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Circadian locomoter output cycles protein kaput (UniProt: O08785; also known as mCLOCK; EC: 2.3.1.48) is encoded by the Clock gene (Gene ID: 12753) in murine species. CLOCK acts as a transcriptional activator that forms a core component of the circadian clock. CLOCK contains 2 PAS domains (aa 107-177 Pas1 domain; aa 262-332 Pas2 domain) and has a nuclear localization signaling sequence (aa 32-47). The major components of circadian clock include CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Transcription and translation of core clock components play a critical role in rhythm generation, whereas delays imposed by post-translational modifications are important for determining the period (tau) of the rhythms. CLOCK forms a heterodimer with ARNTL/BMAL1 and this heterodimer is required for E-box-dependent transactivation and for CLOCK nuclear translocation and degradation. It is also essential for phosphorylation of both CLOCK and ARNTL/BMAL1. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and non-histone proteins, including ARNTL/BMAL1. CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2 are reported to form the positive limb of the feedback loop, and as a heterodimer activate the transcription of core clock genes and clock-controlled genes. PER1/2/3 and CRY1/2 act as transcriptional repressors and form the negative limb of the feedback loop and inhibit transcription activation. CLOCK is expressed equally in brain, eye, testes, ovaries, liver, heart, lung, and kidney. In the brain, expression is abundant in the suprachiasmatic nuclei, pyriform cortex, and in the hippocampus.,官网链接:https://www.sigmaaldrich.cn/product/mm/abe2598m
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