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Protein

Aryl hydrocarbon receptor

Gene

AHR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820).3 Publications

GO - Molecular functioni

  • aryl hydrocarbon receptor activity Source: InterPro
  • DNA binding Source: DFLAT
  • DNA binding transcription factor activity Source: UniProtKB
  • E-box binding Source: UniProtKB
  • enhancer binding Source: MGI
  • Hsp90 protein binding Source: BHF-UCL
  • nuclear receptor activity Source: UniProtKB
  • protein dimerization activity Source: DFLAT
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific double-stranded DNA binding Source: UniProtKB
  • TBP-class protein binding Source: CAFA
  • TFIID-class transcription factor binding Source: CAFA
  • transcription coactivator binding Source: CAFA
  • 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
  • cAMP-mediated signaling Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cellular response to 2,3,7,8-tetrachlorodibenzodioxine Source: UniProtKB
  • cellular response to cAMP Source: UniProtKB
  • cellular response to forskolin Source: UniProtKB
  • 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 by RNA polymerase II 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 by RNA polymerase II Source: DFLAT
  • response to toxic substance Source: UniProtKB
  • response to xenobiotic stimulus Source: UniProtKB
  • transcription by RNA polymerase II 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
MIMi600253 gene
neXtProtiNX_P35869

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
Mutagenesisi40R → D: Decreases transcription factor activity. 1 Publication1
Mutagenesisi50L → D: Interfers with transcription factor activity. 1 Publication1
Mutagenesisi74V → D: Interfers with transcription factor activity. 1 Publication1
Mutagenesisi79A → D: Interfers with transcription factor activity. 1 Publication1
Mutagenesisi82F → D: Interfers with transcription factor activity. 1 Publication1
Mutagenesisi118L → D: Interfers with transcription factor activity. 1 Publication1
Mutagenesisi122L → D: Interfers with transcription factor activity. 1 Publication1
Mutagenesisi136F → D: Interfers with transcription factor activity. 1 Publication1
Mutagenesisi154I → D: Interfers with transcription factor activity. 1 Publication1
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
GuidetoPHARMACOLOGYi2951

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
ProteomicsDBi55159

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

Homodimer (By similarity). Binds MYBBP1A (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. 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). Interacts with ARNT; the heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • Hsp90 protein binding Source: BHF-UCL
  • protein dimerization activity Source: DFLAT
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • 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, 48 interactors
CORUMiP35869
DIPiDIP-946N
ELMiP35869
IntActiP35869, 14 interactors
STRINGi9606.ENSP00000242057

Chemistry databases

BindingDBiP35869

Structurei

Secondary structure

1848
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 52Combined sources18
Beta strandi54 – 56Combined sources3
Helixi58 – 61Combined sources4
Helixi66 – 86Combined sources21
Helixi113 – 121Combined sources9
Beta strandi122 – 124Combined sources3
Beta strandi126 – 130Combined sources5
Beta strandi134 – 138Combined sources5
Helixi142 – 146Combined sources5
Helixi150 – 152Combined sources3
Turni153 – 155Combined sources3
Helixi158 – 161Combined sources4
Helixi164 – 174Combined sources11
Beta strandi217 – 224Combined sources8
Beta strandi235 – 246Combined sources12
Beta strandi262 – 270Combined sources9

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni38 – 66DNA-binding1 PublicationAdd BLAST29
Regioni118 – 126Required for maintaining the overall integrity of the AHR:ARNT heterodimer and its transcriptional activityBy similarity9
Regioni266 – 268Required for maintaining the overall integrity of the AHR:ARNT heterodimer and its transcriptional activityBy similarity3

Compositional bias

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

Domaini

The PAS 1 domain is essential for dimerization and also required for AHR:ARNT heterodimerization.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3560 Eukaryota
ENOG410XRZH LUCA
GeneTreeiENSGT00910000144132
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
IPR039091 AHR/AHRR
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR001610 PAC
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
IPR013655 PAS_fold_3
PANTHERiPTHR10649 PTHR10649, 1 hit
PTHR10649:SF9 PTHR10649:SF9, 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: July 18, 2018
This is version 194 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

3D-structure, 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
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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