Insulin-like growth factor 1 receptor
| Name | Insulin-like growth factor 1 receptor |
|---|---|
| Synonyms |
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| Gene Name | IGF1R |
| Organism | Human |
| 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
Processes
Components
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| 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 |
| GenBank Protein ID | 804990 |
| UniProtKB ID | P08069 |
| UniProtKB Entry Name | IGF1R_HUMAN |
| 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 |
| GenBank Gene ID | X04434 |
| GeneCard ID | Not Available |
| GenAtlas ID | IGF1R |
| HGNC ID | HGNC:5465 |
| Chromosome Location | 15 |
| Locus | 15q26.3 |
| References |
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