Aryl hydrocarbon receptor

UniProt P35869 Organism Homo sapiens Gene AHR, BHLHE76

Also known as: AHR, BHLHE76

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. Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation. 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). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists. Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands. 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. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1. The heterodimer ARNT:AHR binds to the dioxin response element (DRE) of target gene promoters and activates their transcription.

Classification

Family (Pfam): PF00010 HLH, PF00989 PAS, PF08447 PAS_3
InterPro: AHR/AHRR, AHR_bHLH, bHLH_dom, HLH_DNA-bd_sf, PAC, PAS, PAS-like_dom_sf, PAS_fold, PAS_fold_3
Functional cluster: Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 3

5NJ8 X-ray 3.30A
7ZUB EM 2.85A
8QMO EM 2.76A

A predicted model is available from AlphaFold.

Gene Ontology · 46

Disease associations

retinitis pigmentosa 85 MONDO:0032689
foveal hypoplasia 3 MONDO:0975805

Drugs targeting this protein · 1

TAPINAROF agonist

Related proteins · sequence + function similarity

Aryl hydrocarbon receptor 0.96
Aryl hydrocarbon receptor 0.94
Aryl hydrocarbon receptor 0.91
Aryl hydrocarbon receptor 0.91
Aryl hydrocarbon receptor 0.90
Aryl hydrocarbon receptor 0.90
Aryl hydrocarbon receptor 0.90
Aryl hydrocarbon receptor 0.89
Aryl hydrocarbon receptor 0.88
Aryl hydrocarbon receptor nuclear translocator 0.79
Aryl hydrocarbon receptor nuclear translocator 0.78
Aryl hydrocarbon receptor nuclear translocator 0.78

Co-cited proteins · studied together in the literature

Aryl hydrocarbon receptor 4 shared papers
L-amino-acid oxidase 2 shared papers
Protein mono-ADP-ribosyltransferase TIPARP 2 shared papers
Aryl hydrocarbon receptor nuclear translocator 2 shared papers
Protein mono-ADP-ribosyltransferase TIPARP 1 shared papers
Influenza virus NS1A-binding protein 1 shared papers
Aryl hydrocarbon receptor nuclear translocator 1 shared papers
Aryl hydrocarbon receptor 1 shared papers
Cytochrome P450 1A1 1 shared papers
Nuclear receptor coactivator 7 1 shared papers
L-amino-acid oxidase 1 shared papers
Ubiquitin-like protein NEDD8 1 shared papers

Literature · 31 cited papers

Novel biallelic AHR splice site mutation cause isolated foveal hypoplasia in Saudi patient: a case report. Ophthalmic Genet. · 2022
The role of DNA-binding and ARNT dimerization on the nucleo-cytoplasmic translocation of the aryl hydrocarbon receptor. Sci. Rep. · 2021
Gene and protein expression in subjects with a nystagmus-associated AHR mutation. Front. Genet. · 2020
An endogenous indole pyruvate pathway for tryptophan metabolism mediated by IL4I1. J. Agric. Food Chem. · 2020
IL4I1 is a metabolic immune checkpoint that activates the AHR and promotes tumor progression. Cell · 2020
Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus. Brain · 2019
Characterization of TCDD-Inducible Poly-ADP-Ribose Polymerase (TIPARP/ARTD14) Catalytic Activity. Biochem. J. · 2018
A splicing mutation in aryl hydrocarbon receptor associated with retinitis pigmentosa. Hum. Mol. Genet. · 2018
Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene Activation. Structure · 2017
2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon receptor transactivation. Nucleic Acids Res. · 2013
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
The search for endogenous activators of the aryl hydrocarbon receptor. Chem. Res. Toxicol. · 2008
… and 19 more in the literature graph

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