##gff-version 3 Q60855 UniProtKB Chain 1 656 . . . ID=PRO_0000086607;Note=Receptor-interacting serine/threonine-protein kinase 1 Q60855 UniProtKB Domain 17 290 . . . Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 Q60855 UniProtKB Domain 568 654 . . . Note=Death;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00064 Q60855 UniProtKB Region 291 567 . . . Note=Interaction with SQSTM1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q13546 Q60855 UniProtKB Region 327 373 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q60855 UniProtKB Region 388 423 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q60855 UniProtKB Motif 520 536 . . . Note=RIP homotypic interaction motif (RHIM);Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:18442983,ECO:0000269|PubMed:27819681,ECO:0000269|PubMed:27819682;Dbxref=PMID:18442983,PMID:27819681,PMID:27819682 Q60855 UniProtKB Compositional bias 328 368 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q60855 UniProtKB Compositional bias 401 423 . . . Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q60855 UniProtKB Active site 138 138 . . . Note=Proton acceptor;Ontology_term=ECO:0000255,ECO:0000255,ECO:0000269,ECO:0000269;evidence=ECO:0000255|PROSITE-ProRule:PRU00159,ECO:0000255|PROSITE-ProRule:PRU10027,ECO:0000269|PubMed:24557836,ECO:0000269|PubMed:31827280;Dbxref=PMID:24557836,PMID:31827280 Q60855 UniProtKB Binding site 23 31 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 Q60855 UniProtKB Binding site 45 45 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 Q60855 UniProtKB Site 325 326 . . . Note=Cleavage%3B by CASP8;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:31511692,ECO:0000269|PubMed:31827280,ECO:0000269|PubMed:31827281;Dbxref=PMID:31511692,PMID:31827280,PMID:31827281 Q60855 UniProtKB Modified residue 6 6 . . . Note=Phosphoserine%3B by IKKA and IKKB;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Modified residue 25 25 . . . Note=Phosphoserine%3B by IKKA and IKKB;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Modified residue 161 161 . . . Note=Phosphoserine%3B by RIPK3 and autocatalysis;Ontology_term=ECO:0000255;evidence=ECO:0000255 Q60855 UniProtKB Modified residue 166 166 . . . Note=Phosphoserine%3B by autocatalysis;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:27819682,ECO:0000269|PubMed:28701375,ECO:0000269|PubMed:29440439,ECO:0000269|PubMed:30988283,ECO:0000269|PubMed:31519886,ECO:0000269|PubMed:31519887;Dbxref=PMID:27819682,PMID:28701375,PMID:29440439,PMID:30988283,PMID:31519886,PMID:31519887 Q60855 UniProtKB Modified residue 169 169 . . . Note=Phosphothreonine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Modified residue 304 304 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q13546 Q60855 UniProtKB Modified residue 313 313 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:21183079;Dbxref=PMID:21183079 Q60855 UniProtKB Modified residue 321 321 . . . Note=Phosphoserine%3B by MAP3K7;Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:28842570,ECO:0007744|PubMed:21183079;Dbxref=PMID:21183079,PMID:28842570 Q60855 UniProtKB Modified residue 332 332 . . . Note=Phosphoserine%3B by MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Modified residue 334 334 . . . Note=Phosphoserine%3B by MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Modified residue 383 383 . . . Note=Phosphotyrosine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q13546 Q60855 UniProtKB Cross-link 376 376 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:31519886,ECO:0000269|PubMed:31519887;Dbxref=PMID:31519886,PMID:31519887 Q60855 UniProtKB Mutagenesis 6 6 . . . Note=Loss of phosphorylation. Does not protect cells from TNF-induced cell death. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Mutagenesis 6 6 . . . Note=Phophomimetic mutant. Does not protect cells from TNF-induced cell death. S->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Mutagenesis 25 25 . . . Note=Loss of phosphorylation. Does not protect cells from TNF-induced cell death. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Mutagenesis 25 25 . . . Note=Phophomimetic mutant. Significant loss of kinase activity. Protects cells from TNF-induced cell death. S->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Mutagenesis 45 45 . . . Note=Loss of kinase activity. Protects cells from TNF-induced cell death. K->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30988283;Dbxref=PMID:30988283 Q60855 UniProtKB Mutagenesis 45 45 . . . Note=Loss of kinase activity. K->M;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29440439;Dbxref=PMID:29440439 Q60855 UniProtKB Mutagenesis 138 138 . . . Note=Abolished protein kinase activity and ability to regulate apoptosis and necroptosis. Knockin mice are viable. D->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24557836;Dbxref=PMID:24557836 Q60855 UniProtKB Mutagenesis 138 138 . . . Note=Loss of kinase activity. D->N;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:29440439,ECO:0000269|PubMed:31511692,ECO:0000269|PubMed:31827280,ECO:0000269|PubMed:31827281;Dbxref=PMID:29440439,PMID:31511692,PMID:31827280,PMID:31827281 Q60855 UniProtKB Mutagenesis 321 321 . . . Note=Loss of phosphorylation. Promotes activation of its kinase activity%2C proteolytic cleavage%2C ubiquitination and interaction with FADD to mediate apoptosis. Loss of phosphorylation at Ser-332 and Ser-334%3B when associated with A-332%3B A-334 and A-336. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 321 321 . . . Note=Inhibits its proteolytic cleavage and interaction with FADD. Promotes its interaction with RIPK3 to mediate necroptosis%3B when associated with E-332%3B E-334 and E-336. S->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 325 325 . . . Note=Loss of CASP8-mediated cleavage. Promotes both FADD-dependent apoptosis and RIPK3-dependent necroptosis%2C thus leading to embryonic lethality at midgestation stages in knockin mice. Heterozygous knockin mice are viable and grossly normal%2C but are hyperresponsive to inflammatory stimuli. D->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:30867408,ECO:0000269|PubMed:31511692,ECO:0000269|PubMed:31827281;Dbxref=PMID:30867408,PMID:31511692,PMID:31827281 Q60855 UniProtKB Mutagenesis 325 325 . . . Note=Loss of CASP8-mediated cleavage. Embryonic lethality in knockin mice. Promotes activation of the protein kinase activity%2C leading to increased cell death. D->V%2CH;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:31827280;Dbxref=PMID:31827280 Q60855 UniProtKB Mutagenesis 332 332 . . . Note=Loss of phosphorylation at Ser-332 and Ser-334%3B when associated with A-321%3B A-334 and A-336. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 332 332 . . . Note=Promotes its interaction with RIPK3 to mediate necroptosis%3B when associated with E-321%3B E-334 and E-336. S->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 334 334 . . . Note=Loss of phosphorylation at Ser-332 and Ser-334%3B when associated with A-321%3B A-332 and A-336. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 334 334 . . . Note=Promotes its interaction with RIPK3 to mediate necroptosis%3B when associated with E-321%3B E-332 and E-336. S->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 336 336 . . . Note=Loss of phosphorylation at Ser-332 and Ser-334%3B when associated with A-321%3B A-332 and A-334. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 336 336 . . . Note=Promotes its interaction with RIPK3 to mediate necroptosis%3B when associated with E-321%3B E-332 and E-334. S->E;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28842570;Dbxref=PMID:28842570 Q60855 UniProtKB Mutagenesis 376 376 . . . Note=Loss of ubiquitination. Decreases TNF-alpha-mediated NF-kappaB activation. Increases interaction with CFLAR%2C CASP8%2C FADD and RIPK3. Decreases interaction with MAP3K7. Enhances kinase activity and promotes apoptosis and necroptosis. Knockin mice display early embryonic lethality resulting from excessive cell death and severe inflammation. K->R;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:31519886,ECO:0000269|PubMed:31519887;Dbxref=PMID:31519886,PMID:31519887 Q60855 UniProtKB Mutagenesis 529 531 . . . Note=In RIPK1(mRHIM)%3B perinatal lethality in knockin mice caused by Ripk3- and Zbp1-dependent necroptosis. Lethality is prevented by Ripk3%2C Mlkl or Zbp1 deficiency. Knockin mice do not show defects caused by Casp8-dependent apoptosis observed in knockout mice. QIG->AAA;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:27819681,ECO:0000269|PubMed:27819682;Dbxref=PMID:27819681,PMID:27819682 Q60855 UniProtKB Mutagenesis 584 584 . . . Note=Blocks homodimerization%2C activation of its kinase activity%2C formation of complex IIa%2C necroptosis and apoptosis. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29440439;Dbxref=PMID:29440439 Q60855 UniProtKB Sequence conflict 66 66 . . . Note=M->K;Ontology_term=ECO:0000305;evidence=ECO:0000305