MAVS_RAT
ID MAVS_RAT Reviewed; 507 AA.
AC Q66HG9;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Mitochondrial antiviral-signaling protein;
DE Short=MAVS;
DE AltName: Full=Interferon beta promoter stimulator protein 1;
DE Short=IPS-1;
DE AltName: Full=Virus-induced-signaling adapter;
DE Short=VISA;
GN Name=Mavs; Synonyms=Ips1, Visa;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Required for innate immune defense against viruses. Acts
CC downstream of DHX33, DDX58/RIG-I and IFIH1/MDA5, which detect
CC intracellular dsRNA produced during viral replication, to coordinate
CC pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to
CC the subsequent induction of antiviral cytokines such as IFN-beta and
CC RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to
CC create an antiviral cellular state. Upon viral infection, peroxisomal
CC MAVS induces the rapid interferon-independent expression of defense
CC factors that provide short-term protection, whereas mitochondrial MAVS
CC activates an interferon-dependent signaling pathway with delayed
CC kinetics, which amplifies and stabilizes the antiviral response. May
CC activate the same pathways following detection of extracellular dsRNA
CC by TLR3. May protect cells from apoptosis.
CC {ECO:0000250|UniProtKB:Q7Z434}.
CC -!- SUBUNIT: Self-associates and polymerizes (via CARD domains) to form 400
CC nM long three-stranded helical filaments on mitochondria, filament
CC nucleation requires interaction with DDX58/RIG-I whose CARD domains act
CC as a template for filament assembly. Interacts with DDX58/RIG-I,
CC IFIH1/MDA5, TRAF2, TRAF6 and C1QBP. May interact with FADD, RIPK1, CHUK
CC and IKBKB. Interacts (when phosphorylated) with IRF3; following
CC activation and phosphorylation on the pLxIS motif by TBK1, recruits
CC IRF3. Interacts with NLRX1. Interaction with NLRX1 requires the CARD
CC domain. Interacts with PSMA7 (By similarity). Interacts with TRAFD1 (By
CC similarity). Interacts (via C-terminus) with PCBP2 in a complex
CC containing MAVS/IPS1, PCBP2 and ITCH. Interacts with CYLD. Interacts
CC with SRC. Interacts with DHX58/LGP2 and IKBKE. Interacts with STING1.
CC Interacts with IFIT3 (via N-terminus). Interacts with TBK1 only in the
CC presence of IFIT3. Interacts with TTLL12; the interaction prevents MAVS
CC binding to TBK1 and IKBKE (By similarity). Interacts with MUL1.
CC Interacts with ANKRD17. Interacts with NDFIP1. Interacts with SMURF1;
CC the interaction is mediated by NDFIP1 and leads to MAVS ubiquitination
CC and degradation. Interacts with UBXN1; this interaction inhibits MAVS-
CC mediated antiviral pathway. Interacts (via C-terminus) with GPATCH3;
CC the interaction is markedly increased upon viral infection. Directly
CC interacts (via CARD domain) with ATG5 and ATG12, either as ATG5 and
CC ATG12 monomers or as ATG12-ATG5 conjugates (By similarity). Interacts
CC with DHX33 (via the helicase C-terminal domain) (By similarity).
CC Interacts with DDX3X (via C-terminus); this interaction may occur
CC rapidly, but transiently after viral infection (By similarity). The
CC interaction with DDX3X potentiates MAVS-mediated IFNB induction (By
CC similarity). Conversely inhibition of this interaction prevents MAVS-
CC mediated IFNB induction (By similarity). Transiently interacts with
CC TRAF3 early during viral infection (By similarity). Interacts with CLPB
CC (By similarity). Interacts with TRAF3IP3 (By similarity). Interacts
CC with TOMM70; the interaction is enhanced by virus infection (By
CC similarity). Interacts with ZNFX1 (By similarity). Interacts with DHX15
CC (By similarity). Interacts with N4BP3; this interaction promotes the
CC polyubiquitination of MAVS (By similarity).
CC {ECO:0000250|UniProtKB:Q7Z434, ECO:0000250|UniProtKB:Q8VCF0}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q7Z434}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q7Z434}. Peroxisome
CC {ECO:0000250|UniProtKB:Q7Z434}.
CC -!- DOMAIN: Both CARD and transmembrane domains are essential for antiviral
CC function. The CARD domain is responsible for interaction with
CC DDX58/RIG-i and IFIH1/MDA5 (By similarity).
CC {ECO:0000250|UniProtKB:Q7Z434}.
CC -!- DOMAIN: The transmembrane domain and residues 288-424 are essential for
CC its interaction with DHX58/LGP2. {ECO:0000250|UniProtKB:Q7Z434}.
CC -!- DOMAIN: The pLxIS motif constitutes an IRF3-binding motif: following
CC phosphorylation by TBK1, the phosphorylated pLxIS motif of MAVS
CC recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to
CC induce type-I interferons and other cytokines.
CC {ECO:0000250|UniProtKB:Q7Z434}.
CC -!- PTM: Following activation, phosphorylated by TBK1 at Ser-422 in the
CC pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding
CC motif, leading to recruitment of the transcription factor IRF3 to
CC induce type-I interferons and other cytokines.
CC {ECO:0000250|UniProtKB:Q7Z434}.
CC -!- PTM: Ubiquitinated. Undergoes 'Lys-48'-linked polyubiquitination
CC catalyzed by ITCH; ITCH-dependent polyubiquitination is mediated by the
CC interaction with PCBP2 and leads to MAVS/IPS1 proteasomal degradation.
CC Ubiquitinated by RNF125, leading to its degradation by the proteasome.
CC Undergoes 'Lys-48'-linked ubiquitination catalyzed by SMURF1. Undergoes
CC 'Lys-63'-linked ubiquitination leading to enhanced interaction between
CC MAVS and TRAF2. {ECO:0000250|UniProtKB:Q7Z434}.
CC -!- PTM: Proteolytically cleaved by apoptotic caspases during apoptosis,
CC leading to its inactivation. Cleavage by CASP3 during virus-induced
CC apoptosis inactivates it, preventing cytokine overproduction.
CC {ECO:0000250|UniProtKB:Q7Z434}.
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DR EMBL; BC081869; AAH81869.1; -; mRNA.
DR RefSeq; NP_001005556.1; NM_001005556.1.
DR RefSeq; XP_006235096.1; XM_006235034.3.
DR RefSeq; XP_006235097.1; XM_006235035.3.
DR RefSeq; XP_006235098.1; XM_006235036.2.
DR RefSeq; XP_008760401.1; XM_008762179.2.
DR AlphaFoldDB; Q66HG9; -.
DR SMR; Q66HG9; -.
DR IntAct; Q66HG9; 1.
DR MINT; Q66HG9; -.
DR STRING; 10116.ENSRNOP00000033476; -.
DR iPTMnet; Q66HG9; -.
DR PhosphoSitePlus; Q66HG9; -.
DR jPOST; Q66HG9; -.
DR PaxDb; Q66HG9; -.
DR PRIDE; Q66HG9; -.
DR Ensembl; ENSRNOT00000090764; ENSRNOP00000073053; ENSRNOG00000025295.
DR GeneID; 311430; -.
DR KEGG; rno:311430; -.
DR UCSC; RGD:1359371; rat.
DR CTD; 57506; -.
DR RGD; 1359371; Mavs.
DR eggNOG; ENOG502SAUA; Eukaryota.
DR GeneTree; ENSGT00510000049120; -.
DR InParanoid; Q66HG9; -.
DR OMA; CVYQSYQ; -.
DR OrthoDB; 887440at2759; -.
DR PhylomeDB; Q66HG9; -.
DR TreeFam; TF333444; -.
DR Reactome; R-RNO-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-RNO-936440; Negative regulators of DDX58/IFIH1 signaling.
DR PRO; PR:Q66HG9; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000025295; Expressed in heart and 19 other tissues.
DR Genevisible; Q66HG9; RN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; ISO:RGD.
DR GO; GO:0005777; C:peroxisome; ISO:RGD.
DR GO; GO:0050700; F:CARD domain binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0035591; F:signaling adaptor activity; ISO:RGD.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISS:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISO:RGD.
DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; ISO:RGD.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD.
DR GO; GO:0071660; P:positive regulation of IP-10 production; ISO:RGD.
DR GO; GO:0002735; P:positive regulation of myeloid dendritic cell cytokine production; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0060760; P:positive regulation of response to cytokine stimulus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:RGD.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; ISO:RGD.
DR GO; GO:1900063; P:regulation of peroxisome organization; ISO:RGD.
DR GO; GO:0039529; P:RIG-I signaling pathway; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR CDD; cd08811; CARD_IPS1; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR031964; CARD_dom.
DR InterPro; IPR042144; CARD_IPS1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR026148; Mt_antiviral_sig_pro_met.
DR PANTHER; PTHR21446:SF6; PTHR21446:SF6; 1.
DR Pfam; PF16739; CARD_2; 1.
PE 1: Evidence at protein level;
KW Antiviral defense; Immunity; Innate immunity; Membrane; Methylation;
KW Mitochondrion; Mitochondrion outer membrane; Peroxisome; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..507
FT /note="Mitochondrial antiviral-signaling protein"
FT /id="PRO_0000144098"
FT TOPO_DOM 1..482
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 483..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..507
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250"
FT DOMAIN 10..77
FT /note="CARD"
FT REGION 10..77
FT /note="Required for interaction with NLRX1"
FT /evidence="ECO:0000250"
FT REGION 123..238
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..147
FT /note="Interaction with TRAF2"
FT /evidence="ECO:0000250"
FT REGION 153..158
FT /note="Interaction with TRAF6"
FT /evidence="ECO:0000250"
FT REGION 250..326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..507
FT /note="Interaction with DHX33"
FT /evidence="ECO:0000250|UniProtKB:Q8VCF0"
FT REGION 350..401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 435..440
FT /note="Interaction with TRAF6"
FT /evidence="ECO:0000250"
FT MOTIF 419..422
FT /note="pLxIS motif"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
FT COMPBIAS 277..326
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..394
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..473
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 408..409
FT /note="Cleavage; by CASP3"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCF0"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
FT MOD_RES 234
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCF0"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCF0"
FT MOD_RES 422
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000250|UniProtKB:Q7Z434"
SQ SEQUENCE 507 AA; 53805 MW; D2924B1E34CADE47 CRC64;
MTFAEEKTYK YIRYNHSKFC CVDVLEILPY LSCLTTSDQD RLRASYKQLG NQGTLWELFN
TLQRRPGWVE VFIRALRICE LPGLAEQVTR VYQSYLPPGA SLHSLDPLQS PRIPTTVSEP
SAFAAGHTIP DSGFQDKPGY PKPVQDTQPP KSPVENSEEP PQANFGAIPR MSGDSLISSP
NPPALSPQPS REHPEQEPEL GGPSTANVDS VPIATYGPVS PTVSFQPLPR IAPRTNLSPG
VTVSALSAKT TLSSSSTGSA FAKGAGDQAK AATCVSTKEG VPTNSVTTSS VPSIKPVPVN
TMSSKLPIST KSTAATPSTV PTNIAPSKLP INSVYTGIVP SKVTASVAKA SASTMPPERN
NKQAKETLEA PATVVTTGSS LTRPDISSRS LHSGPELSKP GVLVSQVDNE PFSACSMDLA
ISPSTSLGSE PNHGPEENEY SSFRIQVDKS PSVDLLGSPE PLATQQSPEE EEPCASSVSW
AKWLGATSAL LAAFLAVMLY RSRHLAQ
