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
Circadian rhythm
hsa04710

All organismsOrtholog table
Module
SCF-BTRC complex [PATH:hsa04710]
Disease
H00688  
Familial advanced sleep phase syndrome
Other DBs
BSID: 
GO: 
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]
LOC400927-CSNK1E readthrough; K08960 casein kinase 1, epsilon [EC:2.7.11.1] [KO:K08960] [EC:2.7.11.1]
5187  
PER1; period circadian clock 1 [KO:K02633]
8863  
PER3; period circadian clock 3 [KO:K02633]
8864  
PER2; period circadian clock 2 [KO:K02633]
1407  
CRY1; cryptochrome circadian clock 1 [KO:K02295]
1408  
CRY2; cryptochrome circadian clock 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]
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)
Reference
  Authors
Panda S, Hogenesch JB, Kay SA.
  Title
Circadian rhythms from flies to human.
  Journal
Nature 417:329-35 (2002)
Reference
  Authors
Harmer SL, Panda S, Kay SA.
  Title
Molecular bases of circadian rhythms.
  Journal
Annu Rev Cell Dev Biol 17:215-53 (2001)
Reference
  Authors
Young MW, Kay SA.
  Title
Time zones: a comparative genetics of circadian clocks.
  Journal
Nat Rev Genet 2:702-15 (2001)
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)
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)
Reference
  Authors
Fu L, Lee CC.
  Title
The circadian clock: pacemaker and tumour suppressor.
  Journal
Nat Rev Cancer 3:350-61 (2003)
Reference
  Authors
Schibler U, Sassone-Corsi P.
  Title
A web of circadian pacemakers.
  Journal
Cell 111:919-22 (2002)
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)
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)
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)
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)
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)
KO pathway
 

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