ID IGF1R_RAT Reviewed; 1370 AA. AC P24062; DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 02-SEP-2026, entry version 216. 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 Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=7758167; DOI=10.1161/01.res.76.6.963; RA Du J., Delafontaine P.; RT "Inhibition of vascular smooth muscle cell growth through antisense RT transcription of a rat insulin-like growth factor I receptor cDNA."; RL Circ. Res. 76:963-972(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-364. RC STRAIN=Sprague-Dawley; RX PubMed=2477843; DOI=10.1073/pnas.86.19.7451; RA Werner H., Woloschak M., Adamo M., Shen-Orr Z., Roberts C.T. Jr., RA Leroith D.; RT "Developmental regulation of the rat insulin-like growth factor I receptor RT gene."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7451-7455(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 913-1017. RX PubMed=1530648; DOI=10.1016/0006-291x(92)91287-z; RA Kurachi H., Jobo K., Ohta M., Kawasaki T., Itoh N.; RT "A new member of the insulin receptor family, insulin receptor-related RT receptor, is expressed preferentially in the kidney."; RL Biochem. Biophys. Res. Commun. 187:934-939(1992). RN [4] RP FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH INSR. RX PubMed=16803852; DOI=10.1152/ajpendo.00565.2005; RA Johansson G.S., Arnqvist H.J.; RT "Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid RT insulin/IGF-I receptors in vascular smooth muscle cells."; RL Am. J. Physiol. 291:E1124-E1130(2006). 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, ECO:0000269|PubMed:16803852}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- ACTIVITY REGULATION: Activated by autophosphorylation at Tyr-1162, Tyr- CC 1166 and Tyr-1167 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). Dephosphorylated by PTPN1 (By 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 (By similarity). Interacts with SOCS1, SOCS2 and SOCS3 (By CC similarity). Interacts with 14-3-3 proteins (By similarity). Interacts CC with NMD2 (By similarity). Interacts with MAP3K5 (By similarity). CC Interacts with STAT3. Found in a ternary complex with IGF1 and CC ITGAV:ITGB3 or ITGA6:ITGB4 (By similarity). Interacts (nascent CC precursor form) with ZFAND2B (By similarity). CC {ECO:0000250|UniProtKB:P08069}. 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 (By similarity). Autophosphorylation occurs in trans, i.e. one CC subunit of the dimeric receptor phosphorylates tyrosine residues on the CC other subunit (By similarity). Autophosphorylation occurs in a CC sequential manner; Tyr-1166 is predominantly phosphorylated first, CC followed by phosphorylation of Tyr-1162 and Tyr-1167 (By similarity). CC While every single phosphorylation increases kinase activity, all three CC tyrosine residues in the kinase activation loop (Tyr-1162, Tyr-1166 and CC Tyr-1167) have to be phosphorylated for optimal activity (By CC similarity). Can be autophosphorylated at additional tyrosine residues CC (in vitro) (By similarity). Autophosphorylated is followed by CC phosphorylation of juxtamembrane tyrosines and C-terminal serines (By CC similarity). May also be phosphorylated at Tyr-1162 and Tyr-1167 by CC mTORC2 (By similarity). Phosphorylation of Tyr-981 is required for CC IRS1- and SHC1-binding (By similarity). Phosphorylation of Ser-1279 by CC GSK-3beta restrains kinase activity and promotes cell surface CC expression, it requires a priming phosphorylation at Ser-1283 (By CC similarity). Dephosphorylated by PTPN1 (By similarity). CC {ECO:0000250|UniProtKB:P08069, ECO:0000250|UniProtKB:Q60751}. CC -!- PTM: Polyubiquitinated at Lys-1169 and Lys-1172 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 -!- 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; L29232; AAA41392.1; -; mRNA. DR EMBL; M27293; AAA41384.1; -; mRNA. DR RefSeq; NP_434694.1; NM_052807.3. DR AlphaFoldDB; P24062; -. DR SMR; P24062; -. DR BioGRID; 247747; 2. DR FunCoup; P24062; 1305. DR STRING; 10116.ENSRNOP00000019267; -. DR BindingDB; P24062; -. DR ChEMBL; CHEMBL1075098; -. DR GlyCosmos; P24062; 16 sites, No reported glycans. DR GlyGen; P24062; 17 sites, 1 O-linked glycan (1 site). DR iPTMnet; P24062; -. DR PhosphoSitePlus; P24062; -. DR PaxDb; 10116-ENSRNOP00000019267; -. DR GeneID; 25718; -. DR KEGG; rno:25718; -. DR UCSC; RGD:2869; rat. DR AGR; RGD:2869; -. DR CTD; 3480; -. DR RGD; 2869; Igf1r. DR eggNOG; KOG4258; Eukaryota. DR HOGENOM; CLU_000288_166_0_1; -. DR InParanoid; P24062; -. DR OMA; FRGYAFK; -. DR PhylomeDB; P24062; -. DR BRENDA; 2.7.10.1; 5301. DR Reactome; R-RNO-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R). DR Reactome; R-RNO-2428928; IRS-related events triggered by IGF1R. DR Reactome; R-RNO-2428933; SHC-related events triggered by IGF1R. DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling. DR PRO; PR:P24062; -. DR Proteomes; UP000002494; Chromosome 1. DR ExpressionAtlas; P24062; baseline and differential. DR GO; GO:0035867; C:alphav-beta3 integrin-IGF-1-IGF1R complex; ISO:RGD. DR GO; GO:0030424; C:axon; IDA:RGD. DR GO; GO:0005901; C:caveola; IDA:RGD. DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD. DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:1902911; C:protein kinase complex; ISO:RGD. DR GO; GO:0043235; C:signaling receptor complex; ISO:RGD. DR GO; GO:0030315; C:T-tubule; IDA:RGD. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:RGD. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0043559; F:insulin binding; ISO:RGD. DR GO; GO:0005009; F:insulin receptor activity; IBA:GO_Central. DR GO; GO:0005158; F:insulin receptor binding; ISO:RGD. DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:RGD. DR GO; GO:0005520; F:insulin-like growth factor binding; ISS:UniProtKB. DR GO; GO:0031994; F:insulin-like growth factor I binding; ISO:RGD. DR GO; GO:0005010; F:insulin-like growth factor receptor activity; IDA:RGD. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:RGD. DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD. DR GO; GO:0005198; F:structural molecule activity; ISS:UniProtKB. DR GO; GO:0030325; P:adrenal gland development; ISO:RGD. DR GO; GO:0097242; P:amyloid-beta clearance; ISO:RGD. DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD. DR GO; GO:0007409; P:axonogenesis; IMP:RGD. DR GO; GO:0007420; P:brain development; ISO:RGD. DR GO; GO:0003230; P:cardiac atrium development; IEP:RGD. DR GO; GO:1904045; P:cellular response to aldosterone; IEP:RGD. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:RGD. DR GO; GO:1904385; P:cellular response to angiotensin; IEP:RGD. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD. DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD. DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IPI:RGD. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD. DR GO; GO:0071393; P:cellular response to progesterone stimulus; IEP:RGD. DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEP:RGD. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IPI:RGD. DR GO; GO:0034224; P:cellular response to zinc ion starvation; IEP:RGD. DR GO; GO:0090398; P:cellular senescence; IEP:RGD. DR GO; GO:0021549; P:cerebellum development; IMP:RGD. DR GO; GO:0097062; P:dendritic spine maintenance; IGI:ARUK-UCL. DR GO; GO:0008544; P:epidermis development; ISO:RGD. DR GO; GO:0030010; P:establishment of cell polarity; IMP:RGD. DR GO; GO:0044849; P:estrous cycle; IMP:RGD. DR GO; GO:0031017; P:exocrine pancreas development; ISO:RGD. DR GO; GO:0021766; P:hippocampus development; IEP:RGD. DR GO; GO:0006955; P:immune response; ISO:RGD. DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:ARUK-UCL. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0030238; P:male sex determination; ISO:RGD. DR GO; GO:0030879; P:mammary gland development; ISO:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:1904193; P:negative regulation of cholangiocyte apoptotic process; IMP:RGD. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; IMP:RGD. DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISS:UniProtKB. DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IMP:RGD. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD. DR GO; GO:0031175; P:neuron projection development; IDA:RGD. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISO:RGD. DR GO; GO:0048680; P:positive regulation of axon regeneration; IMP:RGD. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:RGD. DR GO; GO:0048639; P:positive regulation of developmental growth; ISO:RGD. DR GO; GO:0051054; P:positive regulation of DNA metabolic process; IMP:RGD. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD. DR GO; GO:0051446; P:positive regulation of meiotic cell cycle; ISO:RGD. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:RGD. DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; IMP:RGD. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:RGD. DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; IGI:ARUK-UCL. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD. DR GO; GO:0090031; P:positive regulation of steroid hormone biosynthetic process; IMP:BHF-UCL. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; ISO:RGD. DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; ISO:RGD. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD. DR GO; GO:0046328; P:regulation of JNK cascade; ISS:UniProtKB. DR GO; GO:0043279; P:response to alkaloid; IEP:RGD. DR GO; GO:0045471; P:response to ethanol; IDA:RGD. DR GO; GO:0009725; P:response to hormone; IEP:RGD. DR GO; GO:0032868; P:response to insulin; IEP:RGD. DR GO; GO:1902065; P:response to L-glutamate; IDA:RGD. DR GO; GO:0035094; P:response to nicotine; IEP:RGD. DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD. DR GO; GO:0033197; P:response to vitamin E; IEP:RGD. DR GO; GO:0045056; P:transcytosis; ISO:RGD. DR CDD; cd00063; FN3; 3. DR CDD; cd00064; FU; 1. DR CDD; cd05032; PTKc_InsR_like; 1. DR FunFam; 2.60.40.10:FF:002810; Insulin-like growth factor 1 receptor; 1. DR FunFam; 1.10.510.10:FF:000050; Tyrosine-protein kinase receptor; 1. DR FunFam; 2.10.220.10:FF:000007; Tyrosine-protein kinase receptor; 1. DR FunFam; 2.60.40.10:FF:000087; Tyrosine-protein kinase receptor; 1. DR FunFam; 2.60.40.10:FF:002452; Tyrosine-protein kinase receptor; 1. DR FunFam; 3.30.200.20:FF:000026; Tyrosine-protein kinase receptor; 1. DR FunFam; 3.80.20.20:FF:000001; Tyrosine-protein kinase receptor; 1. DR FunFam; 3.80.20.20:FF:000002; Tyrosine-protein kinase receptor; 1. DR Gene3D; 2.10.220.10; Hormone Receptor, Insulin-like Growth Factor Receptor 1, Chain A, domain 2; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 3.80.20.20; Receptor L-domain; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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; IPR050122; RTK. 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 PANTHER; PTHR24416:SF106; INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. 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; Fibronectin type III; 3. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF52058; L domain-like; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50853; FN3; 3. 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 2: Evidence at transcript level; KW ATP-binding; Cell membrane; Cleavage on pair of basic residues; KW Disulfide bond; Glycoprotein; Isopeptide bond; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; KW Signal; Transferase; Transmembrane; Transmembrane helix; KW 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_0000016685" FT CHAIN 742..1370 FT /note="Insulin-like growth factor 1 receptor beta chain" FT /id="PRO_0000016686" 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..1370 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" 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 835..928 FT /note="Fibronectin type-III 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1000..1275 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1304..1370 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 1305..1321 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1322..1331 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1136 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 1162 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P08069" FT MOD_RES 1166 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 1279 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000250|UniProtKB:Q60751" FT MOD_RES 1283 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60751" 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:0000255" FT CARBOHYD 748 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 757 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 765 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 901 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 914 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 33..52 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 150..178 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 182..205 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 192..211 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 215..224 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 219..230 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 231..239 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 235..248 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 251..260 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 264..276 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 282..303 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 307..321 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 324..328 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 332..354 FT /evidence="ECO:0000250|UniProtKB:P08069" FT DISULFID 456..489 FT /evidence="ECO:0000250|UniProtKB:P08069" FT CROSSLNK 1169 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P08069" FT CROSSLNK 1172 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P08069" FT CONFLICT 985..986 FT /note="AD -> PY (in Ref. 3; no nucleotide entry)" FT /evidence="ECO:0000305" SQ SEQUENCE 1370 AA; 155396 MW; A5946897A41CB145 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 GECMQECPSG 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 RQPQDGYLFR HNYCSKDKIP IRKYADGTID VEEVTENPKT EVCGGDKGPC CACPKTEAEK QAEKEEAEYR KVFENFLHNS IFVPRPERRR RDVLQVANTT 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 NNLVLIPPSL SKMIQMAGEI ADGMAYLNAN KFVHRDLAAR NCMVAEDFTV KIGDFGMTRD IYETDYYRKG GKGLLPVRWM SPESLKDGVF TTHSDVWSFG VVLWEIATLA EQPYQGLSNE QVLRFVMEGG LLDKPDNCPD MLFELMRMCW QYNPKMRPSF LEIIGSIKDE MEPSFQEVSF YYSEENKPPE PEELEMELEL EPENMESVPL DPSASSASLP LPERHSGHKA ENGPGVLVLR ASFDERQPYA HMNGGRANER ALPLPQSSTC //