Summary of ARNTL
ARNTL (aka BMAL1) increases functionality in the circadian clock . It is associated with major depressive disorders, heightened responses to antidepressants, and is a key component in the functionality of the bodys circadian clock [R]. Disruptions in the circadian rhythms contribute to cardiovascular diseases, cancer, metabolic syndromes and aging.
ARNTL/BMAL1 increases muscle production and decreases fat cell creation.
ARNTL plays an important role in adult hippocampal neurogenesis. Increases the expression of enzymes that increase hormonal production, and also the genes involved in hair growth.
ARNTL/BMAL1 has also been identified as a candidate gene for susceptibility to hypertension, diabetes, and obesity, and mutations in BMAL1 have been linked to infertility, gluconeogenesis and lipogenesis problems, and altered sleep patterns.
Protein names
Recommended name:
Aryl hydrocarbon receptor nuclear translocator-like protein 1Alternative name(s):
Basic-helix-loop-helix-PAS protein MOP3Brain and muscle ARNT-like 1
Class E basic helix-loop-helix protein 5
bHLHe5
Member of PAS protein 3
PAS domain-containing protein 3
bHLH-PAS protein JAP3
- RS11022756 (ARNTL) ??
- RS11022775 (ARNTL) ??
- RS2278749 (ARNTL) ??
- RS3816358 (ARNTL) ??
- RS3816360 (ARNTL) ??
- RS4757144 (ARNTL) ??
- RS6486121 (ARNTL) ??
- RS6486122 (ARNTL) ??
- RS7950226 (ARNTL) ??
- RS9633835 (ARNTL) ??
- RS969485 (ARNTL) ??
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Top Gene-Substance Interactions
ARNTL Interacts with These Diseases
| Disease | Score |
Fixes
Reduced activity of the ARNTL gene causes the circadian rhythm to become disrupted, which leads to behavioral symptoms of depression (such as despair and hopelessness) in both humans and animals [R, R]. Therefore, you can potentially counteract your risk by increasing the activity of the ARNTL gene.
A good first step would be to avoid factors that may be further reducing your levels of ARNTL gene activity, such as being exposed to light during the evening and night time [R].
Exposure to cold can give your ARNTL levels a boost by activating a protein called PGC-1α, which increases the production of the ARNTL gene [R, R].
DHA -also stops palmitate induced decrease in BMAL1 (R).
Pathways:
Chronic activation of GSK3 impaired rhythmicity of BMAL1. Furthermore, chronic inhibition of GSK3 enhanced the amplitude and shortened the period of PER2 rhythms in SCN cultures [R].
Others:
Substances That Increase ARNTL
| Substances | Interaction | Organism | Category |
Substances That Decrease ARNTL
| Substances | Interaction | Organism | Category |
Advanced Summary
One mice study indicated that deleting the gene causes a breakdown of the circadian clock, and development issues in the population [R].
Regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NRF2 . Inhibits the mTORC1 signaling pathway; Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity and increases MAOA .
Mutations in the ARNTL gene cause disruptions in the resulting protein, which in turn cause incompatibility with other transcription factors, resulting in circadian arrhythmicity [R].
Variations of the ARNTL gene, as well as two other genes, CRY2 and PER2, have been found to be associated with unipolar depression, perhaps due to the disruption of the circadian clock as well as other psychotic disorders [R1, R2].
ARNTL increases vasopressin, an important hormone that regulates water retention the kidney [R1, R2].
Advanced information: ARNTL binds with CLOCK, which increases the expression of Period and Cryptochrome genes [R]. Cycles between promotion and repression of the regulatory loops take approximately 24 hours, representing one circadian clock [R]. Regulation of the ARNTL protein by competitive binding within the ARNTL promotor region; ARNTL/CLOCK bind to promoter regions EV-Erb and ROR/ß genes as well to begin production of their proteins, which in turn regulate ANTL by binding to the promoter region [R].
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Hair follicles (at protein level). Highly expressed in the adult brain, skeletal muscle and heart.
Enzyme Regulation:
The redox state of the cell can modulate the transcriptional activity of the CLOCK-ARNTL/BMAL1 and NPAS2-ARNTL/BMAL1 heterodimers; NADH and NADPH enhance the DNA-binding activity of the heterodimers.
Molecular Function:
- Aryl Hydrocarbon Receptor Binding
- Core Promoter Binding
- Dna Binding
- E-Box Binding
- Hsp90 Protein Binding
- Repressing Transcription Factor Binding
- Sequence-Specific Dna Binding
- Transcription Factor Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
- Transcription Regulatory Region Sequence-Specific Dna Binding
- Core Promoter Sequence-Specific Dna Binding
- Transcriptional Activator Activity, Rna Polymerase Ii Transcription Factor Binding
Biological Processes:
- Circadian Regulation Of Gene Expression
- Circadian Rhythm
- Negative Regulation Of Fat Cell Differentiation
- Negative Regulation Of Glucocorticoid Receptor Signaling Pathway
- Negative Regulation Of Tor Signaling
- Negative Regulation Of Transcription, Dna-Templated
- Oxidative Stress-Induced Premature Senescence
- Positive Regulation Of Canonical Wnt Signaling Pathway
- Positive Regulation Of Circadian Rhythm
- Positive Regulation Of Skeletal Muscle Cell Differentiation
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Proteasome-Mediated Ubiquitin-Dependent Protein Catabolic Process
- Regulation Of Cell Cycle
- Regulation Of Cellular Senescence
- Regulation Of Hair Cycle
- Regulation Of Insulin Secretion
- Regulation Of Neurogenesis
- Regulation Of Transcription, Dna-Templated
- Regulation Of Type B Pancreatic Cell Development
- Response To Redox State
- Spermatogenesis
- Transcription, Dna-Templated
- Maternal Process Involved In Parturition
- Protein Import Into Nucleus, Translocation
- Regulation Of Protein Catabolic Process