KEGG   PATHWAY: rno04710
Entry
rno04710                    Pathway                                
Name
Circadian rhythm - Rattus norvegicus (rat)
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
rno04710  Circadian rhythm
rno04710

Other DBs
GO: 0007623
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
114519  Nfil3; nuclear factor interleukin-3-regulated protein [KO:K09059]
117095  Bhlhe41; class E basic helix-loop-helix protein 41 [KO:K03730]
170917  Cry2; cryptochrome-2 [KO:K02295]
24309  Dbp; D site-binding protein isoform 1 [KO:K09056]
252917  Nr1d1; nuclear receptor subfamily 1 group D member 1 isoform 1 [KO:K03728]
25520  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
259241  Nr1d2; nuclear receptor subfamily 1 group D member 2 [KO:K08531]
287280  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
287422  Per1; period circadian protein homolog 1 [KO:K21944]
29657  Bmal1; basic helix-loop-helix ARNT-like protein 1 [KO:K02296]
299691  Cry1; cryptochrome-1 [KO:K02295]
300084  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
300807  Rora; nuclear receptor ROR-alpha isoform X1 [KO:K08532]
301518  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
303024  Fbxw11; F-box/WD repeat-containing protein 11 isoform 1 [KO:K03362]
306129  Fbxl3; F-box/LRR-repeat protein 3 [KO:K10269]
306750  Fbxl21; F-box/LRR-repeat protein 21 [KO:K10287]
309288  Rorb; nuclear receptor ROR-beta [KO:K08533]
316351  Npas2; neuronal PAS domain-containing protein 2 [KO:K09026]
361765  Btrc; F-box/WD repeat-containing protein 1A [KO:K03362]
362356  Cul1; cullin-1 [KO:K03347]
368158  Rorc; nuclear receptor ROR-gamma [KO:K08534]
373545  Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform 1 [KO:K07200]
58822  Csnk1e; casein kinase I [KO:K08960] [EC:2.7.11.1]
60447  Clock; circadian locomoter output cycles protein kaput isoform 1 [KO:K02223] [EC:2.3.1.48]
63840  Per2; period circadian protein homolog 2 [KO:K02633]
64462  Csnk1d; casein kinase I isoform delta isoform 1 [KO:K08959] [EC:2.7.11.1]
64562  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
65248  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
78962  Per3; period circadian protein homolog 3 [KO:K21945]
78975  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
79431  Bhlhe40; class E basic helix-loop-helix protein 40 [KO:K03729]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
83803  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
Compound
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
Reference
  Authors
Takahashi JS
  Title
Transcriptional architecture of the mammalian circadian clock.
  Journal
Nat Rev Genet 18:164-179 (2017)
DOI:10.1038/nrg.2016.150
Reference
  Authors
Wang S, Li F, Lin Y, Wu B
  Title
Targeting REV-ERBalpha for therapeutic purposes: promises and challenges.
  Journal
Theranostics 10:4168-4182 (2020)
DOI:10.7150/thno.43834
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
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
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
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
Related
pathway
rno04010  MAPK signaling pathway
rno04120  Ubiquitin mediated proteolysis
rno04713  Circadian entrainment
KO pathway
ko04710   

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