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mitochondrial antiviral-signaling protein; MAVS; CARD adapter inducing interferon beta; cardif; interferon beta promoter stimulator protein 1; IPS-1; NF-kappa-B-activating protein 031N; virus-induced-signaling adapter; VISA (MAVS, IPS1, KIAA1271, VISA)
Function:
1) innate immune defense against viruses
2) acts downstream of DDX58 & IFIH1
a) detection of intracellular dsRNA produced during viral replication
b) activation of NF-kappa-B, IRF3 & IRF7
c) induction of antiviral cytokines
- IFN-beta, RANTES
3) peroxisomal & mitochondrial MAVS act sequentially to create an antiviral cellular state
a) upon viral infection, peroxisomal MAVS induces rapid interferon-independent expression of defense factors that provide short-term protection
b) mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies & stabilizes the antiviral response
4) may activate the same pathways following detection of extracellular dsRNA by TLR3
5) may protect cells from apoptosis
6) ubiquitinated
a) undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH
b) ITCH-dependent polyubiquitination is mediated by the interaction with PCBP2 & leads to MAVS/IPS1 proteasomal degradation
7) interacts with DDX58, IFIH1, TRAF2, TRAF6
8) may interact with IRF3, FADD, RIPK1, IKBKE, CHUK, IKBKB
9) interacts with & is cleaved by HCV & hepatitis GB virus B NS3/4A proteases
10) interacts with & is cleaved by HHAV protein 3ABC
11) interacts with NLRX1
- interaction with NLRX1 requires the CARD domain
12) interacts with PSMA7
13) interacts with TRAFD1
14) interacts (via C-terminus) with PCBP2 in a complex containing MAVS/IPS1, PCBP2 & ITCH
14) interacts with CYLD
15) interacts with SRC
16) interacts with DHX58/LGP2 & IKBKE
17) interacts with TMEM173/MITA
18) interacts with IFIT3 (via N-terminus)
19) interacts with TBK1 only in the presence of IFIT3
Structure:
- both CARD & transmembrane domains are essential for antiviral function
- the CARD domain is responsible for interaction with DDX58/RIG-I & IFIH1/MDA5
- the transmembrane domain & residues 300-444 are essential for its interaction with DHX58/LGP2
- contains 1 CARD domain
Compartment:
- mitochondrial outer membrane
- peroxisome
Alternative splicing: named isoforms=3
Expression:
- expressed in T-cells, monocytes, epithelial cells, hepatocytes
- ubiquitously expressed
- highest levels in heart, skeletal muscle, liver, placenta, peripheral blood leukocytes
Pathology:
- cleavage by hepatitis C virus NS3/4A protease complex leads to inactivation
General
mitochondrial membrane protein
phosphoprotein
Properties
SIZE: entity length = 540 aa
MW = 57 kD
COMPARTMENT: mitochondria
peroxisome
MOTIF: CARD domain {10-77}
MOTIF: NLRX1 interaction {10-77}
proline-rich region
SITE: 103-153
MOTIF: proline residue (SEVERAL)
TRAF2 interaction {143-147}
Thr phosphorylation site {T147}
Ser phosphorylation site {S152}
TRAF6 interaction {153-158}
MOTIF: Ser phosphorylation site {S157}
Thr phosphorylation site {T163}
Ser phosphorylation site {S165}
Ser phosphorylation site {S222}
Ser phosphorylation site {S233}
Thr phosphorylation site {T234}
Ser phosphorylation site {S253}
Ser phosphorylation site {S258}
Ser phosphorylation site {S366}
Ser phosphorylation site {S373}
Ser phosphorylation site {S375}
Thr phosphorylation site {T398}
proteolytic site {427-428}
TRAF6 interaction {455-460}
proteolytic site {508-509}
transmembrane domain {514-534}
Mitochondrial intermembrane {535-540}
Database Correlations
OMIM 609676
UniProt Q7Z434
Entrez Gene 57506
Kegg hsa:57506
References
UniProt :accession Q7Z434