Aryl hydrocarbon receptor precursor

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Reviewed, UniProtKB/Swiss-Prot P35869 (AHR_HUMAN)

Last modified June 16, 2009. Version 100. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Aryl hydrocarbon receptor
      Short name=Ah receptor
      Short name=AhR
Alternative name(s):
    Class E basic helix-loop-helix protein 76
      Short name=bHLHe76

Gene names

Name:	AHR
Synonyms:	BHLHE76

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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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.

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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.8 Ref.9
Subunit structure	Binds MYBBP1A 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. Interacts with NEDD8 and IVNS1ABP.
Subcellular location	Cytoplasm. Nucleus. Note: Initially cytoplasmic; upon binding with ligand and interaction with a HSP90, it translocates to the nucleus.
Tissue specificity	Expressed in all tissues tested including blood, brain, heart, kidney, liver, lung, pancreas and skeletal muscle. Ref.2 Ref.7
Induction	Induced or repressed by TGF-beta and dioxin in a cell-type specific fashion. Repressed by cAMP, retinoic acid, and TPA. Ref.10
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain. Contains 1 PAC (PAS-associated C-terminal) domain. Contains 2 PAS (PER-ARNT-SIM) domains.

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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
Gene Ontology (GO)
Biological process	apoptosis Ref.11 Traceable author statement. Source: UniProtKB cell cycle Ref.11 Traceable author statement. Source: UniProtKB response to stress Ref.8 Inferred from direct assay. Source: UniProtKB response to xenobiotic stimulus Ref.8 Inferred from direct assay. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro transcription from RNA polymerase II promoter Ref.9 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.9 Inferred from direct assay. Source: UniProtKB
Molecular function	Hsp90 protein binding Inferred from direct assay. Source: UniProtKB ligand-dependent nuclear receptor activity Ref.9 Inferred from direct assay. Source: UniProtKB transcription factor activity Inferred from direct assay. Source: MGI transcription factor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
AIP	O00170	1	EBI-80780,EBI-704197
EBNA3	P12977	4	EBI-80780,EBI-993115	From a different organism.
NCOA7	Q8NI08	1	EBI-80780,EBI-80799
NCOR2	Q9Y618	1	EBI-80780,EBI-80830

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 10

By similarity

PRO_0000013450

Chain

11 – 848

838

Aryl hydrocarbon receptor

PRO_0000013451

Regions

Domain

41 – 81

Helix-loop-helix motif

Domain

111 – 181

PAS 1

Domain

275 – 342

PAS 2

Domain

348 – 386

PAC

DNA binding

13 – 40

Basic motif

Compositional bias

600 – 640

Gln-rich

Natural variations

Natural variant

517

P → S Ref.18

VAR_015516

Natural variant

554

R → K: dbSNP rs2066853. Ref.15 Ref.16 Ref.17

VAR_009281

Natural variant

570

V → I: dbSNP rs4986826. Ref.18 Ref.16

VAR_009282

Natural variant

786

M → V Ref.17

VAR_015517

Experimental info

Mutagenesis

381

V → A: Increases specific ligand binding. Ref.8

Mutagenesis

381

V → D: Abolishes specific ligand binding. Ref.8

Mutagenesis

381

V → L or G: No effect on specific ligand binding. Ref.8

Sequence conflict

191

E → EG in AAA92082. Ref.6

Sequence conflict

340 – 341

MI → SD Ref.7

Sequence conflict

807 – 848

LNETY…SSGFL → FK in BAA03857. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

P35869-1 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: 1BFE022871B7B028
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FASTA

848

96,147

        10         20         30         40         50         60 
MNSSSANITY ASRKRRKPVQ KTVKPIPAEG IKSNPSKRHR DRLNTELDRL ASLLPFPQDV 

        70         80         90        100        110        120 
INKLDKLSVL RLSVSYLRAK SFFDVALKSS PTERNGGQDN CRAANFREGL NLQEGEFLLQ 

       130        140        150        160        170        180 
ALNGFVLVVT TDALVFYASS TIQDYLGFQQ SDVIHQSVYE LIHTEDRAEF QRQLHWALNP 

       190        200        210        220        230        240 
SQCTESGQGI EEATGLPQTV VCYNPDQIPP ENSPLMERCF ICRLRCLLDN SSGFLAMNFQ 

       250        260        270        280        290        300 
GKLKYLHGQK KKGKDGSILP PQLALFAIAT PLQPPSILEI RTKNFIFRTK HKLDFTPIGC 

       310        320        330        340        350        360 
DAKGRIVLGY TEAELCTRGS GYQFIHAADM LYCAESHIRM IKTGESGMIV FRLLTKNNRW 

       370        380        390        400        410        420 
TWVQSNARLL YKNGRPDYII VTQRPLTDEE GTEHLRKRNT KLPFMFTTGE AVLYEATNPF 

       430        440        450        460        470        480 
PAIMDPLPLR TKNGTSGKDS ATTSTLSKDS LNPSSLLAAM MQQDESIYLY PASSTSSTAP 

       490        500        510        520        530        540 
FENNFFNESM NECRNWQDNT APMGNDTILK HEQIDQPQDV NSFAGGHPGL FQDSKNSDLY 

       550        560        570        580        590        600 
SIMKNLGIDF EDIRHMQNEK FFRNDFSGEV DFRDIDLTDE ILTYVQDSLS KSPFIPSDYQ 

       610        620        630        640        650        660 
QQQSLALNSS CMVQEHLHLE QQQQHHQKQV VVEPQQQLCQ KMKHMQVNGM FENWNSNQFV 

       670        680        690        700        710        720 
PFNCPQQDPQ QYNVFTDLHG ISQEFPYKSE MDSMPYTQNF ISCNQPVLPQ HSKCTELDYP 

       730        740        750        760        770        780 
MGSFEPSPYP TTSSLEDFVT CLQLPENQKH GLNPQSAIIT PQTCYAGAVS MYQCQPEPQH 

       790        800        810        820        830        840 
THVGQMQYNP VLPGQQAFLN KFQNGVLNET YPAELNNINN TQTTTHLQPL HHPSEARPFP 


DLTSSGFL

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Ah receptor cDNA: analysis for highly conserved sequences." Itoh S., Kamataki T. Nucleic Acids Res. 21:3578-3578(1993) [PubMed: 8393992] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Cloning and expression of a human Ah receptor cDNA." Dolwick K.M., Schmidt J.V., Carver L.A., Swanson H.I., Bradfield C.A. Mol. Pharmacol. 44:911-917(1993) [PubMed: 8246913] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]	"Human arylhydrocarbon receptor: functional expression and chromosomal assignment to 7p21." Ema M., Matsushita N., Sogawa K., Ariyama T., Inazawa J., Nemoto T., Ota M., Oshimura M., Fujii-Kuriyama Y. J. Biochem. 116:845-851(1994) [PubMed: 7883760] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"Complete structural characterisation of the human aryl hydrocarbon receptor gene." Bennett P., Ramsden D.B., Williams A.C. Clin. Mol. Pathol. 49:M12-M16(1996) [PubMed: 16696038] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-235; 388-461 AND 764-848.
[7]	"Interindividual difference in expression of human Ah receptor and related P450 genes." Hayashi S., Watanabe J., Nakachi K., Eguchi H., Gotoh O., Kawajiri K. Carcinogenesis 15:801-806(1994) [PubMed: 7515333] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 236-341, TISSUE SPECIFICITY.
[8]	"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: 7961644] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF VAL-381.
[9]	"Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex." Nguyen T.A., Hoivik D., Lee J.-E., Safe S. Arch. Biochem. Biophys. 367:250-257(1999) [PubMed: 10395741] [Abstract] Cited for: FUNCTION, SUBUNIT.
[10]	"Cell-specific regulation of human aryl hydrocarbon receptor expression by transforming growth factor-beta(1)." Wolff S., Harper P.A., Wong J.M.Y., Mostert V., Wang Y., Abel J. Mol. Pharmacol. 59:716-724(2001) [PubMed: 11259615] [Abstract] Cited for: INDUCTION.
[11]	"Role of the aryl hydrocarbon receptor in cell cycle regulation." Puga A., Xia Y., Elferink C. Chem. Biol. Interact. 141:117-130(2002) [PubMed: 12213388] [Abstract] Cited for: REVIEW ON ROLE IN CELL CYCLE.
[12]	"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: 12215427] [Abstract] Cited for: INTERACTION WITH NEDD8.
[13]	"The aryl hydrocarbon receptor signaling pathway is modified through interactions with a Kelch protein." Dunham E.E., Stevens E.A., Glover E., Bradfield C.A. Mol. Pharmacol. 70:8-15(2006) [PubMed: 16582008] [Abstract] Cited for: INTERACTION WITH IVNS1ABP.
[14]	"Polymorphisms in the human AH receptor." Harper P.A., Wong J.M.Y., Lam M.S.M., Okey A.B. Chem. Biol. Interact. 141:161-187(2002) [PubMed: 12213390] [Abstract] Cited for: REVIEW ON VARIANTS.
[15]	"Polymorphisms of human Ah receptor gene are not involved in lung cancer." Kawajiri K., Watanabe J., Eguchi H., Nakachi K., Kiyohara C., Hayashi S. Pharmacogenetics 5:151-158(1995) [PubMed: 7550366] [Abstract] Cited for: VARIANT LYS-554.
[16]	"Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor and GSTM1 polymorphisms." Smart J., Daly A.K. Pharmacogenetics 10:11-24(2000) [PubMed: 10739168] [Abstract] Cited for: VARIANTS LYS-554 AND ILE-570.
[17]	"Polymorphisms of human aryl hydrocarbon receptor (AhR) gene in a French population: relationship with CYP1A1 inducibility and lung cancer." Cauchi S., Stucker I., Solas C., Laurent-Puig P., Cenee S., Hemon D., Jacquet M., Kremers P., Beaune P., Massaad-Massade L. Carcinogenesis 22:1819-1824(2001) [PubMed: 11698344] [Abstract] Cited for: VARIANTS LYS-554 AND VAL-786.
[18]	"Human aryl hydrocarbon receptor polymorphisms that result in loss of CYP1A1 induction." Wong J.M.Y., Okey A.B., Harper P.A. Biochem. Biophys. Res. Commun. 288:990-996(2001) [PubMed: 11689007] [Abstract] Cited for: VARIANTS SER-517 AND ILE-570.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	D16354 mRNA. Translation: BAA03857.1. L19872 mRNA. Translation: AAA16210.1. AC003075 Genomic DNA. No translation available. BC069390 mRNA. Translation: AAH69390.1. BC070080 mRNA. Translation: AAH70080.1. U28063 , U27656, U27657, U28060, U28061, U28062 Genomic DNA. Translation: AAA92082.1. U28064 Genomic DNA. Translation: AAA92083.1. U28066, U28065 Genomic DNA. Translation: AAA92084.1. D38044 Genomic DNA. Translation: BAA07235.1.
IPI	IPI00021008.
PIR	S59514.
RefSeq	NP_001612.1.
UniGene	Hs.171189
3D structure databases
DisProt	DP00381.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:946N.
IntAct	P35869. 6 interactions.
PTM databases
PhosphoSite	P35869.
Proteomic databases
PRIDE	P35869.
Genome annotation databases
Ensembl	ENSG00000106546. Homo sapiens. [Contig view]
GeneID	196.
KEGG	hsa:196.
Organism-specific databases
GeneCards	GC07P017304.
H-InvDB	HIX0033619.
HGNC	HGNC:348. AHR.
HPA	CAB005072.
MIM	600253. gene.
PharmGKB	PA24641.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P35869.
HOVERGEN	P35869.
OMA	P35869. QQDESIY.
Gene expression databases
Bgee	P35869.
CleanEx	HS_AHR.
Family and domain databases
InterPro	IPR001092. HLH_basic. 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]
PROSITE	PS50888. HLH. 1 hit. PS50113. PAC. False negative. PS50112. PAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	786.
SOURCE	Search...

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Entry information

Entry name

AHR_HUMAN

Accession

Primary (citable) accession number: P35869
Secondary accession number(s): Q13728, Q13803, Q13804

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	July 15, 1998
Last modified:	June 16, 2009
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents