From Wikipedia, the free encyclopedia
  (Redirected from IFIH1)
Jump to: navigation, search
Interferon induced with helicase C domain 1
Protein IFIH1 PDB 2RQB.png
Rendering based on PDB 2RQB.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols IFIH1 ; AGS7; Hlcd; IDDM19; MDA-5; MDA5; RLR-2
External IDs OMIM606951 MGI1918836 HomoloGene32535 GeneCards: IFIH1 Gene
EC number
RNA expression pattern
PBB GE IFIH1 219209 at tn.png
More reference expression data
Species Human Mouse
Entrez 64135 71586
Ensembl ENSG00000115267 ENSMUSG00000026896
UniProt Q9BYX4 Q8R5F7
RefSeq (mRNA) NM_022168 NM_001164477
RefSeq (protein) NP_071451 NP_001157949
Location (UCSC) Chr 2:
163.12 – 163.18 Mb
Chr 2:
62.6 – 62.65 Mb
PubMed search [1] [2]

MDA5 (Melanoma Differentiation-Associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the IFIH1 gene.[1] 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.[2] For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2.[3] The signaling cascades in MDA5 is initiated via CARD domain.[4]

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.[1]

Clinical significance[edit]

Mutations in IFIH1/MDA5 are associated to Singleton-Merten Syndrome .[5]


  1. ^ a b "Entrez Gene: IFIH1 interferon induced with helicase C domain 1". 
  2. ^ Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S.; Takeuchi; Mikamo-Satoh; Hirai; Kawai; Matsushita; Hiiragi; Dermody; Fujita; Akira (Jul 2008). "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5". J Exp Med. 205 (7): 1601–1610. doi:10.1084/jem.20080091. PMC 2442638. PMID 18591409. 
  3. ^ Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O; Kato; Kumagai; Yoneyama; Sato; Matsushita; Tsujimura; Fujita; Akira; Takeuchi (January 2010). "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses". Proc. Natl. Acad. Sci. U.S.A. 107 (4): 1512–7. Bibcode:2010PNAS..107.1512S. doi:10.1073/pnas.0912986107. PMC 2824407. PMID 20080593. 
  4. ^ Takeuchi, O; Akira, S (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. 
  5. ^ Rutsch, F; MacDougall, M; Lu, C; Buers, I; Mamaeva, O; Nitschke, Y; Rice, G. I.; Erlandsen, H; Kehl, H. G.; Thiele, H; Nürnberg, P; Höhne, W; Crow, Y. J.; Feigenbaum, A; Hennekam, R. C. (2015). "A Specific IFIH1 Gain-of-function Mutation Causes Singleton-Merten Syndrome". The American Journal of Human Genetics. doi:10.1016/j.ajhg.2014.12.014. PMID 25620204.  edit

Further reading[edit]