{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9ULU4","secondaryAccessions":["B3KVL2","B7Z2A8","B7Z3E0","B7Z680","B7ZM62","E1P5U5","F5H0X3","H7C0U2","J3KPU3","Q13517","Q2HXV1","Q2HXV2","Q2HXV3","Q2HXV4","Q2HXV7","Q2HXV8","Q2HXV9","Q2HXW0","Q2HXW1","Q2HXW2","Q4JJ94","Q4JJ95","Q5TH09","Q5TH11","Q6MZM1","Q8WXC5","Q9H1F3","Q9H1F4","Q9H1F5","Q9H1L8","Q9H1L9","Q9H2G5","Q9NYN3","Q9UIX6"],"uniProtkbId":"ZMYD8_HUMAN","entryAudit":{"firstPublicDate":"2002-11-25","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-11-25","entryVersion":221,"sequenceVersion":2},"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:0000303","source":"PubMed","id":"25593309"}],"value":"MYND-type zinc finger-containing chromatin reader ZMYND8"}},"alternativeNames":[{"fullName":{"value":"Cutaneous T-cell lymphoma-associated antigen se14-3"},"shortNames":[{"value":"CTCL-associated antigen se14-3"}]},{"fullName":{"value":"Protein kinase C-binding protein 1"}},{"fullName":{"value":"Rack7"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"27477906"}],"value":"Transcription coregulator ZMYND8"}},{"fullName":{"value":"Zinc finger MYND domain-containing protein 8"}}]},"genes":[{"geneName":{"value":"ZMYND8"},"synonyms":[{"value":"KIAA1125"},{"value":"PRKCBP1"},{"value":"RACK7"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25593309"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26655721"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27477906"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27732854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30134174"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31965980"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33323928"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35916866"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36064715"}],"value":"Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11003709"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25593309"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27477906"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27732854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28966017"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30134174"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31965980"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33323928"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35916866"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36064715"}],"value":"Monomer and homodimer (PubMed:30134174). Interacts with NuRD subcomplexes containing GATAD2A (PubMed:27732854). Interacts with the histone deacetylase NuRD complex subunit CHD4; the interaction is direct, appears to occur with monomeric ZMYND8, and is increased following DNA damage (PubMed:25593309, PubMed:30134174, PubMed:36064715). Interacts (via N-terminus) with the P-TEFb complex subunit CCNT1 (via central region); the interaction is direct and the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex (PubMed:30134174). Interacts (via N-terminus) with DBN1 (via ADF-H domain); the interaction leads to sequestering of ZMYND8 in the cytoplasm (PubMed:28966017, PubMed:35916866). Interacts with the P-TEFb complex subunit CDK9; the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex (PubMed:30134174). Interacts with EZH2; the interaction is dependent on the presence of chromatin (PubMed:33323928, PubMed:36064715). Interacts (via MYND domain) with the NuRD complex subunit GATAD2A (PubMed:27732854, PubMed:35916866). Interacts with histone H3 (via N-terminus) that is both methylated at 'Lys-4' (H3K4me1) and acetylated at 'Lys-14' (H3K14ac), with histone H3 (via N-terminus) unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-14' (H3K14ac), and with histone H3 (via N-terminus) di-methylated at 'Lys-36' (H3K36me2) (PubMed:25593309, PubMed:26655721, PubMed:27477906, PubMed:31965980). Interacts (via Bromo domain) with histone H4 acetylated at 'Lys-16' (H4K16ac) (PubMed:25593309, PubMed:26655721, PubMed:31965980). Interacts with HDAC1 (PubMed:25593309, PubMed:36064715). Interacts with HDAC2 (PubMed:25593309). Interacts with KDM1A (PubMed:25593309, PubMed:27477906). Interacts with KDM5C (PubMed:33323928). Interacts with KDM5D (PubMed:27477906). Interacts in vitro with PRKCB (PubMed:11003709). Interacts with RNA polymerase II subunit POLR2A phosphorylated at 'Ser-5' (PubMed:26655721). Interacts with ZNF592 (PubMed:30134174). Interacts with ZNF687 (PubMed:30134174). Does not interact with GATAD2B (PubMed:27732854)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9ULU4","intActId":"EBI-765834"},"interactantTwo":{"uniProtKBAccession":"P41182","geneName":"BCL6","intActId":"EBI-765407"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9ULU4","intActId":"EBI-765834"},"interactantTwo":{"uniProtKBAccession":"Q16643","geneName":"DBN1","intActId":"EBI-351394"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9ULU4","intActId":"EBI-765834"},"interactantTwo":{"uniProtKBAccession":"Q13627","geneName":"DYRK1A","intActId":"EBI-1053596"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9ULU4-14","intActId":"EBI-12169985"},"interactantTwo":{"uniProtKBAccession":"Q6FHY5","geneName":"MEOX2","intActId":"EBI-16439278"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25593309"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27732854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28966017"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36064715"}],"value":"Sequestered in the cytoplasm through the interaction with DBN1 (PubMed:28966017). Localizes to sites of DNA damage in a KAT5-dependent and DNA poly (ADP-ribose)-dependent manner (PubMed:25593309, PubMed:27732854). On chromatin, localizes to demethylated regions, active promoters, and transcription start sites (PubMed:27732854, PubMed:36064715)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25593309"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27477906"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27732854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28966017"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25593309"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26655721"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27732854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31965980"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36064715"}],"value":"Chromosome","id":"SL-0468"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28966017"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9ULU4-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9ULU4-2"],"sequenceIds":["VSP_000566","VSP_000568"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q9ULU4-3"],"sequenceIds":["VSP_000564","VSP_000568"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q9ULU4-4"],"sequenceIds":["VSP_000565","VSP_000568"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["Q9ULU4-5"],"sequenceIds":["VSP_000563","VSP_000567"],"isoformSequenceStatus":"Described"},{"name":{"value":"6"},"isoformIds":["Q9ULU4-6"],"sequenceIds":["VSP_000564","VSP_000568","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"7"},"isoformIds":["Q9ULU4-7"],"sequenceIds":["VSP_000563","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"8"},"isoformIds":["Q9ULU4-8"],"sequenceIds":["VSP_000563","VSP_017096","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"9"},"isoformIds":["Q9ULU4-9"],"sequenceIds":["VSP_000568","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"10"},"isoformIds":["Q9ULU4-10"],"sequenceIds":["VSP_000563"],"isoformSequenceStatus":"Described"},{"name":{"value":"11"},"isoformIds":["Q9ULU4-11"],"sequenceIds":["VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"12"},"isoformIds":["Q9ULU4-12"],"sequenceIds":["VSP_000563","VSP_000568"],"isoformSequenceStatus":"Described"},{"name":{"value":"13"},"isoformIds":["Q9ULU4-13"],"sequenceIds":["VSP_000563","VSP_000568","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"14"},"isoformIds":["Q9ULU4-14"],"sequenceIds":["VSP_000563","VSP_000567","VSP_000568"],"isoformSequenceStatus":"Described"},{"name":{"value":"15"},"isoformIds":["Q9ULU4-15"],"sequenceIds":["VSP_000563","VSP_000567","VSP_053400","VSP_000568"],"isoformSequenceStatus":"Described"},{"name":{"value":"16"},"isoformIds":["Q9ULU4-16"],"sequenceIds":["VSP_000563","VSP_000567","VSP_000568","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"17"},"isoformIds":["Q9ULU4-17"],"sequenceIds":["VSP_000563","VSP_000567","VSP_017096"],"isoformSequenceStatus":"Described"},{"name":{"value":"18"},"isoformIds":["Q9ULU4-18"],"sequenceIds":["VSP_000563","VSP_000567","VSP_053400"],"isoformSequenceStatus":"Described"},{"name":{"value":"19"},"isoformIds":["Q9ULU4-19"],"sequenceIds":["VSP_054810","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"20"},"isoformIds":["Q9ULU4-20"],"sequenceIds":["VSP_054811","VSP_000567"],"isoformSequenceStatus":"Described"},{"name":{"value":"21"},"isoformIds":["Q9ULU4-21"],"sequenceIds":["VSP_000567","VSP_000568"],"isoformSequenceStatus":"Described"},{"name":{"value":"22"},"isoformIds":["Q9ULU4-22"],"sequenceIds":["VSP_000563","VSP_000568","VSP_054814","VSP_000570"],"isoformSequenceStatus":"Described"},{"name":{"value":"23"},"isoformIds":["Q9ULU4-23"],"sequenceIds":["VSP_000567","VSP_054812","VSP_000568","VSP_000570"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11003709"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11149944"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35916866"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36064715"}],"value":"Expressed in neurons (at protein level) (PubMed:36064715). Absent in astrocytes (at protein level) (PubMed:36064715). Expressed in all tissues examined with highest expression in brain, lung, pancreas, and placenta (PubMed:11003709, PubMed:35916866). Expressed in cutaneous T-cell lymphomas (CTCL) (PubMed:11149944)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35916866"}],"value":"Highly expressed in fetal brain, with decreasing expression in postnatal stages"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26655721"}],"value":"Induced by all-trans-retinoic acid (ATRA) (at protein level)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25593309"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26655721"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27732854"}],"value":"The bromo domain is required for interaction with histone 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