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Aryl hydrocarbon Receptor

OverviewProducts

Domain

The PAS 1 domain is essential for dimerization and also required for AHR:ARNT heterodimerization.

Function

Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:30373764, PubMed:23275542, PubMed:7961644, PubMed:32818467). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:30373764, PubMed:23275542, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32866000, PubMed:32818467). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820).

Involvement in disease

Retinitis pigmentosa 85

RP85

A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP85 is an autosomal recessive form manifesting as early-onset progressive difficulty to adapt in dim light and gradually decreasing visual acuity in both eyes.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Mono-ADP-ribosylated, leading to inhibit transcription activator activity of AHR.

Tissue specificity

Expressed in all tissues tested including blood, brain, heart, kidney, liver, lung, pancreas and skeletal muscle. Expressed in retinal photoreceptors (PubMed:29726989).

Cellular localization

  • Cytoplasm
  • Nucleus
  • Initially cytoplasmic; upon binding with ligand and interaction with a HSP90, it translocates to the nucleus.

Alternative names

  • Aryl hydrocarbon receptor
  • Ah receptor
  • AhR
  • Class E basic helix-loop-helix protein 76
  • bHLHe76
  • BHLHE76
  • AHR

Database links

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

  • Epigenetics
  • Immunology & Infectious Disease

Molecular weight

96147Da