DDX41

DDX41
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2P6N
Identifiers
Aliases	DDX41 , ABS, MPLPF, DEAD-box helicase 41
External IDs	OMIM: 608170; MGI: 1920185; HomoloGene: 9431; GeneCards: DDX41; OMA:DDX41 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) [1] Band 5q35.3 Start 177,511,577 bp [1] End 177,516,961 bp [1]
Gene location (Mouse) Chr. Chromosome 13 (mouse) [2] Band 13|13 B1 Start 55,678,223 bp [2] End 55,684,471 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte right frontal lobe anterior cingulate cortex sural nerve mucosa of transverse colon right hemisphere of cerebellum stromal cell of endometrium prefrontal cortex nucleus accumbens monocyte Top expressed in primitive streak right kidney proximal tubule granulocyte spermatocyte embryo ventricular zone epiblast embryo neural layer of retina More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding nucleotide binding helicase activity metal ion binding protein binding nucleic acid binding hydrolase activity ATP binding RNA binding Cellular component cytosol catalytic step 2 spliceosome membrane endoplasmic reticulum nucleus spliceosomal complex nucleolus cytoplasm Biological process cellular response to interferon-beta mRNA processing regulation of type I interferon production defense response to virus RNA secondary structure unwinding RNA splicing positive regulation of type I interferon production positive regulation of transcription by RNA polymerase II apoptotic process mRNA splicing, via spliceosome cell population proliferation cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51428 72935 Ensembl ENSG00000183258 ENSMUSG00000021494 UniProt Q9UJV9 Q91VN6 RefSeq (mRNA) NM_016222 NM_001321732 NM_001321830 NM_134059 RefSeq (protein) NP_001308661 NP_001308759 NP_057306 NP_598820 Location (UCSC) Chr 5: 177.51 – 177.52 Mb Chr 13: 55.68 – 55.68 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Probable ATP-dependent RNA helicase DDX41 is an enzyme that in humans is encoded by the DDX41 gene. ^{[5] [6]}

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 the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The function of this member has not been determined. Based on studies in Drosophila, the gene is widely required during post-transcriptional gene expression. ^[6] Germ line DDX41 mutations define a unique subtype of myeloid neoplasms. ^[7]

Function

DDX41 is believed to take part in several cell functions. It is mainly concentrated in the nucleus of the cell, but it can also be expressed in the cytoplasm. ^{[8] [9]} In the cytoplasm it takes part in the Interferon I production pathway by recognizing foreign cytoplasmic DNA and signaling STING. ^[10] It has been observed that hypomorphic DDX41 mutations impair the immune system response to viral and bacterial infections. In the nucleus, DDX41 is believed to regulate the transcriptional elongation process signaling Pol II to slow down the elongation while the splicing process is taking place. Under-expression and inhibition of DDX41 have been shown to lead to the formation of an R-loop which results in transcriptional errors with no specific patterns. ^[8] DDX41 is also believed to take part in the ribosome biogenesis process, given its implications in the processing of snoRNA. ^[11]

It has been shown that DDX41 germ-line mutations are associated with myelodysplastic syndrome and acute myeloid leukemia. ^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000183258 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021494 – 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. Irion U, Leptin M (December 1999). "Developmental and cell biological functions of the Drosophila DEAD-box protein abstrakt". Current Biology. 9 (23): 1373–1381. Bibcode:1999CBio....9.1373I. doi: 10.1016/S0960-9822(00)80082-2 . PMID   10607561. S2CID   16448276.
6. "Entrez Gene: DDX41 DEAD (Asp-Glu-Ala-Asp) box polypeptide 41".
7. Makishima H, Saiki R, Nannya Y, Korotev S, Gurnari C, Takeda J, et al. (February 2023). "Germ line DDX41 mutations define a unique subtype of myeloid neoplasms". Blood. 141 (5): 534–549. doi: 10.1182/blood.2022018221 . PMC   10935555 . PMID   36322930. S2CID   253266118.
8. Shinriki S, Hirayama M, Nagamachi A, Yokoyama A, Kawamura T, Kanai A, et al. (November 2022). "DDX41 coordinates RNA splicing and transcriptional elongation to prevent DNA replication stress in hematopoietic cells". Leukemia. 36 (11): 2605–2620. doi:10.1038/s41375-022-01708-9. PMC   9613458 . PMID   36229594.
9. Jiang Y, Zhu Y, Qiu W, Liu YJ, Cheng G, Liu ZJ, et al. (January 2017). "Structural and functional analyses of human DDX41 DEAD domain". Protein & Cell. 8 (1): 72–76. doi:10.1007/s13238-016-0351-9. PMC   5233616 . PMID   27928732.
10. Omura H, Oikawa D, Nakane T, Kato M, Ishii R, Ishitani R, et al. (October 2016). "Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide". Scientific Reports. 6 (1): 34756. Bibcode:2016NatSR...634756O. doi:10.1038/srep34756. PMC   5056382 . PMID   27721487.
11. Tungalag S, Shinriki S, Hirayama M, Nagamachi A, Kanai A, Inaba T, et al. (June 2023). "Ribosome profiling analysis reveals the roles of DDX41 in translational regulation". International Journal of Hematology. 117 (6): 876–888. doi:10.1007/s12185-023-03558-2. PMID   36780110. S2CID   256826641.
12. Churpek J (1993). "DDX41-Associated Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia". NIH. Gene Reviews. PMID   34723452.

Further reading

• Kim K, Ong F, Sasaki K (January 2023). "Current Understanding of DDX41 Mutations in Myeloid Neoplasms". Cancers. 15 (2): 344. doi: 10.3390/cancers15020344 . PMC   9857085 . PMID   36672294.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ (April 2002). "Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis". RNA. 8 (4): 426–439. doi:10.1017/S1355838202021088. PMC   1370266 . PMID   11991638.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. Bibcode:2004PNAS..10112130B. doi: 10.1073/pnas.0404720101 . PMC   514446 . PMID   15302935.
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, et al. (January 2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77–83. Bibcode:2005Natur.433...77A. doi:10.1038/nature03207. PMID   15635413. S2CID   4344740.
• Abdul-Ghani M, Hartman KL, Ngsee JK (July 2005). "Abstrakt interacts with and regulates the expression of sorting nexin-2". Journal of Cellular Physiology. 204 (1): 210–218. doi:10.1002/jcp.20285. PMC   2963638 . PMID   15690390.
• Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R (April 2006). "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5391–5396. Bibcode:2006PNAS..103.5391N. doi: 10.1073/pnas.0507066103 . PMC   1459365 . PMID   16565220.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.