| + |
GSK3B | down-regulates 
phosphorylation
|
ARNTL |
0.378 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-162786 |
Ser17 |
STISDFMsPGPTDLL |
Homo sapiens |
|
| pmid |
sentence |
| 20049328 |
Gsk3beta phosphorylates bmal1 specifically on ser 17 and thr 21 and primes it for ubiquitylation. In the absence of gsk3beta-mediated phosphorylation, bmal1 becomes stabilized and bmal1 dependent circadian gene expression is dampened. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-162790 |
Thr21 |
DFMSPGPtDLLSSSL |
Homo sapiens |
|
| pmid |
sentence |
| 20049328 |
Gsk3beta phosphorylates bmal1 specifically on ser 17 and thr 21 and primes it for ubiquitylation. In the absence of gsk3beta-mediated phosphorylation, bmal1 becomes stabilized and bmal1 dependent circadian gene expression is dampened. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AKT2 | down-regulates activity
phosphorylation
|
ARNTL |
0.354 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-280177 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27576939 |
Consistent with mass spectrometry results, constitutive active Akt2 (Akt2-CA) induced wild-type (WT) Bmal1 protein phosphorylation, which was abolished by a serine to alanine mutation at Ser42 residue (S42A) but not a S422A/S513A double mutation, as shown by immunoblot assay with phospho-Akt substrate antiserum ( xref ).|In line with the in vivo results, overexpression of Akt2-CA strikingly lowered Bmal1 protein abundance in the nucleus in primary hepatocytes (XREF_FIG and XREF_SUPPLEMENTARY). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NR1D1 | down-regulates quantity by repression
transcriptional regulation
|
ARNTL |
0.689 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268005 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24577401 |
A retinoic acid receptor-related orphan receptor (ROR) response element within the BMAL1 promoter is responsive to both ROR and REV-ERB (encoded by the genes NR1D1 and NR1D2); ROR activates the transcription of BMAL1, whereas REV-ERB suppresses its transcription. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267983 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
RORB | up-regulates quantity by expression 
transcriptional regulation
|
ARNTL |
0.47 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268003 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24737872 |
As RORs function as transcriptional activators and their expression correlates with histone acetylation and chromatin accessibility, RORs are thought to function as positive regulators of Bmal1 expression at its peak levels, whereas REV-ERBs block ROR and negatively regulate Bmal1 at the trough of its expression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266852 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18418469 |
RORβ and RORγ are also able to induce Bmal1 activity; however, RORα4 appears the most effective in inducing this activity. The ROREs in the Bmal1 promoter also bind ROR receptors. Overexpression of RORα1 and RORα4 induces Bmal1-promoter activity by interacting with these ROREs |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
RORC | up-regulates quantity by expression
transcriptional regulation
|
ARNTL |
0.492 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268004 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24737872 |
As RORs function as transcriptional activators and their expression correlates with histone acetylation and chromatin accessibility, RORs are thought to function as positive regulators of Bmal1 expression at its peak levels, whereas REV-ERBs block ROR and negatively regulate Bmal1 at the trough of its expression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
TOP1 | down-regulates quantity by repression
transcriptional regulation
|
ARNTL |
0.339 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277354 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 22904072 |
We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ARNTL | up-regulates quantity by expression 
transcriptional regulation
|
PER2 |
0.755 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253629 |
|
|
|
|
| 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 |
| + |
PPARGC1A | up-regulates quantity by expression
transcriptional regulation
|
ARNTL |
0.54 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268031 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17476214 |
Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
ARNTL | down-regulates quantity by repression
transcriptional regulation
|
VWF |
0.322 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253704 |
|
|
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 |
| + |
ARNTL | up-regulates quantity by expression
transcriptional regulation
|
CRY1 |
0.936 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253626 |
|
|
|
|
| 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 |
| + |
ARNTL | up-regulates quantity by expression
transcriptional regulation
|
PER1 |
0.742 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253628 |
|
|
|
|
| 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 |
| + |
ARNTL | up-regulates quantity by expression
transcriptional regulation
|
PPARA |
0.613 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268025 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 16556735 |
We demonstrate that PPARalpha plays a specific role in the peripheral circadian control because it is required to maintain the circadian rhythm of the master clock gene brain and muscle Arnt-like protein 1 (bmal1) in vivo. This regulation occurs via a direct binding of PPARalpha on a potential PPARalpha response element located in the bmal1 promoter. Reversely, BMAL1 is an upstream regulator of PPARalpha gene expression. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Tissue: |
Liver |
| Pathways: | Circadian clock |
| + |
ARNTL | down-regulates activity
binding
|
MAGEL2 |
0.365 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253517 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22208286 |
Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPARA | up-regulates quantity by expression
transcriptional regulation
|
ARNTL |
0.613 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268024 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 16556735 |
We demonstrate that PPARalpha plays a specific role in the peripheral circadian control because it is required to maintain the circadian rhythm of the master clock gene brain and muscle Arnt-like protein 1 (bmal1) in vivo. This regulation occurs via a direct binding of PPARalpha on a potential PPARalpha response element located in the bmal1 promoter. Reversely, BMAL1 is an upstream regulator of PPARalpha gene expression. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Circadian clock |
| + |
ARNTL | form complex 
binding
|
CLOCK/BMAL1 |
0.784 |
| 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 |
| + |
NR1D1 | down-regulates quantity by repression 
transcriptional regulation
|
ARNTL |
0.689 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253719 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21881539 |
Concomitant attenuation of NR1D1 downregulation (-2.4-fold compared with -4.1-fold in placebo; P=0.04), a transcriptional repressor of ARNTL, supported the view that ramipril might modulate glucose homeostasis pathways involving the NR1D1 ARNTL axis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
NR1D2 | down-regulates quantity by repression
transcriptional regulation
|
ARNTL |
0.462 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268006 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24577401 |
A retinoic acid receptor-related orphan receptor (ROR) response element within the BMAL1 promoter is responsive to both ROR and REV-ERB (encoded by the genes NR1D1 and NR1D2); ROR activates the transcription of BMAL1, whereas REV-ERB suppresses its transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
ARNTL | up-regulates quantity by expression
transcriptional regulation
|
PER3 |
0.554 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253630 |
|
|
|
|
| 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 |
| + |
PPARG | up-regulates quantity by expression
transcriptional regulation
|
ARNTL |
0.392 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268026 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 19041764 |
Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Circadian clock |
| + |
RORA | up-regulates quantity by expression
transcriptional regulation
|
ARNTL |
0.704 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268002 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24737872 |
As RORs function as transcriptional activators and their expression correlates with histone acetylation and chromatin accessibility, RORs are thought to function as positive regulators of Bmal1 expression at its peak levels, whereas REV-ERBs block ROR and negatively regulate Bmal1 at the trough of its expression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267982 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
RAI1 | up-regulates quantity by expression
transcriptional regulation
|
ARNTL |
0.314 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266843 |
|
|
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 |
| Pathways: | Circadian clock |
| + |
ARNTL | up-regulates quantity by expression
transcriptional regulation
|
CRY2 |
0.936 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253627 |
|
|
|
|
| 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 |
4.0
ARNTL
- 
- 