InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: MAVS

Summary

InnateDB Gene

IDBG-49080.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAVS

Gene Name

mitochondrial antiviral signaling protein

Synonyms

Species

Homo sapiens

Ensembl Gene

ENSG00000088888

Encoded Proteins

IDBP-364593

mitochondrial antiviral signaling protein

IDBP-364599

mitochondrial antiviral signaling protein

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 19036819

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.

PMID 16177806

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.

PMID 16125763

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.

PMID 20032188

MAVS facilitates cell death by disrupting the mitochondrial membrane potential and by activating caspases.

PMID 20140199

MAVS-dependent RIG-I-like receptor (RLR) signalling regulates the quantity, quality, and balance of the immune response to West Nile virus (WNV) infection.

PMID 20451243

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.

PMID 20554965

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.

PMID 20661427

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.

PMID 20699220

MAVS (IPS1) plays an important role in regulating the host anti-viral response by binding to viral polymerase and inhibiting IFN-beta production.

PMID 21110072

MAVS negatively regulates the stability of voltage-dependent anion channel 1 (VDAC1) and thereby inhibits apoptosis in the response to release of cytochrome c.

PMID 21454965

The MAVS signalling pathway in non-myeloid cells is crucial for dsRNA-mediated natural killer cell activation. (Demonstrated in murine model)

PMID 22844514

Tyrosine phosphorylation of MAVS at amino acid residue Tyr9 is critical for the induction of IFNB signalling.

PMID 23028806

MAVS mRNA is degraded in response to foreign RNA and poly(I:C) to suppress hyper-immune reaction in late-phase antiviral signalling.

PMID 23582325

MAVS is required for optimal NLRP3 inflammasome activity by mediating mitochondrial recruitment of NLRP3.

PMID 23555247

MAVS is targeted by enterovirus protease to evade antiviral immunity.

PMID 23951545

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.

PMID 24651600

Upon viral infection, MAVS recruits MKK7 onto mitochondria, leading to the induction of apoptosis by MAP2K7 activated MAPK9

PMID 25463536

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.

PMID 25816776

RNA cleavage products, catalyzed by RNASEL, bind to DHX33 to facilitate the formation of a complex with MAVS and NLRP3 during viral infection.

PMID 27213432

HACE1 plays an inhibitory role in virus-induced signalling by disrupting the MAVS-TRAF3 complex.

PMID 26246171

MARCH5 modulates MAVS-mediated antiviral signalling, preventing excessive immune reactions.

PMID 26385923

MAVS directly interacts with TRAF6 through its potential TRAF6-binding motif 2.

InnateDB Annotation from Orthologs

Summary

PMID 21454965

[Mus musculus] The Mavs signalling pathway in non-myeloid cells is crucial for dsRNA-mediated natural killer cell activation.

PMID 22844514

[Mus musculus] Tyrosine phosphorylation of Mavs at amino acid residue Tyr9 is critical for the induction of Ifnb signalling. (Demonstrated in human)

PMID 23499490

[Mus musculus] Upon infection with encephalitic Bunyavirus, RIG-I/MAVS signalling activates SARM1 to mediate neuronal cell death.

PMID 23754752

[Mus musculus] MAVS binds to VDAC1 to trigger viral-induced apoptosis.

PMID 24362933

[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.

PMID 26079065

[Mus musculus] Antiviral response to rotavirus in infected macrophages is fully Mavs-dependent.

PMID 25897172

[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.

PMID 26633895

[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.

PMID 26246171

[Mus musculus] March5 modulates Mavs-mediated antiviral signalling, preventing excessive immune reactions.

PMID 26348439

[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

ENST00000428216	ENSP00000401980
ENST00000416600	ENSP00000413749

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 156 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.

Experimentally validated
Total	156 [view]
Protein-Protein	156 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	11 [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:0007165	signal transduction
GO:0016032	viral process
GO:0032480	negative regulation of type I interferon production
GO:0032481	positive 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:0039529	RIG-I signaling pathway
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 sequence-specific DNA binding transcription factor activity
GO:0051607	defense response to virus
GO:0060340	positive regulation of type I interferon-mediated signaling pathway
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

Cellular Component

GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005777	peroxisome
GO:0005778	peroxisomal membrane
GO:0016021	integral component of membrane
GO:0031966	mitochondrial membrane

Orthologs

Species

Mus musculus

Bos taurus

Gene ID

Gene Order

ENSMUSG00000037523

View Gene Order

ENSBTAG00000013545

Not yet available

Pathways

NETPATH

REACTOME

REACT_24938

TRAF6 mediated IRF7 activation pathway

REACT_25271

Negative regulators of RIG-I/MDA5 signaling pathway

REACT_25026

TRAF3-dependent IRF activation pathway pathway

REACT_24969

TRAF6 mediated NF-kB activation pathway

REACT_25039

NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway

REACT_25359

RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway

REACT_6802

Innate Immune System pathway

REACT_6900

Immune System pathway

KEGG

hsa04622

RIG-I-like receptor signaling pathway pathway

hsa04623

Cytosolic DNA-sensing pathway pathway

hsa05160

Hepatitis C pathway

INOH

PID NCI

Cross-References

SwissProt

Q7Z434

TrEMBL

UniProt Splice Variant

Entrez Gene

57506

UniGene

Hs.570362

RefSeq

NM_001206491 NM_020746

HUGO

HGNC:29233

OMIM

609676

CCDS

CCDS56176 CCDS33437

HPRD

13847

IMGT

EMBL

AB033097 AB097003 AB232371 AK023799 AK123956 AK130992 AK291785 AK296897 AL109804 AL353194 BC044952 CH471133 DQ167126 DQ174270 DQ181928 EF467323 EF467324

GenPept

AAH44952 AAZ80417 ABA19229 ABA54890 ABR24161 ABR24162 BAA86585 BAB14684 BAC77356 BAC85473 BAC85734 BAE79738 BAF84474 BAG59455 CAI11041 CAI18851 EAX10481

RNA Seq Atlas

57506