CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006498
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Insulin receptor substrate 1 
Protein Synonyms/Alias
 IRS-1 
Gene Name
 IRS1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
52EYYENEKKWRHKSSAacetylation[1]
61RHKSSAPKRSIPLESacetylation[1]
867RLSLGDPKASTLPRAubiquitination[2]
Reference
 [1] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 
Functional Description
 May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity). 
Sequence Annotation
 DOMAIN 12 115 PH.
 DOMAIN 160 264 IRS-type PTB.
 REGION 3 137 Mediates interaction with PHIP (By
 REGION 896 898 GRB2-binding (By similarity).
 MOTIF 465 468 YXXM motif 1.
 MOTIF 551 554 YXXM motif 2.
 MOTIF 612 615 YXXM motif 3.
 MOTIF 632 635 YXXM motif 4.
 MOTIF 662 665 YXXM motif 5.
 MOTIF 732 735 YXXM motif 6.
 MOTIF 941 944 YXXM motif 7.
 MOTIF 989 992 YXXM motif 8.
 MOTIF 1012 1015 YXXM motif 9.
 MOD_RES 3 3 Phosphoserine (By similarity).
 MOD_RES 99 99 Phosphoserine; by CK2 (By similarity).
 MOD_RES 270 270 Phosphoserine; by RPS6KB1.
 MOD_RES 307 307 Phosphoserine; by RPS6KB1.
 MOD_RES 312 312 Phosphoserine; by IKKB and MAPK8.
 MOD_RES 329 329 Phosphoserine (By similarity).
 MOD_RES 345 345 Phosphoserine (By similarity).
 MOD_RES 348 348 Phosphoserine.
 MOD_RES 465 465 Phosphotyrosine; by INSR (By similarity).
 MOD_RES 612 612 Phosphotyrosine; by INSR.
 MOD_RES 629 629 Phosphoserine.
 MOD_RES 632 632 Phosphotyrosine; by INSR.
 MOD_RES 636 636 Phosphoserine.
 MOD_RES 662 662 Phosphotyrosine.
 MOD_RES 794 794 Phosphoserine; by AMPK and SIK2.
 MOD_RES 896 896 Phosphotyrosine; by INSR (By similarity).
 MOD_RES 941 941 Phosphotyrosine; by INSR.
 MOD_RES 989 989 Phosphotyrosine; by INSR (By similarity).
 MOD_RES 1101 1101 Phosphoserine; by RPS6KB1 and PKC/PRKCQ.
 MOD_RES 1145 1145 Phosphoserine (By similarity).
 MOD_RES 1179 1179 Phosphotyrosine; by INSR (By similarity).
 MOD_RES 1223 1223 Phosphoserine (By similarity).
 MOD_RES 1229 1229 Phosphotyrosine; by INSR (By similarity).  
Keyword
 3D-structure; Complete proteome; Diabetes mellitus; Disease mutation; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Transducer. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1242 AA 
Protein Sequence
MASPPESDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE KKWRHKSSAP 60
KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE AEQDSWYQAL LQLHNRAKGH 120
HDGAAALGAG GGGGSCSGSS GLGEAGEDLS YGDVPPGPAF KEVWQVILKP KGLGQTKNLI 180
GIYRLCLTSK TISFVKLNSE AAAVVLQLMN IRRCGHSENF FFIEVGRSAV TGPGEFWMQV 240
DDSVVAQNMH ETILEAMRAM SDEFRPRSKS QSSSNCSNPI SVPLRRHHLN NPPPSQVGLT 300
RRSRTESITA TSPASMVGGK PGSFRVRASS DGEGTMSRPA SVDGSPVSPS TNRTHAHRHR 360
GSARLHPPLN HSRSIPMPAS RCSPSATSPV SLSSSSTSGH GSTSDCLFPR RSSASVSGSP 420
SDGGFISSDE YGSSPCDFRS SFRSVTPDSL GHTPPARGEE ELSNYICMGG KGPSTLTAPN 480
GHYILSRGGN GHRCTPGTGL GTSPALAGDE AASAADLDNR FRKRTHSAGT SPTITHQKTP 540
SQSSVASIEE YTEMMPAYPP GGGSGGRLPG HRHSAFVPTR SYPEEGLEMH PLERRGGHHR 600
PDSSTLHTDD GYMPMSPGVA PVPSGRKGSG DYMPMSPKSV SAPQQIINPI RRHPQRVDPN 660
GYMMMSPSGG CSPDIGGGPS SSSSSSNAVP SGTSYGKLWT NGVGGHHSHV LPHPKPPVES 720
SGGKLLPCTG DYMNMSPVGD SNTSSPSDCY YGPEDPQHKP VLSYYSLPRS FKHTQRPGEP 780
EEGARHQHLR LSTSSGRLLY AATADDSSSS TSSDSLGGGY CGARLEPSLP HPHHQVLQPH 840
LPRKVDTAAQ TNSRLARPTR LSLGDPKAST LPRAREQQQQ QQPLLHPPEP KSPGEYVNIE 900
FGSDQSGYLS GPVAFHSSPS VRCPSQLQPA PREEETGTEE YMKMDLGPGR RAAWQESTGV 960
EMGRLGPAPP GAASICRPTR AVPSSRGDYM TMQMSCPRQS YVDTSPAAPV SYADMRTGIA 1020
AEEVSLPRAT MAAASSSSAA SASPTGPQGA AELAAHSSLL GGPQGPGGMS AFTRVNLSPN 1080
RNQSAKVIRA DPQGCRRRHS SETFSSTPSA TRVGNTVPFG AGAAVGGGGG SSSSSEDVKR 1140
HSSASFENVW LRPGELGGAP KEPAKLCGAA GGLENGLNYI DLDLVKDFKQ CPQECTPEPQ 1200
PPPPPPPHQP LGSGESSSTR RSSEDLSAYA SISFQKQPED RQ 1242 
Gene Ontology
 GO:0005901; C:caveola; IDA:BHF-UCL.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005899; C:insulin receptor complex; ISS:BHF-UCL.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB.
 GO:0005543; F:phospholipid binding; IEA:InterPro.
 GO:0005080; F:protein kinase C binding; ISS:BHF-UCL.
 GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
 GO:0004871; F:signal transducer activity; TAS:ProtInc.
 GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; ISS:BHF-UCL.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0042593; P:glucose homeostasis; TAS:BHF-UCL.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; IPI:UniProtKB.
 GO:0048009; P:insulin-like growth factor receptor signaling pathway; IPI:UniProtKB.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
 GO:0016042; P:lipid catabolic process; IEA:Compara.
 GO:0030879; P:mammary gland development; IEA:Compara.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:BHF-UCL.
 GO:0046676; P:negative regulation of insulin secretion; IDA:BHF-UCL.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; IDA:BHF-UCL.
 GO:0030335; P:positive regulation of cell migration; IEA:Compara.
 GO:0008284; P:positive regulation of cell proliferation; NAS:BHF-UCL.
 GO:0032000; P:positive regulation of fatty acid beta-oxidation; IMP:BHF-UCL.
 GO:2001275; P:positive regulation of glucose import in response to insulin stimulus; IDA:BHF-UCL.
 GO:0045725; P:positive regulation of glycogen biosynthetic process; IMP:BHF-UCL.
 GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISS:BHF-UCL.
 GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Compara.
 GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:BHF-UCL.
 GO:0043491; P:protein kinase B signaling cascade; IEA:Compara.
 GO:0034504; P:protein localization to nucleus; IEA:Compara.
 GO:0010468; P:regulation of gene expression; IEA:Compara. 
Interpro
 IPR002404; Insln_rcpt_S1.
 IPR011993; PH_like_dom.
 IPR001849; Pleckstrin_homology. 
Pfam
 PF02174; IRS
 PF00169; PH 
SMART
 SM00233; PH
 SM00310; PTBI 
PROSITE
 PS51064; IRS_PTB
 PS50003; PH_DOMAIN 
PRINTS
 PR00628; INSULINRSI.