AHR_RAT
ID AHR_RAT Reviewed; 853 AA.
AC P41738; O88930; O89105;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 25-MAR-2003, sequence version 2.
DT 25-MAY-2022, entry version 174.
DE RecName: Full=Aryl hydrocarbon receptor;
DE Short=Ah receptor;
DE Short=AhR;
DE Flags: Precursor;
GN Name=Ahr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=Fischer 344, and Sprague-Dawley; TISSUE=Liver, and Placenta;
RX PubMed=8065918; DOI=10.1093/nar/22.15.3038;
RA Carver L.A., Hogenesch J.B., Bradfield C.A.;
RT "Tissue specific expression of the rat Ah-receptor and ARNT mRNAs.";
RL Nucleic Acids Res. 22:3038-3044(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 236-251 AND
RP 702-708, FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7812217;
RA Elferink C.J., Whitlock J.P. Jr.;
RT "Dioxin-dependent, DNA sequence-specific binding of a multiprotein complex
RT containing the Ah receptor.";
RL Receptor 4:157-173(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS HAN/WISTAR ALA-497;
RP HAN/WISTAR-DV; HAN/WISTAR-SIV AND HAN/WISTAR-LIV.
RC STRAIN=Han/Wistar, Long Evans, and Sprague-Dawley;
RX PubMed=9658193; DOI=10.1124/mol.54.1.86;
RA Pohjanvirta R., Wong J.M.Y., Li W., Harper P.A., Tuomisto J., Okey A.B.;
RT "Point mutation in intron sequence causes altered carboxyl-terminal
RT structure in the aryl hydrocarbon receptor of the most 2,3,7,8-
RT tetrachlorodibenzo-p-dioxin-resistant rat strain.";
RL Mol. Pharmacol. 54:86-93(1998).
RN [4]
RP INDUCTION.
RX PubMed=11755109; DOI=10.1016/s0006-2952(01)00820-6;
RA Franc M.A., Pohjanvirta R., Tuomisto J., Okey A.B.;
RT "In vivo up-regulation of aryl hydrocarbon receptor expression by 2,3,7,8-
RT tetrachlorodibenzo-p-dioxin (TCDD) in a dioxin-resistant rat model.";
RL Biochem. Pharmacol. 62:1565-1578(2001).
RN [5]
RP REVIEW ON ROLE IN CELL CYCLE.
RX PubMed=12213388; DOI=10.1016/s0009-2797(02)00069-8;
RA Puga A., Xia Y., Elferink C.;
RT "Role of the aryl hydrocarbon receptor in cell cycle regulation.";
RL Chem. Biol. Interact. 141:117-130(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 (PubMed:7812217). 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:7812217}.
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 -!- INTERACTION:
CC P41738; P41739: Arnt; NbExp=2; IntAct=EBI-1162880, EBI-1162920;
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=P41738-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P41738-2; Sequence=VSP_002091;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested including brain,
CC heart, kidney, liver, lung, spleen, skeletal muscle and thymus.
CC {ECO:0000269|PubMed:7812217, ECO:0000269|PubMed:8065918}.
CC -!- INDUCTION: Induced or repressed by TGF-beta in a cell-specific fashion.
CC Repressed by dioxin, retinoic acid, and TPA.
CC {ECO:0000269|PubMed:11755109}.
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; U09000; AAA56897.1; -; mRNA.
DR EMBL; U04860; AAA19451.1; -; mRNA.
DR EMBL; AF082124; AAC35168.1; -; mRNA.
DR EMBL; AF082125; AAC35169.1; -; mRNA.
DR EMBL; AF082126; AAC35170.1; -; mRNA.
DR PIR; S58375; S58375.
DR AlphaFoldDB; P41738; -.
DR SMR; P41738; -.
DR BioGRID; 247719; 4.
DR IntAct; P41738; 2.
DR STRING; 10116.ENSRNOP00000006618; -.
DR BindingDB; P41738; -.
DR ChEMBL; CHEMBL5400; -.
DR iPTMnet; P41738; -.
DR PhosphoSitePlus; P41738; -.
DR PaxDb; P41738; -.
DR PRIDE; P41738; -.
DR UCSC; RGD:2074; rat. [P41738-1]
DR RGD; 2074; Ahr.
DR eggNOG; KOG3560; Eukaryota.
DR InParanoid; P41738; -.
DR PhylomeDB; P41738; -.
DR Reactome; R-RNO-211945; Phase I - Functionalization of compounds.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR Reactome; R-RNO-211981; Xenobiotics.
DR Reactome; R-RNO-8937144; Aryl hydrocarbon receptor signalling.
DR PRO; PR:P41738; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0017162; F:aryl hydrocarbon receptor binding; ISO:RGD.
DR GO; GO:0051087; F:chaperone binding; ISO:RGD.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB.
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; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0017025; F:TBP-class protein binding; ISO:RGD.
DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; ISO:RGD.
DR GO; GO:0015643; F:toxic substance binding; IDA:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; ISO:RGD.
DR GO; GO:0008015; P:blood circulation; ISO:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISO:RGD.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0001974; P:blood vessel remodeling; ISO:RGD.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0043010; P:camera-type eye development; ISO:RGD.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISO:RGD.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; ISO:RGD.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0000902; P:cell morphogenesis; ISO:RGD.
DR GO; GO:1904613; P:cellular response to 2,3,7,8-tetrachlorodibenzodioxine; IDA:UniProtKB.
DR GO; GO:1904682; P:cellular response to 3-methylcholanthrene; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; ISO:RGD.
DR GO; GO:1904322; P:cellular response to forskolin; ISO:RGD.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0003243; P:circumferential growth involved in left ventricle morphogenesis; ISO:RGD.
DR GO; GO:0061009; P:common bile duct development; ISO:RGD.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:RGD.
DR GO; GO:0048732; P:gland development; ISO:RGD.
DR GO; GO:0072102; P:glomerulus morphogenesis; ISO:RGD.
DR GO; GO:0002376; P:immune system process; ISO:RGD.
DR GO; GO:0060993; P:kidney morphogenesis; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0002260; P:lymphocyte homeostasis; ISO:RGD.
DR GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; IDA:RGD.
DR GO; GO:1903170; P:negative regulation of calcium ion transmembrane transport; IDA:RGD.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IDA:RGD.
DR GO; GO:0060547; P:negative regulation of necrotic cell death; ISO:RGD.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:RGD.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IDA:RGD.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; ISO:RGD.
DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; ISO:RGD.
DR GO; GO:0001541; P:ovarian follicle development; IMP:RGD.
DR GO; GO:0045793; P:positive regulation of cell size; ISO:RGD.
DR GO; GO:0040010; P:positive regulation of growth rate; ISO:RGD.
DR GO; GO:0045899; P:positive regulation of RNA polymerase II transcription preinitiation complex assembly; ISO:RGD.
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:0035166; P:post-embryonic hemopoiesis; ISO:RGD.
DR GO; GO:0030850; P:prostate gland development; ISO:RGD.
DR GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:0030888; P:regulation of B cell proliferation; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0048608; P:reproductive structure development; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IMP:RGD.
DR GO; GO:0009636; P:response to toxic substance; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0048745; P:smooth muscle tissue development; ISO:RGD.
DR GO; GO:0048536; P:spleen development; ISO:RGD.
DR GO; GO:0043029; P:T cell homeostasis; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0060841; P:venous blood vessel development; ISO:RGD.
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 1: Evidence at protein level;
KW Activator; ADP-ribosylation; Alternative splicing; Biological rhythms;
KW Cell cycle; Cytoplasm; Direct protein sequencing; DNA-binding; Nucleus;
KW Receptor; Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT PROPEP 1..9
FT /evidence="ECO:0000250|UniProtKB:P30561"
FT /id="PRO_0000013464"
FT CHAIN 10..853
FT /note="Aryl hydrocarbon receptor"
FT /id="PRO_0000013465"
FT DOMAIN 26..79
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 116..179
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 273..340
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 346..384
FT /note="PAC"
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 429..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 142..376
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8065918"
FT /id="VSP_002091"
FT VARIANT 497
FT /note="V -> A (in strain: Han/Wistar, Han/Wistar-dv, Han/
FT Wistar-siv and Han/Wistar-liv)"
FT /evidence="ECO:0000269|PubMed:9658193"
FT VARIANT 766..808
FT /note="Missing (in strain: Han/Wistar-dv)"
FT VARIANT 809..853
FT /note="FQSPSILNEAYSADLSSIGHLQTAAHLPRLAEAQPLPDITPSGFL -> IRA
FT FYRE (in strain: Han/Wistar-siv and Han/Wistar-liv)"
FT CONFLICT 74
FT /note="S -> T (in Ref. 1; AAA56897)"
FT /evidence="ECO:0000305"
FT CONFLICT 659
FT /note="A -> V (in Ref. 1; AAA56897)"
FT /evidence="ECO:0000305"
FT CONFLICT 679..682
FT /note="YSLF -> ICLL (in Ref. 1; AAA56897)"
FT /evidence="ECO:0000305"
FT CONFLICT 739
FT /note="A -> V (in Ref. 1; AAA56897)"
FT /evidence="ECO:0000305"
FT CONFLICT 744
FT /note="D -> E (in Ref. 1; AAA56897)"
FT /evidence="ECO:0000305"
FT CONFLICT 770
FT /note="A -> G (in Ref. 1; AAA56897)"
FT /evidence="ECO:0000305"
FT CONFLICT 787
FT /note="H -> D (in Ref. 1; AAA56897)"
FT /evidence="ECO:0000305"
FT CONFLICT 794
FT /note="Q -> H (in Ref. 2; AAA19451)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 853 AA; 96227 MW; 4EED0EE795FF1327 CRC64;
MSSGANITYA SRKRRKPVQK TVKPVPAEGI KSNPSKRHRD RLNTELDRLA SLLPFPQDVI
NKLDKLSVLR LSVSYLRAKS FFDVALKSTP ADRSRGQDQC RAQVRDWQDL QEGEFLLQAL
NGFVLVVTAD ALVFYASSTI QDYLGFQQSD VIHQSVYELI HTEDRAEFQR QLHWALNPSQ
CTDSAQGVDE THGLPQPAVY YTPDQLPPEN TAFMERCFRC RLRCLLDNSS GFLAMNFQGR
LKYLHGQNKK GKDGALLPPQ LALFAIATPL QPPSILEIRT KNFIFRTKHK LDFTPIGCDA
KGQLILGYTE VELCNKGSGY QFIHAADMLH CAESHIRMIK TGESGMTVFR LLAKHSRWRW
VQSNARLIYR NGRPDYIIAT QRPLTDEEGR EHLQKRSMTL PFMFATGEAV LYEISSPFSP
IMDPLPIRTK SNTSRKDWAP QSTPSKDSFH PNSLMSALIQ QDESIYLCPP SSPAPLDSHF
LMDSMSECGS WQGSFAVASN EALLKHEEIR HTQDVNLTLS GGPSELFPDN KNNDLYSIMR
NLGIDFEDIR SMQNEEFFRT DSSGEVDFKD IDITDEILTY VQDSLNNSTL LNSACQQQPV
SQHLSCMLQE RLQLEQQQQL QQQHPTQTLE PQRQLCQVEV PQHELGQKTK HMQVNGMFAS
WNPAPPVSFS CPQQERKHYS LFSGLQGTAQ EFPYKSEVDS MPYTQNFAPC NQSLLPEHSK
GTQLDFPGRD FERSLHPNAS NLEDFVSCLQ VPENQRHGIN SQSAMVSPQA YYAGAMSMYQ
CQAGPQHTPV DQMQYSPEIP GSQAFLSKFQ SPSILNEAYS ADLSSIGHLQ TAAHLPRLAE
AQPLPDITPS GFL
