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

Disease
H00688  Familial advanced sleep phase syndrome
H00689  Delayed sleep phase syndrome
H02346  Intellectual developmental disorder with short stature, facial anomalies, and speech defects
Other DBs
GO: 0007623
Orthology
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
K02296  aryl hydrocarbon receptor nuclear translocator-like protein 1
K02223  circadian locomoter output cycles kaput protein [EC:2.3.1.48]
K09026  neuronal PAS domain-containing protein 2
K03728  nuclear receptor subfamily 1 group D member 1
K08532  RAR-related orphan receptor alpha
K08533  RAR-related orphan receptor beta
K08534  RAR-related orphan receptor gamma
K03729  class B basic helix-loop-helix protein 2
K03730  class B basic helix-loop-helix protein 3
K03868  RING-box protein 1 [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
K10269  F-box and leucine-rich repeat protein 3
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
K05870  cyclic AMP-responsive element-binding protein 1
Compound
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
Reference
  Authors
Camacho F, Cilio M, Guo Y, Virshup DM, Patel K, Khorkova O, Styren S, Morse B, Yao Z, Keesler GA.
  Title
Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2.
  Journal
FEBS Lett 489:159-65 (2001)
DOI:10.1016/S0014-5793(00)02434-0
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
Harmer SL, Panda S, Kay SA.
  Title
Molecular bases of circadian rhythms.
  Journal
Annu Rev Cell Dev Biol 17:215-53 (2001)
DOI:10.1146/annurev.cellbio.17.1.215
Reference
  Authors
Young MW, Kay SA.
  Title
Time zones: a comparative genetics of circadian clocks.
  Journal
Nat Rev Genet 2:702-15 (2001)
DOI:10.1038/35088576
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
Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U.
  Title
The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator.
  Journal
Cell 110:251-60 (2002)
DOI:10.1016/S0092-8674(02)00825-5
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
Hogenesch JB, Gu YZ, Moran SM, Shimomura K, Radcliffe LA, Takahashi JS, Bradfield CA.
  Title
The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors.
  Journal
J Neurosci 20:RC83 (2000)
DOI:10.1523/JNEUROSCI.20-13-j0002.2000
Reference
  Authors
Shirogane T, Jin J, Ang XL, Harper JW
  Title
SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein.
  Journal
J Biol Chem 280:26863-72 (2005)
DOI:10.1074/jbc.M502862200
Reference
  Authors
Busino L, Bassermann F, Maiolica A, Lee C, Nolan PM, Godinho SI, Draetta GF, Pagano M
  Title
SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins.
  Journal
Science 316:900-4 (2007)
DOI:10.1126/science.1141194
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
Reference
  Authors
Mertens I, Husson SJ, Janssen T, Lindemans M, Schoofs L
  Title
PACAP and PDF signaling in the regulation of mammalian and insect circadian rhythms.
  Journal
Peptides 28:1775-83 (2007)
DOI:10.1016/j.peptides.2007.05.005
Related
pathway
ko04010  MAPK signaling pathway
ko04120  Ubiquitin mediated proteolysis
ko04713  Circadian entrainment
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