MDA5

IFIH1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIFIH1, AGS7, Hlcd, IDDM19, MDA-5, MDA5, RLR-2, SGMRT1, interferon induced with helicase C domain 1
External IDsOMIM: 606951 MGI: 1918836 HomoloGene: 32535 GeneCards: IFIH1
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2q24.2Start162,267,079 bp[1]
End162,318,703 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

64135

71586

Ensembl

ENSG00000115267

ENSMUSG00000026896

UniProt

Q9BYX4

Q8R5F7

RefSeq (mRNA)

NM_022168

NM_001164477
NM_027835

RefSeq (protein)

NP_071451

NP_001157949
NP_082111

Location (UCSC)Chr 2: 162.27 – 162.32 MbChr 2: 62.6 – 62.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

MDA5 (Melanoma Differentiation-Associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the IFIH1 gene.[5] MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor (recognizing dsRNA) that is a sensor for viruses. MDA5 typically recognizes dsRNA that is over 2000nts in length.[6] For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2.[7] The signaling cascades in MDA5 is initiated via CARD domain.[8]

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 that is upregulated in response to treatment with beta-interferon (IFNB) and a protein kinase C-activating compound, mezerein (MEZ). Irreversible reprogramming of melanomas can be achieved by treatment with both these agents; treatment with either agent alone only achieves reversible differentiation.[5]

Clinical significance

Mutations in IFIH1/MDA5 are associated to Singleton-Merten Syndrome [9] and to Aicardi–Goutières syndrome.

Antibodies against MDA5 are associated to amyopathic dermatomyositis with rapidly progressive interstitial lung disease.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000115267 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026896 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. 1 2 "Entrez Gene: IFIH1 interferon induced with helicase C domain 1".
  6. ↑ Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S (July 2008). "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5". The Journal of Experimental Medicine. 205 (7): 1601–10. doi:10.1084/jem.20080091. PMC 2442638. PMID 18591409.
  7. ↑ Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O (January 2010). "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses". Proceedings of the National Academy of Sciences of the United States of America. 107 (4): 1512–7. Bibcode:2010PNAS..107.1512S. doi:10.1073/pnas.0912986107. PMC 2824407. PMID 20080593.
  8. ↑ Takeuchi O, Akira S (February 2008). "MDA5/RIG-I and virus recognition". Current Opinion in Immunology. 20 (1): 17–22. doi:10.1016/j.coi.2008.01.002. PMID 18272355.
  9. ↑ Rutsch F, MacDougall M, Lu C, Buers I, Mamaeva O, Nitschke Y, Rice GI, Erlandsen H, Kehl HG, Thiele H, Nürnberg P, Höhne W, Crow YJ, Feigenbaum A, Hennekam RC (February 2015). "A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome". American Journal of Human Genetics. 96 (2): 275–82. doi:10.1016/j.ajhg.2014.12.014. PMC 4320263. PMID 25620204.

Further reading

  • Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB (January 2002). "mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties". Proceedings of the National Academy of Sciences of the United States of America. 99 (2): 637–42. Bibcode:2002PNAS...99..637K. doi:10.1073/pnas.022637199. PMC 117358. PMID 11805321.
  • Kovacsovics M, Martinon F, Micheau O, Bodmer JL, Hofmann K, Tschopp J (May 2002). "Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation". Current Biology. 12 (10): 838–43. doi:10.1016/S0960-9822(02)00842-4. PMID 12015121.
  • Cocude C, Truong MJ, Billaut-Mulot O, Delsart V, Darcissac E, Capron A, Mouton Y, Bahr GM (December 2003). "A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication". The Journal of General Virology. 84 (Pt 12): 3215–25. doi:10.1099/vir.0.19300-0. PMID 14645903.
  • Kang DC, Gopalkrishnan RV, Lin L, Randolph A, Valerie K, Pestka S, Fisher PB (March 2004). "Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene". Oncogene. 23 (9): 1789–800. doi:10.1038/sj.onc.1207300. PMID 14676839.
  • Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE (December 2004). "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter". Proceedings of the National Academy of Sciences of the United States of America. 101 (49): 17264–9. Bibcode:2004PNAS..10117264A. doi:10.1073/pnas.0407639101. PMC 535396. PMID 15563593.
  • Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M, Akira S, Yonehara S, Kato A, Fujita T (September 2005). "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity". Journal of Immunology. 175 (5): 2851–8. doi:10.4049/jimmunol.175.5.2851. PMID 16116171.
  • Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S (October 2005). "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction". Nature Immunology. 6 (10): 981–8. doi:10.1038/ni1243. PMID 16127453.
  • Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J (October 2005). "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus". Nature. 437 (7062): 1167–72. Bibcode:2005Natur.437.1167M. doi:10.1038/nature04193. PMID 16177806.
  • Lin L, Su Z, Lebedeva IV, Gupta P, Boukerche H, Rai T, Barber GN, Dent P, Sarkar D, Fisher PB (November 2006). "Activation of Ras/Raf protects cells from melanoma differentiation-associated gene-5-induced apoptosis". Cell Death and Differentiation. 13 (11): 1982–93. doi:10.1038/sj.cdd.4401899. PMID 16575407.
  • Smyth DJ, Cooper JD, Bailey R, Field S, Burren O, Smink LJ, Guja C, Ionescu-Tirgoviste C, Widmer B, Dunger DB, Savage DA, Walker NM, Clayton DG, Todd JA (June 2006). "A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region". Nature Genetics. 38 (6): 617–9. doi:10.1038/ng1800. PMID 16699517.
  • Berghäll H, Sirén J, Sarkar D, Julkunen I, Fisher PB, Vainionpää R, Matikainen S (July 2006). "The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines". Microbes and Infection. 8 (8): 2138–44. doi:10.1016/j.micinf.2006.04.005. PMID 16782388.
  • Sirén J, Imaizumi T, Sarkar D, Pietilä T, Noah DL, Lin R, Hiscott J, Krug RM, Fisher PB, Julkunen I, Matikainen S (July 2006). "Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines". Microbes and Infection. 8 (8): 2013–20. doi:10.1016/j.micinf.2006.02.028. PMID 16797201.
  • Barral PM, Morrison JM, Drahos J, Gupta P, Sarkar D, Fisher PB, Racaniello VR (April 2007). "MDA-5 is cleaved in poliovirus-infected cells". Journal of Virology. 81 (8): 3677–84. doi:10.1128/JVI.01360-06. PMC 1866155. PMID 17267501.
  • Marinou I, Montgomery DS, Dickson MC, Binks MH, Moore DJ, Bax DE, Wilson AG (2007). "The interferon induced with helicase domain 1 A946T polymorphism is not associated with rheumatoid arthritis". Arthritis Research & Therapy. 9 (2): R40. doi:10.1186/ar2179. PMC 1906818. PMID 17442111.
  • Sutherland A, Davies J, Owen CJ, Vaikkakara S, Walker C, Cheetham TD, James RA, Perros P, Donaldson PT, Cordell HJ, Quinton R, Pearce SH (August 2007). "Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility". The Journal of Clinical Endocrinology and Metabolism. 92 (8): 3338–41. doi:10.1210/jc.2007-0173. PMID 17535987.
  • Matsukura S, Kokubu F, Kurokawa M, Kawaguchi M, Ieki K, Kuga H, Odaka M, Suzuki S, Watanabe S, Homma T, Takeuchi H, Nohtomi K, Adachi M (2007). "Role of RIG-I, MDA-5, and PKR on the expression of inflammatory chemokines induced by synthetic dsRNA in airway epithelial cells". International Archives of Allergy and Immunology. 143 Suppl 1: 80–3. doi:10.1159/000101411. PMID 17541283.
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