Mitochondrial antiviral-signaling protein

Mitochondrial antiviral signaling protein
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2VGQ​, 3J6C​, 3J6J​, 3RC5​, 4P4H​
Identifiers
Symbols	MAVS ; CARDIF; IPS-1; IPS1; VISA
External IDs	OMIM: 609676 MGI: 2444773 HomoloGene: 17004 GeneCards: MAVS Gene
Gene ontology Molecular function • signal transducer activity • protein binding • protein kinase binding • CARD domain binding Cellular component • mitochondrion • mitochondrial outer membrane • peroxisomal membrane • integral component of membrane • mitochondrial membrane Biological process • positive regulation of protein phosphorylation • activation of innate immune response • positive regulation of defense response to virus by host • signal transduction • viral process • negative regulation of type I interferon production • positive regulation of interferon-alpha production • positive regulation of interferon-beta production • positive regulation of interleukin-8 production • positive regulation of tumor necrosis factor production • positive regulation of protein import into nucleus, translocation • RIG-I signaling pathway • defense response to bacterium • positive regulation of transcription factor import into nucleus • positive regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of viral genome replication • innate immune response • positive regulation of transcription from RNA polymerase II promoter • positive regulation of sequence-specific DNA binding transcription factor activity • defense response to virus • positive regulation of type I interferon-mediated signaling pathway • cellular response to exogenous dsRNA • positive regulation of chemokine (C-C motif) ligand 5 production • positive regulation of IP-10 production • regulation of peroxisome organization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	57506	228607
Ensembl	ENSG00000088888	ENSMUSG00000037523
UniProt	Q7Z434	Q8VCF0
RefSeq (mRNA)	NM_001206491	NM_001206382
RefSeq (protein)	NP_001193420	NP_001193311
Location (UCSC)	Chr 20: 3.85 – 3.88 Mb	Chr 2: 131.23 – 131.25 Mb
PubMed search

Mitochondrial antiviral-signaling protein (MAVS) is a protein that in humans is encoded by the MAVS gene.^[1][2][3] The protein is also known by the names VISA (virus-induced signaling adapter), IPS-1 and Cardif. Aggregated MAVS forms protease resistant prion-like aggregates that activate IRF3 dimerization.^[4]

Function

Double-stranded RNA viruses are recognized in a cell type-dependent manner by the transmembrane receptor TLR3 or by the cytoplasmic RNA helicases MDA5 and RIGI. These interactions initiate signaling pathways that differ in their initial steps but converge in the activation of the protein kinases IKKA (CHUK) and IKKB (IKBKB; MIM 603258), which activate NFKB, or TBK1 and IKBKE (IKBKE), which activate IRF3. Activated IRF3 and NFKB induce transcription of IFNβ (IFNB1). For the TLR3 pathway, the intermediary molecule before the pathways converge is the cytoplasmic protein TRIF (TICAM1). For RIGI, the intermediary protein is mitochondria-bound MAVS.^[3][5]

References

1. Seth RB, Sun L, Ea CK, Chen ZJ (Sep 2005). "Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3". Cell 122 (5): 669–82. doi:10.1016/j.cell.2005.08.012. PMID 16125763.
2. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB (Sep 2005). "VISA is an adapter protein required for virus-triggered IFN-beta signaling". Mol Cell 19 (6): 727–40. doi:10.1016/j.molcel.2005.08.014. PMID 16153868.
3. "Entrez Gene: VISA virus-induced signaling adapter".
4. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ (Aug 5, 2011). "MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response.". Cell 146 (3): 448–61. doi:10.1016/j.cell.2011.06.041. PMC 3179916. PMID 21782231.
5. Sen GC, Sarkar SN (2005). "Hitching RIG to action". Nat. Immunol. 6 (11): 1074–6. doi:10.1038/ni1105-1074. PMID 16239922.

Further reading

• Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O (2000). "Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.". DNA Res. 6 (5): 337–45. doi:10.1093/dnares/6.5.337. PMID 10574462.
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.". Oncogene 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501.
• Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S (2005). "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction.". Nat. Immunol. 6 (10): 981–8. doi:10.1038/ni1243. PMID 16127453.
• Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J (2005). "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus.". Nature 437 (7062): 1167–72. doi:10.1038/nature04193. PMID 16177806.
• Li XD, Sun L, Seth RB, Pineda G, Chen ZJ (2006). "Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity.". Proc. Natl. Acad. Sci. U.S.A. 102 (49): 17717–22. doi:10.1073/pnas.0508531102. PMC 1308909. PMID 16301520.
• Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (2006). "Transcriptome analysis of human gastric cancer.". Mamm. Genome 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID 16341674.
• Loo YM, Owen DM, Li K, Erickson AK, Johnson CL, Fish PM, Carney DS, Wang T, Ishida H, Yoneyama M, Fujita T, Saito T, Lee WM, Hagedorn CH, Lau DT, Weinman SA, Lemon SM, Gale M (2006). "Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection.". Proc. Natl. Acad. Sci. U.S.A. 103 (15): 6001–6. doi:10.1073/pnas.0601523103. PMC 1458687. PMID 16585524.
• Cheng G, Zhong J, Chisari FV (2006). "Inhibition of dsRNA-induced signaling in hepatitis C virus-infected cells by NS3 protease-dependent and -independent mechanisms.". Proc. Natl. Acad. Sci. U.S.A. 103 (22): 8499–504. doi:10.1073/pnas.0602957103. PMC 1482521. PMID 16707574.
• Lin R, Lacoste J, Nakhaei P, Sun Q, Yang L, Paz S, Wilkinson P, Julkunen I, Vitour D, Meurs E, Hiscott J (2006). "Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage.". J. Virol. 80 (12): 6072–83. doi:10.1128/JVI.02495-05. PMC 1472616. PMID 16731946.
• Saha SK, Pietras EM, He JQ, Kang JR, Liu SY, Oganesyan G, Shahangian A, Zarnegar B, Shiba TL, Wang Y, Cheng G (2006). "Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif.". EMBO J. 25 (14): 3257–63. doi:10.1038/sj.emboj.7601220. PMC 1523175. PMID 16858409.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization.". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.
• Opitz B, Vinzing M, van Laak V, Schmeck B, Heine G, Günther S, Preissner R, Slevogt H, N'Guessan PD, Eitel J, Goldmann T, Flieger A, Suttorp N, Hippenstiel S (2007). "Legionella pneumophila induces IFNbeta in lung epithelial cells via IPS-1 and IRF3, which also control bacterial replication.". J. Biol. Chem. 281 (47): 36173–9. doi:10.1074/jbc.M604638200. PMID 16984921.
• Chen Z, Benureau Y, Rijnbrand R, Yi J, Wang T, Warter L, Lanford RE, Weinman SA, Lemon SM, Martin A, Li K (2007). "GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS.". J. Virol. 81 (2): 964–76. doi:10.1128/JVI.02076-06. PMC 1797450. PMID 17093192.
• Hirata Y, Broquet AH, Menchén L, Kagnoff MF (2007). "Activation of innate immune defense mechanisms by signaling through RIG-I/IPS-1 in intestinal epithelial cells.". J. Immunol. 179 (8): 5425–32. doi:10.4049/jimmunol.179.8.5425. PMID 17911629.
• Zeng W, Xu M, Liu S, Sun L, Chen ZJ (2009). "Key Role of Ubc5 and Lysine-63 Polyubiquitination in Viral Activation of IRF3.". Mol Cell 140 (3): 315–25. doi:10.1016/j.molcel.2009.09.037. PMID 19854139.
• Liu S, Chen J, Cai X, Wu J, Chen X, Wu Y, Sun L and Chen ZJ (2013). "MAVS Recruits Multiple Ubiquitin E3 Ligases to Activate Antiviral Signaling Cascades.". Elife 2 (e00785). doi:10.7554/eLife.00785. PMID 23951545.
• Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, and Chen ZJ (2015). "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation.". Science 347 (6227). doi:10.1126/science.aaa2630. PMID 25636800.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.