ID IRS1_MOUSE Reviewed; 1233 AA. AC P35569; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 02-SEP-2026, entry version 209. DE RecName: Full=Insulin receptor substrate 1; DE Short=IRS-1; GN Name=Irs1; Synonyms=Irs-1; 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]. RX PubMed=8167159; DOI=10.1016/0167-4889(94)90261-5; RA Araki E., Haag B.L. III, Kahn C.R.; RT "Cloning of the mouse insulin receptor substrate-1 (IRS-1) gene and RT complete sequence of mouse IRS-1."; RL Biochim. Biophys. Acta 1221:353-356(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8448209; DOI=10.1016/0167-4781(93)90222-y; RA Keller S.R., Aebersold R., Garner C.W., Lienhard G.E.; RT "The insulin-elicited 160 kDa phosphotyrosine protein in mouse adipocytes RT is an insulin receptor substrate 1: identification by cloning."; RL Biochim. Biophys. Acta 1172:323-326(1993). RN [3] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=7526222; DOI=10.1038/372186a0; RA Araki E., Lipes M.A., Patti M.E., Bruening J.C., Haag B. III, Johnson R.S., RA Kahn C.R.; RT "Alternative pathway of insulin signalling in mice with targeted disruption RT of the IRS-1 gene."; RL Nature 372:186-190(1994). RN [4] RP INTERACTION WITH FER. RX PubMed=11006284; DOI=10.1074/jbc.m006665200; RA Iwanishi M., Czech M.P., Cherniack A.D.; RT "The protein-tyrosine kinase fer associates with signaling complexes RT containing insulin receptor substrate-1 and phosphatidylinositol 3- RT kinase."; RL J. Biol. Chem. 275:38995-39000(2000). RN [5] RP INTERACTION WITH PHIP. RX PubMed=11018022; DOI=10.1074/jbc.c000611200; RA Farhang-Fallah J., Yin X., Trentin G., Cheng A.M., Rozakis-Adcock M.; RT "Cloning and characterization of PHIP, a novel insulin receptor substrate-1 RT pleckstrin homology domain interacting protein."; RL J. Biol. Chem. 275:40492-40497(2000). RN [6] RP TISSUE SPECIFICITY. RX PubMed=10749573; DOI=10.1172/jci9017; RA Ogata N., Chikazu D., Kubota N., Terauchi Y., Tobe K., Azuma Y., Ohta T., RA Kadowaki T., Nakamura K., Kawaguchi H.; RT "Insulin receptor substrate-1 in osteoblast is indispensable for RT maintaining bone turnover."; RL J. Clin. Invest. 105:935-943(2000). RN [7] RP PHOSPHORYLATION AT SER-789. RX PubMed=11598104; DOI=10.1074/jbc.c100483200; RA Jakobsen S.N., Hardie D.G., Morrice N., Tornqvist H.E.; RT "5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse RT C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside."; RL J. Biol. Chem. 276:46912-46916(2001). RN [8] RP INTERACTION WITH UBTF AND PIK3CA, AND EFFECT ON CELL AND BODY SIZE. RX PubMed=15197263; DOI=10.1073/pnas.0403328101; RA Drakas R., Tu X., Baserga R.; RT "Control of cell size through phosphorylation of upstream binding factor 1 RT by nuclear phosphatidylinositol 3-kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 101:9272-9276(2004). RN [9] RP FUNCTION, AND INTERACTION WITH SH2B1 AND JAK1. RX PubMed=15316008; DOI=10.1074/jbc.m408495200; RA Duan C., Li M., Rui L.; RT "SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated RT activation of the phosphatidylinositol 3-kinase pathway in response to RT leptin."; RL J. Biol. Chem. 279:43684-43691(2004). RN [10] RP PHOSPHORYLATION AT SER-632. RX PubMed=16098829; DOI=10.1016/j.cmet.2005.06.011; RA Furukawa N., Ongusaha P., Jahng W.J., Araki K., Choi C.S., Kim H.J., RA Lee Y.H., Kaibuchi K., Kahn B.B., Masuzaki H., Kim J.K., Lee S.W., RA Kim Y.B.; RT "Role of Rho-kinase in regulation of insulin action and glucose RT homeostasis."; RL Cell Metab. 2:119-129(2005). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340 AND SER-1097, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325; SER-414; SER-887; RP SER-1096 AND SER-1097, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and RC Spleen; 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 [13] RP INTERACTION WITH EIF2AK2. RX PubMed=22948222; DOI=10.1210/en.2012-1400; RA Carvalho-Filho M.A., Carvalho B.M., Oliveira A.G., Guadagnini D., Ueno M., RA Dias M.M., Tsukumo D.M., Hirabara S.M., Reis L.F., Curi R., RA Carvalheira J.B., Saad M.J.; RT "Double-stranded RNA-activated protein kinase is a key modulator of insulin RT sensitivity in physiological conditions and in obesity in mice."; RL Endocrinology 153:5261-5274(2012). RN [14] RP UBIQUITINATION. RX PubMed=23142081; DOI=10.1016/j.molcel.2012.09.029; RA Kim S.J., DeStefano M.A., Oh W.J., Wu C.C., Vega-Cotto N.M., Finlan M., RA Liu D., Su B., Jacinto E.; RT "mTOR complex 2 regulates proper turnover of insulin receptor substrate-1 RT via the ubiquitin ligase subunit Fbw8."; RL Mol. Cell 48:875-887(2012). RN [15] RP PHOSPHORYLATION AT SER-612. RX PubMed=24187137; DOI=10.1074/jbc.m113.500736; RA Seldin M.M., Lei X., Tan S.Y., Stanson K.P., Wei Z., Wong G.W.; RT "Skeletal muscle-derived myonectin activates the mammalian target of RT rapamycin (mTOR) pathway to suppress autophagy in liver."; RL J. Biol. Chem. 288:36073-36082(2013). RN [16] RP INTERACTION WITH GKAP1, AND PHOSPHORYLATION. RX PubMed=25586176; DOI=10.1074/jbc.m114.624759; RA Ando Y., Shinozawa Y., Iijima Y., Yu B.C., Sone M., Ooi Y., Watanaka Y., RA Chida K., Hakuno F., Takahashi S.; RT "Tumor necrosis factor (TNF)-alpha-induced repression of GKAP42 protein RT levels through cGMP-dependent kinase (cGK)-Ialpha causes insulin resistance RT in 3T3-L1 adipocytes."; RL J. Biol. Chem. 290:5881-5892(2015). RN [17] RP INTERACTION WITH DGKZ, AND IDENTIFICATION IN A COMPLEX WITH DGKZ AND RP PIP5K1A. RX PubMed=27739494; DOI=10.1038/srep35438; RA Liu T., Yu B., Kakino M., Fujimoto H., Ando Y., Hakuno F., Takahashi S.I.; RT "A novel IRS-1-associated protein, DGKzeta regulates GLUT4 translocation in RT 3T3-L1 adipocytes."; RL Sci. Rep. 6:35438-35438(2016). CC -!- FUNCTION: Signaling adapter protein that participates in the signal CC transduction from two prominent receptor tyrosine kinases, insulin CC receptor/INSR and insulin-like growth factor I receptor/IGF1R. Plays CC therefore an important role in development, growth, glucose homeostasis CC as well as lipid metabolism (PubMed:7526222). Upon phosphorylation by CC the insulin receptor, functions as a signaling scaffold that propagates CC insulin action through binding to SH2 domain-containing proteins CC including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 CC (By similarity). Recruitment of GRB2 leads to the activation of the CC guanine nucleotide exchange factor SOS1 which in turn triggers the CC Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the CC PI3K/AKT pathway is responsible for most of insulin metabolic effects CC in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of CC gene expression and in cooperation with the PI3K pathway regulates cell CC growth and differentiation (By similarity). Acts a positive regulator CC of the Wnt/beta-catenin signaling pathway through suppression of DVL2 CC autophagy-mediated degradation leading to cell proliferation (By CC similarity). {ECO:0000250|UniProtKB:P35568, CC ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:7526222}. CC -!- SUBUNIT: Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By CC similarity). Interacts with ROCK1 (By similarity). Interacts with GRB2 CC (By similarity). Interacts with SOCS7 (By similarity). Interacts (via CC IRS-type PTB domain) with IGF1R and INSR (via the tyrosine- CC phosphorylated NPXY motif) (By similarity). Interacts with UBTF and CC PIK3CA (PubMed:15197263). Interacts (via PH domain) with PHIP CC (PubMed:11018022). Interacts with FER (PubMed:11006284). Interacts with CC ALK (By similarity). Interacts with EIF2AK2/PKR (PubMed:22948222). CC Interacts with GKAP1 (PubMed:25586176). Interacts with DGKZ in the CC absence of insulin; insulin stimulation decreases this interaction CC (PubMed:27739494). Found in a ternary complex with DGKZ and PIP5K1A in CC the absence of insulin stimulation (PubMed:27739494). Interacts with CC SQSTM1; the interaction is disrupted by the presence of tensin TNS2 (By CC similarity). Interacts with NCK1 (via SH2 domain). Interacts with NCK2 CC (via SH3 domain) (By similarity). Interacts with SH2B1; this CC interaction enhances leptin-induced activation of the PI3-kinase CC pathway (PubMed:15316008). Interacts with DVL2; this interaction CC promotes the Wnt/beta-catenin signaling pathway (By similarity). CC {ECO:0000250|UniProtKB:P35568, ECO:0000250|UniProtKB:P35570, CC ECO:0000269|PubMed:11006284, ECO:0000269|PubMed:11018022, CC ECO:0000269|PubMed:15197263, ECO:0000269|PubMed:15316008, CC ECO:0000269|PubMed:22948222, ECO:0000269|PubMed:25586176, CC ECO:0000269|PubMed:27739494}. CC -!- INTERACTION: CC P35569; Q03963: Eif2ak2; NbExp=2; IntAct=EBI-400825, EBI-2603444; CC P35569; P26450: Pik3r1; NbExp=3; IntAct=EBI-400825, EBI-641764; CC P35569; Q1XH17: Trim72; NbExp=4; IntAct=EBI-400825, EBI-16034016; CC P35569; Q13625-2: TP53BP2; Xeno; NbExp=2; IntAct=EBI-400825, EBI-287091; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P35568}. Nucleus CC {ECO:0000250|UniProtKB:P35568}. Note=Nuclear or cytoplasmic CC localization of IRS1 correlates with the transition from proliferation CC to chondrogenic differentiation. {ECO:0000250|UniProtKB:P35568}. CC -!- TISSUE SPECIFICITY: Expressed in osteoblasts, but not in osteoclasts. CC {ECO:0000269|PubMed:10749573}. CC -!- PTM: Serine phosphorylation of IRS1 is a mechanism for insulin CC resistance. Ser-307 phosphorylation inhibits insulin action through CC disruption of IRS1 interaction with the insulin receptor (By CC similarity). Phosphorylation of Tyr-891 is required for GRB2-binding CC (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-265, Ser- CC 302, Ser-632 and Ser-1097 by RPS6KB1; phosphorylation induces CC accelerated degradation of IRS1 (By similarity). Phosphorylated on CC tyrosine residues in response to insulin (PubMed:25586176). In skeletal CC muscles, dephosphorylated on Tyr-608 by TNS2 under anabolic conditions; CC dephosphorylation results in the proteasomal degradation of IRS1 (By CC similarity). {ECO:0000250|UniProtKB:P35568, CC ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:25586176}. CC -!- PTM: Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent CC manner, leading to its degradation: the Cul7-RING(FBXW8) complex CC recognizes and binds IRS1 previously phosphorylated by S6 kinase CC (RPS6KB1 or RPS6KB2) (PubMed:23142081). Ubiquitinated by TRAF4 through CC 'Lys-29' linkage; this ubiquitination regulates the interaction of IRS1 CC with IGFR and IRS1 tyrosine phosphorylation upon IGF1 stimulation (By CC similarity). {ECO:0000250|UniProtKB:P35568, CC ECO:0000269|PubMed:23142081}. CC -!- PTM: S-nitrosylation at by BLVRB inhibits its activity. CC {ECO:0000250|UniProtKB:P35568}. CC -!- DISRUPTION PHENOTYPE: IRS1 deletion mice show impaired intrauterine CC growth, resistance to insulin and insulin-like growth factor-I/IGF1, CC and abnormal glucose tolerance. {ECO:0000269|PubMed:7526222}. 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; L24563; AAA39335.1; -; mRNA. DR EMBL; X69722; CAA49378.1; -; mRNA. DR PIR; S30185; S30185. DR RefSeq; NP_034700.2; NM_010570.4. DR PDB; 1AYB; X-ray; 3.00 A; P=887-898. DR PDB; 5AXI; X-ray; 2.50 A; E=606-610. DR AlphaFoldDB; P35569; -. DR BMRB; P35569; -. DR MDRepo; P35569; -. DR SMR; P35569; -. DR BioGRID; 200788; 23. DR DIP; DIP-32456N; -. DR FunCoup; P35569; 1612. DR IntAct; P35569; 51. DR MINT; P35569; -. DR STRING; 10090.ENSMUSP00000063795; -. DR GlyGen; P35569; 4 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (2 sites). DR iPTMnet; P35569; -. DR PhosphoSitePlus; P35569; -. DR SwissPalm; P35569; -. DR jPOST; P35569; -. DR PaxDb; 10090-ENSMUSP00000063795; -. DR PeptideAtlas; P35569; -. DR ProteomicsDB; 269333; -. DR Pumba; P35569; -. DR DNASU; 16367; -. DR GeneID; 16367; -. DR KEGG; mmu:16367; -. DR AGR; MGI:99454; -. DR CTD; 3667; -. DR MGI; MGI:99454; Irs1. DR eggNOG; ENOG502QUNU; Eukaryota. DR InParanoid; P35569; -. DR OrthoDB; 946068at2759; -. DR PhylomeDB; P35569; -. DR Reactome; R-MMU-109704; PI3K Cascade. DR Reactome; R-MMU-112399; IRS-mediated signalling. DR Reactome; R-MMU-112412; SOS-mediated signalling. DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling. DR Reactome; R-MMU-1266695; Interleukin-7 signaling. DR Reactome; R-MMU-198203; PI3K/AKT activation. DR Reactome; R-MMU-201556; Signaling by ALK. DR Reactome; R-MMU-2428928; IRS-related events triggered by IGF1R. DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-MMU-74713; IRS activation. DR Reactome; R-MMU-74749; Signal attenuation. DR Reactome; R-MMU-9842663; Signaling by LTK. DR BioGRID-ORCS; 16367; 6 hits in 76 CRISPR screens. DR EvolutionaryTrace; P35569; -. DR PRO; PR:P35569; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P35569; protein. DR GO; GO:0005901; C:caveola; ISO:GO_Central. DR GO; GO:0036064; C:ciliary basal body; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:GO_Central. DR GO; GO:0005899; C:insulin receptor complex; ISO:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0005158; F:insulin receptor binding; ISS:UniProtKB. DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB. DR GO; GO:0141038; F:phosphatidylinositol 3-kinase activator activity; IMP:MGI. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IDA:MGI. DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:GO_Central. DR GO; GO:0019904; F:protein domain specific binding; ISO:GO_Central. DR GO; GO:0019901; F:protein kinase binding; IDA:MGI. DR GO; GO:0005080; F:protein kinase C binding; ISO:GO_Central. DR GO; GO:0044877; F:protein-containing complex binding; ISO:GO_Central. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:MGI. DR GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB. DR GO; GO:0035591; F:signaling adaptor activity; ISO:GO_Central. DR GO; GO:0030159; F:signaling receptor complex adaptor activity; ISO:GO_Central. DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IDA:MGI. DR GO; GO:0071398; P:cellular response to fatty acid; IMP:ARUK-UCL. DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:MGI. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:GO_Central. DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:MGI. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IDA:MGI. DR GO; GO:0016042; P:lipid catabolic process; IMP:MGI. DR GO; GO:0030879; P:mammary gland development; IGI:MGI. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:GO_Central. DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:GO_Central. DR GO; GO:0090275; P:negative regulation of somatostatin secretion; ISO:GO_Central. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:GO_Central. DR GO; GO:0030335; P:positive regulation of cell migration; IGI:MGI. DR GO; GO:0046326; P:positive regulation of D-glucose import across plasma membrane; ISO:GO_Central. DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; ISO:GO_Central. DR GO; GO:0070094; P:positive regulation of glucagon secretion; ISO:GO_Central. DR GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:GO_Central. DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:GO_Central. DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:GO_Central. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IGI:MGI. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI. DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:GO_Central. DR GO; GO:0034504; P:protein localization to nucleus; IDA:MGI. DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI. DR GO; GO:0031000; P:response to caffeine; ISO:GO_Central. DR GO; GO:0045471; P:response to ethanol; ISO:GO_Central. DR GO; GO:0032868; P:response to insulin; ISO:GO_Central. DR CDD; cd01257; PH_IRS; 1. DR CDD; cd01204; PTB_IRS; 1. DR FunFam; 2.30.29.30:FF:000029; Insulin receptor substrate 1; 1. DR FunFam; 2.30.29.30:FF:000129; Insulin receptor substrate 1; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 2. DR InterPro; IPR039011; IRS. DR InterPro; IPR002404; IRS_PTB. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR PANTHER; PTHR10614; INSULIN RECEPTOR SUBSTRATE; 1. DR PANTHER; PTHR10614:SF11; INSULIN RECEPTOR SUBSTRATE 1; 1. DR Pfam; PF02174; IRS; 1. DR Pfam; PF00169; PH; 1. DR PRINTS; PR00628; INSULINRSI. DR SMART; SM01244; IRS; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00310; PTBI; 1. DR SUPFAM; SSF50729; PH domain-like; 2. DR PROSITE; PS51064; IRS_PTB; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PDBsum; 1AYB; -. DR PDBsum; 5AXI; -. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Isopeptide bond; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; S-nitrosylation; Transducer; Ubl conjugation. FT CHAIN 1..1233 FT /note="Insulin receptor substrate 1" FT /id="PRO_0000084237" FT DOMAIN 12..115 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 155..259 FT /note="IRS-type PTB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389" FT REGION 3..133 FT /note="Mediates interaction with PHIP" FT /evidence="ECO:0000250" FT REGION 257..425 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 651..720 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 766..985 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 891..893 FT /note="GRB2-binding" FT /evidence="ECO:0000250" FT REGION 1015..1137 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1178..1233 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 460..463 FT /note="YXXM motif 1" FT MOTIF 546..549 FT /note="YXXM motif 2" FT MOTIF 608..611 FT /note="YXXM motif 3" FT MOTIF 628..631 FT /note="YXXM motif 4" FT MOTIF 658..661 FT /note="YXXM motif 5" FT MOTIF 727..730 FT /note="YXXM motif 6" FT MOTIF 935..938 FT /note="YXXM motif 7" FT MOTIF 983..986 FT /note="YXXM motif 8" FT MOTIF 1006..1009 FT /note="YXXM motif 9" FT COMPBIAS 264..276 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 349..358 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 378..399 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 407..419 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 662..689 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 771..780 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 785..794 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 801..810 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1032..1042 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1043..1052 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1069..1081 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1116..1129 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1203..1227 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 3 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 99 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 265 FT /note="Phosphoserine; by RPS6KB1" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 302 FT /note="Phosphoserine; by RPS6KB1" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 307 FT /note="Phosphoserine; by IKKB, MAPK8 and RPS6KB1" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 318 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 325 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 340 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355" FT MOD_RES 343 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 414 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 441 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 448 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 460 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 522 FT /note="Phosphoserine; by RPS6KB1" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 608 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 612 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:24187137" FT MOD_RES 628 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 632 FT /note="Phosphoserine; by RPS6KB1 and ROCK2" FT /evidence="ECO:0000305|PubMed:16098829" FT MOD_RES 658 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 789 FT /note="Phosphoserine; by AMPK and SIK2" FT /evidence="ECO:0000269|PubMed:11598104" FT MOD_RES 887 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 891 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 935 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35568" FT MOD_RES 983 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 1096 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1097 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 1173 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35570" FT MOD_RES 1220 FT /note="Phosphotyrosine; by INSR" FT /evidence="ECO:0000250|UniProtKB:P35570" FT CROSSLNK 1180 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P35568" FT CONFLICT 1038..1039 FT /note="Missing (in Ref. 2)" FT /evidence="ECO:0000305" FT CONFLICT 1182 FT /note="H -> R (in Ref. 2; CAA49378)" FT /evidence="ECO:0000305" FT STRAND 890..892 FT /evidence="ECO:0007829|PDB:1AYB" SQ SEQUENCE 1233 AA; 130723 MW; C0E9B2D890DADD87 CRC64; MASPPDTDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE KKWRHKSSAP KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE AEQDSWYQAL LQLHNRAKAH HDGAGGGCGG SCSGSSGVGE AGEDLSYDTG PGPAFKEVWQ VILKPKGLGQ TKNLIGIYRL CLTSKTISFV KLNSEAAAVV LQLMNIRRCG HSENFFFIEV GRSAVTGPGE FWMQVDDSVV AQNMHETILE AMRAMSDEFR PRSKSQSSSS CSNPISVPLR RHHLNNPPPS QVGLTRRSRT ESITATSPAS MVGGKPGSFR VRASSDGEGT MSRPASVDGS PVSPSTNRTH AHRHRGSSRL HPPLNHSRSI PMPSSRCSPS ATSPVSLSSS STSGHGSTSD CLFPRRSSAS VSGSPSDGGF ISSDEYGSSP CDFRSSFRSV TPDSLGHTPP ARGEEELSNY ICMGGKGAST LAAPNGHYIL SRGGNGHRYI PGANLGTSPA LPGDEAAGAA DLDNRFRKRT HSAGTSPTIS HQKTPSQSSV ASIEEYTEMM PAAYPPGGGS GGRLPGYRHS AFVPTHSYPE EGLEMHHLER RGGHHRPDTS NLHTDDGYMP MSPGVAPVPS NRKGNGDYMP MSPKSVSAPQ QIINPIRRHP QRVDPNGYMM MSPSGSCSPD IGGGSSSSSS ISAAPSGSSY GKPWTNGVGG HHTHALPHAK PPVESGGGKL LPCTGDYMNM SPVGDSNTSS PSECYYGPED PQHKPVLSYY SLPRSFKHTQ RPGEPEEGAR HQHLRLSSSS GRLRYTATAE DSSSSTSSDS LGGGYCGARP ESSLTHPHHH VLQPHLPRKV DTAAQTNSRL ARPTRLSLGD PKASTLPRVR EQQQQQQSSL HPPEPKSPGE YVNIEFGSGQ PGYLAGPATS RSSPSVRCPP QLHPAPREET GSEEYMNMDL GPGRRATWQE SGGVELGRIG PAPPGSATVC RPTRSVPNSR GDYMTMQIGC PRQSYVDTSP VAPVSYADMR TGIAAEKASL PRPTGAAPPP SSTASSSASV TPQGATAEQA THSSLLGGPQ GPGGMSAFTR VNLSPNHNQS AKVIRADTQG CRRRHSSETF SAPTRAGNTV PFGAGAAVGG SGGGGGGGSE DVKRHSSASF ENVWLRPGDL GGVSKESAPV CGAAGGLEKS LNYIDLDLAK EHSQDCPSQQ QSLPPPPPHQ PLGSNEGNSP RRSSEDLSNY ASISFQKQPE DRQ //