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Gene Ontology Classifications
Symbol
Name
ID
Clock
circadian locomotor output cycles kaput
MGI:99698

Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Clock. (This text reflects annotations as of Tuesday, May 26, 2015.)
Summary from NCBI RefSeq


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]
Summary text based on GO annotations supported by experimental evidence in mouse
Summary text based on GO annotations supported by experimental evidence in other organisms
Summary text based on GO annotations supported by structural data
Summary text for additional MGI annotations
References
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  6. Bertolucci C et al. (2008) Evidence for an overlapping role of CLOCK and NPAS2 transcription factors in liver circadian oscillators. Mol Cell Biol, 28:3070-5. (PubMed:18316400)
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  14. Goriki A et al. (2014) A novel protein, CHRONO, functions as a core component of the mammalian circadian clock. PLoS Biol, 12:e1001839. (PubMed:24736997)
  15. Hamaguchi H et al. (2004) Expression of the gene for Dec2, a basic helix-loop-helix transcription factor, is regulated by a molecular clock system. Biochem J, 382:43-50. (PubMed:15147242)
  16. Han DH et al. (2014) Modulation of glucocorticoid receptor induction properties by core circadian clock proteins. Mol Cell Endocrinol, 383:170-80. (PubMed:24378737)
  17. Hara Y et al. (2009) Molecular characterization of Mybbp1a as a co-repressor on the Period2 promoter. Nucleic Acids Res, 37:1115-26. (PubMed:19129230)
  18. Honma S et al. (2002) Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature, 419:841-4. (PubMed:12397359)
  19. Huang N et al. (2012) Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex. Science, 337:189-94. (PubMed:22653727)
  20. Itoh R et al. (2013) Imaging of heme/hemeproteins in nucleus of the living cells expressing heme-binding nuclear receptors. FEBS Lett, 587:2131-6. (PubMed:23735699)
  21. Katada S et al. (2010) The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol, 17:1414-21. (PubMed:21113167)
  22. Kawamoto T et al. (2004) A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation. Biochem Biophys Res Commun, 313:117-24. (PubMed:14672706)
  23. Kondratov RV et al. (2003) BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system. Genes Dev, 17:1921-32. (PubMed:12897057)
  24. Koyanagi S et al. (2011) cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene. J Biol Chem, 286:32416-23. (PubMed:21768648)
  25. Lande-Diner L et al. (2013) A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery. Proc Natl Acad Sci U S A, 110:16021-16026. (PubMed:24043798)
  26. Langmesser S et al. (2008) Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK. BMC Mol Biol, 9:41. (PubMed:18430226)
  27. Lee C et al. (2004) Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol, 24:584-94. (PubMed:14701732)
  28. Li DQ et al. (2013) Metastasis-associated protein 1 is an integral component of the circadian molecular machinery. Nat Commun, 4:2545. (PubMed:24089055)
  29. Li MD et al. (2013) O-GlcNAc signaling entrains the circadian clock by inhibiting BMAL1/CLOCK ubiquitination. Cell Metab, 17:303-10. (PubMed:23395176)
  30. Li Y et al. (2004) DNA binding, but not interaction with Bmal1, is responsible for DEC1-mediated transcription regulation of the circadian gene mPer1. Biochem J, 382:895-904. (PubMed:15193144)
  31. Marcheva B et al. (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature, 466:627-31. (PubMed:20562852)
  32. Miki T et al. (2013) p53 regulates Period2 expression and the circadian clock. Nat Commun, 4:2444. (PubMed:24051492)
  33. Nader N et al. (2009) Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J, 23:1572-83. (PubMed:19141540)
  34. Nakahata Y et al. (2008) The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell, 134:329-40. (PubMed:18662547)
  35. Ozber N et al. (2010) Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction. BMC Mol Biol, 11:69. (PubMed:20840750)
  36. Peruquetti RL et al. (2012) Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA processing granule of male germ cells. PLoS One, 7:e42695. (PubMed:22900038)
  37. Ramsey KM et al. (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science, 324:651-4. (PubMed:19299583)
  38. Richards J et al. (2013) A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na+ retention. Am J Physiol Renal Physiol, 305:F1697-704. (PubMed:24154698)
  39. Richards J et al. (2014) A role for the circadian clock protein Per1 in the regulation of the NaCl co-transporter (NCC) and the with-no-lysine kinase (WNK) cascade in mouse distal convoluted tubule cells. J Biol Chem, 289:11791-806. (PubMed:24610784)
  40. Sasaki M et al. (2009) Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription. J Biol Chem, 284:25149-59. (PubMed:19605937)
  41. Sato F et al. (2004) Functional analysis of the basic helix-loop-helix transcription factor DEC1 in circadian regulation. Interaction with BMAL1. Eur J Biochem, 271:4409-19. (PubMed:15560782)
  42. Schoenhard JA et al. (2003) Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. J Mol Cell Cardiol, 35:473-81. (PubMed:12738229)
  43. Shim HS et al. (2007) Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock. EMBO Rep, 8:366-71. (PubMed:17347670)
  44. Spengler ML et al. (2012) Core circadian protein CLOCK is a positive regulator of NF-kappaB-mediated transcription. Proc Natl Acad Sci U S A, 109:E2457-65. (PubMed:22895791)
  45. Stashi E et al. (2014) SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm. Cell Rep, 6:633-45. (PubMed:24529706)
  46. Takahata S et al. (1998) Transcriptionally active heterodimer formation of an Arnt-like PAS protein, Arnt3, with HIF-1a, HLF, and clock. Biochem Biophys Res Commun, 248:789-94. (PubMed:9704006)
  47. Vitaterna MH et al. (1994) Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science, 264:719-25. (PubMed:8171325)
  48. Wallach T et al. (2013) Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions. PLoS Genet, 9:e1003398. (PubMed:23555304)
  49. Ward SM et al. (2010) The transcriptional repressor ID2 can interact with the canonical clock components CLOCK and BMAL1 and mediate inhibitory effects on mPer1 expression. J Biol Chem, 285:38987-9000. (PubMed:20861012)
  50. Xu CX et al. (2010) Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene. Toxicol Sci, 115:98-108. (PubMed:20106950)
  51. Ye R et al. (2011) Biochemical analysis of the canonical model for the mammalian circadian clock. J Biol Chem, 286:25891-902. (PubMed:21613214)
  52. Yoshitane H et al. (2012) JNK regulates the photic response of the mammalian circadian clock. EMBO Rep, 13:455-61. (PubMed:22441692)
  53. Yujnovsky I et al. (2006) Signaling mediated by the dopamine D2 receptor potentiates circadian regulation by CLOCK:BMAL1. Proc Natl Acad Sci U S A, 103:6386-91. (PubMed:16606840)
  54. Zhao WN et al. (2007) CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol, 9:268-75. (PubMed:17310242)



Go Annotations in Tabular Form (Text View) (GO Graph)

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Gene Ontology Evidence Code Abbreviations:

  EXP Inferred from experiment
  IAS Inferred from ancestral sequence
  IBA Inferred from biological aspect of ancestor
  IBD Inferred from biological aspect of descendant
  IC Inferred by curator
  IDA Inferred from direct assay
  IEA Inferred from electronic annotation
  IGI Inferred from genetic interaction
  IKR Inferred from key residues
  IMP Inferred from mutant phenotype
  IMR Inferred from missing residues
  IPI Inferred from physical interaction
  IRD Inferred from rapid divergence
  ISS Inferred from sequence or structural similarity
  ISO Inferred from sequence orthology
  ISA Inferred from sequence alignment
  ISM Inferred from sequence model
  NAS Non-traceable author statement
  ND No biological data available
  RCA Reviewed computational analysis
  TAS Traceable author statement

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last database update
07/28/2015
MGI 5.22
The Jackson Laboratory