{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P0DTC3","uniProtkbId":"AP3A_SARS2","entryAudit":{"firstPublicDate":"2020-04-22","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2020-04-22","entryVersion":30,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Severe acute respiratory syndrome coronavirus 2","commonName":"2019-nCoV","synonyms":["SARS-CoV-2"],"taxonId":2697049,"lineage":["Viruses","Riboviria","Orthornavirae","Pisuviricota","Pisoniviricetes","Nidovirales","Cornidovirineae","Coronaviridae","Orthocoronavirinae","Betacoronavirus","Sarbecovirus","Betacoronavirus pandemicum"]},"organismHosts":[{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606}],"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"ORF3a protein"},"shortNames":[{"value":"ORF3a"}]},"alternativeNames":[{"fullName":{"value":"Accessory protein 3a"}},{"fullName":{"value":"Protein 3a"}},{"fullName":{"value":"Protein U274"}},{"fullName":{"value":"Protein X1"}}]},"genes":[{"orfNames":[{"value":"3a"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33157038"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33422265"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34158638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35239449"}],"value":"Plays a role in viral egress via lysosomal trafficking (PubMed:33157038, PubMed:33422265). Forms homotetrameric ion channels (viroporins) localized at endosomes and lysosomes, that may induce deacidification of lysosomes, allowing safe egress of virions via lysosomal trafficking (PubMed:33157038, PubMed:33422265, PubMed:34158638). Also blocks autolysosome formation by binding and sequestering the host component VPS39 for homotypic fusion and protein sorting (HOPS) on late endosomes (PubMed:33422265). This prevents fusion of autophagosomes with lysosomes, disrupting autophagy and facilitating virus egress (PubMed:33422265). Induces host RETREG1/FAM134B-dependent reticulophagy by interacting with host HMGB1 and enhancing the association between HMGB1 and host BECN1 (PubMed:35239449). This induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection (PubMed:35239449)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P59632"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33422265"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34158638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35239449"}],"value":"Homodimer (PubMed:34158638), a subset forms homotetramer of two homodimers linked non covalently (PubMed:34158638). Interacts with M, S and E proteins. Also interacts with the accessory protein 7a (By similarity). Interacts with host VPS39, sequestering it on late endosomes (PubMed:33422265). Interacts with host HMGB1; the interaction enhances the association between HMGB1 and host BECN1, promoting reticulophagy (PubMed:35239449). Interacts with HMOX1; the interaction promotes ORF3A-induced autophagy but is unlikely to be involved in ORF3A-mediated induction of reticulophagy (PubMed:35239449)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"P0DTC3","geneName":"3a","intActId":"EBI-25475894"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"P0DTD8","geneName":"7b","intActId":"EBI-25475914"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q9Y673","geneName":"ALG5","intActId":"EBI-11725055"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q01518","geneName":"CAP1","intActId":"EBI-2808398"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"P09601","geneName":"HMOX1","intActId":"EBI-2806151"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q86UT5-2","geneName":"NHERF4","intActId":"EBI-8299496"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q8TEW8","geneName":"PARD3B","intActId":"EBI-2861929"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q5T2W1","geneName":"PDZK1","intActId":"EBI-349819"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"P49796-4","geneName":"RGS3","intActId":"EBI-12006708"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q12846","geneName":"STX4","intActId":"EBI-744942"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q8NBJ7","geneName":"SUMF2","intActId":"EBI-723091"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q9UH99","geneName":"SUN2","intActId":"EBI-1044964"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q07157","geneName":"TJP1","intActId":"EBI-79553"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q9P2Y5","geneName":"UVRAG","intActId":"EBI-2952704"},"numberOfExperiments":6,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"P51809","geneName":"VAMP7","intActId":"EBI-1052205"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q96JC1","geneName":"VPS39","intActId":"EBI-1050197"},"numberOfExperiments":19,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"P49754","geneName":"VPS41","intActId":"EBI-2130459"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P0DTC3","intActId":"EBI-25475894"},"interactantTwo":{"uniProtKBAccession":"Q8NAF0","geneName":"ZNF579","intActId":"EBI-6164383"},"numberOfExperiments":2,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P59632"}],"value":"The cell surface expressed protein can undergo endocytosis. 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