KEGG   PATHWAY: mmu04710
mmu04710                    Pathway                                
Circadian rhythm - Mus musculus (house mouse)
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
mmu04710  Circadian rhythm

Other DBs
GO: 0007623
Mus musculus (house mouse) [GN:mmu]
19883  Rora; RAR-related orphan receptor alpha [KO:K08532]
225998  Rorb; RAR-related orphan receptor beta [KO:K08533]
19885  Rorc; RAR-related orphan receptor gamma [KO:K08534]
217166  Nr1d1; nuclear receptor subfamily 1, group D, member 1 [KO:K03728]
353187  Nr1d2; nuclear receptor subfamily 1, group D, member 2 [KO:K08531]
18030  Nfil3; nuclear factor, interleukin 3, regulated [KO:K09059]
11865  Arntl; aryl hydrocarbon receptor nuclear translocator-like [KO:K02296]
13170  Dbp; D site albumin promoter binding protein [KO:K09056]
20893  Bhlhe40; basic helix-loop-helix family, member e40 [KO:K03729]
79362  Bhlhe41; basic helix-loop-helix family, member e41 [KO:K03730]
104318  Csnk1d; casein kinase 1, delta [KO:K08959] [EC:]
27373  Csnk1e; casein kinase 1, epsilon [KO:K08960] [EC:]
18626  Per1; period circadian clock 1 [KO:K21944]
18627  Per2; period circadian clock 2 [KO:K02633]
18628  Per3; period circadian clock 3 [KO:K21945]
12952  Cry1; cryptochrome 1 (photolyase-like) [KO:K02295]
12953  Cry2; cryptochrome 2 (photolyase-like) [KO:K02295]
12753  Clock; circadian locomotor output cycles kaput [KO:K02223] [EC:]
18143  Npas2; neuronal PAS domain protein 2 [KO:K09026]
12912  Creb1; cAMP responsive element binding protein 1 [KO:K05870]
105787  Prkaa1; protein kinase, AMP-activated, alpha 1 catalytic subunit [KO:K07198] [EC:]
108079  Prkaa2; protein kinase, AMP-activated, alpha 2 catalytic subunit [KO:K07198] [EC:]
19079  Prkab1; protein kinase, AMP-activated, beta 1 non-catalytic subunit [KO:K07199]
108097  Prkab2; protein kinase, AMP-activated, beta 2 non-catalytic subunit [KO:K07199]
19082  Prkag1; protein kinase, AMP-activated, gamma 1 non-catalytic subunit [KO:K07200]
241113  Prkag3; protein kinase, AMP-activated, gamma 3 non-catalytic subunit [KO:K07200]
108099  Prkag2; protein kinase, AMP-activated, gamma 2 non-catalytic subunit [KO:K07200]
56438  Rbx1; ring-box 1 [KO:K03868] [EC:]
26965  Cul1; cullin 1 [KO:K03347]
21402  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
103583  Fbxw11; F-box and WD-40 domain protein 11 [KO:K03362]
12234  Btrc; beta-transducin repeat containing protein [KO:K03362]
213311  Fbxl21; F-box and leucine-rich repeat protein 21 [KO:K10287]
50789  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)
mmu04010  MAPK signaling pathway
mmu04120  Ubiquitin mediated proteolysis
mmu04713  Circadian entrainment
KO pathway

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