CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000264
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Insulin receptor substrate 4 
Protein Synonyms/Alias
 IRS-4; 160 kDa phosphotyrosine protein; py160; Phosphoprotein of 160 kDa; pp160 
Gene Name
 IRS4 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
99HRRYFVLKLETADAPubiquitination[1]
202SRLILESKRRRCGTLubiquitination[1]
240DVWQVIVKPRGLGHRubiquitination[1, 2, 3]
248PRGLGHRKELSGVFRubiquitination[1]
477EEGNPQGKEDQEGSGubiquitination[1]
598GKGSGSGKGSDGDGEubiquitination[1]
618KKRSYFGKLTQSKQQubiquitination[2, 3]
623FGKLTQSKQQQMPPPubiquitination[1, 4]
646PAGGTGGKGKSGGRFubiquitination[1, 2, 3]
671TKECKEAKEVKDAEIacetylation[5]
671TKECKEAKEVKDAEIubiquitination[1]
674CKEAKEVKDAEIPEGubiquitination[1]
729PQNVSASKKRHSRSPubiquitination[1, 4]
803PQGGSSSKSWSSYFSubiquitination[1, 2, 3, 4]
835YVPMLPGKFLGRGLDubiquitination[1, 2, 3, 4]
843FLGRGLDKEVSYNWDubiquitination[2, 3]
866SGEGSFSKPGDGGSPubiquitination[1]
875GDGGSPSKPSDHEPPubiquitination[1]
897NRLSFITKGYKIKPKubiquitination[1, 2, 3, 4]
928YVNMDFTKRESNTPAubiquitination[1, 2, 3, 4]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] 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] 
Functional Description
 Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2. 
Sequence Annotation
 DOMAIN 78 199 PH.
 DOMAIN 231 335 IRS-type PTB.
 REGION 678 800 CRK-binding.
 REGION 895 897 GRB2-binding.
 MOTIF 487 490 YXXM motif 1.
 MOTIF 700 703 YXXM motif 2.
 MOTIF 717 720 YXXM motif 3.
 MOTIF 743 746 YXXM motif 4.
 MOTIF 779 782 YXXM motif 5.
 MOTIF 828 831 YXXM motif 6.
 MOTIF 921 924 YXXM motif 7.
 MOD_RES 921 921 Phosphotyrosine.  
Keyword
 Cell membrane; Complete proteome; Direct protein sequencing; Membrane; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Transducer. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1257 AA 
Protein Sequence
MASCSFTRDQ ATRRLRGAAA AAAAALAAVV TTPLLSSGTP TALIGTGSSC PGAMWLSTAT 60
GSRSDSESEE EDLPVGEEVC KRGYLRKQKH GHRRYFVLKL ETADAPARLE YYENARKFRH 120
SVRAAAAAAA AAASGAAIPP LIPPRRVITL YQCFSVSQRA DARYRHLIAL FTQDEYFAMV 180
AENESEQESW YLLLSRLILE SKRRRCGTLG AQPDGEPAAL AAAAAAEPPF YKDVWQVIVK 240
PRGLGHRKEL SGVFRLCLTD EEVVFVRLNT EVASVVVQLL SIRRCGHSEQ YFFLEVGRST 300
VIGPGELWMQ VDDCVVAQNM HELFLEKMRA LCADEYRARC RSYSISIGAH LLTLLSARRH 360
LGLVPLEPGG WLRRSRFEQF CHLRAIGDGE DEMLFTRRFV TPSEPVAHSR RGRLHLPRGR 420
RSRRAVSVPA SFFRRLAPSP ARPRHPAEAP NNGARLSSEV SGSGSGNFGE EGNPQGKEDQ 480
EGSGGDYMPM NNWGSGNGRG SGGGQGSNGQ GSSSHSSGGN QCSGEGQGSR GGQGSNGQGS 540
GGNQCSRDGQ GTAGGHGSGG GQRPGGGHGS GGGQGPGDGH GSGGGKNSGG GKGSGSGKGS 600
DGDGERGKSL KKRSYFGKLT QSKQQQMPPP PPPPPPPPPA GGTGGKGKSG GRFRLYFCVD 660
RGATKECKEA KEVKDAEIPE GAARGPHRAR AFDEDEDDPY VPMRPGVATP LVSSSDYMPM 720
APQNVSASKK RHSRSPFEDS RGYMMMFPRV SPPPAPSPPK APDTNKEDDS KDNDSESDYM 780
FMAPGAGAIP KNPRNPQGGS SSKSWSSYFS LPNPFRSSPL GQNDNSEYVP MLPGKFLGRG 840
LDKEVSYNWD PKDAASKPSG EGSFSKPGDG GSPSKPSDHE PPKNKAKRPN RLSFITKGYK 900
IKPKPQKPTH EQREADSSSD YVNMDFTKRE SNTPAPSTQG LPDSWGIIAE PRQSAFSNYV 960
NVEFGVPFPN PANDLSDLLR AIPRANPLSL DSARWPLPPL PLSATGSNAI EEEGDYIEVI 1020
FNSAMTPAMA LADSAIRYDA ETGRIYVVDP FSECCMDISL SPSRCSEPPP VARLLQEEEQ 1080
ERRRPQSRSQ SFFAAARAAV SAFPTDSLER DLSPSSAPAV ASAAEPTLAL SQVVAAASAL 1140
AAAPGIGAAA AAAGFDSASA RWFQPVANAA DAEAVRGAQD VAGGSNPGAH NPSANLARGD 1200
NQAGGAAAAA AAPEPPPRSR RVPRPPERED SDNDDDTHVR MDFARRDNQF DSPKRGR 1257 
Gene Ontology
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0005543; F:phospholipid binding; IEA:InterPro.
 GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc.
 GO:0004871; F:signal transducer activity; TAS:ProtInc. 
Interpro
 IPR002404; Insln_rcpt_S1.
 IPR011993; PH_like_dom.
 IPR001849; Pleckstrin_homology. 
Pfam
 PF02174; IRS 
SMART
 SM00233; PH
 SM00310; PTBI 
PROSITE
 PS51064; IRS_PTB
 PS50003; PH_DOMAIN 
PRINTS
 PR00628; INSULINRSI.