{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P33076","secondaryAccessions":["A0A0B4J1S1","A0N0N9","D3DUG0","E9PFE0","Q29675","Q8SNB8","Q96KL4"],"uniProtkbId":"C2TA_HUMAN","entryAudit":{"firstPublicDate":"1993-10-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2025-06-18","entryVersion":221,"sequenceVersion":4},"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":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"MHC class II transactivator"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"CIITA"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11172716"}],"value":"2.3.1.-"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24036077"}],"value":"2.7.11.1"}]}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:7067"}],"value":"CIITA"},"synonyms":[{"value":"MHC2TA"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11172716"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16600381"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17493635"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24036077"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32855215"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40608405"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7749984"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8402893"}],"value":"Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter (PubMed:16600381, PubMed:17493635, PubMed:7749984, PubMed:8402893, PubMed:40608405). Does not bind DNA (PubMed:16600381, PubMed:17493635, PubMed:7749984, PubMed:8402893). May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both PubMed:8402893, PubMed:7749984, (PubMed:16600381, PubMed:17493635). Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter (PubMed:16600381, PubMed:17493635, PubMed:7749984, PubMed:8402893). Also mediates enhanced MHC class I transcription; the promoter element requirements for CIITA-mediated transcription are distinct from those of constitutive MHC class I transcription, and CIITA can functionally replace TAF1 at these genes. Activates CD74 transcription (PubMed:32855215). Exhibits intrinsic GTP-stimulated acetyltransferase activity (PubMed:11172716). Exhibits serine/threonine protein kinase activity: can phosphorylate the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF, histone H2B at 'Ser-37' and other histones (in vitro) (PubMed:24036077). Has antiviral activity against Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Induces resistance by up-regulation of the p41 isoform of CD74, which blocks cathepsin-mediated cleavage of viral glycoproteins, thereby preventing viral fusion (PubMed:32855215)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12919287"}],"value":"Exhibits dominant-negative suppression of MHC class II gene expression"}],"commentType":"FUNCTION","molecule":"Isoform 3"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:17989"},{"database":"Rhea","id":"RHEA-COMP:9863"},{"database":"Rhea","id":"RHEA-COMP:11604"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29999"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:83421"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24036077"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:46608"},{"database":"Rhea","id":"RHEA-COMP:11060"},{"database":"Rhea","id":"RHEA-COMP:11605"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30013"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:61977"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24036077"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17493635"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20937824"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23007646"}],"value":"Interacts with ZXDA and ZXDC (PubMed:17493635). Interacts with PML (isoform PML-2) (PubMed:23007646). Interacts with TAF7; interaction inhibits CIITA acetyltransferase activity, thereby repressing transcription (PubMed:20937824)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40608405"}],"value":"(Microbial infection) Interacts with human cytomegalovirus protein US28; this interaction decreases host HLA class II expression"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P33076","intActId":"EBI-1538819"},"interactantTwo":{"uniProtKBAccession":"P48382","geneName":"RFX5","intActId":"EBI-923266"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P33076","intActId":"EBI-1538819"},"interactantTwo":{"uniProtKBAccession":"Q96EB6","geneName":"SIRT1","intActId":"EBI-1802965"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P33076","intActId":"EBI-1538819"},"interactantTwo":{"uniProtKBAccession":"P98168","geneName":"ZXDA","intActId":"EBI-1538980"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P33076","intActId":"EBI-1538819"},"interactantTwo":{"uniProtKBAccession":"Q2QGD7","geneName":"ZXDC","intActId":"EBI-1538838"},"numberOfExperiments":6,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23007646"}],"value":"Recruited to PML body by PML"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11172716"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23007646"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23007646"}],"value":"Nucleus, PML body","id":"SL-0465"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P33076-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P33076-2"],"sequenceIds":["VSP_055099","VSP_055102","VSP_055103"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"hCIITA'"}],"isoformIds":["P33076-3"],"sequenceIds":["VSP_055099","VSP_055100","VSP_055101"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["P33076-4"],"sequenceIds":["VSP_055102","VSP_055103"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11172716"}],"value":"The acetyltransferase domain is necessary for activation of both class I and class II transcription"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11172716"}],"value":"The GTP-binding motif doesn't confer GTPase activity but promotes nuclear localization"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24036077"}],"value":"Autophosphorylated, affecting interaction with TAF7"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"MHC class II deficiency 1","diseaseAccession":"DI-00171","acronym":"MHC2D1","description":"An autosomal recessive immunologic disorder characterized by the loss of expression of MHC class II antigens on antigen-presenting cells. Affected individuals present in early infancy with severe recurrent bacterial, viral, fungal and parasitic infections, usually affecting the gastrointestinal and respiratory tracts.","diseaseCrossReference":{"database":"MIM","id":"209920"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10501838"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11466404"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11862382"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7749984"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8402893"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"WEB RESOURCE","resourceName":"CIITAbase","resourceUrl":"https://databases.lovd.nl/shared/genes/CIITA","ftp":false,"note":"CIITA mutation db"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and 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