Insulin receptor

Details

Name
Insulin receptor
Synonyms
  • 2.7.10.1
  • IR
Gene Name
INSR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036940|Insulin receptor
MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHL
QILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYAL
VIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNE
ECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECL
GNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQG
CHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGC
TVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETL
EIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQE
RNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQ
NVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFS
DERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWE
RQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQIL
KELEESSFRKTFEDYLHNVVFVPRKTSSGTGAEDPRPSRKRRSLGDVGNVTVAVPTVAAF
PNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYV
SARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCV
SRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIG
PLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSR
EKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKG
FTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMA
AEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPV
RWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDN
CPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEME
FEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSN
PS
Number of residues
1382
Molecular Weight
156331.465
Theoretical pI
6.18
GO Classification
Functions
ATP binding / GTP binding / insulin binding / insulin receptor substrate binding / insulin-activated receptor activity / insulin-like growth factor I binding / insulin-like growth factor II binding / insulin-like growth factor receptor binding / phosphatidylinositol 3-kinase binding / protein tyrosine kinase activity / PTB domain binding / receptor signaling protein tyrosine kinase activity
Processes
activation of MAPK activity / activation of protein kinase activity / activation of protein kinase B activity / adrenal gland development / carbohydrate metabolic process / cellular response to growth factor stimulus / cellular response to insulin stimulus / epidermis development / exocrine pancreas development / G-protein coupled receptor signaling pathway / glucose homeostasis / heart morphogenesis / insulin receptor signaling pathway / male gonad development / male sex determination / peptidyl-tyrosine autophosphorylation / 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 glycolytic process / positive regulation of MAPK cascade / positive regulation of meiotic cell cycle / positive regulation of mitotic nuclear division / positive regulation of nitric oxide biosynthetic process / positive regulation of protein kinase B signaling / positive regulation of protein phosphorylation / positive regulation of respiratory burst / positive regulation of transcription, DNA-templated / protein autophosphorylation / protein heterotetramerization / regulation of embryonic development / regulation of female gonad development / regulation of transcription, DNA-templated / signal transduction by protein phosphorylation / transformation of host cell by virus
Components
caveola / endosome membrane / extracellular exosome / insulin receptor complex / integral component of plasma membrane / intracellular membrane-bounded organelle / membrane / plasma membrane / receptor complex
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which 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/PKB 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. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
Pfam Domain Function
Transmembrane Regions
957-979
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020443|Insulin receptor (INSR)
ATGGCCACCGGGGGCCGGCGGGGGGCGGCGGCCGCGCCGCTGCTGGTGGCGGTGGCCGCG
CTGCTACTGGGCGCCGCGGGCCACCTGTACCCCGGAGAGGTGTGTCCCGGCATGGATATC
CGGAACAACCTCACTAGGTTGCATGAGCTGGAGAATTGCTCTGTCATCGAAGGACACTTG
CAGATACTCTTGATGTTCAAAACGAGGCCCGAAGATTTCCGAGACCTCAGTTTCCCCAAA
CTCATCATGATCACTGATTACTTGCTGCTCTTCCGGGTCTATGGGCTCGAGAGCCTGAAG
GACCTGTTCCCCAACCTCACGGTCATCCGGGGATCACGACTGTTCTTTAACTACGCGCTG
GTCATCTTCGAGATGGTTCACCTCAAGGAACTCGGCCTCTACAACCTGATGAACATCACC
CGGGGTTCTGTCCGCATCGAGAAGAACAATGAGCTCTGTTACTTGGCCACTATCGACTGG
TCCCGTATCCTGGATTCCGTGGAGGATAATTACATCGTGTTGAACAAAGATGACAACGAG
GAGTGTGGAGACATCTGTCCGGGTACCGCGAAGGGCAAGACCAACTGCCCCGCCACCGTC
ATCAACGGGCAGTTTGTCGAACGATGTTGGACTCATAGTCACTGCCAGAAAGTTTGCCCG
ACCATCTGTAAGTCACACGGCTGCACCGCCGAAGGCCTCTGTTGCCACAGCGAGTGCCTG
GGCAACTGTTCTCAGCCCGACGACCCCACCAAGTGCGTGGCCTGCCGCAACTTCTACCTG
GACGGCAGGTGTGTGGAGACCTGCCCGCCCCCGTACTACCACTTCCAGGACTGGCGCTGT
GTGAACTTCAGCTTCTGCCAGGACCTGCACCACAAATGCAAGAACTCGCGGAGGCAGGGC
TGCCACCAGTACGTCATTCACAACAACAAGTGCATCCCTGAGTGTCCCTCCGGGTACACG
ATGAATTCCAGCAACTTGCTGTGCACCCCATGCCTGGGTCCCTGTCCCAAGGTGTGCCAC
CTCCTAGAAGGCGAGAAGACCATCGACTCGGTGACGTCTGCCCAGGAGCTCCGAGGATGC
ACCGTCATCAACGGGAGTCTGATCATCAACATTCGAGGAGGCAACAATCTGGCAGCTGAG
CTAGAAGCCAACCTCGGCCTCATTGAAGAAATTTCAGGGTATCTAAAAATCCGCCGATCC
TACGCTCTGGTGTCACTTTCCTTCTTCCGGAAGTTACGTCTGATTCGAGGAGAGACCTTG
GAAATTGGGAACTACTCCTTCTATGCCTTGGACAACCAGAACCTAAGGCAGCTCTGGGAC
TGGAGCAAACACAACCTCACCATCACTCAGGGGAAACTCTTCTTCCACTATAACCCCAAA
CTCTGCTTGTCAGAAATCCACAAGATGGAAGAAGTTTCAGGAACCAAGGGGCGCCAGGAG
AGAAACGACATTGCCCTGAAGACCAATGGGGACCAGGCATCCTGTGAAAATGAGTTACTT
AAATTTTCTTACATTCGGACATCTTTTGACAAGATCTTGCTGAGATGGGAGCCGTACTGG
CCCCCCGACTTCCGAGACCTCTTGGGGTTCATGCTGTTCTACAAAGAGGCCCCTTATCAG
AATGTGACGGAGTTCGACGGGCAGGATGCGTGTGGTTCCAACAGTTGGACGGTGGTAGAC
ATTGACCCACCCCTGAGGTCCAACGACCCCAAATCACAGAACCACCCAGGGTGGCTGATG
CGGGGTCTCAAGCCCTGGACCCAGTATGCCATCTTTGTGAAGACCCTGGTCACCTTTTCG
GATGAACGCCGGACCTATGGGGCCAAGAGTGACATCATTTATGTCCAGACAGATGCCACC
AACCCCTCTGTGCCCCTGGATCCAATCTCAGTGTCTAACTCATCATCCCAGATTATTCTG
AAGTGGAAACCACCCTCCGACCCCAATGGCAACATCACCCACTACCTGGTTTTCTGGGAG
AGGCAGGCGGAAGACAGTGAGCTGTTCGAGCTGGATTATTGCCTCAAAGGGCTGAAGCTG
CCCTCGAGGACCTGGTCTCCACCATTCGAGTCTGAAGATTCTCAGAAGCACAACCAGAGT
GAGTATGAGGATTCGGCCGGCGAATGCTGCTCCTGTCCAAAGACAGACTCTCAGATCCTG
AAGGAGCTGGAGGAGTCCTCGTTTAGGAAGACGTTTGAGGATTACCTGCACAACGTGGTT
TTCGTCCCCAGAAAAACCTCTTCAGGCACTGGTGCCGAGGACCCTAGGCCATCTCGGAAA
CGCAGGTCCCTTGGCGATGTTGGGAATGTGACGGTGGCCGTGCCCACGGTGGCAGCTTTC
CCCAACACTTCCTCGACCAGCGTGCCCACGAGTCCGGAGGAGCACAGGCCTTTTGAGAAG
GTGGTGAACAAGGAGTCGCTGGTCATCTCCGGCTTGCGACACTTCACGGGCTATCGCATC
GAGCTGCAGGCTTGCAACCAGGACACCCCTGAGGAACGGTGCAGTGTGGCAGCCTACGTC
AGTGCGAGGACCATGCCTGAAGCCAAGGCTGATGACATTGTTGGCCCTGTGACGCATGAA
ATCTTTGAGAACAACGTCGTCCACTTGATGTGGCAGGAGCCGAAGGAGCCCAATGGTCTG
ATCGTGCTGTATGAAGTGAGTTATCGGCGATATGGTGATGAGGAGCTGCATCTCTGCGTC
TCCCGCAAGCACTTCGCTCTGGAACGGGGCTGCAGGCTGCGTGGGCTGTCACCGGGGAAC
TACAGCGTGCGAATCCGGGCCACCTCCCTTGCGGGCAACGGCTCTTGGACGGAACCCACC
TATTTCTACGTGACAGACTATTTAGACGTCCCGTCAAATATTGCAAAAATTATCATCGGC
CCCCTCATCTTTGTCTTTCTCTTCAGTGTTGTGATTGGAAGTATTTATCTATTCCTGAGA
AAGAGGCAGCCAGATGGGCCGCTGGGACCGCTTTACGCTTCTTCAAACCCTGAGTATCTC
AGTGCCAGTGATGTGTTTCCATGCTCTGTGTACGTGCCGGACGAGTGGGAGGTGTCTCGA
GAGAAGATCACCCTCCTTCGAGAGCTGGGGCAGGGCTCCTTCGGCATGGTGTATGAGGGC
AATGCCAGGGACATCATCAAGGGTGAGGCAGAGACCCGCGTGGCGGTGAAGACGGTCAAC
GAGTCAGCCAGTCTCCGAGAGCGGATTGAGTTCCTCAATGAGGCCTCGGTCATGAAGGGC
TTCACCTGCCATCACGTGGTGCGCCTCCTGGGAGTGGTGTCCAAGGGCCAGCCCACGCTG
GTGGTGATGGAGCTGATGGCTCACGGAGACCTGAAGAGCTACCTCCGTTCTCTGCGGCCA
GAGGCTGAGAATAATCCTGGCCGCCCTCCCCCTACCCTTCAAGAGATGATTCAGATGGCG
GCAGAGATTGCTGACGGGATGGCCTACCTGAACGCCAAGAAGTTTGTGCATCGGGACCTG
GCAGCGAGAAACTGCATGGTCGCCCATGATTTTACTGTCAAAATTGGAGACTTTGGAATG
ACCAGAGACATCTATGAAACGGATTACTACCGGAAAGGGGGCAAGGGTCTGCTCCCTGTA
CGGTGGATGGCACCGGAGTCCCTGAAGGATGGGGTCTTCACCACTTCTTCTGACATGTGG
TCCTTTGGCGTGGTCCTTTGGGAAATCACCAGCTTGGCAGAACAGCCTTACCAAGGCCTG
TCTAATGAACAGGTGTTGAAATTTGTCATGGATGGAGGGTATCTGGATCAACCCGACAAC
TGTCCAGAGAGAGTCACTGACCTCATGCGCATGTGCTGGCAATTCAACCCCAAGATGAGG
CCAACCTTCCTGGAGATTGTCAACCTGCTCAAGGACGACCTGCACCCCAGCTTTCCAGAG
GTGTCGTTCTTCCACAGCGAGGAGAACAAGGCTCCCGAGAGTGAGGAGCTGGAGATGGAG
TTTGAGGACATGGAGAATGTGCCCCTGGACCGTTCCTCGCACTGTCAGAGGGAGGAGGCG
GGGGGCCGGGATGGAGGGTCCTCGCTGGGTTTCAAGCGGAGCTACGAGGAACACATCCCT
TACACACACATGAACGGAGGCAAGAAAAACGGGCGGATTCTGACCTTGCCTCGGTCCAAT
CCTTCCTAA
Chromosome Location
19
Locus
19p13.3-p13.2
External Identifiers
ResourceLink
UniProtKB IDP06213
UniProtKB Entry NameINSR_HUMAN
GenBank Protein ID307070
GenBank Gene IDM10051
GenAtlas IDINSR
HGNC IDHGNC:6091
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00030Insulin Humanapproved, investigationalyesagonistDetails
DB00047Insulin glargineapprovedyesagonistDetails
DB00071Insulin PorkapprovedyesbinderDetails
DB03909Adenosine-5'-[Beta, Gamma-Methylene]TriphosphateexperimentalunknownDetails
DB05120AT1391investigationalunknownDetails
DB05115NN344investigationalunknownDetails
DB01307Insulin DetemirapprovedyesagonistDetails
DB00046Insulin LisproapprovedyesagonistDetails
DB01306Insulin AspartapprovedyesagonistDetails
DB01309Insulin GlulisineapprovedyesagonistDetails
DB01277Mecaserminapproved, investigationalunknownDetails
DB08513[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACIDexperimentalunknownDetails
DB09564Insulin DegludecapprovedyesligandDetails
DB09129Chromic chlorideapprovedyesactivatorDetails
DB12267Brigatinibapproved, investigationalnobindingDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB14751Mecasermin rinfabateapprovedunknownDetails