DDX5 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 5)

2011-08-01   Zhi-Ren Liu 

Departments of Biology, Georgia State University, Atlanta, GA 30303, USA





DDX5/p68 RNA helicase is expressed in dividing cells of different vertebrates. Transcription of p68 RNA helicase gene generates a single mRNA precusor with 13 exons and 12 introns. Alternative splicing produces two mRNA transcripts, 2.3 kb and 4.4 kb (Rössler et al., 2000). The 2.3 kb mRNA transcript codes full length p68, while no translational product from the 4.4 kb mRNA transcript is detected in cellular and tissue extracts (Rössler et al., 2000).
Atlas Image
Diagram of pre-mRNA of p68 RNA helicase. The red bars are exons and the blue thin lines are introns.


Atlas Image
Domain structure of p68 RNA helicase. Functional sequence motifs are marked.


Size of p68; 614 amino acids, 69 kDa.


Expressed in almost all tissue types. Its expression is increased in cancer cells.


Dominately localized in the cell nucleus. It is also found in the cytoplasm in various physiological conditions. p68 is a nucleocytoplasm shuttling protein (Wang et al., 2009).


Pre-mRNA splicing. The protein was demonstrated to associate with spliceosome by mass-spectroscopy and an RNA-protein crosslinking analyses (Hartmuth et al., 2002; Liu et al., 1997; Neubauer et al., 1998). p68 is functionally involved in assemble of the splicesome by mediating the U1 snRNP and the 5ss interaction (Liu, 2002). p68 RNA helicase is also shown to regulate the splice site selection in the alternative splicing of several growth related genes, such as c-H-ras and tau (Kar et al., 2011; Guil et al., 2003).

Transcriptional regulation. The protein is shown to involve in transcriptional regulation by different mechanism of actions dependent on each individual regulated gene and biological processes (Stevenson et al., 1998; Endoh et al., 1999; Yang et al., 2005; Kahlina et al., 2004; Wei and Hu, 2001; Warner et al., 2004). p68 may regulate gene transcription by direct interaction with transcription factors or activators, such as p53, ERalpha (Endoh et al., 1999; Bates et al., 2005), or by mediating chromatin remodeling, such as modulating chromatin remodeling complex (Carter et al., 2010).

Epithelial-Mesenchymal-Transition (EMT). p68 becomes phosphorylated at Y593 upon growth factor stimulation by c-Abl. The tyrosine phosphorylation of p68 mediates growth factor stimulated Epithelial-Mesenchymal-Transition (EMT) (Yang et al., 2006).

Other functions. (1) p68 RNA helicase is shown to unwind the human let-7 microRNA precursor duplex. The protein is required for let-7-directed silencing of gene expression (Salzman et al., 2007). p68 is an indispensible part of Drosha complex. Its activity is required for primary miRNA and rRNA processing (Fukuda et al., 2007). (2) It is also demonstrated that the RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation (Caretti et al., 2006). (3) Phosphorylation of p68 at Thr residues mediates cell apoptosis (Yang et al., 2007).


Yeast DBP2.



Very few mutations of p68 gene were reported. A recent study shows that a S480A mutation in hepatic stellate cells is associated with hepatic fibrosis (Guo et al., 2010).

Implicated in

Entity name
Colon cancer
p68 expression is significantly increased in colon cancer (Shin et al., 2007). Phosphorylation of p68 at Tyr correlation with colon cancer metastasis (Yang et al., 2006; Yang et al., 2005).
Phosphorylation of p68 at tyrosine can be used as a diagnosis/prognosis marker for cancer.


Pubmed IDLast YearTitleAuthors
156601292005The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor.Bates GJ et al
170114932006The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation.Caretti G et al
206761352010Phosphorylated p68 RNA helicase activates Snail1 transcription by promoting HDAC1 dissociation from the Snail1 promoter.Carter CL et al
117536512001Overexpression and poly-ubiquitylation of the DEAD-box RNA helicase p68 in colorectal tumours.Causevic M et al
104097271999Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha.Endoh H et al
24517861988Nuclear protein with sequence homology to translation initiation factor eIF-4A.Ford MJ et al
174357482007DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs.Fukuda T et al
126655902003Roles of hnRNP A1, SR proteins, and p68 helicase in c-H-ras alternative splicing regulation.Guil S et al
200229622010A DDX5 S480A polymorphism is associated with increased transcription of fibrogenic genes in hepatic stellate cells.Guo J et al
124779342002Protein composition of human prespliceosomes isolated by a tobramycin affinity-selection method.Hartmuth K et al
24719391989RNA helicase activity associated with the human p68 protein.Hirling H et al
118234732002The ATPase, RNA unwinding, and RNA binding activities of recombinant p68 RNA helicase.Huang Y et al
25277461989Nuclear protein p68 is an RNA-dependent ATPase.Iggo RD et al
174854822007Redundant role of DEAD box proteins p68 (Ddx5) and p72/p82 (Ddx17) in ribosome biogenesis and cell proliferation.Jalal C et al
104546301999A chicken embryo protein related to the mammalian DEAD box protein p68 is tightly associated with the highly purified protein-RNA complex of 5-MeC-DNA glycosylase.Jost JP et al
153045012004p68 DEAD box RNA helicase expression in keratinocytes. Regulation, nucleolar localization, and functional connection to proliferation and vascular endothelial growth factor gene expression.Kahlina K et al
213433382011RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5' splice site.Kar A et al
61595511980SV40 large T shares an antigenic determinant with a cellular protein of molecular weight 68,000.Lane DP et al
94096141997Crosslinking of the U5 snRNP-specific 116-kDa protein to RNA hairpins that block step 2 of splicing.Liu ZR et al
121012382002p68 RNA helicase is an essential human splicing factor that acts at the U1 snRNA-5' splice site duplex.Liu ZR et al
97315291998Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex.Neubauer G et al
106487852000Structure and expression of the human p68 RNA helicase gene.Rössler OG et al
125279172003Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300.Rossow KL et al
177240232007P68 RNA helicase unwinds the human let-7 microRNA precursor duplex and is required for let-7-directed silencing of gene expression.Salzman DW et al
176997602007Involvement of RNA helicases p68 and p72 in colon cancer.Shin S et al
96649001998Expression of the 'dead box' RNA helicase p68 is developmentally and growth regulated and correlates with organ differentiation/maturation in the fetus.Stevenson RJ et al
197869862009P68 RNA helicase is a nucleocytoplasmic shuttling protein.Wang H et al
154649842004Functional interaction between Smad, CREB binding protein, and p68 RNA helicase.Warner DR et al
117256462001[The study of P68 RNA helicase on cell transformation].Wei Y et al
173846752007A double tyrosine phosphorylation of P68 RNA helicase confers resistance to TRAIL-induced apoptosis.Yang L et al

Other Information

Locus ID:

NCBI: 1655
MIM: 180630
HGNC: 2746
Ensembl: ENSG00000108654


dbSNP: 1655
ClinVar: 1655
TCGA: ENSG00000108654


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
175400402007Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data using a block bootstrap re-sampling scheme.138
209660462010Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA.102
170182822006P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin.100
156601292005The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor.85
188295512008The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer.78
176997602007Involvement of RNA helicases p68 and p72 in colon cancer.62
187941522008A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: identification of DDX5-ETV4 fusion protein in prostate cancer.55
249104392014RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation.53
121012382002p68 RNA helicase is an essential human splicing factor that acts at the U1 snRNA-5' splice site duplex.50
126655902003Roles of hnRNP A1, SR proteins, and p68 helicase in c-H-ras alternative splicing regulation.49


Zhi-Ren Liu

DDX5 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 5)

Atlas Genet Cytogenet Oncol Haematol. 2011-08-01

Online version: http://atlasgeneticsoncology.org/gene/40290/ddx5