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ARNT aryl hydrocarbon receptor nuclear translocator

Identity

Other namesHIF-1b
HGNC (Hugo) ARNT
Location 1q21
Location_base_pair Starts at 149048810 and ends at 149115810 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Note The gene is about 65 kb in size and has 22 exons
Transcription 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.
Pseudogene No pseudogenes for ARNT are known.

Protein

 
  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.
Description The 87 kDa protein is comprised of 789 amino acids (if exon 5 is included) or 774 amino acids (if exon 5 is excluded).
Expression ARNT is expressed ubiquitously.
Localisation ARNT is a nuclear protein in most cell types, although it may also be located in the cytosol, particularly during embryogenesis.
Function 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.

Homology 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.

Mutations

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

Implicated in

Note Involved in a t(1;12)(q21;p13) translocation with EVT6 fusion in acute myeloblastic leukemia.
Disease Leukemia, Myelocytic, Acute AML-M2
Prognosis Unknown.
Hybrid/Mutated 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.
  

External links

Nomenclature
HGNC (Hugo)ARNT   700
Entrez_Gene (NCBI)ARNT  405  aryl hydrocarbon receptor nuclear translocator
Cards
AtlasARNTID223ch1q21
GeneCards (Weizmann)ARNT
Ensembl (Hinxton)ENSG00000143437 [Gene_View]  ARNT [Vega]
AceView (NCBI)ARNT
Genatlas (Paris)ARNT
euGene (Indiana)405
SOURCE (Stanford)NM_001668 NM_178426 NM_178427
Gene Expression (Array Express) ENSG00000143437
Genomic and cartography
GoldenPath (UCSC)ARNT  -  1q21   chr1:149048810-149115810 -  1q21   [Description]    (hg18-Mar_2006)
EnsemblARNT - 1q21 [CytoView]
Mapping of homologs : NCBIARNT [Mapview]
OMIM126110   
Gene and transcription
Gene : Genbank (Entrez)AB209877 AF001307 AK223459 AK290177 AK291705
Reference sequence (RefSeq transcript) :SRSNM_001668 NM_178426 NM_178427
Reference transcript : EntrezNM_001668 NM_178426 NM_178427
RefSeq genomic : SRSAC_000044 AC_000133 NC_000001 NT_004487 NW_001838529 NW_925683
RefSeq genomic : EntrezAC_000044 AC_000133 NC_000001 NT_004487 NW_001838529 NW_925683
Consensus coding sequences : CCDS NCBIARNT
Cluster EST : UnigeneHs.632446 [ SRS ] Hs.632446 [ NCBI ]
Alternative Splicing : Fast-db (Paris)17248
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP27540 (SRS) P27540 (Expasy) P27540 (Uniprot)
With graphics : InterProP27540
Splice isoforms : VarSplice FASTAP27540(VarSplice FASTA)
Domaine pattern : Prosite (SRS)HLH (PS50888)    PAC (PS50113)    PAS (PS50112)   
Domain pattern : Prosite (Expaxy)HLH (PS50888)    PAC (PS50113)    PAS (PS50112)   
Domains : Interpro (SRS)HLH_DNA-bd_dom    HLH_DNA_bd    Nuc_translocat    PAC    PAS    PAS_fold    PAS_fold_3   
Domains : Interpro (EBI)HLH_DNA-bd_dom    HLH_DNA_bd    Nuc_translocat    PAC    PAS    PAS_fold    PAS_fold_3   
Related proteins : CluSTrP27540
Domain families : Pfam SRSHLH (PF00010)    PAS (PF00989)    PAS_3 (PF08447)   
Domain families : Pfam SangerHLH (PF00010)    PAS (PF00989)    PAS_3 (PF08447)   
Domain families : Pfam NCBIpfam00010    pfam00989    pfam08447   
Domain families : Smart EMBLHLH (SM00353)  PAC (SM00086)  PAS (SM00091)  
Blocks (Seattle)P27540
Crystal structure of protein : PDB SRS1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P   
Crystal structure of protein : PDBSum1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P   
Crystal structure of protein : IMB1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P   
Crystal structure of protein : PDB RSDB1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P   
HPRD00524
Protein Interaction databases
DIP (DOE-UCLA)P27540
IntAct (EBI)P27540
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIARNT
SNP : GeneSNP UtahARNT
SNP : HGBaseARNT
Genetic variants : HAPMAPARNT
Somatic Mutations in Cancer : COSMICARNT 
Mutations and Diseases : HGMDARNT
Hereditary diseases : OMIM126110   
Hereditary diseases : GENETests126110   
Diseases : Genetic AssociationARNT
General knowledge
Homologs : HomoloGeneARNT
Homology/Alignments : Family Browser UCSCARNT
Phylogenetic Trees/Animal Genes : TreeFamARNT
Chemical/Protein Interactions : CTD405
Keywords Ontology : AmiGOresponse to hypoxia  embryonic placenta development  positive regulation of endothelial cell proliferation  RNA polymerase II transcription factor activity, enhancer binding  transcription coactivator activity  signal transducer activity  nucleus  cytoplasm  regulation of transcription, DNA-dependent  signal transduction  positive regulation vascular endothelial growth factor production  aryl hydrocarbon receptor binding  cell differentiation  positive regulation of vascular endothelial growth factor receptor signaling pathway  mRNA transcription from RNA polymerase II promoter  positive regulation of gene-specific transcription  sequence-specific DNA binding  regulation of transcription from RNA polymerase II promoter in response to oxidative stress  positive regulation of erythrocyte differentiation  positive regulation of glycolysis  positive regulation of transcription  positive regulation of transcription from RNA polymerase II promoter  positive regulation of hormone biosynthetic process  protein heterodimerization activity  
Keywords Ontology : EGO-EBIresponse to hypoxia  embryonic placenta development  positive regulation of endothelial cell proliferation  RNA polymerase II transcription factor activity, enhancer binding  transcription coactivator activity  signal transducer activity  nucleus  cytoplasm  regulation of transcription, DNA-dependent  signal transduction  positive regulation vascular endothelial growth factor production  aryl hydrocarbon receptor binding  cell differentiation  positive regulation of vascular endothelial growth factor receptor signaling pathway  mRNA transcription from RNA polymerase II promoter  positive regulation of gene-specific transcription  sequence-specific DNA binding  regulation of transcription from RNA polymerase II promoter in response to oxidative stress  positive regulation of erythrocyte differentiation  positive regulation of glycolysis  positive regulation of transcription  positive regulation of transcription from RNA polymerase II promoter  positive regulation of hormone biosynthetic process  protein heterodimerization activity  
Pathways : BIOCARTAAhr Signal Transduction Pathway [Genes]    Erythropoietin mediated neuroprotection through NF-kB [Genes]    Hypoxia-Inducible Factor in the Cardiovascular System [Genes]    VEGF, Hypoxia, and Angiogenesis [Genes]   
Pathways : KEGG
Other databases
Probes
Probes : ImagenesARNT Related clones (RZPD - Berlin)
Literature
PubMed92 Pubmed reference(s) in Entrez
PubGeneARNT

Bibliography

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REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written10-2004Oliver Hankinson
UCLA Medical Center, Center for the Health Sciences, Box 951732,Los Angeles, CA 90095-1732, USA

Citation

This paper should be referenced as such :
Hankinson O . ARNT aryl hydrocarbon receptor nuclear translocator. Atlas Genet Cytogenet Oncol Haematol. October 2004 .
URL : http://AtlasGeneticsOncology.org/Genes/ARNTID223ch1q21.html

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