MDA5

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IFIH1
Protein IFIH1 PDB 2RQB.png
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)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for IFIH1
Genomic location for IFIH1
Band2q24.2Start162,267,079 bp[1]
End162,318,703 bp[1]
RNA expression pattern
PBB GE IFIH1 219209 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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[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 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[edit]

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[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115267 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026896 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b "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[edit]