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Protein Page:
InsR (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
InsR a receptor tyrosine kinase that mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). The holoenzyme is cleaved into two chains, the alpha and beta subunits. The active complex is a tetramer containing 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains constitute the ligand- binding domain, while the beta chains carry the kinase domain. Interacts with SORBS1 but dissociates from it following insulin stimulation. Familial mutations associated with insulin resistant diabetes, acanthosis nigricans, pineal hyperplasia, and polycystic ovary syndrome. SNP variants may be associated with polycystic ovary syndrome, atypical migraine and diabetic hyperlipidemia. Mutations also cause leprechaunism, a severe insulin resistance syndrome causing growth retardation and death in early infancy. Two isoforms of the human protein are produced by alternative splicing. The Short isoform has a higher affinity for insulin than the longer. Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta. Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas. Note: This description may include information from UniProtKB.
Protein type: Protein kinase, tyrosine (receptor); Protein kinase, TK; EC 2.7.10.1; Membrane protein, integral; Kinase, protein; TK group; InsR family
Cellular Component: membrane; integral to plasma membrane; plasma membrane; endosome membrane; caveola; receptor complex
Molecular Function: GTP binding; PTB domain binding; receptor signaling protein tyrosine kinase activity; insulin-like growth factor II binding; insulin binding; insulin-like growth factor receptor binding; protein binding; insulin-like growth factor I binding; insulin receptor substrate binding; protein-tyrosine kinase activity; phosphoinositide 3-kinase binding; ATP binding; insulin receptor activity
Biological Process: heart morphogenesis; positive regulation of nitric oxide biosynthetic process; peptidyl-tyrosine phosphorylation; activation of MAPK activity; protein amino acid autophosphorylation; regulation of embryonic development; positive regulation of glycogen biosynthetic process; exocrine pancreas development; glucose homeostasis; positive regulation of glucose import; positive regulation of MAPKKK cascade; regulation of transcription, DNA-dependent; male sex determination; positive regulation of cell proliferation; protein heterotetramerization; positive regulation of developmental growth; positive regulation of mitosis; activation of protein kinase B; positive regulation of protein kinase B signaling cascade; G-protein coupled receptor protein signaling pathway; cellular response to insulin stimulus; carbohydrate metabolic process; positive regulation of glycolysis; insulin receptor signaling pathway; activation of protein kinase activity; positive regulation of protein amino acid phosphorylation; positive regulation of DNA replication; positive regulation of cell migration; transformation of host cell by virus
Reference #:  P06213 (UniProtKB)
Alt. Names/Synonyms: CD220; HHF5; INSR; Insulin receptor; Insulin receptor subunit alpha; Insulin receptor subunit beta; IR
Gene Symbols: INSR
Molecular weight: 156,333 Da
Basal Isoelectric point: 5.83  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Insulin Receptor Signaling  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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InsR

Protein Structure Not Found.

Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
cell cycle regulation: Y999‑p, Y1355‑p, Y1361‑p
cell growth, altered: Y1355‑p, Y1361‑p
transcription, altered: Y1189‑p, Y1190‑p
activity, induced: Y999‑p
enzymatic activity, induced: Y999‑p, Y1185‑p, Y1189‑p, Y1190‑p, S1216‑p, S1217‑p, S1221‑p, Y1355‑p, Y1361‑p
enzymatic activity, inhibited: Y992‑p, Y1011‑p, S1332‑p, S1333‑p, T1375‑p
molecular association, regulation: Y999‑p, Y1185‑p, Y1189‑p, Y1190‑p
phosphorylation: Y999‑p, S1033‑p, S1062‑p, S1064‑p, Y1190‑p, S1354‑p, T1375‑p
protein conformation: Y1355‑p, Y1361‑p
receptor internalization, altered: Y999‑p, Y1185‑p, Y1189‑p, Y1190‑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
 

Show Multiple Sequence Alignment


 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

► Hide Isoforms
 
0 1 Y94-p YLLLFRVyGLEsLKD
0 1 S98-p FRVyGLEsLKDLFPN
0 5 T361-p AQELRGCtVINGsLI
0 1 S366-p GCtVINGsLIINIRG
0 2 S400-p GYLKIRRsyALVSLs
0 2 Y401-p YLKIRRsyALVSLsF
0 2 S407-p syALVSLsFFRKLRL
0 1 S464-p YNPKLCLsEIHKMEE
0 1 T715-p ECCSCPKtDsQILKE
0 1 S717-p CSCPKtDsQILKELE
0 1 T731-p EESSFRKtFEDYLHN
0 1 Y818-p GLRHFTGyRIELQAC
0 1 S929-p SVRIRATsLAGNGSW
0 1 T940-p NGSWTEPtYFYVTDY
3 0 Y992-p DGPLGPLyASSNPEy
21 0 Y999-p yASSNPEyLSASDVF
1 0 S1001 SSNPEyLSASDVFPC
5 1 Y1011-p DVFPCSVyVPDEWEV
0 1 K1022 EWEVSREKITLLREL
5 0 S1033-p LRELGQGsFGMVYEG
0 13 K1047-ub GNARDIIkGEAETRV
0 19 K1057-ub AETRVAVkTVNEsAs
3 1 S1062-p AVkTVNEsAsLRERI
3 2 S1064-p kTVNEsAsLRERIEF
1 2 Y1149-p EIADGMAyLNAKKFV
34 455 Y1185-p FGMTRDIyEtDyyRK
0 45 T1187-p MTRDIyEtDyyRKGG
36 711 Y1189-p RDIyEtDyyRKGGKG
34 114 Y1190-p DIyEtDyyRKGGKGL
1 0 S1216-p KDGVFTTssDMWsFG
1 0 S1217-p DGVFTTssDMWsFGV
1 0 S1221-p TTssDMWsFGVVLWE
3 0 S1314-p EENKAPEsEELEMEF
2 0 S1332-p ENVPLDRssHCQREE
2 0 S1333-p NVPLDRssHCQREEA
3 1 S1348-p GGRDGGSsLGFkRsy
0 2 K1352-m1 GGSsLGFkRsyEEHI
0 1 K1352-ub GGSsLGFkRsyEEHI
2 4 S1354-p SsLGFkRsyEEHIPy
14 6 Y1355-p sLGFkRsyEEHIPyt
14 15 Y1361-p syEEHIPytHMNGGK
0 6 T1362-p yEEHIPytHMNGGKK
6 8 T1375-p KKNGRILtLPRSNPS
3021 : Phospho-IGF-I Receptor beta (Tyr1131)/Insulin Receptor beta (Tyr1146) Antibody
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
3024 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
3918 : Phospho-IGF-1 Receptor beta (Tyr1135) (DA7A8) Rabbit mAb
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
3024 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
3026 : Phospho-Insulin Receptor beta (Tyr1345) (14A4) Rabbit mAb
3023 : Phospho-Insulin Receptor beta (Tyr1361) (84B2) Rabbit mAb
  InsR iso2  
Y94 YLLLFRVYGLESLKD
S98 FRVYGLESLKDLFPN
T361 AQELRGCTVINGSLI
S366 GCTVINGSLIINIRG
S400 GYLKIRRSYALVSLS
Y401 YLKIRRSYALVSLSF
S407 SYALVSLSFFRKLRL
S464 YNPKLCLSEIHKMEE
T715 ECCSCPKTDSQILKE
S717 CSCPKTDSQILKELE
T731 EESSFRKTFEDYLHN
Y806 GLRHFTGYRIELQAC
S917 SVRIRATSLAGNGSW
T928 NGSWTEPTYFYVTDY
Y980 DGPLGPLYASSNPEy
Y987-p YASSNPEyLsASDVF
S989-p SSNPEyLsASDVFPC
Y999 DVFPCSVYVPDEWEV
K1010 EWEVSREKITLLREL
S1021 LRELGQGSFGMVYEG
K1035 GNARDIIKGEAETRV
K1045 AETRVAVKTVNESAS
S1050 AVKTVNESASLRERI
S1052 KTVNESASLRERIEF
Y1137 EIADGMAYLNAKKFV
Y1173-p FGMTRDIyETDyyRK
T1175 MTRDIyETDyyRKGG
Y1177-p RDIyETDyyRKGGKG
Y1178-p DIyETDyyRKGGKGL
S1204 KDGVFTTSSDMWSFG
S1205 DGVFTTSSDMWSFGV
S1209 TTSSDMWSFGVVLWE
S1302-p EENKAPEsEELEMEF
S1320 ENVPLDRSSHCQREE
S1321 NVPLDRSSHCQREEA
S1336-p GGRDGGSsLGFKRSy
K1340 GGSsLGFKRSyEEHI
K1340 GGSsLGFKRSyEEHI
S1342 SsLGFKRSyEEHIPy
Y1343-p sLGFKRSyEEHIPyT
Y1349-p SyEEHIPyTHMNGGK
T1350 yEEHIPyTHMNGGKK
T1363-p KKNGRILtLPRSNPS
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
3918 : Phospho-IGF-1 Receptor beta (Tyr1135) (DA7A8) Rabbit mAb
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
  mouse

 
Y94 YLLLFRVYGLESLKD
S98 FRVYGLESLKDLFPN
T361 AQELRGCTVINGSLI
S366 GCTVINGSLIINIRG
S400 GFLKIRRSYALVSLS
Y401 FLKIRRSYALVSLSF
S407 SYALVSLSFFRKLHL
S464 YNPKLCLSEIHKMEE
T717 ECCSCPKTDSQILKE
S719 CSCPKTDSQILKELE
T733 EESSFRKTFEDYLHN
Y808 GLRHFTGYRIELQAC
S919 SVRVRATSLAGNGSW
T930 NGSWTEPTYFYVTDY
Y982 DGPMGPLYASSNPEy
Y989-p YASSNPEyLSASDVF
S991 SSNPEyLSASDVFPS
Y1001-p DVFPSSVyVPDEWEV
K1012-ub EWEVPREkITLLREL
S1023 LRELGQGSFGMVYEG
K1037-ub GNAKDIIkGEAETRV
K1047-ub AETRVAVkTVNEsAs
S1052-p AVkTVNEsAsLRERI
S1054-p kTVNEsAsLRERIEF
Y1139 EIADGMAYLNAKKFV
Y1175-p FGMTRDIyEtDyyRK
T1177-p MTRDIyEtDyyRKGG
Y1179-p RDIyEtDyyRKGGKG
Y1180-p DIyEtDyyRKGGKGL
S1206 KDGVFTASSDMWSFG
S1207 DGVFTASSDMWSFGV
S1211 TASSDMWSFGVVLWE
S1304 EENKAPESEELEMEF
S1322 ENVPLDRSSHCQREE
S1323 NVPLDRSSHCQREEA
S1338 GGREGGSSLSIKRty
K1342 GGSSLSIKRtyDEHI
K1342 GGSSLSIKRtyDEHI
T1344-p SSLSIKRtyDEHIPy
Y1345-p SLSIKRtyDEHIPyt
Y1351-p tyDEHIPytHMNGGK
T1352-p yDEHIPytHMNGGKK
T1365 KKNGRVLTLPRSNPS
3021 : Phospho-IGF-I Receptor beta (Tyr1131)/Insulin Receptor beta (Tyr1146) Antibody
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
3024 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
3918 : Phospho-IGF-1 Receptor beta (Tyr1135) (DA7A8) Rabbit mAb
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
3024 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
  rat

 
Y93 YLLLFRVYGLESLKD
S97 FRVYGLESLKDLFPN
T360 AQELRGCTVINGSLI
S365 GCTVINGSLIINIRG
S399 GFLKIRRSYALVSLS
Y400 FLKIRRSYALVSLSF
S406 SYALVSLSFFRKLHL
S463 YNPKLCLSEIHKMEE
T716 ECCSCPKTDSQILKE
S718 CSCPKTDSQILKELE
T732 EESSFRKTFEDYLHN
Y819 GLRHFTGYRIELQAC
S930 SVRVRATSLAGNGSW
T941 NGSWTEPTYFYVTDY
Y993 DGPMGPLYASSNPEy
Y1000-p YASSNPEyLSASDVF
S1002 SSNPEyLSASDVFPS
Y1012 DVFPSSVYVPDEWEV
K1023 EWEVPREKITLLREL
S1034-p LRELGQGsFGMVYEG
K1048 GNAKDIIKGEVETRV
K1058 VETRVAVKTVNESAS
S1063 AVKTVNESASLRERI
S1065 KTVNESASLRERIEF
Y1150 EIADGMAYLNAKKFV
Y1186-p FGMTRDIyETDyyRK
T1188 MTRDIyETDyyRKGG
Y1190-p RDIyETDyyRKGGKG
Y1191-p DIyETDyyRKGGKGL
S1217 KDGVFTASSDMWSFG
S1218 DGVFTASSDMWSFGV
S1222 TASSDMWSFGVVLWE
S1315 EENKAPESEELEMEF
S1333 ENVPLDRSSHCQREE
S1334 NVPLDRSSHCQREEA
S1349 GCREGGSSLSIKRTy
K1353 GGSSLSIKRTyDEHI
K1353 GGSSLSIKRTyDEHI
T1355 SSLSIKRTyDEHIPy
Y1356-p SLSIKRTyDEHIPyT
Y1362-p TyDEHIPyTHMNGGK
T1363 yDEHIPyTHMNGGKK
T1376-p KKNGRVLtLPRSNPS
3021 : Phospho-IGF-I Receptor beta (Tyr1131)/Insulin Receptor beta (Tyr1146) Antibody
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
3024 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
3918 : Phospho-IGF-1 Receptor beta (Tyr1135) (DA7A8) Rabbit mAb
2969 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb (Biotinylated)
3024 : Phospho-IGF-I Receptor beta (Tyr1135/1136)/Insulin Receptor beta (Tyr1150/1151) (19H7) Rabbit mAb
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