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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

Alias_namesLKP
DDX9
DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 9
DEAH (Asp-Glu-Ala-His) box helicase 9
Alias_symbol (synonym)RHA
Other aliasNDHII
NDH2
leukophysin
HGNC (Hugo) DHX9
LocusID (NCBI) 1660
Atlas_Id 44879
Location 1q25.3  [Link to chromosome band 1q25]
Location_base_pair Starts at 182839304 and ends at 182887982 bp from pter ( according to hg19-Feb_2009)  [Mapping DHX9.png]

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

Aromatic residues are required for RNA helicase A mediated transactivation.
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Int J Mol Med. 2003 Aug;12(2):175-80.
PMID 12851713
 
The nuclear import of RNA helicase A is mediated by importin-alpha3.
Aratani S, Oishi T, Fujita H, Nakazawa M, Fujii R, Imamoto N, Yoneda Y, Fukamizu A, Nakajima T.
Biochem Biophys Res Commun. 2006 Feb 3;340(1):125-33.
PMID 16375861
 
A functional interaction between RHA and Ubc9, an E2-like enzyme specific for Sumo-1.
Argasinska J, Zhou K, Donnelly RJ, Hay RT, Lee CG.
J Mol Biol. 2004 Jul 30;341(1):15-25.
PMID 15312759
 
Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase and stimulates its exonuclease activity.
Friedemann J, Grosse F, Zhang S.
J Biol Chem. 2005 Sep 2;280(35):31303-13. Epub 2005 Jul 1.
PMID 15995249
 
A Role of RNA Helicase A in cis-Acting Transactivation Response Element-mediated Transcriptional Regulation of Human Immunodeficiency Virus Type 1.
Fujii R, Okamoto M, Aratani S, Oishi T, Ohshima T, Taira K, Baba M, Fukamizu A, Nakajima T.
J Biol Chem. 2001 Feb 23;276(8):5445-51. Epub 2000 Nov 28.
PMID 11096080
 
Genetic sequence variations of BRCA1-interacting genes AURKA, BAP1, BARD1 and DHX9 in French Canadian Families with high risk of breast cancer.
Guenard F, Labrie Y, Ouellette G, Joly Beauparlant C, Durocher F.
J Hum Genet. 2009;54(3):152-61. Epub 2009 Feb 6.
PMID 19197335
 
RNA helicase A is necessary for translation of selected messenger RNAs.
Hartman TR, Qian S, Bolinger C, Fernandez S, Schoenberg DR, Boris-Lawrie K.
Nat Struct Mol Biol. 2006 Jun;13(6):509-16. Epub 2006 May 7.
PMID 16680162
 
ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A.
Ishiguro A, Ideta M, Mikoshiba K, Chen DJ, Aruga J.
J Biol Chem. 2007 Mar 30;282(13):9983-95. Epub 2007 Jan 23.
PMID 17251188
 
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.
Lee CG, Eki T, Okumura K, Nogami M, Soares Vda C, Murakami Y, Hanaoka F, Hurwitz J.
Somat Cell Mol Genet. 1999 Jan;25(1):33-9.
PMID 10925702
 
The p53 target protein Wig-1 binds hnRNP A2/B1 and RNA Helicase A via RNA.
Prahl M, Vilborg A, Palmberg C, Jornvall H, Asker C, Wiman KG.
FEBS Lett. 2008 Jun 25;582(15):2173-7. Epub 2008 Jun 2.
PMID 18519039
 
RNA helicase A interacts with RISC in human cells and functions in RISC loading.
Robb GB, Rana TM.
Mol Cell. 2007 May 25;26(4):523-37.
PMID 17531811
 
Association of RNA helicase a with human immunodeficiency virus type 1 particles.
Roy BB, Hu J, Guo X, Russell RS, Guo F, Kleiman L, Liang C.
J Biol Chem. 2006 May 5;281(18):12625-35. Epub 2006 Mar 8.
PMID 16527808
 
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.
Schlegel BP, Starita LM, Parvin JD.
Oncogene. 2003 Feb 20;22(7):983-91.
PMID 12592385
 
Specific interaction between RNA helicase A and Tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus.
Tang H, Wong-Staal F.
J Biol Chem. 2000 Oct 20;275(42):32694-700.
PMID 10924507
 
RNA helicase A interacts with nuclear factor kappaB p65 and functions as a transcriptional coactivator.
Tetsuka T, Uranishi H, Sanda T, Asamitsu K, Yang JP, Wong-Staal F, Okamoto T.
Eur J Biochem. 2004 Sep;271(18):3741-51.
PMID 15355351
 
Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A.
Toretsky JA, Erkizan V, Levenson A, Abaan OD, Parvin JD, Cripe TP, Rice AM, Lee SB, Uren A.
Cancer Res. 2006 Jun 1;66(11):5574-81.
PMID 16740692
 
Characterization of RNA helicase A as component of STAT6-dependent enhanceosome.
Valineva T, Yang J, Silvennoinen O.
Nucleic Acids Res. 2006;34(14):3938-46. Epub 2006 Aug 12.
PMID 16914450
 
Analysis of the RNA helicase A gene in human lung cancer.
Wei X, Pacyna-Gengelbach M, Schluns K, An Q, Gao Y, Cheng S, Petersen I.
Oncol Rep. 2004 Jan;11(1):253-8.
PMID 14654934
 
A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element.
Westberg C, Yang JP, Tang H, Reddy TR, Wong-Staal F.
J Biol Chem. 2000 Jul 14;275(28):21396-401.
PMID 10748171
 
Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses.
Yang JP, Tang H, Reddy TR, Wong-Staal F.
J Biol Chem. 2001 Aug 17;276(33):30694-700. Epub 2001 Jun 11.
PMID 11402034
 
Nuclear DNA helicase II/RNA helicase A binds to filamentous actin.
Zhang S, Buder K, Burkhardt C, Schlott B, Gorlach M, Grosse F.
J Biol Chem. 2002 Jan 4;277(1):843-53. Epub 2001 Oct 30.
PMID 11687588
 
Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism.
Zhang S, Grosse F.
Acta Biochim Biophys Sin (Shanghai). 2004 Mar;36(3):177-83. (REVIEW)
PMID 15202501
 
Nucleolar localization of murine nuclear DNA helicase II (RNA helicase A).
Zhang S, Herrmann C, Grosse F.
J Cell Sci. 1999 Aug;112 ( Pt 16):2693-703.
PMID 10413677
 
Nuclear DNA helicase II (RNA helicase A) binds to an F-actin containing shell that surrounds the nucleolus.
Zhang S, Kohler C, Hemmerich P, Grosse F.
Exp Cell Res. 2004 Feb 15;293(2):248-58.
PMID 14729462
 
DNA-dependent protein kinase (DNA-PK) phosphorylates nuclear DNA helicase II/RNA helicase A and hnRNP proteins in an RNA-dependent manner.
Zhang S, Schlott B, Gorlach M, Grosse F.
Nucleic Acids Res. 2004 Jan 2;32(1):1-10. Print 2004.
PMID 14704337
 
RNA helicase A in the MEF1 transcription factor complex up-regulates the MDR1 gene in multidrug-resistant cancer cells.
Zhong X, Safa AR.
J Biol Chem. 2004 Apr 23;279(17):17134-41. Epub 2004 Feb 9.
PMID 14769796
 
RNA helicase A interacts with dsDNA and topoisomerase IIalpha.
Zhou K, Choe KT, Zaidi Z, Wang Q, Mathews MB, Lee CG.
Nucleic Acids Res. 2003 May 1;31(9):2253-60.
PMID 12711669
 

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


External links

Nomenclature
HGNC (Hugo)DHX9   2750
Cards
AtlasDHX9ID45879ch1q25
Entrez_Gene (NCBI)DHX9  1660  DExH-box helicase 9
AliasesDDX9; LKP; NDH2; NDHII; 
RHA
GeneCards (Weizmann)DHX9
Ensembl hg19 (Hinxton)ENSG00000135829 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000135829 [Gene_View]  chr1:182839304-182887982 [Contig_View]  DHX9 [Vega]
ICGC DataPortalENSG00000135829
TCGA cBioPortalDHX9
AceView (NCBI)DHX9
Genatlas (Paris)DHX9
WikiGenes1660
SOURCE (Princeton)DHX9
Genetics Home Reference (NIH)DHX9
Genomic and cartography
GoldenPath hg38 (UCSC)DHX9  -     chr1:182839304-182887982 +  1q25.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)DHX9  -     1q25.3   [Description]    (hg19-Feb_2009)
EnsemblDHX9 - 1q25.3 [CytoView hg19]  DHX9 - 1q25.3 [CytoView hg38]
Mapping of homologs : NCBIDHX9 [Mapview hg19]  DHX9 [Mapview hg38]
OMIM603115   
Gene and transcription
Genbank (Entrez)AA836637 AB451248 AB451372 AF086352 AK096582
RefSeq transcript (Entrez)NM_001357 NM_030588
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)DHX9
Cluster EST : UnigeneHs.191518 [ NCBI ]
CGAP (NCI)Hs.191518
Alternative Splicing GalleryENSG00000135829
Gene ExpressionDHX9 [ NCBI-GEO ]   DHX9 [ EBI - ARRAY_EXPRESS ]   DHX9 [ SEEK ]   DHX9 [ MEM ]
Gene Expression Viewer (FireBrowse)DHX9 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1660
GTEX Portal (Tissue expression)DHX9
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ08211   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ08211  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ08211
Splice isoforms : SwissVarQ08211
Catalytic activity : Enzyme3.6.4.13 [ Enzyme-Expasy ]   3.6.4.133.6.4.13 [ IntEnz-EBI ]   3.6.4.13 [ BRENDA ]   3.6.4.13 [ KEGG ]   
PhosPhoSitePlusQ08211
Domaine pattern : Prosite (Expaxy)DEAH_ATP_HELICASE (PS00690)    DS_RBD (PS50137)    HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)   
Domains : Interpro (EBI)DEAD/DEAH_box_helicase_dom    DNA/RNA_helicase_DEAH_CS    dsRBD_dom    DUF1605    Helicase-assoc_dom    Helicase_ATP-bd    Helicase_C    P-loop_NTPase   
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)  
Conserved Domain (NCBI)DHX9
DMDM Disease mutations1660
Blocks (Seattle)DHX9
PDB (SRS)3LLM    3VYX    3VYY   
PDB (PDBSum)3LLM    3VYX    3VYY   
PDB (IMB)3LLM    3VYX    3VYY   
PDB (RSDB)3LLM    3VYX    3VYY   
Structural Biology KnowledgeBase3LLM    3VYX    3VYY   
SCOP (Structural Classification of Proteins)3LLM    3VYX    3VYY   
CATH (Classification of proteins structures)3LLM    3VYX    3VYY   
SuperfamilyQ08211
Human Protein AtlasENSG00000135829
Peptide AtlasQ08211
HPRD04386
IPIIPI00844578   IPI00921264   
Protein Interaction databases
DIP (DOE-UCLA)Q08211
IntAct (EBI)Q08211
FunCoupENSG00000135829
BioGRIDDHX9
STRING (EMBL)DHX9
ZODIACDHX9
Ontologies - Pathways
QuickGOQ08211
Ontology : AmiGOmRNA splicing, via spliceosome  RNA polymerase II transcription factor binding  osteoblast differentiation  DNA binding  RNA binding  RNA helicase activity  ATP-dependent DNA helicase activity  ATP-dependent RNA helicase activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  centrosome  cytosol  RNA processing  membrane  intracellular ribonucleoprotein complex  positive regulation of type I interferon production  DNA duplex unwinding  cytoplasmic ribonucleoprotein granule  rhythmic process  CRD-mediated mRNA stabilization  CRD-mediated mRNA stability complex  nuclear stress granule  protein localization to cytoplasmic stress granule  
Ontology : EGO-EBImRNA splicing, via spliceosome  RNA polymerase II transcription factor binding  osteoblast differentiation  DNA binding  RNA binding  RNA helicase activity  ATP-dependent DNA helicase activity  ATP-dependent RNA helicase activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  centrosome  cytosol  RNA processing  membrane  intracellular ribonucleoprotein complex  positive regulation of type I interferon production  DNA duplex unwinding  cytoplasmic ribonucleoprotein granule  rhythmic process  CRD-mediated mRNA stabilization  CRD-mediated mRNA stability complex  nuclear stress granule  protein localization to cytoplasmic stress granule  
REACTOMEQ08211 [protein]
REACTOME PathwaysR-HSA-933542 [pathway]   
NDEx NetworkDHX9
Atlas of Cancer Signalling NetworkDHX9
Wikipedia pathwaysDHX9
Orthology - Evolution
OrthoDB1660
GeneTree (enSembl)ENSG00000135829
Phylogenetic Trees/Animal Genes : TreeFamDHX9
HOVERGENQ08211
HOGENOMQ08211
Homologs : HomoloGeneDHX9
Homology/Alignments : Family Browser (UCSC)DHX9
Gene fusions - Rearrangements
Fusion : MitelmanDHX9/PRELID1 [1q25.3/5q35.3]  
Fusion : MitelmanDHX9/ZBTB37 [1q25.3/1q25.1]  [t(1;1)(q25;q25)]  
Fusion: TCGADHX9 1q25.3 PRELID1 5q35.3 PRAD
Fusion: TCGADHX9 1q25.3 ZBTB37 1q25.1 SKCM
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDHX9 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DHX9
dbVarDHX9
ClinVarDHX9
1000_GenomesDHX9 
Exome Variant ServerDHX9
ExAC (Exome Aggregation Consortium)DHX9 (select the gene name)
Genetic variants : HAPMAP1660
Genomic Variants (DGV)DHX9 [DGVbeta]
DECIPHERDHX9 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisDHX9 
Mutations
ICGC Data PortalDHX9 
TCGA Data PortalDHX9 
Broad Tumor PortalDHX9
OASIS PortalDHX9 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDHX9  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDHX9
intOGen PortalDHX9
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch DHX9
DgiDB (Drug Gene Interaction Database)DHX9
DoCM (Curated mutations)DHX9 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DHX9 (select a term)
intoGenDHX9
NCG5 (London)DHX9
Cancer3DDHX9(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603115   
Orphanet
MedgenDHX9
Genetic Testing Registry DHX9
NextProtQ08211 [Medical]
TSGene1660
GENETestsDHX9
Target ValidationDHX9
Huge Navigator DHX9 [HugePedia]
snp3D : Map Gene to Disease1660
BioCentury BCIQDHX9
ClinGenDHX9
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1660
Chemical/Pharm GKB GenePA27232
Clinical trialDHX9
Miscellaneous
canSAR (ICR)DHX9 (select the gene name)
Probes
Litterature
PubMed193 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDHX9
EVEXDHX9
GoPubMedDHX9
iHOPDHX9
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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