AHR_MUSMC
ID AHR_MUSMC Reviewed; 848 AA.
AC Q8R4S6;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 25-MAY-2022, entry version 127.
DE RecName: Full=Aryl hydrocarbon receptor;
DE Short=Ah receptor;
DE Short=AhR;
DE Flags: Precursor;
GN Name=Ahr;
OS Mus musculus castaneus (Southeastern Asian house mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10091 {ECO:0000312|EMBL:AAL89730.1};
RN [1] {ECO:0000312|EMBL:AAL89730.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CAST/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; AF405565; AAL89730.1; -; mRNA.
DR AlphaFoldDB; Q8R4S6; -.
DR SMR; Q8R4S6; -.
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: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_0000013456"
FT CHAIN 10..848
FT /note="Aryl hydrocarbon receptor"
FT /id="PRO_0000013457"
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 266..336
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140,
FT ECO:0000305"
FT DOMAIN 342..383
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 260..262
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 421..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 848 AA; 95013 MW; 169FF90123CF2D58 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 GMTVFRLLAK HSRWRWVQSN
ARLIYRNGRP DYIIVTQRPL TDEEGREHLQ KRSTSLPFMF ATGEAVLYEI SSPFSPIMDP
LPIRTKSNTS RKDWAPQSTP SKDSFHPSSL MSALIQQDES IYLCPPSSPA PLDSHFLMGS
VSKCGSWQDS FAAAGSEAAL KHEQIGHAQD VNLALSGGPS ELFPDNKNND LYNIMRNLGI
DFEDIRSMQN EEFFRTDSTA AGEVDFKDID ITDEILTYMQ DSLNNSTLMN SACQQQPVTQ
HLSCMLQERL QLEQQQQLQQ PPPQALEPQQ QLCQMVCPQQ DLGPKHTQIN GTFASWNPTP
PVSFNCPQQE LKHYQLFSSL QGTAQEFPYK PEVDSVPYTQ NFAPCNQPLL PEHSKSVQLD
FPGRDFEPSL HPTTSNLDFV SCLQVPENQS HGINSQSAMV SPQAYYAGAM SMYQCQPGPQ
RTPVDQTQYS SEIPGSQAFL SKVQSRGIFN ETYSSDLSSI GHAAQTTGHL HHLAEARPLP
DITPGGFL
