{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O75569","secondaryAccessions":["A8K3I6","Q53G24","Q6X7T5","Q8NDK4"],"uniProtkbId":"PRKRA_HUMAN","entryAudit":{"firstPublicDate":"2006-02-21","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1998-11-01","entryVersion":214,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Interferon-inducible double-stranded RNA-dependent protein kinase activator A"}},"alternativeNames":[{"fullName":{"value":"PKR-associated protein X"}},{"fullName":{"value":"PKR-associating protein X"}},{"fullName":{"value":"Protein activator of the interferon-induced protein kinase"}},{"fullName":{"value":"Protein kinase, interferon-inducible double-stranded RNA-dependent activator"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:9438"}],"value":"PRKRA"},"synonyms":[{"value":"PACT"},{"value":"RAX"}],"orfNames":[{"value":"HSD-14"},{"value":"HSD14"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9WTX2"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10336432"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11238927"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16424907"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16982605"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17452327"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9687506"}],"value":"Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-dependent manner (By similarity). May function as regulator of gastric epithelial differentiation (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11238927"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16424907"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16982605"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17452327"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18096616"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18421256"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23870315"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9687506"}],"value":"Homodimer. Interacts with EIF2AK2/PKR through its DRBM domains. Interacts with DICER1, AGO2 and TARBP2. Also able to interact with dsRNA. Interacts with UBC9 (By similarity). Forms a complex with UBC9 and p53/TP53 (By similarity). Interacts with DUS2L (via DRBM domain). Interacts with RIGI"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21228243"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23870315"}],"value":"(Microbial infection) Interacts with ebolavirus protein VP35; this interaction inhibits the interaction between RIGI and PRKRA. In addition, this interaction disrupts the interaction between VP35 and the viral polymerase L. So the VP35-PRKRA interaction plays a critical role in determining the outcome of ebolavirus infection (PubMed:23870315). The interaction PRKRA-VP35 also prevents PRKRA binding to DICER1 and thus allows the virus to counteract host RNA silencing (PubMed:21228243)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29084250"}],"value":"(Microbial infection) Interacts with human herpesvirus 8 protein MTA/ORF57; this interaction inhibits stress granule 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Phosphorylation at Ser-246 appears to be a prerequisite for subsequent phosphorylation at Ser-287. Phosphorylation at Ser-246 and Ser-287 are necessary for activation of EIF2AK2/PKR under conditions of stress"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Dystonia 16","diseaseAccession":"DI-00420","acronym":"DYT16","description":"An early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. 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