Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator. As a part of the histone-deacetylase multiprotein complex (NuRD), regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA. In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A. Acts as a transcriptional coactivator of BCAS3, PAX5 and SUMO2, independent of the NuRD complex. Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3. Regulates p53-dependent and -independent DNA repair processes following genotoxic stress. Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair. Plays an important role in tumorigenesis, tumor invasion, and metastasis. Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner. Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles. Positively regulates the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1. Regulates deacetylation of ARNTL/BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression. Isoform Short binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses. With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation. Widely expressed. High expression in brain, liver, kidney, and cardiac muscle, ovaries, adrenal glands and virgin mammary glands. Higher in tumors than in adjacent normal tissue from the same individual. Up-regulated in a wide variety of cancers including breast, liver, ovarian, and colorectal cancer and its expression levels are closely correlated with tumor aggressiveness and metastasis. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Motility/polarity/chemotaxis; Nuclear receptor co-regulator; Transcription, coactivator/corepressor
Molecular Function: chromatin binding; DNA binding; enzyme binding; histone deacetylase binding; metal ion binding; protein binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; RNA polymerase II-specific DNA-binding transcription factor binding; sequence-specific DNA binding; transcription coactivator activity; transcription corepressor activity
Biological Process: chromatin remodeling; circadian regulation of gene expression; double-strand break repair; entrainment of circadian clock by photoperiod; epigenetic regulation of gene expression; histone deacetylation; locomotor rhythm; negative regulation of DNA-templated transcription; negative regulation of transcription by RNA polymerase II; positive regulation of DNA-templated transcription; positive regulation of protein autoubiquitination; proteasome-mediated ubiquitin-dependent protein catabolic process; regulation of cell fate specification; regulation of DNA-templated transcription; regulation of stem cell differentiation; response to ionizing radiation; rhythmic process; secretory granule organization