ID AHR_MOUSE Reviewed; 848 AA. AC P30561; Q8QZX6; Q8R4S3; Q99P79; Q9QVY1; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 25-MAR-2003, sequence version 3. DT 27-MAR-2024, entry version 211. DE RecName: Full=Aryl hydrocarbon receptor; DE Short=Ah receptor; DE Short=AhR; DE Flags: Precursor; GN Name=Ahr; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND VARIANTS ILE-324; LEU-348; RP LEU-471; SER-533; LEU-589 AND ALA-758. RC STRAIN=C57L; TISSUE=Hepatoma; RX PubMed=1314586; DOI=10.1016/0006-291x(92)91185-s; RA Ema M., Sogawa K., Watanabe N., Chujoh Y., Matsushita N., Gotoh O., RA Funae Y., Fujii-Kuriyama Y.; RT "cDNA cloning and structure of mouse putative Ah receptor."; RL Biochem. Biophys. Res. Commun. 184:246-253(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 10-36; 232-261; 335-350 AND RP 636-646, AND VARIANTS ILE-324; LEU-348; LEU-471; SER-533; LEU-589 AND RP ALA-758. RC STRAIN=C57BL/6J, and C57L; TISSUE=Liver; RX PubMed=1325649; DOI=10.1073/pnas.89.17.8185; RA Burbach K.M., Poland A., Bradfield C.A.; RT "Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated RT transcription factor."; RL Proc. Natl. Acad. Sci. U.S.A. 89:8185-8189(1992). RN [3] RP NUCLEOTIDE SEQUENCE, AND VARIANTS ILE-324; LEU-348; VAL-375; LEU-471; RP SER-533; LEU-589 AND ALA-758. RC STRAIN=C57BL/6J, and DBA/2J; RX PubMed=8148872; DOI=10.1097/00008571-199312000-00005; RA Chang C.-Y., Smith D.R., Prasad V.S., Sidman C.L., Nebert D.W., Puga A.; RT "Ten nucleotide differences, five of which cause amino acid changes, are RT associated with the Ah receptor locus polymorphism of C57BL/6 and DBA/2 RT mice."; RL Pharmacogenetics 3:312-321(1993). RN [4] RP NUCLEOTIDE SEQUENCE. RX PubMed=8408082; DOI=10.1016/s0021-9258(20)80668-1; RA Schmidt J.V., Carver L.A., Bradfield C.A.; RT "Molecular characterization of the murine Ahr gene. Organization, promoter RT analysis, and chromosomal assignment."; RL J. Biol. Chem. 268:22203-22209(1993). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANTS ILE-324; LEU-348; VAL-375; RP LEU-471; SER-533; LEU-589 AND ALA-758, AND CHARACTERIZATION OF VARIANTS RP ILE-324; VAL-375; LEU-471; SER-533 AND LEU-589. RC STRAIN=C57BL/6J, and DBA/2J; TISSUE=Liver; RX PubMed=7961644; DOI=10.1016/s0021-9258(18)46990-6; RA Ema M., Ohe N., Suzuki M., Mimura J., Sogawa K., Ikawa S., RA Fujii-Kuriyama Y.; RT "Dioxin binding activities of polymorphic forms of mouse and human RT arylhydrocarbon receptors."; RL J. Biol. Chem. 269:27337-27343(1994). RN [6] RP NUCLEOTIDE SEQUENCE, FUNCTION, VARIANTS ILE-324; LEU-348; VAL-375; LEU-471; RP SER-533; LEU-589; ALA-758; VAL-808; ASP-821 AND VAL-824, AND RP CHARACTERIZATION OF VARIANTS LEU-348 AND VAL-375. RC STRAIN=C57BL/6J; RX PubMed=7969080; RA Poland A., Palen D., Glover E.; RT "Analysis of the four alleles of the murine aryl hydrocarbon receptor."; RL Mol. Pharmacol. 46:915-921(1994). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-348; VAL-375; ILE-589 RP AND ALA-758. RC STRAIN=129/SvJ; RA Hadd A.G., Nguyen L.P., Garrigues C.S., Thomas R.S., Rank D.R., Penn S.G., RA LaPres J.J., Roach D., Blaga I., Schneider J., Shilova K., Bradfield C.A., RA Jovanovich S.B.; RT "Mouse aryl-hydrocarbon receptor (AhR) genomic region."; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-324; LEU-348; VAL-375; RP LEU-471; SER-533; ILE-589 AND ALA-758. RC STRAIN=A/J, BALB/cBY, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J, and SJL/J; RX PubMed=11875369; DOI=10.1097/00008571-200203000-00009; RA Thomas R.S., Penn S.G., Holden K., Bradfield C.A., Rank D.R.; RT "Sequence variation and phylogenetic history of the mouse Ahr gene."; RL Pharmacogenetics 12:151-163(2002). RN [9] RP PROTEIN SEQUENCE OF 10-36. RX PubMed=1846217; RA Bradfield C.A., Glover E., Poland A.; RT "Purification and N-terminal amino acid sequence of the Ah receptor from RT the C57BL/6J mouse."; RL Mol. Pharmacol. 39:13-19(1991). RN [10] RP INDUCTION. RX PubMed=8806768; DOI=10.1006/abbi.1996.0378; RA FitzGerald C.T., Fernandez-Salguero P., Gonzalez F.J., Nebert D.W., RA Puga A.; RT "Differential regulation of mouse Ah receptor gene expression in cell lines RT of different tissue origins."; RL Arch. Biochem. Biophys. 333:170-178(1996). RN [11] RP FUNCTION. RX PubMed=8806883; DOI=10.1006/taap.1996.0210; RA Fernandez-Salguero P.M., Hilbert D.M., Rudikoff S., Ward J.M., RA Gonzalez F.J.; RT "Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8- RT tetrachlorodibenzo-p-dioxin-induced toxicity."; RL Toxicol. Appl. Pharmacol. 140:173-179(1996). RN [12] RP FUNCTION. RX PubMed=9427285; DOI=10.1046/j.1365-2443.1997.1490345.x; RA Mimura J., Yamashita K., Nakamura K., Morita M., Takagi T.N., Nakao K., RA Ema M., Sogawa K., Yasuda M., Katsuki M., Fujii-Kuriyama Y.; RT "Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) RT in mice lacking the Ah (dioxin) receptor."; RL Genes Cells 2:645-654(1997). RN [13] RP FUNCTION. RX PubMed=10973493; DOI=10.1073/pnas.190256997; RA Lahvis G.P., Lindell S.L., Thomas R.S., McCuskey R.S., Murphy C., RA Glover E., Bentz M., Southard J., Bradfield C.A.; RT "Portosystemic shunting and persistent fetal vascular structures in aryl RT hydrocarbon receptor-deficient mice."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10442-10447(2000). RN [14] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=10639156; DOI=10.1073/pnas.97.2.779; RA Shimizu Y., Nakatsuru Y., Ichinose M., Takahashi Y., Kume H., Mimura J., RA Fujii-Kuriyama Y., Ishikawa T.; RT "Benzoapyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon RT receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 97:779-782(2000). RN [15] RP INTERACTION WITH MYBBP1A. RX PubMed=11956195; DOI=10.1074/jbc.m200740200; RA Jones L.C., Okino S.T., Gonda T.J., Whitlock J.P. Jr.; RT "Myb-binding protein 1a augments AhR-dependent gene expression."; RL J. Biol. Chem. 277:22515-22519(2002). RN [16] RP REVIEW ON ROLE IN CELL CYCLE. RX PubMed=12213388; DOI=10.1016/s0009-2797(02)00069-8; RA Puga A., Xia Y., Elferink C.; RT "Role of the aryl hydrocarbon receptor in cell cycle regulation."; RL Chem. Biol. Interact. 141:117-130(2002). RN [17] RP INTERACTION WITH NEDD8, LACK OF NEDDYLATION, SUBCELLULAR LOCATION, AND RP DEVELOPMENTAL STAGE. RX PubMed=12215427; DOI=10.1074/jbc.m202413200; RA Antenos M., Casper R.F., Brown T.J.; RT "Interaction with Nedd8, a ubiquitin-like protein, enhances the RT transcriptional activity of the aryl hydrocarbon receptor."; RL J. Biol. Chem. 277:44028-44034(2002). RN [18] RP INTERACTION WITH HSP90AB1. RX PubMed=15581363; DOI=10.1021/bi048736m; RA Ogiso H., Kagi N., Matsumoto E., Nishimoto M., Arai R., Shirouzu M., RA Mimura J., Fujii-Kuriyama Y., Yokoyama S.; RT "Phosphorylation analysis of 90 kDa heat shock protein within the cytosolic RT arylhydrocarbon receptor complex."; RL Biochemistry 43:15510-15519(2004). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BMAL1. RX PubMed=20106950; DOI=10.1093/toxsci/kfq022; RA Xu C.X., Krager S.L., Liao D.F., Tischkau S.A.; RT "Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl RT hydrocarbon receptor-mediated regulation of Period1 gene."; RL Toxicol. Sci. 115:98-108(2010). RN [20] RP DISRUPTION PHENOTYPE. RX PubMed=29726989; DOI=10.1093/hmg/ddy165; RA Zhou Y., Li S., Huang L., Yang Y., Zhang L., Yang M., Liu W., Ramasamy K., RA Jiang Z., Sundaresan P., Zhu X., Yang Z.; RT "A splicing mutation in aryl hydrocarbon receptor associated with retinitis RT pigmentosa."; RL Hum. Mol. Genet. 27:2563-2572(2018). RN [21] RP FUNCTION. RX PubMed=33436590; DOI=10.1038/s41467-020-20461-0; RA Kim J.H., Matsubara T., Lee J., Fenollar-Ferrer C., Han K., Kim D., Jia S., RA Chang C.J., Yang H., Nagano T., Krausz K.W., Yim S.H., Gonzalez F.J.; RT "Lysosomal SLC46A3 modulates hepatic cytosolic copper homeostasis."; RL Nat. Commun. 12:290-290(2021). RN [22] {ECO:0007744|PDB:4M4X} RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 110-267 OF HOMODIMER, MUTAGENESIS RP OF GLU-112; PHE-115; LEU-116; ALA-119; LEU-120; VAL-124; PHE-260 AND RP ILE-262, DOMAIN, REGION, SUBUNIT, AND INTERACTION WITH ARNT. RX PubMed=24001774; DOI=10.1128/mcb.00698-13; RA Wu D., Potluri N., Kim Y., Rastinejad F.; RT "Structure and dimerization properties of the aryl hydrocarbon receptor RT PAS-A domain."; RL Mol. Cell. Biol. 33:4346-4356(2013). RN [23] {ECO:0007744|PDB:5V0L} RP X-RAY CRYSTALLOGRAPHY (4.00 ANGSTROMS) OF 29-267 IN COMPLEXES WITH ARNT AND RP DNA, MUTAGENESIS OF ARG-39; LEU-42; ASN-43; LEU-49; LYS-65; ARG-70; RP PHE-115; LEU-120; PHE-134; ILE-152; LYS-238 AND LEU-240, SUBCELLULAR RP LOCATION, FUNCTION, AND INTERACTION WITH ARNT. RX PubMed=28396409; DOI=10.1073/pnas.1617035114; RA Seok S.H., Lee W., Jiang L., Molugu K., Zheng A., Li Y., Park S., RA Bradfield C.A., Xing Y.; RT "Structural hierarchy controlling dimerization and target DNA recognition RT in the AHR transcriptional complex."; RL Proc. Natl. Acad. Sci. U.S.A. 114:5431-5436(2017). CC -!- FUNCTION: Ligand-activated transcription factor that enables cells to CC adapt to changing conditions by sensing compounds from the environment, CC diet, microbiome and cellular metabolism, and which plays important CC roles in development, immunity and cancer (PubMed:10639156, CC PubMed:10973493, PubMed:1314586, PubMed:7961644, PubMed:7969080, CC PubMed:8806883, PubMed:9427285, PubMed:33436590). Upon ligand binding, CC translocates into the nucleus, where it heterodimerizes with ARNT and CC induces transcription by binding to xenobiotic response elements (XRE) CC (By similarity). Regulates a variety of biological processes, including CC angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility CC and immune modulation (PubMed:20106950, PubMed:28396409). Xenobiotics CC can act as ligands: upon xenobiotic-binding, activates the expression CC of multiple phase I and II xenobiotic chemical metabolizing enzyme CC genes (such as the CYP1A1 gene) (PubMed:10639156, PubMed:10973493, CC PubMed:1314586, PubMed:7961644, PubMed:7969080, PubMed:8806883, CC PubMed:9427285). Mediates biochemical and toxic effects of halogenated CC aromatic hydrocarbons (By similarity). Next to xenobiotics, natural CC ligands derived from plants, microbiota, and endogenous metabolism are CC potent AHR agonists (By similarity). Tryptophan (Trp) derivatives CC constitute an important class of endogenous AHR ligands (By CC similarity). Acts as a negative regulator of anti-tumor immunity: CC indoles and kynurenic acid generated by Trp catabolism act as ligand CC and activate AHR, thereby promoting AHR-driven cancer cell motility and CC suppressing adaptive immunity (By similarity). Regulates the circadian CC clock by inhibiting the basal and circadian expression of the core CC circadian component PER1 (By similarity). Inhibits PER1 by repressing CC the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 CC (PubMed:20106950). The heterodimer ARNT:AHR binds to core DNA sequence CC 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene CC promoters and activates their transcription (PubMed:28396409). CC {ECO:0000250|UniProtKB:P35869, ECO:0000269|PubMed:10639156, CC ECO:0000269|PubMed:10973493, ECO:0000269|PubMed:1314586, CC ECO:0000269|PubMed:20106950, ECO:0000269|PubMed:28396409, CC ECO:0000269|PubMed:33436590, ECO:0000269|PubMed:7961644, CC ECO:0000269|PubMed:7969080, ECO:0000269|PubMed:8806883, CC ECO:0000269|PubMed:9427285}. CC -!- SUBUNIT: Homodimer (PubMed:24001774). Heterodimer; efficient DNA CC binding requires dimerization with another bHLH protein (By CC similarity). Interacts with ARNT; the heterodimer ARNT:AHR binds to CC core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) CC of target gene promoters and activates their transcription CC (PubMed:24001774, PubMed:28396409). Binds MYBBP1A (PubMed:11956195). CC Interacts with coactivators including SRC-1, RIP140 and NOCA7, and with CC the corepressor SMRT. Interacts with NEDD8 and IVNS1ABP CC (PubMed:12215427). Interacts with BMAL1 (PubMed:20106950). Interacts CC with HSP90AB1 (PubMed:15581363). Interacts with TIPARP; leading to CC mono-ADP-ribosylation of AHR and subsequent inhibition of AHR (By CC similarity). {ECO:0000250|UniProtKB:P35869, CC ECO:0000269|PubMed:11956195, ECO:0000269|PubMed:12215427, CC ECO:0000269|PubMed:15581363, ECO:0000269|PubMed:20106950, CC ECO:0000269|PubMed:24001774, ECO:0000269|PubMed:28396409}. CC -!- INTERACTION: CC P30561; P79832: arnt; Xeno; NbExp=2; IntAct=EBI-78863, EBI-958635; CC P30561; O94763: URI1; Xeno; NbExp=2; IntAct=EBI-78863, EBI-357067; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12215427, CC ECO:0000269|PubMed:28396409}. Nucleus {ECO:0000269|PubMed:12215427, CC ECO:0000269|PubMed:20106950, ECO:0000269|PubMed:28396409}. CC Note=Initially cytoplasmic; upon binding with ligand and interaction CC with a HSP90, it translocates to the nucleus. CC {ECO:0000269|PubMed:20106950, ECO:0000269|PubMed:28396409}. CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested including brain, CC heart, kidney, liver, lung, muscle, ovary, skin, spleen and thymus. CC {ECO:0000269|PubMed:10639156}. CC -!- DEVELOPMENTAL STAGE: Between 10 dpc and 12 dpc, abundantly expressed in CC neuroepithelium, branchial arches, cranial nerves, liver, heart and CC spinal ganglia. {ECO:0000269|PubMed:12215427}. CC -!- INDUCTION: Induced or repressed by TGF-beta and dioxin in a cell-type CC specific fashion. Repressed by cAMP, retinoic acid, and TPA. CC {ECO:0000269|PubMed:8806768}. CC -!- DOMAIN: The PAS 1 domain is essential for dimerization and also CC required for AHR:ARNT heterodimerization. CC {ECO:0000269|PubMed:24001774}. CC -!- PTM: Mono-ADP-ribosylated, leading to inhibit transcription activator CC activity of AHR. {ECO:0000250|UniProtKB:P35869}. CC -!- POLYMORPHISM: There are four common alleles; AHRB1; AHRB2; AHRB3 and CC AHRD. The sequence of AHRB2 is shown here. CC -!- DISRUPTION PHENOTYPE: AHR knockdown in the retina results in reduced CC electroretinogram responses, thinning of the outer segment, and CC degeneration of photoreceptors. {ECO:0000269|PubMed:29726989}. CC -!- MISCELLANEOUS: Although it interacts with NEDD8, it does not seem to be CC neddylated. {ECO:0000269|PubMed:12215427}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D38417; BAA07469.1; -; mRNA. DR EMBL; M94623; AAA02896.1; -; Unassigned_DNA. DR EMBL; L19749; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19750; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19751; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19752; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19753; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19754; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19755; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19756; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19757; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19758; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; L19759; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR EMBL; D38416; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AF325111; AAK13443.1; -; Genomic_DNA. DR EMBL; AF405560; AAL89725.1; -; mRNA. DR EMBL; AF405561; AAL89726.1; -; mRNA. DR EMBL; AF405562; AAL89727.1; -; mRNA. DR EMBL; AF405563; AAL89728.1; -; mRNA. DR EMBL; AF405566; AAL89731.1; -; mRNA. DR EMBL; AF405567; AAL89732.1; -; mRNA. DR EMBL; AF405570; AAL89735.1; -; mRNA. DR PIR; A46266; A46266. DR RefSeq; NP_038492.1; NM_013464.4. DR PDB; 4M4X; X-ray; 2.55 A; A/B=110-267. DR PDB; 5V0L; X-ray; 4.00 A; B=29-267. DR PDB; 7Y04; EM; 3.50 A; E=1-398. DR PDB; 8H77; EM; 3.20 A; E=1-437. DR PDBsum; 4M4X; -. DR PDBsum; 5V0L; -. DR PDBsum; 7Y04; -. DR PDBsum; 8H77; -. DR AlphaFoldDB; P30561; -. DR EMDB; EMD-33537; -. DR EMDB; EMD-34519; -. DR SMR; P30561; -. DR BioGRID; 198037; 9. DR CORUM; P30561; -. DR DIP; DIP-222N; -. DR IntAct; P30561; 8. DR STRING; 10090.ENSMUSP00000112137; -. DR BindingDB; P30561; -. DR ChEMBL; CHEMBL6099; -. DR GuidetoPHARMACOLOGY; 2951; -. DR iPTMnet; P30561; -. DR PhosphoSitePlus; P30561; -. DR MaxQB; P30561; -. DR PaxDb; 10090-ENSMUSP00000112137; -. DR ProteomicsDB; 281961; -. DR DNASU; 11622; -. DR GeneID; 11622; -. DR KEGG; mmu:11622; -. DR AGR; MGI:105043; -. DR CTD; 196; -. DR MGI; MGI:105043; Ahr. DR eggNOG; KOG3560; Eukaryota. DR InParanoid; P30561; -. DR OrthoDB; 5360131at2759; -. DR PhylomeDB; P30561; -. DR Reactome; R-MMU-211945; Phase I - Functionalization of compounds. DR Reactome; R-MMU-211976; Endogenous sterols. DR Reactome; R-MMU-211981; Xenobiotics. DR Reactome; R-MMU-8937144; Aryl hydrocarbon receptor signalling. DR BioGRID-ORCS; 11622; 2 hits in 82 CRISPR screens. DR ChiTaRS; Ahr; mouse. DR PRO; PR:P30561; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P30561; Protein. DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:DFLAT. DR GO; GO:0034752; C:cytosolic aryl hydrocarbon receptor complex; TAS:DFLAT. DR GO; GO:0034753; C:nuclear aryl hydrocarbon receptor complex; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0005667; C:transcription regulator complex; TAS:MGI. DR GO; GO:0052869; F:arachidonic acid omega-hydroxylase activity; ISO:MGI. DR GO; GO:0017162; F:aryl hydrocarbon receptor binding; IPI:UniProtKB. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0017025; F:TBP-class protein binding; ISO:MGI. DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; ISO:MGI. DR GO; GO:0015643; F:toxic substance binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI. DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI. DR GO; GO:0030183; P:B cell differentiation; TAS:DFLAT. DR GO; GO:0001782; P:B cell homeostasis; IMP:DFLAT. DR GO; GO:0001922; P:B-1 B cell homeostasis; TAS:DFLAT. DR GO; GO:0008015; P:blood circulation; IMP:DFLAT. DR GO; GO:0001568; P:blood vessel development; IMP:DFLAT. DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:DFLAT. DR GO; GO:0001974; P:blood vessel remodeling; IMP:DFLAT. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:DFLAT. DR GO; GO:0043010; P:camera-type eye development; IMP:DFLAT. DR GO; GO:0019933; P:cAMP-mediated signaling; ISO:MGI. DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; IMP:DFLAT. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0000902; P:cell morphogenesis; IMP:DFLAT. DR GO; GO:1904613; P:cellular response to 2,3,7,8-tetrachlorodibenzodioxine; IDA:UniProt. DR GO; GO:1904682; P:cellular response to 3-methylcholanthrene; IDA:UniProtKB. DR GO; GO:0071320; P:cellular response to cAMP; ISO:MGI. DR GO; GO:1904322; P:cellular response to forskolin; ISO:MGI. DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; ISO:MGI. DR GO; GO:0097237; P:cellular response to toxic substance; ISO:MGI. DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:UniProtKB. DR GO; GO:0003243; P:circumferential growth involved in left ventricle morphogenesis; IMP:DFLAT. DR GO; GO:0048732; P:gland development; IMP:MGI. DR GO; GO:0072102; P:glomerulus morphogenesis; IMP:DFLAT. DR GO; GO:0002376; P:immune system process; IMP:DFLAT. DR GO; GO:0060993; P:kidney morphogenesis; IMP:DFLAT. DR GO; GO:0001889; P:liver development; IMP:DFLAT. DR GO; GO:0002260; P:lymphocyte homeostasis; IMP:DFLAT. DR GO; GO:1903170; P:negative regulation of calcium ion transmembrane transport; ISO:MGI. DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:MGI. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:MGI. DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; ISO:MGI. DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IMP:DFLAT. DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0045906; P:negative regulation of vasoconstriction; IMP:DFLAT. DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; ISO:MGI. DR GO; GO:0001541; P:ovarian follicle development; ISO:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:0045793; P:positive regulation of cell size; IMP:DFLAT. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0040010; P:positive regulation of growth rate; IMP:DFLAT. DR GO; GO:0045899; P:positive regulation of RNA polymerase II transcription preinitiation complex assembly; IDA:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0035166; P:post-embryonic hemopoiesis; IMP:DFLAT. DR GO; GO:0030850; P:prostate gland development; IMP:MGI. DR GO; GO:0034504; P:protein localization to nucleus; ISO:MGI. DR GO; GO:1903409; P:reactive oxygen species biosynthetic process; ISO:MGI. DR GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB. DR GO; GO:0030888; P:regulation of B cell proliferation; ISO:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI. DR GO; GO:0060420; P:regulation of heart growth; TAS:DFLAT. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0048608; P:reproductive structure development; IMP:MGI. DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI. DR GO; GO:0009636; P:response to toxic substance; ISO:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB. DR GO; GO:0048536; P:spleen development; IMP:DFLAT. DR GO; GO:0043029; P:T cell homeostasis; IMP:DFLAT. DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0001944; P:vasculature development; IMP:UniProtKB. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:MGI. DR CDD; cd11436; bHLH-PAS_AhR; 1. DR CDD; cd00130; PAS; 2. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR Gene3D; 3.30.450.20; PAS domain; 2. DR InterPro; IPR039091; AHR/AHRR. DR InterPro; IPR033348; AHR_bHLH. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR001610; PAC. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR013767; PAS_fold. DR InterPro; IPR013655; PAS_fold_3. DR PANTHER; PTHR10649; ARYL HYDROCARBON RECEPTOR; 1. DR PANTHER; PTHR10649:SF9; ARYL HYDROCARBON RECEPTOR; 1. DR Pfam; PF00010; HLH; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF08447; PAS_3; 1. DR SMART; SM00353; HLH; 1. DR SMART; SM00086; PAC; 1. DR SMART; SM00091; PAS; 2. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS50112; PAS; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; ADP-ribosylation; Biological rhythms; Cell cycle; KW Cytoplasm; Direct protein sequencing; DNA-binding; Nucleus; Receptor; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation. FT PROPEP 1..9 FT /evidence="ECO:0000269|PubMed:1325649, FT ECO:0000269|PubMed:1846217" FT /id="PRO_0000013452" FT CHAIN 10..848 FT /note="Aryl hydrocarbon receptor" FT /id="PRO_0000013453" FT DOMAIN 26..79 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT DOMAIN 116..179 FT /note="PAS 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 269..336 FT /note="PAS 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 342..380 FT /note="PAC" FT REGION 1..38 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 37..65 FT /note="DNA-binding" FT /evidence="ECO:0000250|UniProtKB:P35869" FT REGION 49..81 FT /note="Required for maintaining the overall integrity of FT the AHR:ARNT heterodimer and its transcriptional activity" FT /evidence="ECO:0000250|UniProtKB:P35869" FT REGION 116..124 FT /note="Required for maintaining the overall integrity of FT the AHR:ARNT heterodimer and its transcriptional activity" FT /evidence="ECO:0000269|PubMed:24001774" FT REGION 260..262 FT /note="Required for maintaining the overall integrity of FT the AHR:ARNT heterodimer and its transcriptional activity" FT /evidence="ECO:0000269|PubMed:24001774" FT REGION 421..449 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 12..15 FT /note="Nuclear localization signal 1" FT /evidence="ECO:0000250|UniProtKB:P35869" FT MOTIF 36..41 FT /note="Nuclear localization signal 2" FT /evidence="ECO:0000250|UniProtKB:P35869" FT MOTIF 63..71 FT /note="Nuclear export signal" FT /evidence="ECO:0000250|UniProtKB:P35869" FT COMPBIAS 422..449 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 324 FT /note="M -> I (in allele AHRB1; no increase in specific FT ligand binding)" FT /evidence="ECO:0000269|PubMed:11875369, FT ECO:0000269|PubMed:1314586, ECO:0000269|PubMed:1325649, FT ECO:0000269|PubMed:7961644, ECO:0000269|PubMed:7969080, FT ECO:0000269|PubMed:8148872" FT VARIANT 348 FT /note="F -> L (in allele AHRB1 and allele AHRD; no FT reduction in specific ligand binding)" FT /evidence="ECO:0000269|PubMed:11875369, FT ECO:0000269|PubMed:1314586, ECO:0000269|PubMed:1325649, FT ECO:0000269|PubMed:7961644, ECO:0000269|PubMed:7969080, FT ECO:0000269|PubMed:8148872, ECO:0000269|Ref.7" FT VARIANT 375 FT /note="A -> V (in allele AHRD; reduced specific ligand FT binding)" FT /evidence="ECO:0000269|PubMed:11875369, FT ECO:0000269|PubMed:7961644, ECO:0000269|PubMed:7969080, FT ECO:0000269|PubMed:8148872, ECO:0000269|Ref.7" FT VARIANT 471 FT /note="P -> L (in allele AHRB1; no increase in specific FT ligand binding)" FT /evidence="ECO:0000269|PubMed:11875369, FT ECO:0000269|PubMed:1314586, ECO:0000269|PubMed:1325649, FT ECO:0000269|PubMed:7961644, ECO:0000269|PubMed:7969080, FT ECO:0000269|PubMed:8148872" FT VARIANT 533 FT /note="N -> S (in allele AHRB1; no increase in specific FT ligand binding)" FT /evidence="ECO:0000269|PubMed:11875369, FT ECO:0000269|PubMed:1314586, ECO:0000269|PubMed:1325649, FT ECO:0000269|PubMed:7961644, ECO:0000269|PubMed:7969080, FT ECO:0000269|PubMed:8148872" FT VARIANT 589 FT /note="M -> I (in allele AHRD)" FT /evidence="ECO:0000269|PubMed:11875369, ECO:0000269|Ref.7" FT VARIANT 589 FT /note="M -> L (in allele AHRB1; no increase in specific FT ligand binding)" FT /evidence="ECO:0000269|PubMed:1314586, FT ECO:0000269|PubMed:1325649, ECO:0000269|PubMed:7961644, FT ECO:0000269|PubMed:7969080, ECO:0000269|PubMed:8148872" FT VARIANT 758 FT /note="T -> A (in allele AHRB1 and allele AHRD)" FT /evidence="ECO:0000269|PubMed:11875369, FT ECO:0000269|PubMed:1314586, ECO:0000269|PubMed:1325649, FT ECO:0000269|PubMed:7961644, ECO:0000269|PubMed:7969080, FT ECO:0000269|PubMed:8148872, ECO:0000269|Ref.7" FT VARIANT 806..848 FT /note="Missing (in allele AHRB1)" FT VARIANT 808 FT /note="I -> V (in allele AHRB3)" FT /evidence="ECO:0000269|PubMed:7969080" FT VARIANT 821 FT /note="G -> D (in allele AHRB3)" FT /evidence="ECO:0000269|PubMed:7969080" FT VARIANT 824 FT /note="A -> V (in allele AHRB3)" FT /evidence="ECO:0000269|PubMed:7969080" FT VARIANT 843..848 FT /note="TPGGFL -> SHLVGSCSSHARMKFIQEQDTGTVRVGHQYYFSKTFDSCI FT (in allele AHRB3)" FT MUTAGEN 39 FT /note="R->D: Drastically reduces the binding affinity of FT AHR?ARNT to dioxin response element (DRE). Impairs FT ligand-induced nuclear translocation of AHR." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 42 FT /note="L->E: Significantly reduces binding affinities of FT the AHR?ARNT heterodimer to DRE." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 43 FT /note="N->A: Reduces the binding affinity of AHR?ARNT to FT the DRE by more than 10-fold." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 49 FT /note="L->E: Reduces the AHR induction transcription FT activity by 50%. Increases ligand-induced nuclear FT translocation of AHR." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 65 FT /note="K->E: Reduces the binding affinity of AHR?ARNT to FT the DRE by more than 10-fold." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 70 FT /note="R->D: Drastically reduces the AHR transcription FT activity induction. Increases constitutive AHR nuclear FT translocation in the absence of ligands. Reduces binding FT affinity for the DRE by more than 30-fold in vitro." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 112 FT /note="E->A: Reduces transcription activity. Decreases FT interaction with ARNT." FT /evidence="ECO:0000269|PubMed:24001774" FT MUTAGEN 115 FT /note="F->A: Highly disrupts the dimerization ability of FT AHR." FT /evidence="ECO:0000269|PubMed:24001774" FT MUTAGEN 115 FT /note="F->D: Highly disrupts the dimerization ability of FT AHR. Reduces the AHR transcription factor activity FT induction by 50%." FT /evidence="ECO:0000269|PubMed:24001774, FT ECO:0000269|PubMed:28396409" FT MUTAGEN 116 FT /note="L->E: Highly disrupts the dimerization ability of FT AHR. Reduces transcription activity. Decreases interaction FT with ARNT." FT /evidence="ECO:0000269|PubMed:24001774" FT MUTAGEN 119 FT /note="A->D: Highly disrupts the dimerization ability of FT AHR. Reduces transcription activity. Impairs interaction FT with ARNT." FT /evidence="ECO:0000269|PubMed:24001774" FT MUTAGEN 120 FT /note="L->D: Significantly reduces binding affinities of FT the AHR?ARNT heterodimer to DRE." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 120 FT /note="L->E: Highly disrupts the dimerization ability of FT AHR. Reduces transcription activity. Impairs interaction FT with ARNT." FT /evidence="ECO:0000269|PubMed:24001774" FT MUTAGEN 124 FT /note="V->D: Highly disrupts the dimerization ability of FT AHR. Reduces transcription activity. Impairs interaction FT with ARNT." FT /evidence="ECO:0000269|PubMed:24001774" FT MUTAGEN 134 FT /note="F->D: Reduces the AHR induction activity by ~50%. FT Translocates to the nucleus at a high level." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 152 FT /note="I->D: Completely abolished the AHR induction FT activity, the ligand-induced nuclear translocation of AHR, FT and drastically reduced DRE-binding in vitro." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 238 FT /note="K->D: Significantly reduces binding affinities of FT the AHR:ARNT heterodimer to DRE." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 240 FT /note="L->D: Significantly reduces binding affinities of FT the AHR:ARNT heterodimer to DRE." FT /evidence="ECO:0000269|PubMed:28396409" FT MUTAGEN 260 FT /note="F->D: Reduces transcription activity. Impairs FT interaction with ARNT." FT /evidence="ECO:0000269|PubMed:24001774" FT MUTAGEN 262 FT /note="I->D: Reduces transcription activity. Decreases FT interaction with ARNT." FT /evidence="ECO:0000269|PubMed:24001774" FT CONFLICT 74 FT /note="S -> T (in Ref. 2 and 3)" FT /evidence="ECO:0000305" FT CONFLICT 132..133 FT /note="LV -> FL (in Ref. 1 and 4)" FT /evidence="ECO:0000305" FT CONFLICT 171..172 FT /note="QL -> HV (in Ref. 1 and 4)" FT /evidence="ECO:0000305" FT CONFLICT 351 FT /note="H -> N (in Ref. 5; D38416)" FT /evidence="ECO:0000305" FT HELIX 110..113 FT /evidence="ECO:0007829|PDB:4M4X" FT HELIX 114..119 FT /evidence="ECO:0007829|PDB:4M4X" FT STRAND 120..128 FT /evidence="ECO:0007829|PDB:4M4X" FT STRAND 131..136 FT /evidence="ECO:0007829|PDB:4M4X" FT HELIX 140..143 FT /evidence="ECO:0007829|PDB:4M4X" FT HELIX 148..151 FT /evidence="ECO:0007829|PDB:4M4X" FT HELIX 156..158 FT /evidence="ECO:0007829|PDB:4M4X" FT TURN 162..164 FT /evidence="ECO:0007829|PDB:4M4X" FT HELIX 165..172 FT /evidence="ECO:0007829|PDB:4M4X" FT STRAND 211..219 FT /evidence="ECO:0007829|PDB:4M4X" FT STRAND 225..240 FT /evidence="ECO:0007829|PDB:4M4X" FT STRAND 256..265 FT /evidence="ECO:0007829|PDB:4M4X" FT STRAND 281..285 FT /evidence="ECO:0007829|PDB:8H77" FT STRAND 291..294 FT /evidence="ECO:0007829|PDB:8H77" FT HELIX 296..301 FT /evidence="ECO:0007829|PDB:8H77" FT HELIX 306..311 FT /evidence="ECO:0007829|PDB:8H77" FT TURN 312..314 FT /evidence="ECO:0007829|PDB:8H77" FT HELIX 321..324 FT /evidence="ECO:0007829|PDB:8H77" FT TURN 325..327 FT /evidence="ECO:0007829|PDB:8H77" FT HELIX 328..336 FT /evidence="ECO:0007829|PDB:8H77" FT STRAND 342..348 FT /evidence="ECO:0007829|PDB:8H77" FT STRAND 354..365 FT /evidence="ECO:0007829|PDB:8H77" FT STRAND 367..380 FT /evidence="ECO:0007829|PDB:8H77" FT HELIX 382..390 FT /evidence="ECO:0007829|PDB:8H77" FT HELIX 392..394 FT /evidence="ECO:0007829|PDB:8H77" SQ SEQUENCE 848 AA; 95017 MW; AA1560FA83DDD03C CRC64; MSSGANITYA SRKRRKPVQK TVKPIPAEGI KSNPSKRHRD RLNTELDRLA SLLPFPQDVI NKLDKLSVLR LSVSYLRAKS FFDVALKSTP ADRNGGQDQC RAQIRDWQDL QEGEFLLQAL NGFVLVVTAD ALVFYASSTI QDYLGFQQSD VIHQSVYELI HTEDRAEFQR QLHWALNPDS AQGVDEAHGP PQAAVYYTPD QLPPENASFM ERCFRCRLRC LLDNSSGFLA MNFQGRLKYL HGQNKKGKDG ALLPPQLALF AIATPLQPPS ILEIRTKNFI FRTKHKLDFT PIGCDAKGQL ILGYTEVELC TRGSGYQFIH AADMLHCAES HIRMIKTGES GMTVFRLFAK HSRWRWVQSN ARLIYRNGRP DYIIATQRPL TDEEGREHLQ KRSTSLPFMF ATGEAVLYEI SSPFSPIMDP LPIRTKSNTS RKDWAPQSTP SKDSFHPSSL MSALIQQDES IYLCPPSSPA PLDSHFLMGS VSKCGSWQDS FAAAGSEAAL KHEQIGHAQD VNLALSGGPS ELFPDNKNND LYNIMRNLGI DFEDIRSMQN EEFFRTDSTA AGEVDFKDID ITDEILTYVQ DSLNNSTLMN SACQQQPVTQ HLSCMLQERL QLEQQQQLQQ PPPQALEPQQ QLCQMVCPQQ DLGPKHTQIN GTFASWNPTP PVSFNCPQQE LKHYQLFSSL QGTAQEFPYK PEVDSVPYTQ NFAPCNQPLL PEHSKSVQLD FPGRDFEPSL HPTTSNLDFV SCLQVPENQS HGINSQSTMV SPQAYYAGAM SMYQCQPGPQ RTPVDQTQYS SEIPGSQAFL SKVQSRGIFN ETYSSDLSSI GHAAQTTGHL HHLAEARPLP DITPGGFL //