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Reviewed, UniProtKB/Swiss-Prot P35869 (AHR_HUMAN)

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

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length848 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AIPO001701EBI-80780,EBI-704197
EBNA3P129774EBI-80780,EBI-993115From a different organism.
NCOA7Q8NI081EBI-80780,EBI-80799
NCOR2Q9Y6181EBI-80780,EBI-80830

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 1010 By similarity
PRO_0000013450
Chain11 – 848838Aryl hydrocarbon receptor
PRO_0000013451

Regions

Domain41 – 8141Helix-loop-helix motif
Domain111 – 18171PAS 1
Domain275 – 34268PAS 2
Domain348 – 38639PAC
DNA binding13 – 4028Basic motif
Compositional bias600 – 64041Gln-rich

Natural variations

Natural variant5171P → S Ref.18
VAR_015516
Natural variant5541R → K: dbSNP rs2066853. Ref.15 Ref.16 Ref.17
VAR_009281
Natural variant5701V → I: dbSNP rs4986826. Ref.18 Ref.16
VAR_009282
Natural variant7861M → V Ref.17
VAR_015517

Experimental info

Mutagenesis3811V → A: Increases specific ligand binding. Ref.8
Mutagenesis3811V → D: Abolishes specific ligand binding. Ref.8
Mutagenesis3811V → L or G: No effect on specific ligand binding. Ref.8
Sequence conflict1911E → EG in AAA92082. Ref.6
Sequence conflict340 – 3412MI → SD Ref.7
Sequence conflict807 – 84842LNETY…SSGFL → FK in BAA03857. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P35869-1 [UniParc].

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

FASTA84896,147
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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].
[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.

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 expand/collapse EMBL AC list , 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.
IPIIPI00021008.
PIRS59514.
RefSeqNP_001612.1.
UniGeneHs.171189

3D structure databases

DisProtDP00381.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:946N.
IntActP35869. 6 interactions.

PTM databases

PhosphoSiteP35869.

Proteomic databases

PRIDEP35869.

Genome annotation databases

EnsemblENSG00000106546. Homo sapiens. [Contig view]
GeneID196.
KEGGhsa:196.

Organism-specific databases

GeneCardsGC07P017304.
H-InvDBHIX0033619.
HGNCHGNC:348. AHR.
HPACAB005072.
MIM600253. gene.
PharmGKBPA24641.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP35869.
HOVERGENP35869.
OMAP35869. QQDESIY.

Gene expression databases

BgeeP35869.
CleanExHS_AHR.

Family and domain databases

InterProIPR001092. HLH_basic.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
[Graphical view]
PfamPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
PROSITEPS50888. HLH. 1 hit.
PS50113. PAC. False negative.
PS50112. PAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio786.
SOURCESearch...

Entry information

Entry nameAHR_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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 · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents