KEGG   PATHWAY: ko04710
Entry
ko04710                     Pathway                                
Name
Circadian rhythm
Description
Circadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of cell-autonomous transcription-translation feedback loops that drive rhythmic, 24-hour expression patterns of core clock components. The first negative feedback loop is a rhythmic transcription of period genes (PER1, PER2, and PER3) and chryptochrome genes (CRY1 and CRY2). PER and CRY proteins form a heterodimer, which acts on the CLOCK/BMAL1 heterodimer to repress its own transcription. PER and CRY proteins are phosphorylated by casein kinase epsilon (CKIepsilon), which leads to degradation and restarting of the cycle. The second loop is a positive feedback loop driven by the CLOCK/BMAL1 heterodimer, which initiates transcription of target genes containing E-box cis-regulatory enhancer sequences.
Class
Organismal Systems; Environmental adaptation
Pathway map
ko04710  Circadian rhythm
ko04710

Other DBs
GO: 0007623
Orthology
K08532  RAR-related orphan receptor alpha
K08533  RAR-related orphan receptor beta
K08534  RAR-related orphan receptor gamma
K03728  nuclear receptor subfamily 1 group D member 1
K08531  nuclear receptor subfamily 1 group D member 2
K09059  nuclear factor, interleukin 3 regulated
K02296  aryl hydrocarbon receptor nuclear translocator-like protein 1
K09056  albumin D box-binding protein
K03729  class B basic helix-loop-helix protein 2
K03730  class B basic helix-loop-helix protein 3
K08959  casein kinase 1, delta [EC:2.7.11.1]
K08960  casein kinase 1, epsilon [EC:2.7.11.1]
K21944  period circadian protein 1
K02633  period circadian protein 2
K21945  period circadian protein 3
K02295  cryptochrome
K02223  circadian locomoter output cycles kaput protein [EC:2.3.1.48]
K09026  neuronal PAS domain-containing protein 2
K05870  cyclic AMP-responsive element-binding protein 1
K07198  5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.11]
K07199  5'-AMP-activated protein kinase, regulatory beta subunit
K07200  5'-AMP-activated protein kinase, regulatory gamma subunit
K03868  E3 ubiquitin-protein ligase RBX1 [EC:2.3.2.32]
K03347  cullin 1
K03094  S-phase kinase-associated protein 1
K03362  F-box and WD-40 domain protein 1/11
K10287  F-box and leucine-rich repeat protein 21
K10269  F-box and leucine-rich repeat protein 3
Compound
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
Reference
  Authors
Takahashi JS
  Title
Transcriptional architecture of the mammalian circadian clock.
  Journal
Nat Rev Genet 18:164-179 (2017)
DOI:10.1038/nrg.2016.150
Reference
  Authors
Wang S, Li F, Lin Y, Wu B
  Title
Targeting REV-ERBalpha for therapeutic purposes: promises and challenges.
  Journal
Theranostics 10:4168-4182 (2020)
DOI:10.7150/thno.43834
Reference
  Authors
Panda S, Hogenesch JB, Kay SA.
  Title
Circadian rhythms from flies to human.
  Journal
Nature 417:329-35 (2002)
DOI:10.1038/417329a
Reference
  Authors
Honma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, Kato Y, Honma K.
  Title
Dec1 and Dec2 are regulators of the mammalian molecular clock.
  Journal
Nature 419:841-4 (2002)
DOI:10.1038/nature01123
Reference
  Authors
Fu L, Lee CC.
  Title
The circadian clock: pacemaker and tumour suppressor.
  Journal
Nat Rev Cancer 3:350-61 (2003)
DOI:10.1038/nrc1072
Reference
  Authors
Schibler U, Sassone-Corsi P.
  Title
A web of circadian pacemakers.
  Journal
Cell 111:919-22 (2002)
DOI:10.1016/S0092-8674(02)01225-4
Reference
  Authors
Takahashi JS, Hong HK, Ko CH, McDearmon EL
  Title
The genetics of mammalian circadian order and disorder: implications for physiology and disease.
  Journal
Nat Rev Genet 9:764-75 (2008)
DOI:10.1038/nrg2430
Related
pathway
ko04010  MAPK signaling pathway
ko04120  Ubiquitin mediated proteolysis
ko04713  Circadian entrainment
LinkDB

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