Entry |
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Name |
Circadian entrainment - Homo sapiens (human)
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Description |
Circadian entrainment is a fundamental property by which the period of the internal biological clock is entrained by recurring exogenous signals, such that the organism's endocrine and behavioral rhythms are synchronized to environmental cues. In mammals, a master clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and may synchronize circadian oscillators in peripheral tissues. Light signal is the dominant synchronizer for master SCN clock. Downstream from the retina, glutamate and PACAP are released and trigger the activation of signal transduction cascades, including CamKII and nNOS activity, cAMP- and cGMP-dependent protein kinases, and mitogen-activated protein kinase (MAPK). Of non-photic entrainment, important phase shifting capabilities have been found for melatonin, which inhibits light-induced phase shifts through inhibition of adenylate cyclase (AC). Multiple entrainment pathways converge into CREB regulation. In turn, phosphorylated CREB activates clock gene expression.
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Class |
Organismal Systems; Environmental adaptation
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Pathway map |

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Drug |
D02689 | Ramelteon (JAN/USAN/INN) |
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Other DBs |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
2902 | GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208] |
2903 | GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209] |
2904 | GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210] |
2905 | GRIN2C; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211] |
2906 | GRIN2D; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212] |
815 | CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17] |
817 | CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17] |
816 | CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17] |
818 | CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17] |
1385 | CREB1; cAMP responsive element binding protein 1 [KO:K05870] |
3708 | ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958] |
3710 | ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960] |
9722 | NOS1AP; nitric oxide synthase 1 adaptor protein [KO:K16513] |
51655 | RASD1; ras related dexamethasone induced 1 [KO:K07843] |
2770 | GNAI1; G protein subunit alpha i1 [KO:K04630] |
2773 | GNAI3; G protein subunit alpha i3 [KO:K04630] |
2771 | GNAI2; G protein subunit alpha i2 [KO:K04630] |
2775 | GNAO1; G protein subunit alpha o1 [KO:K04534] |
2790 | GNG10; G protein subunit gamma 10 [KO:K04545] |
2791 | GNG11; G protein subunit gamma 11 [KO:K04546] |
2792 | GNGT1; G protein subunit gamma transducin 1 [KO:K04548] |
2793 | GNGT2; G protein subunit gamma transducin 2 [KO:K04549] |
2890 | GRIA1; glutamate ionotropic receptor AMPA type subunit 1 [KO:K05197] |
2891 | GRIA2; glutamate ionotropic receptor AMPA type subunit 2 [KO:K05198] |
2892 | GRIA3; glutamate ionotropic receptor AMPA type subunit 3 [KO:K05199] |
2893 | GRIA4; glutamate ionotropic receptor AMPA type subunit 4 [KO:K05200] |
8913 | CACNA1G; calcium voltage-gated channel subunit alpha1 G [KO:K04854] |
8912 | CACNA1H; calcium voltage-gated channel subunit alpha1 H [KO:K04855] |
8911 | CACNA1I; calcium voltage-gated channel subunit alpha1 I [KO:K04856] |
116 | ADCYAP1; adenylate cyclase activating polypeptide 1 [KO:K05262] |
117 | ADCYAP1R1; ADCYAP receptor type I [KO:K04587] |
775 | CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850] |
776 | CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851] |
3760 | KCNJ3; potassium inwardly rectifying channel subfamily J member 3 [KO:K04997] |
3762 | KCNJ5; potassium inwardly rectifying channel subfamily J member 5 [KO:K04999] |
3763 | KCNJ6; potassium inwardly rectifying channel subfamily J member 6 [KO:K05000] |
3765 | KCNJ9; potassium inwardly rectifying channel subfamily J member 9 [KO:K05002] |
5187 | PER1; period circadian regulator 1 [KO:K21944] |
8864 | PER2; period circadian regulator 2 [KO:K02633] |
8863 | PER3; period circadian regulator 3 [KO:K21945] |
2353 | FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379] |
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Compound |
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Reference |
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Authors |
Brown TM, Piggins HD |
Title |
Electrophysiology of the suprachiasmatic circadian clock. |
Journal |
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Reference |
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Authors |
Dickson L, Finlayson K |
Title |
VPAC and PAC receptors: From ligands to function. |
Journal |
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Reference |
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Authors |
Golombek DA, Rosenstein RE |
Title |
Physiology of circadian entrainment. |
Journal |
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Reference |
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Authors |
Dubocovich ML, Markowska M |
Title |
Functional MT1 and MT2 melatonin receptors in mammals. |
Journal |
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Reference |
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Authors |
Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J |
Title |
International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. |
Journal |
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Reference |
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Authors |
Hardeland R |
Title |
Melatonin: signaling mechanisms of a pleiotropic agent. |
Journal |
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Reference |
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Authors |
Golombek DA, Ferreyra GA, Agostino PV, Murad AD, Rubio MF, Pizzio GA, Katz ME, Marpegan L, Bekinschtein TA |
Title |
From light to genes: moving the hands of the circadian clock. |
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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Reference |
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Authors |
Kim DY, Choi HJ, Kim JS, Kim YS, Jeong DU, Shin HC, Kim MJ, Han HC, Hong SK, Kim YI |
Title |
Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock. |
Journal |
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Reference |
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Authors |
Agostino PV, Ferreyra GA, Murad AD, Watanabe Y, Golombek DA |
Title |
Diurnal, circadian and photic regulation of calcium/calmodulin-dependent kinase II and neuronal nitric oxide synthase in the hamster suprachiasmatic nuclei. |
Journal |
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Reference |
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Authors |
Ferreyra GA, Golombek DA |
Title |
Rhythmicity of the cGMP-related signal transduction pathway in the mammalian circadian system. |
Journal |
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Reference |
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Authors |
Butcher GQ, Lee B, Cheng HY, Obrietan K |
Title |
Light stimulates MSK1 activation in the suprachiasmatic nucleus via a PACAP-ERK/MAP kinase-dependent mechanism. |
Journal |
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Reference |
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Authors |
Hamada T, Niki T, Ziging P, Sugiyama T, Watanabe S, Mikoshiba K, Ishida N |
Title |
Differential expression patterns of inositol trisphosphate receptor types 1 and 3 in the rat suprachiasmatic nucleus. |
Journal |
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Reference |
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Authors |
Diaz-Munoz M, Dent MA, Granados-Fuentes D, Hall AC, Hernandez-Cruz A, Harrington ME, Aguilar-Roblero R |
Title |
Circadian modulation of the ryanodine receptor type 2 in the SCN of rodents. |
Journal |
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Reference |
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Authors |
Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH |
Title |
Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. |
Journal |
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Reference |
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Authors |
Takahashi H, Umeda N, Tsutsumi Y, Fukumura R, Ohkaze H, Sujino M, van der Horst G, Yasui A, Inouye ST, Fujimori A, Ohhata T, Araki R, Abe M |
Title |
Mouse dexamethasone-induced RAS protein 1 gene is expressed in a circadian rhythmic manner in the suprachiasmatic nucleus. |
Journal |
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Reference |
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Authors |
Cheng HY, Dziema H, Papp J, Mathur DP, Koletar M, Ralph MR, Penninger JM, Obrietan K |
Title |
The molecular gatekeeper Dexras1 sculpts the photic responsiveness of the mammalian circadian clock. |
Journal |
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Related pathway |
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KO pathway |
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LinkDB |
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