ARNTL/2-CLOCK heterodimers activate E-box element (3'- CACGTG-5') transcription of a number of proteins of the circadian clock. Activates transcription of PER1 and PER2. This transcription is inhibited in a feedback loop by PER and CRY proteins. Has intrinsic histone acetyltransferase activity and this enzymatic function contributes to chromatin-remodeling events implicated in circadian control of gene expression. Acetylates primarily histones H3 and H4. Acetylates also a non-histone substrate: ARNTL. Plays a role in DNA damage response (DDR) signaling during the S phase. Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with ARNTL is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation. Binds weakly ARNTL and ARNTL2 to form heterodimers which bind poorly to the E-box motif. Expressed in all tissues examined including spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocytes, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Highest levels in testis and skeletal muscle. Low levels in thymus, lung and liver. Expressed in all brain regions with highest levels in cerebellum. Highly expressed in the suprachiasmatic nucleus (SCN). Note: This description may include information from UniProtKB.
Protein type: DNA binding protein; Acetyltransferase; Transcription factor; EC 188.8.131.52
Molecular Function: protein dimerization activity; signal transducer activity; protein binding; histone acetyltransferase activity; DNA binding; sequence-specific DNA binding; chromatin DNA binding; transcription factor activity
Biological Process: circadian rhythm; transcription from RNA polymerase II promoter; proteasomal ubiquitin-dependent protein catabolic process; establishment and/or maintenance of chromatin architecture; positive regulation of transcription, DNA-dependent; response to redox state; signal transduction; activation of NF-kappaB transcription factor; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-dependent; photoperiodism; DNA damage checkpoint; spermatogenesis; positive regulation of transcription from RNA polymerase II promoter; histone acetylation; circadian regulation of gene expression; negative regulation of transcription, DNA-dependent; regulation of insulin secretion; regulation of hair cycle
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.