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In a histone deacetylase-dependent manner represses the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Abrogates the interaction of BMAL1 with the transcriptional coactivator CREBBP and can repress the histone acetyl-transferase activity of the CLOCK-BMAL1 heterodimer, reducing histone acetylation of its target genes. Rhythmically binds the E-box elements (5'-CACGTG-3') on circadian gene promoters and its occupancy shows circadian oscillation antiphasic to BMAL1. Interacts with the glucocorticoid receptor (NR3C1) and contributes to the repressive function in the glucocorticoid response"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24385426"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24736997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24737000"}],"value":"Interacts with BMAL1, PER2, CRY2, BHLHE41, HDAC1 NR3C1"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q3TQ03","intActId":"EBI-16101489"},"interactantTwo":{"uniProtKBAccession":"Q99PV5","geneName":"Bhlhe41","intActId":"EBI-6143801"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q3TQ03","intActId":"EBI-16101489"},"interactantTwo":{"uniProtKBAccession":"Q9WTL8","geneName":"Bmal1","intActId":"EBI-644534"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q3TQ03","intActId":"EBI-16101489"},"interactantTwo":{"uniProtKBAccession":"Q9R194","geneName":"Cry2","intActId":"EBI-1266619"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q3TQ03","intActId":"EBI-16101489"},"interactantTwo":{"uniProtKBAccession":"O09106","geneName":"Hdac1","intActId":"EBI-301912"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q3TQ03","intActId":"EBI-16101489"},"interactantTwo":{"uniProtKBAccession":"O54943","geneName":"Per2","intActId":"EBI-1266779"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"value":"Co-localizes with the CLOCK-BMAL1 heterodimer in the PML body"}]},"subcellularLocations":[{"location":{"value":"Nucleus","id":"SL-0191"}},{"location":{"value":"Nucleus, PML body","id":"SL-0465"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24736997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24737000"}],"value":"Expression in the liver oscillates in a circadian manner with highest levels at Zeitgeber time (ZT) 12 hours (at protein level). Expression in the heart, lung, stomach and kidney oscillate in a circadian manner with highest levels at approximately circadian time (CT) 12 hours. Its expression levels peak at circadian time 12 hours (CT12), 8 hours earlier than the peak of PER1/2 and CRY1/2 transcriptional repressors (peak CT20-CT24). Thus, it can repress the CLOCK-BMAL1 activity in a different time window compared to CRY and PER proteins"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24385426"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24736997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24737000"}],"value":"Mice exhibit a longer circadian period of locomotor activity, alteration in the expression of core clock genes and impairment of the response of the circadian clock to stress. The peaks of DBP, NR1D1 and PER1 gene expression persists longer in the liver between Zeitgeber times (ZT) 12-14 hours"}],"commentType":"DISRUPTION PHENOTYPE"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":375,"modifier":"EXACT"}},"description":"Circadian-associated transcriptional repressor","featureId":"PRO_0000251194"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":102,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":192,"modifier":"EXACT"},"end":{"value":218,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":351,"modifier":"EXACT"},"end":{"value":375,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":32,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":33,"modifier":"EXACT"},"end":{"value":46,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Sequence conflict","location":{"start":{"value":337,"modifier":"EXACT"},"end":{"value":337,"modifier":"EXACT"}},"description":"in Ref. 1; 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