P35869 (AHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 TGFB1 and dioxin in a cell-type specific fashion. Repressed by cAMP, retinoic acid, and 12-O-tetradecanoyl phorbol-13 acetate (TPA). Ref.12
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 Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement Ref.13. Source: UniProtKB blood vessel development Non-traceable author statement PubMed 19538249. Source: DFLAT cell cycle Traceable author statement Ref.13. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of RNA polymerase II transcriptional preinitiation complex assembly Inferred from electronic annotation. Source: Compara prostate gland development Inferred from electronic annotation. Source: Compara regulation of B cell proliferation Inferred from direct assay PubMed 15681594. Source: DFLAT response to stress Inferred from direct assay Ref.10. Source: UniProtKB xenobiotic metabolic process Traceable author statement PubMed 19538249. Source: DFLAT
Cellular_component	cytosolic aryl hydrocarbon receptor complex Traceable author statement PubMed 19538249. Source: DFLAT transcription factor complex Traceable author statement PubMed 19538249. Source: DFLAT
Molecular_function	Hsp90 protein binding Inferred from direct assay PubMed 9079689. Source: BHF-UCL RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from direct assay Ref.11. Source: UniProtKB protein heterodimerization activity Traceable author statement PubMed 19538249. Source: DFLAT sequence-specific DNA binding Inferred from electronic annotation. Source: Compara transcription regulatory region DNA binding Inferred from direct assay PubMed 15681594. Source: DFLAT
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARNT	P27540	5	EBI-80780,EBI-80809
EBNA3	P12977	5	EBI-80780,EBI-993115	From a different organism.
NCOA7	Q8NI08	2	EBI-80780,EBI-80799
NCOR2	Q9Y618	2	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	27 – 80	54	bHLH
	Domain	111 – 181	71	PAS 1
	Domain	275 – 342	68	PAS 2
	Domain	348 – 386	39	PAC
	Compositional bias	600 – 640	41	Gln-rich
Natural variations
	Natural variant	517	1	P → S. Ref.20		VAR_015516
	Natural variant	554	1	R → K. Ref.17 Ref.18 Ref.19 Corresponds to variant rs2066853 [ dbSNP | Ensembl ].		VAR_009281
	Natural variant	570	1	V → I. Ref.18 Ref.20 Corresponds to variant rs4986826 [ dbSNP | Ensembl ].		VAR_009282
	Natural variant	786	1	M → V. Ref.19		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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. NM_001621.4.
UniGene	Hs.171189.
3D structure databases
DisProt	DP00381.
ProteinModelPortal	P35869.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-946N.
IntAct	P35869. 11 interactions.
STRING	9606.ENSP00000242057.
PTM databases
PhosphoSite	P35869.
Polymorphism databases
DMDM	3041653.
Proteomic databases
PaxDb	P35869.
PRIDE	P35869.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000242057; ENSP00000242057; ENSG00000106546. ENST00000463496; ENSP00000436466; ENSG00000106546.
GeneID	196.
KEGG	hsa:196.
UCSC	uc011jxz.1. human.
Organism-specific databases
CTD	196.
GeneCards	GC07P017304.
HGNC	HGNC:348. AHR.
HPA	CAB005072. HPA029722. HPA029723.
MIM	600253. gene.
neXtProt	NX_P35869.
PharmGKB	PA24641.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG253623.
HOGENOM	HOG000252935.
HOVERGEN	HBG007313.
InParanoid	P35869.
KO	K09093.
OMA	QQLCQKM.
OrthoDB	EOG42BX7X.
PhylomeDB	P35869.
Gene expression databases
Bgee	P35869.
CleanEx	HS_AHR.
Genevestigator	P35869.
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	P35869.
ChEMBL	CHEMBL3201.
ChiTaRS	AHR. human.
GenomeRNAi	196.
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:	May 1, 2013
This is version 139 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.