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CLOCK 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: Acetyltransferase; DNA-binding; EC; Transcription factor
Chromosomal Location of Human Ortholog: 4q12
Cellular Component: chromosome; intracellular membrane-bound organelle; nucleoplasm; nucleus; transcription factor complex
Molecular Function: chromatin DNA binding; DNA binding; histone acetyltransferase activity; protein binding; sequence-specific DNA binding; transcription factor activity
Biological Process: activation of NF-kappaB transcription factor; circadian regulation of gene expression; circadian rhythm; DNA damage checkpoint; negative regulation of transcription, DNA-dependent; photoperiodism; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; proteasomal ubiquitin-dependent protein catabolic process; regulation of hair cycle; regulation of insulin secretion; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-dependent; response to redox state; signal transduction; spermatogenesis
Reference #:  O15516 (UniProtKB)
Alt. Names/Synonyms: BHLHE8; circadian locomoter output cycles kaput protein; Circadian locomoter output cycles protein kaput; Class E basic helix-loop-helix protein 8; CLOCK; clock homolog (mouse); hCLOCK; KAT13D; KIAA0334
Gene Symbols: CLOCK
Molecular weight: 95,304 Da
Basal Isoelectric point: 6.51  Predict pI for various phosphorylation states
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