ID:CLOCK_HUMAN DESCRIPTION: RecName: Full=Circadian locomoter output cycles protein kaput; Short=hCLOCK; EC=2.3.1.48; AltName: Full=Class E basic helix-loop-helix protein 8; Short=bHLHe8; FUNCTION: ARNTL/2-CLOCK heterodimers activate E-box element (5'- CACGTG-3') 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 (By similarity). Acetylates primarily histones H3 and H4 (By similarity). Acetylates also a non-histone substrate: ARNTL (By similarity). Plays a role in DNA damage response (DDR) signaling during the S phase. CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl- [histone]. SUBUNIT: 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 (By similarity). SUBCELLULAR LOCATION: Nucleus. Chromosome. Cytoplasm (By similarity). Nucleus (By similarity). Note=Shuffling between the cytoplasm and the nucleus is under circadian regulation and is ARNTL-dependent. Phosphorylated form located in the nucleus (By similarity). Localizes to sites of DNA damage in a H2AX- independent manner. TISSUE SPECIFICITY: 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). PTM: Phosphorylation is dependent on CLOCK-ARNTL heterodimer formation (By similarity). MISCELLANEOUS: CLOCK-ARNTL double mutations within the PAS domains result in syngernistic desensitization to high levels of CRY on repression of CLOCK-ARNTL transcriptional activity of PER1 and disrupt circadian rhythmicity. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain. SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains. SEQUENCE CAUTION: Sequence=BAA20792.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15516
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0004402 histone acetyltransferase activity GO:0005515 protein binding GO:0016740 transferase activity GO:0016746 transferase activity, transferring acyl groups GO:0031490 chromatin DNA binding GO:0043565 sequence-specific DNA binding GO:0046983 protein dimerization activity GO:0070888 E-box binding
Biological Process: GO:0000077 DNA damage checkpoint GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006473 protein acetylation GO:0006974 cellular response to DNA damage stimulus GO:0007165 signal transduction GO:0007283 spermatogenesis GO:0007623 circadian rhythm GO:0009648 photoperiodism GO:0016573 histone acetylation GO:0032922 circadian regulation of gene expression GO:0042634 regulation of hair cycle GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048511 rhythmic process GO:0050729 positive regulation of inflammatory response GO:0050796 regulation of insulin secretion GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051775 response to redox state GO:0071479 cellular response to ionizing radiation GO:2000074 regulation of type B pancreatic cell development GO:2000323 negative regulation of glucocorticoid receptor signaling pathway
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
