Summary of AHR
This receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450.
AHR binds several exogenous ligands such as natural plant flavonoids, polyphenolics and indoles, as well as synthetic polycyclic aromatic hydrocarbons and dioxin-like compounds. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones. Upon ligand binding to chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the chaperones dissociate resulting in AhR translocating into the nucleusand dimerizing with ARNT (AhR nuclear translocator), leading to changes in gene transcription.
Ahr ligands have been generally classified into two categories, synthetic or naturally occurring. The first ligands to be discovered were synthetic and members of the halogenated aromatic hydrocarbons (polychlorinated dibenzodioxins, dibenzofurans and biphenyls) and polycyclic aromatic hydrocarbons (3-methylcholanthrene,benzo[a]pyrene, benzanthracenes and benzoflavones).
Naturally occurring compounds that have been identified as ligands of Ahr include derivatives of tryptophan such as indigo dye and indirubin, tetrapyrroles such as bilirubin, the arachidonic acid metabolites lipoxin A4 andprostaglandin G, modified low-density lipoprotein and several dietary carotenoids.
7-ketocholesterol competitively inhibits Ahr signal transduction,
The Function of AHR
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Protein names
Recommended name:
Aryl hydrocarbon receptorAlternative name(s):
Ah receptorAhR
Class E basic helix-loop-helix protein 76
bHLHe76
- RS1636744 (AHR) ??
- RS2066853 (AHR) ??
- RS2282885 (AHR) ??
- RS7811989 (AHR) ??
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Top Gene-Substance Interactions
AHR Interacts with These Diseases
Disease | Score |
Substances That Increase AHR
Substances | Interaction | Organism | Category |
Substances That Decrease AHR
Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Expressed in all tissues tested including blood, brain, heart, kidney, liver, lung, pancreas and skeletal muscle.
Induction:
Induced or repressed by TGFB1 and dioxin in a cell-type specific fashion. Repressed by cAMP, retinoic acid, and 12-O-tetradecanoyl phorbol-13 acetate (TPA).
Molecular Function:
- Aryl Hydrocarbon Receptor Activity
- Dna Binding
- E-Box Binding
- Enhancer Binding
- Hsp90 Protein Binding
- Protein Dimerization Activity
- Protein Heterodimerization Activity
- Rna Polymerase Ii Transcription Factor Activity, Ligand-Activated Sequence-Specific Dna Binding
- Transcription Factor Activity, Sequence-Specific Dna Binding
- Transcription Factor Binding
- Transcription Regulatory Region Dna Binding
Biological Processes:
- Apoptotic Process
- Blood Vessel Development
- Cell Cycle
- Circadian Regulation Of Gene Expression
- Negative Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Regulation Of B Cell Proliferation
- Regulation Of Gene Expression
- Regulation Of Transcription, Dna-Templated
- Regulation Of Transcription From Rna Polymerase Ii Promoter
- Response To Toxic Substance
- Response To Xenobiotic Stimulus
- Transcription From Rna Polymerase Ii Promoter
- Xenobiotic Metabolic Process
- Cellular Response To Glucocorticoid Stimulus
- Ovarian Follicle Development
- Response To Estradiol