AHR_RABIT
ID AHR_RABIT Reviewed; 847 AA.
AC O02747;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 25-MAY-2022, entry version 130.
DE RecName: Full=Aryl hydrocarbon receptor;
DE Short=Ah receptor;
DE Short=AhR;
GN Name=AHR;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=9022676; DOI=10.1111/j.1432-1033.1996.0512r.x;
RA Takahashi Y., Nakayama K., Shimojima T., Itoh S., Kamataki T.;
RT "Expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon
RT receptor nuclear translocator (Arnt) in adult rabbits known to be non-
RT responsive to cytochrome P-450 1A1 (CYP1A1) inducers.";
RL Eur. J. Biochem. 242:512-518(1996).
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:9022676). Upon ligand
CC binding, translocates into the nucleus, where it heterodimerizes with
CC ARNT and induces transcription by binding to xenobiotic response
CC elements (XRE). Regulates a variety of biological processes, including
CC angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility
CC and immune modulation. Xenobiotics can act as ligands: upon xenobiotic-
CC binding, activates the expression of multiple phase I and II xenobiotic
CC chemical 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-ARNTL/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 (By
CC similarity). {ECO:0000250|UniProtKB:P35869,
CC ECO:0000269|PubMed:9022676}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer; efficient DNA binding
CC requires dimerization with another bHLH protein (By similarity). Binds
CC MYBBP1A (By similarity). Interacts with coactivators including SRC-1,
CC RIP140 and NOCA7, and with the corepressor SMRT. Interacts with NEDD8
CC and IVNS1ABP (By similarity). Interacts with ARNTL/BMAL1. Interacts
CC with HSP90AB1 (By similarity). Interacts with ARNT; the heterodimer
CC ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin
CC response element (DRE) of target gene promoters and activates their
CC transcription. Interacts with TIPARP; leading to mono-ADP-ribosylation
CC of 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; D38226; BAA19930.1; -; mRNA.
DR RefSeq; NP_001075674.1; NM_001082205.1.
DR AlphaFoldDB; O02747; -.
DR SMR; O02747; -.
DR STRING; 9986.ENSOCUP00000003361; -.
DR BindingDB; O02747; -.
DR ChEMBL; CHEMBL4725; -.
DR PRIDE; O02747; -.
DR GeneID; 100008995; -.
DR KEGG; ocu:100008995; -.
DR CTD; 196; -.
DR eggNOG; KOG3560; Eukaryota.
DR InParanoid; O02747; -.
DR OrthoDB; 174264at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IEA:InterPro.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IEA:InterPro.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR033348; AHR.
DR InterPro; IPR039091; AHR/AHRR.
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; PTHR10649; 1.
DR PANTHER; PTHR10649:SF9; PTHR10649:SF9; 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; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 1.
PE 2: Evidence at transcript level;
KW Activator; ADP-ribosylation; Biological rhythms; Cytoplasm; DNA-binding;
KW Nucleus; Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..847
FT /note="Aryl hydrocarbon receptor"
FT /id="PRO_0000127116"
FT DOMAIN 27..80
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 120..173
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 281..336
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 346..384
FT /note="PAC"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 38..66
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P35869"
FT REGION 117..125
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 430..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 825..847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 847 AA; 94437 MW; 097DEBA6BF467F6C CRC64;
MNGGGANITY ASRKRRKPVQ KTVKPIPAEG IKSNPSKRHR DRLNTELDRL ASLLPFPQDV
INKLDKLSVL RLSVSYLRAK SFFDVALKSS SADRNGGQDP CRAKFGEGLN LQEGEFLLQA
LNGFVLVVTV DALVFYASST IQDYLGFQQS DVIHQSVYEL IHTEDRAEFQ RQLHWALNPS
QCTDPGQGAD ETHGLPQPVY YNPDQLPPEN SSFMERCFIC RLRCLLDNSS GFLAMNFQGR
LKFLHGQNKK GKDGSLLPPQ LALFAIATPL QPPSILEIRT KNFIFRTKHK LDFTPTGCDA
KGQIVLGYTE AELCMRGSGY QFIHAADMLY CAESHIRMIK TGESGLAVFR LLTKDNRWAW
VQSNARFIYK NGRPDFIIAT QRPLTDEEGR EHLLKRNTKL PFMFTTGEAV LYEMTSPFPP
IMDPLPIRPK SGTCGKDSAT KPTPSKDSVH PSSLLSALMQ QDESIYLYPP SSNAPFERNF
FTESLNECSN WPENVASVAG GSVLKHEQIG QSQEVSPAFS GDQTVLFPDN KNCDLYNIMK
NLGVDFEDIK NMQNEEFFGA DFSGEVDFRD IDITDEILTY VQDSLNKSPF GSPGYQPQPA
TALNSSCMVQ ERLQLGPPQQ PPCRSEQATV EPQQQLCQKM EHMQVNSMFA NWSANQPVPF
SEPQQDLQPY SVFTDFHTAD QAFPYTAAMN TMPYTQNFTP CNQTVAPQHS RCTQLDFAMG
NFDSSPYPST SNLEDFVTCL QVPDRQTHGG NPQSAMVAPQ TCYAGAVSMY QCQPGPAHTL
MGQMQCEPPV PGPEAFLNKF PNGGMLNETY PADLHDINNT VASTHLPPLH HPSEARPFPD
LASGRLL
