Reviewed, UniProtKB/Swiss-Prot P35869 (AHR_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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.10 Ref.11
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. Ref.11 Ref.14 Ref.15
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.9
Induction	Induced or repressed by TGF-beta and dioxin in a cell-type specific fashion. Repressed by cAMP, retinoic acid, and TPA. Ref.12
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.

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
Gene Ontology (GO)
Biological process	apoptosis Ref.13 Traceable author statement. Source: UniProtKB cell cycle Ref.13 Traceable author statement. Source: UniProtKB response to stress Ref.10 Inferred from direct assay. Source: UniProtKB response to xenobiotic stimulus Ref.10 Inferred from direct assay. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro transcription from RNA polymerase II promoter Ref.11 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.11 Inferred from direct assay. Source: UniProtKB
Molecular function	Hsp90 protein binding Inferred from direct assay. Source: UniProtKB ligand-dependent nuclear receptor activity Ref.11 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...

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 10	10	By similarity		PRO_0000013450
	Chain	11 – 848	838	Aryl hydrocarbon receptor		PRO_0000013451
Regions
	Domain	41 – 81	41	Helix-loop-helix motif
	Domain	111 – 181	71	PAS 1
	Domain	275 – 342	68	PAS 2
	Domain	348 – 386	39	PAC
	DNA binding	13 – 40	28	Basic motif
	Compositional bias	600 – 640	41	Gln-rich
Natural variations
	Natural variant	517	1	P → S		VAR_015516
	Natural variant	554	1	R → K: dbSNP rs2066853. Ref.17 Ref.18 Ref.19		VAR_009281
	Natural variant	570	1	V → I: dbSNP rs4986826. Ref.18 Ref.20		VAR_009282
	Natural variant	786	1	M → V		VAR_015517
Experimental info
	Mutagenesis	381	1	V → A: Increases specific ligand binding. Ref.10
	Mutagenesis	381	1	V → D: Abolishes specific ligand binding. Ref.10
	Mutagenesis	381	1	V → L or G: No effect on specific ligand binding. Ref.10
	Sequence conflict	191	1	E → EG in AAA92082. Ref.8
	Sequence conflict	340 – 341	2	MI → SD Ref.9
	Sequence conflict	807 – 848	42	LNETY…SSGFL → FK in BAA03857. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P35869-1 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 1BFE022871B7B028	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

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]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D16354 mRNA. Translation: BAA03857.1. L19872 mRNA. Translation: AAA16210.1. AC003075 Genomic DNA. No translation available. CH236948 Genomic DNA. Translation: EAL24281.1. CH471073 Genomic DNA. Translation: EAW93686.1. 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.
STRING	P35869.
PTM databases
PhosphoSite	P35869.
Proteomic databases
PRIDE	P35869.
Genome annotation databases
Ensembl	ENST00000242057; ENSP00000242057; ENSG00000106546; Homo sapiens. [Genome view] ENST00000401808; ENSP00000385642; ENSG00000106546; Homo sapiens. [Genome view]
GeneID	196.
KEGG	hsa:196.
UCSC	uc003stu.1. human.
Organism-specific databases
CTD	196.
GeneCards	GC07P017304.
H-InvDB	HIX0033619.
HGNC	HGNC:348. AHR.
HPA	CAB005072.
MIM	600253. gene.
PharmGKB	PA24641.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG715104.
HOVERGEN	P35869.
InParanoid	P35869.
OMA	PQTCYAG.
OrthoDB	EOG94N1C9.
PhylomeDB	P35869.
Gene expression databases
ArrayExpress	P35869.
Bgee	P35869.
CleanEx	HS_AHR.
Genevestigator	P35869.
Family and domain databases
InterPro	IPR001092. HLH_DNA-bd_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]
PROSITE	PS50888. HLH. 1 hit. PS50113. PAC. False negative. PS50112. PAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	786.
SOURCE	Search...

Entry information

Entry name

AHR_HUMAN

Accession

Primary (citable) accession number: P35869
Secondary accession number(s): A4D130 , Q13728, Q13803, Q13804

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	July 15, 1998
Last modified:	January 19, 2010
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.