{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9UPP1","secondaryAccessions":["B3KMV4","B7Z911","Q5H9U5","Q5JPR9","Q5JPS0","Q5JPS2","Q5JPS3","Q5VUJ4","Q7Z6D4","Q9HAH2"],"uniProtkbId":"PHF8_HUMAN","entryAudit":{"firstPublicDate":"2004-07-19","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2005-08-16","entryVersion":198,"sequenceVersion":3},"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":"Histone lysine demethylase PHF8"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622853"}],"value":"1.14.11.-"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20101266"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20208542"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20346720"}],"value":"1.14.11.65"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:20672"}],"value":"Lysine demethylase 7B"}},{"fullName":{"value":"PHD finger protein 8"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"[histone H3]-dimethyl-L-lysine(36) demethylase PHF8"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"[histone H3]-dimethyl-L-lysine(9) demethylase PHF8"}}]},"genes":[{"geneName":{"value":"PHF8"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:20672"}],"value":"KDM7B"},{"value":"KIAA1111"},{"value":"ZNF422"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0CH95"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19843542"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20023638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20101266"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20208542"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20346720"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20421419"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20531378"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20548336"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622853"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31691806"}],"value":"Histone lysine demethylase with selectivity for mono- and dimethylated residues. It plays an essential role in cell cycle progression and rDNA transcription (PubMed:19843542, PubMed:20531378, PubMed:20548336, PubMed:20622854). Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks (PubMed:20101266, PubMed:20208542, PubMed:20346720, PubMed:20622853, PubMed:20622854). Displays a very low intrinsic activity toward dimethylated H3 'Lys-27' (H3K27Me2) (PubMed:20346720). May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo (PubMed:19843542, PubMed:20023638, PubMed:20346720). Involved in cell cycle progression by being required to control G1-S transition (PubMed:20622854). Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes (PubMed:20531378). Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3 (PubMed:20023638, PubMed:20346720, PubMed:20421419). Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements (PubMed:31691806). Required for brain development, probably by regulating expression of neuron-specific genes (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 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Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (PubMed:32051553)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9UPP1","intActId":"EBI-1560800"},"interactantTwo":{"uniProtKBAccession":"Q96QS3","geneName":"ARX","intActId":"EBI-11107474"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPP1","intActId":"EBI-1560800"},"interactantTwo":{"uniProtKBAccession":"Q06330","geneName":"RBPJ","intActId":"EBI-632552"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPP1","intActId":"EBI-1560800"},"interactantTwo":{"uniProtKBAccession":"Q9Y462","geneName":"ZNF711","intActId":"EBI-2849152"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPP1-2","intActId":"EBI-6601215"},"interactantTwo":{"uniProtKBAccession":"P51610-1","geneName":"HCFC1","intActId":"EBI-396188"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPP1-2","intActId":"EBI-6601215"},"interactantTwo":{"uniProtKBAccession":"Q15156","geneName":"PML-RAR","intActId":"EBI-867256"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UPP1-2","intActId":"EBI-6601215"},"interactantTwo":{"uniProtKBAccession":"P10276","geneName":"RARA","intActId":"EBI-413374"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622854"}],"value":"Recruited to H3K4me3 sites on chromatin during interphase (PubMed:20622854). Dissociates from chromatin when cells enter mitosis (PubMed:20622854)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19843542"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622854"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20208542"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20531378"}],"value":"Nucleus, nucleolus","id":"SL-0188"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9UPP1-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9UPP1-2"],"sequenceIds":["VSP_014964"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q9UPP1-3"],"sequenceIds":["VSP_014965"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q9UPP1-4"],"sequenceIds":["VSP_014964","VSP_014965","VSP_043640"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["Q9UPP1-5"],"sequenceIds":["VSP_014964","VSP_054019","VSP_054020","VSP_054021"],"isoformSequenceStatus":"Described"}]},{"texts":[{"value":"The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2"}],"commentType":"DOMAIN"},{"texts":[{"value":"The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622854"}],"value":"Phosphorylation at Ser-69 and Ser-120 are required for dissociation from chromatin and accumulation of H4K20Me1 levels during prophase"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Intellectual developmental disorder, X-linked, syndromic, Siderius type","diseaseAccession":"DI-01966","acronym":"MRXSSD","description":"A syndrome characterized by mild to borderline intellectual disability with or without cleft lip/cleft palate.","diseaseCrossReference":{"database":"MIM","id":"300263"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16199551"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17661819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20101266"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20208542"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20346720"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20421419"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20548336"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622853"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20622854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31691806"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the JHDM1 histone demethylase family. 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