IRS1_RAT
ID IRS1_RAT Reviewed; 1235 AA.
AC P35570;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Insulin receptor substrate 1;
DE Short=IRS-1;
DE AltName: Full=pp185;
GN Name=Irs1; Synonyms=Irs-1;
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], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1648180; DOI=10.1038/352073a0;
RA Sun X.-J., Rothenberg P.L., Kahn C.R., Backer J.M., Araki E., Wilden P.A.,
RA Cahill D.A., Goldstein B.J., White M.F.;
RT "Structure of the insulin receptor substrate IRS-1 defines a unique signal
RT transduction protein.";
RL Nature 352:73-77(1991).
RN [2]
RP PROTEIN SEQUENCE OF 44-51; 173-178; 223-243; 489-506; 635-646; 932-947 AND
RP 1098-1106.
RX PubMed=2022647; DOI=10.1016/s0021-9258(18)92976-5;
RA Rothenberg P.L., Lane W.S., Karasik A., Backer J.M., White M.F., Kahn C.R.;
RT "Purification and partial sequence analysis of pp185, the major cellular
RT substrate of the insulin receptor tyrosine kinase.";
RL J. Biol. Chem. 266:8302-8311(1991).
RN [3]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH PIK3R1.
RX PubMed=1380456; DOI=10.1002/j.1460-2075.1992.tb05426.x;
RA Backer J.M., Myers M.G. Jr., Shoelson S.E., Chin D.J., Sun X.-J.,
RA Miralpeix M., Hu P., Margolis B., Skolnik E.Y., Schlessinger J.,
RA White M.F.;
RT "Phosphatidylinositol 3'-kinase is activated by association with IRS-1
RT during insulin stimulation.";
RL EMBO J. 11:3469-3479(1992).
RN [4]
RP INTERACTION WITH GRB2.
RX PubMed=8491186; DOI=10.1002/j.1460-2075.1993.tb05842.x;
RA Skolnik E.Y., Lee C.-H., Batzer A.G., Vicentini L.M., Zhou M., Daly R.J.,
RA Myers M.J. Jr., Backer J.M., Ullrich A., White M.F., Schlessinger J.;
RT "The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-
RT phosphorylated IRS1 and Shc: implications for insulin control of ras
RT signalling.";
RL EMBO J. 12:1929-1936(1993).
RN [5]
RP PHOSPHORYLATION AT TYR-460; TYR-608; TYR-628; TYR-895; TYR-939; TYR-987;
RP TYR-1172 AND TYR-1222.
RX PubMed=7504175; DOI=10.1128/mcb.13.12.7418-7428.1993;
RA Sun X.-J., Crimmins D.L., Myers M.G. Jr., Miralpeix M., White M.F.;
RT "Pleiotropic insulin signals are engaged by multisite phosphorylation of
RT IRS-1.";
RL Mol. Cell. Biol. 13:7418-7428(1993).
RN [6]
RP PHOSPHORYLATION AT SER-99 AND THR-502.
RX PubMed=8349691; DOI=10.1016/s0021-9258(17)46824-4;
RA Tanasijevic M.J., Myers M.G. Jr., Thoma R.S., Crimmins D.L., White M.F.,
RA Sacks D.B.;
RT "Phosphorylation of the insulin receptor substrate IRS-1 by casein kinase
RT II.";
RL J. Biol. Chem. 268:18157-18166(1993).
RN [7]
RP INTERACTION WITH PHIP, AND MUTAGENESIS OF TRP-106.
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 [8]
RP PHOSPHORYLATION AT SER-307.
RX PubMed=11606564; DOI=10.1074/jbc.m101521200;
RA Aguirre V., Werner E.D., Giraud J., Lee Y.H., Shoelson S.E., White M.F.;
RT "Phosphorylation of Ser307 in insulin receptor substrate-1 blocks
RT interactions with the insulin receptor and inhibits insulin action.";
RL J. Biol. Chem. 277:1531-1537(2002).
RN [9]
RP PHOSPHORYLATION AT SER-789.
RX PubMed=12006586; DOI=10.1074/jbc.m201494200;
RA Qiao L.Y., Zhande R., Jetton T.L., Zhou G., Sun X.-J.;
RT "In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a
RT novel serine kinase in insulin-resistant rodents.";
RL J. Biol. Chem. 277:26530-26539(2002).
RN [10]
RP INTERACTION WITH ROCK1, AND PHOSPHORYLATION.
RX PubMed=11739394; DOI=10.1074/jbc.m110508200;
RA Begum N., Sandu O.A., Ito M., Lohmann S.M., Smolenski A.;
RT "Active Rho kinase (ROK-alpha) associates with insulin receptor substrate-1
RT and inhibits insulin signaling in vascular smooth muscle cells.";
RL J. Biol. Chem. 277:6214-6222(2002).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-343; THR-441; THR-448
RP AND SER-891, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [12]
RP INTERACTION WITH GKAP1.
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 [13]
RP INTERACTION WITH DGKZ.
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: May mediate the control of various cellular processes by
CC insulin. When phosphorylated by the insulin receptor binds specifically
CC to various cellular proteins containing SH2 domains such as
CC phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates
CC phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit.
CC {ECO:0000269|PubMed:1380456}.
CC -!- SUBUNIT: Interacts with SOCS7 (By similarity). Interacts (via IRS-type
CC PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY
CC motif) (By similarity). Interacts with UBTF, FER and PIK3CA (By
CC similarity). Interacts (via phosphorylated YXXM motifs) with PIK3R1
CC (PubMed:1380456). Interacts with ROCK1 (PubMed:11739394). Interacts
CC (via PH domain) with PHIP (PubMed:11018022). Interacts with GRB2
CC (PubMed:8491186). Interacts with ALK (By similarity). Interacts with
CC EIF2AK2/PKR (By similarity). Interacts with GKAP1 (PubMed:25586176).
CC Interacts with DGKZ in the absence of insulin; insulin stimulation
CC decreases this interaction (PubMed:27739494). Found in a ternary
CC complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By
CC similarity). {ECO:0000250|UniProtKB:P35568,
CC ECO:0000250|UniProtKB:P35569, ECO:0000269|PubMed:11018022,
CC ECO:0000269|PubMed:11739394, ECO:0000269|PubMed:1380456,
CC ECO:0000269|PubMed:25586176, ECO:0000269|PubMed:27739494,
CC ECO:0000269|PubMed:8491186}.
CC -!- INTERACTION:
CC P35570; Q9EPH8: Pabpc1; NbExp=2; IntAct=EBI-520230, EBI-919825;
CC P35570; Q63787: Pik3r1; NbExp=2; IntAct=EBI-520230, EBI-518443;
CC P35570; P39688: Fyn; Xeno; NbExp=4; IntAct=EBI-520230, EBI-524514;
CC P35570; P62993: GRB2; Xeno; NbExp=5; IntAct=EBI-520230, EBI-401755;
CC P35570; P06213: INSR; Xeno; NbExp=5; IntAct=EBI-520230, EBI-475899;
CC P35570; Q8VDD9: Phip; Xeno; NbExp=2; IntAct=EBI-520230, EBI-1369766;
CC P35570; P27986: PIK3R1; Xeno; NbExp=2; IntAct=EBI-520230, EBI-79464;
CC P35570; Q04759: PRKCQ; Xeno; NbExp=2; IntAct=EBI-520230, EBI-374762;
CC P35570; P18031: PTPN1; Xeno; NbExp=3; IntAct=EBI-520230, EBI-968788;
CC P35570; Q06124: PTPN11; Xeno; NbExp=3; IntAct=EBI-520230, EBI-297779;
CC P35570; Q13625-2: TP53BP2; Xeno; NbExp=4; IntAct=EBI-520230, EBI-287091;
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, and Ser-789
CC phosphorylation is increased in the liver of insulin-resistant rats
CC (PubMed:11606564, PubMed:12006586, PubMed:7504175). Phosphorylation of
CC Tyr-895 is required for GRB2-binding. Phosphorylated by ALK.
CC Phosphorylated at Ser-265, Ser-302, Ser-632 and Ser-1100 by RPS6KB1;
CC phosphorylation induces accelerated degradation of IRS1 (By
CC similarity). Phosphorylated on tyrosine residues in response to insulin
CC (By similarity). In skeletal muscles, dephosphorylated on Tyr-608 by
CC TNS2 under anabolic conditions; dephosphorylation results in the
CC proteasomal degradation of IRS1 (By similarity).
CC {ECO:0000250|UniProtKB:P35568, ECO:0000250|UniProtKB:P35569,
CC ECO:0000269|PubMed:11606564, ECO:0000269|PubMed:12006586,
CC ECO:0000269|PubMed:7504175}.
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). {ECO:0000250}.
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DR EMBL; X58375; CAA41264.1; -; mRNA.
DR PIR; S16948; S16948.
DR RefSeq; NP_037101.1; NM_012969.1.
DR PDB; 5WRK; X-ray; 2.62 A; P=607-614.
DR PDB; 5WRL; X-ray; 3.10 A; P=627-634.
DR PDB; 5WRM; X-ray; 2.60 A; P=657-664.
DR PDBsum; 5WRK; -.
DR PDBsum; 5WRL; -.
DR PDBsum; 5WRM; -.
DR AlphaFoldDB; P35570; -.
DR BMRB; P35570; -.
DR SMR; P35570; -.
DR BioGRID; 247500; 14.
DR CORUM; P35570; -.
DR DIP; DIP-664N; -.
DR ELM; P35570; -.
DR IntAct; P35570; 23.
DR MINT; P35570; -.
DR STRING; 10116.ENSRNOP00000019579; -.
DR BindingDB; P35570; -.
DR ChEMBL; CHEMBL1163110; -.
DR iPTMnet; P35570; -.
DR PhosphoSitePlus; P35570; -.
DR PaxDb; P35570; -.
DR PRIDE; P35570; -.
DR GeneID; 25467; -.
DR KEGG; rno:25467; -.
DR UCSC; RGD:2922; rat.
DR CTD; 3667; -.
DR RGD; 2922; Irs1.
DR eggNOG; ENOG502QUNU; Eukaryota.
DR InParanoid; P35570; -.
DR OrthoDB; 298675at2759; -.
DR PhylomeDB; P35570; -.
DR Reactome; R-RNO-109704; PI3K Cascade.
DR Reactome; R-RNO-112399; IRS-mediated signalling.
DR Reactome; R-RNO-112412; SOS-mediated signalling.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-1266695; Interleukin-7 signaling.
DR Reactome; R-RNO-198203; PI3K/AKT activation.
DR Reactome; R-RNO-201556; Signaling by ALK.
DR Reactome; R-RNO-2428928; IRS-related events triggered by IGF1R.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-74713; IRS activation.
DR Reactome; R-RNO-74749; Signal attenuation.
DR PRO; PR:P35570; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005901; C:caveola; ISO:RGD.
DR GO; GO:0036064; C:ciliary basal body; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005899; C:insulin receptor complex; IMP:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005158; F:insulin receptor binding; IMP:RGD.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:RGD.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IDA:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0005080; F:protein kinase C binding; IPI:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; ISO:RGD.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IMP:BHF-UCL.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:1904385; P:cellular response to angiotensin; IEP:RGD.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IEP:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR GO; GO:0071478; P:cellular response to radiation; IEP:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; ISO:RGD.
DR GO; GO:0030879; P:mammary gland development; ISO:RGD.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0090275; P:negative regulation of somatostatin secretion; IMP:BHF-UCL.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; ISO:RGD.
DR GO; GO:0070094; P:positive regulation of glucagon secretion; IMP:BHF-UCL.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:RGD.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:RGD.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:RGD.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISO:RGD.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0043491; P:protein kinase B signaling; ISO:RGD.
DR GO; GO:0034504; P:protein localization to nucleus; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0031000; P:response to caffeine; IDA:RGD.
DR GO; GO:0032868; P:response to insulin; ISO:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IDA:UniProtKB.
DR CDD; cd01204; PTB_IRS; 1.
DR Gene3D; 2.30.29.30; -; 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; PTHR10614; 1.
DR Pfam; PF02174; IRS; 1.
DR Pfam; PF00169; PH; 1.
DR PRINTS; PR00628; INSULINRSI.
DR SMART; SM00233; PH; 1.
DR SMART; SM00310; PTBI; 1.
DR PROSITE; PS51064; IRS_PTB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Phosphoprotein;
KW Reference proteome; Repeat; Transducer; Ubl conjugation.
FT CHAIN 1..1235
FT /note="Insulin receptor substrate 1"
FT /id="PRO_0000084238"
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:0000269|PubMed:11018022"
FT REGION 258..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 520..539
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 669..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 766..921
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 895..897
FT /note="GRB2-binding"
FT REGION 1024..1165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1177..1235
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 939..942
FT /note="YXXM motif 7"
FT MOTIF 987..990
FT /note="YXXM motif 8"
FT MOTIF 1010..1013
FT /note="YXXM motif 9"
FT COMPBIAS 261..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..311
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 362..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 521..539
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 669..693
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 769..783
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 784..812
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 867..887
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1029..1052
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1070..1088
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1191..1205
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1206..1229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 99
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8349691"
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:0000250|UniProtKB:P35569"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 441
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 448
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 460
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000269|PubMed:7504175"
FT MOD_RES 502
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:8349691"
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:0000269|PubMed:7504175"
FT MOD_RES 628
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000269|PubMed:7504175"
FT MOD_RES 632
FT /note="Phosphoserine; by RPS6KB1 and ROCK2"
FT /evidence="ECO:0000250|UniProtKB:P35569"
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:12006586"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 895
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000269|PubMed:7504175"
FT MOD_RES 939
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000269|PubMed:7504175"
FT MOD_RES 987
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000269|PubMed:7504175"
FT MOD_RES 1099
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 1100
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 1172
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000269|PubMed:7504175"
FT MOD_RES 1222
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000269|PubMed:7504175"
FT MUTAGEN 106
FT /note="W->A: Loss of interaction with PHIP."
FT /evidence="ECO:0000269|PubMed:11018022"
FT CONFLICT 1098
FT /note="H -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1235 AA; 131178 MW; A274BC7540CA85C5 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 PRTKSQSSSS CSNPISVPLR RHHLNNPPPS QVGLTRRSRT
ESITATSPAS MVGGKPGSFR VRASSDGEGT MSRPASVDGS PVSPSTNRTH AHRHRGSSRL
HPPLNHSRSI PMPSSRCSPS ATSPVSLSSS STSGHGSTSD CLFPRRSSAS VSGSPSDGGF
ISSDEYGSSP CDFRSSFRSV TPDSLGHTPP ARGEEELSNY ICMGGKGAST LTAPNGHYIL
SRGGNGHRYI PGATMGTSPA LTGDEAAGAA DLDNRFRKRT HSAGTSPTIS HQKTPSQSSV
VSIEEYTEMM PAAYPPGGGS GGRLPGYRHS AFVPTHSYPE EGLEMHHLER RGGHHRPDSS
NLHTDDGYMP MSPGVAPVPS NRKGNGDYMP MSPKSVSAPQ QIINPIRRHP QRVDPNGYMM
MSPSGSCSPD IGGGSCSSSS ISAAPSGSSY GKPWTNGVGG HHTHALPHAK PPVESGGGKL
LPCTGDYMNM SPVGDSNTSS PSECYYGPED PQHKPVLSYY SLPRSFKHTQ RPGEPEEGAR
HQHLRLSSSS GRLRYTATAE DSSSSTSSDS LGGGYCGARP ESSVTHPHHH ALQPHLPRKV
DTAAQTNSRL ARPTRLSLGD PKASTLPRVR EQQQQQQQQQ QSSLHPPEPK SPGEYVNIEF
GSGQPGYLAG PATSRSSPSV RCLPQLHPAP REETGSEEYM NMDLGPGRRA TWQESGGVEL
GRVGPAPPGA ASICRPTRSV PNSRGDYMTM QIGCPRQSYV DTSPVAPVSY ADMRTGIAAE
KVSLPRTTGA APPPSSTASA SASVTPQGAA EQAAHSSLLG GPQGPGGMSA FTRVNLSPNH
NQSAKVIRAD TQGCRRRHSS ETFSAPTRAA NTVSFGAGAA GGGSGGGSED VKRHSSASFE
NVWLRPGDLG GASKESAPGC GAAGGLEKSL NYIDLDLVKD VKQHPQDCPS QQQSLPPPPP
HQPLGSNEGS SPRRSSEDLS TYASINFQKQ PEDRQ
