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Protein Page:
INSR (mouse)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
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: Kinase, protein; Membrane protein, integral; Protein kinase, tyrosine (receptor); EC 2.7.10.1; Protein kinase, TK; TK group; InsR family
Cellular Component: caveola; cell soma; cytosol; endosome; integral to plasma membrane; intracellular membrane-bound organelle; membrane; nucleus; plasma membrane; receptor complex; synapse
Molecular Function: 3-phosphoinositide-dependent protein kinase binding; ATP binding; GTP binding; insulin binding; insulin receptor activity; insulin receptor substrate binding; insulin-like growth factor I binding; insulin-like growth factor II binding; insulin-like growth factor receptor binding; lipoic acid binding; phosphoinositide 3-kinase binding; protein binding; protein complex binding; protein domain specific binding; protein kinase activity; protein kinase binding; protein phosphatase binding; protein-tyrosine kinase activity; PTB domain binding; receptor signaling protein tyrosine kinase activity
Biological Process: activation of MAPK activity; activation of protein kinase activity; activation of protein kinase B; adrenal gland development; cellular response to insulin stimulus; epidermis development; exocrine pancreas development; G-protein coupled receptor protein signaling pathway; glucose homeostasis; heart morphogenesis; insulin receptor signaling pathway; male gonad development; male sex determination; negative regulation of protein amino acid phosphorylation; negative regulation of transporter activity; organ morphogenesis; peptidyl-tyrosine phosphorylation; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of developmental growth; positive regulation of DNA replication; positive regulation of glucose import; positive regulation of glycogen biosynthetic process; positive regulation of glycolysis; positive regulation of MAPKKK cascade; positive regulation of meiotic cell cycle; positive regulation of mitosis; positive regulation of nitric oxide biosynthetic process; positive regulation of phosphorylation; positive regulation of protein amino acid phosphorylation; positive regulation of protein kinase B signaling cascade; positive regulation of transcription, DNA-dependent; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein heterotetramerization; regulation of embryonic development; regulation of hydrogen peroxide metabolic process; regulation of transcription, DNA-dependent; transformation of host cell by virus
Reference #:  P15208 (UniProtKB)
Alt. Names/Synonyms: 4932439J01Rik; CD220; D630014A15Rik; Insr; Insulin receptor; Insulin receptor subunit alpha; Insulin receptor subunit beta; IR
Gene Symbols: Insr
Molecular weight: 155,610 Da
Basal Isoelectric point: 5.64  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
Select Structure to View Below

INSR

Protein Structure Not Found.
Download PyMol Script
Download ChimeraX Script

Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
cell cycle regulation: Y1175‑p, Y1179‑p
cell motility, altered: Y1175‑p, Y1179‑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



 LTP 

LTP: 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.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       mouse

 
0 1 T85 FPKLIMITDYLLLFR
0 1 Y87 KLIMITDYLLLFRVY
0 1 Y94 YLLLFRVYGLESLKD
0 1 S98 FRVYGLESLKDLFPN
0 5 T361 AQELRGCTVINGSLI
0 1 S366 GCTVINGSLIINIRG
0 2 S400 GFLKIRRSYALVSLS
0 3 Y401 FLKIRRSYALVSLSF
0 2 S407 SYALVSLSFFRKLHL
0 1 T419‑p LHLIRGEtLEIGNYs
0 1 S426‑p tLEIGNYsFYALDNQ
0 1 T447‑p DWSKHNLtITQGKLF
0 1 Y457‑p QGKLFFHyNPKLCLS
0 1 S464 yNPKLCLSEIHKMEE
0 1 S684 LKGLKLPSRTWSPPF
0 1 T717 ECCSCPKTDSQILKE
0 1 S719 CSCPKTDSQILKELE
0 1 T733 EESSFRKTFEDYLHN
0 1 Y808 GLRHFTGYRIELQAC
0 1 S919 SVRVRATSLAGNGSW
0 1 T930 NGSWTEPTYFYVTDY
3 0 Y982 DGPMGPLYASSNPEy
21 0 Y989‑p YASSNPEyLSASDVF
1 0 S991 SSNPEyLSASDVFPS
5 2 Y1001‑p DVFPSSVyVPDEWEV
0 1 K1012‑ub EWEVPREkITLLREL
5 0 S1023 LRELGQGSFGMVYEG
0 2 Y1028 QGSFGMVYEGNAKDI
0 13 K1037‑ub GNAKDIIkGEAETRV
0 19 K1047‑ub AETRVAVkTVNEsAs
3 1 S1052‑p AVkTVNEsAsLRERI
3 2 S1054‑p kTVNEsAsLRERIEF
1 1 Y1139 EIADGMAYLNAKKFV
34 465 Y1175‑p FGMTRDIyEtDyyRK
0 48 T1177‑p MTRDIyEtDyyRKGG
40 718 Y1179‑p RDIyEtDyyRKGGkG
38 116 Y1180‑p DIyEtDyyRKGGkGL
0 2 K1185‑ub DyyRKGGkGLLPVRW
1 0 S1206 KDGVFTASSDMWSFG
1 0 S1207 DGVFTASSDMWSFGV
1 0 S1211 TASSDMWSFGVVLWE
3 0 S1304 EENKAPESEELEMEF
2 0 S1322 ENVPLDRSSHCQREE
2 0 S1323 NVPLDRSSHCQREEA
0 2 S1337‑p AGGREGGssLsIKRt
3 3 S1338‑p GGREGGssLsIKRty
0 5 S1340‑p REGGssLsIKRtyDE
0 2 K1342 GGssLsIKRtyDEHI
0 1 K1342 GGssLsIKRtyDEHI
2 4 T1344‑p ssLsIKRtyDEHIPy
14 7 Y1345‑p sLsIKRtyDEHIPyt
14 18 Y1351‑p tyDEHIPytHMNGGK
0 6 T1352‑p yDEHIPytHMNGGKK
6 9 T1365‑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
  human

► Hide Isoforms
 
T85‑p FPKLIMItDyLLLFR
Y87‑p KLIMItDyLLLFRVy
Y94‑p yLLLFRVyGLEsLKD
S98‑p FRVyGLEsLKDLFPN
T361‑p AQELRGCtVINGsLI
S366‑p GCtVINGsLIINIRG
S400‑p GYLKIRRsyALVSLs
Y401‑p YLKIRRsyALVSLsF
S407‑p syALVSLsFFRKLRL
T419 LRLIRGETLEIGNYS
S426 TLEIGNYSFYALDNQ
T447‑p DWSKHNLtITQGKLF
Y457‑p QGKLFFHyNPKLCLs
S464‑p yNPKLCLsEIHKMEE
S682‑p LKGLKLPsRTWSPPF
T715‑p ECCSCPKtDsQILKE
S717‑p CSCPKtDsQILKELE
T731‑p EESSFRKtFEDYLHN
Y818‑p GLRHFTGyRIELQAC
S929‑p SVRIRATsLAGNGSW
T940‑p NGSWTEPtYFYVTDY
Y992‑p DGPLGPLyASSNPEy
Y999‑p yASSNPEyLSASDVF
S1001 SSNPEyLSASDVFPC
Y1011‑p DVFPCSVyVPDEWEV
K1022 EWEVSREKITLLREL
S1033‑p LRELGQGsFGMVyEG
Y1038‑p QGsFGMVyEGNARDI
K1047‑ub GNARDIIkGEAETRV
K1057‑ub AETRVAVkTVNEsAs
S1062‑p AVkTVNEsAsLRERI
S1064‑p kTVNEsAsLRERIEF
Y1149‑p EIADGMAyLNAKKFV
Y1185‑p FGMTRDIyEtDyyRK
T1187‑p MTRDIyEtDyyRKGG
Y1189‑p RDIyEtDyyRKGGkG
Y1190‑p DIyEtDyyRKGGkGL
K1195‑ub DyyRKGGkGLLPVRW
S1216‑p KDGVFTTssDMWsFG
S1217‑p DGVFTTssDMWsFGV
S1221‑p TTssDMWsFGVVLWE
S1314‑p EENKAPEsEELEMEF
S1332‑p ENVPLDRssHCQREE
S1333‑p NVPLDRssHCQREEA
S1347 AGGRDGGSsLGFkRs
S1348‑p GGRDGGSsLGFkRsy
G1350 RDGGSsLGFkRsyEE
K1352‑m1 GGSsLGFkRsyEEHI
K1352‑ub GGSsLGFkRsyEEHI
S1354‑p SsLGFkRsyEEHIPy
Y1355‑p sLGFkRsyEEHIPyt
Y1361‑p syEEHIPytHMNGGK
T1362‑p yEEHIPytHMNGGKK
T1375‑p KKNGRILtLPRSNPS
3026 : Phospho-Insulin Receptor beta (Tyr1345) (14A4) Rabbit mAb
3023 : Phospho-Insulin Receptor beta (Tyr1361) (84B2) Rabbit mAb
  INSR iso2  
T85 FPKLIMITDYLLLFR
Y87 KLIMITDYLLLFRVY
Y94 YLLLFRVYGLESLKD
S98 FRVYGLESLKDLFPN
T361 AQELRGCTVINGSLI
S366 GCTVINGSLIINIRG
S400 GYLKIRRSYALVSLS
Y401 YLKIRRSYALVSLSF
S407 SYALVSLSFFRKLRL
T419 LRLIRGETLEIGNYS
S426 TLEIGNYSFYALDNQ
T447 DWSKHNLTITQGKLF
Y457 QGKLFFHYNPKLCLS
S464 YNPKLCLSEIHKMEE
S682 LKGLKLPSRTWSPPF
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
Y1026 QGSFGMVYEGNARDI
K1035 GNARDIIKGEAETRV
K1045 AETRVAVKTVNESAS
S1050 AVKTVNESASLRERI
S1052 KTVNESASLRERIEF
Y1137 EIADGMAYLNAKKFV
Y1173‑p FGMTRDIyETDyyRK
T1175 MTRDIyETDyyRKGG
Y1177‑p RDIyETDyyRKGGKG
Y1178‑p DIyETDyyRKGGKGL
K1183 DyyRKGGKGLLPVRW
S1204 KDGVFTTSSDMWSFG
S1205 DGVFTTSSDMWSFGV
S1209 TTSSDMWSFGVVLWE
S1302‑p EENKAPEsEELEMEF
S1320 ENVPLDRSSHCQREE
S1321 NVPLDRSSHCQREEA
S1335 AGGRDGGSsLGFKRS
S1336‑p GGRDGGSsLGFKRSy
G1338 RDGGSsLGFKRSyEE
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)
  rat

 
T84 FPKLIMITDYLLLFR
Y86 KLIMITDYLLLFRVY
Y93 YLLLFRVYGLESLKD
S97 FRVYGLESLKDLFPN
T360 AQELRGCTVINGSLI
S365 GCTVINGSLIINIRG
S399 GFLKIRRSYALVSLS
Y400 FLKIRRSYALVSLSF
S406 SYALVSLSFFRKLHL
T418 LHLIRGETLEIGNYS
S425 TLEIGNYSFYALDNQ
T446 DWNKHNLTITQGKLF
Y456 QGKLFFHYNPKLCLS
S463 YNPKLCLSEIHKMEE
S683 LKGLKLPSRTWSPPF
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
Y1039 QGsFGMVYEGNAKDI
K1048 GNAKDIIKGEVETRV
K1058 VETRVAVKTVNESAS
S1063 AVKTVNESASLRERI
S1065 KTVNESASLRERIEF
Y1150 EIADGMAYLNAKKFV
Y1186‑p FGMTRDIyETDyyRK
T1188 MTRDIyETDyyRKGG
Y1190‑p RDIyETDyyRKGGKG
Y1191‑p DIyETDyyRKGGKGL
K1196 DyyRKGGKGLLPVRW
S1217 KDGVFTASSDMWSFG
S1218 DGVFTASSDMWSFGV
S1222 TASSDMWSFGVVLWE
S1315 EENKAPESEELEMEF
S1333 ENVPLDRSSHCQREE
S1334 NVPLDRSSHCQREEA
S1348 AGCREGGSSLsIKRT
S1349 GCREGGSSLsIKRTy
S1351‑p REGGSSLsIKRTyDE
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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