AHR_DELLE
ID AHR_DELLE Reviewed; 845 AA.
AC Q95LD9;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Aryl hydrocarbon receptor;
DE Short=Ah receptor;
DE Short=AhR;
DE Flags: Precursor;
GN Name=AHR;
OS Delphinapterus leucas (Beluga whale).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Odontoceti;
OC Monodontidae; Delphinapterus.
OX NCBI_TaxID=9749;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=11606800; DOI=10.1093/toxsci/64.1.41;
RA Jensen B.A., Hahn M.E.;
RT "cDNA cloning and characterization of a high affinity aryl hydrocarbon
RT receptor in a cetacean, the beluga, Delphinapterus leucas.";
RL Toxicol. Sci. 64:41-56(2001).
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-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.
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 ARNTL/BMAL1. Interacts with HSP90AB1
CC (By similarity). Interacts with TIPARP; leading to mono-ADP-
CC ribosylation 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 -!- PTM: Mono-ADP-ribosylated, leading to inhibit transcription activator
CC activity of AHR. {ECO:0000250|UniProtKB:P35869}.
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DR EMBL; AF332999; AAL04031.1; -; mRNA.
DR AlphaFoldDB; Q95LD9; -.
DR SMR; Q95LD9; -.
DR STRING; 9749.Q95LD9; -.
DR Ensembl; ENSDLET00000030004; ENSDLEP00000027298; ENSDLEG00000019698.
DR OrthoDB; 174264at2759; -.
DR Proteomes; UP000248483; Unplaced.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IEA:InterPro.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IEA:Ensembl.
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: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; IEA:Ensembl.
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: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:0030888; P:regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
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; Cell cycle; Cytoplasm;
KW DNA-binding; Nucleus; Receptor; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation.
FT PROPEP 1..10
FT /evidence="ECO:0000250|UniProtKB:P30561"
FT /id="PRO_0000045166"
FT CHAIN 11..845
FT /note="Aryl hydrocarbon receptor"
FT /id="PRO_0000045167"
FT DOMAIN 27..80
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 110..180
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 274..341
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 347..385
FT /note="PAC"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 820..845
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 845 AA; 95413 MW; 8E83DB9EE0D946D8 CRC64;
MNSSSASITY ASRKRRKPVQ KTVKPVPAEG IKSNPSKRHR DRLNTELDRL ASLLPFPQDV
VNKLDKLSVL RLSVSYLRAK SFFDVALKST PADRNGVQDN CRTKFREGLN LQEGEFLLQA
LNGFVLVVTT DALVFYASST IQDYLGFQQS DVIHQSVYEL IHTEDRAEFQ RQLHWALNPS
QCPDSGQKMD EANGLSQPAV YYNPDQVPPE NSSSMERCFV CRLRCLLDNS SGFLAMNFQG
RLKYLHGQNK KGKDGSILPP QLALFAIATP LQPPSILEIR TKNFIFRTKH KLDFTPTGCD
AKGRIVLGYT EAELCMRGSG YQFIHAADML YCAEYHIRMI KTGESGLIVF RLLTKDNRWT
WVQSNARLVY KNGRPDYIIA TQRPLTDEEG TEHLRKRNLK LPFMFTTGEA VLYEVTNPFP
PIMDPLPIRT KNGAGGKDSA TKSTLSKDFL NPSSLLNAMM QQDESIYLYP ASSSTPFERN
FFSDSQNECS NWQNNVAPMG SDDILKHEQI GQSQEMNPTL SGDHAGLFPD NRNSDLYSIM
KHLGIDFEDI KHMQQNEEFF RTDFSGEDDF RDIDLTDEIL TYVEDSLNKS ALGCSGYHPQ
QSMALNPSCM VQEHLQLEQQ EQRQQHQKHR AVEQQQLCQK MQHMQVNGMF ANWSSNQSGP
FNCPQPDLQQ YDVFSDVPGT SQEFPYKSEI DTMPYAQNFI PCSQSVLPPH SKGTQLDFPI
GDFEPAPYPT TSSNLEDFVT CLQVPQSQRH GLNPQSAIVT PQTCYTGAVS MYQCQPEAQH
SHVAQMQYNP TVPGPQAFLN KFQNGGVLNE TYPAELNSIN NTQPTTHLHP SEARPFSDLT
SSGFL
