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Protein

Aryl hydrocarbon receptor nuclear translocator

Gene

ARNT

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

Functioni

Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). 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:28396409).By similarity1 Publication

GO - Molecular functioni

  • aryl hydrocarbon receptor activity Source: Ensembl
  • aryl hydrocarbon receptor binding Source: BHF-UCL
  • DNA binding transcription factor activity Source: ProtInc
  • enhancer binding Source: MGI
  • 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
  • transcription coactivator activity Source: ProtInc
  • transcription factor binding Source: BHF-UCL

GO - Biological processi

  • cell differentiation Source: Ensembl
  • embryonic placenta development Source: Ensembl
  • mRNA transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of endothelial cell proliferation Source: BHF-UCL
  • positive regulation of erythrocyte differentiation Source: BHF-UCL
  • positive regulation of glycolytic process Source: BHF-UCL
  • positive regulation of hormone biosynthetic process Source: BHF-UCL
  • positive regulation of protein sumoylation Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: Ensembl
  • positive regulation of vascular endothelial growth factor production Source: BHF-UCL
  • positive regulation of vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL
  • regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
  • regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: BHF-UCL
  • response to hypoxia Source: BHF-UCL
  • transcription, DNA-templated Source: ProtInc
  • xenobiotic metabolic process Source: Reactome

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor
R-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
SignaLinkiP27540
SIGNORiP27540

Protein family/group databases

MoonDBiP27540 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Aryl hydrocarbon receptor nuclear translocator
Short name:
ARNT protein
Alternative name(s):
Class E basic helix-loop-helix protein 2
Short name:
bHLHe2
Dioxin receptor, nuclear translocator
Hypoxia-inducible factor 1-beta
Short name:
HIF-1-beta
Short name:
HIF1-beta
Gene namesi
Name:ARNT
Synonyms:BHLHE2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143437.20
HGNCiHGNC:700 ARNT
MIMi126110 gene
neXtProtiNX_P27540

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91R → A: Diminishes DNA interaction. 1 Publication1
Mutagenesisi93N → A: Diminishes DNA interaction. 1 Publication1
Mutagenesisi94H → A: Severely diminishes DNA interaction. 1 Publication1
Mutagenesisi98E → A: Severely diminishes DNA interaction. 1 Publication1
Mutagenesisi99R → A: Diminishes DNA interaction. 1 Publication1
Mutagenesisi101R → A: Severely diminishes DNA interaction. 1 Publication1
Mutagenesisi102R → A: Severely diminishes DNA interaction. 1 Publication1

Organism-specific databases

DisGeNETi405
OpenTargetsiENSG00000143437
PharmGKBiPA24994

Chemistry databases

ChEMBLiCHEMBL5618

Polymorphism and mutation databases

BioMutaiARNT
DMDMi114163

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001271182 – 789Aryl hydrocarbon receptor nuclear translocatorAdd BLAST788

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Cross-linki58Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei77PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP27540
MaxQBiP27540
PaxDbiP27540
PeptideAtlasiP27540
PRIDEiP27540
ProteomicsDBi54398
54399 [P27540-2]
54400 [P27540-3]

PTM databases

iPTMnetiP27540
PhosphoSitePlusiP27540

Expressioni

Gene expression databases

BgeeiENSG00000143437
CleanExiHS_ARNT
ExpressionAtlasiP27540 baseline and differential
GenevisibleiP27540 HS

Organism-specific databases

HPAiCAB004318
HPA001759

Interactioni

Subunit structurei

Monomer. Homodimer only upon binding to a DNA (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Interacts with TACC3 (By similarity). Interacts with HIF1A, EPAS1, NPAS1 and NPAS3; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:20699359, PubMed:16181639) (By similarity). Forms a heterodimer with AHRR, as well as with other bHLH proteins (Probable). Interacts with NOCA7 (PubMed:10395741). Interacts with TACC3 (By similarity). Interacts with AHR; 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:28396409). Interacts with SIM1 and NPAS4 (By similarity).By similarity1 Publication4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • aryl hydrocarbon receptor binding Source: BHF-UCL
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi106898, 60 interactors
CORUMiP27540
DIPiDIP-30886N
ELMiP27540
IntActiP27540, 28 interactors
MINTiP27540
STRINGi9606.ENSP00000351407

Structurei

Secondary structure

1789
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi356 – 358Combined sources3
Beta strandi362 – 367Combined sources6
Beta strandi371 – 376Combined sources6
Helixi380 – 384Combined sources5
Helixi388 – 390Combined sources3
Turni391 – 393Combined sources3
Helixi396 – 399Combined sources4
Turni402 – 404Combined sources3
Helixi405 – 415Combined sources11
Turni416 – 420Combined sources5
Beta strandi423 – 430Combined sources8
Beta strandi436 – 446Combined sources11
Turni449 – 451Combined sources3
Beta strandi456 – 463Combined sources8

3D structure databases

ProteinModelPortaliP27540
SMRiP27540
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27540

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini89 – 142bHLHPROSITE-ProRule annotationAdd BLAST54
Domaini161 – 235PAS 1PROSITE-ProRule annotationAdd BLAST75
Domaini349 – 419PAS 2PROSITE-ProRule annotationAdd BLAST71
Domaini424 – 467PACAdd BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni88 – 128DNA-binding1 PublicationAdd BLAST41
Regioni112 – 264Required for heterodimer formation with EPAS1By similarityAdd BLAST153
Regioni112 – 168Required for heterodimer formation with HIF1ABy similarityAdd BLAST57
Regioni167 – 171Mediates the transcription activity and dimerization of the AHR:ARNT complexBy similarity5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi99 – 102Poly-Arg4
Compositional biasi503 – 507Poly-Gln5
Compositional biasi710 – 769Gln-richAdd BLAST60
Compositional biasi738 – 741Poly-Ser4

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IQ5T Eukaryota
ENOG410XVHF LUCA
GeneTreeiENSGT00760000118788
HOGENOMiHOG000234380
HOVERGENiHBG000164
InParanoidiP27540
KOiK09097
OMAiVEFCHPE
OrthoDBiEOG091G03AI
PhylomeDBiP27540
TreeFamiTF319983

Family and domain databases

CDDicd00083 HLH, 1 hit
cd00130 PAS, 2 hits
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR001067 Nuc_translocat
IPR001610 PAC
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
PfamiView protein in Pfam
PF00010 HLH, 1 hit
PF00989 PAS, 1 hit
PRINTSiPR00785 NCTRNSLOCATR
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00086 PAC, 1 hit
SM00091 PAS, 2 hits
SUPFAMiSSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 4 hits
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 2 hits

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P27540-1) [UniParc]FASTAAdd to basket
Also known as: Long

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAATTANPEM TSDVPSLGPA IASGNSGPGI QGGGAIVQRA IKRRPGLDFD
60 70 80 90 100
DDGEGNSKFL RCDDDQMSND KERFARSDDE QSSADKERLA RENHSEIERR
110 120 130 140 150
RRNKMTAYIT ELSDMVPTCS ALARKPDKLT ILRMAVSHMK SLRGTGNTST
160 170 180 190 200
DGSYKPSFLT DQELKHLILE AADGFLFIVS CETGRVVYVS DSVTPVLNQP
210 220 230 240 250
QSEWFGSTLY DQVHPDDVDK LREQLSTSEN ALTGRILDLK TGTVKKEGQQ
260 270 280 290 300
SSMRMCMGSR RSFICRMRCG SSSVDPVSVN RLSFVRNRCR NGLGSVKDGE
310 320 330 340 350
PHFVVVHCTG YIKAWPPAGV SLPDDDPEAG QGSKFCLVAI GRLQVTSSPN
360 370 380 390 400
CTDMSNVCQP TEFISRHNIE GIFTFVDHRC VATVGYQPQE LLGKNIVEFC
410 420 430 440 450
HPEDQQLLRD SFQQVVKLKG QVLSVMFRFR SKNQEWLWMR TSSFTFQNPY
460 470 480 490 500
SDEIEYIICT NTNVKNSSQE PRPTLSNTIQ RPQLGPTANL PLEMGSGQLA
510 520 530 540 550
PRQQQQQTEL DMVPGRDGLA SYNHSQVVQP VTTTGPEHSK PLEKSDGLFA
560 570 580 590 600
QDRDPRFSEI YHNINADQSK GISSSTVPAT QQLFSQGNTF PPTPRPAENF
610 620 630 640 650
RNSGLAPPVT IVQPSASAGQ MLAQISRHSN PTQGATPTWT PTTRSGFSAQ
660 670 680 690 700
QVATQATAKT RTSQFGVGSF QTPSSFSSMS LPGAPTASPG AAAYPSLTNR
710 720 730 740 750
GSNFAPETGQ TAGQFQTRTA EGVGVWPQWQ GQQPHHRSSS SEQHVQQPPA
760 770 780
QQPGQPEVFQ EMLSMLGDQS NSYNNEEFPD LTMFPPFSE
Length:789
Mass (Da):86,636
Last modified:August 1, 1992 - v1
Checksum:i2E278F8E62BFBF6D
GO
Isoform 2 (identifier: P27540-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     77-91: Missing.

Show »
Length:774
Mass (Da):84,948
Checksum:i0653070528296044
GO
Isoform 3 (identifier: P27540-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.
     319-323: Missing.

Note: No experimental confirmation available.
Show »
Length:775
Mass (Da):85,296
Checksum:i74839AACC350CB6B
GO
Isoform 4 (identifier: P27540-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     601-602: Missing.

Show »
Length:787
Mass (Da):86,366
Checksum:i956940ABFFF1E71A
GO

Sequence cautioni

The sequence BAD93114 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAD38953 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti627R → H in BAG36518 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024280430R → Q. Corresponds to variant dbSNP:rs2229175Ensembl.1
Natural variantiVAR_014819511D → N. Corresponds to variant dbSNP:rs1805133Ensembl.1
Natural variantiVAR_018906517D → E1 PublicationCorresponds to variant dbSNP:rs10305741Ensembl.1
Natural variantiVAR_020189706P → L. Corresponds to variant dbSNP:rs2275237Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0365321 – 9Missing in isoform 3. 1 Publication9
Alternative sequenceiVSP_00209277 – 91Missing in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_036533319 – 323Missing in isoform 3. 1 Publication5
Alternative sequenceiVSP_055030601 – 602Missing in isoform 4. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M69238 mRNA Translation: AAA51777.1
Y18859
, AJ251863, AJ404851, AJ404852, AJ404853, AJ404854 Genomic DNA Translation: CAC21446.1
AK290177 mRNA Translation: BAF82866.1
AK293027 mRNA Translation: BAF85716.1
AK313780 mRNA Translation: BAG36518.1
AB209877 mRNA Translation: BAD93114.1 Different initiation.
AL834279 mRNA Translation: CAD38953.1 Different initiation.
AY430083 Genomic DNA Translation: AAQ96598.1
AL355860 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53510.1
CH471121 Genomic DNA Translation: EAW53513.1
CCDSiCCDS65641.1 [P27540-3]
CCDS65642.1 [P27540-4]
CCDS970.1 [P27540-1]
CCDS971.1 [P27540-2]
PIRiI59550
RefSeqiNP_001184254.1, NM_001197325.1
NP_001272964.1, NM_001286035.1 [P27540-3]
NP_001272965.1, NM_001286036.1 [P27540-4]
NP_001659.1, NM_001668.3 [P27540-1]
NP_848514.1, NM_178427.2 [P27540-2]
XP_016856778.1, XM_017001289.1 [P27540-3]
UniGeneiHs.632446

Genome annotation databases

EnsembliENST00000354396; ENSP00000346372; ENSG00000143437 [P27540-4]
ENST00000358595; ENSP00000351407; ENSG00000143437 [P27540-1]
ENST00000505755; ENSP00000427571; ENSG00000143437 [P27540-2]
ENST00000515192; ENSP00000423851; ENSG00000143437 [P27540-3]
GeneIDi405
KEGGihsa:405
UCSCiuc001evr.2 human [P27540-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiARNT_HUMAN
AccessioniPrimary (citable) accession number: P27540
Secondary accession number(s): B2R9H1
, C4AMA1, F8WAP6, Q59ED4, Q5QP39, Q8NDC7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: July 18, 2018
This is version 201 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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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