DDX20

Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the DDX20 gene.[5][6]

DDX20
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2OXC, 3B7G
Identifiers
Aliases	DDX20, DP103, GEMIN3, DEAD-box helicase 20
External IDs	OMIM: 606168 MGI: 1858415 HomoloGene: 5214 GeneCards: DDX20
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p13.2 Start 111,755,245 bp[1] End 111,768,000 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 F2.2 Start 105,678,270 bp[2] End 105,687,574 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • protein binding, bridging • nucleotide binding • GO:0008026 helicase activity • protein domain specific binding • histone deacetylase binding • GO:0001948 protein binding • nucleic acid binding • repressing transcription factor binding • hydrolase activity • ATP binding Cellular component • SMN-Sm protein complex • cytosol • membrane • transcriptional repressor complex • nucleoplasm • SMN complex • RNA polymerase II transcription repressor complex • cytoskeleton • cell nucleus • Gemini of coiled bodies • cytoplasm • nuclear body • nucleolus Biological process • RNA processing • spliceosomal tri-snRNP complex assembly • mRNA processing • regulation of steroid biosynthetic process • negative regulation of transcription from RNA polymerase II promoter • oogenesis • spliceosomal snRNP assembly • RNA secondary structure unwinding • RNA splicing • positive regulation of apoptotic process • negative regulation of transcription, DNA-templated • negative regulation of cell proliferation • nuclear import Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	11218	53975
Ensembl	ENSG00000064703	ENSMUSG00000027905
UniProt	Q9UHI6	Q9JJY4
RefSeq (mRNA)	NM_007204	NM_017397
RefSeq (protein)	NP_009135	NP_059093
Location (UCSC)	Chr 1: 111.76 – 111.77 Mb	Chr 3: 105.68 – 105.69 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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 has an ATPase activity and is a component of the survival of motor neuron (SMN) complex.[6] SMN is the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs.[6]

Biological Implication

Previous research has revealed that DDX20 may act as a tumor suppressor in hepatocellular carcinoma and as a tumor promoter in breast cancer. DDX20 deficiency enhances NF-κB activity by impairing the NF-κB-suppressive action of microRNAs, and suggest that dysregulation of the microRNA machinery components may also be involved in pathogenesis in various human diseases.[7] Such as miRNA-140 which acts as a liver tumor suppressor, and due to a deficiency of DDX20, miRNA-140 function gets impair, this subsequent functional impairment of miRNAs could lead to hepatocarcinogenesis. Similarly,[8] DDX20 may promote the progression of Prostate cancer (PCa) through the NF-κB pathway.[9] In a clinical based study it has been observed that positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. It makes DP103 has potential as a therapeutic target for breast cancer treatment.[10]

Interactions

DDX20 has been shown to interact with:

• EIF2C2,[11][12]
• GEMIN4,[11][13][14]
• GEMIN5,[11][15]
• LSM2,[16]
• SMN1,[11][13][16][17]
• SNRPB,[16]
• SNRPD3[16] and
• SNRPG,[16]
• SNRPD1,[16]
• SNRPD2,[16]
• SNRPE,[16]
• SNRPF,[16] and
• SIP1.[11][16]

References

1. GRCh38: Ensembl release 89: ENSG00000064703 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027905 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Grundhoff AT, Kremmer E, Türeci O, Glieden A, Gindorf C, Atz J, Mueller-Lantzsch N, Schubach WH, Grässer FA (July 1999). "Characterization of DP103, a novel DEAD box protein that binds to the Epstein-Barr virus nuclear proteins EBNA2 and EBNA3C". J Biol Chem. 274 (27): 19136–44. doi:10.1074/jbc.274.27.19136. PMID 10383418.
6. "Entrez Gene: DDX20 DEAD (Asp-Glu-Ala-Asp) box polypeptide 20".
7. Takata, Akemi; Otsuka, Motoyuki; Yoshikawa, Takeshi; Kishikawa, Takahiro; Kudo, Yotaro; Goto, Tadashi; Yoshida, Haruhiko; Koike, Kazuhiko (2012-04-13). "A miRNA machinery component DDX20 controls NF-κB via microRNA-140 function". Biochemical and Biophysical Research Communications. 420 (3): 564–569. doi:10.1016/j.bbrc.2012.03.034. ISSN 1090-2104. PMID 22445758.
8. Takata, Akemi; Otsuka, Motoyuki; Yoshikawa, Takeshi; Kishikawa, Takahiro; Hikiba, Yohko; Obi, Shuntaro; Goto, Tadashi; Kang, Young Jun; Maeda, Shin (January 2013). "MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression". Hepatology. 57 (1): 162–170. doi:10.1002/hep.26011. ISSN 1527-3350. PMC 3521841. PMID 22898998.
9. Chen, Weiguo; Zhou, Peng; Li, Xiaowei (June 2016). "High expression of DDX20 enhances the proliferation and metastatic potential of prostate cancer cells through the NF-κB pathway". International Journal of Molecular Medicine. 37 (6): 1551–1557. doi:10.3892/ijmm.2016.2575. ISSN 1791-244X. PMC 4866965. PMID 27121695.
10. Shin, Eun Myoung; Hay, Hui Sin; Lee, Moon Hee; Goh, Jen Nee; Tan, Tuan Zea; Sen, Yin Ping; Lim, See Wee; Yousef, Einas M.; Ong, Hooi Tin (September 2014). "DEAD-box helicase DP103 defines metastatic potential of human breast cancers". The Journal of Clinical Investigation. 124 (9): 3807–3824. doi:10.1172/JCI73451. ISSN 1558-8238. PMC 4151228. PMID 25083991.
11. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G (March 2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes Dev. 16 (6): 720–8. doi:10.1101/gad.974702. PMC 155365. PMID 11914277.
12. Nelson PT, Hatzigeorgiou AG, Mourelatos Z (March 2004). "miRNP:mRNA association in polyribosomes in a human neuronal cell line". RNA. 10 (3): 387–94. doi:10.1261/rna.5181104. PMC 1370934. PMID 14970384.
13. Carnegie GK, Sleeman JE, Morrice N, Hastie CJ, Peggie MW, Philp A, Lamond AI, Cohen PT (May 2003). "Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs". J. Cell Sci. 116 (Pt 10): 1905–13. doi:10.1242/jcs.00409. PMID 12668731.
14. Charroux B, Pellizzoni L, Perkinson RA, Yong J, Shevchenko A, Mann M, Dreyfuss G (March 2000). "Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli". J. Cell Biol. 148 (6): 1177–86. doi:10.1083/jcb.148.6.1177. PMC 2174312. PMID 10725331.
15. Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G (February 2002). "Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins". J. Biol. Chem. 277 (7): 5631–6. doi:10.1074/jbc.M109448200. PMID 11714716.
16. Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G (December 1999). "Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems". J. Cell Biol. 147 (6): 1181–94. doi:10.1083/jcb.147.6.1181. PMC 2168095. PMID 10601333.
17. Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U (August 2000). "Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins". Hum. Mol. Genet. 9 (13): 1977–86. doi:10.1093/hmg/9.13.1977. PMID 10942426.

Further reading

• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G (2000). "Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems". J. Cell Biol. 147 (6): 1181–94. doi:10.1083/jcb.147.6.1181. PMC 2168095. PMID 10601333.
• Charroux B, Pellizzoni L, Perkinson RA, Yong J, Shevchenko A, Mann M, Dreyfuss G (2000). "Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli". J. Cell Biol. 148 (6): 1177–86. doi:10.1083/jcb.148.6.1177. PMC 2174312. PMID 10725331.
• Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U (2000). "Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins". Hum. Mol. Genet. 9 (13): 1977–86. doi:10.1093/hmg/9.13.1977. PMID 10942426.
• Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G (2001). "A functional interaction between the survival motor neuron complex and RNA polymerase II". J. Cell Biol. 152 (1): 75–85. doi:10.1083/jcb.152.1.75. PMC 2193649. PMID 11149922.
• Friesen WJ, Paushkin S, Wyce A, Massenet S, Pesiridis GS, Van Duyne G, Rappsilber J, Mann M, Dreyfuss G (2001). "The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins". Mol. Cell. Biol. 21 (24): 8289–300. doi:10.1128/MCB.21.24.8289-8300.2001. PMC 99994. PMID 11713266.
• Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G (2002). "Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins". J. Biol. Chem. 277 (7): 5631–6. doi:10.1074/jbc.M109448200. PMID 11714716.
• Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G (2002). "Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component". J. Biol. Chem. 277 (9): 7540–5. doi:10.1074/jbc.M110141200. PMID 11748230.
• Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G (2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes Dev. 16 (6): 720–8. doi:10.1101/gad.974702. PMC 155365. PMID 11914277.
• Klappacher GW, Lunyak VV, Sykes DB, Sawka-Verhelle D, Sage J, Brard G, Ngo SD, Gangadharan D, Jacks T, Kamps MP, Rose DW, Rosenfeld MG, Glass CK (2002). "An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation". Cell. 109 (2): 169–80. doi:10.1016/S0092-8674(02)00714-6. PMID 12007404.
• Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G (2002). "Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex". J. Biol. Chem. 277 (35): 31957–62. doi:10.1074/jbc.M203478200. PMID 12065586.
• Narayanan U, Ospina JK, Frey MR, Hebert MD, Matera AG (2003). "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta". Hum. Mol. Genet. 11 (15): 1785–95. doi:10.1093/hmg/11.15.1785. PMC 1630493. PMID 12095920.
• Carnegie GK, Sleeman JE, Morrice N, Hastie CJ, Peggie MW, Philp A, Lamond AI, Cohen PT (2004). "Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs". J. Cell Sci. 116 (Pt 10): 1905–13. doi:10.1242/jcs.00409. PMID 12668731.
• Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
• Nelson PT, Hatzigeorgiou AG, Mourelatos Z (2004). "miRNP:mRNA association in polyribosomes in a human neuronal cell line". RNA. 10 (3): 387–94. doi:10.1261/rna.5181104. PMC 1370934. PMID 14970384.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.