IRS1_CHLAE
ID IRS1_CHLAE Reviewed; 1251 AA.
AC Q28224;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 102.
DE RecName: Full=Insulin receptor substrate 1;
DE Short=IRS-1;
GN Name=IRS1;
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7488107; DOI=10.1006/bbrc.1995.2627;
RA Wang L., Hayashi H., Mitani Y., Ishii K., Ohnishi T., Niwa Y., Kido H.,
RA Ebina Y.;
RT "Cloning of a cDNA encoding a 190-kDa insulin receptor substrate-1-like
RT protein of simian COS cells.";
RL Biochem. Biophys. Res. Commun. 216:321-328(1995).
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with SOCS7. Interacts (via phosphorylated YXXM
CC motifs) with PIK3R1. Interacts with ROCK1. Interacts with GRB2.
CC Interacts with SOCS7. Interacts (via IRS-type PTB domain) with IGF1R
CC and INSR (via the tyrosine-phosphorylated NPXY motif). Interacts with
CC UBTF and PIK3CA. Interacts (via PH domain) with PHIP. Interacts with
CC FER (By similarity). Interacts with EIF2AK2/PKR (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Serine phosphorylation of IRS1 is a mechanism for insulin
CC resistance. Ser-312 phosphorylation inhibits insulin action through
CC disruption of IRS1 interaction with the insulin receptor (By
CC similarity). Phosphorylation of Tyr-905 is required for GRB2-binding
CC (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-
CC 307, Ser-636 and Ser-1109 by RPS6KB1; phosphorylation induces
CC accelerated degradation of IRS1. Phosphorylated on tyrosine residues in
CC response to insulin (By similarity). In skeletal muscles,
CC dephosphorylated on Tyr-612 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:P35569, ECO:0000250|UniProtKB:P35570}.
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; D64157; BAA11026.1; -; mRNA.
DR AlphaFoldDB; Q28224; -.
DR BMRB; Q28224; -.
DR SMR; Q28224; -.
DR IntAct; Q28224; 1.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0043548; F:phosphatidylinositol 3-kinase binding; ISS:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS: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 2: Evidence at transcript level;
KW Phosphoprotein; Repeat; Transducer; Ubl conjugation.
FT CHAIN 1..1251
FT /note="Insulin receptor substrate 1"
FT /id="PRO_0000084234"
FT DOMAIN 12..115
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 160..264
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 3..137
FT /note="Mediates interaction with PHIP"
FT /evidence="ECO:0000250"
FT REGION 262..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 594..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 668..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 734..753
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 769..946
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 905..907
FT /note="GRB2-binding"
FT /evidence="ECO:0000250"
FT REGION 1091..1124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1130..1149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1195..1251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 465..468
FT /note="YXXM motif 1"
FT MOTIF 551..554
FT /note="YXXM motif 2"
FT MOTIF 612..615
FT /note="YXXM motif 3"
FT MOTIF 632..635
FT /note="YXXM motif 4"
FT MOTIF 662..665
FT /note="YXXM motif 5"
FT MOTIF 730..733
FT /note="YXXM motif 6"
FT MOTIF 950..953
FT /note="YXXM motif 7"
FT MOTIF 998..1001
FT /note="YXXM motif 8"
FT MOTIF 1021..1024
FT /note="YXXM motif 9"
FT COMPBIAS 266..281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 675..692
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 734..748
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 772..786
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 787..815
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 870..894
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 919..934
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1108..1123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1204..1220
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1221..1251
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 270
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 307
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 312
FT /note="Phosphoserine; by IKKB, MAPK8 and RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 446
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35570"
FT MOD_RES 453
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 465
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35570"
FT MOD_RES 527
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 612
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35570"
FT MOD_RES 629
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 632
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35570"
FT MOD_RES 636
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 662
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 792
FT /note="Phosphoserine; by AMPK and SIK2"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 901
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 905
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35570"
FT MOD_RES 950
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 998
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35570"
FT MOD_RES 1109
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35569"
FT MOD_RES 1110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35568"
FT MOD_RES 1188
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35570"
FT MOD_RES 1238
FT /note="Phosphotyrosine; by INSR"
FT /evidence="ECO:0000250|UniProtKB:P35570"
SQ SEQUENCE 1251 AA; 133054 MW; 924CCAC3BE68EB98 CRC64;
MASPPESDGF SDVRKVGYLR KPKSMHKRFF VLRAASETGD PARLEYYENE KKWRHKSSAP
KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE AEQDSWYQAL LQLHNRAKGH
HDGAAALGAG GGGGSCSGSS GLGEAGEDLS YGDVPPGPAF KEVWQVILKP KGLGQTKNLI
GIYRLCLTSK TISFVKLNSE AAAVVLQLMN IRRCGHSENF FFIEVGRSAV TGPGEFWMQV
DDSVVAQNMH ETILEAMRAM SDEFRPRSKS QSSSNCSNPI SVPLRRHHLN NPPPSQVGLT
RRSRTESITA TSPASMVGGK PGSFRVRASS DGEGTMSRPA SVDGSPVSPS TNRTHAHRHR
GSARLHPPLN HSRSIPMPAS RCSPSATSPV SLSSSSTSGH GSTSDCLFPR RSSASVSGSP
SDGGFISSDE YGSSPCDFRS SFRSVTPDSL GHTPPARGEE ELSNYICMGG KGPSTLTAPN
GHYILSRGGN GHRYTPGTGL GTSPALAGDE ASSAADLDNR FRKRTHSAGT SPTITHQKTP
SQSSVASIEE YTEMMPAYPP GGGSGGRLPG HRHSAFVPTH SYPEEGLEMH PLERRGGHHR
PDSSTLHTDD GYMPMSPGVA PVPSSRKGSG DYMPMSPKSV SAPQQIINPI RRHPQRVDPN
GYMMMSPSGG CSPDIGGGPS SSSSSTVPSG SSYGKLWTKG VGAHNSQVLL HPKPPVESSG
GKLLPCTGDY MNMSPVGDSN TSSPSDCYYG PEDPQHKPVL SYYSLPRSFK HTQRPGEPEE
GARHQHLRLS TSSGRLLYAA TADDSSSSTS SDSLGGGYCG ARLEPSLPHP HHQVLQPHLP
RKVDTAAQTN SRLARPTRLS LGDPKASTLP RAREQQQQQQ QQQQQQQQQQ QPLLHPPEPK
SPGEYVNIEF GSDQPGYLSG PVASRSSPSV RCPSQLQPAP REEETGTEEY MKMDLGPGRR
AAWQESTGVE MGRLGPAPPG AASICRPTRA VPSSRGDYMT MQMSCPRQSY VDTSPIAPVS
YADMRTGIAA EEVSLPRATM AAAASSSAAS ASPTGPQGAA ELAAHSSLLG GAQGPGGMSA
FTRVNLSPNR NQSAKVIRAD PQGCRRRHSS ETFSSTPSAT RVGNTVPFGA GAAIGGSGGS
SSSSEDVKRH SSASFENVWL RPGELGGAPK EPAQLCGAAG GLENGLNYID LDLVKDFKQR
PQECTPQPQP PPPPPPHQPL GSSESSSTRR SSEDLSAYAS ISFQKQPEDL Q
