ARNT (aryl hydrocarbon receptor nuclear translocator)

2004-10-01   Oliver Hankinson 

UCLA Medical Center, Center for the Health Sciences, Box 951732,Los Angeles, CA 90095-1732, USA


Atlas Image
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics



The gene is about 65 kb in size and has 22 exons.


Five alternative transcriptional start sites have been identified, located from 27 to 147 nucleotides 5 to the ATG translational initiation codon. There are two alternative polyadenylation sites, giving rise to transcripts of about 2,600 and 4,200 nucleotides. The 45 nucleotide exon 5 is an alternative exon and is spliced out in approximately half of the transcripts. This proportion does not seem to vary much between different tissues.No observable effects on the resulting protein due to omission of exon 5 have been noted. A transcript of about 1,300 nucleotides is observed in some breast cancers and may be due to an alternative splicing event leading to elimination of the 3 end of the transcript.


No pseudogenes for ARNT are known.


Atlas Image
bHLH, basic helix-loop-helix domain; PAS, Per/ARNT/Sim homology domain; A and B, the two approximately 50 amino-acid degenerative direct repeats within the PAS domain; Q-rich, glutamine-rich transactivation domain.


The 87 kDa protein is comprised of 789 amino acids (if exon 5 is included) or 774 amino acids (if exon 5 is excluded).


ARNT is expressed ubiquitously.


ARNT is a nuclear protein in most cell types, although it may also be located in the cytosol, particularly during embryogenesis.


ARNT serves as the dimerization partner for a number of other bHLH-PAS proteins, whose activity is modulated either by exogenous chemicals (the aryl hydrocarbon receptor ( AHR)), or by hypoxia (hypoxia inducible factors 1,2 and 3 alpha [HIF-1a, HIF-2a and HIF-3a), or which show restricted expression (e.g. SIM-1). The AHR/ARNT dimer activates transcription of several genes involved in metabolism of foreign chemicals, including CYP1A1, CYP1B1, and NADP(H): oxidoreductase ( NQO1). Transcriptional activation of these genes depends upon prior binding of AHR to xenobiotic ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and benzo(a)pyrene. The AHR/ARNT dimer and ARNT itself can also impact signaling by the eostrogen receptor. The HIF-1a (and 2a and 3a) proteins are stabilized and activated by hypoxia (and hypoglycemia) and activate transcription of several genes involved in adapting to these adverse conditions, including the genes for erythropoietin ( EPO), vascular endothelial growth factor ( VEGF), and a number of enzymes of glycolysis. Unlike the AHR/ARNT and HIF/ARNT dimers, the SIM-1/ARNT dimer is probably not conditionally regulated. The above dimers bind specific DNA sequences in the regulatory regions of the responsive genes. The half-site for ARNT is on the 3 side of the recognition sequence and is 5-GTG-3. The sequence of the other half of the binding site depends upon the identity of the dimerization partner. DNA binding of ARNT is mediated by its basic region. There is evidence that the PAS region may also be involved. Dimerization between ARNT and other bHLH-PAS proteins is mediated by their HLH and PAS regions. The transcriptional activation domain of ARNT is located towards its carboxy terminus. ARNT appears capable of binding the E-box sequence 5-CACGTG-3, although the affinity of ARNT for itself appears relatively low and no genes responsive to the homodimer have been identified.


Two ARNT-related genes, ARNT-2 and ARNT-3 (also called BMAL-1 or MOP3) have been identified. ARNT-2 is more restricted in expression than ARNT, but appears to dimerize with the same partner proteins as ARNT. ARNT-3 has a somewhat different dimerization potential than ARNT.



Several polymorphisms have been identified. None has shown an association with any disease.

Implicated in

Involved in a t(1;12)(q21;p13) translocation with EVT6 fusion in acute myeloblastic leukemia.
Leukemia, Myelocytic, Acute AML-M2
Hybrid gene
Amino-terminal half of TEL fused to the complete coding sequence of ARNT except for its 8 amino-terminal amino acids. The reciprocal translocation probably contributes little if at all to the cancer phenotype.


Pubmed IDLast YearTitleAuthors
77002401995Orientation of the heterodimeric aryl hydrocarbon (dioxin) receptor complex on its asymmetric DNA recognition sequence.Bacsi SG et al
154858062004Recruitment of thyroid hormone receptor/retinoblastoma-interacting protein 230 by the aryl hydrocarbon receptor nuclear translocator is required for the transcriptional response to both dioxin and hypoxia.Beischlag TV et al
127543772003The basic helix-loop-helix-PAS protein ARNT functions as a potent coactivator of estrogen receptor-dependent transcription.Brunnberg S et al
18520761991Cloning of a factor required for activity of the Ah (dioxin) receptor.Hoffman EC et al
82443751993The Ah receptor nuclear translocator gene (ARNT) is located on q21 of human chromosome 1 and on mouse chromosome 3 near Cf-3.Johnson B et al
113811392001Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt.Keith B et al
93984421997ARNT-deficient mice and placental differentiation.Kozak KR et al
91215571997Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT.Maltepe E et al
127741242003Modulation of oestrogen receptor signalling by association with the activated dioxin receptor.Ohtake F et al
80653411994Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT).Reisz-Porszasz S et al
13170621992Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor.Reyes H et al
108290782000The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.Salomon-Nguyen F et al
120325872002Variability of the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene.Scheel J et al
111293422000Genomic structure of the human Ah receptor nuclear translocator gene (hARNT).Scheel J et al
93955311997A mutation in the aryl hydrocarbon receptor (AHR) in a cultured mammalian cell line identifies a novel region of AHR that affects DNA binding.Sun W et al
75928391995DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins.Swanson HI et al
145977632003Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function.Takagi S et al
123547702002The aryl hydrocarbon receptor nuclear transporter is modulated by the SUMO-1 conjugation system.Tojo M et al
147645922004Patent ductus venosus and dioxin resistance in mice harboring a hypomorphic Arnt allele.Walisser JA et al
75399181995Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.Wang GL et al
93282851997Aryl hydrocarbon (Ah) nonresponsiveness in estrogen receptor-negative MDA-MB-231 cells is associated with expression of a variant arnt protein.Wilson CL et al
86629571996The role of the aryl hydrocarbon receptor nuclear translocator (ARNT) in hypoxic induction of gene expression. Studies in ARNT-deficient cells.Wood SM et al

Other Information

Locus ID:

NCBI: 405
MIM: 126110
HGNC: 700
Ensembl: ENSG00000143437


dbSNP: 405
ClinVar: 405
TCGA: ENSG00000143437


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Renal cell carcinomaKEGGko05211
Pathways in cancerKEGGhsa05200
Renal cell carcinomaKEGGhsa05211
Chemical carcinogenesisKEGGhsa05204
Chemical carcinogenesisKEGGko05204
HIF-1 signaling pathwayKEGGhsa04066
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Fatty acid, triacylglycerol, and ketone body metabolismREACTOMER-HSA-535734
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)REACTOMER-HSA-400206
PPARA activates gene expressionREACTOMER-HSA-1989781
Biological oxidationsREACTOMER-HSA-211859
Phase 1 - Functionalization of compoundsREACTOMER-HSA-211945
Cytochrome P450 - arranged by substrate typeREACTOMER-HSA-211897
Endogenous sterolsREACTOMER-HSA-211976
Cellular responses to stressREACTOMER-HSA-2262752
Cellular response to hypoxiaREACTOMER-HSA-2262749
Regulation of Hypoxia-inducible Factor (HIF) by oxygenREACTOMER-HSA-1234174
Regulation of gene expression by Hypoxia-inducible FactorREACTOMER-HSA-1234158
Aryl hydrocarbon receptor signallingREACTOMER-HSA-8937144

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
160072142005Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways.188
160960552005Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes.172
127741242003Modulation of oestrogen receptor signalling by association with the activated dioxin receptor.142
165544182006Hypoxia-inducible factors in the kidney.110
204780512010MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1alpha/HIF-1beta.96
191295022009Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor.89
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
197306832009The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.59
158377952005ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription.52
120240422002Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex.51


Oliver Hankinson

ARNT (aryl hydrocarbon receptor nuclear translocator)

Atlas Genet Cytogenet Oncol Haematol. 2004-10-01

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