DDX3X

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DDX3X
Protein DDX3X PDB 2i4i.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases DDX3X, DBX, DDX14, DDX3, HLP2, CAP-Rf, MRX102, DEAD-box helicase 3, X-linked
External IDs MGI: 103064 HomoloGene: 3425 GeneCards: DDX3X
RNA expression pattern
PBB GE DDX3X 201210 at fs.png

PBB GE DDX3X 212514 x at fs.png

PBB GE DDX3X 201211 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001193416
NM_001193417
NM_001356
NM_024005

NM_010028

RefSeq (protein)

NP_001180345
NP_001180346
NP_001347

NP_034158.1
NP_034158

Location (UCSC) Chr X: 41.33 – 41.36 Mb Chr X: 13.28 – 13.29 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the DDX3X gene.[3][4][5]

Function[edit]

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.[5]

Role in cancer[edit]

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.[6] Increased expression of DDX3X by HIF1A in hypoxia is initiated by the direct binding of HIF1A to the HIF1A response element,[6] 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.[6]

In HeLa cells DDX3X is reported to control cell cycle progression through Cyclin E1.[7] 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.[7]

Clinical significance[edit]

Mutations of the DDX3X gene are also associated with medulloblastoma.[8][9][10]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ a b "Entrez Gene: DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked". 
  6. ^ a b c "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. 
  7. ^ a b "DDX3 Regulates Cell Growth through Translational Control of Cyclin E1". Molecular and Cellular Biology. November 2010. doi:10.1128/MCB.00560-10. 
  8. ^ Robinson G, Parker M, Kranenburg TA, et al. (June 2012). "Novel mutations target distinct subgroups of medulloblastoma". Nature. 488 (7409): 43–48. doi:10.1038/nature11213. 
  9. ^ 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 3662966Freely accessible. PMID 22832583. 
  10. ^ Pugh TJ, Weeraratne SD, Archer TC, et al. (July 2012). "Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations". Nature. 488: 106–110. doi:10.1038/nature11329. PMC 3413789Freely accessible. PMID 22820256. 

Further reading[edit]