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DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9)

Written2009-07Frédéric Guénard, Francine Durocher
Cancer Genomics Laboratory, Oncology, Molecular Endocrinology Research Centre, CRCHUL, CHUQ, Laval University, Québec, G1V 4G2, Canada

(Note : for Links provided by Atlas : click)

Identity

Other aliasDDX9
LKP
NDHII
RHA
NDH2
leukophysin
LocusID (NCBI) 1660
Atlas_Id 44879
Location 1q25.3  [Link to chromosome band 1q25]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Description The gene spans 48.5 kb and is composed of 27 exons.
Transcription Transcription start is 163 bp upstream of first ATG of the DHX9 ORF. The translation start site is located in exon 2 and there is a sole isoform ubiquitously expressed.
Pseudogene DHX9 pseudogene (DHX9P) is located at 13q22.

Protein

 
  Structure of DHX9. dsRBD, double-stranded RNA binding domain; RGG, arginine and glycine-rich region; NTD, nuclear transport domain.
Description Monomeric 140 kDa protein. Human DHX9 is 1270 amino acids. It contains an helicase catalytic domain flanked by two double-stranded RNA binding domains (dsRBD) at the N-terminus and an RGG-box at the C terminus. A bidirectional nuclear transport domain is located at the C terminus.
Expression All tissues tested, ubiquitous expression.
Localisation DHX9 shuttles between the nucleus and the cytoplasm.
Function DHX9 is a nucleic-acid helicase that unwinds double-stranded DNA and RNA in a nucleotide dependent manner. It acts as a transcriptional coactivator which stimulates transcription by interacting with the transcriptional coactivator CBP/p300, the breast cancer protein BRCA1, the RNA polymerase II and has an important role in the assembly of STAT6 transcriptosome.
DHX9 plays a role in regulating chromatin structure by interacting physically and functionally with topoisomerase IIa.
It mediates the attachment of nuclear ribonucleoprotein complexes to actin filaments, which may be related to RNA processing and transport. DHX9 interacts with the survival motor neuron which plays a role in the assembly and regeneration of small nuclear ribonucleoproteins and spliceosomes.
DHX9 acts as a nuclear shuttle protein promoting the export of mRNA transcripts through binding to TAP and HAP95.
In the cytoplasm, DHX9 is preferentially associated with actively translating polyribosomes and is necessary for efficient translation of RNAs that contain a highly structured 5'UTR.
DHX9 might be necessary for maintaining genomic stability as it plays a role in promoting the DNA processing function of WRN. Overexpression of a truncated DHX9 peptide prevents normal BRCA1 function, such as BRCA1 association with nuclear foci following DNA damage. DHX9 associates with gH2AX after DNA damage, suggesting a role for DHX9 in DNA repair.
DHX9 is also necessary for early embryonic development in mice.
Homology Sequence analysis revealed that DHX9 contains seven helicase core motifs that are conserved among the DEX[D/H] helicase superfamily. DHX9 is highly conserved among man, cow, mouse, worm, and fruit fly.

Mutations

Note DHX9 truncating mutations were reported to affect the interaction with BRCA1 and RNA polymerase II, and to result in decreased transcriptional activity of BRCA1.
In mammals, DHX9-knockout mice are embryonic lethal for homozygous DHX9 mutants. DHX9 is thus necessary for early embryonic development in mice. It was also suggested that DHX9 is required for the survival and differentiation of embryonic ectoderm.
DHX9 maps to chromosome 1q25 near a major susceptibility locus for prostate cancer.

Implicated in

Note
  
Entity Lung cancer
Note DHX9 is over-expressed in tumor samples compared to normal lung tissues. There was a tendency for higher expression levels in small cell lung cancer compared to non-small cell carcinomas.
Prognosis There was no correlation with tumor stage and survival.
  
  
Entity Breast cancer
Note Involvement of DHX9 in breast cancer susceptibility was analyzed in a cohort of breast cancer individuals from non-BRCA1/BRCA2 French Canadian families. This study did not identify any deleterious truncating mutation or aberrant splicing in the DHX9 gene. It was concluded that studies on much bigger cohorts are needed to fully evaluate the association of variants identified with breast cancer risk.
  
  
Entity Systemic lupus erythematosus (SLE)
Note Anti-DHX9 is a new serologic marker for SLE. The production of anti-DHX9 may depend on a process restricted to early SLE, or it may be highly sensitive to treatment.
Disease Systemic lupus erythematosus (SLE) is a largely genetically based disease in which environmental factors are also involved. SLE is an autoimmune disease characterized by autoantibody production and involvement of multiple organ systems. Variable manifestations and outcome reflect the clinical heterogeneity of the disease. It is characterized by acute and chronic inflammation of various tissues of the body including joints, kidneys, mucous membranes, and blood vessel walls.
Prognosis Among patients with SLE, anti-DHX9 was common in young patients and at an early stage of the disease.
  

Bibliography

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The nuclear import of RNA helicase A is mediated by importin-alpha3.
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A functional interaction between RHA and Ubc9, an E2-like enzyme specific for Sumo-1.
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Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase and stimulates its exonuclease activity.
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A Role of RNA Helicase A in cis-Acting Transactivation Response Element-mediated Transcriptional Regulation of Human Immunodeficiency Virus Type 1.
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Genetic sequence variations of BRCA1-interacting genes AURKA, BAP1, BARD1 and DHX9 in French Canadian Families with high risk of breast cancer.
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RNA helicase A is necessary for translation of selected messenger RNAs.
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ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A.
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The human RNA helicase A (DDX9) gene maps to the prostate cancer susceptibility locus at chromosome band 1q25 and its pseudogene (DDX9P) to 13q22, respectively.
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The p53 target protein Wig-1 binds hnRNP A2/B1 and RNA Helicase A via RNA.
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RNA helicase A interacts with RISC in human cells and functions in RISC loading.
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Association of RNA helicase a with human immunodeficiency virus type 1 particles.
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Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses.
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Citation

This paper should be referenced as such :
Guénard F, Durocher F
DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/DHX9ID44879ch1q25.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  t(1;1)(p33;q25) DHX9/TAL1
DHX9/NPL (1q25)
t(1;1)(p33;q25) DHX9/TAL1
DHX9/NPL (1q25)


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  DHX9/ZBTB37 (1q25)
t(1;5)(q25;q35) DHX9/PRELID1


External links

Nomenclature
Cards
AtlasDHX9ID44879ch1q25.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)1660
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:33:45 CEST 2018

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