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

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11, 3416, 373227173, 5, 12, 1929, 3521, 24, 29, 308, 2810, 1429, 351572533, 374935322021, 24, 29, 3026273, 5, 19cytosolnucleoplasmp-S-ARNTL CCRN4L gene p-S-ARNTL PPARA:RXRACoactivator complexPER1 geneBHLHE41p-S-ARNTL BMAL2:CLOCKBHLHE40TBL1XR1 p-BMAL1:p-CLOCK,NPAS2:AVP geneNR3C1 NR1D1 EP300 PPARA Coactivators of PPARalpha PPARGC1A p-CLOCK,p-NPAS2 p-BMAL1:p-CLOCK,NPAS2:CRY1 geneBHLHE40 geneBHLHE41 gene Ligands of PPARA NR1D1:heme:Corepressors:NR1D1 geneRORA:Coactivator:NR1D1 geneferriheme b p-S-ARNTL p-CLOCK,p-NPAS2 p-CLOCK,p-NPAS2 p-BMAL1:p-CLOCK,NPAS2:DBP geneNR1D1p-BMAL1:p-CLOCK,NPAS2:PPARA genep-S133-CREB1 p-S-ARNTL DBP gene p-CLOCK,p-NPAS2 CRY1 geneCCRN4L geneSIK1PPARA gene p-CLOCK,p-NPAS2 TBL1X p-BMAL1:p-CLOCK,NPAS2:NR1D1 genep-BMAL1:p-CLOCK,NPAS2NR1D1 geneBHLHE40 gene NAMPT geneAVP genePPARAp-BMAL1:p-CLOCK,NPAS2:BHLHE41 genep-BMAL1:p-CLOCK,NPAS2:RORA geneNCOR1 RORA geneCCRN4LPER2 geneRORA gene PER1 gene p-BMAL1:p-CLOCK,NPAS2:BHLHE40 genep-CLOCK,p-NPAS2 ARNTL2 p-S-ARNTL AVP(20-28)NR1D1 gene PER1 gene NR1D1 gene RXRA NAMPT gene Peroxisome Proliferator Receptor Element (PPRE) NR1D1 gene NRIP1 CRY2 geneRORAp-CLOCK,p-NPAS2 p-S-ARNTL p-CLOCK,p-NPAS2 p-CLOCK,p-NPAS2 RORA p-BMAL1:p-CLOCK,NPAS2:CCRN4L geneCRTC1 HIF1Ap-BMAL1:p-CLOCK,NPAS2:PER1 geneF7 gene p-S-ARNTL CRY2PER1p-BMAL1:p-CLOCK,NPAS2:NAMPT geneDBPSERPINE1p-BMAL1:p-CLOCK,NPAS2:SERPINE1 genep-S-ARNTL PER2p-S-ARNTL p-S-ARNTL PER2 gene p-CLOCK,p-NPAS2 SERPINE1 Gene p-CLOCK,p-NPAS2 F7 genep-S-ARNTL NR3C1:DexamethasoneDBP genep-S-ARNTL p-S-ARNTL p-BMAL1:p-CLOCK,NPAS2:PER2 geneSERPINE1 Genep-CLOCK,p-NPAS2 pro-factor VIICRY1DEXA NAMPTp-CLOCK,p-NPAS2 BHLHE41 geneAVP gene HDAC3 p-BMAL1:p-CLOCK,NPAS2:F7 geneCLOCK p-CLOCK,p-NPAS2 p-CLOCK,p-NPAS2 PPARA geneCRY1 gene p-CREB:CRTC1:PER1genep-S-ARNTL 356, 131221, 24, 29, 303, 5, 1922, 362, 18123, 31


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. 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 Europe PMC Scholia
  2. 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 Europe PMC Scholia
  3. Muñoz E, Baler R.; ''The circadian E-box: when perfect is not good enough.''; PubMed Europe PMC Scholia
  4. Greenberg D, Miao CH, Ho WT, Chung DW, Davie EW.; ''Liver-specific expression of the human factor VII gene.''; PubMed Europe PMC Scholia
  5. 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 Europe PMC Scholia
  6. Rakhshandehroo M, Hooiveld G, Müller M, Kersten S.; ''Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.''; PubMed Europe PMC Scholia
  7. 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 Europe PMC Scholia
  8. 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 Europe PMC Scholia
  9. Tamaru T, Hirayama J, Isojima Y, Nagai K, Norioka S, Takamatsu K, Sassone-Corsi P.; ''CK2alpha phosphorylates BMAL1 to regulate the mammalian clock.''; PubMed Europe PMC Scholia
  10. 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 Europe PMC Scholia
  11. 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 Europe PMC Scholia
  12. 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 Europe PMC Scholia
  13. 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 Europe PMC Scholia
  14. Muñoz E, Brewer M, Baler R.; ''Circadian Transcription. Thinking outside the E-Box.''; PubMed Europe PMC Scholia
  15. 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 Europe PMC Scholia
  16. 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 Europe PMC Scholia
  17. Oishi K, Shirai H, Ishida N.; ''CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPARalpha) in mice.''; PubMed Europe PMC Scholia
  18. Khatib ZA, Inaba T, Valentine M, Look AT.; ''Chromosomal localization and cDNA cloning of the human DBP and TEF genes.''; PubMed Europe PMC Scholia
  19. 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 Europe PMC Scholia
  20. 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 Europe PMC Scholia
  21. 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 Europe PMC Scholia
  22. Dardente H, Fortier EE, Martineau V, Cermakian N.; ''Cryptochromes impair phosphorylation of transcriptional activators in the clock: a general mechanism for circadian repression.''; PubMed Europe PMC Scholia
  23. 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 Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114763view16:25, 25 January 2021ReactomeTeamReactome version 75
113207view11:27, 2 November 2020ReactomeTeamReactome version 74
112431view15:37, 9 October 2020ReactomeTeamReactome version 73
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
ARNTL2 ProteinQ8WYA1 (Uniprot-TrEMBL)
AVP gene ProteinENSG00000101200 (Ensembl)
AVP geneENSG00000101200 (Ensembl)
AVP(20-28)ProteinP01185 (Uniprot-TrEMBL)
BHLHE40 gene ProteinENSG00000134107 (Ensembl)
BHLHE40 geneENSG00000134107 (Ensembl)
BHLHE40ProteinO14503 (Uniprot-TrEMBL)
BHLHE41 gene ProteinENSG00000123095 (Ensembl)
BHLHE41 geneENSG00000123095 (Ensembl)
BHLHE41ProteinQ9C0J9 (Uniprot-TrEMBL)
BMAL2:CLOCKComplexR-HSA-879827 (Reactome)
CCRN4L gene ProteinENSG00000151014 (Ensembl)
CCRN4L geneENSG00000151014 (Ensembl)
CCRN4LProteinQ9UK39 (Uniprot-TrEMBL)
CLOCK ProteinO15516 (Uniprot-TrEMBL)
CRTC1 ProteinQ6UUV9 (Uniprot-TrEMBL)
CRY1 gene ProteinENSG00000008405 (Ensembl)
CRY1 geneENSG00000008405 (Ensembl)
CRY1ProteinQ16526 (Uniprot-TrEMBL)
CRY2 geneENSG00000121671 (Ensembl)
CRY2ProteinQ49AN0 (Uniprot-TrEMBL)
Coactivators of PPARalpha R-HSA-400216 (Reactome)
DBP gene ProteinENSG00000105516 (Ensembl)
DBP geneENSG00000105516 (Ensembl)
DBPProteinQ10586 (Uniprot-TrEMBL)
DEXA MetaboliteCHEBI:41879 (ChEBI)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
F7 gene ProteinENSG00000057593 (Ensembl)
F7 geneENSG00000057593 (Ensembl)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HIF1AProteinQ16665 (Uniprot-TrEMBL)
Ligands of PPARA R-ALL-400149 (Reactome) PPAR-alpha is most efficiently activated by polyunsaturated fatty acids having 18-20 carbon groups and 3-5 double bonds.
NAMPT gene ProteinENSG00000105835 (Ensembl)
NAMPT geneENSG00000105835 (Ensembl)
NAMPTProteinP43490 (Uniprot-TrEMBL)
NCOR1 ProteinO75376 (Uniprot-TrEMBL)
NR1D1 ProteinP20393 (Uniprot-TrEMBL)
NR1D1 gene ProteinENSG00000126368 (Ensembl)
NR1D1 geneENSG00000126368 (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 geneENSG00000179094 (Ensembl)
PER1ProteinO15534 (Uniprot-TrEMBL)
PER2 gene ProteinENSG00000132326 (Ensembl)
PER2 geneENSG00000132326 (Ensembl)
PER2ProteinO15055 (Uniprot-TrEMBL)
PPARA ProteinQ07869 (Uniprot-TrEMBL)
PPARA gene ProteinENSG00000186951 (Ensembl)
PPARA geneENSG00000186951 (Ensembl)
PPARA:RXRA Coactivator complexComplexR-HSA-400154 (Reactome)
PPARAProteinQ07869 (Uniprot-TrEMBL)
PPARGC1A ProteinQ9UBK2 (Uniprot-TrEMBL)
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 geneENSG00000069667 (Ensembl)
RORA:Coactivator:NR1D1 geneComplexR-HSA-5663260 (Reactome)
RORAProteinP35398 (Uniprot-TrEMBL)
RXRA ProteinP19793 (Uniprot-TrEMBL)
SERPINE1 Gene ProteinENSG00000106366 (Ensembl)
SERPINE1 GeneENSG00000106366 (Ensembl)
SERPINE1ProteinP05121 (Uniprot-TrEMBL)
SIK1ProteinP57059 (Uniprot-TrEMBL)
TBL1X ProteinO60907 (Uniprot-TrEMBL)
TBL1XR1 ProteinQ9BZK7 (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-CLOCK,p-NPAS2 R-HSA-421319 (Reactome)
p-CREB:CRTC1:PER1 geneComplexR-HSA-5656495 (Reactome)
p-S-ARNTL ProteinO00327 (Uniprot-TrEMBL)
p-S133-CREB1 ProteinP16220 (Uniprot-TrEMBL)
pro-factor VIIProteinP08709 (Uniprot-TrEMBL)

Annotated Interactions

View all...
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)
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)
pro-factor VIIArrowR-HSA-549428 (Reactome)
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