MDA5

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MDA5
MDA5
according to PDB  2RQB
other names

IFIH1

Existing structural data : 2RQB , 3B6E , 3GA3 , 4GL2

Properties of human protein
Mass / length primary structure 116.6 kilodaltons / 1,025 amino acids (isoform 1)

25 kilodaltons 221 amino acids (isoform 2)

Isoforms 2
Identifier
Gene names MDA5 AGS7, Hlcd, IDDM19, MDA-5, RLR-2
External IDs
Enzyme classification
EC, category 3.6.4.13
Orthologue
human House mouse
Entrez 64135 71586
Ensemble ENSG00000115267 ENSMUSG00000026896
UniProt Q9BYX4 Q8R5F7
Refseq (mRNA) NM_022168 NM_001164477
Refseq (protein) NP_071451 NP_001157949
Gene locus Chr 2: 162.27 - 162.32 Mb Chr 2: 62.6 - 62.65 Mb
PubMed search 64135 71586

MDA5 ( English melanoma differentiation-associated protein 5 , Melanoma differentiation antigen 5 ') is a resistance factor against RNA viruses with double-stranded genome in mammals from the family of RIG-I-like receptors (RLR).

properties

The MDA5 is a pattern recognition receptor for ds RNA in the cytosol . The MDA5 protein consists of three functional parts. The binding of dsRNA to the C terminus activates a helicase function in the middle of the MDA5 , which is used to defend against viruses containing dsRNA. After binding of dsRNA, the N- terminal CARD protein domain ( caspase recruitment domain ) contained in the MDA5 induces type 1 interferons via the protein IPS-1 (synonym VISA , Cardif ). The strongest activation of MDA5 occurs by dsRNA over 2000 base pairs in length. The RLR LGP2 is involved in the antiviral function of the MDA5 . By binding to dsRNA, MDA5 proteins form a fiber-like structure.

The IFIH1 gene codes for the MDA5 protein . The Singleton-Merten syndrome is caused by mutations of IFIH1 causes and mutations at IFIH1 are at the origin of Aicardi syndrome Goutières involved. Mutations in the MDA5 are suspected to be involved in lupus erythematosus .

literature

Individual evidence

  1. ^ O. Takeuchi, S. Akira: MDA5 / RIG-I and virus recognition. In: Current opinion in immunology. Volume 20, Number 1, February 2008, ISSN  0952-7915 , pp. 17-22, doi : 10.1016 / j.coi.2008.01.002 , PMID 18272355 .
  2. A. Szabo, E. Rajnavolgyi: Collaboration of Toll-like and RIG-I-like receptors in human dendritic cells: tRIGgering antiviral innate immune responses. In: American journal of clinical and experimental immunology. Volume 2, number 3, 2013, ISSN  2164-7712 , pp. 195-207, PMID 24179728 , PMC 3808934 (free full text).
  3. H. Kato, O. Takeuchi, E. Mikamo-Satoh, R. Hirai, T. Kawai, K. Matsushita, A. Hiiragi, TS Dermody, T. Fujita, S. Akira: Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. In: The Journal of experimental medicine. Volume 205, number 7, July 2008, ISSN  1540-9538 , pp. 1601-1610, doi : 10.1084 / jem.20080091 , PMID 18591409 , PMC 2442638 (free full text).
  4. T. Satoh, H. Kato, Y. Kumagai, M. Yoneyama, S. Sato, K. Matsushita, T. Tsujimura, T. Fujita, S. Akira, O. Takeuchi: LGP2 is a positive regulator of RIG-I - and MDA5-mediated antiviral responses. In: Proceedings of the National Academy of Sciences . Volume 107, number 4, January 2010, ISSN  1091-6490 , pp. 1512-1517, doi : 10.1073 / pnas.0912986107 , PMID 20080593 , PMC 2824407 (free full text).
  5. Y. Del Toro Duany, B. Wu, S. Hur: MDA5-filament, dynamics and disease. In: Current opinion in virology. [Electronic publication before printing] February 2015, ISSN  1879-6265 , doi : 10.1016 / j.coviro.2015.01.011 , PMID 25676875 .
  6. F. Rutsch, M. MacDougall, C. Lu, I. Buers, O. Mamaeva, Y. Nitschke, GI Rice, H. Erlandsen, HG Kehl, H. Thiele, P. Nürnberg, W. Höhne, YJ Crow, A. Feigenbaum, RC Hennekam: A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome. In: American Journal of Human Genetics . Volume 96, number 2, February 2015, ISSN  1537-6605 , pp. 275-282, doi : 10.1016 / j.ajhg.2014.12.014 , PMID 25620204 , PMC 4320263 (free full text).
  7. L. Oliveira, NA Sinicato, M. Postal, S. Appenzeller, TB Niewold: Dysregulation of antiviral helicase pathways in systemic lupus erythematosus. In: Frontiers in genetics. Volume 5, 2014, ISSN  1664-8021 , p. 418, doi : 10.3389 / fgene.2014.00418 , PMID 25505487 , PMC 4243696 (free full text).