##gff-version 3 P19525 UniProtKB Initiator methionine 1 1 . . . Note=Removed;Ontology_term=ECO:0000269,ECO:0007744,ECO:0007744;evidence=ECO:0000269|Ref.13,ECO:0007744|PubMed:22223895,ECO:0007744|PubMed:22814378;Dbxref=PMID:22223895,PMID:22814378 P19525 UniProtKB Chain 2 551 . . . ID=PRO_0000085945;Note=Interferon-induced%2C double-stranded RNA-activated protein kinase P19525 UniProtKB Domain 9 77 . . . Note=DRBM 1;Ontology_term=ECO:0000255,ECO:0000269;evidence=ECO:0000255|PROSITE-ProRule:PRU00266,ECO:0000269|PubMed:9736623;Dbxref=PMID:9736623 P19525 UniProtKB Domain 100 167 . . . Note=DRBM 2;Ontology_term=ECO:0000255,ECO:0000269;evidence=ECO:0000255|PROSITE-ProRule:PRU00266,ECO:0000269|PubMed:9736623;Dbxref=PMID:9736623 P19525 UniProtKB Domain 267 538 . . . Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 P19525 UniProtKB Repeat 331 343 . . . Note=1 P19525 UniProtKB Repeat 345 357 . . . Note=2 P19525 UniProtKB Region 2 180 . . . Note=(Microbial infection) Interaction with HCV NS5A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17267064;Dbxref=PMID:17267064 P19525 UniProtKB Region 202 222 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P19525 UniProtKB Region 266 551 . . . Note=Interaction with TRAF5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15121867;Dbxref=PMID:15121867 P19525 UniProtKB Region 266 362 . . . Note=Dimerization;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16179258;Dbxref=PMID:16179258 P19525 UniProtKB Region 331 357 . . . Note=2 X 13 AA approximate repeats P19525 UniProtKB Region 379 496 . . . Note=Interaction with EIF2S1/EIF-2ALPHA;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16179258;Dbxref=PMID:16179258 P19525 UniProtKB Active site 414 414 . . . Note=Proton acceptor;Ontology_term=ECO:0000255,ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159,ECO:0000255|PROSITE-ProRule:PRU10027 P19525 UniProtKB Binding site 273 281 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 P19525 UniProtKB Binding site 296 296 . . . . P19525 UniProtKB Binding site 432 432 . . . Ontology_term=ECO:0000305,ECO:0000305;evidence=ECO:0000305|PubMed:16179258,ECO:0000305|PubMed:31246429;Dbxref=PMID:16179258,PMID:31246429 P19525 UniProtKB Modified residue 2 2 . . . Note=N-acetylalanine;Ontology_term=ECO:0000269,ECO:0007744,ECO:0007744;evidence=ECO:0000269|Ref.13,ECO:0007744|PubMed:22223895,ECO:0007744|PubMed:22814378;Dbxref=PMID:22223895,PMID:22814378 P19525 UniProtKB Modified residue 83 83 . . . Note=Phosphoserine;Ontology_term=ECO:0000269,ECO:0007744,ECO:0007744,ECO:0007744;evidence=ECO:0000269|PubMed:11152499,ECO:0007744|PubMed:18669648,ECO:0007744|PubMed:19690332,ECO:0007744|PubMed:20068231;Dbxref=PMID:11152499,PMID:18669648,PMID:19690332,PMID:20068231 P19525 UniProtKB Modified residue 88 88 . . . Note=Phosphothreonine%3B by autocatalysis;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Modified residue 89 89 . . . Note=Phosphothreonine%3B by autocatalysis;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Modified residue 90 90 . . . Note=Phosphothreonine%3B by autocatalysis;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Modified residue 101 101 . . . Note=Phosphotyrosine%3B by autocatalysis;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16373505;Dbxref=PMID:16373505 P19525 UniProtKB Modified residue 162 162 . . . Note=Phosphotyrosine%3B by autocatalysis;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16373505;Dbxref=PMID:16373505 P19525 UniProtKB Modified residue 242 242 . . . Note=Phosphoserine%3B by autocatalysis;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Modified residue 255 255 . . . Note=Phosphothreonine%3B by autocatalysis;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Modified residue 258 258 . . . Note=Phosphothreonine%3B by autocatalysis;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Modified residue 293 293 . . . Note=Phosphotyrosine%3B by autocatalysis;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16373505;Dbxref=PMID:16373505 P19525 UniProtKB Modified residue 446 446 . . . Note=Phosphothreonine%3B by autocatalysis;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11337501,ECO:0000269|PubMed:16179258;Dbxref=PMID:11337501,PMID:16179258 P19525 UniProtKB Modified residue 451 451 . . . Note=Phosphothreonine%3B by autocatalysis;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11337501,ECO:0000269|PubMed:20685959;Dbxref=PMID:11337501,PMID:20685959 P19525 UniProtKB Modified residue 456 456 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:18669648;Dbxref=PMID:18669648 P19525 UniProtKB Modified residue 542 542 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:23186163;Dbxref=PMID:23186163 P19525 UniProtKB Cross-link 69 69 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23229543;Dbxref=PMID:23229543 P19525 UniProtKB Cross-link 159 159 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23229543;Dbxref=PMID:23229543 P19525 UniProtKB Alternative sequence 263 303 . . . ID=VSP_046177;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303|Ref.7 P19525 UniProtKB Natural variant 11 11 . . . ID=VAR_084260;Note=In LEUDEN%3B uncertain significance%3B reduced phosphorylation of eukaryotic translation initiation factor 2-alpha in patient cells. M->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 32 32 . . . ID=VAR_084261;Note=In LEUDEN%3B uncertain significance. N->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 32 32 . . . ID=VAR_086715;Note=In DYT33%3B uncertain significance%3B gain-of-function variant resulting in increased levels of phosphorylated EIF2AK2 and EIF2A in patient cells compared to controls. N->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:33236446;Dbxref=PMID:33236446 P19525 UniProtKB Natural variant 97 97 . . . ID=VAR_084262;Note=In LEUDEN%3B uncertain significance. S->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 109 109 . . . ID=VAR_084263;Note=In LEUDEN%3B uncertain significance. A->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 109 109 . . . ID=VAR_084264;Note=In LEUDEN%3B uncertain significance. A->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 114 114 . . . ID=VAR_084265;Note=Found in a patient with dysmorphic facies%2C syndactyly%2C congenital microcephaly and global developmental delay%3B uncertain significance. L->Q;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 130 130 . . . ID=VAR_086716;Note=In DYT33%3B gain-of-function variant resulting in increased levels of phosphorylated EIF2AK2 and EIF2A in patient cells compared to controls. G->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:33236446,ECO:0000269|PubMed:33866603,ECO:0000269|PubMed:35146068;Dbxref=PMID:33236446,PMID:33866603,PMID:35146068 P19525 UniProtKB Natural variant 133 133 . . . ID=VAR_084266;Note=In LEUDEN%3B uncertain significance%3B reduced phosphorylation of eukaryotic translation initiation factor 2-alpha in patient cells. Y->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 138 138 . . . ID=VAR_086717;Note=In DYT33%3B uncertain significance. G->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:33236446;Dbxref=PMID:33236446 P19525 UniProtKB Natural variant 325 325 . . . ID=VAR_084267;Note=In LEUDEN%3B uncertain significance. G->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 428 428 . . . ID=VAR_040474;Note=V->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17344846;Dbxref=dbSNP:rs56219559,PMID:17344846 P19525 UniProtKB Natural variant 439 439 . . . ID=VAR_040475;Note=In a lung adenocarcinoma sample%3B somatic mutation. L->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17344846;Dbxref=PMID:17344846 P19525 UniProtKB Natural variant 461 461 . . . ID=VAR_084268;Note=In LEUDEN%3B uncertain significance%3B reduced phosphorylation of eukaryotic translation initiation factor 2-alpha in patient cells. S->C;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:32197074;Dbxref=PMID:32197074 P19525 UniProtKB Natural variant 506 506 . . . ID=VAR_040476;Note=I->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17344846;Dbxref=dbSNP:rs34821155,PMID:17344846 P19525 UniProtKB Mutagenesis 59 60 . . . Note=In FL-PKR-2AI%3B moderate loss of activity but no effect on dsRNA binding. SK->AA;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11337501;Dbxref=PMID:11337501 P19525 UniProtKB Mutagenesis 60 60 . . . Note=Impairs dsRNA binding but not dimerization or activity. K->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11337501;Dbxref=PMID:11337501 P19525 UniProtKB Mutagenesis 67 67 . . . Note=Significant loss of activity%3B loss of dsRNA binding and dimerization. A->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11337501;Dbxref=PMID:11337501 P19525 UniProtKB Mutagenesis 83 83 . . . Note=No effect on enzymatic activity%3B when associated with A-88%3B A-89 and A-90. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 88 88 . . . Note=No effect on enzymatic activity%3B when associated with A-83%3B A-89 and A-90. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 89 89 . . . Note=No effect on enzymatic activity%3B when associated with A-83%3B A-88 and A-90. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 90 90 . . . Note=No effect on enzymatic activity%3B when associated with A-83%3B A-88 and A-89. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 149 150 . . . Note=In FL-PKR-2AII%3B no effect on activity. TK->AA;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11337501;Dbxref=PMID:11337501 P19525 UniProtKB Mutagenesis 242 242 . . . Note=Moderate loss of activity%3B when associated with A-255 and A-258. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 244 296 . . . Note=Loss of activity. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11337501;Dbxref=PMID:11337501 P19525 UniProtKB Mutagenesis 255 255 . . . Note=Moderate loss of activity%3B when associated with A-242 and A-255. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 258 258 . . . Note=Moderate loss of activity. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 296 296 . . . Note=Loss of activity. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11152499;Dbxref=PMID:11152499 P19525 UniProtKB Mutagenesis 446 446 . . . Note=Significant loss of activity and impairs autophosphorylation of T-451. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11337501;Dbxref=PMID:11337501 P19525 UniProtKB Mutagenesis 451 451 . . . Note=Loss of activity. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11337501;Dbxref=PMID:11337501 P19525 UniProtKB Mutagenesis 486 486 . . . Note=15-fold decrease in K3L binding affinity and thus resistance of mutated PKR to K3L inhibition. D->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18971339;Dbxref=PMID:18971339 P19525 UniProtKB Mutagenesis 489 489 . . . Note=Loss of PKR inhibition by HCMV protein TRS1. F->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27780231;Dbxref=PMID:27780231 P19525 UniProtKB Mutagenesis 496 496 . . . Note=No effect on PKR inhibition by HCMV protein TRS1. T->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27780231;Dbxref=PMID:27780231 P19525 UniProtKB Mutagenesis 502 502 . . . Note=No effect on PKR inhibition by HCMV protein TRS1. I->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27780231;Dbxref=PMID:27780231 P19525 UniProtKB Mutagenesis 506 506 . . . Note=No effect on PKR inhibition by HCMV protein TRS1. I->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27780231;Dbxref=PMID:27780231 P19525 UniProtKB Mutagenesis 510 510 . . . Note=No effect on PKR inhibition by HCMV protein TRS1. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27780231;Dbxref=PMID:27780231 P19525 UniProtKB Mutagenesis 516 516 . . . Note=No effect on PKR inhibition by HCMV protein TRS1. Q->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27780231;Dbxref=PMID:27780231 P19525 UniProtKB Sequence conflict 102 102 . . . Note=I->M;Ontology_term=ECO:0000305;evidence=ECO:0000305 P19525 UniProtKB Sequence conflict 224 224 . . . Note=S->R;Ontology_term=ECO:0000305;evidence=ECO:0000305 P19525 UniProtKB Sequence conflict 512 512 . . . Note=K->E;Ontology_term=ECO:0000305;evidence=ECO:0000305 P19525 UniProtKB Beta strand 5 7 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Helix 10 21 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Beta strand 26 32 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Turn 35 37 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Beta strand 41 50 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Beta strand 54 56 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Helix 61 76 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Helix 102 111 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Beta strand 115 123 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Beta strand 125 138 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Beta strand 144 149 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Helix 150 167 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1QU6 P19525 UniProtKB Helix 261 266 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 267 274 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 276 278 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 281 286 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Turn 287 289 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 292 299 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 303 305 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 306 314 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 323 332 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 358 366 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 374 380 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 381 383 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 388 407 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 410 412 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A1A P19525 UniProtKB Helix 417 419 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 420 424 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 427 430 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 433 435 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6D3L P19525 UniProtKB Beta strand 437 440 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 457 461 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 468 482 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 488 499 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Beta strand 505 507 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3UIU P19525 UniProtKB Helix 509 518 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 523 525 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19 P19525 UniProtKB Helix 529 539 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2A19