KEGG   PATHWAY: hsa04710Help
Entry
hsa04710                    Pathway                                

Name
Circadian rhythm - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
hsa04710  Circadian rhythm
hsa04710

Ortholog table
Module
hsa_M00380  SCF-BTRC complex [PATH:hsa04710]
Disease
H00688  Familial advanced sleep phase syndrome
H00689  Delayed sleep phase syndrome
Other DBs
BSID: 83084
GO: 0007623
Organism
Homo sapiens (human) [GN:hsa]
Gene
1453  CSNK1D; casein kinase 1 delta [KO:K08959] [EC:2.7.11.1]
1454  CSNK1E; casein kinase 1 epsilon [KO:K08960] [EC:2.7.11.1]
102800317  TPTEP2-CSNK1E; TPTEP2-CSNK1E readthrough [KO:K08960] [EC:2.7.11.1]
5187  PER1; period circadian regulator 1 [KO:K21944]
8864  PER2; period circadian regulator 2 [KO:K02633]
8863  PER3; period circadian regulator 3 [KO:K21945]
1407  CRY1; cryptochrome circadian regulator 1 [KO:K02295]
1408  CRY2; cryptochrome circadian regulator 2 [KO:K02295]
406  ARNTL; aryl hydrocarbon receptor nuclear translocator like [KO:K02296]
9575  CLOCK; clock circadian regulator [KO:K02223] [EC:2.3.1.48]
4862  NPAS2; neuronal PAS domain protein 2 [KO:K09026]
9572  NR1D1; nuclear receptor subfamily 1 group D member 1 [KO:K03728]
6095  RORA; RAR related orphan receptor A [KO:K08532]
6096  RORB; RAR related orphan receptor B [KO:K08533]
6097  RORC; RAR related orphan receptor C [KO:K08534]
8553  BHLHE40; basic helix-loop-helix family member e40 [KO:K03729]
79365  BHLHE41; basic helix-loop-helix family member e41 [KO:K03730]
9978  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
8454  CUL1; cullin 1 [KO:K03347]
6500  SKP1; S-phase kinase associated protein 1 [KO:K03094]
8945  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
23291  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
26224  FBXL3; F-box and leucine rich repeat protein 3 [KO:K10269]
5562  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.11]
5563  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.11]
5564  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
5565  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
5571  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
53632  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
51422  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
1385  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
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
KO pathway
ko04710   
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