{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P15056","secondaryAccessions":["A4D1T4","B6HY61","B6HY62","B6HY63","B6HY64","B6HY65","B6HY66","Q13878","Q3MIN6","Q9UDP8","Q9Y6T3"],"uniProtkbId":"BRAF_HUMAN","entryAudit":{"firstPublicDate":"1990-11-01","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2004-07-19","entryVersion":268,"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":"Serine/threonine-protein kinase B-raf"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21441910"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29433126"}],"value":"2.7.11.1"}]},"alternativeNames":[{"fullName":{"value":"Proto-oncogene B-Raf"}},{"fullName":{"value":"p94"}},{"fullName":{"value":"v-Raf murine sarcoma viral oncogene homolog B1"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:1097"}],"value":"BRAF"},"synonyms":[{"value":"BRAF1"},{"value":"RAFB1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1508179"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21441910"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29433126"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36402789"},{"evidenceCode":"ECO:0000305"}],"value":"Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179)"}],"commentType":"FUNCTION"},{"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":"21441910"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29433126"}]}},{"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":"21441910"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Zn(2+)","evidences":[{"evidenceCode":"ECO:0000250"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29105"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Binds 2 Zn(2+) ions per subunit."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29433126"}],"value":"In quiescent cells, maintained in an inactive state via an intramolecular interaction between the protein kinase and N-terminal domains. Following mitogen-mediated cell activation, binds via its RGB domain to active HRAS (GTP-bound) which releases the inhibitory intramolecular interaction between the two domains. This allows the MAP2K1-mediated dimerization of KSR1 or KSR2, and BRAF which activates BRAF"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18287029"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19710016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21102438"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21441910"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21917714"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27353360"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29433126"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36402789"}],"value":"Monomer (PubMed:19710016). Homodimer (PubMed:19710016, PubMed:36402789). Heterodimerizes with RAF1, and the heterodimer possesses a highly increased kinase activity compared to the respective homodimers or monomers (PubMed:19710016). Heterodimerization is mitogen-regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 activation can induce a negative feedback that promotes the dissociation of the heterodimer by phosphorylating BRAF at Thr-753. Heterodimerizes (via N-terminus) with KSR1 (via N-terminus) or KSR2 (via N-terminus) in a MAP2K1-dependent manner (PubMed:29433126). Interacts with MAP2K1 and MAP2K2 (PubMed:29433126). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts with RIT1. Interacts (via N-terminus) with RGS14 (via RBD domains); the interaction mediates the formation of a ternary complex with RAF1, a ternary complex inhibited by GNAI1 (By similarity). Interacts with DGKH (PubMed:19710016). Interacts with PRMT5 (PubMed:21917714). Interacts with KSR2 (PubMed:21441910). Interacts with AKAP13, MAP2K1 and KSR1. Identified in a complex with AKAP13, MAP2K1 and KSR1 (PubMed:21102438). Interacts with FNIP1 and FNIP2 (PubMed:27353360)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P21399","geneName":"ACO1","intActId":"EBI-2847111"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P31749","geneName":"AKT1","intActId":"EBI-296087"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P10398","geneName":"ARAF","intActId":"EBI-365961"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P49407","geneName":"ARRB1","intActId":"EBI-743313"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"O14965","geneName":"AURKA","intActId":"EBI-448680"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P25311","geneName":"AZGP1","intActId":"EBI-2513837"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q92560","geneName":"BAP1","intActId":"EBI-1791447"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q07817","geneName":"BCL2L1","intActId":"EBI-78035"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q92843","geneName":"BCL2L2","intActId":"EBI-707714"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P15056","geneName":"BRAF","intActId":"EBI-365980"},"numberOfExperiments":14,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P40259","geneName":"CD79B","intActId":"EBI-2873732"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q6P1J9","geneName":"CDC73","intActId":"EBI-930143"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P42772","geneName":"CDKN2B","intActId":"EBI-711280"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P61024","geneName":"CKS1B","intActId":"EBI-456371"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P35221","geneName":"CTNNA1","intActId":"EBI-701918"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q13618","geneName":"CUL3","intActId":"EBI-456129"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q16254","geneName":"E2F4","intActId":"EBI-448943"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q9GZV4","geneName":"EIF5A2","intActId":"EBI-748028"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q7Z589","geneName":"EMSY","intActId":"EBI-6598631"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P18074","geneName":"ERCC2","intActId":"EBI-6380590"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"P28715","geneName":"ERCC5","intActId":"EBI-765885"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"O43524","geneName":"FOXO3","intActId":"EBI-1644164"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P15056","intActId":"EBI-365980"},"interactantTwo":{"uniProtKBAccession":"Q8WXI9","geneName":"GATAD2B","intActId":"EBI-923440"},"numberOfExperiments":3,"orga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LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Colocalizes with RGS14 and RAF1 in both the cytoplasm and membranes"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19710016"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19710016"}],"value":"Cell membrane","id":"SL-0039"}}]},{"texts":[{"value":"Brain and testis"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11410590"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19710016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35768504"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35830882"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.8"}],"value":"Phosphorylation at Ser-365 by SGK1 inhibits its activity (Ref.8, PubMed:11410590). 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