ID AHR_MUSSP Reviewed; 854 AA.
AC Q8R4S2;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 27-MAR-2024, entry version 121.
DE RecName: Full=Aryl hydrocarbon receptor;
DE Short=Ah receptor;
DE Short=AhR;
DE Flags: Precursor;
GN Name=Ahr;
OS Mus spretus (Western Mediterranean mouse) (Algerian mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10096 {ECO:0000312|EMBL:AAL89736.1};
RN [1] {ECO:0000312|EMBL:AAL89736.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=SPRETUS/Ei;
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).
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. 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 Regulates a variety of biological processes, including angiogenesis,
CC hematopoiesis, drug and lipid metabolism, cell motility and immune
CC modulation. Xenobiotics can act as ligands: upon xenobiotic-binding,
CC activates the expression of multiple phase I and II xenobiotic chemical
CC metabolizing enzyme genes (such as the CYP1A1 gene). Mediates
CC biochemical and toxic effects of halogenated aromatic hydrocarbons.
CC Next to xenobiotics, natural ligands derived from plants, microbiota,
CC and endogenous metabolism are potent AHR agonists. Tryptophan (Trp)
CC derivatives constitute an important class of endogenous AHR ligands.
CC Acts as a negative regulator of anti-tumor immunity: indoles and
CC kynurenic acid generated by Trp catabolism act as ligand and activate
CC AHR, thereby promoting AHR-driven cancer cell motility and suppressing
CC adaptive immunity. Regulates the circadian clock by inhibiting the
CC basal and circadian expression of the core circadian component PER1.
CC Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated
CC transcriptional activation of PER1. 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 {ECO:0000250|UniProtKB:P35869}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer; efficient DNA binding
CC requires dimerization with another bHLH protein. Interacts with ARNT;
CC the heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within
CC the dioxin response element (DRE) of target gene promoters and
CC activates their transcription (By similarity). Binds MYBBP1A (By
CC similarity). Interacts with coactivators including SRC-1, RIP140 and
CC NOCA7, and with the corepressor SMRT. Interacts with NEDD8 and IVNS1ABP
CC (By similarity). Interacts with BMAL1. Interacts with HSP90AB1 (By
CC similarity). Interacts with TIPARP; leading to mono-ADP-ribosylation of
CC AHR and subsequent inhibition of AHR (By similarity).
CC {ECO:0000250|UniProtKB:P30561, ECO:0000250|UniProtKB:P35869}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P30561}. Nucleus
CC {ECO:0000250|UniProtKB:P30561}. Note=Initially cytoplasmic; upon
CC binding with ligand and interaction with a HSP90, it translocates to
CC the nucleus. {ECO:0000250|UniProtKB:P30561}.
CC -!- DOMAIN: The PAS 1 domain is essential for dimerization and also
CC required for AHR:ARNT heterodimerization.
CC {ECO:0000250|UniProtKB:P30561}.
CC -!- PTM: Mono-ADP-ribosylated, leading to inhibit transcription activator
CC activity of AHR. {ECO:0000250|UniProtKB:P35869}.
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DR EMBL; AF405571; AAL89736.1; -; mRNA.
DR AlphaFoldDB; Q8R4S2; -.
DR SMR; Q8R4S2; -.
DR MGI; MGI:105043; Ahr.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0034753; C:nuclear aryl hydrocarbon receptor complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProt.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; IEA:Ensembl.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProt.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0017025; F:TBP-class protein binding; IEA:Ensembl.
DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; IEA:Ensembl.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl.
DR GO; GO:0019933; P:cAMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:1904322; P:cellular response to forskolin; IEA:Ensembl.
DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; IEA:Ensembl.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:0030888; P:regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISS:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IEA:InterPro.
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 2: Evidence at transcript level;
KW Activator; ADP-ribosylation; Biological rhythms; Cell cycle; Cytoplasm;
KW DNA-binding; Nucleus; Receptor; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT PROPEP 1..9
FT /evidence="ECO:0000250|UniProtKB:P30561"
FT /id="PRO_0000013462"
FT CHAIN 10..854
FT /note="Aryl hydrocarbon receptor"
FT /id="PRO_0000013463"
FT DOMAIN 26..79
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 111..175
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140,
FT ECO:0000305"
FT DOMAIN 270..340
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140,
FT ECO:0000305"
FT DOMAIN 346..387
FT /note="PAC"
FT /evidence="ECO:0000305"
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:0000250|UniProtKB:P30561"
FT REGION 264..266
FT /note="Required for maintaining the overall integrity of
FT the AHR:ARNT heterodimer and its transcriptional activity"
FT /evidence="ECO:0000250|UniProtKB:P30561"
FT REGION 425..452
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 426..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 854 AA; 95486 MW; 89E8F304B4B9847E CRC64;
MSSGANITYA SRKRRKPVQK TVKPIPAEGI KSNPSKRHRD RLNTELDRLA SLLPFPQDVI
NKLDKLSVLR LSVSYLRAKS FFDVALKSTP ADRNGGQDQC RAQIRDWQNL QEGEFLLQAL
NGFVLVVTAD ALVFYASSTI QDYLGFQQSD VIHQSVYELI HTEDRAEFQR QLHWALNPSQ
CTDSAQGVDE AHGPPQAAVY YTPDQLPPEN ASFMERCFRC RLRCLLDNSS GFLAMNFQGR
LKYLHGQNKK GKDGALLPPQ LALFAIATPL QPPSILEIRT KNFIFRTKHK LDFTPIGCDA
KGQLILGYTE VELCTRGSGY QFIHAADMLH CAESHIRMIK TGESGMTVFR LLAKHSRWRW
VQSNARLIYR NGRPDYIIAT QRPLTDEEGR EHLQKRSMSL PFMFATGEAV LYEISSPFSP
IMDPLPIRTK SNTSRKDWAP QSTPSKDSFH PSSLMSALIQ QDESIYLCPP SSPAPLDSHF
LMGSVSKCGS WQDSFAATGS EAALKHEQIG HAQDVNLALS GGPSELFPDN KNNDLYSIMR
DLGIDFEDIR SMQNEEFFRT DSTAAAAGEV DFKDIDITDE ILTYVQDSLN NSTLLNSACQ
QQPVTQHLSC MLQERLQLEQ QQQLQQPPPQ ALEPQQQLCQ MVCPQQDLGP KHTQINGTFA
SWNPTPPVSF NCPQQELKHY QIFSSLQGTA QEFPYKPEVD SVPYTQNFAP CNQPLLPEHS
KSVQLDFPGR DFEPSLHPTT SNLDFVSCLQ VPENQSHGIN SQSAMVSPQA YYAGAMSMYQ
CQPGPQRTPV DQTQYGSEIP GSQAFLSKVQ SRGVFNETYS SDLSSIGHAA QTTGHLHHLA
EARPLPDITP GGFL
//
