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P08069

- IGF1R_HUMAN

UniProt

P08069 - IGF1R_HUMAN

Protein

Insulin-like growth factor 1 receptor

Gene

IGF1R

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 175 (01 Oct 2014)
      Sequence version 1 (01 Aug 1988)
      Previous versions | rss
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    Functioni

    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.

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.10 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

    Activated by autophosphorylation at Tyr-1165, Tyr-1161 and Tyr-1166 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop.11 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei1033 – 10331ATP
    Active sitei1135 – 11351Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1005 – 10139ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. identical protein binding Source: IntAct
    3. insulin binding Source: BHF-UCL
    4. insulin-like growth factor-activated receptor activity Source: UniProtKB
    5. insulin-like growth factor binding Source: UniProtKB
    6. insulin-like growth factor I binding Source: BHF-UCL
    7. insulin receptor binding Source: BHF-UCL
    8. insulin receptor substrate binding Source: UniProtKB
    9. phosphatidylinositol 3-kinase binding Source: UniProtKB
    10. protein binding Source: UniProtKB
    11. protein tyrosine kinase activity Source: UniProtKB

    GO - Biological processi

    1. axonogenesis Source: Ensembl
    2. brain development Source: Ensembl
    3. establishment of cell polarity Source: Ensembl
    4. exocrine pancreas development Source: Ensembl
    5. immune response Source: BHF-UCL
    6. inactivation of MAPKK activity Source: UniProtKB
    7. insulin-like growth factor receptor signaling pathway Source: UniProtKB
    8. insulin receptor signaling pathway Source: ProtInc
    9. male sex determination Source: Ensembl
    10. mammary gland development Source: Ensembl
    11. negative regulation of apoptotic process Source: UniProtKB
    12. negative regulation of muscle cell apoptotic process Source: Ensembl
    13. negative regulation of protein kinase B signaling Source: Ensembl
    14. peptidyl-tyrosine autophosphorylation Source: MGI
    15. phosphatidylinositol 3-kinase signaling Source: BHF-UCL
    16. phosphatidylinositol-mediated signaling Source: BHF-UCL
    17. positive regulation of cell migration Source: BHF-UCL
    18. positive regulation of cell proliferation Source: ProtInc
    19. positive regulation of cytokinesis Source: Ensembl
    20. positive regulation of DNA replication Source: BHF-UCL
    21. positive regulation of MAPK cascade Source: Ensembl
    22. positive regulation of protein kinase B signaling Source: Ensembl
    23. positive regulation of steroid hormone biosynthetic process Source: Ensembl
    24. prostate gland epithelium morphogenesis Source: Ensembl
    25. protein autophosphorylation Source: UniProtKB
    26. protein heterooligomerization Source: Ensembl
    27. protein tetramerization Source: UniProtKB
    28. regulation of JNK cascade Source: UniProtKB
    29. response to vitamin E Source: Ensembl
    30. signal transduction Source: ProtInc

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    ReactomeiREACT_150139. SHC-related events triggered by IGF1R.
    REACT_150203. IRS-related events triggered by IGF1R.
    REACT_150359. Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
    SignaLinkiP08069.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Insulin-like growth factor 1 receptor (EC:2.7.10.1)
    Alternative name(s):
    Insulin-like growth factor I receptor
    Short name:
    IGF-I receptor
    CD_antigen: CD221
    Cleaved into the following 2 chains:
    Gene namesi
    Name:IGF1R
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:5465. IGF1R.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication

    GO - Cellular componenti

    1. caveola Source: Ensembl
    2. integral component of plasma membrane Source: UniProtKB
    3. intracellular membrane-bounded organelle Source: BHF-UCL
    4. membrane Source: BHF-UCL
    5. neuron projection Source: Ensembl
    6. plasma membrane Source: Reactome
    7. receptor complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Insulin-like growth factor 1 resistance (IGF1RES) [MIM:270450]: A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti138 – 1381R → Q in IGF1RES; has decreased IGF1R function. 1 Publication
    VAR_034891
    Natural varianti145 – 1451K → N in IGF1RES; has decreased IGF1R function. 1 Publication
    VAR_034892
    Natural varianti739 – 7391R → Q in IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. 1 Publication
    VAR_034895

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi980 – 9801Y → F: Reduces tyrosine phosphorylation. Abolishes interaction with IRS1 and SHC1. Does not abolish interaction with PIK3R1, nor with GRB10. 2 Publications
    Mutagenesisi1033 – 10331K → A: Kinase inactive. Abolishes tyrosine phosphorylation and abolishes interaction with IRS1, SHC1 and PIK3R1. 1 Publication
    Mutagenesisi1280 – 12801Y → F: No effect on GRB10-binding. 1 Publication
    Mutagenesisi1281 – 12811Y → F: No effect on GRB10-binding. 1 Publication
    Mutagenesisi1346 – 13461Y → F: Loss of GRB10-binding. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi270450. phenotype.
    Orphaneti73273. Growth delay due to insulin-like growth factor I resistance.
    PharmGKBiPA29698.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 30302 PublicationsAdd
    BLAST
    Chaini31 – 736706Insulin-like growth factor 1 receptor alpha chainPRO_0000016681Add
    BLAST
    Chaini741 – 1367627Insulin-like growth factor 1 receptor beta chainPRO_0000016682Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi33 ↔ 521 Publication
    Glycosylationi51 – 511N-linked (GlcNAc...)1 Publication
    Glycosylationi102 – 1021N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi135 – 1351N-linked (GlcNAc...)1 Publication
    Disulfide bondi150 ↔ 1781 Publication
    Disulfide bondi182 ↔ 2051 Publication
    Disulfide bondi192 ↔ 2111 Publication
    Disulfide bondi215 ↔ 2241 Publication
    Disulfide bondi219 ↔ 2301 Publication
    Disulfide bondi231 ↔ 2391 Publication
    Disulfide bondi235 ↔ 2481 Publication
    Glycosylationi244 – 2441N-linked (GlcNAc...)1 Publication
    Disulfide bondi251 ↔ 2601 Publication
    Disulfide bondi264 ↔ 2761 Publication
    Disulfide bondi282 ↔ 3031 Publication
    Disulfide bondi307 ↔ 3211 Publication
    Glycosylationi314 – 3141N-linked (GlcNAc...)1 Publication
    Disulfide bondi324 ↔ 3281 Publication
    Disulfide bondi332 ↔ 3531 Publication
    Glycosylationi417 – 4171N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi438 – 4381N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi455 ↔ 4881 Publication
    Glycosylationi534 – 5341N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi607 – 6071N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi622 – 6221N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi640 – 6401N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi747 – 7471N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi756 – 7561N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi764 – 7641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi900 – 9001N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi913 – 9131N-linked (GlcNAc...)Sequence Analysis
    Modified residuei980 – 9801Phosphotyrosine1 Publication
    Modified residuei1161 – 11611Phosphotyrosine; by autocatalysis3 Publications
    Modified residuei1165 – 11651Phosphotyrosine; by autocatalysis3 Publications
    Modified residuei1166 – 11661Phosphotyrosine; by autocatalysis3 Publications
    Cross-linki1168 – 1168Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Cross-linki1171 – 1171Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Modified residuei1278 – 12781Phosphoserine; by GSK3-betaBy similarity
    Modified residuei1282 – 12821PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner; Tyr-1165 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1161 and Tyr-1166. While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal activity. Can be autophosphorylated at additional tyrosine residues (in vitro). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding. Phosphorylation of Ser-1278 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1282. Dephosphorylated by PTPN1 By similarity.By similarity
    Polyubiquitinated at Lys-1168 and Lys-1171 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation.6 Publications
    Sumoylated with SUMO1.1 Publication
    Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment.1 Publication

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP08069.
    PaxDbiP08069.
    PeptideAtlasiP08069.
    PRIDEiP08069.

    PTM databases

    PhosphoSiteiP08069.

    Expressioni

    Tissue specificityi

    Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney.4 Publications

    Gene expression databases

    ArrayExpressiP08069.
    BgeeiP08069.
    CleanExiHS_IGF1R.
    GenevestigatoriP08069.

    Organism-specific databases

    HPAiCAB010268.

    Interactioni

    Subunit structurei

    Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Forms a hybrid receptor with INSR, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with GNB2L1/RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with STAT3.22 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-475981,EBI-475981
    ARHGEF12Q9NZN57EBI-475981,EBI-821440
    CAMPP499133EBI-475981,EBI-6378485
    CrkQ640103EBI-475981,EBI-2906540From a different organism.
    CSKP412405EBI-475981,EBI-1380630
    CTNNB1P352223EBI-475981,EBI-491549
    IGF1P050195EBI-475981,EBI-7902275
    INSP013174EBI-475981,EBI-3989070From a different organism.
    LEF1Q9UJU25EBI-475981,EBI-926131
    MDM2Q009872EBI-475981,EBI-389668
    PIK3R1P279864EBI-475981,EBI-79464
    PTPN1P180313EBI-475981,EBI-968788
    PTPN11Q061243EBI-475981,EBI-297779
    SHC1P29353-22EBI-475981,EBI-1000553
    TAGLNQ019952EBI-475981,EBI-1054248

    Protein-protein interaction databases

    BioGridi109701. 50 interactions.
    DIPiDIP-476N.
    IntActiP08069. 42 interactions.
    MINTiMINT-85902.
    STRINGi9606.ENSP00000268035.

    Structurei

    Secondary structure

    1
    1367
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi37 – 415
    Helixi43 – 497
    Beta strandi53 – 575
    Beta strandi59 – 657
    Beta strandi68 – 703
    Beta strandi80 – 834
    Beta strandi85 – 928
    Helixi96 – 983
    Beta strandi115 – 1217
    Beta strandi138 – 1447
    Helixi157 – 1604
    Helixi164 – 1663
    Beta strandi168 – 1714
    Helixi175 – 1784
    Turni183 – 1886
    Beta strandi194 – 1996
    Beta strandi201 – 2033
    Beta strandi205 – 2095
    Helixi217 – 2193
    Beta strandi235 – 2417
    Beta strandi247 – 2559
    Beta strandi257 – 2637
    Beta strandi269 – 2713
    Turni272 – 2743
    Beta strandi275 – 2773
    Helixi279 – 2835
    Beta strandi297 – 2993
    Beta strandi302 – 3065
    Beta strandi311 – 3155
    Beta strandi321 – 3233
    Beta strandi325 – 3273
    Beta strandi331 – 34111
    Helixi345 – 3473
    Turni349 – 3524
    Beta strandi354 – 3629
    Helixi375 – 3784
    Beta strandi383 – 3864
    Beta strandi388 – 3925
    Turni415 – 4173
    Beta strandi418 – 4236
    Turni434 – 4363
    Beta strandi440 – 4434
    Beta strandi445 – 4517
    Helixi456 – 46611
    Beta strandi474 – 4774
    Turni479 – 4813
    Beta strandi980 – 9823
    Helixi983 – 9853
    Turni990 – 9923
    Helixi996 – 9983
    Beta strandi999 – 10079
    Beta strandi1009 – 102214
    Beta strandi1025 – 103410
    Beta strandi1037 – 10393
    Helixi1041 – 105313
    Helixi1054 – 10563
    Beta strandi1065 – 10695
    Beta strandi1071 – 10744
    Beta strandi1076 – 10805
    Helixi1087 – 110014
    Helixi1109 – 112820
    Helixi1138 – 11403
    Beta strandi1141 – 11433
    Beta strandi1149 – 11513
    Helixi1155 – 11573
    Helixi1159 – 11646
    Helixi1168 – 11703
    Beta strandi1171 – 11744
    Helixi1176 – 11783
    Helixi1181 – 11866
    Helixi1191 – 120717
    Turni1212 – 12154
    Helixi1218 – 12269
    Helixi1239 – 124810
    Helixi1253 – 12553
    Helixi1259 – 12668
    Helixi1267 – 12693
    Helixi1274 – 12774
    Turni1279 – 12813
    Turni1283 – 12853

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IGRX-ray2.60A31-492[»]
    1JQHX-ray2.10A/B/C979-1286[»]
    1K3AX-ray2.10A988-1286[»]
    1M7NX-ray2.70A/B974-1294[»]
    1P4OX-ray1.50A/B974-1294[»]
    2OJ9X-ray2.00A982-1286[»]
    2ZM3X-ray2.50A/B/C/D981-1286[»]
    3D94X-ray2.30A986-1286[»]
    3F5PX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L/M/R/S/T981-1286[»]
    3I81X-ray2.08A982-1286[»]
    3LVPX-ray3.00A/B/C/D951-1286[»]
    3LW0X-ray1.79A/B/C/D983-1286[»]
    3NW5X-ray2.14A982-1286[»]
    3NW6X-ray2.20A982-1286[»]
    3NW7X-ray2.11A982-1286[»]
    3O23X-ray2.10A982-1286[»]
    3QQUX-ray2.90A/B/C/D988-1286[»]
    ProteinModelPortaliP08069.
    SMRiP08069. Positions 30-924, 957-1317.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP08069.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini741 – 935195ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini960 – 1367408CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei936 – 95924HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini491 – 609119Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini610 – 70899Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini735 – 82894Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini834 – 92794Fibronectin type-III 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini999 – 1274276Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi977 – 9804IRS1- and SHC1-binding

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
    Contains 4 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000038045.
    HOVERGENiHBG006134.
    InParanoidiP08069.
    KOiK05087.
    OMAiNRCQKMC.
    OrthoDBiEOG73RB9N.
    PhylomeDBiP08069.
    TreeFamiTF351636.

    Family and domain databases

    Gene3Di2.60.40.10. 4 hits.
    3.80.20.20. 2 hits.
    InterProiIPR000494. EGF_rcpt_L.
    IPR003961. Fibronectin_type3.
    IPR006211. Furin-like_Cys-rich_dom.
    IPR006212. Furin_repeat.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016246. Tyr_kinase_insulin-like_rcpt.
    IPR002011. Tyr_kinase_rcpt_2_CS.
    [Graphical view]
    PfamiPF00041. fn3. 1 hit.
    PF00757. Furin-like. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF01030. Recep_L_domain. 2 hits.
    [Graphical view]
    PIRSFiPIRSF000620. Insulin_receptor. 1 hit.
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00060. FN3. 3 hits.
    SM00261. FU. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 4 hits.
    SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 1 hit.
    PROSITEiPS50853. FN3. 4 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P08069-1 [UniParc]FASTAAdd to Basket

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    MKSGSGGGSP TSLWGLLFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE     50
    NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF 100
    PNLTVIRGWK LFYNYALVIF EMTNLKDIGL YNLRNITRGA IRIEKNADLC 150
    YLSTVDWSLI LDAVSNNYIV GNKPPKECGD LCPGTMEEKP MCEKTTINNE 200
    YNYRCWTTNR CQKMCPSTCG KRACTENNEC CHPECLGSCS APDNDTACVA 250
    CRHYYYAGVC VPACPPNTYR FEGWRCVDRD FCANILSAES SDSEGFVIHD 300
    GECMQECPSG FIRNGSQSMY CIPCEGPCPK VCEEEKKTKT IDSVTSAQML 350
    QGCTIFKGNL LINIRRGNNI ASELENFMGL IEVVTGYVKI RHSHALVSLS 400
    FLKNLRLILG EEQLEGNYSF YVLDNQNLQQ LWDWDHRNLT IKAGKMYFAF 450
    NPKLCVSEIY RMEEVTGTKG RQSKGDINTR NNGERASCES DVLHFTSTTT 500
    SKNRIIITWH RYRPPDYRDL ISFTVYYKEA PFKNVTEYDG QDACGSNSWN 550
    MVDVDLPPNK DVEPGILLHG LKPWTQYAVY VKAVTLTMVE NDHIRGAKSE 600
    ILYIRTNASV PSIPLDVLSA SNSSSQLIVK WNPPSLPNGN LSYYIVRWQR 650
    QPQDGYLYRH NYCSKDKIPI RKYADGTIDI EEVTENPKTE VCGGEKGPCC 700
    ACPKTEAEKQ AEKEEAEYRK VFENFLHNSI FVPRPERKRR DVMQVANTTM 750
    SSRSRNTTAA DTYNITDPEE LETEYPFFES RVDNKERTVI SNLRPFTLYR 800
    IDIHSCNHEA EKLGCSASNF VFARTMPAEG ADDIPGPVTW EPRPENSIFL 850
    KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN 900
    YTARIQATSL SGNGSWTDPV FFYVQAKTGY ENFIHLIIAL PVAVLLIVGG 950
    LVIMLYVFHR KRNNSRLGNG VLYASVNPEY FSAADVYVPD EWEVAREKIT 1000
    MSRELGQGSF GMVYEGVAKG VVKDEPETRV AIKTVNEAAS MRERIEFLNE 1050
    ASVMKEFNCH HVVRLLGVVS QGQPTLVIME LMTRGDLKSY LRSLRPEMEN 1100
    NPVLAPPSLS KMIQMAGEIA DGMAYLNANK FVHRDLAARN CMVAEDFTVK 1150
    IGDFGMTRDI YETDYYRKGG KGLLPVRWMS PESLKDGVFT TYSDVWSFGV 1200
    VLWEIATLAE QPYQGLSNEQ VLRFVMEGGL LDKPDNCPDM LFELMRMCWQ 1250
    YNPKMRPSFL EIISSIKEEM EPGFREVSFY YSEENKLPEP EELDLEPENM 1300
    ESVPLDPSAS SSSLPLPDRH SGHKAENGPG PGVLVLRASF DERQPYAHMN 1350
    GGRKNERALP LPQSSTC 1367
    Length:1,367
    Mass (Da):154,793
    Last modified:August 1, 1988 - v1
    Checksum:iAE8A735F87F745C8
    GO

    Sequence cautioni

    The sequence BAG11657.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti928 – 9292TG → R in BAG11657. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti105 – 1051V → L in a renal chromophobe sample; somatic mutation. 1 Publication
    VAR_041424
    Natural varianti138 – 1381R → Q in IGF1RES; has decreased IGF1R function. 1 Publication
    VAR_034891
    Natural varianti145 – 1451K → N in IGF1RES; has decreased IGF1R function. 1 Publication
    VAR_034892
    Natural varianti388 – 3881V → M.1 Publication
    Corresponds to variant rs45445894 [ dbSNP | Ensembl ].
    VAR_018855
    Natural varianti437 – 4371R → H.1 Publication
    Corresponds to variant rs34516635 [ dbSNP | Ensembl ].
    VAR_034893
    Natural varianti511 – 5111R → Q.
    Corresponds to variant rs33958176 [ dbSNP | Ensembl ].
    VAR_034894
    Natural varianti595 – 5951R → H.1 Publication
    Corresponds to variant rs56248469 [ dbSNP | Ensembl ].
    VAR_041425
    Natural varianti605 – 6051R → H.1 Publication
    Corresponds to variant rs45553041 [ dbSNP | Ensembl ].
    VAR_018856
    Natural varianti739 – 7391R → Q in IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R. 1 Publication
    VAR_034895
    Natural varianti808 – 8081H → R.
    Corresponds to variant rs34061581 [ dbSNP | Ensembl ].
    VAR_034896
    Natural varianti828 – 8281A → T.
    Corresponds to variant rs35224135 [ dbSNP | Ensembl ].
    VAR_034897
    Natural varianti857 – 8571N → S.1 Publication
    Corresponds to variant rs45611935 [ dbSNP | Ensembl ].
    VAR_041426
    Natural varianti1338 – 13381A → T.1 Publication
    Corresponds to variant rs34102392 [ dbSNP | Ensembl ].
    VAR_041427
    Natural varianti1347 – 13471A → V in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041428

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X04434 mRNA. Translation: CAA28030.1.
    AB425196 mRNA. Translation: BAG11657.1. Different initiation.
    AY332722 Genomic DNA. Translation: AAP81165.1.
    AC055807 Genomic DNA. No translation available.
    AC069029 Genomic DNA. No translation available.
    AC118658 Genomic DNA. No translation available.
    AC118660 Genomic DNA. No translation available.
    BC113610 mRNA. Translation: AAI13611.1.
    BC113612 mRNA. Translation: AAI13613.1.
    M69229 Genomic DNA. Translation: AAB59399.1.
    CCDSiCCDS10378.1.
    PIRiA25690. IGHUR1.
    RefSeqiNP_000866.1. NM_000875.4.
    NP_001278787.1. NM_001291858.1.
    UniGeneiHs.643120.
    Hs.714012.

    Genome annotation databases

    EnsembliENST00000268035; ENSP00000268035; ENSG00000140443.
    GeneIDi3480.
    KEGGihsa:3480.
    UCSCiuc002bul.3. human.

    Polymorphism databases

    DMDMi124240.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs
    Wikipedia

    IGF-1 receptor entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X04434 mRNA. Translation: CAA28030.1 .
    AB425196 mRNA. Translation: BAG11657.1 . Different initiation.
    AY332722 Genomic DNA. Translation: AAP81165.1 .
    AC055807 Genomic DNA. No translation available.
    AC069029 Genomic DNA. No translation available.
    AC118658 Genomic DNA. No translation available.
    AC118660 Genomic DNA. No translation available.
    BC113610 mRNA. Translation: AAI13611.1 .
    BC113612 mRNA. Translation: AAI13613.1 .
    M69229 Genomic DNA. Translation: AAB59399.1 .
    CCDSi CCDS10378.1.
    PIRi A25690. IGHUR1.
    RefSeqi NP_000866.1. NM_000875.4.
    NP_001278787.1. NM_001291858.1.
    UniGenei Hs.643120.
    Hs.714012.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IGR X-ray 2.60 A 31-492 [» ]
    1JQH X-ray 2.10 A/B/C 979-1286 [» ]
    1K3A X-ray 2.10 A 988-1286 [» ]
    1M7N X-ray 2.70 A/B 974-1294 [» ]
    1P4O X-ray 1.50 A/B 974-1294 [» ]
    2OJ9 X-ray 2.00 A 982-1286 [» ]
    2ZM3 X-ray 2.50 A/B/C/D 981-1286 [» ]
    3D94 X-ray 2.30 A 986-1286 [» ]
    3F5P X-ray 2.90 A/B/C/D/E/F/G/H/I/J/K/L/M/R/S/T 981-1286 [» ]
    3I81 X-ray 2.08 A 982-1286 [» ]
    3LVP X-ray 3.00 A/B/C/D 951-1286 [» ]
    3LW0 X-ray 1.79 A/B/C/D 983-1286 [» ]
    3NW5 X-ray 2.14 A 982-1286 [» ]
    3NW6 X-ray 2.20 A 982-1286 [» ]
    3NW7 X-ray 2.11 A 982-1286 [» ]
    3O23 X-ray 2.10 A 982-1286 [» ]
    3QQU X-ray 2.90 A/B/C/D 988-1286 [» ]
    ProteinModelPortali P08069.
    SMRi P08069. Positions 30-924, 957-1317.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109701. 50 interactions.
    DIPi DIP-476N.
    IntActi P08069. 42 interactions.
    MINTi MINT-85902.
    STRINGi 9606.ENSP00000268035.

    Chemistry

    BindingDBi P08069.
    ChEMBLi CHEMBL1957.
    DrugBanki DB00047. Insulin Glargine recombinant.
    DB00046. Insulin Lyspro recombinant.
    DB00030. Insulin recombinant.
    DB00071. Insulin, porcine.
    DB01277. Mecasermin.
    GuidetoPHARMACOLOGYi 1801.

    PTM databases

    PhosphoSitei P08069.

    Polymorphism databases

    DMDMi 124240.

    Proteomic databases

    MaxQBi P08069.
    PaxDbi P08069.
    PeptideAtlasi P08069.
    PRIDEi P08069.

    Protocols and materials databases

    DNASUi 3480.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000268035 ; ENSP00000268035 ; ENSG00000140443 .
    GeneIDi 3480.
    KEGGi hsa:3480.
    UCSCi uc002bul.3. human.

    Organism-specific databases

    CTDi 3480.
    GeneCardsi GC15P099192.
    HGNCi HGNC:5465. IGF1R.
    HPAi CAB010268.
    MIMi 147370. gene.
    270450. phenotype.
    neXtProti NX_P08069.
    Orphaneti 73273. Growth delay due to insulin-like growth factor I resistance.
    PharmGKBi PA29698.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000038045.
    HOVERGENi HBG006134.
    InParanoidi P08069.
    KOi K05087.
    OMAi NRCQKMC.
    OrthoDBi EOG73RB9N.
    PhylomeDBi P08069.
    TreeFami TF351636.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    Reactomei REACT_150139. SHC-related events triggered by IGF1R.
    REACT_150203. IRS-related events triggered by IGF1R.
    REACT_150359. Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
    SignaLinki P08069.

    Miscellaneous databases

    ChiTaRSi IGF1R. human.
    EvolutionaryTracei P08069.
    GeneWikii Insulin-like_growth_factor_1_receptor.
    GenomeRNAii 3480.
    NextBioi 13682.
    PROi P08069.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P08069.
    Bgeei P08069.
    CleanExi HS_IGF1R.
    Genevestigatori P08069.

    Family and domain databases

    Gene3Di 2.60.40.10. 4 hits.
    3.80.20.20. 2 hits.
    InterProi IPR000494. EGF_rcpt_L.
    IPR003961. Fibronectin_type3.
    IPR006211. Furin-like_Cys-rich_dom.
    IPR006212. Furin_repeat.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016246. Tyr_kinase_insulin-like_rcpt.
    IPR002011. Tyr_kinase_rcpt_2_CS.
    [Graphical view ]
    Pfami PF00041. fn3. 1 hit.
    PF00757. Furin-like. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF01030. Recep_L_domain. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF000620. Insulin_receptor. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00060. FN3. 3 hits.
    SM00261. FU. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 4 hits.
    SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 1 hit.
    PROSITEi PS50853. FN3. 4 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity."
      Ullrich A., Gray A., Tam A.W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Bon T.L., Kathuria S., Chen E., Jacobs S., Francke U., Ramachandran J., Fujita-Yamaguchi Y.
      EMBO J. 5:2503-2512(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-56; 446-453; 503-524; 561-579; 668-672 AND 721-729.
      Tissue: Placenta.
    2. "Insulin-like growth factor I receptor gene structure."
      Abbot A.M., Bueno R., Pedrini M.T., Murray J.M., Smith R.J.
      J. Biol. Chem. 267:10759-10763(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. Nagase T., Kikuno R.F., Yamakawa H., Ohara O.
      Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Fetal brain.
    4. NIEHS SNPs program
      Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-388 AND HIS-605.
    5. "Analysis of the DNA sequence and duplication history of human chromosome 15."
      Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
      , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
      Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    7. "Analysis of the human type I insulin-like growth factor receptor promoter region."
      Cooke D.W., Bankert L.A., Roberts C.T. Jr., Leroith D., Casella S.J.
      Biochem. Biophys. Res. Commun. 177:1113-1120(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31.
    8. "Characterization of human placental insulin-like growth factor-I/insulin hybrid receptors by protein microsequencing and purification."
      Kasuya J., Paz I.B., Maddux B.A., Goldfine I.D., Hefta S.A., Fujita-Yamaguchi Y.
      Biochemistry 32:13531-13536(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 31-45 AND 741-750, FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
      Tissue: Placenta.
    9. "A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes."
      Lee S.-T., Strunk K.M., Spritz R.A.
      Oncogene 8:3403-3410(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1137-1193, TISSUE SPECIFICITY.
      Tissue: Melanocyte.
    10. "Interaction of the alpha beta dimers of the insulin-like growth factor I receptor is required for receptor autophosphorylation."
      Tollefsen S.E., Stoszek R.M., Thompson K.
      Biochemistry 30:48-54(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, AUTOPHOSPHORYLATION.
    11. "Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity."
      Soos M.A., Field C.E., Siddle K.
      Biochem. J. 290:419-426(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
    12. "Role of tyrosine kinase activity in signal transduction by the insulin-like growth factor-I (IGF-I) receptor. Characterization of kinase-deficient IGF-I receptors and the action of an IGF-I-mimetic antibody (alpha IR-3)."
      Kato H., Faria T.N., Stannard B., Roberts C.T. Jr., LeRoith D.
      J. Biol. Chem. 268:2655-2661(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION.
    13. "Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor."
      Craparo A., O'Neill T.J., Gustafson T.A.
      J. Biol. Chem. 270:15639-15643(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS1; SHC1 AND PIK3R1, MUTAGENESIS OF TYR-980 AND LYS-1033, PHOSPHORYLATION AT TYR-980.
    14. "Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting."
      Bailyes E.M., Nave B.T., Soos M.A., Orr S.R., Hayward A.C., Siddle K.
      Biochem. J. 327:209-215(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FORMATION OF A HYBRID RECEPTOR WITH INSR, TISSUE SPECIFICITY.
    15. "14-3-3 proteins interact with the insulin-like growth factor receptor but not the insulin receptor."
      Furlanetto R.W., Dey B.R., Lopaczynski W., Nissley S.P.
      Biochem. J. 327:765-771(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH 14-3-3 PROTEINS.
    16. "Distribution of insulin/insulin-like growth factor-I hybrid receptors in human tissues."
      Federici M., Porzio O., Zucaro L., Fusco A., Borboni P., Lauro D., Sesti G.
      Mol. Cell. Endocrinol. 129:121-126(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FORMATION OF A HYBRID RECEPTOR WITH INSR, TISSUE SPECIFICITY.
    17. "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor."
      Dey B.R., Spence S.L., Nissley P., Furlanetto R.W.
      J. Biol. Chem. 273:24095-24101(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SOCS1 AND SOCS2.
    18. "beta-arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor."
      Lin F.-T., Daaka Y., Lefkowitz R.J.
      J. Biol. Chem. 273:31640-31643(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB1 AND ARRB2.
    19. "The IGF-I receptor in cancer research."
      Baserga R.
      Exp. Cell Res. 253:1-6(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CANCER.
    20. "Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis."
      Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A., Swamy O.R., Leone M.E., Riedel H.
      Mol. Cell. Biol. 19:6217-6228(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GRB10, MUTAGENESIS OF TYR-980; TYR-1280; TYR-1281 AND TYR-1346.
    21. "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor."
      Dey B.R., Furlanetto R.W., Nissley P.
      Biochem. Biophys. Res. Commun. 278:38-43(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SOCS3.
    22. "Autophosphorylation of the insulin-like growth factor I receptor cytoplasmic domain."
      Lopaczynski W., Terry C., Nissley P.
      Biochem. Biophys. Res. Commun. 279:955-960(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: AUTOPHOSPHORYLATION.
    23. "Mechanism of STAT3 activation by insulin-like growth factor I receptor."
      Zong C.S., Chan J., Levy D.E., Horvath C., Sadowski H.B., Wang L.H.
      J. Biol. Chem. 275:15099-15105(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ACTIVATION OF STAT3.
    24. "Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease."
      Hellawell G.O., Turner G.D., Davies D.R., Poulsom R., Brewster S.F., Macaulay V.M.
      Cancer Res. 62:2942-2950(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    25. "Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved."
      Pandini G., Frasca F., Mineo R., Sciacca L., Vigneri R., Belfiore A.
      J. Biol. Chem. 277:39684-39695(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
    26. "RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix."
      Hermanto U., Zong C.S., Li W., Wang L.H.
      Mol. Cell. Biol. 22:2345-2365(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GNB2L1.
    27. "Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits apoptosis signal-regulating kinase 1 (ASK1)."
      Galvan V., Logvinova A., Sperandio S., Ichijo H., Bredesen D.E.
      J. Biol. Chem. 278:13325-13332(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MAP3K5.
    28. "Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor."
      Girnita L., Girnita A., Larsson O.
      Proc. Natl. Acad. Sci. U.S.A. 100:8247-8252(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION BY MDM2, INTERACTION WITH MDM2.
    29. "Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth."
      Girnita A., Girnita L., del Prete F., Bartolazzi A., Larsson O., Axelson M.
      Cancer Res. 64:236-242(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    30. "{beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase."
      Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A., Lefkowitz R.J., Larsson O.
      J. Biol. Chem. 280:24412-24419(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB1 AND ARRB2.
    31. "JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like growth factor and negatively regulated by suppressor of cytokine signaling-3."
      Yadav A., Kalita A., Dhillon S., Banerjee K.
      J. Biol. Chem. 280:31830-31840(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH STAT3.
    32. "Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant."
      Slaaby R., Schaeffer L., Lautrup-Larsen I., Andersen A.S., Shaw A.C., Mathiasen I.S., Brandt J.
      J. Biol. Chem. 281:25869-25874(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR.
    33. "The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma-secretase-mediated intramembrane proteolysis."
      McElroy B., Powell J.C., McCarthy J.V.
      Biochem. Biophys. Res. Commun. 358:1136-1141(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
    34. "The insulin-like growth factor 1 receptor in cancer: old focus, new future."
      Hartog H., Wesseling J., Boezen H.M., van der Graaf W.T.
      Eur. J. Cancer 43:1895-1904(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON IGF1R IN CANCER.
    35. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    36. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    37. "Development and validation of a method for profiling post-translational modification activities using protein microarrays."
      Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., Spruck C.
      PLoS ONE 5:E11332-E11332(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION.
    38. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    39. "Polyubiquitination of insulin-like growth factor I receptor (IGF-IR) activation loop promotes antibody-induced receptor internalization and down-regulation."
      Mao Y., Shang Y., Pham V.C., Ernst J.A., Lill J.R., Scales S.J., Zha J.
      J. Biol. Chem. 286:41852-41861(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT LYS-1168 AND LYS-1171.
    40. "Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor."
      Garrett T.P., McKern N.M., Lou M., Frenkel M.J., Bentley J.D., Lovrecz G.O., Elleman T.C., Cosgrove L.J., Ward C.W.
      Nature 394:395-399(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 31-492, DISULFIDE BONDS, GLYCOSYLATION AT ASN-51; ASN-135; ASN-244 AND ASN-314.
    41. "Structure and autoregulation of the insulin-like growth factor 1 receptor kinase."
      Favelyukis S., Till J.H., Hubbard S.R., Miller W.T.
      Nat. Struct. Biol. 8:1058-1063(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 988-1286 IN COMPLEX WITH AMP-PCP AND PEPTIDE SUBSTRATE, CATALYTIC ACTIVITY, ACTIVE SITE, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166.
    42. "Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation."
      Pautsch A., Zoephel A., Ahorn H., Spevak W., Hauptmann R., Nar H.
      Structure 9:955-965(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 981-1286 IN COMPLEX WITH ANP, AUTOPHOSPHORYLATION, ACTIVE SITE, IDENTIFICATION BY MASS SPECTROMETRY.
    43. "Crystal structure of the Apo, unactivated insulin-like growth factor-1 receptor kinase. Implication for inhibitor specificity."
      Munshi S., Kornienko M., Hall D.L., Reid J.C., Waxman L., Stirdivant S.M., Darke P.L., Kuo L.C.
      J. Biol. Chem. 277:38797-38802(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 974-1294.
    44. "Structure of apo, unactivated insulin-like growth factor-1 receptor kinase at 1.5 A resolution."
      Munshi S., Hall D.L., Kornienko M., Darke P.L., Kuo L.C.
      Acta Crystallogr. D 59:1725-1730(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 974-1294.
    45. "Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)."
      Velaparthi U., Wittman M., Liu P., Stoffan K., Zimmermann K., Sang X., Carboni J., Li A., Attar R., Gottardis M., Greer A., Chang C.Y., Jacobsen B.L., Sack J.S., Sun Y., Langley D.R., Balasubramanian B., Vyas D.
      Bioorg. Med. Chem. Lett. 17:2317-2321(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 982-1286 IN COMPLEX WITH BENZIMIDAZOLE PYRIDINONE INHIBITOR, CATALYTIC ACTIVITY, ENZYME REGULATION.
    46. "Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment."
      Mayer S.C., Banker A.L., Boschelli F., Di L., Johnson M., Kenny C.H., Krishnamurthy G., Kutterer K., Moy F., Petusky S., Ravi M., Tkach D., Tsou H.R., Xu W.
      Bioorg. Med. Chem. Lett. 18:3641-3645(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 981-1286, PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166.
    47. "Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor."
      Wu J., Li W., Craddock B.P., Foreman K.W., Mulvihill M.J., Ji Q.S., Miller W.T., Hubbard S.R.
      EMBO J. 27:1985-1994(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 986-1286 IN COMPLEX WITH INHIBITOR PQIP, SUBUNIT, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, ACTIVE SITE, ENZYME REGULATION.
    48. "Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment."
      Miller L.M., Mayer S.C., Berger D.M., Boschelli D.H., Boschelli F., Di L., Du X., Dutia M., Floyd M.B., Johnson M., Kenny C.H., Krishnamurthy G., Moy F., Petusky S., Tkach D., Torres N., Wu B., Xu W.
      Bioorg. Med. Chem. Lett. 19:62-66(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 981-1286 IN COMPLEX WITH 3-CYANOQUINOLINE INHIBITOR, CATALYTIC ACTIVITY, ENZYME REGULATION, PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166.
    49. Cited for: X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 982-1286 IN COMPLEX WITH BMS-754807, CATALYTIC ACTIVITY, ENZYME REGULATION.
    50. Cited for: X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 983-1286 IN COMPLEX WITH MSC1609119A-1, CATALYTIC ACTIVITY, ENZYME REGULATION.
    51. "Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase."
      Sampognaro A.J., Wittman M.D., Carboni J.M., Chang C., Greer A.F., Hurlburt W.W., Sack J.S., Vyas D.M.
      Bioorg. Med. Chem. Lett. 20:5027-5030(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 982-1286 IN COMPLEXES WITH INHIBITORS, CATALYTIC ACTIVITY, ENZYME REGULATION.
    52. Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 951-1286 IN COMPLEX WITH BIS-AZAINDOLE INHIBITOR, AUTOPHOSPHORYLATION, ENZYME REGULATION.
    53. "Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: advantages in comparison with competitive inhibitors."
      Lesuisse D., Mauger J., Nemecek C., Maignan S., Boiziau J., Harlow G., Hittinger A., Ruf S., Strobel H., Nair A., Ritter K., Malleron J.L., Dagallier A., El-Ahmad Y., Guilloteau J.P., Guizani H., Bouchard H., Venot C.
      Bioorg. Med. Chem. Lett. 21:2224-2228(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 982-1286 IN COMPLEX WITH HYDANTOIN DERIVATIVE, CATALYTIC ACTIVITY, ENZYME REGULATION.
    54. Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 988-1286 IN COMPLEX WITH 2,4-BIS-ARYLAMINO-1,3-PYRIMIDINE INHIBITOR, CATALYTIC ACTIVITY, ENZYME REGULATION.
    55. Cited for: VARIANTS IGF1RES GLN-138 AND ASN-145, CHARACTERIZATION OF VARIANTS IGF1RES GLN-138 AND ASN-145.
    56. "Mutation at cleavage site of insulin-like growth factor receptor in a short-stature child born with intrauterine growth retardation."
      Kawashima Y., Kanzaki S., Yang F., Kinoshita T., Hanaki K., Nagaishi J., Ohtsuka Y., Hisatome I., Ninomoya H., Nanba E., Fukushima T., Takahashi S.
      J. Clin. Endocrinol. Metab. 90:4679-4687(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT IGF1RES GLN-739, CHARACTERIZATION OF VARIANT IGF1RES GLN-739.
    57. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-105; HIS-437; HIS-595; SER-857; THR-1338 AND VAL-1347.

    Entry informationi

    Entry nameiIGF1R_HUMAN
    AccessioniPrimary (citable) accession number: P08069
    Secondary accession number(s): B1B5Y2, Q14CV2, Q9UCC0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: August 1, 1988
    Last modified: October 1, 2014
    This is version 175 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3