MDA5
MDA5 | ||
---|---|---|
according to PDB 2RQB | ||
other names |
IFIH1 |
|
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
- D. Luo: Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like receptors. In: RNA biology. Volume 11, number 1, 2014, ISSN 1555-8584 , pp. 25-32, doi : 10.4161 / rna.27717 , PMID 24457940 , PMC 3929420 (free full text).
- DC Rawling, AM Pyle: Parts, assembly and operation of the RIG-I family of motors. In: Current opinion in structural biology. Volume 25, April 2014, ISSN 1879-033X , pp. 25-33, doi : 10.1016 / j.sbi.2013.11.011 , PMID 24878341 , PMC 4070197 (free full text).
- M. Yoneyama, K. Onomoto, M. Jogi, T. Akaboshi, T. Fujita: Viral RNA detection by RIG-I-like receptors. In: Current opinion in immunology. Volume 32C, February 2015, ISSN 1879-0372 , pp. 48-53, doi : 10.1016 / j.coi.2014.12.012 , PMID 25594890 .
- E. Dixit, JC Kagan: Intracellular pathogen detection by RIG-I-like receptors. In: Advances in immunology. Volume 117, 2013, ISSN 1557-8445 , pp. 99-125, doi : 10.1016 / B978-0-12-410524-9.00004-9 , PMID 23611287 , PMC 3947775 (free full text).
- KR Rodriguez, AM Bruns, CM Horvath: MDA5 and LGP2: accomplices and antagonists of antiviral signal transduction. In: Journal of virology. Volume 88, number 15, August 2014, ISSN 1098-5514 , pp. 8194-8200, doi : 10.1128 / JVI.00640-14 , PMID 24850739 , PMC 4135949 (free full text).
Individual evidence
- ^ 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 .
- ↑ 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).
- ↑ 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).
- ↑ 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).
- ↑ 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 .
- ↑ 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).
- ↑ 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).