ARNT

Identity

Other names	HIF-1b
HGNC	ARNT
Location	1q21

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	ARNT   700
Entrez_Gene	ARNT  405  aryl hydrocarbon receptor nuclear translocator
	Cards
Atlas	ARNTID223ch1q21
GeneCards	ARNT
Ensembl	ARNT [Search_View]   ENSG00000143437 [Gene_View]
Genatlas	ARNT
GeneLynx	ARNT
eGenome	ARNT
euGene	405
	Genomic and cartography
GoldenPath	ARNT  -  1q21   chr1:149048810-149115810 -  1q21   [Description]    (hg18-Mar_2006)
Ensembl	ARNT - 1q21 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	ARNT
	Gene and transcription
Genbank	AB209877 [ ENTREZ ]
Genbank	AF001307 [ ENTREZ ]
Genbank	AK223459 [ ENTREZ ]
Genbank	AK290177 [ ENTREZ ]
Genbank	AK291705 [ ENTREZ ]
RefSeq	NM_001668 [ SRS ]    NM_001668 [ ENTREZ ]
RefSeq	NM_178426 [ SRS ]    NM_178426 [ ENTREZ ]
RefSeq	NM_178427 [ SRS ]    NM_178427 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NT_004487 [ SRS ]    NT_004487 [ ENTREZ ]
RefSeq	NW_001838529 [ SRS ]    NW_001838529 [ ENTREZ ]
RefSeq	NW_925683 [ SRS ]    NW_925683 [ ENTREZ ]
AceView	ARNT AceView - NCBI
Unigene	Hs.632446 [ SRS ]    Hs.632446 [ NCBI ]     HS632446 [ spliceNest ]
Fast-db	17248 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O43392 [ SRS]    O43392 [ EXPASY ]     O43392 [ INTERPRO ]     O43392 [ UNIPROT ]
Prosite	PS50888 HLH [ SRS ]    PS50888 HLH [ Expasy ]
Prosite	PS50112 PAS [ SRS ]    PS50112 PAS [ Expasy ]
Interpro	IPR001092 HLH_basic [ SRS ]    IPR001092 HLH_basic [ EBI ]
Interpro	IPR011598 HLH_DNA_bd [ SRS ]    IPR011598 HLH_DNA_bd [ EBI ]
Interpro	IPR001067 Nuc_translocat [ SRS ]    IPR001067 Nuc_translocat [ EBI ]
Interpro	IPR000014 PAS [ SRS ]    IPR000014 PAS [ EBI ]
Interpro	IPR013767 PAS_fold [ SRS ]    IPR013767 PAS_fold [ EBI ]
CluSTr	O43392
Pfam	PF00010 HLH [ SRS ]    PF00010 HLH [ Sanger ]    pfam00010 [ NCBI-CDD ]
Pfam	PF00989 PAS [ SRS ]    PF00989 PAS [ Sanger ]    pfam00989 [ NCBI-CDD ]
Smart	SM00353 HLH [EMBL]
Smart	SM00091 PAS [EMBL]
Blocks	O43392
HPRD	00524
	Protein Interaction databases
DIP	O43392
IntAct	O43392
	Polymorphism : SNP, mutations, diseases
OMIM	126110    [ map ]
GENECLINICS	126110
SNP	ARNT [dbSNP-NCBI]
SNP	NM_001668 [SNP-NCI]
SNP	NM_178426 [SNP-NCI]
SNP	NM_178427 [SNP-NCI]
SNP	ARNT [GeneSNPs - Utah]  ARNT] [HGBASE - SRS]
HAPMAP	ARNT [HAPMAP]
COSMIC	ARNT [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	ARNT
	General knowledge
Family Browser	ARNT [UCSC Family Browser]
SOURCE	NM_001668
SOURCE	NM_178426
SOURCE	NM_178427
SMD	Hs.632446
SAGE	Hs.632446
GO	response to hypoxia [Amigo]  response to hypoxia
GO	positive regulation of endothelial cell proliferation [Amigo]  positive regulation of endothelial cell proliferation
GO	transcription factor activity [Amigo]  transcription factor activity
GO	RNA polymerase II transcription factor activity, enhancer binding [Amigo]  RNA polymerase II transcription factor activity, enhancer binding
GO	transcription coactivator activity [Amigo]  transcription coactivator activity
GO	signal transducer activity [Amigo]  signal transducer activity
GO	receptor activity [Amigo]  receptor activity
GO	aryl hydrocarbon receptor nuclear translocator activity [Amigo]  aryl hydrocarbon receptor nuclear translocator activity
GO	nucleus [Amigo]  nucleus
GO	nucleus [Amigo]  nucleus
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	signal transduction [Amigo]  signal transduction
GO	positive regulation vascular endothelial growth factor production [Amigo]  positive regulation vascular endothelial growth factor production
GO	transcription activator activity [Amigo]  transcription activator activity
GO	aryl hydrocarbon receptor binding [Amigo]  aryl hydrocarbon receptor binding
GO	positive regulation of vascular endothelial growth factor receptor signaling pathway [Amigo]  positive regulation of vascular endothelial growth factor receptor signaling pathway
GO	mRNA transcription from RNA polymerase II promoter [Amigo]  mRNA transcription from RNA polymerase II promoter
GO	positive regulation of gene-specific transcription [Amigo]  positive regulation of gene-specific transcription
GO	sequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GO	regulation of transcription from RNA polymerase II promoter in response to oxidative stress [Amigo]  regulation of transcription from RNA polymerase II promoter in response to oxidative stress
GO	positive regulation of erythrocyte differentiation [Amigo]  positive regulation of erythrocyte differentiation
GO	positive regulation of glycolysis [Amigo]  positive regulation of glycolysis
GO	positive regulation of hormone biosynthetic process [Amigo]  positive regulation of hormone biosynthetic process
GO	protein heterodimerization activity [Amigo]  protein heterodimerization activity
BIOCARTA	Ahr Signal Transduction Pathway    [Genes]
BIOCARTA	Erythropoietin mediated neuroprotection through NF-kB    [Genes]
BIOCARTA	Hypoxia-Inducible Factor in the Cardiovascular System    [Genes]
BIOCARTA	VEGF, Hypoxia, and Angiogenesis    [Genes]
PubGene	ARNT
TreeFam	ARNT
CTD	405 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	ARNT Related clones (RZPD - Berlin)
	PubMed
PubMed	70 Pubmed reference(s) in LocusLink

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Contributor(s)

Written	10-2004	Oliver 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. Atlas Genet Cytogenet Oncol Haematol. October 2004 . URL : http://AtlasGeneticsOncology.org/Genes/ARNTID223ch1q21.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:12:11 2008