AHR_MUSCR
ID AHR_MUSCR Reviewed; 854 AA.
AC Q8R4S7;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 25-MAY-2022, entry version 111.
DE RecName: Full=Aryl hydrocarbon receptor;
DE Short=Ah receptor;
DE Short=AhR;
DE Flags: Precursor;
GN Name=Ahr;
OS Mus caroli (Ryukyu mouse) (Ricefield mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10089 {ECO:0000312|EMBL:AAL89729.1};
RN [1] {ECO:0000312|EMBL:AAL89729.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CAROLI/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-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 -!- 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; AF405564; AAL89729.1; -; mRNA.
DR AlphaFoldDB; Q8R4S7; -.
DR SMR; Q8R4S7; -.
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:0005634; C:nucleus; 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:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1904682; P:cellular response to 3-methylcholanthrene; 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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
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; 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; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT PROPEP 1..9
FT /evidence="ECO:0000250|UniProtKB:P30561"
FT /id="PRO_0000013454"
FT CHAIN 10..854
FT /note="Aryl hydrocarbon receptor"
FT /id="PRO_0000013455"
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 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 432..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 434..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 854 AA; 95715 MW; 8B74C05031BB1D0C CRC64;
MSSGANITYA SRKRRKPVQK TVKPIPAEGI KSNPSKRHRD RLNTELDRLA SLLPFPQDVI
NKLDKLSVLR LSVSYLRAKS FFDVALKSTP ADRNGGQDQC RAQIRDWQDL QEGEFLLQAL
NGFVLVVTAD ALVFYASSTI QDYLGFQQSD VIHQSVYELI HTEDRAEFQR QLHWALNPSQ
CTDSAQGVDE AHGPPQTAVY YTPDQLPPEN ASFMERCFRC RLRCLLDNSS GFLAMNFQGR
LKYLHGQNKK GKDGALLPPQ LALFAIATPL QPPSILEIRT KNFIFRTKHK LDFTPSGCDA
KGQLILGYTE VELCTRGSGY QFIHAADMLH CAESHIRMIK TGESGMTVFR LLAKHSRWRW
VQSNARLIYR NGRPDYIIAT QRPLTDEEGR EHLQKRSMSL PFMFATGEAV LYEISSPFSP
IMDPLPIRAK SNTSRKDWAP QSTPSKDSFH PSSLMSALIQ QDESIYLCPP SSPAPLDSHF
LMGSVSKCGS WQDSFAAAGS EAALKHEQIG HAQDVNLALS GGPSELFPDN KNNDLYSIMR
NLGIDFEDIR SMQNEEFFRT DSTATGEVDF KDIDITDEIL TYVQDSLNNS TLLNSACQQQ
PVTQHLSCML QERLQLEQQQ QQQLQQPPTQ ALEPQQQLCQ MECPQQDLGQ RHTQINGSFA
SWNPTPPVSF NCPQQELKHY HLFSSLQGTA QEFPYKPEVD GMPYTQNFAP CNQPLLPEHS
KSVQLDFPGR DFEPSLHPTT SNLDFVSCLQ VPENQSHGIN SQSAMVSPQT YYAGAMSMYQ
CQPGPQHTPV DQTQYSSEIP GSQAFLSKVQ SRGVFNETYP SDLSSIGHAA QTTGHLHHLA
EARPLPDITP GGFL
