Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   
X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

ARNT (aryl hydrocarbon receptor nuclear translocator)

Identity

Other namesHIF-1b
HGNC (Hugo) ARNT
LocusID (NCBI) 405
Location 1q21
Location_base_pair Starts at 150782181 and ends at 150849244 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

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]  chr1:150782181-150849244 [Contig_View]  ARNT [Vega]
AceView (NCBI)ARNT
Genatlas (Paris)ARNT
euGene (Indiana)405
SOURCE (Stanford)NM_001197325 NM_001668 NM_178426 NM_178427
Genomic and cartography
GoldenPath (UCSC)ARNT  -  1q21   chr1:150782181-150849244 -  1q21   [Description]    (hg19-Feb_2009)
EnsemblARNT - 1q21 [CytoView]
Mapping of homologs : NCBIARNT [Mapview]
OMIM126110   
Gene and transcription
Genbank (Entrez)AB209877 AF001307 AK223459 AK290177 AK291705
RefSeq transcript (SRS)NM_001197325 NM_001668 NM_178426 NM_178427
RefSeq transcript (Entrez)NM_001197325 NM_001668 NM_178426 NM_178427
RefSeq genomic (SRS)AC_000133 NC_000001 NG_011848 NG_028248 NT_004487 NW_001838529
RefSeq genomic (Entrez)AC_000133 NC_000001 NG_011848 NG_028248 NT_004487 NW_001838529
Consensus coding sequences : CCDS (NCBI)ARNT
Cluster EST : UnigeneHs.632446 [ SRS ] Hs.632446 [ NCBI ]
Alternative Splicing : Fast-db (Paris)17248
Alternative Splicing GalleryENSG00000143437
Gene ExpressionARNT [ NCBI-GEO ]   ARNT [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP27540 (SRS) P27540 (Uniprot)
With graphics : InterProP27540
Splice isoforms : SwissVarP27540(Swissvar)
Domaine pattern : Prosite (SRS)HLH (PS50888)    PAC (PS50113)    PAS (PS50112)   
Domaine pattern : Prosite (Expaxy)HLH (PS50888)    PAC (PS50113)    PAS (PS50112)   
Domains : Interpro (SRS)HLH_DNA-bd    Nuc_translocat    PAC    PAS    PAS_fold    PAS_fold_3   
Domains : Interpro (EBI)HLH_DNA-bd    Nuc_translocat    PAC    PAS    PAS_fold    PAS_fold_3   
Related proteins : CluSTrP27540
Domain families : Pfam (SRS)HLH (PF00010)    PAS (PF00989)    PAS_3 (PF08447)   
Domain families : Pfam (Sanger)HLH (PF00010)    PAS (PF00989)    PAS_3 (PF08447)   
Domain families : Pfam (NCBI)pfam00010    pfam00989    pfam08447   
Domain families : Smart (EMBL)HLH (SM00353)  PAC (SM00086)  PAS (SM00091)  
Blocks (Seattle)P27540
PDB (SRS)1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P    3H7W    3H82   
PDB (PDBSum)1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P    3H7W    3H82   
PDB (IMB)1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P    3H7W    3H82   
PDB (RSDB)1D7G    1X0O    2A24    2ARN    2B02    2HV1    2K7S    3F1N    3F1O    3F1P    3H7W    3H82   
Human Protein AtlasENSG00000143437
HPRD00524
IPIIPI00514749   IPI00218287   IPI00922490   IPI00910290   IPI00964540   IPI00965109   IPI00968237   
Protein Interaction databases
DIP (DOE-UCLA)P27540
IntAct (EBI)P27540
FunCoupENSG00000143437
REACTOMEARNT
BioGRIDARNT
InParanoidP27540
Interologous Interaction database P27540
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ARNT
SNP (GeneSNP Utah)ARNT
SNP : HGBaseARNT
Genetic variants : HAPMAPARNT
Cancer Gene: CensusARNT 
Somatic Mutations in Cancer : COSMICARNT 
CONAN: Copy Number AnalysisARNT 
Translocation Breakpoints in Cancer : TICdbARNT 
Mutations and Diseases : HGMDARNT
OMIM126110   
GENETests126110   
Disease Genetic AssociationARNT
Huge Navigator ARNT [HugePedia]  ARNT [HugeCancerGEM]
Genomic VariantsARNT
snp3D : Map Gene to Disease405
General knowledge
Homologs : HomoloGeneARNT
Homology/Alignments : Family Browser (UCSC)ARNT
Phylogenetic Trees/Animal Genes : TreeFamARNT
Chemical/Protein Interactions : CTD405
Chemical/Pharm GKB GenePA24994
Clinical trialARNT
Cancer Resource (Charite)ENSG00000143437
Ontology : AmiGOresponse to hypoxia  embryonic placenta development  positive regulation of endothelial cell proliferation  sequence-specific DNA binding transcription factor activity  sequence-specific distal enhancer binding RNA polymerase II transcription factor activity  transcription coactivator activity  signal transducer activity  aryl hydrocarbon receptor activity  protein binding  nucleus  transcription factor complex  cytoplasm  transcription, DNA-dependent  regulation of transcription, DNA-dependent  transcription factor binding  positive regulation vascular endothelial growth factor production  aryl hydrocarbon receptor binding  cell differentiation  positive regulation of vascular endothelial growth factor receptor signaling pathway  positive regulation of protein sumoylation  mRNA transcription from RNA polymerase II promoter  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, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  positive regulation of hormone biosynthetic process  protein heterodimerization activity  
Ontology : EGO-EBIresponse to hypoxia  embryonic placenta development  positive regulation of endothelial cell proliferation  sequence-specific DNA binding transcription factor activity  sequence-specific distal enhancer binding RNA polymerase II transcription factor activity  transcription coactivator activity  signal transducer activity  aryl hydrocarbon receptor activity  protein binding  nucleus  transcription factor complex  cytoplasm  transcription, DNA-dependent  regulation of transcription, DNA-dependent  transcription factor binding  positive regulation vascular endothelial growth factor production  aryl hydrocarbon receptor binding  cell differentiation  positive regulation of vascular endothelial growth factor receptor signaling pathway  positive regulation of protein sumoylation  mRNA transcription from RNA polymerase II promoter  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, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  positive regulation of hormone biosynthetic process  protein heterodimerization activity  
Pathways : BIOCARTAHypoxia-Inducible Factor in the Cardiovascular System [Genes]    Erythropoietin mediated neuroprotection through NF-kB [Genes]    VEGF, Hypoxia, and Angiogenesis [Genes]    Ahr Signal Transduction Pathway [Genes]   
Other databases
Probes
Probes : ImagenesARNT Related clones (RZPD - Berlin)
Litterature
PubMed117 Pubmed reference(s) in Entrez
PubGeneARNT
iHOPARNT

Bibliography

Cloning of a factor required for activity of the Ah (dioxin) receptor.
Hoffman EC, Reyes H, Chu FF, Sander F, Conley LH, Brooks BA, Hankinson O
Science (New York, N.Y.). 1991 ; 252 (5008) : 954-958.
PMID 1852076
 
Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor.
Reyes H, Reisz-Porszasz S, Hankinson O
Science (New York, N.Y.). 1992 ; 256 (5060) : 1193-1195.
PMID 1317062
 
The Ah receptor nuclear translocator gene (ARNT) is located on q21 of human chromosome 1 and on mouse chromosome 3 near Cf-3.
Johnson B, Brooks BA, Heinzmann C, Diep A, Mohandas T, Sparkes RS, Reyes H, Hoffman E, Lange E, Gatti RA
Genomics. 1993 ; 17 (3) : 592-598.
PMID 8244375
 
Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT).
Reisz-Porszasz S, Probst MR, Fukunaga BN, Hankinson O
Molecular and cellular biology. 1994 ; 14 (9) : 6075-6086.
PMID 8065341
 
Orientation of the heterodimeric aryl hydrocarbon (dioxin) receptor complex on its asymmetric DNA recognition sequence.
Bacsi SG, Reisz-Porszasz S, Hankinson O
Molecular pharmacology. 1995 ; 47 (3) : 432-438.
PMID 7700240
 
DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins.
Swanson HI, Chan WK, Bradfield CA
The Journal of biological chemistry. 1995 ; 270 (44) : 26292-26302.
PMID 7592839
 
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
Wang GL, Jiang BH, Rue EA, Semenza GL
Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (12) : 5510-5514.
PMID 7539918
 
The role of the aryl hydrocarbon receptor nuclear translocator (ARNT) in hypoxic induction of gene expression. Studies in ARNT-deficient cells.
Wood SM, Gleadle JM, Pugh CW, Hankinson O, Ratcliffe PJ
The Journal of biological chemistry. 1996 ; 271 (25) : 15117-15123.
PMID 8662957
 
ARNT-deficient mice and placental differentiation.
Kozak KR, Abbott B, Hankinson O
Developmental biology. 1997 ; 191 (2) : 297-305.
PMID 9398442
 
Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT.
Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC
Nature. 1997 ; 386 (6623) : 403-407.
PMID 9121557
 
A 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, Zhang J, Hankinson O
The Journal of biological chemistry. 1997 ; 272 (50) : 31845-31854.
PMID 9395531
 
Aryl hydrocarbon (Ah) nonresponsiveness in estrogen receptor-negative MDA-MB-231 cells is associated with expression of a variant arnt protein.
Wilson CL, Thomsen J, Hoivik DJ, Wormke MT, Stanker L, Holtzapple C, Safe SH
Archives of biochemistry and biophysics. 1997 ; 346 (1) : 65-73.
PMID 9328285
 
The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.
Salomon-Nguyen F, Della-Valle V, Mauchauffe M, Busson-Le Coniat M, Ghysdael J, Berger R, Bernard OA
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (12) : 6757-6762.
PMID 10829078
 
Genomic structure of the human Ah receptor nuclear translocator gene (hARNT).
Scheel J, Schrenk D
Human genetics. 2000 ; 107 (4) : 397-399.
PMID 11129342
 
Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt.
Keith B, Adelman DM, Simon MC
Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (12) : 6692-6697.
PMID 11381139
 
Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex.
Beischlag TV, Wang S, Rose DW, Torchia J, Reisz-Porszasz S, Muhammad K, Nelson WE, Probst MR, Rosenfeld MG, Hankinson O
Molecular and cellular biology. 2002 ; 22 (12) : 4319-4333.
PMID 12024042
 
Variability of the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene.
Scheel J, Hussong R, Schrenk D, Schmitz HJ
Journal of human genetics. 2002 ; 47 (5) : 217-224.
PMID 12032587
 
The aryl hydrocarbon receptor nuclear transporter is modulated by the SUMO-1 conjugation system.
Tojo M, Matsuzaki K, Minami T, Honda Y, Yasuda H, Chiba T, Saya H, Fujii-Kuriyama Y, Nakao M
The Journal of biological chemistry. 2002 ; 277 (48) : 46576-46585.
PMID 12354770
 
The basic helix-loop-helix-PAS protein ARNT functions as a potent coactivator of estrogen receptor-dependent transcription.
Brunnberg S, Pettersson K, Rydin E, Matthews J, Hanberg A, Pongratz I
Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (11) : 6517-6522.
PMID 12754377
 
Modulation of oestrogen receptor signalling by association with the activated dioxin receptor.
Ohtake F, Takeyama K, Matsumoto T, Kitagawa H, Yamamoto Y, Nohara K, Tohyama C, Krust A, Mimura J, Chambon P, Yanagisawa J, Fujii-Kuriyama Y, Kato S
Nature. 2003 ; 423 (6939) : 545-550.
PMID 12774124
 
Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function.
Takagi S, Tojo H, Tomita S, Sano S, Itami S, Hara M, Inoue S, Horie K, Kondoh G, Hosokawa K, Gonzalez FJ, Takeda J
The Journal of clinical investigation. 2003 ; 112 (9) : 1372-1382.
PMID 14597763
 
Recruitment 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, Taylor RT, Rose DW, Yoon D, Chen Y, Lee WH, Rosenfeld MG, Hankinson O
The Journal of biological chemistry. 2004 ; 279 (52) : 54620-54628.
PMID 15485806
 
Patent ductus venosus and dioxin resistance in mice harboring a hypomorphic Arnt allele.
Walisser JA, Bunger MK, Glover E, Harstad EB, Bradfield CA
The Journal of biological chemistry. 2004 ; 279 (16) : 16326-16331.
PMID 14764592
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

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

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38129/1/10-2004-ARNTID223ch1q21.pdf   [ Bibliographic record ]

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Apr 28 15:09:02 CEST 2012
Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.