CLOCK Antibody – Rabbit Polyclonal

The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with Arntl (Bmal1) that binds E-box enhancer elements upstream of Period (Per1, Per2, Per3) and Cryptochrome (Cry1, Cry2) genes and activates transcription of these genes. Per and Cry proteins heterodimerize and repress their own transcription by interacting in a feedback loop with Clock/Arntl complexes. Polymorphisms in this gene may be associated with behavioral changes, obesity, and metabolic syndrome. Two transcripts encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2014]

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).

Protein type: EC 2.3.1.48; Acetyltransferase; DNA-binding; Transcription factor

Cellular Component: chromosome; cytoplasm; intracellular membrane-bound organelle; nucleolus; nucleoplasm; nucleus; perichromatin fibrils; rough endoplasmic reticulum; transcription factor complex

Molecular Function: chromatin DNA binding; DNA binding; histone acetyltransferase activity; protein binding; protein dimerization activity; sequence-specific DNA binding; transcription factor activity; transcription factor binding; transferase activity; transferase activity, transferring acyl groups

Biological Process: activation of NF-kappaB transcription factor; circadian regulation of gene expression; circadian rhythm; DNA damage checkpoint; histone acetylation; negative regulation of transcription, DNA-dependent; positive regulation of inflammatory response; 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, DNA-dependent; response to DNA damage stimulus; response to redox state; rhythmic process; spermatogenesis; transcription, DNA-dependent