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

Identity

Other namesDDX9
LKP
NDHII
RHA
NDH2
leukophysin
HGNC (Hugo) DHX9
LocusID (NCBI) 1660
Location 1q25.3
Location_base_pair Starts at 182808439 and ends at 182857117 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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

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.
  

External links

Nomenclature
HGNC (Hugo)DHX9   2750
Entrez_Gene (NCBI)DHX9  1660  DEAH (Asp-Glu-Ala-His) box polypeptide 9
Cards
AtlasDHX9ID702ch1q25
GeneCards (Weizmann)DHX9
Ensembl (Hinxton)ENSG00000135829 [Gene_View]  chr1:182808439-182857117 [Contig_View]  DHX9 [Vega]
AceView (NCBI)DHX9
Genatlas (Paris)DHX9
SOURCE (Stanford)NM_001357 NM_030588
Genomic and cartography
GoldenPath (UCSC)DHX9  -  1q25.3   chr1:182808439-182857117 +  1q25   [Description]    (hg19-Feb_2009)
EnsemblDHX9 - 1q25 [CytoView]
Mapping of homologs : NCBIDHX9 [Mapview]
OMIM603115   
Gene and transcription
Genbank (Entrez)AA836637 AB451248 AB451372 AF086352 AK096582
RefSeq transcript (SRS)NM_001357 NM_030588
RefSeq transcript (Entrez)NM_001357 NM_030588
RefSeq genomic (SRS)AC_000133 NC_000001 NC_018912 NG_029930 NT_004487 NW_001838533 NW_004077999
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NG_029930 NT_004487 NW_001838533 NW_004077999
Consensus coding sequences : CCDS (NCBI)DHX9
Cluster EST : UnigeneHs.191518 [ SRS ] Hs.191518 [ NCBI ]
CGAP (NCI)Hs.191518
Alternative Splicing GalleryENSG00000135829
Gene ExpressionDHX9 [ NCBI-GEO ]   DHX9 [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ08211 (SRS) Q08211 (Uniprot)
NextProtQ08211
With graphics : InterProQ08211
Splice isoforms : SwissVarQ08211(Swissvar)
Domaine pattern : Prosite (SRS)DEAH_ATP_HELICASE (PS00690)    DS_RBD (PS50137)    HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)   
Domaine pattern : Prosite (Expaxy)DEAH_ATP_HELICASE (PS00690)    DS_RBD (PS50137)    HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)   
Domains : Interpro (SRS)DNA/RNA_helicase_DEAD/DEAH_N    DNA/RNA_helicase_DEAH_CS    Ds-RNA-bd    dsRNA-bd-like_dom    DUF1605    Helicase-assoc_dom    Helicase_ATP-bd    Helicase_C   
Domains : Interpro (EBI)DNA/RNA_helicase_DEAD/DEAH_N    DNA/RNA_helicase_DEAH_CS    Ds-RNA-bd    dsRNA-bd-like_dom    DUF1605    Helicase-assoc_dom    Helicase_ATP-bd    Helicase_C   
Related proteins : CluSTrQ08211
Domain families : Pfam (SRS)DEAD (PF00270)    dsrm (PF00035)    HA2 (PF04408)    Helicase_C (PF00271)    OB_NTP_bind (PF07717)   
Domain families : Pfam (Sanger)DEAD (PF00270)    dsrm (PF00035)    HA2 (PF04408)    Helicase_C (PF00271)    OB_NTP_bind (PF07717)   
Domain families : Pfam (NCBI)pfam00270    pfam00035    pfam04408    pfam00271    pfam07717   
Domain families : Smart (EMBL)DEXDc (SM00487)  DSRM (SM00358)  HA2 (SM00847)  HELICc (SM00490)  
DMDM1660
Blocks (Seattle)Q08211
PDB (SRS)3LLM    3VYX    3VYY   
PDB (PDBSum)3LLM    3VYX    3VYY   
PDB (IMB)3LLM    3VYX    3VYY   
PDB (RSDB)3LLM    3VYX    3VYY   
Human Protein AtlasENSG00000135829
HPRD04386
IPIIPI00844578   IPI00921264   
Protein Interaction databases
DIP (DOE-UCLA)Q08211
IntAct (EBI)Q08211
FunCoupENSG00000135829
REACTOMEDHX9
Protein Interaction Database1660
BioGRIDDHX9
InParanoidQ08211
Interologous Interaction database Q08211
IntegromeDBDHX9
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)DHX9
SNP (GeneSNP Utah)DHX9
SNP : HGBaseDHX9
Genetic variants : HAPMAPDHX9
Somatic Mutations in Cancer : COSMICDHX9 
CONAN: Copy Number AnalysisDHX9 
Mutations and Diseases : HGMDDHX9
OMIM603115   
GENETests603115   
Disease Genetic AssociationDHX9
Huge Navigator DHX9 [HugePedia]  DHX9 [HugeCancerGEM]
Genomic VariantsDHX9  DHX9 [DGVbeta]
ClinVarDHX9
snp3D : Map Gene to Disease1660
General knowledge
Homologs : HomoloGeneDHX9
Homology/Alignments : Family Browser (UCSC)DHX9
Phylogenetic Trees/Animal Genes : TreeFamDHX9
Catalytic activity : Enzyme3.6.4.13 [ Enzyme-Expasy ]   3.6.4.13 [ Enzyme-SRS ]   3.6.4.13 [ IntEnz-EBI ]   3.6.4.13 [ BRENDA ]   3.6.4.13 [ KEGG ]   
Chemical/Protein Interactions : CTD1660
Chemical/Pharm GKB GenePA27232
Clinical trialDHX9
Cancer Resource (Charite)ENSG00000135829
Ontology : AmiGOmRNA splicing, via spliceosome  RNA polymerase II transcription factor binding  DNA binding  RNA helicase activity  double-stranded RNA binding  ATP-dependent DNA helicase activity  ATP-dependent RNA helicase activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleolus  cytoplasm  centrosome  circadian rhythm  RNA splicing  gene expression  ribonucleoprotein complex  cellular response to heat  CRD-mediated mRNA stabilization  CRD-mediated mRNA stability complex  
Ontology : EGO-EBImRNA splicing, via spliceosome  RNA polymerase II transcription factor binding  DNA binding  RNA helicase activity  double-stranded RNA binding  ATP-dependent DNA helicase activity  ATP-dependent RNA helicase activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleolus  cytoplasm  centrosome  circadian rhythm  RNA splicing  gene expression  ribonucleoprotein complex  cellular response to heat  CRD-mediated mRNA stabilization  CRD-mediated mRNA stability complex  
Other databases
Probes
Litterature
PubMed143 Pubmed reference(s) in Entrez
PubGeneDHX9
iHOPDHX9

Bibliography

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Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells.
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RNA helicase A interacts with dsDNA and topoisomerase IIalpha.
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Nucleic Acids Res. 2003 May 1;31(9):2253-60.
PMID 12711669
 
A functional interaction between RHA and Ubc9, an E2-like enzyme specific for Sumo-1.
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J Mol Biol. 2004 Jul 30;341(1):15-25.
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RNA helicase A interacts with nuclear factor kappaB p65 and functions as a transcriptional coactivator.
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Eur J Biochem. 2004 Sep;271(18):3741-51.
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Analysis of the RNA helicase A gene in human lung cancer.
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Nuclear DNA helicase II (RNA helicase A) binds to an F-actin containing shell that surrounds the nucleolus.
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DNA-dependent protein kinase (DNA-PK) phosphorylates nuclear DNA helicase II/RNA helicase A and hnRNP proteins in an RNA-dependent manner.
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RNA helicase A in the MEF1 transcription factor complex up-regulates the MDR1 gene in multidrug-resistant cancer cells.
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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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The nuclear import of RNA helicase A is mediated by importin-alpha3.
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RNA helicase A is necessary for translation of selected messenger RNAs.
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Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A.
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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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RNA helicase A interacts with RISC in human cells and functions in RISC loading.
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PMID 17531811
 
The p53 target protein Wig-1 binds hnRNP A2/B1 and RNA Helicase A via RNA.
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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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Contributor(s)

Written07-2009Frédéric Guénard, Francine Durocher
Cancer Genomics Laboratory, Oncology and Molecular Endocrinology Research Centre, CRCHUL, CHUQ and Laval University, Québec, G1V 4G2, Canada

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. July 2009 .
URL : http://AtlasGeneticsOncology.org/Genes/DHX9ID702ch1q25.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/44773/1/07-2009-DHX9ID702ch1q25.pdf   [ Bibliographic record ]

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