KEGG   PATHWAY: hsa04710
hsa04710                    Pathway                                
Circadian rhythm - Homo sapiens (human)
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.
Organismal Systems; Environmental adaptation
Pathway map
hsa04710  Circadian rhythm

Other DBs
GO: 0007623
Homo sapiens (human) [GN:hsa]
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]
9572  NR1D1; nuclear receptor subfamily 1 group D member 1 [KO:K03728]
9975  NR1D2; nuclear receptor subfamily 1 group D member 2 [KO:K08531]
4783  NFIL3; nuclear factor, interleukin 3 regulated [KO:K09059]
406  BMAL1; basic helix-loop-helix ARNT like 1 [KO:K02296]
1628  DBP; D-box binding PAR bZIP transcription factor [KO:K09056]
8553  BHLHE40; basic helix-loop-helix family member e40 [KO:K03729]
79365  BHLHE41; basic helix-loop-helix family member e41 [KO:K03730]
1453  CSNK1D; casein kinase 1 delta [KO:K08959] [EC:]
1454  CSNK1E; casein kinase 1 epsilon [KO:K08960] [EC:]
102800317  TPTEP2-CSNK1E; TPTEP2-CSNK1E readthrough [KO:K08960] [EC:]
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]
9575  CLOCK; clock circadian regulator [KO:K02223] [EC:]
4862  NPAS2; neuronal PAS domain protein 2 [KO:K09026]
1385  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
5562  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:]
5563  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:]
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]
9978  RBX1; ring-box 1 [KO:K03868] [EC:]
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]
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
Takahashi JS
Transcriptional architecture of the mammalian circadian clock.
Nat Rev Genet 18:164-179 (2017)
Wang S, Li F, Lin Y, Wu B
Targeting REV-ERBalpha for therapeutic purposes: promises and challenges.
Theranostics 10:4168-4182 (2020)
Panda S, Hogenesch JB, Kay SA.
Circadian rhythms from flies to human.
Nature 417:329-35 (2002)
Honma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, Kato Y, Honma K.
Dec1 and Dec2 are regulators of the mammalian molecular clock.
Nature 419:841-4 (2002)
Fu L, Lee CC.
The circadian clock: pacemaker and tumour suppressor.
Nat Rev Cancer 3:350-61 (2003)
Schibler U, Sassone-Corsi P.
A web of circadian pacemakers.
Cell 111:919-22 (2002)
Takahashi JS, Hong HK, Ko CH, McDearmon EL
The genetics of mammalian circadian order and disorder: implications for physiology and disease.
Nat Rev Genet 9:764-75 (2008)
hsa04010  MAPK signaling pathway
hsa04120  Ubiquitin mediated proteolysis
hsa04713  Circadian entrainment
KO pathway

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