Entry 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 adaptationBRITE hierarchy
Pathway map Ortholog table Other DBs Organism Homo sapiens (human) [GN:
hsa ]
Gene 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 ]
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 ]
4862 NPAS2; neuronal PAS domain protein 2 [KO:K09026 ]
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
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 ]
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 ]
Compound Reference Authors Takahashi JS
Title Transcriptional architecture of the mammalian circadian clock.
Journal Reference Authors Wang S, Li F, Lin Y, Wu B
Title Targeting REV-ERBalpha for therapeutic purposes: promises and challenges.
Journal Reference Authors Panda S, Hogenesch JB, Kay SA.
Title Circadian rhythms from flies to human.
Journal 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 Reference Authors Fu L, Lee CC.
Title The circadian clock: pacemaker and tumour suppressor.
Journal Reference Authors Schibler U, Sassone-Corsi P.
Title A web of circadian pacemakers.
Journal 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 Related KO pathway LinkDB All DBs
