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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:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, 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, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, 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:32818467, PubMed:32866000). 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-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).SUBUNIT Homodimer (By similarity). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (PubMed:10395741, PubMed:28602820). Interacts with ARNT; 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, PubMed:34521881). Binds MYBBP1A (By similarity). Interacts with coactivators including SRC-1, RIP140 and NOCA7, and with the corepressor SMRT (PubMed:10395741). Interacts with NEDD8 and IVNS1ABP (PubMed:12215427, PubMed:16582008). Interacts with BMAL1 (By similarity). Interacts with HSP90AB1 (By similarity). Interacts with TIPARP; leading to mono-ADP-ribosylation of AHR and subsequent inhibition of AHR (PubMed:23275542, PubMed:30373764).INTERACTION Initially cytoplasmic; upon binding with ligand and interaction with a HSP90, it translocates to the nucleus.TISSUE SPECIFICITY Expressed in all tissues tested including blood, brain, heart, kidney, liver, lung, pancreas and skeletal muscle. Expressed in retinal photoreceptors (PubMed:29726989).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).DOMAIN The PAS 1 domain is essential for dimerization and also required for AHR:ARNT heterodimerization.PTM Mono-ADP-ribosylated, leading to inhibit transcription activator activity of AHR.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.
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