IGF1R_MOUSE
ID IGF1R_MOUSE Reviewed; 1373 AA.
AC Q60751; O70438; Q62123;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 3.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Insulin-like growth factor 1 receptor;
DE EC=2.7.10.1;
DE AltName: Full=Insulin-like growth factor I receptor;
DE Short=IGF-I receptor;
DE AltName: CD_antigen=CD221;
DE Contains:
DE RecName: Full=Insulin-like growth factor 1 receptor alpha chain;
DE Contains:
DE RecName: Full=Insulin-like growth factor 1 receptor beta chain;
DE Flags: Precursor;
GN Name=Igf1r;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Navarro M., Garandel V., Barenton B., Bernardi H.;
RT "Cloning of cDNA for the mouse insulin-like growth factor I receptor.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-329.
RC STRAIN=CD-1; TISSUE=Kidney;
RX PubMed=8234298; DOI=10.1073/pnas.90.21.10360;
RA Wada J., Liu Z.Z., Alvares K., Kumar A., Wallner E.I., Makino H.,
RA Kanwar Y.S.;
RT "Cloning of cDNA for the alpha subunit of mouse insulin-like growth factor
RT I receptor and the role of the receptor in metanephric development.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10360-10364(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1134-1203.
RX PubMed=2482828; DOI=10.1016/0378-1119(89)90465-4;
RA Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J.;
RT "The application of the polymerase chain reaction to cloning members of the
RT protein tyrosine kinase family.";
RL Gene 85:67-74(1989).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=8402901; DOI=10.1016/s0092-8674(05)80084-4;
RA Liu J.P., Baker J., Perkins A.S., Robertson E.J., Efstratiadis A.;
RT "Mice carrying null mutations of the genes encoding insulin-like growth
RT factor I (Igf-1) and type 1 IGF receptor (Igf1r).";
RL Cell 75:59-72(1993).
RN [5]
RP ACTIVITY REGULATION.
RX PubMed=11884589; DOI=10.1128/mcb.22.7.1998-2010.2002;
RA Buckley D.A., Cheng A., Kiely P.A., Tremblay M.L., O'Connor R.;
RT "Regulation of insulin-like growth factor type I (IGF-I) receptor kinase
RT activity by protein tyrosine phosphatase 1B (PTP-1B) and enhanced IGF-I-
RT mediated suppression of apoptosis and motility in PTP-1B-deficient
RT fibroblasts.";
RL Mol. Cell. Biol. 22:1998-2010(2002).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-748 AND ASN-901.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-641; ASN-757 AND ASN-765.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP PHOSPHORYLATION AT SER-1280 AND SER-1284.
RX PubMed=22685298; DOI=10.1074/jbc.m112.385757;
RA Kelly G.M., Buckley D.A., Kiely P.A., Adams D.R., O'Connor R.;
RT "Serine phosphorylation of the insulin-like growth factor I (IGF-1)
RT receptor C-terminal tail restrains kinase activity and cell growth.";
RL J. Biol. Chem. 287:28180-28194(2012).
RN [10]
RP INTERACTION WITH ZFAND2B.
RX PubMed=26692333; DOI=10.1038/nm.4013;
RA Osorio F.G., Soria-Valles C., Santiago-Fernandez O., Bernal T.,
RA Mittelbrunn M., Colado E., Rodriguez F., Bonzon-Kulichenko E., Vazquez J.,
RA Porta-de-la-Riva M., Ceron J., Fueyo A., Li J., Green A.R., Freije J.M.,
RA Lopez-Otin C.;
RT "Loss of the proteostasis factor AIRAPL causes myeloid transformation by
RT deregulating IGF-1 signaling.";
RL Nat. Med. 22:91-96(2016).
CC -!- FUNCTION: Receptor tyrosine kinase which mediates actions of insulin-
CC like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and
CC insulin (INS) with a lower affinity. The activated IGF1R is involved in
CC cell growth and survival control. IGF1R is crucial for tumor
CC transformation and survival of malignant cell. Ligand binding activates
CC the receptor kinase, leading to receptor autophosphorylation, and
CC tyrosines phosphorylation of multiple substrates, that function as
CC signaling adapter proteins including, the insulin-receptor substrates
CC (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins
CC lead to the activation of two main signaling pathways: the PI3K-AKT/PKB
CC pathway and the Ras-MAPK pathway. The result of activating the MAPK
CC pathway is increased cellular proliferation, whereas activating the
CC PI3K pathway inhibits apoptosis and stimulates protein synthesis.
CC Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K
CC (PIK3R1), leading to activation of several downstream substrates,
CC including protein AKT/PKB. AKT phosphorylation, in turn, enhances
CC protein synthesis through mTOR activation and triggers the
CC antiapoptotic effects of IGFIR through phosphorylation and inactivation
CC of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS
CC by phosphorylated IRS1 or Shc leads to recruitment of Ras and
CC activation of the ras-MAPK pathway. In addition to these two main
CC signaling pathways IGF1R signals also through the Janus kinase/signal
CC transducer and activator of transcription pathway (JAK/STAT).
CC Phosphorylation of JAK proteins can lead to phosphorylation/activation
CC of signal transducers and activators of transcription (STAT) proteins.
CC In particular activation of STAT3, may be essential for the
CC transforming activity of IGF1R. The JAK/STAT pathway activates gene
CC transcription and may be responsible for the transforming activity. JNK
CC kinases can also be activated by the IGF1R. IGF1 exerts inhibiting
CC activities on JNK activation via phosphorylation and inhibition of
CC MAP3K5/ASK1, which is able to directly associate with the IGF1R (By
CC similarity). When present in a hybrid receptor with INSR, binds IGF1
CC (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Activated by autophosphorylation at Tyr-1163, Tyr-
CC 1167 and Tyr-1168 on the kinase activation loop; phosphorylation at all
CC three tyrosine residues is required for optimal kinase activity.
CC Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone,
CC isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-
CC 1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde,
CC picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors
CC bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric
CC inhibitor and binds close to the DFG motif and the activation loop (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Tetramer of 2 alpha and 2 beta chains linked by disulfide
CC bonds. The alpha chains contribute to the formation of the ligand-
CC binding domain, while the beta chain carries the kinase domain.
CC Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in
CC vitro when autophosphorylated on tyrosine residues. Forms a hybrid
CC receptor with INSR, the hybrid is a tetramer consisting of 1 alpha
CC chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of
CC IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts
CC with RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-
CC 3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with
CC STAT3. Found in a ternary complex with IGF1 and ITGAV:ITGB3 or
CC ITGA6:ITGB4 (By similarity). Interacts (nascent precursor form) with
CC ZFAND2B (PubMed:26692333). {ECO:0000250|UniProtKB:P08069,
CC ECO:0000269|PubMed:26692333}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- PTM: Autophosphorylated on tyrosine residues in response to ligand
CC binding. Autophosphorylation occurs in trans, i.e. one subunit of the
CC dimeric receptor phosphorylates tyrosine residues on the other subunit.
CC Autophosphorylation occurs in a sequential manner; Tyr-1167 is
CC predominantly phosphorylated first, followed by phosphorylation of Tyr-
CC 1163 and Tyr-1168. While every single phosphorylation increases kinase
CC activity, all three tyrosine residues in the kinase activation loop
CC (Tyr-1163, Tyr-1167 and Tyr-1168) have to be phosphorylated for optimal
CC activity. Can be autophosphorylated at additional tyrosine residues (in
CC vitro). Autophosphorylated is followed by phosphorylation of
CC juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr-
CC 981 is required for IRS1- and SHC1-binding (By similarity).
CC Phosphorylation of Ser-1280 by GSK-3beta restrains kinase activity and
CC promotes cell surface expression, it requires a priming phosphorylation
CC at Ser-1284. Dephosphorylated by PTPN1. {ECO:0000250,
CC ECO:0000269|PubMed:22685298}.
CC -!- PTM: Polyubiquitinated at Lys-1170 and Lys-1173 through both 'Lys-48'
CC and 'Lys-29' linkages, promoting receptor endocytosis and subsequent
CC degradation by the proteasome. Ubiquitination is facilitated by pre-
CC existing phosphorylation (By similarity). {ECO:0000250}.
CC -!- PTM: Sumoylated with SUMO1. {ECO:0000250}.
CC -!- PTM: Controlled by regulated intramembrane proteolysis (RIP). Undergoes
CC metalloprotease-dependent constitutive ectodomain shedding to produce a
CC membrane-anchored 52 kDa C-Terminal fragment which is further processed
CC by presenilin gamma-secretase to yield an intracellular 50 kDa fragment
CC (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are 45% of the size of wild-type
CC littermates at birth, and die shortly due to severe organ hypoplasia.
CC {ECO:0000269|PubMed:8402901}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF056187; AAC12782.1; -; mRNA.
DR EMBL; U00182; AAC52123.1; -; mRNA.
DR EMBL; M33422; AAA40013.1; -; mRNA.
DR PIR; A48805; A48805.
DR PIR; JH0113; JH0113.
DR RefSeq; NP_034643.2; NM_010513.2.
DR PDB; 6PYH; EM; 4.30 A; A/D=31-1292.
DR PDBsum; 6PYH; -.
DR AlphaFoldDB; Q60751; -.
DR SMR; Q60751; -.
DR BioGRID; 200548; 7.
DR IntAct; Q60751; 2.
DR MINT; Q60751; -.
DR STRING; 10090.ENSMUSP00000005671; -.
DR BindingDB; Q60751; -.
DR ChEMBL; CHEMBL5381; -.
DR GlyConnect; 2392; 2 N-Linked glycans (2 sites).
DR GlyGen; Q60751; 16 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; Q60751; -.
DR PhosphoSitePlus; Q60751; -.
DR MaxQB; Q60751; -.
DR PaxDb; Q60751; -.
DR PeptideAtlas; Q60751; -.
DR PRIDE; Q60751; -.
DR ProteomicsDB; 267294; -.
DR DNASU; 16001; -.
DR GeneID; 16001; -.
DR KEGG; mmu:16001; -.
DR CTD; 3480; -.
DR MGI; MGI:96433; Igf1r.
DR eggNOG; KOG4258; Eukaryota.
DR InParanoid; Q60751; -.
DR OrthoDB; 223327at2759; -.
DR PhylomeDB; Q60751; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
DR Reactome; R-MMU-2428928; IRS-related events triggered by IGF1R.
DR Reactome; R-MMU-2428933; SHC-related events triggered by IGF1R.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR BioGRID-ORCS; 16001; 13 hits in 77 CRISPR screens.
DR ChiTaRS; Igf1r; mouse.
DR PRO; PR:Q60751; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q60751; protein.
DR GO; GO:0035867; C:alphav-beta3 integrin-IGF-1-IGF1R complex; ISO:MGI.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:1902911; C:protein kinase complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0030315; C:T-tubule; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0043559; F:insulin binding; ISO:MGI.
DR GO; GO:0005009; F:insulin receptor activity; IBA:GO_Central.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISS:UniProtKB.
DR GO; GO:0005520; F:insulin-like growth factor binding; IPI:MGI.
DR GO; GO:0031994; F:insulin-like growth factor I binding; ISO:MGI.
DR GO; GO:0005010; F:insulin-like growth factor receptor activity; ISS:UniProtKB.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB.
DR GO; GO:0140318; F:protein transporter activity; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005198; F:structural molecule activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0030325; P:adrenal gland development; IGI:CACAO.
DR GO; GO:0097242; P:amyloid-beta clearance; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; ISO:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:MGI.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:MGI.
DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; ISO:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:MGI.
DR GO; GO:0021549; P:cerebellum development; ISO:MGI.
DR GO; GO:0097062; P:dendritic spine maintenance; ISO:MGI.
DR GO; GO:0008544; P:epidermis development; IMP:MGI.
DR GO; GO:0030010; P:establishment of cell polarity; ISO:MGI.
DR GO; GO:0044849; P:estrous cycle; ISO:MGI.
DR GO; GO:0031017; P:exocrine pancreas development; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030238; P:male sex determination; IMP:MGI.
DR GO; GO:0030879; P:mammary gland development; IMP:MGI.
DR GO; GO:0000165; P:MAPK cascade; IMP:MGI.
DR GO; GO:0140014; P:mitotic nuclear division; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:1904193; P:negative regulation of cholangiocyte apoptotic process; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:MGI.
DR GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; ISO:MGI.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:MGI.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; ISO:MGI.
DR GO; GO:0048680; P:positive regulation of axon regeneration; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0032467; P:positive regulation of cytokinesis; ISO:MGI.
DR GO; GO:0048639; P:positive regulation of developmental growth; IMP:CACAO.
DR GO; GO:0051054; P:positive regulation of DNA metabolic process; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0051446; P:positive regulation of meiotic cell cycle; IGI:CACAO.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:MGI.
DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:MGI.
DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0090031; P:positive regulation of steroid hormone biosynthetic process; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IGI:CACAO.
DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; IMP:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0046328; P:regulation of JNK cascade; ISO:MGI.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:1902065; P:response to L-glutamate; ISO:MGI.
DR GO; GO:0045056; P:transcytosis; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00063; FN3; 3.
DR CDD; cd00064; FU; 1.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.80.20.20; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016246; Tyr_kinase_insulin-like_rcpt.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PIRSF; PIRSF000620; Insulin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00261; FU; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; SSF49265; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS50853; FN3; 4.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane;
KW Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..737
FT /note="Insulin-like growth factor 1 receptor alpha chain"
FT /id="PRO_0000016683"
FT CHAIN 742..1373
FT /note="Insulin-like growth factor 1 receptor beta chain"
FT /id="PRO_0000016684"
FT TOPO_DOM 742..936
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 937..960
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 961..1373
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 490..610
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 611..709
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 735..829
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 835..928
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1000..1276
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1283..1373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 978..981
FT /note="IRS1- and SHC1-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 1291..1305
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1137
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 1006..1014
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1034
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 981
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT MOD_RES 1163
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT MOD_RES 1167
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT MOD_RES 1168
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT MOD_RES 1280
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:22685298"
FT MOD_RES 1284
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22685298"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 608
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 641
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 748
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 757
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 901
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 914
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..52
FT /evidence="ECO:0000250"
FT DISULFID 150..178
FT /evidence="ECO:0000250"
FT DISULFID 182..205
FT /evidence="ECO:0000250"
FT DISULFID 192..211
FT /evidence="ECO:0000250"
FT DISULFID 215..224
FT /evidence="ECO:0000250"
FT DISULFID 219..230
FT /evidence="ECO:0000250"
FT DISULFID 231..239
FT /evidence="ECO:0000250"
FT DISULFID 235..248
FT /evidence="ECO:0000250"
FT DISULFID 251..260
FT /evidence="ECO:0000250"
FT DISULFID 264..276
FT /evidence="ECO:0000250"
FT DISULFID 282..303
FT /evidence="ECO:0000250"
FT DISULFID 307..321
FT /evidence="ECO:0000250"
FT DISULFID 324..328
FT /evidence="ECO:0000250"
FT DISULFID 332..354
FT /evidence="ECO:0000250"
FT DISULFID 456..489
FT /evidence="ECO:0000250"
FT CROSSLNK 1170
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT CROSSLNK 1173
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P08069"
FT CONFLICT 58..59
FT /note="FL -> LV (in Ref. 2; AAC52123)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="C -> S (in Ref. 2; AAC52123)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="D -> G (in Ref. 2; AAC52123)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="E -> V (in Ref. 2; AAC52123)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="C -> S (in Ref. 2; AAC52123)"
FT /evidence="ECO:0000305"
FT CONFLICT 1134
FT /note="V -> I (in Ref. 3; AAA40013)"
FT /evidence="ECO:0000305"
FT CONFLICT 1145
FT /note="V -> D (in Ref. 3; AAA40013)"
FT /evidence="ECO:0000305"
FT CONFLICT 1202
FT /note="V -> I (in Ref. 3; AAA40013)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1373 AA; 155788 MW; 5EE3B72EF101E379 CRC64;
MKSGSGGGSP TSLWGLVFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGFLH
ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVIF
EMTNLKDIGL YNLRNITRGA IRIEKNADLC YLSTIDWSLI LDAVSNNYIV GNKPPKECGD
LCPGTLEEKP MCEKTTINNE YNYRCWTTNR CQKMCPSVCG KRACTENNEC CHPECLGSCH
TPDDNTTCVA CRHYYYKGVC VPACPPGTYR FEGWRCVDRD FCANIPNAES SDSDGFVIHD
DECMQECPSG FIRNSTQSMY CIPCEGPCPK VCGDEEKKTK TIDSVTSAQM LQGCTILKGN
LLINIRRGNN IASELENFMG LIEVVTGYVK IRHSHALVSL SFLKNLRLIL GEEQLEGNYS
FYVLDNQNLQ QLWDWNHRNL TVRSGKMYFA FNPKLCVSEI YRMEEVTGTK GRQSKGDINT
RNNGERASCE SDVLRFTSTT TWKNRIIITW HRYRPPDYRD LISFTVYYKE APFKNVTEYD
GQDACGSNSW NMVDVDLPPN KEGEPGILLH GLKPWTQYAV YVKAVTLTMV ENDHIRGAKS
EILYIRTNAS VPSIPLDVLS ASNSSSQLIV KWNPPTLPNG NLSYYIVRWQ RQPQDGYLYR
HNYCSKDKIP IRKYADGTID VEEVTENPKT EVCGGDKGPC CACPKTEAEK QAEKEEAEYR
KVFENFLHNS IFVPRPERRR RDVMQVANTT MSSRSRNTTV ADTYNITDPE EFETEYPFFE
SRVDNKERTV ISNLRPFTLY RIDIHSCNHE AEKLGCSASN FVFARTMPAE GADDIPGPVT
WEPRPENSIF LKWPEPENPN GLILMYEIKY GSQVEDQREC VSRQEYRKYG GAKLNRLNPG
NYTARIQATS LSGNGSWTDP VFFYVPAKTT YENFMHLIIA LPVAILLIVG GLVIMLYVFH
RKRNNSRLGN GVLYASVNPE YFSAADVYVP DEWEVAREKI TMNRELGQGS FGMVYEGVAK
GVVKDEPETR VAIKTVNEAA SMRERIEFLN EASVMKEFNC HHVVRLLGVV SQGQPTLVIM
ELMTRGDLKS YLRSLRPEVE QNNLVLIPPS LSKMIQMAGE IADGMAYLNA NKFVHRDLAA
RNCMVAEDFT VKIGDFGMTR DIYETDYYRK GGKGLLPVRW MSPESLKDGV FTTHSDVWSF
GVVLWEIATL AEQPYQGLSN EQVLRFVMEG GLLDKPDNCP DMLFELMRMC WQYNPKMRPS
FLEIIGSIKD EMEPSFQEVS FYYSEENKPP EPEELEMELE MEPENMESVP LDPSASSASL
PLPERHSGHK AENGPGPGVL VLRASFDERQ PYAHMNGGRA NERALPLPQS STC
