BMAL1:CLOCK,NPAS2 activates circadian gene expression (Homo sapiens)

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4, 322, 26, 30, 3418, 21, 29162871411, 2618, 21, 29, 35228, 1011132, 26, 30, 341411, 261910, 3365, 271, 31251920nucleoplasmcytosolNCOA1 p-S-ARNTL PER2 genePPARA:RXRACoactivator complexp-S-CLOCK AVP(20-28)p-S-CLOCK CLOCK p-S-NPAS2 BMAL2:CLOCKDBPp-S-CLOCK p-BMAL1:p-CLOCK,NPAS2:PPARA genep-S-CLOCK NAMPTCRY1 geneNCOA6 p-S-ARNTL NCOA2 p-S-CLOCK NAMPT gene p-S-CLOCK NR3C1 p-CREB:CRTC1:PER1genep-BMAL1:p-CLOCK,NPAS2:CRY1 genePER1p-S-ARNTL p-S-NPAS2 AVP genep-S-CLOCK PPARACRY2p-S-ARNTL ALA NR3C1:DexamethasoneF7 geneEPA SERPINE1 GeneCRY1 gene RORA genep-BMAL1:p-CLOCK,NPAS2:PER2 genep-S-CLOCK Palm PER1 gene NR1D1 gene p-BMAL1:p-CLOCK,NPAS2p-S-ARNTL PPARA p-BMAL1:p-CLOCK,NPAS2:BHLHE40 genep-S-CLOCK p-S-ARNTL RXRA TBL1X p-S-ARNTL BHLHE40 genep-S-NPAS2 NR1D1 gene p-S-NPAS2 PPARA geneEP300 F7(21-466)PER2 gene SERPINE1BHLHE41 genep-S-NPAS2 DEXA p-S-CLOCK CCRN4Lp-S-NPAS2 AA BHLHE40 gene DBP geneBHLHE41HELZ2 PPARGC1A TBL1XR1 p-BMAL1:p-CLOCK,NPAS2:F7 genep-BMAL1:p-CLOCK,NPAS2:CCRN4L geneBHLHE41 gene p-S-NPAS2 ARNTL2 p-BMAL1:p-CLOCK,NPAS2:BHLHE41 genePER1 gene NR1D1NR1D1 gene HDAC3 p-S133-CREB1 p-BMAL1:p-CLOCK,NPAS2:DBP geneCRY2 geneCRTC1 NR1D1 AVP gene BHLHE40SMARCD3 p-S-NPAS2 CREBBP p-BMAL1:p-CLOCK,NPAS2:RORA genep-S-ARNTL RORACARM1 SERPINE1 Gene p-S-CLOCK p-BMAL1:p-CLOCK,NPAS2:SERPINE1 genep-S-CLOCK ferriheme b CCRN4L gene p-S-NPAS2 PER2p-S-CLOCK p-S-CLOCK CRY1DBP gene TGS1 CHD9 CCRN4L geneRORA:Coactivator:NR1D1 genep-S-NPAS2 p-S-NPAS2 NR1D1 geneNRIP1 RORA p-S-ARNTL MED1 SIK1p-S-ARNTL p-S-CLOCK PPARA gene p-BMAL1:p-CLOCK,NPAS2:NAMPT genep-S-ARNTL p-S-NPAS2 NCOR1 p-S-ARNTL F7 gene p-S-ARNTL HIF1Ap-S-NPAS2 p-BMAL1:p-CLOCK,NPAS2:PER1 geneLINA p-BMAL1:p-CLOCK,NPAS2:AVP genep-BMAL1:p-CLOCK,NPAS2:NR1D1 geneNR1D1:heme:Corepressors:NR1D1 genep-S-NPAS2 RORA gene p-S-ARNTL p-S-NPAS2 p-S-ARNTL Peroxisome Proliferator Receptor Element (PPRE) NAMPT genePER1 gene3, 1518, 21, 291112, 1723359, 242, 26, 30, 34


Description

As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) and BMAL1:NPAS2 (ARNTL:NPAS2) heterodimers bind to sequence elements (E boxes) in the promoters of target genes and enhance transcription (Gekakis et al. 1998, reviewed in Munoz and Baler 2003). View original pathway at:Reactome.

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Bibliography

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  1. Schoenhard JA, Smith LH, Painter CA, Eren M, Johnson CH, Vaughan DE.; ''Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2.''; PubMed
  2. Maemura K, de la Monte SM, Chin MT, Layne MD, Hsieh CM, Yet SF, Perrella MA, Lee ME.; ''CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.''; PubMed
  3. Kawamoto T, Noshiro M, Sato F, Maemura K, Takeda N, Nagai R, Iwata T, Fujimoto K, Furukawa M, Miyazaki K, Honma S, Honma Ki, Kato Y.; ''A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation.''; PubMed
  4. Hagen FS, Gray CL, O'Hara P, Grant FJ, Saari GC, Woodbury RG, Hart CE, Insley M, Kisiel W, Kurachi K.; ''Characterization of a cDNA coding for human factor VII.''; PubMed
  5. Thim L, Bjoern S, Christensen M, Nicolaisen EM, Lund-Hansen T, Pedersen AH, Hedner U.; ''Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells.''; PubMed
  6. van der Bom JG, Bots ML, Haverkate F, Kluft C, Grobbee DE.; ''The 4G5G polymorphism in the gene for PAI-1 and the circadian oscillation of plasma PAI-1.''; PubMed
  7. Khatib ZA, Inaba T, Valentine M, Look AT.; ''Chromosomal localization and cDNA cloning of the human DBP and TEF genes.''; PubMed
  8. Ognjanovic S, Bao S, Yamamoto SY, Garibay-Tupas J, Samal B, Bryant-Greenwood GD.; ''Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes.''; PubMed
  9. Fisch S, Gray S, Heymans S, Haldar SM, Wang B, Pfister O, Cui L, Kumar A, Lin Z, Sen-Banerjee S, Das H, Petersen CA, Mende U, Burleigh BA, Zhu Y, Pinto YM, Liao R, Jain MK.; ''Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy.''; PubMed
  10. Juge-Aubry C, Pernin A, Favez T, Burger AG, Wahli W, Meier CA, Desvergne B.; ''DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.''; PubMed
  11. Fujimoto K, Shen M, Noshiro M, Matsubara K, Shingu S, Honda K, Yoshida E, Suardita K, Matsuda Y, Kato Y.; ''Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins.''; PubMed
  12. Muñoz E, Baler R.; ''The circadian E-box: when perfect is not good enough.''; PubMed
  13. Sausville E, Carney D, Battey J.; ''The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line.''; PubMed
  14. Tamaru T, Hirayama J, Isojima Y, Nagai K, Norioka S, Takamatsu K, Sassone-Corsi P.; ''CK2alpha phosphorylates BMAL1 to regulate the mammalian clock.''; PubMed
  15. Chong NW, Codd V, Chan D, Samani NJ.; ''Circadian clock genes cause activation of the human PAI-1 gene promoter with 4G/5G allelic preference.''; PubMed
  16. Muñoz E, Brewer M, Baler R.; ''Circadian Transcription. Thinking outside the E-Box.''; PubMed
  17. Greenberg D, Miao CH, Ho WT, Chung DW, Davie EW.; ''Liver-specific expression of the human factor VII gene.''; PubMed
  18. Oishi K, Shirai H, Ishida N.; ''CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPARalpha) in mice.''; PubMed
  19. Rakhshandehroo M, Hooiveld G, Müller M, Kersten S.; ''Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.''; PubMed
  20. Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ.; ''Role of the CLOCK protein in the mammalian circadian mechanism.''; PubMed
  21. Dardente H, Fortier EE, Martineau V, Cermakian N.; ''Cryptochromes impair phosphorylation of transcriptional activators in the clock: a general mechanism for circadian repression.''; PubMed
  22. Li R, Yue J, Zhang Y, Zhou L, Hao W, Yuan J, Qiang B, Ding JM, Peng X, Cao JM.; ''CLOCK/BMAL1 regulates human nocturnin transcription through binding to the E-box of nocturnin promoter.''; PubMed
  23. Mukherjee R, Jow L, Noonan D, McDonnell DP.; ''Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators.''; PubMed

History

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CompareRevisionActionTimeUserComment
101335view11:22, 1 November 2018ReactomeTeamreactome version 66
100873view20:55, 31 October 2018ReactomeTeamreactome version 65
100414view19:29, 31 October 2018ReactomeTeamreactome version 64
99963view16:14, 31 October 2018ReactomeTeamreactome version 63
99518view14:47, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99160view12:41, 31 October 2018ReactomeTeamreactome version 62
93861view13:41, 16 August 2017ReactomeTeamreactome version 61
93426view11:23, 9 August 2017ReactomeTeamreactome version 61
87095view14:29, 18 July 2016MkutmonOntology Term : 'transcription pathway' added !
86513view09:19, 11 July 2016ReactomeTeamreactome version 56
83343view10:51, 18 November 2015ReactomeTeamVersion54
81499view13:02, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AA MetaboliteCHEBI:15843 (ChEBI)
ALA MetaboliteCHEBI:27432 (ChEBI)
ARNTL2 ProteinQ8WYA1 (Uniprot-TrEMBL)
AVP gene ProteinENSG00000101200 (Ensembl)
AVP geneGeneProductENSG00000101200 (Ensembl)
AVP(20-28)ProteinP01185 (Uniprot-TrEMBL)
BHLHE40 gene ProteinENSG00000134107 (Ensembl)
BHLHE40 geneGeneProductENSG00000134107 (Ensembl)
BHLHE40ProteinO14503 (Uniprot-TrEMBL)
BHLHE41 gene ProteinENSG00000123095 (Ensembl)
BHLHE41 geneGeneProductENSG00000123095 (Ensembl)
BHLHE41ProteinQ9C0J9 (Uniprot-TrEMBL)
BMAL2:CLOCKComplexR-HSA-879827 (Reactome)
CARM1 ProteinQ86X55 (Uniprot-TrEMBL)
CCRN4L gene ProteinENSG00000151014 (Ensembl)
CCRN4L geneGeneProductENSG00000151014 (Ensembl)
CCRN4LProteinQ9UK39 (Uniprot-TrEMBL)
CHD9 ProteinQ3L8U1 (Uniprot-TrEMBL)
CLOCK ProteinO15516 (Uniprot-TrEMBL)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CRTC1 ProteinQ6UUV9 (Uniprot-TrEMBL)
CRY1 gene ProteinENSG00000008405 (Ensembl)
CRY1 geneGeneProductENSG00000008405 (Ensembl)
CRY1ProteinQ16526 (Uniprot-TrEMBL)
CRY2 geneGeneProductENSG00000121671 (Ensembl)
CRY2ProteinQ49AN0 (Uniprot-TrEMBL)
DBP gene ProteinENSG00000105516 (Ensembl)
DBP geneGeneProductENSG00000105516 (Ensembl)
DBPProteinQ10586 (Uniprot-TrEMBL)
DEXA MetaboliteCHEBI:41879 (ChEBI)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EPA MetaboliteCHEBI:28364 (ChEBI)
F7 gene ProteinENSG00000057593 (Ensembl)
F7 geneGeneProductENSG00000057593 (Ensembl)
F7(21-466)ProteinP08709 (Uniprot-TrEMBL)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HELZ2 ProteinQ9BYK8 (Uniprot-TrEMBL)
HIF1AProteinQ16665 (Uniprot-TrEMBL)
LINA MetaboliteCHEBI:17351 (ChEBI)
MED1 ProteinQ15648 (Uniprot-TrEMBL) MED1 is a component of each of the various Mediator complexes, that function as transcription co-activators. The MED1-containing compolexes include the DRIP, ARC, TRIP and CRSP compllexes.
NAMPT gene ProteinENSG00000105835 (Ensembl)
NAMPT geneGeneProductENSG00000105835 (Ensembl)
NAMPTProteinP43490 (Uniprot-TrEMBL)
NCOA1 ProteinQ15788 (Uniprot-TrEMBL)
NCOA2 ProteinQ15596 (Uniprot-TrEMBL)
NCOA6 ProteinQ14686 (Uniprot-TrEMBL)
NCOR1 ProteinO75376 (Uniprot-TrEMBL)
NR1D1 ProteinP20393 (Uniprot-TrEMBL)
NR1D1 gene ProteinENSG00000126368 (Ensembl)
NR1D1 geneGeneProductENSG00000126368 (Ensembl)
NR1D1:heme:Corepressors:NR1D1 geneComplexR-HSA-5663262 (Reactome)
NR1D1ProteinP20393 (Uniprot-TrEMBL)
NR3C1 ProteinP04150 (Uniprot-TrEMBL)
NR3C1:DexamethasoneComplexR-HSA-879850 (Reactome)
NRIP1 ProteinP48552 (Uniprot-TrEMBL)
PER1 gene ProteinENSG00000179094 (Ensembl)
PER1 geneGeneProductENSG00000179094 (Ensembl)
PER1ProteinO15534 (Uniprot-TrEMBL)
PER2 gene ProteinENSG00000132326 (Ensembl)
PER2 geneGeneProductENSG00000132326 (Ensembl)
PER2ProteinO15055 (Uniprot-TrEMBL)
PPARA ProteinQ07869 (Uniprot-TrEMBL)
PPARA gene ProteinENSG00000186951 (Ensembl)
PPARA geneGeneProductENSG00000186951 (Ensembl)
PPARA:RXRA Coactivator complexComplexR-HSA-400154 (Reactome)
PPARAProteinQ07869 (Uniprot-TrEMBL)
PPARGC1A ProteinQ9UBK2 (Uniprot-TrEMBL)
Palm MetaboliteCHEBI:15756 (ChEBI)
Peroxisome Proliferator Receptor Element (PPRE) R-NUL-422139 (Reactome) Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
RORA ProteinP35398 (Uniprot-TrEMBL)
RORA gene ProteinENSG00000069667 (Ensembl)
RORA geneGeneProductENSG00000069667 (Ensembl)
RORA:Coactivator:NR1D1 geneComplexR-HSA-5663260 (Reactome)
RORAProteinP35398 (Uniprot-TrEMBL)
RXRA ProteinP19793 (Uniprot-TrEMBL)
SERPINE1 Gene ProteinENSG00000106366 (Ensembl)
SERPINE1 GeneGeneProductENSG00000106366 (Ensembl)
SERPINE1ProteinP05121 (Uniprot-TrEMBL)
SIK1ProteinP57059 (Uniprot-TrEMBL)
SMARCD3 ProteinQ6STE5 (Uniprot-TrEMBL)
TBL1X ProteinO60907 (Uniprot-TrEMBL)
TBL1XR1 ProteinQ9BZK7 (Uniprot-TrEMBL)
TGS1 ProteinQ96RS0 (Uniprot-TrEMBL)
ferriheme b MetaboliteCHEBI:36144 (ChEBI)
p-BMAL1:p-CLOCK,NPAS2:AVP geneComplexR-HSA-5663184 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:BHLHE40 geneComplexR-HSA-5663107 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:BHLHE41 geneComplexR-HSA-5663121 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:CCRN4L geneComplexR-HSA-5663134 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:CRY1 geneComplexR-HSA-5663148 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:DBP geneComplexR-HSA-5663186 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:F7 geneComplexR-HSA-5663136 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:NAMPT geneComplexR-HSA-5663154 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:NR1D1 geneComplexR-HSA-5663173 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PER1 geneComplexR-HSA-5663110 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PER2 geneComplexR-HSA-5663176 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PPARA geneComplexR-HSA-5663137 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:RORA geneComplexR-HSA-5669290 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:SERPINE1 geneComplexR-HSA-5663104 (Reactome)
p-BMAL1:p-CLOCK,NPAS2ComplexR-HSA-421315 (Reactome)
p-CREB:CRTC1:PER1 geneComplexR-HSA-5656495 (Reactome)
p-S-ARNTL ProteinO00327 (Uniprot-TrEMBL)
p-S-CLOCK ProteinO15516 (Uniprot-TrEMBL)
p-S-NPAS2 ProteinQ99743 (Uniprot-TrEMBL)
p-S133-CREB1 ProteinP16220 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
AVP geneR-HSA-5663165 (Reactome)
AVP geneR-HSA-879782 (Reactome)
AVP(20-28)ArrowR-HSA-879782 (Reactome)
BHLHE40 geneR-HSA-5663170 (Reactome)
BHLHE40 geneR-HSA-879798 (Reactome)
BHLHE40ArrowR-HSA-879798 (Reactome)
BHLHE41 geneR-HSA-5663105 (Reactome)
BHLHE41 geneR-HSA-879770 (Reactome)
BHLHE41ArrowR-HSA-879770 (Reactome)
BMAL2:CLOCKArrowR-HSA-549364 (Reactome)
CCRN4L geneR-HSA-549424 (Reactome)
CCRN4L geneR-HSA-5663138 (Reactome)
CCRN4LArrowR-HSA-549424 (Reactome)
CRY1 geneR-HSA-549467 (Reactome)
CRY1 geneR-HSA-5663120 (Reactome)
CRY1ArrowR-HSA-549467 (Reactome)
CRY2 geneR-HSA-549470 (Reactome)
CRY2ArrowR-HSA-549470 (Reactome)
DBP geneR-HSA-5663132 (Reactome)
DBP geneR-HSA-879762 (Reactome)
DBPArrowR-HSA-879762 (Reactome)
F7 geneR-HSA-549428 (Reactome)
F7 geneR-HSA-5663127 (Reactome)
F7(21-466)ArrowR-HSA-549428 (Reactome)
HIF1AArrowR-HSA-1368133 (Reactome)
NAMPT geneR-HSA-1368889 (Reactome)
NAMPT geneR-HSA-5663122 (Reactome)
NAMPTArrowR-HSA-1368889 (Reactome)
NR1D1 geneR-HSA-549475 (Reactome)
NR1D1 geneR-HSA-5663155 (Reactome)
NR1D1:heme:Corepressors:NR1D1 geneTBarR-HSA-549475 (Reactome)
NR1D1ArrowR-HSA-549475 (Reactome)
NR3C1:DexamethasoneArrowR-HSA-549493 (Reactome)
PER1 geneR-HSA-549533 (Reactome)
PER1 geneR-HSA-5663174 (Reactome)
PER1ArrowR-HSA-549533 (Reactome)
PER2 geneR-HSA-549493 (Reactome)
PER2 geneR-HSA-5663118 (Reactome)
PER2ArrowR-HSA-549493 (Reactome)
PPARA geneR-HSA-5663156 (Reactome)
PPARA geneR-HSA-879724 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-879724 (Reactome)
PPARAArrowR-HSA-879724 (Reactome)
R-HSA-1368133 (Reactome) The RORA gene is transcribed to yield mRNA and the mRNA is transcribed to yield protein.
R-HSA-1368889 (Reactome) The NAMPT (NamPRT) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer enhances transcription of NAMPT.
R-HSA-549364 (Reactome) The PAI-1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The PAI-1 gene shows circadian expression due to direct transcriptional activation by the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer and the BMAL2:CLOCK (CLIF:CLOCK, ARNTL2:CLOCK) heterodimer.
R-HSA-549424 (Reactome) The NOCTURNIN gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The NOCTURNIN gene shows circadian expression because the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds an E-box element in the NOCTURNIN promoter and activates transcription.
R-HSA-549428 (Reactome) The FACTOR VII (F7) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. In mouse the F7 gene shows circadian expression due to activation by the Bmal1:Clock (Arntl:Clock) heterodimer.
R-HSA-549467 (Reactome) The CRYPTOCHROME-1 (CRY1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. CRY1 mRNA and protein show circadian expression. The promoter of the CRY1 gene contains an E-box which is bound by the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer (and probably also the BMAL1:NPAS2 heterodimer), which activates transcription of CRY1.
R-HSA-549470 (Reactome) The CRYPTOCHROME-2 (CRY2) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, the CRY2 protein shows circadian rhythm in the suprachiasmatic nucleus (SCN) and in peripheral tissues. The mRNA shows circadian rhythm in muscle but not in the SCN. Expression is dependent on CLOCK.
R-HSA-549475 (Reactome) The NR1D1 (REV-ERBA) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. In mouse the Rev-erba gene shows circadian expression due to transactivation by the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer. REV-ERBA binds the promoter of its own gene and represses its own expression (Adelmont et al. 1996).
R-HSA-549493 (Reactome) The PERIOD-2 (PER2) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The promoter of the PER2 gene contains an E-box which binds the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer (and probably also the BMAL1:NPAS2 (ARNTL:NPAS2) heterodimer). The BMAL1:CLOCK heterodimer activates transcription of PER2.
R-HSA-549533 (Reactome) The PERIOD-1 (PER1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The promoter of the PER1 gene contains E-boxes which are bound by the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer (and probably also the BMAL1:NPAS2 (ARNTL:NPAS2) heterodimer). The BMAL1:CLOCK heterodimer activates transcription of PER1.
R-HSA-5663105 (Reactome) As inferred from mouse, the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds E-box elements in the promoter of the DEC2 (BHLHE41, BHLHB3) gene and activates transcription of DEC2.
R-HSA-5663118 (Reactome) As inferred from mouse, the phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds a noncanonical E-box in the promoter of the PER2 gene and activates transcription of PER2. NPAS2 is predicted to act redundantly with CLOCK.
R-HSA-5663120 (Reactome) The phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds an E-box in the promoter of the CRY1 gene and activates transcription of CRY1. NPAS2 is predicted to act redundantly with CLOCK.
R-HSA-5663122 (Reactome) As inferred from mouse, the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds an E-box element in the promoter of the NAMPT gene and enhances transcription.
R-HSA-5663124 (Reactome) The phosphorylated BMAL1:CLOCK (ARNTL) heterodimer binds an E-box in the promoter of the PAI-1 gene and activate transcription of PAI-1. NPAS2 is predicted to act redundantly with CLOCK.
R-HSA-5663127 (Reactome) Activation of FACTOR VII expression by phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) is inferred from mouse. NPAS2 is predicted to act redundantly with CLOCK.
R-HSA-5663132 (Reactome) As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind E-boxes in the promoter of the DBP gene and activate transcription of DBP.
R-HSA-5663138 (Reactome) The phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds an E-box element in the promoter of the NOCTURNIN gene and activates transcription of NOCTURNIN. NPAS2 is predicted to act redundantly with CLOCK.
R-HSA-5663155 (Reactome) Activation of NR1D1 (REV-ERBA) expression by phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) is inferred from mouse. NPAS2 is predicted to act redundantly with CLOCK.
R-HSA-5663156 (Reactome) As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind E-boxes in the second intron of the PPARA gene and activate transcription of PPARA.
R-HSA-5663165 (Reactome) As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind an E-box enhancer in the AVP promoter and activate transcription of AVP.
R-HSA-5663170 (Reactome) BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind E-boxes in the promoter of the DEC1 (BHLHE40, BHLHB2) gene and activate transcription of DEC1.
R-HSA-5663174 (Reactome) The phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds E-boxes in the promoter of the PER1 gene and activates transcription of PER1. NPAS2 is predicted to act redundantly with CLOCK.
R-HSA-5669302 (Reactome) As inferred from mouse homologs, the p-BMAL1:p-CLOCK,NPAS2 heterodimer binds the promoter of the RORA gene and activates transcription.
R-HSA-879724 (Reactome) The PPARA gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind the scond intron of the PPARA gene and activate transcription of PPARA.
R-HSA-879762 (Reactome) The DBP gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind E-boxes in the DBP promoter and activate transcription of DBP.
R-HSA-879770 (Reactome) The DEC2 (BHLHE41, BHLHB3) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer binds E-box elements in the DEC2 promoter and activates transcription of DEC2.
R-HSA-879782 (Reactome) The AVP gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind an E-box enhancer in the promoter of the AVP gene and activate transcription of AVP.
R-HSA-879798 (Reactome) The DEC1 (BHLHE40, BHLHB2) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The DEC1 gene contains E-box elements in its promoter which bind the BMAL:CLOCK (ARNTL:CLOCK) heterodimer and confer circadian rhythm on its expression.
RORA geneR-HSA-1368133 (Reactome)
RORA geneR-HSA-5669302 (Reactome)
RORA:Coactivator:NR1D1 geneArrowR-HSA-549475 (Reactome)
RORAArrowR-HSA-1368133 (Reactome)
SERPINE1 GeneR-HSA-549364 (Reactome)
SERPINE1 GeneR-HSA-5663124 (Reactome)
SERPINE1ArrowR-HSA-549364 (Reactome)
SIK1TBarR-HSA-549533 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:AVP geneArrowR-HSA-5663165 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:AVP geneArrowR-HSA-879782 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:BHLHE40 geneArrowR-HSA-5663170 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:BHLHE40 geneArrowR-HSA-879798 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:BHLHE41 geneArrowR-HSA-5663105 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:BHLHE41 geneArrowR-HSA-879770 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:CCRN4L geneArrowR-HSA-549424 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:CCRN4L geneArrowR-HSA-5663138 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:CRY1 geneArrowR-HSA-549467 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:CRY1 geneArrowR-HSA-5663120 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:DBP geneArrowR-HSA-5663132 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:DBP geneArrowR-HSA-879762 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:F7 geneArrowR-HSA-549428 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:F7 geneArrowR-HSA-5663127 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:NAMPT geneArrowR-HSA-1368889 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:NAMPT geneArrowR-HSA-5663122 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:NR1D1 geneArrowR-HSA-549475 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:NR1D1 geneArrowR-HSA-5663155 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PER1 geneArrowR-HSA-549533 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PER1 geneArrowR-HSA-5663174 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PER2 geneArrowR-HSA-549493 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PER2 geneArrowR-HSA-5663118 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PPARA geneArrowR-HSA-5663156 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:PPARA geneArrowR-HSA-879724 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:RORA geneArrowR-HSA-1368133 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:RORA geneArrowR-HSA-5669302 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:SERPINE1 geneArrowR-HSA-549364 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:SERPINE1 geneArrowR-HSA-5663124 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663105 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663118 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663120 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663122 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663124 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663127 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663132 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663138 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663155 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663156 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663165 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663170 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5663174 (Reactome)
p-BMAL1:p-CLOCK,NPAS2R-HSA-5669302 (Reactome)
p-CREB:CRTC1:PER1 geneArrowR-HSA-549533 (Reactome)
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