Entry |
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Name |
Circadian rhythm - Homo sapiens (human)
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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.
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Class |
Organismal Systems; Environmental adaptation
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Pathway map |

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Module |
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Disease |
H00688 | Familial advanced sleep phase syndrome |
H00689 | Delayed sleep phase syndrome |
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Other DBs |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
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] |
406 | ARNTL; aryl hydrocarbon receptor nuclear translocator like [KO:K02296] |
4862 | NPAS2; neuronal PAS domain protein 2 [KO:K09026] |
9572 | NR1D1; nuclear receptor subfamily 1 group D member 1 [KO:K03728] |
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] |
8553 | BHLHE40; basic helix-loop-helix family member e40 [KO:K03729] |
79365 | BHLHE41; basic helix-loop-helix family member e41 [KO:K03730] |
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] |
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] |
1385 | CREB1; cAMP responsive element binding protein 1 [KO:K05870] |
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Compound |
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Reference |
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Authors |
Camacho F, Cilio M, Guo Y, Virshup DM, Patel K, Khorkova O, Styren S, Morse B, Yao Z, Keesler GA. |
Title |
Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. |
Journal |
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Reference |
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Authors |
Panda S, Hogenesch JB, Kay SA. |
Title |
Circadian rhythms from flies to human. |
Journal |
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Reference |
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Authors |
Harmer SL, Panda S, Kay SA. |
Title |
Molecular bases of circadian rhythms. |
Journal |
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Reference |
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Authors |
Young MW, Kay SA. |
Title |
Time zones: a comparative genetics of circadian clocks. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U. |
Title |
The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. |
Journal |
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Reference |
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Authors |
Fu L, Lee CC. |
Title |
The circadian clock: pacemaker and tumour suppressor. |
Journal |
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Reference |
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Authors |
Schibler U, Sassone-Corsi P. |
Title |
A web of circadian pacemakers. |
Journal |
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Reference |
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Authors |
Hogenesch JB, Gu YZ, Moran SM, Shimomura K, Radcliffe LA, Takahashi JS, Bradfield CA. |
Title |
The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors. |
Journal |
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Reference |
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Authors |
Shirogane T, Jin J, Ang XL, Harper JW |
Title |
SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. |
Journal |
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Reference |
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Authors |
Busino L, Bassermann F, Maiolica A, Lee C, Nolan PM, Godinho SI, Draetta GF, Pagano M |
Title |
SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. |
Journal |
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Reference |
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Authors |
Takahashi JS, Hong HK, Ko CH, McDearmon EL |
Title |
The genetics of mammalian circadian order and disorder: implications for physiology and disease. |
Journal |
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Reference |
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Authors |
Mertens I, Husson SJ, Janssen T, Lindemans M, Schoofs L |
Title |
PACAP and PDF signaling in the regulation of mammalian and insect circadian rhythms. |
Journal |
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KO pathway |
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LinkDB |
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