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Protein

Aryl hydrocarbon receptor

Gene

AHR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.2 Publications

GO - Molecular functioni

  • aryl hydrocarbon receptor activity Source: InterPro
  • DNA binding Source: DFLAT
  • E-box binding Source: UniProtKB
  • enhancer binding Source: MGI
  • Hsp90 protein binding Source: BHF-UCL
  • protein dimerization activity Source: DFLAT
  • protein heterodimerization activity Source: DFLAT
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: UniProtKB
  • TBP-class protein binding Source: CAFA
  • TFIID-class transcription factor binding Source: CAFA
  • transcription coactivator binding Source: CAFA
  • transcription factor activity, sequence-specific DNA binding Source: MGI
  • transcription factor binding Source: BHF-UCL
  • transcription regulatory region DNA binding Source: DFLAT

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • blood vessel development Source: DFLAT
  • cell cycle Source: UniProtKB-KW
  • circadian regulation of gene expression Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: GO_Central
  • regulation of B cell proliferation Source: DFLAT
  • regulation of gene expression Source: DFLAT
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: DFLAT
  • response to toxic substance Source: UniProtKB
  • response to xenobiotic stimulus Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: UniProtKB
  • xenobiotic metabolic process Source: DFLAT

Keywordsi

Molecular functionActivator, DNA-binding, Receptor, Repressor
Biological processBiological rhythms, Cell cycle, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-211945. Phase I - Functionalization of compounds.
R-HSA-211976. Endogenous sterols.
R-HSA-211981. Xenobiotics.
R-HSA-8937144. Aryl hydrocarbon receptor signalling.
SignaLinkiP35869.
SIGNORiP35869.

Names & Taxonomyi

Protein namesi
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 namesi
Name:AHR
Synonyms:BHLHE76
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106546.12.
HGNCiHGNC:348. AHR.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi381V → A: Increases specific ligand binding. 1 Publication1
Mutagenesisi381V → D: Abolishes specific ligand binding. 1 Publication1
Mutagenesisi381V → L or G: No effect on specific ligand binding. 1 Publication1

Organism-specific databases

DisGeNETi196.
OpenTargetsiENSG00000106546.
PharmGKBiPA24641.

Chemistry databases

ChEMBLiCHEMBL3201.
DrugBankiDB01076. Atorvastatin.
DB00499. Flutamide.
DB01404. Ginseng.
DB01097. Leflunomide.
DB00379. Mexiletine.
DB00393. Nimodipine.

Polymorphism and mutation databases

BioMutaiAHR.
DMDMi3041653.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000134501 – 10By similarity10
ChainiPRO_000001345111 – 848Aryl hydrocarbon receptorAdd BLAST838

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP35869.
MaxQBiP35869.
PaxDbiP35869.
PeptideAtlasiP35869.
PRIDEiP35869.

PTM databases

iPTMnetiP35869.
PhosphoSitePlusiP35869.

Expressioni

Tissue specificityi

Expressed in all tissues tested including blood, brain, heart, kidney, liver, lung, pancreas and skeletal muscle.2 Publications

Inductioni

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).1 Publication

Gene expression databases

BgeeiENSG00000106546.
CleanExiHS_AHR.
ExpressionAtlasiP35869. baseline and differential.
GenevisibleiP35869. HS.

Organism-specific databases

HPAiCAB005072.
HPA029722.
HPA029723.

Interactioni

Subunit structurei

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. Interacts with ARNTL/BMAL1. Interacts with HSP90AB1 (By similarity).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • Hsp90 protein binding Source: BHF-UCL
  • protein dimerization activity Source: DFLAT
  • protein heterodimerization activity Source: DFLAT
  • TBP-class protein binding Source: CAFA
  • TFIID-class transcription factor binding Source: CAFA
  • transcription coactivator binding Source: CAFA
  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi106699. 47 interactors.
CORUMiP35869.
DIPiDIP-946N.
ELMiP35869.
IntActiP35869. 12 interactors.
MINTiMINT-6597538.
STRINGi9606.ENSP00000242057.

Chemistry databases

BindingDBiP35869.

Structurei

3D structure databases

DisProtiDP00381.
ProteinModelPortaliP35869.
SMRiP35869.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 80bHLHPROSITE-ProRule annotationAdd BLAST54
Domaini111 – 181PAS 1PROSITE-ProRule annotationAdd BLAST71
Domaini275 – 342PAS 2PROSITE-ProRule annotationAdd BLAST68
Domaini348 – 386PACAdd BLAST39

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi600 – 640Gln-richAdd BLAST41

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3560. Eukaryota.
ENOG410XRZH. LUCA.
GeneTreeiENSGT00860000133766.
HOGENOMiHOG000252935.
HOVERGENiHBG007313.
InParanoidiP35869.
KOiK09093.
OMAiQQLCQKM.
OrthoDBiEOG091G16AJ.
PhylomeDBiP35869.
TreeFamiTF352074.

Family and domain databases

CDDicd00083. HLH. 1 hit.
cd00130. PAS. 2 hits.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR033348. AHR.
IPR011598. bHLH_dom.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
PANTHERiPTHR10649:SF15. PTHR10649:SF15. 1 hit.
PfamiView protein in Pfam
PF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
SMARTiView protein in SMART
SM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
PROSITEiView protein in PROSITE
PS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P35869-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSSSANITY ASRKRRKPVQ KTVKPIPAEG IKSNPSKRHR DRLNTELDRL
60 70 80 90 100
ASLLPFPQDV INKLDKLSVL RLSVSYLRAK SFFDVALKSS PTERNGGQDN
110 120 130 140 150
CRAANFREGL NLQEGEFLLQ ALNGFVLVVT TDALVFYASS TIQDYLGFQQ
160 170 180 190 200
SDVIHQSVYE LIHTEDRAEF QRQLHWALNP SQCTESGQGI EEATGLPQTV
210 220 230 240 250
VCYNPDQIPP ENSPLMERCF ICRLRCLLDN SSGFLAMNFQ GKLKYLHGQK
260 270 280 290 300
KKGKDGSILP PQLALFAIAT PLQPPSILEI RTKNFIFRTK HKLDFTPIGC
310 320 330 340 350
DAKGRIVLGY TEAELCTRGS GYQFIHAADM LYCAESHIRM IKTGESGMIV
360 370 380 390 400
FRLLTKNNRW TWVQSNARLL YKNGRPDYII VTQRPLTDEE GTEHLRKRNT
410 420 430 440 450
KLPFMFTTGE AVLYEATNPF PAIMDPLPLR TKNGTSGKDS ATTSTLSKDS
460 470 480 490 500
LNPSSLLAAM MQQDESIYLY PASSTSSTAP FENNFFNESM NECRNWQDNT
510 520 530 540 550
APMGNDTILK HEQIDQPQDV NSFAGGHPGL FQDSKNSDLY SIMKNLGIDF
560 570 580 590 600
EDIRHMQNEK FFRNDFSGEV DFRDIDLTDE ILTYVQDSLS KSPFIPSDYQ
610 620 630 640 650
QQQSLALNSS CMVQEHLHLE QQQQHHQKQV VVEPQQQLCQ KMKHMQVNGM
660 670 680 690 700
FENWNSNQFV PFNCPQQDPQ QYNVFTDLHG ISQEFPYKSE MDSMPYTQNF
710 720 730 740 750
ISCNQPVLPQ HSKCTELDYP MGSFEPSPYP TTSSLEDFVT CLQLPENQKH
760 770 780 790 800
GLNPQSAIIT PQTCYAGAVS MYQCQPEPQH THVGQMQYNP VLPGQQAFLN
810 820 830 840
KFQNGVLNET YPAELNNINN TQTTTHLQPL HHPSEARPFP DLTSSGFL
Length:848
Mass (Da):96,147
Last modified:July 15, 1998 - v2
Checksum:i1BFE022871B7B028
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti191E → EG in AAA92082 (PubMed:16696038).Curated1
Sequence conflicti340 – 341MI → SD (PubMed:7515333).Curated2
Sequence conflicti807 – 848LNETY…SSGFL → FK in BAA03857 (PubMed:8393992).CuratedAdd BLAST42

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015516517P → S1 PublicationCorresponds to variant dbSNP:rs72552768Ensembl.1
Natural variantiVAR_009281554R → K3 PublicationsCorresponds to variant dbSNP:rs2066853Ensembl.1
Natural variantiVAR_009282570V → I2 PublicationsCorresponds to variant dbSNP:rs4986826Ensembl.1
Natural variantiVAR_015517786M → V1 PublicationCorresponds to variant dbSNP:rs72552769Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5366.1.
PIRiS59514.
RefSeqiNP_001612.1. NM_001621.4.
UniGeneiHs.171189.

Genome annotation databases

EnsembliENST00000242057; ENSP00000242057; ENSG00000106546.
ENST00000463496; ENSP00000436466; ENSG00000106546.
GeneIDi196.
KEGGihsa:196.
UCSCiuc011jxz.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAHR_HUMAN
AccessioniPrimary (citable) accession number: P35869
Secondary accession number(s): A4D130
, Q13728, Q13803, Q13804
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: July 15, 1998
Last modified: September 27, 2017
This is version 185 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot