Insulin-like growth factor 1 receptor

Details

Name
Insulin-like growth factor 1 receptor
Synonyms
  • 2.7.10.1
  • IGF-I receptor
  • Insulin-like growth factor I receptor
Gene Name
IGF1R
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001710|Insulin-like growth factor 1 receptor
MKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLH
ILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIF
EMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGD
LCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCS
APDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHD
GECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNL
LINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSF
YVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTR
NNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDG
QDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSE
ILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRH
NYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRK
VFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFES
RVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTW
EPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGN
YTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHR
KRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKG
VVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIME
LMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARN
CMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGV
VLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFL
EIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRH
SGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC
Number of residues
1367
Molecular Weight
154791.73
Theoretical pI
5.54
GO Classification
Functions
ATP binding / identical protein binding / insulin binding / insulin receptor binding / insulin receptor substrate binding / insulin-like growth factor binding / insulin-like growth factor I binding / insulin-like growth factor-activated receptor activity / phosphatidylinositol 3-kinase binding / protein tyrosine kinase activity
Processes
axonogenesis / brain development / epidermis development / establishment of cell polarity / exocrine pancreas development / immune response / inactivation of MAPKK activity / insulin receptor signaling pathway / insulin-like growth factor receptor signaling pathway / male sex determination / mammary gland development / negative regulation of apoptotic process / negative regulation of muscle cell apoptotic process / negative regulation of protein kinase B signaling / negative regulation of sequence-specific DNA binding transcription factor activity / peptidyl-tyrosine autophosphorylation / phosphatidylinositol 3-kinase signaling / phosphatidylinositol-mediated signaling / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of cytokinesis / positive regulation of DNA replication / positive regulation of MAPK cascade / positive regulation of mitotic nuclear division / positive regulation of protein kinase B signaling / positive regulation of steroid hormone biosynthetic process / prostate gland epithelium morphogenesis / protein autophosphorylation / protein heterooligomerization / protein tetramerization / regulation of JNK cascade / response to vitamin E / signal transduction
Components
caveola / integral component of plasma membrane / intracellular membrane-bounded organelle / membrane / neuron projection / plasma membrane / receptor complex
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.When present in a hybrid receptor with INSR, 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
936-959
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020490|Insulin-like growth factor 1 receptor (IGF1R)
ATGAAGTCTGGCTCCGGAGGAGGGTCCCCGACCTCGCTGTGGGGGCTCCTGTTTCTCTCC
GCCGCGCTCTCGCTCTGGCCGACGAGTGGAGAAATCTGCGGGCCAGGCATCGACATCCGC
AACGACTATCAGCAGCTGAAGCGCCTGGAGAACTGCACGGTGATCGAGGGCTACCTCCAC
ATCCTGCTCATCTCCAAGGCCGAGGACTACCGCAGCTACCGCTTCCCCAAGCTCACGGTC
ATTACCGAGTACTTGCTGCTGTTCCGAGTGGCTGGCCTCGAGAGCCTCGGAGACCTCTTC
CCCAACCTCACGGTCATCCGCGGCTGGAAACTCTTCTACAACTACGCCCTGGTCATCTTC
GAGATGACCAATCTCAAGGATATTGGGCTTTACAACCTGAGGAACATTACTCGGGGGGCC
ATCAGGATTGAGAAAAATGCTGACCTCTGTTACCTCTCCACTGTGGACTGGTCCCTGATC
CTGGATGCGGTGTCCAATAACTACATTGTGGGGAATAAGCCCCCAAAGGAATGTGGGGAC
CTGTGTCCAGGGACCATGGAGGAGAAGCCGATGTGTGAGAAGACCACCATCAACAATGAG
TACAACTACCGCTGCTGGACCACAAACCGCTGCCAGAAAATGTGCCCAAGCACGTGTGGG
AAGCGGGCGTGCACCGAGAACAATGAGTGCTGCCACCCCGAGTGCCTGGGCAGCTGCAGC
GCGCCTGACAACGACACGGCCTGTGTAGCTTGCCGCCACTACTACTATGCCGGTGTCTGT
GTGCCTGCCTGCCCGCCCAACACCTACAGGTTTGAGGGCTGGCGCTGTGTGGACCGTGAC
TTCTGCGCCAACATCCTCAGCGCCGAGAGCAGCGACTCCGAGGGGTTTGTGATCCACGAC
GGCGAGTGCATGCAGGAGTGCCCCTCGGGCTTCATCCGCAACGGCAGCCAGAGCATGTAC
TGCATCCCTTGTGAAGGTCCTTGCCCGAAGGTCTGTGAGGAAGAAAAGAAAACAAAGACC
ATTGATTCTGTTACTTCTGCTCAGATGCTCCAAGGATGCACCATCTTCAAGGGCAATTTG
CTCATTAACATCCGACGGGGGAATAACATTGCTTCAGAGCTGGAGAACTTCATGGGGCTC
ATCGAGGTGGTGACGGGCTACGTGAAGATCCGCCATTCTCATGCCTTGGTCTCCTTGTCC
TTCCTAAAAAACCTTCGCCTCATCCTAGGAGAGGAGCAGCTAGAAGGGAATTACTCCTTC
TACGTCCTCGACAACCAGAACTTGCAGCAACTGTGGGACTGGGACCACCGCAACCTGACC
ATCAAAGCAGGGAAAATGTACTTTGCTTTCAATCCCAAATTATGTGTTTCCGAAATTTAC
CGCATGGAGGAAGTGACGGGGACTAAAGGGCGCCAAAGCAAAGGGGACATAAACACCAGG
AACAACGGGGAGAGAGCCTCCTGTGAAAGTGACGTCCTGCATTTCACCTCCACCACCACG
TCGAAGAATCGCATCATCATAACCTGGCACCGGTACCGGCCCCCTGACTACAGGGATCTC
ATCAGCTTCACCGTTTACTACAAGGAAGCACCCTTTAAGAATGTCACAGAGTATGATGGG
CAGGATGCCTGCGGCTCCAACAGCTGGAACATGGTGGACGTGGACCTCCCGCCCAACAAG
GACGTGGAGCCCGGCATCTTACTACATGGGCTGAAGCCCTGGACTCAGTACGCCGTTTAC
GTCAAGGCTGTGACCCTCACCATGGTGGAGAACGACCATATCCGTGGGGCCAAGAGTGAG
ATCTTGTACATTCGCACCAATGCTTCAGTTCCTTCCATTCCCTTGGACGTTCTTTCAGCA
TCGAACTCCTCTTCTCAGTTAATCGTGAAGTGGAACCCTCCCTCTCTGCCCAACGGCAAC
CTGAGTTACTACATTGTGCGCTGGCAGCGGCAGCCTCAGGACGGCTACCTTTACCGGCAC
AATTACTGCTCCAAAGACAAAATCCCCATCAGGAAGTATGCCGACGGCACCATCGACATT
GAGGAGGTCACAGAGAACCCCAAGACTGAGGTGTGTGGTGGGGAGAAAGGGCCTTGCTGC
GCCTGCCCCAAAACTGAAGCCGAGAAGCAGGCCGAGAAGGAGGAGGCTGAATACCGCAAA
GTCTTTGAGAATTTCCTGCACAACTCCATCTTCGTGCCCAGACCTGAAAGGAAGCGGAGA
GATGTCATGCAAGTGGCCAACACCACCATGTCCAGCCGAAGCAGGAACACCACGGCCGCA
GACACCTACAACATCACCGACCCGGAAGAGCTGGAGACAGAGTACCCTTTCTTTGAGAGC
AGAGTGGATAACAAGGAGAGAACTGTCATTTCTAACCTTCGGCCTTTCACATTGTACCGC
ATCGATATCCACAGCTGCAACCACGAGGCTGAGAAGCTGGGCTGCAGCGCCTCCAACTTC
GTCTTTGCAAGGACTATGCCCGCAGAAGGAGCAGATGACATTCCTGGGCCAGTGACCTGG
GAGCCAAGGCCTGAAAACTCCATCTTTTTAAAGTGGCCGGAACCTGAGAATCCCAATGGA
TTGATTCTAATGTATGAAATAAAATACGGATCACAAGTTGAGGATCAGCGAGAATGTGTG
TCCAGACAGGAATACAGGAAGTATGGAGGGGCCAAGCTAAACCGGCTAAACCCGGGGAAC
TACACAGCCCGGATTCAGGCCACATCTCTCTCTGGGAATGGGTCGTGGACAGATCCTGTG
TTCTTCTATGTCCAGGCCAAAACAGGATATGAAAACTTCATCCATCTGATCATCGCTCTG
CCCGTCGCTGTCCTGTTGATCGTGGGAGGGTTGGTGATTATGCTGTACGTCTTCCATAGA
AAGAGAAATAACAGCAGGCTGGGGAATGGAGTGCTGTATGCCTCTGTGAACCCGGAGTAC
TTCAGCGCTGCTGATGTGTACGTTCCTGATGAGTGGGAGGTGGCTCGGGAGAAGATCACC
ATGAGCCGGGAACTTGGGCAGGGGTCGTTTGGGATGGTCTATGAAGGAGTTGCCAAGGGT
GTGGTGAAAGATGAACCTGAAACCAGAGTGGCCATTAAAACAGTGAACGAGGCCGCAAGC
ATGCGTGAGAGGATTGAGTTTCTCAACGAAGCTTCTGTGATGAAGGAGTTCAATTGTCAC
CATGTGGTGCGATTGCTGGGTGTGGTGTCCCAAGGCCAGCCAACACTGGTCATCATGGAA
CTGATGACACGGGGCGATCTCAAAAGTTATCTCCGGTCTCTGAGGCCAGAAATGGAGAAT
AATCCAGTCCTAGCACCTCCAAGCCTGAGCAAGATGATTCAGATGGCCGGAGAGATTGCA
GACGGCATGGCATACCTCAACGCCAATAAGTTCGTCCACAGAGACCTTGCTGCCCGGAAT
TGCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATTTTGGTATGACGCGAGATATC
TATGAGACAGACTATTACCGGAAAGGAGGGAAAGGGCTGCTGCCCGTGCGCTGGATGTCT
CCTGAGTCCCTCAAGGATGGAGTCTTCACCACTTACTCGGACGTCTGGTCCTTCGGGGTC
GTCCTCTGGGAGATCGCCACACTGGCCGAGCAGCCCTACCAGGGCTTGTCCAACGAGCAA
GTCCTTCGCTTCGTCATGGAGGGCGGCCTTCTGGACAAGCCAGACAACTGTCCTGACATG
CTGTTTGAACTGATGCGCATGTGCTGGCAGTATAACCCCAAGATGAGGCCTTCCTTCCTG
GAGATCATCAGCAGCATCAAAGAGGAGATGGAGCCTGGCTTCCGGGAGGTCTCCTTCTAC
TACAGCGAGGAGAACAAGCTGCCCGAGCCGGAGGAGCTGGACCTGGAGCCAGAGAACATG
GAGAGCGTCCCCCTGGACCCCTCGGCCTCCTCGTCCTCCCTGCCACTGCCCGACAGACAC
TCAGGACACAAGGCCGAGAACGGCCCCGGCCCTGGGGTGCTGGTCCTCCGCGCCAGCTTC
GACGAGAGACAGCCTTACGCCCACATGAACGGGGGCCGCAAGAACGAGCGGGCCTTGCCG
CTGCCCCAGTCTTCGACCTGCTGA
Chromosome Location
15
Locus
15q26.3
External Identifiers
ResourceLink
UniProtKB IDP08069
UniProtKB Entry NameIGF1R_HUMAN
GenBank Protein ID804990
GenBank Gene IDX04434
GenAtlas IDIGF1R
HGNC IDHGNC:5465
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01277Mecaserminapproved, investigationalyesagonistDetails
DB04395Phosphoaminophosphonic Acid-Adenylate EsterexperimentalunknownDetails
DB00030Insulin Humanapproved, investigationalunknownDetails
DB00071Insulin PorkapprovedunknownDetails
DB05023ATL1101investigationalunknownDetails
DB05184XL228investigationalunknownDetails
DB12250CixutumumabinvestigationalunknownDetails
DB05897rhIGFBP-3investigationalunknownDetails
DB06075LinsitinibinvestigationalunknownDetails
DB06343TeprotumumabinvestigationalunknownDetails
DB07156(4Z)-6-bromo-4-({[4-(pyrrolidin-1-ylmethyl)phenyl]amino}methylidene)isoquinoline-1,3(2H,4H)-dioneexperimentalunknownDetails
DB074743-[5-(1H-IMIDAZOL-1-YL)-7-METHYL-1H-BENZIMIDAZOL-2-YL]-4-[(PYRIDIN-2-YLMETHYL)AMINO]PYRIDIN-2(1H)-ONEexperimentalunknownDetails
DB12267Brigatinibapproved, investigationalunknowninhibitorDetails
DB09098Somatremapproved, investigational, withdrawnyesDetails
DB00046Insulin LisproapprovedunknownDetails
DB01307Insulin DetemirapprovedunknownDetails
DB00047Insulin glargineapprovedunknownDetails
DB01306Insulin AspartapprovedunknownDetails
DB01309Insulin GlulisineapprovedunknownDetails
DB09564Insulin DegludecapprovedunknownDetails
DB14751Mecasermin rinfabateapprovedyesagonistDetails