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Important for stability of PR-DUB components and stimulating its ubiquitinase activity (PubMed:36180891). As part of the PR-DUB complex, associates with chromatin enriched in histone marks H3K4me1, H3K4me3, and H3K27Ac, but not in H3K27me3 (PubMed:36180891). The PR-DUB complex is an epigenetic regulator of gene expression, including genes involved in cell growth and survivability (PubMed:36180891). MBD5 and MBD6 containing complexes associate with distinct chromatin regions enriched in genes involved in different pathways (PubMed:36180891). Heterochromatin recruitment is not mediated by DNA methylation (PubMed:20700456). The PR-DUB complex is an epigenetic regulator of gene expression, including genes involved in development, cell communication, signaling, cell proliferation and cell viability (PubMed:36180891)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24634419"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36180891"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"24634419"}],"value":"Core component of the polycomb repressive deubiquitinase (PR-DUB) complex, at least composed of BAP1, one of ASXL1, ASXL2 or (probably) ASXL3, and one of MBD5 or MBD6 (PubMed:24634419, PubMed:36180891). Distinct combinations of ASXL and MBD proteins may preferentially bind specific histone modification marks (PubMed:36180891). The PR-DUB core associates with a number of accessory proteins, including FOXK1, FOXK2, KDM1B, HCFC1 and OGT; KDM1B specifically associates with ASXL2 PR-DUB complexes (Probable). Interacts (via MBD domain) with ASXL1, ASXL2 and ASXL3 (via PHD domain); the interaction is probably direct, mediates association with other PR-DUB complex core components (PubMed:24634419, PubMed:36180891)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9P267-2","intActId":"EBI-17671489"},"interactantTwo":{"uniProtKBAccession":"Q9UHA2","geneName":"SS18L2","intActId":"EBI-10962400"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P267-2","intActId":"EBI-17671489"},"interactantTwo":{"uniProtKBAccession":"P36508","geneName":"ZNF76","intActId":"EBI-7254550"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform 1","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20700456"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24634419"}],"value":"Associates with heterochromatin containing chromocentres in a DNA methylation-independent manner (PubMed:20700456). 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Does not localize to sites of DNA damage (PubMed:24634419)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20700456"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24634419"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"1"},"isoformIds":["Q9P267-1"],"isoformSequenceStatus":"Displayed"},{"name":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"2"},"isoformIds":["Q9P267-2"],"sequenceIds":["VSP_011083","VSP_011084"],"isoformSequenceStatus":"Described"}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20700456"}],"value":"At least 2 isoforms produced by alternative splicing have been identified."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12529184"}],"value":"Detected in heart, placenta, liver, skeletal muscle, kidney and pancreas"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20700456"}],"value":"Possesses a methyl-binding domain (MBD) and a Pro-Trp-Trp-Pro (PWWP) domain (PubMed:20700456). Both MBD and PWWP domains are necessary for chromocentric localization (PubMed:20700456)"}],"commentType":"DOMAIN","molecule":"Isoform 1"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20700456"}],"value":"Possesses a methyl-binding domain (MBD) but lacks the Pro-Trp-Trp-Pro (PWWP) domain"}],"commentType":"DOMAIN","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20700456"}],"value":"The MBD may lack methyl-binding activity"}],"commentType":"DOMAIN"},{"commentType":"DISEASE","disease":{"diseaseId":"Intellectual developmental disorder, autosomal dominant 1","diseaseAccession":"DI-00710","acronym":"MRD1","description":"A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental 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