| + |
CLOCK/BMAL1 | up-regulates quantity by expression 
transcriptional regulation
|
NAMPT |
0.61 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268021 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 19299583 |
Here we report that both the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice. Inhibition of NAMPT promotes oscillation of the clock gene Per2 by releasing CLOCK:BMAL1 from suppression by SIRT1. In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1. Transduction of Clock/Bmal1 into mouse embryonic fibroblasts appeared to up-regulate Nampt expression ∼1.6-fold (Fig. 3E). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Circadian clock |
| + |
CRY2 | down-regulates activity 
binding
|
CLOCK/BMAL1 |
0.929 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267976 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. PER and CRY proteins form heterodimers and suppress the activity of the BMAL1/clock (or NPAS2) completing the feedback loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
CLOCK | form complex 
binding
|
CLOCK/BMAL1 |
0.78 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253709 |
|
|
in vitro |
|
| pmid |
sentence |
| 22653727 |
Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex|The structure of the CLOCK:BMAL1 complex is a starting point for understanding at an atomic level the mechanism driving the mammalian circadian clock. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Circadian clock |
| + |
PER2 | down-regulates activity
binding
|
CLOCK/BMAL1 |
0.763 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267977 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. PER and CRY proteins form heterodimers and suppress the activity of the BMAL1/clock (or NPAS2) completing the feedback loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression 
transcriptional regulation
|
CRY1 |
0.939 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253679 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
SERPINE1 |
0.524 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253712 |
|
|
Homo sapiens |
Colorectal Cancer Cell |
| pmid |
sentence |
| 22198637 |
Both CLOCK:ARNTL and CLOCK:ARNTL2 heterodimers powerfully activate the promoter of the PAI-1 gene, officially called SERPINE1 and located on the seventh chromosome (7q21.3-q22), underlying the circadian variation in circulating PAI-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
PER1 | down-regulates activity
binding
|
CLOCK/BMAL1 |
0.733 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267978 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. PER and CRY proteins form heterodimers and suppress the activity of the BMAL1/clock (or NPAS2) completing the feedback loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
DBP |
0.711 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268029 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 30100984 |
The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family and functions as important regulator of circadian core and output gene expression. Gene expression of DBP itself is under the control of E-box-dependent binding by the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive element binding protein (CREB). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Tissue: |
Liver |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | down-regulates quantity by repression
transcriptional regulation
|
VWF |
0.323 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253703 |
|
|
Mus musculus |
Aorta Endothelium |
| pmid |
sentence |
| 20658528 |
We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
SIRT1 | down-regulates activity
binding
|
CLOCK/BMAL1 |
0.779 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253722 |
|
|
|
|
| pmid |
sentence |
| 19299583 |
Using Per2:luciferase transcriptional reporter assays in HEK293 cells (Fig. 2C-E; S2), we show that inhibition of NAMPT by FK866 led to a significant increase in the CLOCK:BMAL1-driven transcription of the Per2:luciferase reporter (Fig. 2C), indicating that reduced NAMPT-mediated NAD+ biosynthesis released CLOCK:BMAL1 from the SIRT1-dependent suppression. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
CRY1 | down-regulates activity
binding
|
CLOCK/BMAL1 |
0.939 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267975 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. PER and CRY proteins form heterodimers and suppress the activity of the BMAL1/clock (or NPAS2) completing the feedback loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
PER1 |
0.733 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253681 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
PER2 |
0.763 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253682 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
NAMPT | down-regulates 
|
CLOCK/BMAL1 |
0.61 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253721 |
|
|
|
|
| pmid |
sentence |
| 19299583 |
Using Per2:luciferase transcriptional reporter assays in HEK293 cells (Fig. 2C-E; S2), we show that inhibition of NAMPT by FK866 led to a significant increase in the CLOCK:BMAL1-driven transcription of the Per2:luciferase reporter (Fig. 2C), indicating that reduced NAMPT-mediated NAD+ biosynthesis released CLOCK:BMAL1 from the SIRT1-dependent suppression. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
BHLHE40 |
0.664 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253707 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 19032342 |
DEC1 (BHLHB2/Stra13/Sharp2)-a basic helix-loop-helix transcription factor-is known to be involved in various biological phenomena including clock systems and metabolism. In the clock systems, Dec1 expression is dominantly up-regulated by CLOCK : BMAL1 heterodimer, and it exhibits circadian rhythm in the suprachiasmatic nucleus (SCN)-the central circadian pacemaker-and other peripheral tissues. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ARNTL | form complex
binding
|
CLOCK/BMAL1 |
0.78 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253708 |
|
|
in vitro |
|
| pmid |
sentence |
| 22653727 |
Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex|The structure of the CLOCK:BMAL1 complex is a starting point for understanding at an atomic level the mechanism driving the mammalian circadian clock. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
MTA1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253718 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 24089055 |
Here we provide genetic and biochemical evidence that metastasis-associated protein 1 (MTA1), a widely upregulated gene product in human cancers, is an integral component of the circadian molecular machinery. | The CLOCK-BMAL1 heterodimer activates MTA1 transcription through a conserved E-box element at its promoter. MTA1, in turn, interacts with and recruits CLOCK-BMAL1 at its own and CRY1 promoters and promotes their transcription. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
MTA1 | up-regulates activity
binding
|
CLOCK/BMAL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253723 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 24089055 |
Here we provide genetic and biochemical evidence that metastasis-associated protein 1 (MTA1), a widely upregulated gene product in human cancers, is an integral component of the circadian molecular machinery. | The CLOCK-BMAL1 heterodimer activates MTA1 transcription through a conserved E-box element at its promoter. MTA1, in turn, interacts with and recruits CLOCK-BMAL1 at its own and CRY1 promoters and promotes their transcription. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
STAR |
0.285 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253700 |
|
|
Coturnix japonica |
Ovarian Follicle |
| pmid |
sentence |
| 17431006 |
One such gene was identified, encoding steroidogenic acute regulatory protein (StAR), which showed 24-h changes in expression in the F1 follicle coinciding with those of Per2. Evidence that StAR gene expression is clock driven was obtained by showing that its 5' flanking region contains E-box enhancers that bind to CLOCK/BMAL1 heterodimers to activate gene transcription |
|
| Publications: |
1 |
Organism: |
Coturnix Japonica |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
PER3 |
0.572 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253683 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
SIRT6 | up-regulates activity
binding
|
CLOCK/BMAL1 |
0.368 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268157 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25083875 |
SIRT6 is involved in circadian control of gene expression and metabolism. SIRT6 Interacts with CLOCK:BMAL1 and Controls Their Chromatin Recruitment. SIRT6 physically interacts with CLOCK and BMAL1, individually or together, as shown by coimmunoprecipitation (co-IP) (Figures 4A and 4B). SIRT6 directs chromatin recruitment of CLOCK:BMAL1 and SREBP1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
RAI1 | up-regulates quantity by expression
transcriptional regulation
|
CLOCK/BMAL1 |
0.397 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266844 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 22578325 |
Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Tissue: |
Hypothalamus |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
CRY2 |
0.929 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253680 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
3.0
CLOCK/BMAL1
CPX-3229