DDX1 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 1)

2010-06-01   Takahiko Hara , Kiyoko Tanaka 

Stem cell project group, The Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan




Atlas Image
Genomic organization of human DDX1 gene. Boxes and connecting lines indicate exons (omitted in the middle part) and introns, respectively. The ATG transcription initiation site is located in exon 2.


DDX1 gene is located in an approximately 40 kb chromosomal DNA region of 2p24.3 containing at least 27 exons. There are alternatively used exons for exon 2, 16, 19, 21, 23 and 27.


Size of the major mRNA is 2.7 kb.


Atlas Image
Diagram of conserved motifs among DEAD box RNA helicase family proteins.


DDX1 protein is a putative RNA helicase containing the characteristic Asp-Glu-Ala-Asp (DEAD) conserved sequence motif (Linder et al., 1989). It is composed of 740 amino acid residues (82432 Da). Proteins of this family (more than 30 from bacteria to humans) have been described to be implicated in a number of cellular processes involving alteration of RNA secondary structure such as translational initiation, nuclear and mitochondrial RNA splicing, and ribosome/spliceosome assembly (Rocak and Linder, 2004).


DDX1 mRNA is widely expressed in many tissues, but its expression level is highest in testis (Tanaka et al., 2009). DDX1 level tends to be higher in tumor-derived cells than in normal tissues.


DDX1 protein is localized both in the cytoplasm and nucleus of DDX1 gene-amplified neuroblastoma and retinoblastoma cell lines, but mainly located in the nucleus of normal fibroblasts (Godbout et al., 1998).


DDX1 is believed to regulate translational initiation, nuclear hnRNA splicing, ribosome/spliceosome assembly, and mRNA synthesis as a putative ATP-dependent RNA helicase. DDX1 is associated with a pre-mRNA 3-end cleavage protein CstF-64 (Bleoo et al., 2001) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Chen et al., 2002). hnRNP-K is involved in cell migration and cytoplasmic accumulation of hnRNP-K is crucial for metastasis (Inoue et al., 2007). It was reported that DDX1 interacts with nuclear diffusion inhibitory signal (NIS) motif of HIV-1 Rev protein in human astrocytes. Accumulation of DDX1 in astrocytes changed sub-cellular distribution of Rev from nuclear to cytoplasmic (Fang et al., 2005). More recently, it was reported that DDX1 is recruited to the sites of DNA double strand breaks in cells exposed to ionizing radiation and removes single stranded RNAs to facilitate the repair reaction of transcriptionally active regions of the genome (Li et al., 2008).
In retinoblastoma and neuroblastoma cell lines, co-amplification of DDX1 and the proto-oncogene MYCN has been demonstrated (Godbout and Squire, 1993; Godbout et al., 1998). Similar gene amplification of the genomic region containing DDX1 and MYCN was observed in alveolar rhabdomyosarcoma samples (Barr et al., 2009) and Wilms tumor-derived cells (Noguera et al., 2010). Elevated expression of DDX1 mRNA was reported to be a prognostic marker for early recurrence in primary breast cancer (Germain et al., 2010).
Recently, it was demonstrated that DDX1 is essential for the solid tumor formation of a human testicular tumor cell line NEC8 in nude mice (Tanaka et al., 2009). In this case, DDX1 directly bound to the -348 and -329 promoter region of the cyclin-D2 gene and enhanced its transcription. Furthermore, siRNA-mediated knockdown of DDX1 resulted in coordinated down-regulation of stem cell-associated genes located in chromosomal region 12p13. Therefore, DDX1 may function as an essential transcriptional activator for the tumorigenic capacity of testicular germ line tumor-derived cells. In agreement, DDX1 promotes the proliferation of JC virus via the transcriptional activation of its viral promoter (Sunden et al., 2007). It was also reported that DDX1 acts as a co-activator to enhance NF-kappaB-mediated transcription (Ishaq et al., 2009).

Implicated in

Entity name
Retinoblastoma and neuroblastoma
Coamplication of DDX1 and MYCN genes frequently occurs in both retinoblastoma and neuroblastoma cell lines. This is because DDX1 gene is located to chromosome 2p24, 400-kb telomeric to MYCN gene. This type of gene amplification has also been reported in alveolar rhabdomyosarcoma samples and Wilms tumor-derived cells. However, prognostic significance of the DDX1 gene amplification for the clinical outcome is not clear.
Entity name
Testicular tumors
In testicular tumors including seminoma and nonseminoma, significantly higher levels of DDX1 mRNA are expressed. In a nonseminoma-derived cell line NEC8, siRNA-mediated knockdown of DDX1 abrogated their anchorage-independent growth in a semisolid medium and in vivo tumor formation in nude mice.
Entity name
Breast cancer
Expression of DDX1 mRNA and cytoplasmic DDX1 levels are significantly elevated in relapsed breast cancer samples. Thus, DDX1 can be a prognostic biomarker for early recurrence in primary breast cancer.


Pubmed IDLast YearTitleAuthors
194220362009Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group.Barr FG et al
115981902001Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA.Bléoo S et al
121834652002An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K.Chen HC et al
158929702005The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes.Fang J et al
204991592011DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer.Germain DR et al
96948721998Overexpression of a DEAD box protein (DDX1) in neuroblastoma and retinoblastoma cell lines.Godbout R et al
76892211993Amplification of a DEAD box protein gene in retinoblastoma cell lines.Godbout R et al
174834882007Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis.Inoue A et al
190581352009The DEAD-box RNA helicase DDX1 interacts with RelA and enhances nuclear factor kappaB-mediated transcription.Ishaq M et al
187109412008A role for DEAD box 1 at DNA double-strand breaks.Li L et al
25631481989Birth of the D-E-A-D box.Linder P et al
201860102010Gain of MYCN region in a Wilms tumor-derived xenotransplanted cell line.Noguera R et al
149910032004DEAD-box proteins: the driving forces behind RNA metabolism.Rocak S et al
173800542007DDX1 promotes proliferation of the JC virus through transactivation of its promoter.Sunden Y et al
193989532009DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes.Tanaka K et al

Other Information

Locus ID:

NCBI: 1653
MIM: 601257
HGNC: 2734
Ensembl: ENSG00000079785


dbSNP: 1653
ClinVar: 1653
TCGA: ENSG00000079785


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
tRNA processingREACTOMER-HSA-72306
tRNA processing in the nucleusREACTOMER-HSA-6784531

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
155674402004A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev.77
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
205738272010The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication.43
187109412008A role for DEAD box 1 at DNA double-strand breaks.37
248702302014Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors.37
220515122012DDX1 is an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication.34
217634992011Single-molecule studies reveal that DEAD box protein DDX1 promotes oligomerization of HIV-1 Rev on the Rev response element.29
275508102016DEAD Box 1 Facilitates Removal of RNA and Homologous Recombination at DNA Double-Strand Breaks.27
155882852004Alterations in the expression of DEAD-box and other RNA binding proteins during HIV-1 replication.22
204991592011DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer.22


Takahiko Hara ; Kiyoko Tanaka

DDX1 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 1)

Atlas Genet Cytogenet Oncol Haematol. 2010-06-01

Online version: http://atlasgeneticsoncology.org/gene/40283/ddx1