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 Other DBs Organism Homo sapiens (human) [GN:
hsa ]
Gene 1385 CREB1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870 ]
23291 FBXW11; F-box/WD repeat-containing protein 11 isoform C [KO:K03362 ]
406 BMAL1; basic helix-loop-helix ARNT-like protein 1 isoform c [KO:K02296 ]
4783 NFIL3; nuclear factor interleukin-3-regulated protein [KO:K09059 ]
4862 NPAS2; neuronal PAS domain-containing protein 2 [KO:K09026 ]
51422 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform a [KO:K07200 ]
5187 PER1; period circadian protein homolog 1 [KO:K21944 ]
53632 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
5562 PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [KO:K07198 ] [EC:2.7.11.31 ]
5563 PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198 ] [EC:2.7.11.31 ]
5564 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
5565 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
5571 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform 1 [KO:K07200 ]
6095 RORA; nuclear receptor ROR-alpha isoform a [KO:K08532 ]
6096 RORB; nuclear receptor ROR-beta isoform 2 [KO:K08533 ]
6097 RORC; nuclear receptor ROR-gamma isoform a [KO:K08534 ]
6500 SKP1; S-phase kinase-associated protein 1 isoform b [KO:K03094 ]
79365 BHLHE41; class E basic helix-loop-helix protein 41 [KO:K03730 ]
8553 BHLHE40; class E basic helix-loop-helix protein 40 [KO:K03729 ]
8863 PER3; period circadian protein homolog 3 isoform 4 [KO:K21945 ]
8864 PER2; period circadian protein homolog 2 [KO:K02633 ]
8945 BTRC; F-box/WD repeat-containing protein 1A isoform 1 [KO:K03362 ]
9572 NR1D1; nuclear receptor subfamily 1 group D member 1 [KO:K03728 ]
9975 NR1D2; nuclear receptor subfamily 1 group D member 2 isoform 1 [KO:K08531 ]
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
