P30561 (AHR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aryl hydrocarbon receptor
Short name=Ah receptor
Short name=AhR

Gene names

Name:

Ahr

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	848 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Ref.1 Ref.5 Ref.6 Ref.11 Ref.12 Ref.13 Ref.14
Subunit structure	Interacts with IVNS1ABP By similarity. Efficient DNA binding requires dimerization with another bHLH protein. In the nucleus, heterodimer of AHR and ARNT. Interacts with coactivators including SRC-1, RIP140 and NOCA7, and with the corepressor SMRT. Binds MYBBP1A. Interacts with NEDD8. Ref.15 Ref.17
Subcellular location	Cytoplasm. Nucleus. Note: Initially cytoplasmic; upon binding with ligand and interaction with a HSP90, it translocates to the nucleus. Ref.17
Tissue specificity	Expressed in all tissues tested including brain, heart, kidney, liver, lung, muscle, ovary, skin, spleen and thymus. Ref.14
Developmental stage	Between E10 and E12, abundantly expressed in neuroepithelium, branchial arches, cranial nerves, liver, heart and spinal ganglia. Ref.17
Induction	Induced or repressed by TGF-beta and dioxin in a cell-type specific fashion. Repressed by cAMP, retinoic acid, and TPA. Ref.10
Polymorphism	There are four common alleles; AHRB1; AHRB2; AHRB3 and AHRD. The sequence of AHRB2 is shown here.
Miscellaneous	Although it interacts with NEDD8, it does not seem to be neddylated.
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain. Contains 1 PAC (PAS-associated C-terminal) domain. Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	DNA-binding
Molecular function	Activator Receptor
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Traceable author statement PubMed 15681594. Source: DFLAT B-1 B cell homeostasis Traceable author statement PubMed 15681594. Source: DFLAT T cell homeostasis Inferred from mutant phenotype PubMed 7732381. Source: DFLAT apoptotic process Inferred from direct assay Ref.16. Source: UniProtKB blood vessel remodeling Inferred from mutant phenotype Ref.13. Source: DFLAT camera-type eye development Inferred from mutant phenotype Ref.13. Source: DFLAT cell cycle Inferred from direct assay Ref.16. Source: UniProtKB cell morphogenesis Inferred from mutant phenotype Ref.13PubMed 16443691. Source: DFLAT cellular response to cAMP Inferred from direct assay PubMed 17329248. Source: UniProtKB circumferential growth involved in left ventricle morphogenesis Inferred from mutant phenotype PubMed 14644620. Source: DFLAT common bile duct development Inferred from mutant phenotype PubMed 16443691. Source: DFLAT embryonic hemopoiesis Inferred from mutant phenotype PubMed 16443691. Source: DFLAT glomerulus morphogenesis Inferred from mutant phenotype PubMed 14644620. Source: DFLAT kidney morphogenesis Inferred from mutant phenotype PubMed 14644620. Source: DFLAT liver development Inferred from mutant phenotype Ref.13PubMed 16443691PubMed 7732381PubMed 8692887. Source: DFLAT negative regulation of necrotic cell death Inferred from mutant phenotype PubMed 16443691. Source: DFLAT negative regulation of systemic arterial blood pressure Inferred from mutant phenotype PubMed 14644620. Source: DFLAT negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 18223155. Source: MGI negative regulation of vasoconstriction Inferred from mutant phenotype PubMed 14644620. Source: DFLAT patterning of blood vessels Inferred from mutant phenotype Ref.13. Source: DFLAT positive regulation of RNA polymerase II transcriptional preinitiation complex assembly Inferred from direct assay PubMed 8215422. Source: MGI positive regulation of cell size Inferred from mutant phenotype Ref.13. Source: DFLAT positive regulation of growth rate Inferred from mutant phenotype PubMed 7732381PubMed 8692887. Source: DFLAT post-embryonic hemopoiesis Inferred from mutant phenotype PubMed 8692887. Source: DFLAT prostate gland development Inferred from mutant phenotype PubMed 12151645. Source: MGI regulation of blood vessel size Inferred from mutant phenotype PubMed 16443691. Source: DFLAT regulation of heart growth Traceable author statement PubMed 14644620PubMed 16443691. Source: DFLAT response to stress Inferred from direct assay Ref.1. Source: UniProtKB response to toxin Inferred from direct assay PubMed 17329248. Source: UniProtKB smooth muscle tissue development Inferred from mutant phenotype PubMed 16443691. Source: DFLAT spleen development Inferred from mutant phenotype PubMed 7732381PubMed 8692887. Source: DFLAT venous blood vessel development Inferred from mutant phenotype PubMed 16443691. Source: DFLAT xenobiotic metabolic process Traceable author statement PubMed 405846. Source: MGI
Cellular_component	cytosolic aryl hydrocarbon receptor complex Traceable author statement PubMed 17569696. Source: DFLAT nuclear aryl hydrocarbon receptor complex Traceable author statement PubMed 17569696. Source: DFLAT transcription factor complex Traceable author statement PubMed 11025203. Source: MGI
Molecular_function	Hsp90 protein binding Traceable author statement PubMed 17569696. Source: DFLAT RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 18223155. Source: MGI ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from direct assay Ref.1. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay PubMed 1605850. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
arnt	P79832	2	EBI-78863,EBI-958635	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 9	9			PRO_0000013452
	Chain	10 – 848	839	Aryl hydrocarbon receptor		PRO_0000013453
Regions
	Domain	26 – 79	54	bHLH
	Domain	116 – 179	64	PAS 1
	Domain	269 – 336	68	PAS 2
	Domain	342 – 380	39	PAC
	Compositional bias	594 – 648	55	Gln-rich
Natural variations
	Natural variant	324	1	M → I in allele AHRB1; no increase in specific ligand binding. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.8
	Natural variant	348	1	F → L in allele AHRB1 and allele AHRD; no reduction in specific ligand binding. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.7 Ref.8
	Natural variant	375	1	A → V in allele AHRD; reduced specific ligand binding. Ref.3 Ref.5 Ref.6 Ref.7 Ref.8
	Natural variant	471	1	P → L in allele AHRB1; no increase in specific ligand binding. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.8
	Natural variant	533	1	N → S in allele AHRB1; no increase in specific ligand binding. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.8
	Natural variant	589	1	M → I in allele AHRD. Ref.7 Ref.8
	Natural variant	589	1	M → L in allele AHRB1; no increase in specific ligand binding. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6
	Natural variant	758	1	T → A in allele AHRB1 and allele AHRD. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.7 Ref.8
	Natural variant	806 – 848	43	Missing in allele AHRB1.
	Natural variant	808	1	I → V in allele AHRB3. Ref.6
	Natural variant	821	1	G → D in allele AHRB3. Ref.6
	Natural variant	824	1	A → V in allele AHRB3. Ref.6
	Natural variant	843 – 848	6	TPGGFL → SHLVGSCSSHARMKFIQEQD TGTVRVGHQYYFSKTFDSCI in allele AHRB3.
Experimental info
	Sequence conflict	74	1	S → T Ref.2
	Sequence conflict	74	1	S → T Ref.3
	Sequence conflict	132 – 133	2	LV → FL Ref.1
	Sequence conflict	132 – 133	2	LV → FL Ref.4
	Sequence conflict	171 – 172	2	QL → HV Ref.1
	Sequence conflict	171 – 172	2	QL → HV Ref.4
	Sequence conflict	351	1	H → N in D38416. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P30561 [UniParc]. Last modified March 25, 2003. Version 3. Checksum: AA1560FA83DDD03C	FASTA	848	95,017
	10 20 30 40 50 60 MSSGANITYA SRKRRKPVQK TVKPIPAEGI KSNPSKRHRD RLNTELDRLA SLLPFPQDVI 70 80 90 100 110 120 NKLDKLSVLR LSVSYLRAKS FFDVALKSTP ADRNGGQDQC RAQIRDWQDL QEGEFLLQAL 130 140 150 160 170 180 NGFVLVVTAD ALVFYASSTI QDYLGFQQSD VIHQSVYELI HTEDRAEFQR QLHWALNPDS 190 200 210 220 230 240 AQGVDEAHGP PQAAVYYTPD QLPPENASFM ERCFRCRLRC LLDNSSGFLA MNFQGRLKYL 250 260 270 280 290 300 HGQNKKGKDG ALLPPQLALF AIATPLQPPS ILEIRTKNFI FRTKHKLDFT PIGCDAKGQL 310 320 330 340 350 360 ILGYTEVELC TRGSGYQFIH AADMLHCAES HIRMIKTGES GMTVFRLFAK HSRWRWVQSN 370 380 390 400 410 420 ARLIYRNGRP DYIIATQRPL TDEEGREHLQ KRSTSLPFMF ATGEAVLYEI SSPFSPIMDP 430 440 450 460 470 480 LPIRTKSNTS RKDWAPQSTP SKDSFHPSSL MSALIQQDES IYLCPPSSPA PLDSHFLMGS 490 500 510 520 530 540 VSKCGSWQDS FAAAGSEAAL KHEQIGHAQD VNLALSGGPS ELFPDNKNND LYNIMRNLGI 550 560 570 580 590 600 DFEDIRSMQN EEFFRTDSTA AGEVDFKDID ITDEILTYVQ DSLNNSTLMN SACQQQPVTQ 610 620 630 640 650 660 HLSCMLQERL QLEQQQQLQQ PPPQALEPQQ QLCQMVCPQQ DLGPKHTQIN GTFASWNPTP 670 680 690 700 710 720 PVSFNCPQQE LKHYQLFSSL QGTAQEFPYK PEVDSVPYTQ NFAPCNQPLL PEHSKSVQLD 730 740 750 760 770 780 FPGRDFEPSL HPTTSNLDFV SCLQVPENQS HGINSQSTMV SPQAYYAGAM SMYQCQPGPQ 790 800 810 820 830 840 RTPVDQTQYS SEIPGSQAFL SKVQSRGIFN ETYSSDLSSI GHAAQTTGHL HHLAEARPLP DITPGGFL

References

[1]	"cDNA cloning and structure of mouse putative Ah receptor." Ema M., Sogawa K., Watanabe N., Chujoh Y., Matsushita N., Gotoh O., Funae Y., Fujii-Kuriyama Y. Biochem. Biophys. Res. Commun. 184:246-253(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANTS ILE-324; LEU-348; LEU-471; SER-533; LEU-589 AND ALA-758. Strain: C57L. Tissue: Hepatoma.
[2]	"Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor." Burbach K.M., Poland A., Bradfield C.A. Proc. Natl. Acad. Sci. U.S.A. 89:8185-8189(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 10-36; 232-261; 335-350 AND 636-646, VARIANTS ILE-324; LEU-348; LEU-471; SER-533; LEU-589 AND ALA-758. Strain: C57BL/6J and C57L. Tissue: Liver.
[3]	"Ten nucleotide differences, five of which cause amino acid changes, are associated with the Ah receptor locus polymorphism of C57BL/6 and DBA/2 mice." Chang C.-Y., Smith D.R., Prasad V.S., Sidman C.L., Nebert D.W., Puga A. Pharmacogenetics 3:312-321(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE, VARIANTS ILE-324; LEU-348; VAL-375; LEU-471; SER-533; LEU-589 AND ALA-758. Strain: C57BL/6J and DBA/2J.
[4]	"Molecular characterization of the murine Ahr gene. Organization, promoter analysis, and chromosomal assignment." Schmidt J.V., Carver L.A., Bradfield C.A. J. Biol. Chem. 268:22203-22209(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[5]	"Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors." Ema M., Ohe N., Suzuki M., Mimura J., Sogawa K., Ikawa S., Fujii-Kuriyama Y. J. Biol. Chem. 269:27337-27343(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANTS ILE-324; LEU-348; VAL-375; LEU-471; SER-533; LEU-589 AND ALA-758, CHARACTERIZATION OF VARIANTS ILE-324; VAL-375; LEU-471; SER-533 AND LEU-589. Strain: C57BL/6 and DBA/2J. Tissue: Liver.
[6]	"Analysis of the four alleles of the murine aryl hydrocarbon receptor." Poland A., Palen D., Glover E. Mol. Pharmacol. 46:915-921(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE, FUNCTION, VARIANTS ILE-324; LEU-348; VAL-375; LEU-471; SER-533; LEU-589; ALA-758; VAL-808; ASP-821 AND VAL-824, CHARACTERIZATION OF VARIANTS LEU-348 AND VAL-375. Strain: C57BL/6.
[7]	"Mouse aryl-hydrocarbon receptor (AhR) genomic region." Hadd A.G., Nguyen L.P., Garrigues C.S., Thomas R.S., Rank D.R., Penn S.G., LaPres J.J., Roach D., Blaga I., Schneider J., Shilova K., Bradfield C.A., Jovanovich S.B. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-348; VAL-375; ILE-589 AND ALA-758. Strain: 129/SvJ.
[8]	"Sequence variation and phylogenetic history of the mouse Ahr gene." Thomas R.S., Penn S.G., Holden K., Bradfield C.A., Rank D.R. Pharmacogenetics 12:151-163(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ILE-324; LEU-348; VAL-375; LEU-471; SER-533; ILE-589 AND ALA-758. Strain: A/J, BALB/cBY, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J and SJL/J.
[9]	"Purification and N-terminal amino acid sequence of the Ah receptor from the C57BL/6J mouse." Bradfield C.A., Glover E., Poland A. Mol. Pharmacol. 39:13-19(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 10-36.
[10]	"Differential regulation of mouse Ah receptor gene expression in cell lines of different tissue origins." FitzGerald C.T., Fernandez-Salguero P., Gonzalez F.J., Nebert D.W., Puga A. Arch. Biochem. Biophys. 333:170-178(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[11]	"Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity." Fernandez-Salguero P.M., Hilbert D.M., Rudikoff S., Ward J.M., Gonzalez F.J. Toxicol. Appl. Pharmacol. 140:173-179(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor." Mimura J., Yamashita K., Nakamura K., Morita M., Takagi T.N., Nakao K., Ema M., Sogawa K., Yasuda M., Katsuki M., Fujii-Kuriyama Y. Genes Cells 2:645-654(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice." Lahvis G.P., Lindell S.L., Thomas R.S., McCuskey R.S., Murphy C., Glover E., Bentz M., Southard J., Bradfield C.A. Proc. Natl. Acad. Sci. U.S.A. 97:10442-10447(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"Benzoapyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor." Shimizu Y., Nakatsuru Y., Ichinose M., Takahashi Y., Kume H., Mimura J., Fujii-Kuriyama Y., Ishikawa T. Proc. Natl. Acad. Sci. U.S.A. 97:779-782(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[15]	"Myb-binding protein 1a augments AhR-dependent gene expression." Jones L.C., Okino S.T., Gonda T.J., Whitlock J.P. Jr. J. Biol. Chem. 277:22515-22519(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MYBBP1A.
[16]	"Role of the aryl hydrocarbon receptor in cell cycle regulation." Puga A., Xia Y., Elferink C. Chem. Biol. Interact. 141:117-130(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN CELL CYCLE.
[17]	"Interaction with Nedd8, a ubiquitin-like protein, enhances the transcriptional activity of the aryl hydrocarbon receptor." Antenos M., Casper R.F., Brown T.J. J. Biol. Chem. 277:44028-44034(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEDD8, LACK OF NEDDYLATION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D38417 mRNA. Translation: BAA07469.1. M94623 Unassigned DNA. Translation: AAA02896.1. L19749 Unassigned DNA. No translation available. L19750 Unassigned DNA. No translation available. L19751 Unassigned DNA. No translation available. L19752 Unassigned DNA. No translation available. L19753 Unassigned DNA. No translation available. L19754 Unassigned DNA. No translation available. L19755 Unassigned DNA. No translation available. L19756 Unassigned DNA. No translation available. L19757 Unassigned DNA. No translation available. L19758 Unassigned DNA. No translation available. L19759 Unassigned DNA. No translation available. D38416 mRNA. No translation available. AF325111 Genomic DNA. Translation: AAK13443.1. AF405560 mRNA. Translation: AAL89725.1. AF405561 mRNA. Translation: AAL89726.1. AF405562 mRNA. Translation: AAL89727.1. AF405563 mRNA. Translation: AAL89728.1. AF405566 mRNA. Translation: AAL89731.1. AF405567 mRNA. Translation: AAL89732.1. AF405570 mRNA. Translation: AAL89735.1.
IPI	IPI00131277.
PIR	A46266.
RefSeq	NP_038492.1. NM_013464.4.
UniGene	Mm.341377.
3D structure databases
ProteinModelPortal	P30561.
SMR	P30561. Positions 36-386.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-222N.
IntAct	P30561. 4 interactions.
PTM databases
PhosphoSite	P30561.
Proteomic databases
PRIDE	P30561.
Protocols and materials databases
DNASU	11622.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	11622.
KEGG	mmu:11622.
Organism-specific databases
CTD	196.
MGI	MGI:105043. Ahr.
Phylogenomic databases
eggNOG	NOG253623.
HOGENOM	HOG000252935.
HOVERGEN	HBG007313.
KO	K09093.
OrthoDB	EOG42BX7X.
Gene expression databases
Genevestigator	P30561.
GermOnline	ENSMUSG00000019256. Mus musculus.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. IPR001610. PAC. IPR000014. PAS. IPR013767. PAS_fold. IPR013655. PAS_fold_3. [Graphical view]
Pfam	PF00010. HLH. 1 hit. PF00989. PAS. 1 hit. PF08447. PAS_3. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. SM00086. PAC. 1 hit. SM00091. PAS. 2 hits. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. PS50113. PAC. False negative. PS50112. PAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P30561.
ChEMBL	CHEMBL6099.
ChiTaRS	AHR. mouse.
NextBio	279171.
SOURCE	Search...

Entry information

Entry name

AHR_MOUSE

Accession

Primary (citable) accession number: P30561
Secondary accession number(s): Q8QZX6 , Q8R4S3, Q99P79, Q9QVY1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	March 25, 2003
Last modified:	May 1, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program