Homo sapiens Gene: MAVS
Summary
InnateDB Gene IDBG-106954.1
Last Modified 2018-06-05 [Report errors or provide feedback]
Gene Symbol MAVS
Gene Name mitochondrial antiviral signaling protein
Synonyms CARDIF; IPS-1; IPS1; VISA
Species Homo sapiens
Ensembl Gene ENSG00000088888
Encoded Proteins
mitochondrial antiviral signaling protein
mitochondrial antiviral signaling protein
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
MAVS oligomer is essential in the formation of a multiprotein membrane-associated signalling complex that enables downstream activation of IRF3 and NF-kappaB in antiviral innate immunity.
MAVS is a caspase recruitment domain (CARD)-containing adaptor protein that interacts with DDX58 (RIG-I) and recruits CHUK (IKKalpha), IKBKB (IKKbeta) and IKBKE (IKKepsilon) kinases by means of its C-terminal region, leading to the activation of NF-kappaB and IRF3.
MAVS is an adaptor protein that contains an N-terminal caspase recruitment domain (CARD)-like domain and a C-terminal transmembrane domain, both of which are essential for MAVS signalling, while the transmembrane domain also targets MAVS to the mitochondria.
MAVS facilitates cell death by disrupting the mitochondrial membrane potential and by activating caspases.
MAVS-dependent RIG-I-like receptor (RLR) signalling regulates the quantity, quality, and balance of the immune response to West Nile virus (WNV) infection.
MAVS in peroxisomes induces a rapid interferon-independent expression of defence factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signalling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response.
MAVS interacts with hepatitis B virus X protein and this promotes the degradation of MAVS via Lys(136) ubiquitination, preventing the induction of IFN-beta.
MAVS (IPS-1) interacts with MFN1 upon virus-infection or 5'ppp-RNA activation through redistribution of MAVS to form speck-like aggregates in cells.
MAVS (IPS1) plays an important role in regulating the host anti-viral response by binding to viral polymerase and inhibiting IFN-beta production.
MAVS negatively regulates the stability of voltage-dependent anion channel 1 (VDAC1) and thereby inhibits apoptosis in the response to release of cytochrome c.
The MAVS signalling pathway in non-myeloid cells is crucial for dsRNA-mediated natural killer cell activation. (Demonstrated in murine model)
Tyrosine phosphorylation of MAVS at amino acid residue Tyr9 is critical for the induction of IFNB signalling.
MAVS mRNA is degraded in response to foreign RNA and poly(I:C) to suppress hyper-immune reaction in late-phase antiviral signalling.
MAVS is required for optimal NLRP3 inflammasome activity by mediating mitochondrial recruitment of NLRP3.
MAVS is targeted by enterovirus protease to evade antiviral immunity.
The binding of MAVS to Traf2, Traf5, and Traf6 is dependent on virus infection and MAVS polymerization. The TRAF proteins promote ubiquitination that recruits IKBKG binding to the MAVS signalling complex.
Upon viral infection, MAVS recruits MKK7 onto mitochondria, leading to the induction of apoptosis by MAP2K7 activated MAPK9
Macrocyclic NS3-4A resistance-associated amino acid variants (RAVs) with substitutions at residue D168 of the hepatitis C virus protease result in an increased capacity of NS3-4A to cleave MAVS and suppress IFNB1 induction.
RNA cleavage products, catalyzed by RNASEL, bind to DHX33 to facilitate the formation of a complex with MAVS and NLRP3 during viral infection.
HACE1 plays an inhibitory role in virus-induced signalling by disrupting the MAVS-TRAF3 complex.
MARCH5 modulates MAVS-mediated antiviral signalling, preventing excessive immune reactions.
MAVS directly interacts with TRAF6 through its potential TRAF6-binding motif 2.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] The Mavs signalling pathway in non-myeloid cells is crucial for dsRNA-mediated natural killer cell activation.
[Mus musculus] Tyrosine phosphorylation of Mavs at amino acid residue Tyr9 is critical for the induction of Ifnb signalling. (Demonstrated in human)
[Mus musculus] Upon infection with encephalitic Bunyavirus, RIG-I/MAVS signalling activates SARM1 to mediate neuronal cell death.
[Mus musculus] MAVS binds to VDAC1 to trigger viral-induced apoptosis.
[Mus musculus] Plasmodium RNA is a pathogen-associated molecular pattern (PAMP) capable of activating a type I IFN response via the cytosolic pattern recognition receptors Ifih1 and Mavs, as well as via transcription factors Irf3 and Irf7.
[Mus musculus] Antiviral response to rotavirus in infected macrophages is fully Mavs-dependent.
[Mus musculus] Alveolar macrophages detect respiratory syncytial virus (RSV) via the Mavs /Ddx58 pathway and are a major source of type I interferons upon RSV infection.
[Mus musculus] Transgenic picornavirus RNA-dependent RNA polymerase (RdRP) expression in mice produces a quantitatively dramatic, sustained, effective antiviral interferon-stimulated genes (ISG) network, which requires the MDA5-MAVS pathway.
[Mus musculus] March5 modulates Mavs-mediated antiviral signalling, preventing excessive immune reactions.
[Mus musculus] Baiap2l1 recruits Ube2i to sumoylate Pcbp2, which causes its cytoplasmic translocation during viral infection and the sumoylated Pcbp2 associates with Mavs to initiate its degradation, leading to downregulation of antiviral responses.
Entrez Gene
Summary This gene encodes an intermediary protein necessary in the virus-triggered beta interferon signaling pathways. It is required for activation of transcription factors which regulate expression of beta interferon and contributes to antiviral immunity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
Gene Information
Type Protein coding
Genomic Location Chromosome 20:3846799-3876123
Strand Forward strand
Band p13
Transcripts
ENST00000416600 ENSP00000413749
ENST00000428216 ENSP00000401980
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 215 experimentally validated interaction(s) in this database.
They are also associated with 17 interaction(s) predicted by orthology.
Experimentally validated
Total 215 [view]
Protein-Protein 215 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 17 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004871 signal transducer activity
GO:0005515 protein binding
GO:0019901 protein kinase binding
GO:0050700 CARD domain binding
Biological Process
GO:0001934 positive regulation of protein phosphorylation
GO:0002218 activation of innate immune response
GO:0002230 positive regulation of defense response to virus by host
GO:0002376 immune system process
GO:0007165 signal transduction
GO:0016032 viral process
GO:0016579 protein deubiquitination
GO:0032480 negative regulation of type I interferon production
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0032757 positive regulation of interleukin-8 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0033160 positive regulation of protein import into nucleus, translocation
GO:0035549 positive regulation of interferon-beta secretion
GO:0042742 defense response to bacterium
GO:0042993 positive regulation of transcription factor import into nucleus
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045071 negative regulation of viral genome replication
GO:0045087 innate immune response (InnateDB)
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051091 positive regulation of DNA binding transcription factor activity
GO:0051607 defense response to virus
GO:0060340 positive regulation of type I interferon-mediated signaling pathway
GO:0060760 positive regulation of response to cytokine stimulus
GO:0071360 cellular response to exogenous dsRNA
GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production
GO:0071660 positive regulation of IP-10 production
GO:1900063 regulation of peroxisome organization
GO:1902741 positive regulation of interferon-alpha secretion
GO:1904469 positive regulation of tumor necrosis factor secretion
GO:2000778 positive regulation of interleukin-6 secretion
Cellular Component
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005777 peroxisome
GO:0005778 peroxisomal membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0031966 mitochondrial membrane
Orthologs
Species
Bos taurus
Mus musculus
Gene ID
Gene Order
Not yet available
Pathways
NETPATH
REACTOME
TRAF3-dependent IRF activation pathway pathway
Post-translational protein modification pathway
Ovarian tumor domain proteases pathway
Negative regulators of DDX58/IFIH1 signaling pathway
Metabolism of proteins pathway
Immune System pathway
TRAF6 mediated NF-kB activation pathway
Innate Immune System pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
DDX58/IFIH1-mediated induction of interferon-alpha/beta pathway
Deubiquitination pathway
TRAF6 mediated IRF7 activation pathway
KEGG
NOD-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
Hepatitis B pathway
Measles pathway
Influenza A pathway
Herpes simplex infection pathway
INOH
PID NCI
Cross-References
SwissProt Q7Z434
TrEMBL
UniProt Splice Variant
Entrez Gene 57506
UniGene
RefSeq NM_001206491 NM_020746
HUGO HGNC:29233
OMIM 609676
CCDS CCDS33437 CCDS56176
HPRD
IMGT
EMBL AB033097 AB097003 AB232371 AK023799 AK123956 AK130992 AK291785 AK296897 AL109804 AL353194 BC044952 CH471133 DQ167126 DQ174270 DQ181928 EF467323 EF467324 KC415005
GenPept AAH44952 AAZ80417 ABA19229 ABA54890 ABR24161 ABR24162 AGF94754 BAA86585 BAB14684 BAC77356 BAC85473 BAC85734 BAE79738 BAF84474 BAG59455 CAI11041 CAI18851 EAX10481
RNA Seq Atlas 57506