UniProtKB - Q66HG9 (MAVS_RAT)
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Protein
Mitochondrial antiviral-signaling protein
Gene
Mavs
Organism
Rattus norvegicus (Rat)
Status
Functioni
Required for innate immune defense against viruses. Acts downstream of DHX33, DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis (By similarity).By similarity
GO - Molecular functioni
- CARD domain binding Source: RGD
- protein kinase binding Source: RGD
- signal transducer activity Source: RGD
GO - Biological processi
- activation of innate immune response Source: RGD
- cellular response to exogenous dsRNA Source: UniProtKB
- defense response to bacterium Source: UniProtKB
- defense response to virus Source: RGD
- innate immune response Source: UniProtKB
- negative regulation of viral genome replication Source: RGD
- positive regulation of chemokine (C-C motif) ligand 5 production Source: RGD
- positive regulation of defense response to virus by host Source: UniProtKB
- positive regulation of DNA binding transcription factor activity Source: RGD
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: RGD
- positive regulation of interferon-alpha production Source: UniProtKB
- positive regulation of interferon-alpha secretion Source: UniProtKB
- positive regulation of interferon-beta production Source: UniProtKB
- positive regulation of interferon-beta secretion Source: UniProtKB
- positive regulation of interleukin-6 secretion Source: UniProtKB
- positive regulation of interleukin-8 production Source: RGD
- positive regulation of IP-10 production Source: RGD
- positive regulation of protein import into nucleus, translocation Source: RGD
- positive regulation of protein phosphorylation Source: RGD
- positive regulation of response to cytokine stimulus Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: RGD
- positive regulation of transcription factor import into nucleus Source: RGD
- positive regulation of tumor necrosis factor production Source: RGD
- positive regulation of tumor necrosis factor secretion Source: UniProtKB
- positive regulation of type I interferon-mediated signaling pathway Source: RGD
- positive regulation of type I interferon production Source: RGD
- regulation of peroxisome organization Source: RGD
- RIG-I signaling pathway Source: RGD
- signal transduction Source: RGD
Keywordsi
Biological process | Antiviral defense, Immunity, Innate immunity |
Enzyme and pathway databases
Reactomei | R-RNO-936440 Negative regulators of DDX58/IFIH1 signaling |
Names & Taxonomyi
Protein namesi | Recommended name: Mitochondrial antiviral-signaling proteinShort name: MAVS Alternative name(s): Interferon beta promoter stimulator protein 1 Short name: IPS-1 Virus-induced-signaling adapter Short name: VISA |
Gene namesi | Name:Mavs Synonyms:Ips1, Visa |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 1359371 Mavs |
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 482 | CytoplasmicBy similarityAdd BLAST | 482 | |
Transmembranei | 483 – 500 | HelicalSequence analysisAdd BLAST | 18 | |
Topological domaini | 501 – 507 | Mitochondrial intermembraneBy similarity | 7 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion outer membrane, PeroxisomePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000144098 | 1 – 507 | Mitochondrial antiviral-signaling proteinAdd BLAST | 507 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 152 | PhosphoserineCombined sources | 1 | |
Modified residuei | 157 | PhosphoserineBy similarity | 1 | |
Modified residuei | 172 | PhosphoserineBy similarity | 1 | |
Modified residuei | 178 | PhosphoserineBy similarity | 1 | |
Modified residuei | 186 | PhosphoserineBy similarity | 1 | |
Modified residuei | 220 | PhosphoserineBy similarity | 1 | |
Modified residuei | 234 | Asymmetric dimethylarginineBy similarity | 1 | |
Modified residuei | 256 | PhosphoserineBy similarity | 1 | |
Modified residuei | 387 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Ubiquitinated. Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH; ITCH-dependent polyubiquitination is mediated by the interaction with PCBP2 and leads to MAVS/IPS1 proteasomal degradation. Ubiquitinated by RNF125, leading to its degradation by the proteasome. Undergoes 'Lys-48'-linked ubiquitination catalyzed by SMURF1.By similarity
Keywords - PTMi
Methylation, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q66HG9 |
PRIDEi | Q66HG9 |
PTM databases
iPTMneti | Q66HG9 |
PhosphoSitePlusi | Q66HG9 |
Interactioni
Subunit structurei
Self-associates and polymerizes (via CARD domains) to form 400 nM long three-stranded helical filaments on mitochondria, filament nucleation requires interaction with DDX58/RIG-I whose CARD domains act as a template for filament assembly (By similarity). Interacts with DDX58/RIG-I, IFIH1/MDA5, TRAF2, TRAF6 and C1QBP. May interact with IRF3, FADD, RIPK1, IKBKE, CHUK and IKBKB. 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 and ITCH. Interacts with CYLD. Interacts with SRC. Interacts with DHX58/LGP2 and IKBKE. Interacts with TMEM173/MITA. Interacts with IFIT3 (via N-terminus). Interacts with TBK1 only in the presence of IFIT3. Interacts with MUL1. Interacts with ANKRD17. Interacts with NDFIP1 (By similarity). Interacts with SMURF1; the interaction is mediated by NDFIP1 and leads to MAVS ubiquitination and degradation (By similarity). Interacts (via C-terminus) with GPATCH3; the interaction is markedly increased upon viral infection (By similarity). Directly interacts (via CARD domain) with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates (By similarity). Interacts with DHX33 (via the helicase C-terminal domain) (By similarity).By similarity
GO - Molecular functioni
- CARD domain binding Source: RGD
- protein kinase binding Source: RGD
Protein-protein interaction databases
IntActi | Q66HG9 1 interactor. |
MINTi | Q66HG9 |
STRINGi | 10116.ENSRNOP00000033476 |
Structurei
3D structure databases
ProteinModelPortali | Q66HG9 |
SMRi | Q66HG9 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 10 – 77 | CARDAdd BLAST | 68 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 10 – 77 | Required for interaction with NLRX1By similarityAdd BLAST | 68 | |
Regioni | 143 – 147 | Interaction with TRAF2By similarity | 5 | |
Regioni | 153 – 158 | Interaction with TRAF6By similarity | 6 | |
Regioni | 340 – 507 | Interaction with DHX33By similarityAdd BLAST | 168 | |
Regioni | 435 – 440 | Interaction with TRAF6By similarity | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 97 – 233 | Pro-richAdd BLAST | 137 |
Domaini
Both CARD and transmembrane domains are essential for antiviral function. The CARD domain is responsible for interaction with DDX58/RIG-i and IFIH1/MDA5 (By similarity).By similarity
The transmembrane domain and residues 288-424 are essential for its interaction with DHX58/LGP2.By similarity
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG410IS5U Eukaryota ENOG410Y2HK LUCA |
GeneTreei | ENSGT00510000049120 |
HOGENOMi | HOG000231697 |
HOVERGENi | HBG079638 |
InParanoidi | Q66HG9 |
KOi | K12648 |
OMAi | EQDTELG |
OrthoDBi | EOG091G040S |
PhylomeDBi | Q66HG9 |
TreeFami | TF333444 |
Family and domain databases
InterProi | View protein in InterPro IPR031964 CARD_dom IPR026148 Mt_antiviral_sig_pro |
PANTHERi | PTHR21446 PTHR21446, 1 hit |
Pfami | View protein in Pfam PF16739 CARD_2, 1 hit |
i Sequence
Sequence statusi: Complete.
Q66HG9-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTFAEEKTYK YIRYNHSKFC CVDVLEILPY LSCLTTSDQD RLRASYKQLG
60 70 80 90 100
NQGTLWELFN TLQRRPGWVE VFIRALRICE LPGLAEQVTR VYQSYLPPGA
110 120 130 140 150
SLHSLDPLQS PRIPTTVSEP SAFAAGHTIP DSGFQDKPGY PKPVQDTQPP
160 170 180 190 200
KSPVENSEEP PQANFGAIPR MSGDSLISSP NPPALSPQPS REHPEQEPEL
210 220 230 240 250
GGPSTANVDS VPIATYGPVS PTVSFQPLPR IAPRTNLSPG VTVSALSAKT
260 270 280 290 300
TLSSSSTGSA FAKGAGDQAK AATCVSTKEG VPTNSVTTSS VPSIKPVPVN
310 320 330 340 350
TMSSKLPIST KSTAATPSTV PTNIAPSKLP INSVYTGIVP SKVTASVAKA
360 370 380 390 400
SASTMPPERN NKQAKETLEA PATVVTTGSS LTRPDISSRS LHSGPELSKP
410 420 430 440 450
GVLVSQVDNE PFSACSMDLA ISPSTSLGSE PNHGPEENEY SSFRIQVDKS
460 470 480 490 500
PSVDLLGSPE PLATQQSPEE EEPCASSVSW AKWLGATSAL LAAFLAVMLY
RSRHLAQ
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC081869 mRNA Translation: AAH81869.1 |
RefSeqi | NP_001005556.1, NM_001005556.1 XP_006235096.1, XM_006235034.3 XP_006235097.1, XM_006235035.3 XP_006235098.1, XM_006235036.2 XP_008760401.1, XM_008762179.2 |
UniGenei | Rn.34996 |
Genome annotation databases
Ensembli | ENSRNOT00000034146; ENSRNOP00000033476; ENSRNOG00000025295 ENSRNOT00000090764; ENSRNOP00000073053; ENSRNOG00000025295 |
GeneIDi | 311430 |
KEGGi | rno:311430 |
UCSCi | RGD:1359371 rat |
Similar proteinsi
Entry informationi
Entry namei | MAVS_RAT | |
Accessioni | Q66HG9Primary (citable) accession number: Q66HG9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 8, 2005 |
Last sequence update: | October 11, 2004 | |
Last modified: | April 25, 2018 | |
This is version 118 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |