clock proteins


Summary: Basic helix-loop-helix (bHLH) domain-containing proteins that contain intrinsic HISTONE ACETYLTRANSFERASE activity and play important roles in CIRCADIAN RHYTHM regulation. Clock proteins combine with Arntl proteins to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation. This transcriptional activation also sets into motion a time-dependent feedback loop which in turn down-regulates the expression of clock proteins.

Top Publications

  1. Patel V, Eckel Mahan K, Sassone Corsi P, Baldi P. CircadiOmics: integrating circadian genomics, transcriptomics, proteomics and metabolomics. Nat Methods. 2012;9:772-3 pubmed publisher
  2. Schibler U. Mammalian Circadian Cogwheels Are Parts of Macromolecular Machines. Mol Cell. 2017;67:727-729 pubmed publisher
    ..2017) and a mechanism rendering this molecular timekeeper temperature-compensated (Shinohara et al., 2017). ..
  3. Adachi Y, Umeda M, Kawazoe A, Sato T, Ohkawa Y, Kitajima S, et al. The novel heme-dependent inducible protein, SRRD regulates heme biosynthesis and circadian rhythms. Arch Biochem Biophys. 2017;631:19-29 pubmed publisher
    ..The knockout of SRRD arrested the growth of cells, indicating that SRRD plays roles in heme-regulated circadian rhythms and cell proliferation. ..
  4. Futamura A, Shiromaru A, Kuroda T, Honma M, Kinno R, Ono K, et al. [Clocks, Behavior, and Cognition]. Brain Nerve. 2017;69:639-649 pubmed publisher
    ..Stereotypical behaviors in FTD are often considered in contrast to obsessive-compulsive disease (OCD). Studies of OCD have found a close correlation between clinical symptoms, cognitive function, and brain function. ..
  5. Schallner N, Lieberum J, Gallo D, LeBlanc R, Fuller P, Hanafy K, et al. Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity of Subarachnoid Hemorrhage in Mice. Stroke. 2017;48:2565-2573 pubmed publisher
    ..Exposure to CO rescues the loss of HO-1 and thus merits further investigation in patients with SAH. ..
  6. Sobel J, Krier I, Andersin T, Raghav S, Canella D, Gilardi F, et al. Transcriptional regulatory logic of the diurnal cycle in the mouse liver. PLoS Biol. 2017;15:e2001069 pubmed publisher
    ..Together, our temporal DNase I mappings allowed us to decipher the global regulation of diurnal transcription rhythms in the mouse liver. ..
  7. Sharp B, Paquet E, Naef F, Bafna A, Wijnen H. A new promoter element associated with daily time keeping in Drosophila. Nucleic Acids Res. 2017;45:6459-6470 pubmed publisher
    ..Nevertheless, our results indicate that CATAC's enhancer function persists in the absence of CLK/CYC. Thus, CATAC represents a novel cis-regulatory element encoding clock-controlled regulation. ..
  8. Ajabnoor G, Bahijri S, Shaik N, Borai A, Alamoudi A, Al Aama J, et al. Ramadan fasting in Saudi Arabia is associated with altered expression of CLOCK, DUSP and IL-1alpha genes, as well as changes in cardiometabolic risk factors. PLoS ONE. 2017;12:e0174342 pubmed publisher
  9. Rybakowski J, Dmitrzak Weglar M, Kliwicki S, Hauser J. Polymorphism of circadian clock genes and prophylactic lithium response. Bipolar Disord. 2014;16:151-8 pubmed
    ..Of special interest may be polymorphisms of these genes involved both in the predisposition to bipolar mood disorder and the lithium response. ..

More Information


  1. Musiek E, Lim M, Yang G, Bauer A, Qi L, Lee Y, et al. Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration. J Clin Invest. 2013;123:5389-400 pubmed publisher
    Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism...
  2. Kolomeĭchuk S, Makeeva I, Topchieva L, Korneva V, Nemova N. [Association of T3111C polymorphism in 3'-untranslated region of the CLOCK gene with the risk of essential arterial hypertension and coronary artery disease in the Russian population Karelia]. Genetika. 2011;47:1411-5 pubmed
    ..Male CC carriers were characterized by a possible increased risk of EAH: OR (95% CI) = 1.42 (0.56; 3.58). Moreover, the presence of the CC genotype in males could increase the risk of CAD: OR (95% CI) = 1.58 (0.63; 3.93). ..
  3. Otowa T, Tochigi M, Umekage T, Ebisawa T, Kasai K, Kato N, et al. No association between CLOCK gene 3111C/T polymorphism and personality traits in healthy Japanese subjects. Psychiatry Clin Neurosci. 2011;65:604 pubmed publisher
  4. Namihira M, Honma S, Abe H, Tanahashi Y, Ikeda M, Honma K. Daily variation and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the pineal body and different areas of brain in rats. Neurosci Lett. 1999;267:69-72 pubmed
    ..The BMAL1 expressions in these areas were similar to the case in the pineal. These findings indicate that the mammalian clock gene, Clock and BMAL1, are expressed differently in the different areas of the brain and the pineal. ..
  5. Li P, Fu X, Smith N, Ziobro J, Curiel J, Tenga M, et al. Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy. Neuron. 2017;96:387-401.e6 pubmed publisher
    ..Altogether, these data show that disruption of CLOCK alters cortical circuits and may lead to generation of focal epilepsy. ..
  6. Fletcher E, Morgan J, Kennaway D, Bienvenu L, Rickard A, Delbridge L, et al. Deoxycorticosterone/Salt-Mediated Cardiac Inflammation and Fibrosis Are Dependent on Functional CLOCK Signaling in Male Mice. Endocrinology. 2017;158:2906-2917 pubmed publisher
    ..This study demonstrates that the full development of MR-mediated cardiac inflammation and fibrosis is dependent on intact signaling by the circadian protein CLOCK. ..
  7. Lin R, Mo Y, Zha H, Qu Z, Xie P, Zhu Z, et al. CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis. Mol Cell. 2017;68:198-209.e6 pubmed publisher
    ..Taken together, CLOCK modulates metabolic rhythmicity by acting as a rhythmic acetyl-transferase for metabolic enzymes. ..
  8. Jiang N, Wang Z, Cao J, Dong Y, Chen Y. Effect of monochromatic light on circadian rhythmic expression of clock genes in the hypothalamus of chick. J Photochem Photobiol B. 2017;173:476-484 pubmed publisher
    ..Our results also suggest that the circadian clock in the chick hypothalamus such as non-SCN brain region were involved in the regulation of photo information. ..
  9. Riestra P, Gebreab S, Xu R, Khan R, Gaye A, Correa A, et al. Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study. BMC Genet. 2017;18:58 pubmed publisher
    ..In this work, CLOCK gene variants were associated with sleep duration and BMI suggesting that the effects of these polymorphisms on circadian rhythmicity may affect sleep duration and body weight regulation in Africans Americans. ..
  10. Narasimamurthy R, Virshup D. A Flick of the Tail Keeps the Circadian Clock in Line. Mol Cell. 2017;66:437-438 pubmed publisher
    ..In this issue of Molecular Cell, Gustafson et al. (2017) report an additional requirement for accurate timekeeping, a cis/trans conformational flicker in the transcriptional activation domain of the core clock protein BMAL1. ..
  11. Song H, Wang D, De Jesus Perez F, Xie R, Liu Z, Chen C, et al. Rhythmic expressed clock regulates the transcription of proliferating cellular nuclear antigen in teleost retina. Exp Eye Res. 2017;160:21-30 pubmed publisher
    ..Our results also indicate an association between Clock proteins and the upstream region of pcna (proliferating cellular nuclear antigen) gene...
  12. Herichova I. Changes of physiological functions induced by shift work. Endocr Regul. 2013;47:159-70 pubmed
    ..Shift work tolerance is individual. Partial positive selection can be achieved on the basis of several psychological traits. Appropriate schedule can be estimated on the basis of chronotype. ..
  13. Lane J, Tare A, Cade B, Chen T, Punjabi N, Gottlieb D, et al. Common variants in CLOCK are not associated with measures of sleep duration in people of european ancestry from the sleep heart health study. Biol Psychiatry. 2013;74:e33-5 pubmed publisher
  14. Staiger D, Shin J, Johansson M, Davis S. The circadian clock goes genomic. Genome Biol. 2013;14:208 pubmed publisher
    ..Large-scale biology among plant species, as well as comparative genomics of circadian clock architecture and clock-regulated output processes, have greatly advanced our understanding of the endogenous timing system in plants. ..
  15. Eckel Mahan K, Sassone Corsi P. Aging brains and waning clocks on the process of habituation. Aging (Albany NY). 2010;2:320-1 pubmed
  16. Rawashdeh O, Stehle J. Ageing or NOT, clock genes are important for memory processes: an interesting hypothesis raising many questions. Aging (Albany NY). 2010;2:259-60 pubmed