| IED ID | IndEnz0002018890 |
| Enzyme Type ID | protease018890 |
| Protein Name |
Antiviral innate immune response receptor RIG-I DEAD box protein 58 Probable ATP-dependent RNA helicase DDX58 EC 3.6.4.13 RIG-I-like receptor 1 RLR-1 Retinoic acid-inducible gene 1 protein RIG-1 Retinoic acid-inducible gene I protein RIG-I |
| Gene Name | Ddx58 |
| Organism | Mus musculus (Mouse) |
| 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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MTAEQRQNLQAFRDYIKKILDPTYILSYMSSWLEDEEVQYIQAEKNNKGPMEAASLFLQYLLKLQSEGWFQAFLDALYHAGYCGLCEAIESWDFQKIEKLEEHRLLLRRLEPEFKATVDPNDILSELSECLINQECEEIRQIRDTKGRMAGAEKMAECLIRSDKENWPKVLQLALEKDNSKFSELWIVDKGFKRAESKADEDDGAEASSIQIFIQEEPECQNLSQNPGPPSEASSNNLHSPLKPRNYQLELALPAKKGKNTIICAPTGCGKTFVSLLICEHHLKKFPCGQKGKVVFFANQIPVYEQQATVFSRYFERLGYNIASISGATSDSVSVQHIIEDNDIIILTPQILVNNLNNGAIPSLSVFTLMIFDECHNTSKNHPYNQIMFRYLDHKLGESRDPLPQVVGLTASVGVGDAKTAEEAMQHICKLCAALDASVIATVRDNVAELEQVVYKPQKISRKVASRTSNTFKCIISQLMKETEKLAKDVSEELGKLFQIQNREFGTQKYEQWIVGVHKACSVFQMADKEEESRVCKALFLYTSHLRKYNDALIISEDAQMTDALNYLKAFFHDVREAAFDETERELTRRFEEKLEELEKVSRDPSNENPKLRDLYLVLQEEYHLKPETKTILFVKTRALVDALKKWIEENPALSFLKPGILTGRGRTNRATGMTLPAQKCVLEAFRASGDNNILIATSVADEGIDIAECNLVILYEYVGNVIKMIQTRGRGRARDSKCFLLTSSADVIEKEKANMIKEKIMNESILRLQTWDEMKFGKTVHRIQVNEKLLRDSQHKPQPVPDKENKKLLCGKCKNFACYTADIRVVETSHYTVLGDAFKERFVCKPHPKPKIYDNFEKKAKIFCAKQNCSHDWGIFVRYKTFEIPVIKIESFVVEDIVSGVQNRHSKWKDFHFERIQFDPAEMSV |
| Enzyme Length | 926 |
| Uniprot Accession Number | Q6Q899 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 243; /note=ATP; via carbonyl oxygen; /evidence=ECO:0000269|PubMed:21979817; BINDING 248; /note=ATP; /evidence=ECO:0000269|PubMed:21979817 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; |
| DNA Binding | |
| EC Number | 3.6.4.13 |
| Enzyme Function | FUNCTION: Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and proinflammatory cytokines. Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments. The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms. Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons. Ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Sendai virus (SeV), Rhabdoviridae and Flaviviridae. It also detects rotavirus and orthoreovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome. Detects dsRNA produced from non-self dsDNA by RNA polymerase III. May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. {ECO:0000269|PubMed:16039576, ECO:0000269|PubMed:16625202, ECO:0000269|PubMed:17942531, ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 265..272; /note="ATP"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00541, ECO:0000269|PubMed:21979817" |
| Features | Alternative sequence (6); Beta strand (15); Binding site (2); Chain (1); Cross-link (8); Domain (5); Helix (42); Metal binding (4); Modified residue (2); Motif (1); Mutagenesis (1); Nucleotide binding (1); Region (2); Sequence conflict (3); Turn (4) |
| Keywords | 3D-structure;ATP-binding;Acetylation;Alternative splicing;Antiviral defense;Cell junction;Cell membrane;Cell projection;Cytoplasm;Cytoskeleton;Helicase;Hydrolase;Immunity;Innate immunity;Isopeptide bond;Membrane;Metal-binding;Nucleotide-binding;Phosphoprotein;RNA-binding;Reference proteome;Repeat;Tight junction;Ubl conjugation;Zinc |
| Interact With | P22682; Q80ZE3 |
| Induction | INDUCTION: By interferon (IFN). |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell projection, ruffle membrane {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cell junction, tight junction {ECO:0000250}. Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles. {ECO:0000250}. |
| Modified Residue | MOD_RES 771; /note=Phosphothreonine; by CK2; /evidence=ECO:0000250|UniProtKB:O95786; MOD_RES 859; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:O95786 |
| Post Translational Modification | PTM: Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-771 results in inhibition of its activity while dephosphorylation at these sites results in its activation. {ECO:0000250|UniProtKB:O95786}.; PTM: ISGylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation. ISGylation negatively regulates its function in antiviral signaling response. {ECO:0000250|UniProtKB:O95786}.; PTM: Sumoylated, probably by MUL1; inhibiting its polyubiquitination. {ECO:0000250|UniProtKB:O95786}.; PTM: Ubiquitinated. 'Lys-63' ubiquitination by RNF135, which occurs after RNA-binding and homodimerization, releases the autoinhibition of the CARD domains by the RLR CTR domain, an essential step in the activation of the RIG-I signaling pathway. Also ubiquitinated by TRIM4. Also undergoes 'Lys-48' ubiquitination by RNF125 that leads to proteasomal degradation. 'Lys-48' ubiquitination follows viral infection and is enhanced by 'Lys-63'-linked ubiquitination of the CARD domains that promotes interaction with VCP/p97 and subsequent recruitment of RNF125 (By similarity). Within a negative feedback loop involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-813 by CBL also elicits the proteasomal degradation of DDX58 (PubMed:23374343). Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor (By similarity). Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal degradation (By similarity). Deubiquitinated by USP27X that cleaves 'Lys-63'-linked ubiquitin chains and inhibits the innate immune receptor activity (By similarity). {ECO:0000250|UniProtKB:O95786, ECO:0000269|PubMed:23374343}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 3TBK; 6BZH; |
| Mapped Pubmed ID | 12466851; 14610273; 16116171; 16210631; 16286919; 17475874; 17709747; 17893708; 17977974; 18523264; 18548002; 18550535; 18591409; 18650396; 18975620; 18978796; 19115016; 19158679; 19224920; 19474102; 19596990; 19683681; 19733381; 19805092; 19915568; 19936053; 19966212; 20071582; 20080593; 20123960; 20140199; 20360967; 20427526; 20661430; 20875468; 21224412; 21233210; 21267068; 21278304; 21292167; 21336305; 21576486; 21677750; 21703541; 21791617; 21820332; 22008794; 22072774; 22072781; 22138643; 22235281; 22314235; 22402283; 22634618; 22745163; 22778433; 22787226; 22912573; 22912574; 23064150; 23171655; 23209422; 23338611; 23408632; 23499489; 23553835; 23567548; 23644230; 23820901; 23836649; 23918369; 23926323; 23950712; 23966395; 24015671; 24039580; 24270516; 24360797; 24362933; 24412064; 24493797; 24729608; 25005357; 25012502; 25047809; 25064677; 25119032; 25158146; 25172485; 25260755; 25326752; 25456137; 25557055; 25585356; 25758257; 25843799; 26392465; 26466960; 26525917; 26588779; 26862753; 26939124; 27183587; 27349479; 27438481; 27477784; 27506794; 27793594; 28057020; 28276156; 28287082; 28377495; 28424327; 28550197; 28594325; 28634194; 28710430; 29117565; 29492454; 29593341; 30550976; 30842237; 30902547; 30902577; 31139191; 31237466; 31243280; 31335993; 31409781; 31519811; 31595820; 31623059; 31636462; 31843969; 32027733; 32032681; 32152220; 32251420; 32277054; 32336543; 33086056; 33177158; 33459340; 34326461; 34464586; 34619148; |
| Motif | MOTIF 373..376; /note=DECH box |
| Gene Encoded By | |
| Mass | 105,975 |
| Kinetics | |
| Metal Binding | METAL 811; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU01125; METAL 814; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU01125; METAL 865; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU01125; METAL 870; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU01125 |
| Rhea ID | RHEA:13065 |
| Cross Reference Brenda |