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IGF1R (human)

Overview IGF1R a receptor tyrosine kinase that binds insulin-like growth factor 1 (IGF1) with a high affinity and IGF2 with a lower affinity. Functions as an anti-apoptotic agent by enhancing cell survival. Can play a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand- binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Mutated in rare cases of pre- and post-natal growth retardation. One SNP associated with increased human longevity. Increased expression of IGF1R and other pathway members associated with progression and malignancy in a range of cancers. Inhibitors: AG1024, AEW541. Note: This description may include information from UniProtKB. Protein type: Kinase, protein; EC 2.7.10.1; Protein kinase, tyrosine (receptor); Membrane protein, integral; Protein kinase, TK; TK group; InsR family Cellular Component: neuron projection; intracellular membrane-bound organelle; membrane; integral to plasma membrane; caveola Molecular Function: insulin binding; identical protein binding; insulin-like growth factor binding; protein binding; insulin-like growth factor I binding; insulin receptor substrate binding; protein-tyrosine kinase activity; phosphoinositide 3-kinase binding; ATP binding; insulin-like growth factor receptor activity; insulin receptor binding Biological Process: phosphoinositide 3-kinase cascade; inactivation of MAPKK activity; protein heterooligomerization; protein amino acid autophosphorylation; exocrine pancreas development; signal transduction; regulation of JNK cascade; response to vitamin E; positive regulation of MAPKKK cascade; mammary gland development; male sex determination; positive regulation of cell proliferation; protein tetramerization; positive regulation of cytokinesis; negative regulation of protein kinase B signaling cascade; phosphoinositide-mediated signaling; positive regulation of protein kinase B signaling cascade; axonogenesis; insulin-like growth factor receptor signaling pathway; establishment of cell polarity; insulin receptor signaling pathway; immune response; brain development; positive regulation of DNA replication; positive regulation of cell migration; negative regulation of apoptosis Reference #:  P08069 (UniProtKB) Alt. Names/Synonyms: CD221; IGF-I receptor; IGF1R; IGFIR; IGFR; Insulin-like growth factor 1 receptor; Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain; Insulin-like growth factor I receptor; JTK13; MGC142170; MGC142172; MGC18216; soluble IGF1R variant 1; soluble IGF1R variant 2 Gene Symbols: IGF1R Molecular weight: 154,793 Da Basal Isoelectric point: 5.58  Predict pI for various phosphorylation states CST Pathways:  Angiogenesis  |  ESC Pluripotency and Differentiation  |  Tyrosine Kinases Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below IGF1R 1IGR - A=31-492 (human) 1JQH - A/B/C=981-1286 (human) 1K3A - A=988-1286 (human) 1M7N - A/B=974-1294 (human) 1P4O - A/B=974-1294 (human) 2OJ9 - A=982-1286 (human) 2ZM3 - A/D/C/B=981-1286 (human) 3D94 - A=986-1286 (human) 3F5P - S/F/A/J/T/K/E/B/H/M/C/D/R/I/G/L=981-1286 (human) 3I81 - A=982-1286 (human) 3LVP - A/D/C/B=951-1286 (human) 3LW0 - A/D/C/B=983-1286 (human) 3NW5 - A=982-1286 (human) 3NW6 - A=982-1286 (human) 3NW7 - A=982-1286 (human) 3O23 - A=982-1286 (human) 3QQU - A/D/C/B=988-1286 (human)

STRING  |  Scansite  |  KinBase  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 1IGR 1JQH 1K3A 1M7N 1P4O 2OJ9 2ZM3 3D94 3F5P 3I81 3LVP 3LW0 3NW5 3NW6 3NW7 3O23 3QQU  |  ENZYME  |  Phospho3D  |  DISEASE 147370 270450  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene

	Sites Implicated In
apoptosis, altered: Y980‑p, Y1281‑p, S1310‑p, S1311‑p, S1312‑p, S1313‑p cell cycle regulation: Y980‑p cell differentiation, altered: Y980‑p, Y1280‑p, Y1281‑p, S1310‑p, S1311‑p, S1312‑p, S1313‑p, Y1346‑p cell growth, altered: Y980‑p, Y1166‑p, Y1280‑p, Y1281‑p, S1310‑p, S1311‑p, S1312‑p, S1313‑p, Y1346‑p activation: Y980‑p, S1310‑p, S1311‑p, S1312‑p, S1313‑p enzymatic activity, induced: Y1161‑p, Y1165‑p, Y1166‑p, Y1346‑p molecular association, regulation: Y1161‑p, Y1346‑p phosphorylation: Y980‑p, Y1166‑p, S1310‑p, S1311‑p, S1312‑p, S1313‑p protein conformation: Y1161‑p, Y1165‑p, Y1166‑p receptor internalization, altered: Y1161‑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	1		S3-p	_____MKsGsGGGsP
0	1		S5-p	___MKsGsGGGsPts
0	1		S9-p	KsGsGGGsPtsLWGL
0	1		T11-p	GsGGGsPtsLWGLLF
0	1		S12-p	sGGGsPtsLWGLLFL
0	1		T28-p	AALSLWPtsGEICGP
0	1		S29-p	ALSLWPtsGEICGPG
0	1		Y113-p	IRGWKLFyNyALVIF
0	1		Y115-p	GWKLFyNyALVIFEM
0	1		T123-p	ALVIFEMtNLKDIGL
0	1		Y131-p	NLKDIGLyNLRNITR
0	1		R471-m1	EVTGTKGrQSKGDIN
0	1		R480-m1	SKGDINTrNNGERAS
0	1		Y577-p	GLKPWTQyAVyVKAV
0	1		Y580-p	PWTQyAVyVKAVTLT
0	1		S623-p	DVLSASNssSQLIVK
0	1		S624-p	VLSASNssSQLIVKW
2	1		Y973-p	RLGNGVLyASVNPEy
6	1		Y980-p	yASVNPEyFsAADVY
1	0		S982-p	SVNPEyFsAADVYVP
0	1		Y1014-p	QGSFGMVyEGVAKGV
0	1		K1023	GVAKGVVKDEPETRV
0	4		K1033-u	PETRVAIkTVNEAAS
1	0		K1055-s	LNEASVMkEFNCHHV
1	0		K1130-s	MAYLNANkFVHRDLA
1	0		K1150-s	VAEDFTVkIGDFGMT
15	464		Y1161-p	FGMTRDIyEtDyyRK
0	42		T1163-p	MTRDIyEtDyyRKGG
10	718		Y1165-p	RDIyEtDyyRKGGKG
8	116		Y1166-p	DIyEtDyyRKGGKGL
0	1		S1193-p	DGVFTTYsDVWSFGV
1	0		S1278-p	EPGFREVsFyySEEN
5	0		Y1280-p	GFREVsFyySEENKL
5	0		Y1281-p	FREVsFyySEENKLP
2	0		S1310-p	VPLDPSAssssLPLP
2	0		S1311-p	PLDPSAssssLPLPD
2	0		S1312-p	LDPSAssssLPLPDR
2	0		S1313-p	DPSAssssLPLPDRH
1	0		S1321-p	LPLPDRHsGHKAENG
0	4		S1339-p	GVLVLRAsFDERQPy
3	26		Y1346-p	sFDERQPyAHMNGGR
0	1		K1354-m1	AHMNGGRkNERALPL
0	7		T1366-p	LPLPQSStC______

	mouse
S3	_____MKSGSGGGSP
S5	___MKSGSGGGSPTS
S9	KSGSGGGSPTSLWGL
T11	GSGGGSPTSLWGLVF
S12	SGGGSPTSLWGLVFL
T28	AALSLWPTSGEICGP
S29	ALSLWPTSGEICGPG
Y113	IRGWKLFYNYALVIF
Y115	GWKLFYNYALVIFEM
T123	ALVIFEMTNLKDIGL
Y131	NLKDIGLYNLRNITR
R472	EVTGTKGRQSKGDIN
R481	SKGDINTRNNGERAS
Y578	GLKPWTQYAVYVKAV
Y581	PWTQYAVYVKAVTLT
S624	DVLSASNSSSQLIVK
S625	VLSASNSSSQLIVKW
Y974-p	RLGNGVLyASVNPEy
Y981-p	yASVNPEyFSAADVY
S983	SVNPEyFSAADVYVP
Y1015	QGSFGMVYEGVAKGV
K1024-a	GVAKGVVkDEPETRV
K1034-u	PETRVAIkTVNEAAS
K1056	LNEASVMKEFNCHHV
K1132	MAYLNANKFVHRDLA
K1152	VAEDFTVKIGDFGMT
Y1163-p	FGMTRDIyEtDyyRK
T1165-p	MTRDIyEtDyyRKGG
Y1167-p	RDIyEtDyyRKGGKG
Y1168-p	DIyEtDyyRKGGKGL
S1195	DGVFTTHSDVWSFGV
S1280	EPSFQEVSFyySEEN
Y1282-p	SFQEVSFyySEENKP
Y1283-p	FQEVSFyySEENKPP
S1316	VPLDPSASSASLPLP
S1317	PLDPSASSASLPLPE
A1318	LDPSASSASLPLPER
S1319	DPSASSASLPLPERH
S1327	LPLPERHSGHKAENG
S1345-p	GVLVLRAsFDERQPy
Y1352-p	sFDERQPyAHMNGGR
A1360	AHMNGGRANERALPL
T1372-p	LPLPQSStC______

	rat
S3	_____MKSGSGGGSP
S5	___MKSGSGGGSPTS
S9	KSGSGGGSPTSLWGL
T11	GSGGGSPTSLWGLVF
S12	SGGGSPTSLWGLVFL
T28	AALSLWPTSGEICGP
S29	ALSLWPTSGEICGPG
Y113	IRGWKLFYNYALVIF
Y115	GWKLFYNYALVIFEM
T123	ALVIFEMTNLKDIGL
Y131	NLKDIGLYNLRNITR
R472	EVTGTKGRQSKGDIN
R481	SKGDINTRNNGERAS
Y578	GLKPWTQYAVYVKAV
Y581	PWTQYAVYVKAVTLT
S624	DVLSASNSSSQLIVK
S625	VLSASNSSSQLIVKW
Y974	RLGNGVLYASVNPEY
Y981	YASVNPEYFSAADVY
S983	SVNPEYFSAADVYVP
Y1015	QGSFGMVYEGVAKGV
K1024	GVAKGVVKDEPETRV
K1034	PETRVAIKTVNEAAS
K1056	LNEASVMKEFNCHHV
K1131	MAYLNANKFVHRDLA
K1151	VAEDFTVKIGDFGMT
Y1162-p	FGMTRDIyETDyyRK
T1164	MTRDIyETDyyRKGG
Y1166-p	RDIyETDyyRKGGKG
Y1167-p	DIyETDyyRKGGKGL
S1194	DGVFTTHSDVWSFGV
S1279	EPSFQEVSFYYSEEN
Y1281	SFQEVSFYYSEENKP
Y1282	FQEVSFYYSEENKPP
S1315	VPLDPSASSASLPLP
S1316	PLDPSASSASLPLPE
A1317	LDPSASSASLPLPER
S1318	DPSASSASLPLPERH
S1326	LPLPERHSGHKAENG
S1342	GVLVLRASFDERQPY
Y1349	SFDERQPYAHMNGGR
A1357	AHMNGGRANERALPL
T1369	LPLPQSSTC______

	pig
S3	_____MKSGSGGGSP
S5	___MKSGSGGGSPTS
S9	KSGSGGGSPTSLWGL
T11	GSGGGSPTSLWGLLF
S12	SGGGSPTSLWGLLFF
T28	AALSLWPTSGEICGP
S29	ALSLWPTSGEICGPG
Y113	IRGWKLFYNYALVIF
Y115	GWKLFYNYALVIFEM
T123	ALVIFEMTNLKDIGL
Y131	NLKDIGLYNLRNITR
R471	EVTGTKGRQSKGDIN
R480	SKGDINTRNNGERAS
Y577	GLKPWTQYAVYVKAV
Y580	PWTQYAVYVKAVTLT
S623	DVLSASNSSSQLIVK
S624	VLSASNSSSQLIVKW
Y973	RLGNGVLYASVNPEY
Y980	YASVNPEYFSAADVY
S982	SVNPEYFSAADVYVP
Y1014	QGSFGMVYEGVAKGV
K1023	GVAKGVVKDEPETRV
K1033	PETRVAIKTVNEAAS
K1055	LNEASVMKEFNCHHV
K1130	MAYLNANKFVHRDLA
K1150	VAEDFTVKIGDFGMT
Y1161-p	FGMTRDIyETDYYRK
T1163	MTRDIyETDYYRKGG
Y1165	RDIyETDYYRKGGKG
Y1166	DIyETDYYRKGGKGL
S1193	DGVFTTHSDVWSFGV
S1278	EPGFREVSFYYSEEN
Y1280	GFREVSFYYSEENKP
Y1281	FREVSFYYSEENKPP
S1310	VPLDPSASSSSLPLP
S1311	PLDPSASSSSLPLPD
S1312	LDPSASSSSLPLPDR
S1313	DPSASSSSLPLPDRH
S1321	LPLPDRHSGHKAENG
S1339	GVLVLRASFDERQPY
Y1346	SFDERQPYAHMNGGR
K1354	AHMNGGRKNERALPL
T1366	LPLPQSSTC______

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