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

• innate immune defense against viruses
• acts downstream of DDX58 & IFIH1
  • detection of intracellular dsRNA produced during viral replication
  • activation of NF-kappa-B, IRF3 & IRF7
  • induction of antiviral cytokines
    • IFN-beta, RANTES
• peroxisomal & mitochondrial MAVS act sequentially to create an antiviral cellular state
  • upon viral infection, peroxisomal MAVS induces rapid interferon-independent expression of defense factors that provide short-term protection
  • mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies & stabilizes the antiviral response
• may activate the same pathways following detection of extracellular dsRNA by TLR3
• may protect cells from apoptosis
• ubiquitinated
  • undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH
  • ITCH-dependent polyubiquitination is mediated by the interaction with PCBP2 & leads to MAVS/IPS1 proteasomal degradation
• interacts with DDX58, IFIH1, TRAF2, TRAF6
• may interact with IRF3, FADD, RIPK1, IKBKE, CHUK, IKBKB
• interacts with & is cleaved by HCV & hepatitis GB virus B NS3/4A proteases
• interacts with & is cleaved by HHAV protein 3ABC
• interacts with NLRX1
  • interaction with NLRX1 requires the CARD domain
• interacts with PSMA7
• interacts with TRAFD1
• interacts (via C-terminus) with PCBP2 in a complex containing MAVS/IPS1, PCBP2 & ITCH
• interacts with CYLD
• interacts with SRC
• interacts with DHX58/LGP2 & IKBKE
• interacts with TMEM173/MITA
• interacts with IFIT3 (via N-terminus)
• 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

More general terms

• mitochondrial membrane protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=57506
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:57506
• OMIM: https://mirror.omim.org/entry/609676
• UniProt: http://www.uniprot.org/uniprot/Q7Z434.html