DDX3X

DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked

PDB rendering based on 2i4i.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2I4I, 2JGN, 3JRV

Identifiers

Symbols

DDX3X ; DBX; DDX14; DDX3; HLP2

External IDs

OMIM: 300160 MGI: 103064 HomoloGene: 3425 ChEMBL: 5553 GeneCards: DDX3X Gene

EC number

3.6.4.13

Gene ontology
Molecular function	• DNA binding • RNA binding • ATP-dependent DNA helicase activity • ATP-dependent RNA helicase activity • protein binding • ATP binding • transcription factor binding • poly(A) binding • eukaryotic initiation factor 4E binding • ATPase activity • translation initiation factor binding • RNA stem-loop binding • ribosomal small subunit binding • poly(A) RNA binding • mRNA 5'-UTR binding
Cellular component	• nucleus • cytoplasm • mitochondrial outer membrane • eukaryotic translation initiation factor 3 complex • cytoplasmic stress granule • nuclear speck • cytosolic small ribosomal subunit • extracellular vesicular exosome
Biological process	• ATP catabolic process • transcription, DNA-templated • chromosome segregation • extrinsic apoptotic signaling pathway via death domain receptors • response to virus • RNA secondary structure unwinding • viral process • negative regulation of translation • positive regulation of cell growth • negative regulation of cell growth • negative regulation of protein complex assembly • DNA duplex unwinding • positive regulation of interferon-beta production • stress granule assembly • intracellular signal transduction • mature ribosome assembly • positive regulation of apoptotic process • negative regulation of apoptotic process • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • innate immune response • positive regulation of translation • positive regulation of transcription from RNA polymerase II promoter • positive regulation of translational initiation • cellular response to arsenic-containing substance • cellular response to osmotic stress • positive regulation of chemokine (C-C motif) ligand 5 production • intrinsic apoptotic signaling pathway • positive regulation of G1/S transition of mitotic cell cycle • negative regulation of intrinsic apoptotic signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr X:
41.19 – 41.22 Mb

Chr X:
13.28 – 13.29 Mb

PubMed search

ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the DDX3X gene.^[1]^[2]^[3]

Function

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which interacts specifically with hepatitis C virus core protein resulting a change in intracellular location. This gene has a homolog located in the nonrecombining region of the Y chromosome. The protein sequence is 91% identical between this gene and the Y-linked homolog.^[3]

Role in cancer

DDX3X is involved in many different types of cancer. For example, it is abnormally expressed in breast epithelial cancer cells in which its expression is activated by HIF1A during hypoxia.^[4] Increased expression of DDX3X by HIF1A in hypoxia is initiated by the direct binding of HIF1A to the HIF1A response element,^[4] as verified with chromatin immunoprecipitation and luciferase reporter assay. Since the expression of DDX3X is affected by the activity of HIF1A, the co-localization of these proteins has also been demonstrated in MDA-MB-231 xenograft tumor samples.^[4]

In HeLa cells DDX3X is reported to control cell cycle progression through Cyclin E1.^[5] More specifically, DDX3X was shown to directly bind to the 5´ UTR of Cyclin E1 and thereby facilitating the translation of the protein. Increased protein levels of Cyclin E1 was demonstrated to mediate the transition of S phase entry.^[5]

Clinical significance

Mutations of the DDX3X gene are also associated with medulloblastoma.^[6]^[7]^[8]

References

↑ Lahn BT, Page DC (Nov 1997). "Functional coherence of the human Y chromosome". Science 278 (5338): 675–680. doi:10.1126/science.278.5338.675. PMID 9381176.
↑ Park SH, Lee SG, Kim Y, Song K (Oct 1998). "Assignment of a human putative RNA helicase gene, DDX3, to human X chromosome bands p11.3→p11.23". Cytogenet Cell Genet 81 (3–4): 178–179. doi:10.1159/000015022. PMID 9730595.
↑ 3.0 3.1 "Entrez Gene: DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked".
↑ 4.0 4.1 4.2 "Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells". PLoS ONE. 2011-03-23. doi:10.1371/journal.pone.0017563.
↑ 5.0 5.1 "DDX3 Regulates Cell Growth through Translational Control of Cyclin E1". Molecular and Cellular Biology. November 2010. doi:10.1128/MCB.00560-10.
↑ Robinson G, Parker M, Kranenburg TA et al. (June 2012). "Novel mutations target distinct subgroups of medulloblastoma". Nature 488 (7409). doi:10.1038/nature11213.
↑ Jones TW, Jäger N, Kool M et al. (July 2012). "Dissecting the genomic complexity underlying medulloblastoma". Nature 488 (7409): 100–5. doi:10.1038/nature11284. PMC 3662966. PMID 22832583.
↑ Pugh TJ, Weeraratne SD, Archer TC et al. (July 2012). "Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations". Nature. doi:10.1038/nature11329.

Li L; Li HS; Pauza CD et al. (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–934. doi:10.1038/sj.cr.7290370. PMID 16354571.
Owsianka AM, Patel AH (1999). "Hepatitis C virus core protein interacts with a human DEAD box protein DDX3". Virology 257 (2): 330–340. doi:10.1006/viro.1999.9659. PMID 10329544.
Mamiya N, Worman HJ (1999). "Hepatitis C virus core protein binds to a DEAD box RNA helicase". J. Biol. Chem. 274 (22): 15751–15756. doi:10.1074/jbc.274.22.15751. PMID 10336476.
Yagüe J; Alvarez I; Rognan D et al. (2000). "An N-acetylated natural ligand of human histocompatibility leukocyte antigen (HLA)-B39. Classical major histocompatibility complex class I proteins bind peptides with a blocked NH(2) terminus in vivo". J. Exp. Med. 191 (12): 2083–2092. doi:10.1084/jem.191.12.2083. PMC 2193201. PMID 10859333.
Kim YS, Lee SG, Park SH, Song K (2002). "Gene structure of the human DDX3 and chromosome mapping of its related sequences". Mol. Cells 12 (2): 209–14. PMID 11710523.
Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Li J; Hawkins IC; Harvey CD et al. (2003). "Regulation of alternative splicing by SRrp86 and its interacting proteins". Mol. Cell. Biol. 23 (21): 7437–7447. doi:10.1128/MCB.23.21.7437-7447.2003. PMC 207616. PMID 14559993.
Shu H; Chen S; Bi Q et al. (2004). "Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line". Mol. Cell Proteomics 3 (3): 279–286. doi:10.1074/mcp.D300003-MCP200. PMID 14729942.
Bouwmeester T; Bauch A; Ruffner H et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
Gerhard DS; Wagner L; Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Yedavalli VS; Neuveut C; Chi YH et al. (2004). "Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function". Cell 119 (3): 381–392. doi:10.1016/j.cell.2004.09.029. PMID 15507209.
Dayton AI (2006). "Within you, without you: HIV-1 Rev and RNA export". Retrovirology 1: 35. doi:10.1186/1742-4690-1-35. PMC 526764. PMID 15516266.
Krishnan V, Zeichner SL (2006). "Alterations in the expression of DEAD-box and other RNA binding proteins during HIV-1 replication". Retrovirology 1: 42. doi:10.1186/1742-4690-1-42. PMC 543576. PMID 15588285.
Rush J; Moritz A; Lee KA et al. (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455.
Tao WA; Wollscheid B; O'Brien R et al. (2005). "Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry". Nat. Methods 2 (8): 591–598. doi:10.1038/nmeth776. PMID 16094384.
Gevaert K; Staes A; Van Damme J et al. (2006). "Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC". Proteomics 5 (14): 3589–3599. doi:10.1002/pmic.200401217. PMID 16097034.
Rual JF; Venkatesan K; Hao T et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID 16189514.
Chang PC; Chi CW; Chau GY et al. (2006). "DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control". Oncogene 25 (14): 1991–2003. doi:10.1038/sj.onc.1209239. PMID 16301996.

PDB gallery

2i4i: Crystal Structure of human DEAD-box RNA helicase DDX3X

DDX3X

Function

Role in cancer

Clinical significance

References

Further reading