	PSSTASSSASVTPQG
T1041	ASSSASVTPQGATAE
S1074-p	AFTRVNLsPNHNQSA
S1096-p	QGCRRRHssEtFSAP
S1097-p	GCRRRHssEtFSAPt
T1099-p	RRRHssEtFSAPtRA
-	gap
-	gap
T1104-p	sEtFSAPtRAGNTVP
S1136-p	SEDVKRHssASFENV
S1137-p	EDVKRHssASFENVW
S1139	VKRHssASFENVWLR
S1170-p	AAGGLEKsLNyIDLD
Y1173-p	GLEKsLNyIDLDLAK
S1213-p	EGNSPRRssEDLsNy
S1214-p	GNSPRRssEDLsNyA
S1218-p	RRssEDLsNyASISF
Y1220-p	ssEDLsNyASISFQK

	rat
S3	_____MASPPDTDGF
S24-p	GYLRKPKsMHKRFFV
Y46	GGPARLEYYENEKKW
Y47	GPARLEYYENEKKWR
K52	EYYENEKKWRHKSSA
K61	RHKSSAPKRSIPLES
Y87	NKHLVALYTRDEHFA
S99-p	HFAIAADsEAEQDSW
Y147	EAGEDLSYDTGPGPA
K164	EVWQVILKPKGLGQT
Y178	TKNLIGIYRLCLTSK
T263	SDEFRPRTKsQSSSS
S265-p	EFRPRTKsQSSSSCS
S267	RPRTKsQSSSSCSNP
S268	PRTKsQSSSSCSNPI
S269	RTKsQSSSSCSNPIS
S298	QVGLTRRSRTEsITA
T300	GLTRRSRTEsITATs
S302-p	TRRSRTEsITATsPA
T304	RSRTEsITATsPASM
T306	RTEsITATsPASMVG
S307-p	TEsITATsPASMVGG
S310	ITATsPASMVGGKPG
S318-p	MVGGKPGsFRVRAss
S324-p	GsFRVRAssDGEGTM
S325-p	sFRVRAssDGEGTMs
S332-p	sDGEGTMsRPAsVDG
S336-p	GTMsRPAsVDGSPVs
S343-p	sVDGSPVsPSTNRTH
S345	DGSPVsPSTNRTHAH
T346	GSPVsPSTNRTHAHR
S357-p	HAHRHRGssRLHPPL
S358-p	AHRHRGssRLHPPLN
S367	LHPPLNHSRsIPMPS
S369-p	PPLNHSRsIPMPSSR
S407-p	DCLFPRRssASVSGS
S408-p	CLFPRRssASVSGSP
S412	RRssASVSGSPSDGG
S414	ssASVSGSPSDGGFI
S423	SDGGFISSDEYGSSP
S436	SPCDFRSSFRSVTPD
S439	DFRSSFRSVTPDSLG
T441	RSSFRSVTPDSLGHT
S444	FRSVTPDSLGHTPPA
T448	TPDSLGHTPPARGEE
S458	ARGEEELSNyICMGG
Y460-p	GEEELSNyICMGGKG
Y478	LTAPNGHYILSRGGN
S481	PNGHYILSRGGNGHR
I490	GGNGHRYIPGATMGT
S498-p	PGATMGTsPALtGDE
T502-p	MGTsPALtGDEAAGA
T520	DNRFRKRTHsAGTsP
S522-p	RFRKRTHsAGTsPTI
T525	KRTHsAGTsPTISHQ
S526-p	RTHsAGTsPTISHQK
S530	AGTsPTISHQKTPSQ
S570-p	RLPGYRHsAFVPTHS
S599	GGHHRPDSSNLHTDD
S600	GHHRPDSSNLHTDDG
N601	HHRPDSSNLHTDDGy
T604	PDSSNLHTDDGyMPM
Y608-p	NLHTDDGyMPMsPGV
S612-p	DDGyMPMsPGVAPVP
N625	VPSNRKGNGDyMPMs
Y628-p	NRKGNGDyMPMsPKs
S632-p	NGDyMPMsPKsVSAP
S635-p	yMPMsPKsVSAPQQI
Y658	QRVDPNGYMMMSPSG
S662	PNGYMMMSPSGSCSP
S664	GYMMMSPSGSCSPDI
S668	MSPSGSCSPDIGGGS
S675	SPDIGGGSCSSSSIS
S689	SAAPSGSSYGKPWTN
Y690	AAPSGSSYGKPWTNG
Y727	LLPCTGDYMNMSPVG
S731	TGDYMNMSPVGDSNT
S761	KPVLSYYSLPRSFKH
S789-p	QHLRLSSsSGRLRYT
T842	HLPRKVDTAAQTNSR
T854	NSRLARPTRLSLGDP
S891-p	LHPPEPKsPGEyVNI
Y895-p	EPKsPGEyVNIEFGS
S914-g	YLAGPATsRSSPSVR
T934	HPAPREETGSEEyMN
S936	APREETGSEEyMNMD
Y939-p	EETGSEEyMNMDLGP
N982	RPTRSVPNSRGDyMT
S983	PTRSVPNSRGDyMTM
Y987-p	VPNSRGDyMTMQIGC
S1003-p	RQSYVDTsPVAPVsY
S1009-g	TsPVAPVsYADMRTG
Y1010	sPVAPVsYADMRTGI
S1036-g	GAAPPPSsTASAsAS
S1039	PPPSsTASAsASVtP
S1041	PSsTASASASVtPQG
S1041-g	PSsTASAsASVtPQG
T1045-p	ASAsASVtPQGAAEQ
S1077-p	AFTRVNLsPNHNQSA
S1099-p	QGCRRRHssETFSAP
S1100-p	GCRRRHssETFSAPT
T1102	RRRHssETFSAPTRA
-	gap
-	gap
T1107	sETFSAPTRAANTVS
S1135	SEDVKRHSSASFENV
S1136	EDVKRHSSASFENVW
S1138	VKRHSSASFENVWLR
S1169	AAGGLEKSLNyIDLD
Y1172-p	GLEKSLNyIDLDLVK
S1215-p	EGSSPRRssEDLSTy
S1216-p	GSSPRRssEDLSTyA
S1220	RRssEDLSTyASINF
Y1222-p	ssEDLSTyASINFQK

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