##gff-version 3 P35568 UniProtKB Chain 1 1242 . . . ID=PRO_0000084236;Note=Insulin receptor substrate 1 P35568 UniProtKB Domain 12 115 . . . Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00145 P35568 UniProtKB Domain 160 264 . . . Note=IRS-type PTB;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00389 P35568 UniProtKB Region 3 137 . . . Note=Mediates interaction with PHIP;Ontology_term=ECO:0000250;evidence=ECO:0000250 P35568 UniProtKB Region 262 430 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Region 592 616 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Region 668 693 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Region 771 900 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Region 896 898 . . . Note=GRB2-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250 P35568 UniProtKB Region 918 937 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Region 1057 1146 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Region 1190 1242 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Motif 465 468 . . . Note=YXXM motif 1 P35568 UniProtKB Motif 551 554 . . . Note=YXXM motif 2 P35568 UniProtKB Motif 612 615 . . . Note=YXXM motif 3 P35568 UniProtKB Motif 632 635 . . . Note=YXXM motif 4 P35568 UniProtKB Motif 662 665 . . . Note=YXXM motif 5 P35568 UniProtKB Motif 732 735 . . . Note=YXXM motif 6 P35568 UniProtKB Motif 941 944 . . . Note=YXXM motif 7 P35568 UniProtKB Motif 989 992 . . . Note=YXXM motif 8 P35568 UniProtKB Motif 1012 1015 . . . Note=YXXM motif 9 P35568 UniProtKB Compositional bias 266 281 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 293 316 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 376 430 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 592 606 . . . Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 675 693 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 774 788 . . . Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 789 817 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 1071 1087 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 1099 1114 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 1195 1211 . . . Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Compositional bias 1212 1236 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P35568 UniProtKB Modified residue 3 3 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Modified residue 99 99 . . . Note=Phosphoserine%3B by CK2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Modified residue 270 270 . . . Note=Phosphoserine%3B by RPS6KB1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18952604;Dbxref=PMID:18952604 P35568 UniProtKB Modified residue 307 307 . . . Note=Phosphoserine%3B by RPS6KB1;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:18498745,ECO:0000269|PubMed:18952604;Dbxref=PMID:18498745,PMID:18952604 P35568 UniProtKB Modified residue 312 312 . . . Note=Phosphoserine%3B by IKKB%2C MAPK8 and RPS6KB1;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:18498745,ECO:0000269|PubMed:20685959;Dbxref=PMID:18498745,PMID:20685959 P35568 UniProtKB Modified residue 323 323 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:24275569;Dbxref=PMID:24275569 P35568 UniProtKB Modified residue 330 330 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35569 P35568 UniProtKB Modified residue 345 345 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35569 P35568 UniProtKB Modified residue 348 348 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:19690332;Dbxref=PMID:19690332 P35568 UniProtKB Modified residue 419 419 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35569 P35568 UniProtKB Modified residue 446 446 . . . Note=Phosphothreonine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Modified residue 453 453 . . . Note=Phosphothreonine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:24275569;Dbxref=PMID:24275569 P35568 UniProtKB Modified residue 465 465 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Modified residue 527 527 . . . Note=Phosphoserine%3B by RPS6KB1;Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:18498745,ECO:0007744|PubMed:24275569;Dbxref=PMID:18498745,PMID:24275569 P35568 UniProtKB Modified residue 612 612 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:23401856,ECO:0000269|PubMed:30092354;Dbxref=PMID:23401856,PMID:30092354 P35568 UniProtKB Modified residue 616 616 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Modified residue 629 629 . . . Note=Phosphoserine;Ontology_term=ECO:0007744,ECO:0007744;evidence=ECO:0007744|PubMed:17081983,ECO:0007744|PubMed:24275569;Dbxref=PMID:17081983,PMID:24275569 P35568 UniProtKB Modified residue 632 632 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23401856;Dbxref=PMID:23401856 P35568 UniProtKB Modified residue 636 636 . . . Note=Phosphoserine%3B by RPS6KB1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:18498745,ECO:0000269|PubMed:18952604,ECO:0007744|PubMed:17081983;Dbxref=PMID:17081983,PMID:18498745,PMID:18952604 P35568 UniProtKB Modified residue 662 662 . . . Note=Phosphotyrosine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:15592455;Dbxref=PMID:15592455 P35568 UniProtKB Modified residue 794 794 . . . Note=Phosphoserine%3B by AMPK and SIK2;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12624099;Dbxref=PMID:12624099 P35568 UniProtKB Modified residue 892 892 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35569 P35568 UniProtKB Modified residue 896 896 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23401856;Dbxref=PMID:23401856 P35568 UniProtKB Modified residue 941 941 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20685959;Dbxref=PMID:20685959 P35568 UniProtKB Modified residue 989 989 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Modified residue 1100 1100 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35569 P35568 UniProtKB Modified residue 1101 1101 . . . Note=Phosphoserine%3B by RPS6KB1 and PKC/PRKCQ;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15364919,ECO:0000269|PubMed:18952604;Dbxref=PMID:15364919,PMID:18952604 P35568 UniProtKB Modified residue 1179 1179 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Modified residue 1229 1229 . . . Note=Phosphotyrosine%3B by INSR;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P35570 P35568 UniProtKB Natural variant 158 158 . . . ID=VAR_014853;Note=P->R;Dbxref=dbSNP:rs1801108 P35568 UniProtKB Natural variant 209 209 . . . ID=VAR_014854;Note=M->T;Dbxref=dbSNP:rs1801118 P35568 UniProtKB Natural variant 512 512 . . . ID=VAR_005299;Note=A->P;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8104271;Dbxref=dbSNP:rs1801276,PMID:8104271 P35568 UniProtKB Natural variant 608 608 . . . ID=VAR_025320;Note=May contribute to insulin resistance by impairing metabolic signaling through PI3K-dependent pathways. T->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12679424;Dbxref=dbSNP:rs104893642,PMID:12679424 P35568 UniProtKB Natural variant 723 723 . . . ID=VAR_005301;Note=In T2D. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8723689;Dbxref=dbSNP:rs1259467443,PMID:8723689 P35568 UniProtKB Natural variant 809 809 . . . ID=VAR_014855;Note=S->F;Dbxref=dbSNP:rs1801120 P35568 UniProtKB Natural variant 892 892 . . . ID=VAR_014856;Note=S->G;Dbxref=dbSNP:rs1801277 P35568 UniProtKB Natural variant 971 971 . . . ID=VAR_005300;Note=G->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10843189,ECO:0000269|PubMed:14671192,ECO:0000269|PubMed:14707024,ECO:0000269|PubMed:15590636,ECO:0000269|PubMed:8104271;Dbxref=dbSNP:rs1801278,PMID:10843189,PMID:14671192,PMID:14707024,PMID:15590636,PMID:8104271 P35568 UniProtKB Natural variant 1043 1043 . . . ID=VAR_005302;Note=In T2D. S->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10206679;Dbxref=PMID:10206679 P35568 UniProtKB Natural variant 1095 1095 . . . ID=VAR_005303;Note=In T2D. C->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10206679;Dbxref=PMID:10206679 P35568 UniProtKB Natural variant 1137 1137 . . . ID=VAR_021837;Note=D->N;Dbxref=dbSNP:rs3731594 P35568 UniProtKB Mutagenesis 307 307 . . . Note=Impaired degradation by the Cul7-RING(FBXW8) complex%3B when associated with A-312%3B A-527%3B A-636 and A-639. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18498745;Dbxref=PMID:18498745 P35568 UniProtKB Mutagenesis 312 312 . . . Note=Impaired degradation by the Cul7-RING(FBXW8) complex%3B when associated with A-307%3B A-527%3B A-636 and A-639. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18498745;Dbxref=PMID:18498745 P35568 UniProtKB Mutagenesis 527 527 . . . Note=Impaired degradation by the Cul7-RING(FBXW8) complex%3B when associated with A-307%3B A-312%3B A-636 and A-639. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18498745;Dbxref=PMID:18498745 P35568 UniProtKB Mutagenesis 612 612 . . . Note=Induces IRS1 degradation. Y->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23401856;Dbxref=PMID:23401856 P35568 UniProtKB Mutagenesis 632 632 . . . Note=Does not affect IRS1 stability. Y->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23401856;Dbxref=PMID:23401856 P35568 UniProtKB Mutagenesis 636 636 . . . Note=Impaired degradation by the Cul7-RING(FBXW8) complex%3B when associated with A-307%3B A-312%3B A-527 and A-639. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18498745;Dbxref=PMID:18498745 P35568 UniProtKB Mutagenesis 639 639 . . . Note=Impaired degradation by the Cul7-RING(FBXW8) complex%3B when associated with A-307%3B A-312%3B A-527 and A-636. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18498745;Dbxref=PMID:18498745 P35568 UniProtKB Mutagenesis 794 794 . . . Note=Loss of phosphorylation by SIK2. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12624099;Dbxref=PMID:12624099 P35568 UniProtKB Sequence conflict 134 134 . . . Note=G->GG;Ontology_term=ECO:0000305;evidence=ECO:0000305 P35568 UniProtKB Sequence conflict 362 362 . . . Note=S->R;Ontology_term=ECO:0000305;evidence=ECO:0000305 P35568 UniProtKB Sequence conflict 384 384 . . . Note=P->R;Ontology_term=ECO:0000305;evidence=ECO:0000305 P35568 UniProtKB Beta strand 13 20 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Turn 22 24 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Beta strand 27 33 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Turn 37 39 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Beta strand 40 49 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Helix 50 54 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Beta strand 61 65 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Helix 66 68 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Beta strand 69 75 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Beta strand 81 90 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Beta strand 92 96 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Helix 100 113 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QQG P35568 UniProtKB Beta strand 162 172 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Helix 173 176 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Beta strand 181 187 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Beta strand 189 196 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Beta strand 203 207 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Helix 208 210 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Beta strand 211 217 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Beta strand 220 225 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Beta strand 233 239 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Helix 243 262 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5U1M P35568 UniProtKB Beta strand 897 901 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1K3A