| IED ID | IndEnz0002002576 |
| Enzyme Type ID | protease002576 |
| Protein Name |
Mitochondrial antiviral-signaling protein MAVS CARD adapter inducing interferon beta Cardif Interferon beta promoter stimulator protein 1 IPS-1 Putative NF-kappa-B-activating protein 031N Virus-induced-signaling adapter VISA |
| Gene Name | MAVS IPS1 KIAA1271 VISA |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MPFAEDKTYKYICRNFSNFCNVDVVEILPYLPCLTARDQDRLRATCTLSGNRDTLWHLFNTLQRRPGWVEYFIAALRGCELVDLADEVASVYQSYQPRTSDRPPDPLEPPSLPAERPGPPTPAAAHSIPYNSCREKEPSYPMPVQETQAPESPGENSEQALQTLSPRAIPRNPDGGPLESSSDLAALSPLTSSGHQEQDTELGSTHTAGATSSLTPSRGPVSPSVSFQPLARSTPRASRLPGPTGSVVSTGTSFSSSSPGLASAGAAEGKQGAESDQAEPIICSSGAEAPANSLPSKVPTTLMPVNTVALKVPANPASVSTVPSKLPTSSKPPGAVPSNALTNPAPSKLPINSTRAGMVPSKVPTSMVLTKVSASTVPTDGSSRNEETPAAPTPAGATGGSSAWLDSSSENRGLGSELSKPGVLASQVDSPFSGCFEDLAISASTSLGMGPCHGPEENEYKSEGTFGIHVAENPSIQLLEGNPGPPADPDGGPRPQADRKFQEREVPCHRPSPGALWLQVAVTGVLVVTLLVVLYRRRLH |
| Enzyme Length | 540 |
| Uniprot Accession Number | Q7Z434 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Required for innate immune defense against viruses (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20451243, PubMed:23087404, PubMed:20127681, PubMed:21170385, PubMed:24990078). 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 IFNB and RANTES (CCL5) (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20451243, PubMed:23087404, PubMed:25636800, PubMed:20127681, PubMed:21170385, PubMed:20628368, PubMed:33110251). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state (PubMed:20451243). 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 (PubMed:20451243). May activate the same pathways following detection of extracellular dsRNA by TLR3 (PubMed:16153868). May protect cells from apoptosis (PubMed:16125763). {ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20451243, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:24990078, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:33110251}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (8); Beta strand (3); Chain (1); Compositional bias (7); Domain (1); Erroneous initiation (1); Frameshift (1); Helix (8); Modified residue (14); Motif (1); Mutagenesis (23); Natural variant (5); Region (8); Sequence conflict (4); Site (9); Topological domain (2); Transmembrane (1) |
| Keywords | 3D-structure;Alternative splicing;Antiviral defense;Host-virus interaction;Immunity;Innate immunity;Membrane;Methylation;Mitochondrion;Mitochondrion outer membrane;Peroxisome;Phosphoprotein;Reference proteome;Transmembrane;Transmembrane helix;Ubl conjugation |
| Interact With | P00519; P46379; Q07021; Q13137; P27797; P12830; O00571; O95786; P36957; Q9BYX4; Q14164; Q13568; Q9Y2W7; Q8IWA4; Q8TDX7; Q96P20; Q9Y6K5; O43353; O75746; P42224; Q86WV6; Q9UHD2; P37173; Q12933; Q9Y4K3; Q14139; P0DTD8; Q7TFA1; P59636; P0DTC5; Q6WB96; Q69027; A2T3M4; Q9H1Y0; O95786-1; Q9BYX4; Q86UT6-1; Q96EQ8; Q86WV6; P61964; Q91WS2-1 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000269|PubMed:16125763}. Mitochondrion {ECO:0000269|PubMed:11780052, ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:25135833}. Peroxisome {ECO:0000269|PubMed:20451243}. |
| Modified Residue | MOD_RES 152; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"; MOD_RES 157; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 165; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"; MOD_RES 180; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 188; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 215; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 222; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 233; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 234; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 236; /note="Asymmetric dimethylarginine"; /evidence="ECO:0000250|UniProtKB:Q8VCF0"; MOD_RES 253; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 258; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"; MOD_RES 408; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q8VCF0"; MOD_RES 442; /note="Phosphoserine; by TBK1"; /evidence="ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953" |
| Post Translational Modification | PTM: Following activation, phosphorylated by TBK1 at Ser-442 in the pLxIS motif (PubMed:25636800, PubMed:27302953). The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines (PubMed:25636800). {ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953}.; PTM: Ubiquitinated (PubMed:19881509, PubMed:23087404, PubMed:25636800). 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 (PubMed:19881509). Ubiquitinated by RNF125, leading to its degradation by the proteasome (PubMed:17460044). Undergoes 'Lys-48'-linked ubiquitination catalyzed by SMURF1 (PubMed:23087404). {ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:25636800}.; PTM: Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation (PubMed:30878284). Cleavage by CASP3 during virus-induced apoptosis inactivates it, preventing cytokine overproduction (PubMed:30878284). {ECO:0000269|PubMed:30878284}.; PTM: (Microbial infection) Cleaved and degraded by hepatitis A virus (HAV) protein 3ABC allowing the virus to disrupt the activation of host IRF3 through the MDA5 pathway. {ECO:0000269|PubMed:17438296}.; PTM: (Microbial infection) Cleaved by the protease 2A of coxsackievirus B3, poliovirus and enterovirus 71 allowing the virus to disrupt the host type I interferon production. {ECO:0000269|PubMed:24390337, ECO:0000269|PubMed:28253362}.; PTM: (Microbial infection) Cleaved by Seneca Valley virus protease 3C allowing the virus to suppress interferon type-I production. {ECO:0000269|PubMed:28566380}.; PTM: (Microbial infection) Cleaved by HCV protease NS3/4A, thereby preventing the establishment of an antiviral state. {ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:16301520}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); Electron microscopy (3); X-ray crystallography (5) |
| Cross Reference PDB | 2MS7; 2MS8; 2VGQ; 3J6C; 3J6J; 3RC5; 4P4H; 4Z8M; 5JEK; 7DNI; |
| Mapped Pubmed ID | 10421793; 10581243; 11002417; 11717445; 12107169; 12133833; 12221085; 12692549; 12884866; 14703513; 15361868; 16281057; 16306936; 16394098; 16585524; 16585540; 16618810; 16707574; 16731946; 16846591; 16858409; 16914100; 16945160; 16984921; 17190786; 17327220; 17526488; 17911629; 17991829; 18307765; 18550535; 18692023; 18756281; 18761323; 18927075; 18977754; 18984593; 19028691; 19153231; 19193783; 19193793; 19351494; 19380491; 19479062; 19591957; 19644511; 19666475; 19668221; 19690333; 19701189; 19893624; 19902255; 19914245; 20007272; 20019757; 20032188; 20044805; 20154210; 20538852; 20554965; 20661427; 20699220; 20711230; 20877624; 20962078; 21068253; 21102435; 21127988; 21130742; 21187438; 21200404; 21268286; 21421666; 21507982; 21782231; 21865020; 21903422; 21957149; 22000020; 22105485; 22131337; 22301138; 22341464; 22619329; 22623778; 22626058; 22674996; 22792062; 22844514; 22870331; 22901541; 22911572; 23015697; 23028806; 23246644; 23260140; 23308256; 23453971; 23460740; 23542348; 23574001; 23582325; 24048902; 24391214; 24478431; 24529381; 24613846; 24623417; 24643253; 24659800; 24706939; 24722368; 24729608; 24782566; 24889249; 25142606; 25288302; 25416956; 25609814; 25640825; 25833049; 25950488; 26179906; 26183716; 26221961; 26223644; 26317833; 26385923; 26437794; 26512076; 26588843; 26646717; 26733681; 26893477; 26906558; 26954674; 26998762; 27213432; 27226371; 27438769; 27553710; 27593154; 27605671; 27629939; 27652379; 27705941; 27736772; 27899525; 28024153; 28222744; 28471483; 28480979; 28594325; 28607490; 28928438; 28956771; 28965816; 29097393; 29155878; 29165031; 29280086; 29317664; 29385716; 29743353; 29916539; 30258449; 30391331; 30460894; 30463990; 30472208; 30527812; 30930359; 30952814; 31235549; 31270229; 31304625; 31324787; 31806367; 31806368; 31829086; 31881323; 31915282; 31941397; 31968249; 31996459; 32190169; 32301534; 32386456; 32511263; 32776819; 33139700; 33177519; 33205822; 33412226; 33540654; 33582548; 33593967; 33603735; 33628342; 34016972; 34171297; 9008162; 9463386; 9689078; |
| Motif | MOTIF 439..442; /note=pLxIS motif; /evidence=ECO:0000269|PubMed:25636800 |
| Gene Encoded By | |
| Mass | 56,528 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |