DDX58_HUMAN
ID DDX58_HUMAN Reviewed; 925 AA.
AC O95786; A2RU81; Q5HYE1; Q5VYT1; Q9NT04;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Antiviral innate immune response receptor RIG-I {ECO:0000305};
DE AltName: Full=ATP-dependent RNA helicase DDX58 {ECO:0000305|PubMed:19211564};
DE EC=3.6.4.13 {ECO:0000269|PubMed:19211564};
DE AltName: Full=DEAD box protein 58;
DE AltName: Full=RIG-I-like receptor 1;
DE Short=RLR-1;
DE AltName: Full=Retinoic acid-inducible gene 1 protein;
DE Short=RIG-1;
DE AltName: Full=Retinoic acid-inducible gene I protein;
DE Short=RIG-I;
GN Name=DDX58 {ECO:0000312|HGNC:HGNC:19102};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-580.
RA Sun Y.-W.;
RT "RIG-I, a human homolog gene of RNA helicase, is induced by retinoic acid
RT during the differentiation of acute promyelocytic leukemia cell.";
RL Thesis (1997), Shanghai Institute of Hematology, China.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-580, AND INDUCTION.
RX PubMed=11890704; DOI=10.1006/bbrc.2002.6650;
RA Imaizumi T., Aratani S., Nakajima T., Carlson M., Matsumiya T., Tanji K.,
RA Ookawa K., Yoshida H., Tsuchida S., McIntyre T.M., Prescott S.M.,
RA Zimmerman G.A., Satoh K.;
RT "Retinoic acid-inducible gene-I is induced in endothelial cells by LPS and
RT regulates expression of COX-2.";
RL Biochem. Biophys. Res. Commun. 292:274-279(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-748 (ISOFORM 2), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 528-925 (ISOFORMS 1/2), AND VARIANT CYS-7.
RC TISSUE=Skin, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15181474; DOI=10.1139/o04-041;
RA Cui X.-F., Imaizumi T., Yoshida H., Borden E.C., Satoh K.;
RT "Retinoic acid-inducible gene-I is induced by interferon-gamma and
RT regulates the expression of interferon-gamma stimulated gene 15 in MCF-7
RT cells.";
RL Biochem. Cell Biol. 82:401-405(2004).
RN [8]
RP INDUCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15219805; DOI=10.1016/j.lfs.2004.01.030;
RA Imaizumi T., Yagihashi N., Hatakeyama M., Yamashita K., Ishikawa A.,
RA Taima K., Yoshida H., Inoue I., Fujita T., Yagihashi S., Satoh K.;
RT "Expression of retinoic acid-inducible gene-I in vascular smooth muscle
RT cells stimulated with interferon-gamma.";
RL Life Sci. 75:1171-1180(2004).
RN [9]
RP INDUCTION, MUTAGENESIS OF LYS-270, SUBCELLULAR LOCATION, BINDING TO
RP DOUBLE-STRANDED RNA, AND FUNCTION.
RX PubMed=15208624; DOI=10.1038/ni1087;
RA Yoneyama M., Kikuchi M., Natsukawa T., Shinobu N., Imaizumi T.,
RA Miyagishi M., Taira K., Akira S., Fujita T.;
RT "The RNA helicase RIG-I has an essential function in double-stranded RNA-
RT induced innate antiviral responses.";
RL Nat. Immunol. 5:730-737(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH MAVS/IPS1.
RX PubMed=16125763; DOI=10.1016/j.cell.2005.08.012;
RA Seth R.B., Sun L., Ea C.-K., Chen Z.J.;
RT "Identification and characterization of MAVS, a mitochondrial antiviral
RT signaling protein that activates NF-kappaB and IRF 3.";
RL Cell 122:669-682(2005).
RN [11]
RP INTERACTION WITH IKBKE AND TBK1.
RX PubMed=16281057; DOI=10.1038/sj.emboj.7600863;
RA Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B.;
RT "SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-
RT triggered IRF-3 activation pathways.";
RL EMBO J. 24:4018-4028(2005).
RN [12]
RP INDUCTION, MUTAGENESIS OF THR-55 AND LYS-270, BINDING TO DOUBLE-STRANDED
RP RNA, AND FUNCTION.
RX PubMed=15708988; DOI=10.1128/jvi.79.5.2689-2699.2005;
RA Sumpter R. Jr., Loo Y.-M., Foy E., Li K., Yoneyama M., Fujita T.,
RA Lemon S.M., Gale M. Jr.;
RT "Regulating intracellular antiviral defense and permissiveness to hepatitis
RT C virus RNA replication through a cellular RNA helicase, RIG-I.";
RL J. Virol. 79:2689-2699(2005).
RN [13]
RP FUNCTION, AND INTERACTION WITH MAVS/IPS1.
RX PubMed=16153868; DOI=10.1016/j.molcel.2005.08.014;
RA Xu L.-G., Wang Y.-Y., Han K.-J., Li L.-Y., Zhai Z., Shu H.-B.;
RT "VISA is an adapter protein required for virus-triggered IFN-beta
RT Signaling.";
RL Mol. Cell 19:727-740(2005).
RN [14]
RP FUNCTION, AND INTERACTION WITH MAVS/IPS1.
RX PubMed=16127453; DOI=10.1038/ni1243;
RA Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J.,
RA Takeuchi O., Akira S.;
RT "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon
RT induction.";
RL Nat. Immunol. 6:981-988(2005).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND ISGYLATION.
RX PubMed=16009940; DOI=10.1073/pnas.0504754102;
RA Zhao C., Denison C., Huibregtse J.M., Gygi S.P., Krug R.M.;
RT "Human ISG15 conjugation targets both IFN-induced and constitutively
RT expressed proteins functioning in diverse cellular pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10200-10205(2005).
RN [16]
RP INTERACTION WITH TRIM25, DOMAIN, SUBCELLULAR LOCATION, UBIQUITINATION AT
RP LYS-172, AND MUTAGENESIS OF LYS-99; LYS-169; LYS-172; LYS-181; LYS-190 AND
RP LYS-193.
RX PubMed=17392790; DOI=10.1038/nature05732;
RA Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., Takeuchi O.,
RA Akira S., Chen Z., Inoue S., Jung J.U.;
RT "TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated
RT antiviral activity.";
RL Nature 446:916-920(2007).
RN [17]
RP FUNCTION, SUBUNIT, RLR CTR DOMAIN, AND INTERACTION WITH DHX58.
RX PubMed=17190814; DOI=10.1073/pnas.0606699104;
RA Saito T., Hirai R., Loo Y.-M., Owen D., Johnson C.L., Sinha S.C., Akira S.,
RA Fujita T., Gale M. Jr.;
RT "Regulation of innate antiviral defenses through a shared repressor domain
RT in RIG-I and LGP2.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:582-587(2007).
RN [18]
RP UBIQUITINATION.
RX PubMed=17460044; DOI=10.1073/pnas.0611551104;
RA Arimoto K., Takahashi H., Hishiki T., Konishi H., Fujita T., Shimotohno K.;
RT "Negative regulation of the RIG-I signaling by the ubiquitin ligase
RT RNF125.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7500-7505(2007).
RN [19]
RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH CYLD.
RX PubMed=18636086; DOI=10.1038/embor.2008.136;
RA Friedman C.S., O'Donnell M.A., Legarda-Addison D., Ng A., Cardenas W.B.,
RA Yount J.S., Moran T.M., Basler C.F., Komuro A., Horvath C.M., Xavier R.,
RA Ting A.T.;
RT "The tumour suppressor CYLD is a negative regulator of RIG-I-mediated
RT antiviral response.";
RL EMBO Rep. 9:930-936(2008).
RN [20]
RP ISGYLATION.
RX PubMed=18057259; DOI=10.1128/jvi.01650-07;
RA Kim M.J., Hwang S.Y., Imaizumi T., Yoo J.Y.;
RT "Negative feedback regulation of RIG-I-mediated antiviral signaling by
RT interferon-induced ISG15 conjugation.";
RL J. Virol. 82:1474-1483(2008).
RN [21]
RP INTERACTION WITH STING1.
RX PubMed=18724357; DOI=10.1038/nature07317;
RA Ishikawa H., Barber G.N.;
RT "STING is an endoplasmic reticulum adaptor that facilitates innate immune
RT signalling.";
RL Nature 455:674-678(2008).
RN [22]
RP FUNCTION.
RX PubMed=19631370; DOI=10.1016/j.cell.2009.06.015;
RA Chiu Y.-H., Macmillan J.B., Chen Z.J.;
RT "RNA polymerase III detects cytosolic DNA and induces type I interferons
RT through the RIG-I pathway.";
RL Cell 138:576-591(2009).
RN [23]
RP FUNCTION.
RX PubMed=19576794; DOI=10.1016/j.immuni.2009.05.008;
RA Schlee M., Roth A., Hornung V., Hagmann C.A., Wimmenauer V., Barchet W.,
RA Coch C., Janke M., Mihailovic A., Wardle G., Juranek S., Kato H., Kawai T.,
RA Poeck H., Fitzgerald K.A., Takeuchi O., Akira S., Tuschl T., Latz E.,
RA Ludwig J., Hartmann G.;
RT "Recognition of 5' triphosphate by RIG-I helicase requires short blunt
RT double-stranded RNA as contained in panhandle of negative-strand virus.";
RL Immunity 31:25-34(2009).
RN [24]
RP UBIQUITINATION, AND INTERACTION WITH RNF135.
RX PubMed=19017631; DOI=10.1074/jbc.m804259200;
RA Oshiumi H., Matsumoto M., Hatakeyama S., Seya T.;
RT "Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote
RT interferon-beta induction during the early phase of viral infection.";
RL J. Biol. Chem. 284:807-817(2009).
RN [25]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19122199; DOI=10.1074/jbc.m807547200;
RA Mukherjee A., Morosky S.A., Shen L., Weber C.R., Turner J.R., Kim K.S.,
RA Wang T., Coyne C.B.;
RT "Retinoic acid-induced gene-1 (RIG-I) associates with the actin
RT cytoskeleton via caspase activation and recruitment domain-dependent
RT interactions.";
RL J. Biol. Chem. 284:6486-6494(2009).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-270; 372-ASP--HIS-375;
RP 409-THR--SER-411; 633-PHE--THR-636; 697-THR--ASP-701 AND 726-GLN--ARG-730.
RX PubMed=19211564; DOI=10.1074/jbc.m807365200;
RA Bamming D., Horvath C.M.;
RT "Regulation of signal transduction by enzymatically inactive antiviral RNA
RT helicase proteins MDA5, RIG-I, and LGP2.";
RL J. Biol. Chem. 284:9700-9712(2009).
RN [27]
RP INTERACTION WITH SRC.
RX PubMed=19419966; DOI=10.1074/jbc.m808233200;
RA Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., Anthonsen M.W.;
RT "The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-
RT elicited antiviral signaling.";
RL J. Biol. Chem. 284:19122-19131(2009).
RN [28]
RP INTERACTION WITH HRSV PROTEIN NS2 (MICROBIAL INFECTION).
RX PubMed=19193793; DOI=10.1128/jvi.02434-08;
RA Ling Z., Tran K.C., Teng M.N.;
RT "Human respiratory syncytial virus nonstructural protein NS2 antagonizes
RT the activation of beta interferon transcription by interacting with RIG-
RT I.";
RL J. Virol. 83:3734-3742(2009).
RN [29]
RP FUNCTION.
RX PubMed=19609254; DOI=10.1038/ni.1779;
RA Ablasser A., Bauernfeind F., Hartmann G., Latz E., Fitzgerald K.A.,
RA Hornung V.;
RT "RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA
RT polymerase III-transcribed RNA intermediate.";
RL Nat. Immunol. 10:1065-1072(2009).
RN [30]
RP UBIQUITINATION AT LYS-154; LYS-164 AND LYS-172, INTERACTION WITH RNF135,
RP AND MUTAGENESIS OF LYS-154; LYS-164 AND LYS-172.
RX PubMed=19484123; DOI=10.1371/journal.pone.0005760;
RA Gao D., Yang Y.K., Wang R.P., Zhou X., Diao F.C., Li M.D., Zhai Z.H.,
RA Jiang Z.F., Chen D.Y.;
RT "REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-
RT inducible gene-I.";
RL PLoS ONE 4:E5760-E5760(2009).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-858, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [32]
RP INTERACTION WITH NLRC5.
RX PubMed=20434986; DOI=10.1016/j.cell.2010.03.040;
RA Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P.,
RA Zheng S., Chen Z.J., Wang R.F.;
RT "NLRC5 negatively regulates the NF-kappaB and type I interferon signaling
RT pathways.";
RL Cell 141:483-496(2010).
RN [33]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP17L2.
RX PubMed=20368735; DOI=10.1038/cr.2010.41;
RA Chen R., Zhang L., Zhong B., Tan B., Liu Y., Shu H.B.;
RT "The ubiquitin-specific protease 17 is involved in virus-triggered type I
RT IFN signaling.";
RL Cell Res. 20:802-811(2010).
RN [34]
RP REVIEW ON FUNCTION.
RX PubMed=21175414; DOI=10.1615/critrevimmunol.v30.i6.10;
RA Matsumiya T., Stafforini D.M.;
RT "Function and regulation of retinoic acid-inducible gene-I.";
RL Crit. Rev. Immunol. 30:489-513(2010).
RN [35]
RP INTERACTION WITH DDX3X.
RX PubMed=20127681; DOI=10.1002/eji.200940203;
RA Oshiumi H., Sakai K., Matsumoto M., Seya T.;
RT "DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate
RT IFN-beta-inducing potential.";
RL Eur. J. Immunol. 40:940-948(2010).
RN [36]
RP INTERACTION WITH NEW WORLD ARENAVIRUSES PROTEIN Z (MICROBIAL INFECTION).
RX PubMed=20007272; DOI=10.1128/jvi.01362-09;
RA Fan L., Briese T., Lipkin W.I.;
RT "Z proteins of New World arenaviruses bind RIG-I and interfere with type I
RT interferon induction.";
RL J. Virol. 84:1785-1791(2010).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [38]
RP REVIEW ON FUNCTION.
RX PubMed=21616437; DOI=10.1016/j.immuni.2011.05.003;
RA Loo Y.M., Gale M. Jr.;
RT "Immune signaling by RIG-I-like receptors.";
RL Immunity 34:680-692(2011).
RN [39]
RP REVIEW ON FUNCTION.
RX PubMed=21884169; DOI=10.1111/j.1600-065x.2011.01052.x;
RA Kato H., Takahasi K., Fujita T.;
RT "RIG-I-like receptors: cytoplasmic sensors for non-self RNA.";
RL Immunol. Rev. 243:91-98(2011).
RN [40]
RP INTERACTION WITH ARL16.
RX PubMed=21233210; DOI=10.1074/jbc.m110.206896;
RA Yang Y.K., Qu H., Gao D., Di W., Chen H.W., Guo X., Zhai Z.H., Chen D.Y.;
RT "ARF-like protein 16 (ARL16) inhibits RIG-I by binding with its C-terminal
RT domain in a GTP-dependent manner.";
RL J. Biol. Chem. 286:10568-10580(2011).
RN [41]
RP FUNCTION.
RX PubMed=21742966; DOI=10.4049/jimmunol.1100361;
RA Jiang M., Osterlund P., Sarin L.P., Poranen M.M., Bamford D.H., Guo D.,
RA Julkunen I.;
RT "Innate immune responses in human monocyte-derived dendritic cells are
RT highly dependent on the size and the 5' phosphorylation of RNA molecules.";
RL J. Immunol. 187:1713-1721(2011).
RN [42]
RP INTERACTION WITH IFIT3.
RX PubMed=21813773; DOI=10.4049/jimmunol.1100963;
RA Liu X.Y., Chen W., Wei B., Shan Y.F., Wang C.;
RT "IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging
RT MAVS and TBK1.";
RL J. Immunol. 187:2559-2568(2011).
RN [43]
RP REVIEW ON FUNCTION.
RX PubMed=20950133; DOI=10.1089/jir.2010.0057;
RA Onoguchi K., Yoneyama M., Fujita T.;
RT "Retinoic acid-inducible gene-I-like receptors.";
RL J. Interferon Cytokine Res. 31:27-31(2011).
RN [44]
RP PHOSPHORYLATION AT THR-770; SER-854 AND SER-855.
RX PubMed=21068236; DOI=10.1128/jvi.01734-10;
RA Sun Z., Ren H., Liu Y., Teeling J.L., Gu J.;
RT "Phosphorylation of RIG-I by casein kinase II inhibits its antiviral
RT response.";
RL J. Virol. 85:1036-1047(2011).
RN [45]
RP INTERACTION WITH DDX60.
RX PubMed=21791617; DOI=10.1128/mcb.01368-10;
RA Miyashita M., Oshiumi H., Matsumoto M., Seya T.;
RT "DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-
RT like receptor-mediated signaling.";
RL Mol. Cell. Biol. 31:3802-3819(2011).
RN [46]
RP INTERACTION WITH ZC3HAV1, AND SUBCELLULAR LOCATION.
RX PubMed=21102435; DOI=10.1038/ni.1963;
RA Hayakawa S., Shiratori S., Yamato H., Kameyama T., Kitatsuji C.,
RA Kashigi F., Goto S., Kameoka S., Fujikura D., Yamada T., Mizutani T.,
RA Kazumata M., Sato M., Tanaka J., Asaka M., Ohba Y., Miyazaki T.,
RA Imamura M., Takaoka A.;
RT "ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-
RT I during antiviral responses.";
RL Nat. Immunol. 12:37-44(2011).
RN [47]
RP INTERACTION WITH ROTAVIRUS PROTEIN NSP1 (MICROBIAL INFECTION).
RX PubMed=22152002; DOI=10.1186/1743-422x-8-526;
RA Qin L., Ren L., Zhou Z., Lei X., Chen L., Xue Q., Liu X., Wang J., Hung T.;
RT "Rotavirus nonstructural protein 1 antagonizes innate immune response by
RT interacting with retinoic acid inducible gene I.";
RL Virol. J. 8:526-526(2011).
RN [48]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN US11 (MICROBIAL INFECTION).
RX PubMed=22301138; DOI=10.1128/jvi.06713-11;
RA Xing J., Wang S., Lin R., Mossman K.L., Zheng C.;
RT "Herpes simplex virus 1 tegument protein US11 downmodulates the RLR
RT signaling pathway via direct interaction with RIG-I and MDA-5.";
RL J. Virol. 86:3528-3540(2012).
RN [49]
RP SUMOYLATION BY MUL1.
RX PubMed=23399697; DOI=10.1038/icb.2013.7;
RA Jenkins K., Khoo J.J., Sadler A., Piganis R., Wang D., Borg N.A.,
RA Hjerrild K., Gould J., Thomas B.J., Nagley P., Hertzog P.J., Mansell A.;
RT "Mitochondrially localised MUL1 is a novel modulator of antiviral
RT signaling.";
RL Immunol. Cell Biol. 91:321-330(2013).
RN [50]
RP INTERACTION WITH SEC14L1.
RX PubMed=23843640; DOI=10.1128/jvi.01073-13;
RA Li M.T., Di W., Xu H., Yang Y.K., Chen H.W., Zhang F.X., Zhai Z.H.,
RA Chen D.Y.;
RT "Negative regulation of RIG-I-mediated innate antiviral signaling by
RT SEC14L1.";
RL J. Virol. 87:10037-10046(2013).
RN [51]
RP INTERACTION WITH RNF135, DOMAIN, REGION, AND MUTAGENESIS OF LYS-788;
RP LYS-849; LYS-851; LYS-888; LYS-907 AND LYS-909.
RX PubMed=23950712; DOI=10.1371/journal.ppat.1003533;
RA Oshiumi H., Miyashita M., Matsumoto M., Seya T.;
RT "A distinct role of Riplet-mediated K63-Linked polyubiquitination of the
RT RIG-I repressor domain in human antiviral innate immune responses.";
RL PLoS Pathog. 9:E1003533-E1003533(2013).
RN [52]
RP UBIQUITINATION AT LYS-154; LYS-164 AND LYS-172 BY TRIM4.
RX PubMed=24755855; DOI=10.1093/jmcb/mju005;
RA Yan J., Li Q., Mao A.P., Hu M.M., Shu H.B.;
RT "TRIM4 modulates type I interferon induction and cellular antiviral
RT response by targeting RIG-I for K63-linked ubiquitination.";
RL J. Mol. Cell Biol. 6:154-163(2014).
RN [53]
RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION).
RX PubMed=24390337; DOI=10.1128/jvi.02712-13;
RA Feng Q., Langereis M.A., Lork M., Nguyen M., Hato S.V., Lanke K., Emdad L.,
RA Bhoopathi P., Fisher P.B., Lloyd R.E., van Kuppeveld F.J.;
RT "Enterovirus 2Apro targets MDA5 and MAVS in infected cells.";
RL J. Virol. 88:3369-3378(2014).
RN [54]
RP INTERACTION WITH SFTSV NSS (MICROBIAL INFECTION).
RX PubMed=24478431; DOI=10.1128/jvi.03021-13;
RA Santiago F.W., Covaleda L.M., Sanchez-Aparicio M.T., Silvas J.A.,
RA Diaz-Vizarreta A.C., Patel J.R., Popov V., Yu X.J., Garcia-Sastre A.,
RA Aguilar P.V.;
RT "Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic
RT structures correlates with the inhibition of type I interferon responses.";
RL J. Virol. 88:4572-4585(2014).
RN [55]
RP UBIQUITINATION AT LYS-181 BY RNF125, INTERACTION WITH VCP, AND MUTAGENESIS
RP OF LYS-181.
RX PubMed=26471729; DOI=10.15252/embj.201591888;
RA Hao Q., Jiao S., Shi Z., Li C., Meng X., Zhang Z., Wang Y., Song X.,
RA Wang W., Zhang R., Zhao Y., Wong C.C., Zhou Z.;
RT "A non-canonical role of the p97 complex in RIG-I antiviral signaling.";
RL EMBO J. 34:2903-2920(2015).
RN [56]
RP INTERACTION WITH NOP53.
RX PubMed=27824081; DOI=10.1038/srep36226;
RA Wang P., Meng W., Han S.C., Li C.C., Wang X.J., Wang X.J.;
RT "The nucleolar protein GLTSCR2 is required for efficient viral
RT replication.";
RL Sci. Rep. 6:36226-36226(2016).
RN [57]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN UL37 (MICROBIAL INFECTION),
RP DEAMIDATION AT ASN-495 AND ASN-549, AND MUTAGENESIS OF ASN-495 AND ASN-549.
RX PubMed=27866900; DOI=10.1016/j.chom.2016.10.011;
RA Zhao J., Zeng Y., Xu S., Chen J., Shen G., Yu C., Knipe D., Yuan W.,
RA Peng J., Xu W., Zhang C., Xia Z., Feng P.;
RT "A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-
RT Induced Activation.";
RL Cell Host Microbe 20:770-784(2016).
RN [58]
RP INVOLVEMENT IN SGMRT2, VARIANTS SGMRT2 PHE-268 AND ALA-373, AND
RP CHARACTERIZATION OF VARIANTS SGMRT2 PHE-268 AND ALA-373.
RX PubMed=25620203; DOI=10.1016/j.ajhg.2014.11.019;
RA Jang M.A., Kim E.K., Now H., Nguyen N.T., Kim W.J., Yoo J.Y., Lee J.,
RA Jeong Y.M., Kim C.H., Kim O.H., Sohn S., Nam S.H., Hong Y., Lee Y.S.,
RA Chang S.A., Jang S.Y., Kim J.W., Lee M.S., Lim S.Y., Sung K.S., Park K.T.,
RA Kim B.J., Lee J.H., Kim D.K., Kee C., Ki C.S.;
RT "Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten
RT syndrome.";
RL Am. J. Hum. Genet. 96:266-274(2015).
RN [59]
RP INTERACTION WITH RNF123.
RX PubMed=27312109; DOI=10.15252/embr.201541703;
RA Wang S., Yang Y.K., Chen T., Zhang H., Yang W.W., Song S.S., Zhai Z.H.,
RA Chen D.Y.;
RT "RNF123 has an E3 ligase-independent function in RIG-I-like receptor-
RT mediated antiviral signaling.";
RL EMBO Rep. 17:1155-1168(2016).
RN [60]
RP FUNCTION, INTERACTION WITH RNF135; UBE2D3 AND UBE2N, AND UBIQUITINATION AT
RP LYS-48; LYS-96 AND LYS-172 BY RNF135.
RX PubMed=28469175; DOI=10.1038/ncomms15138;
RA Shi Y., Yuan B., Zhu W., Zhang R., Li L., Hao X., Chen S., Hou F.;
RT "Ube2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in
RT antiviral innate immunity.";
RL Nat. Commun. 8:15138-15138(2017).
RN [61]
RP FUNCTION, AND UBIQUITINATION BY TRIM40.
RX PubMed=29117565; DOI=10.1016/j.celrep.2017.10.020;
RA Zhao C., Jia M., Song H., Yu Z., Wang W., Li Q., Zhang L., Zhao W., Cao X.;
RT "The E3 Ubiquitin Ligase TRIM40 Attenuates Antiviral Immune Responses by
RT Targeting MDA5 and RIG-I.";
RL Cell Rep. 21:1613-1623(2017).
RN [62]
RP INTERACTION WITH LRRC25.
RX PubMed=29288164; DOI=10.15252/embj.201796781;
RA Du Y., Duan T., Feng Y., Liu Q., Lin M., Cui J., Wang R.F.;
RT "LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I
RT for autophagic degradation.";
RL EMBO J. 37:351-366(2018).
RN [63]
RP INTERACTION WITH ZCCHC3, AND UBIQUITINATION.
RX PubMed=30193849; DOI=10.1016/j.immuni.2018.08.014;
RA Lian H., Zang R., Wei J., Ye W., Hu M.M., Chen Y.D., Zhang X.N., Guo Y.,
RA Lei C.Q., Yang Q., Luo W.W., Li S., Shu H.B.;
RT "The zinc-finger protein ZCCHC3 binds RNA and facilitates viral RNA sensing
RT and activation of the RIG-I-like receptors.";
RL Immunity 49:438-448(2018).
RN [64]
RP FUNCTION, SUBUNIT, INTERACTION WITH RNF135, AND UBIQUITINATION BY RNF135.
RX PubMed=31006531; DOI=10.1016/j.cell.2019.03.017;
RA Cadena C., Ahmad S., Xavier A., Willemsen J., Park S., Park J.W., Oh S.W.,
RA Fujita T., Hou F., Binder M., Hur S.;
RT "Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate
RT Immunity.";
RL Cell 177:1187-1200(2019).
RN [65]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP27X.
RX PubMed=32027733; DOI=10.1371/journal.ppat.1008293;
RA Tao X., Chu B., Xin D., Li L., Sun Q.;
RT "USP27X negatively regulates antiviral signaling by deubiquitinating RIG-
RT I.";
RL PLoS Pathog. 16:e1008293-e1008293(2020).
RN [66]
RP FUNCTION.
RX DOI=10.1016/j.celrep.2021.109091;
RA Li N., Hui H., Bray B., Gonzalez G.M., Zeller M., Anderson K.G., Knight R.,
RA Smith D., Wang Y., Carlin A.F., Rana T.M.;
RT "METTL3 regulates viral m6A RNA modification and host cell innate immune
RT responses during SARS-CoV-2 infection.";
RL Cell Rep. 0:0-0(2021).
RN [67]
RP INTERACTION WITH RTN3.
RX PubMed=34313226; DOI=10.7554/elife.68958;
RA Yang Z., Wang J., He B., Zhang X., Li X., Kuang E.;
RT "RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25-
RT mediated K63-linked polyubiquitination.";
RL Elife 10:0-0(2021).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 802-925 IN COMPLEX WITH ZINC IONS.
RX PubMed=18243112; DOI=10.1016/j.molcel.2007.10.032;
RA Cui S., Eisenaecher K., Kirchhofer A., Brzozka K., Lammens A., Lammens K.,
RA Fujita T., Conzelmann K.-K., Krug A., Hopfner K.-P.;
RT "The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-
RT I.";
RL Mol. Cell 29:169-179(2008).
RN [69]
RP STRUCTURE BY NMR OF 792-925.
RX PubMed=18242112; DOI=10.1016/j.molcel.2007.11.028;
RA Takahasi K., Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita R.,
RA Gale M. Jr., Inagaki F., Fujita T.;
RT "Nonself RNA-sensing mechanism of RIG-I helicase and activation of
RT antiviral immune responses.";
RL Mol. Cell 29:428-440(2008).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-201 IN COMPLEX WITH MAVS, AND
RP SUBUNIT.
RX PubMed=25018021; DOI=10.1016/j.molcel.2014.06.010;
RA Wu B., Peisley A., Tetrault D., Li Z., Egelman E.H., Magor K.E., Walz T.,
RA Penczek P.A., Hur S.;
RT "Molecular imprinting as a signal-activation mechanism of the viral RNA
RT sensor RIG-I.";
RL Mol. Cell 55:511-523(2014).
CC -!- FUNCTION: Innate immune receptor that senses cytoplasmic viral nucleic
CC acids and activates a downstream signaling cascade leading to the
CC production of type I interferons and pro-inflammatory cytokines
CC (PubMed:15208624, PubMed:16125763, PubMed:15708988, PubMed:16127453,
CC PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199,
CC PubMed:19211564, PubMed:29117565, PubMed:28469175, PubMed:31006531).
CC Forms a ribonucleoprotein complex with viral RNAs on which it
CC homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988).
CC The homooligomerization allows the recruitment of RNF135 an E3
CC ubiquitin-protein ligase that activates and amplifies the RIG-I-
CC mediated antiviral signaling in an RNA length-dependent manner through
CC ubiquitination-dependent and -independent mechanisms (PubMed:28469175,
CC PubMed:31006531). Upon activation, associates with mitochondria
CC antiviral signaling protein (MAVS/IPS1) that activates the IKK-related
CC kinases TBK1 and IKBKE which in turn phosphorylate the interferon
CC regulatory factors IRF3 and IRF7, activating transcription of antiviral
CC immunological genes including the IFN-alpha and IFN-beta interferons
CC (PubMed:28469175, PubMed:31006531). Ligands include 5'-
CC triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in
CC length) (PubMed:15208624, PubMed:15708988, PubMed:19576794,
CC PubMed:19609254, PubMed:21742966). In addition to the 5'-triphosphate
CC moiety, blunt-end base pairing at the 5'-end of the RNA is very
CC essential (PubMed:15208624, PubMed:15708988, PubMed:19576794,
CC PubMed:19609254, PubMed:21742966). Overhangs at the non-
CC triphosphorylated end of the dsRNA RNA have no major impact on its
CC activity (PubMed:15208624, PubMed:15708988, PubMed:19576794,
CC PubMed:19609254, PubMed:21742966). A 3'overhang at the 5'triphosphate
CC end decreases and any 5'overhang at the 5' triphosphate end abolishes
CC its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794,
CC PubMed:19609254, PubMed:21742966). Detects both positive and negative
CC strand RNA viruses including members of the families Paramyxoviridae:
CC Human respiratory syncytial virus and measles virus (MeV),
CC Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae:
CC influenza A and B virus, Flaviviridae: Japanese encephalitis virus
CC (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus
CC (WNV) (PubMed:21616437, PubMed:21884169). It also detects rotaviruses
CC and reoviruses (PubMed:21616437, PubMed:21884169). Detects and binds to
CC SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.66).
CC Also involved in antiviral signaling in response to viruses containing
CC a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370).
CC Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such
CC as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in
CC granulocyte production and differentiation, bacterial phagocytosis and
CC in the regulation of cell migration. {ECO:0000269|PubMed:15208624,
CC ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:16125763,
CC ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868,
CC ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18636086,
CC ECO:0000269|PubMed:19122199, ECO:0000269|PubMed:19211564,
CC ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254,
CC ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21742966,
CC ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:29117565,
CC ECO:0000269|PubMed:31006531, ECO:0000269|Ref.66,
CC ECO:0000303|PubMed:21616437, ECO:0000303|PubMed:21884169}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000269|PubMed:19211564};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000305|PubMed:19211564};
CC -!- SUBUNIT: Monomer; maintained as a monomer in an autoinhibited state.
CC Upon binding of viral RNAs and conformational shift, homooligomerizes
CC and forms filaments on these molecules (PubMed:26471729). Interacts
CC (via tandem CARD domain) with MAVS/IPS1 promoting its filamentation.
CC Interacts with DHX58/LGP2, IKBKE, TBK1 and STING1. Interacts (via CARD
CC domain) with TRIM25 (via SPRY domain). Interacts (double-stranded RNA-
CC bound oligomeric form) with RNF135 (homodimer); involved in RNA length-
CC dependent activation of the RIG-I signaling pathway (PubMed:19017631,
CC PubMed:19484123, PubMed:23950712, PubMed:28469175, PubMed:31006531).
CC Interacts with CYLD. Interacts with NLRC5; blocks the interaction of
CC MAVS/IPS1 to DDX58. Interacts with SRC. Interacts with DDX60. Interacts
CC with isoform 2 of ZC3HAV1 (via zinc-fingers) in an RNA-dependent
CC manner. Interacts (via tandem CARD domain) with SEC14L1; the
CC interaction is direct and impairs the interaction of DDX58 with
CC MAVS/IPS1. Interacts with VCP/p97; interaction is direct and allows the
CC recruitment of RNF125 and subsequent ubiquitination and degradation
CC (PubMed:26471729). Interacts with NOP53; may regulate DDX58 through
CC USP15-mediated 'Lys-63'-linked deubiquitination (PubMed:27824081).
CC Interacts with SIGLEC10, CBL and PTPN11; within a negative feedback
CC loop leading to DDX58 degradation (By similarity). Interacts with
CC LRRC25 (PubMed:29288164). Interacts with ZCCHC3; leading to activation
CC of DDX58/RIG-I (PubMed:30193849). Interacts with RNF123
CC (PubMed:27312109). Interacts with UBE2D3 and UBE2N; E2 ubiquitin
CC ligases involved in RNF135-mediated ubiquitination of DDX58 and
CC activation of the RIG-I signaling pathway (PubMed:28469175). Interacts
CC with IFIT3 (PubMed:21813773). Interacts with DDX3X (PubMed:20127681).
CC Interacts with RTN3 (PubMed:34313226). Interacts with ARL16; this
CC interaction is GTP-dependent and induced upon viral infection; this
CC interaction suppresses the RNA sensing activity of DDX58
CC (PubMed:21233210). {ECO:0000250|UniProtKB:Q6Q899,
CC ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453,
CC ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:16281057,
CC ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:17392790,
CC ECO:0000269|PubMed:18243112, ECO:0000269|PubMed:18636086,
CC ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:19017631,
CC ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:19484123,
CC ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20434986,
CC ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21233210,
CC ECO:0000269|PubMed:21791617, ECO:0000269|PubMed:21813773,
CC ECO:0000269|PubMed:23843640, ECO:0000269|PubMed:23950712,
CC ECO:0000269|PubMed:25018021, ECO:0000269|PubMed:26471729,
CC ECO:0000269|PubMed:27312109, ECO:0000269|PubMed:27824081,
CC ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:29288164,
CC ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:31006531,
CC ECO:0000269|PubMed:34313226}.
CC -!- SUBUNIT: (Microbial infection) Interacts with protein Z of Guanarito
CC virus, Machupo virus, Junin arenavirus and Sabia virus. This
CC interaction disrupts its interaction with MAVS/IPS1, impeding
CC downstream IRF3 and NF-kappa-B activation and resulting in decreased
CC IFN-beta induction (PubMed:20007272). {ECO:0000269|PubMed:20007272}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via CARD domain) with Human
CC respiratory syncytial virus A non-structural protein 2 (NS2) and this
CC interaction disrupts its interaction with MAVS/IPS1, impeding
CC downstream IRF3 activation (PubMed:19193793).
CC {ECO:0000269|PubMed:19193793}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Rotavirus A non-
CC structural protein 1 (NSP1) and this interaction induces down-
CC regulation of DDX58/RIG-I (PubMed:22152002).
CC {ECO:0000269|PubMed:22152002}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC protein US11; this interaction prevents the interaction of MAVS/IPS1 to
CC DDX58 (PubMed:22301138). {ECO:0000269|PubMed:22301138}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC protein UL37; this interaction deaminates DDX58 and inhibits its
CC activation. {ECO:0000269|PubMed:27866900}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Severe fever with
CC thrombocytopenia virus (SFTSV) NSs; this interaction this interaction
CC sequesters DDX58 in NSs-induced cytoplasmic inclusion bodies thereby
CC inhibiting the IFN responses. {ECO:0000269|PubMed:24478431}.
CC -!- INTERACTION:
CC O95786; Q9NQC7: CYLD; NbExp=2; IntAct=EBI-995350, EBI-2117940;
CC O95786; O00571: DDX3X; NbExp=2; IntAct=EBI-995350, EBI-353779;
CC O95786; O95786: DDX58; NbExp=3; IntAct=EBI-995350, EBI-995350;
CC O95786; Q7Z434: MAVS; NbExp=18; IntAct=EBI-995350, EBI-995373;
CC O95786; Q9NZM5: NOP53; NbExp=2; IntAct=EBI-995350, EBI-720156;
CC O95786; O75569: PRKRA; NbExp=5; IntAct=EBI-995350, EBI-713955;
CC O95786; P42224: STAT1; NbExp=4; IntAct=EBI-995350, EBI-1057697;
CC O95786; Q14258: TRIM25; NbExp=10; IntAct=EBI-995350, EBI-2341129;
CC O95786; Q96S55: WRNIP1; NbExp=2; IntAct=EBI-995350, EBI-2513471;
CC O95786; Q7Z2W4: ZC3HAV1; NbExp=3; IntAct=EBI-995350, EBI-922540;
CC O95786; Q7Z2W4-2: ZC3HAV1; NbExp=4; IntAct=EBI-995350, EBI-922559;
CC O95786; P04543: 1B; Xeno; NbExp=2; IntAct=EBI-995350, EBI-3648048;
CC O95786; Q920D5: Casp12; Xeno; NbExp=4; IntAct=EBI-995350, EBI-1374296;
CC O95786; P59596: M; Xeno; NbExp=4; IntAct=EBI-995350, EBI-25487824;
CC O95786; P0DTC9: N; Xeno; NbExp=9; IntAct=EBI-995350, EBI-25475856;
CC O95786; P21699: NSS; Xeno; NbExp=3; IntAct=EBI-995350, EBI-6693910;
CC O95786; PRO_0000449623 [P0DTD1]: rep; Xeno; NbExp=2; IntAct=EBI-995350, EBI-25475864;
CC O95786; P04487: US11; Xeno; NbExp=4; IntAct=EBI-995350, EBI-6150681;
CC O95786; Q6IUF9: Z; Xeno; NbExp=3; IntAct=EBI-995350, EBI-3647473;
CC O95786; Q6IVU5: Z; Xeno; NbExp=3; IntAct=EBI-995350, EBI-3647294;
CC O95786; Q6UY62: Z; Xeno; NbExp=2; IntAct=EBI-995350, EBI-3647496;
CC O95786; Q6UY71: Z; Xeno; NbExp=3; IntAct=EBI-995350, EBI-3647448;
CC O95786; F1BA49; Xeno; NbExp=5; IntAct=EBI-995350, EBI-9687469;
CC O95786-1; Q9H1Y0: ATG5; NbExp=4; IntAct=EBI-15577823, EBI-1047414;
CC O95786-1; O95786-1: DDX58; NbExp=4; IntAct=EBI-15577823, EBI-15577823;
CC O95786-1; Q7Z434-1: MAVS; NbExp=8; IntAct=EBI-15577823, EBI-15577799;
CC O95786-1; Q96EQ8: RNF125; NbExp=5; IntAct=EBI-15577823, EBI-2339208;
CC O95786-1; Q86WV6: STING1; NbExp=2; IntAct=EBI-15577823, EBI-2800345;
CC O95786-1; Q99AU3: NS; Xeno; NbExp=2; IntAct=EBI-15577823, EBI-6150155;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell projection, ruffle membrane.
CC Cytoplasm, cytoskeleton. Cell junction, tight junction.
CC Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies.
CC Associated with the actin cytoskeleton at membrane ruffles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95786-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95786-2; Sequence=VSP_016054;
CC -!- TISSUE SPECIFICITY: Present in vascular smooth cells (at protein
CC level). {ECO:0000269|PubMed:15219805}.
CC -!- INDUCTION: By bacterial lipopolysaccharides (LPS) in endothelial cells.
CC By interferon (IFN). {ECO:0000269|PubMed:11890704,
CC ECO:0000269|PubMed:15181474, ECO:0000269|PubMed:15208624,
CC ECO:0000269|PubMed:15219805, ECO:0000269|PubMed:15708988}.
CC -!- DOMAIN: The RLR CTR domain controls homooligomerization and interaction
CC with MAVS/IPS1. In the absence of viral infection, the protein is
CC maintained as a monomer in an autoinhibited state with the CARD domains
CC masked through intramolecular interactions with the RLR CTR domain.
CC Upon binding to viral RNA and ubiquitination by RNF135, a
CC conformational change releases the autoinhibition promoting further
CC homooligomerization, interaction of the CARD domains with the adapter
CC protein MAVS/IPS1 and activation of the downstream RIG-I signaling
CC pathway. {ECO:0000269|PubMed:23950712}.
CC -!- DOMAIN: The helicase domain is responsible for dsRNA recognition.
CC -!- DOMAIN: The 2 CARD domains are responsible for interaction with and
CC signaling through MAVS/IPS1 and for association with the actin
CC cytoskeleton.
CC -!- DOMAIN: The second CARD domain is the primary site for 'Lys-63'-linked
CC ubiquitination. {ECO:0000269|PubMed:17392790}.
CC -!- PTM: Phosphorylated in resting cells and dephosphorylated in RNA virus-
CC infected cells. Phosphorylation at Thr-770, Ser-854 and Ser-855 results
CC in inhibition of its activity while dephosphorylation at these sites
CC results in its activation. {ECO:0000269|PubMed:21068236}.
CC -!- PTM: Ubiquitinated. 'Lys-63' ubiquitination by RNF135, which occurs
CC after RNA-binding and homodimerization, releases the autoinhibition of
CC the CARD domains by the RLR CTR domain, an essential step in the
CC activation of the RIG-I signaling pathway (PubMed:23950712,
CC PubMed:28469175, PubMed:31006531). Lys-172 is the critical site of
CC ubiquitination for MAVS/IPS1 binding and to induce anti-viral signal
CC transduction (PubMed:17392790, PubMed:30193849). Lys-154, Lys-164 and
CC Lys-172 are shared sites for RNF135-mediated and TRIM4-mediated
CC ubiquitination (PubMed:19017631, PubMed:19484123, PubMed:24755855).
CC Also undergoes 'Lys-48' ubiquitination at Lys-181 by RNF125 that leads
CC to proteasomal degradation (PubMed:17460044, PubMed:26471729). 'Lys-48'
CC ubiquitination follows viral infection and is enhanced by 'Lys-63'-
CC linked ubiquitination of the CARD domains that promotes interaction
CC with VCP/p97 and subsequent recruitment of RNF125 (PubMed:17460044,
CC PubMed:26471729). Within a negative feedback loop involving SIGLEC10
CC and PTPN11, 'Lys-48' ubiquitination at Lys-812 by CBL also elicits the
CC proteasomal degradation of DDX58 (By similarity). Deubiquitinated by
CC CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin
CC chains (PubMed:18636086). Also probably deubiquitinated by
CC USP17L2/USP17 that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin
CC chains and positively regulates the receptor (PubMed:20368735).
CC Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to
CC proteasomal degradation (PubMed:29117565). Deubiquitinated by USP27X
CC that cleaves 'Lys-63'-linked ubiquitin chains and inhibits the innate
CC immune receptor activity (PubMed:32027733).
CC {ECO:0000250|UniProtKB:Q6Q899, ECO:0000269|PubMed:17392790,
CC ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:18636086,
CC ECO:0000269|PubMed:19017631, ECO:0000269|PubMed:19484123,
CC ECO:0000269|PubMed:20368735, ECO:0000269|PubMed:23950712,
CC ECO:0000269|PubMed:24755855, ECO:0000269|PubMed:26471729,
CC ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:30193849,
CC ECO:0000269|PubMed:31006531, ECO:0000269|PubMed:32027733}.
CC -!- PTM: ISGylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-
CC beta stimulation. ISGylation negatively regulates its function in
CC antiviral signaling response. {ECO:0000269|PubMed:16009940,
CC ECO:0000269|PubMed:18057259, ECO:0000269|PubMed:20368735}.
CC -!- PTM: Sumoylated, probably by MUL1; inhibiting its polyubiquitination.
CC {ECO:0000269|PubMed:20368735, ECO:0000269|PubMed:23399697}.
CC -!- PTM: (Microbial infection) Deamidated on 'Asn-495' and 'Asn-549' by
CC herpes simplex virus 1 protein UL37. These modifications eliminate
CC DDX58 detection of viral RNA and restriction of viral replication.
CC {ECO:0000269|PubMed:27866900}.
CC -!- PTM: (Microbial infection) Cleaved by the protease 3C of coxsackievirus
CC B3, poliovirus and enterovirus 71 allowing the virus to disrupt the
CC host type I interferon production. {ECO:0000269|PubMed:24390337}.
CC -!- DISEASE: Singleton-Merten syndrome 2 (SGMRT2) [MIM:616298]: A form of
CC Singleton-Merten syndrome, an autosomal dominant disorder characterized
CC by marked aortic calcification, dental anomalies, osteopenia, acro-
CC osteolysis, and to a lesser extent glaucoma, psoriasis, muscle
CC weakness, and joint laxity. Additional clinical manifestations include
CC particular facial characteristics and abnormal joint and muscle
CC ligaments. SGMRT2 is an atypical form characterized by variable
CC expression of glaucoma, aortic calcification, and skeletal
CC abnormalities, without dental anomalies. {ECO:0000269|PubMed:25620203}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the helicase family. RLR subfamily.
CC {ECO:0000305}.
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DR EMBL; AF038963; AAD19826.1; -; mRNA.
DR EMBL; AL161783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58548.1; -; Genomic_DNA.
DR EMBL; BC132786; AAI32787.1; -; mRNA.
DR EMBL; BC136610; AAI36611.1; -; mRNA.
DR EMBL; BX647917; CAI46068.1; -; mRNA.
DR EMBL; AL137608; CAB70840.1; -; mRNA.
DR CCDS; CCDS6526.1; -. [O95786-1]
DR PIR; T46312; T46312.
DR RefSeq; NP_055129.2; NM_014314.3. [O95786-1]
DR PDB; 2LWD; NMR; -; A=95-190.
DR PDB; 2LWE; NMR; -; A=95-190.
DR PDB; 2QFB; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J=802-925.
DR PDB; 2QFD; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J=802-925.
DR PDB; 2RMJ; NMR; -; A=792-925.
DR PDB; 2YKG; X-ray; 2.50 A; A=230-925.
DR PDB; 3LRN; X-ray; 2.60 A; A/B=803-923.
DR PDB; 3LRR; X-ray; 2.15 A; A/B=803-923.
DR PDB; 3NCU; X-ray; 2.55 A; A/B=792-925.
DR PDB; 3OG8; X-ray; 2.40 A; A/B=802-925.
DR PDB; 3ZD6; X-ray; 2.80 A; A=230-925.
DR PDB; 3ZD7; X-ray; 2.50 A; A=230-925.
DR PDB; 4AY2; X-ray; 2.80 A; A=239-925.
DR PDB; 4BPB; X-ray; 2.58 A; A=230-925.
DR PDB; 4NQK; X-ray; 3.70 A; A/B/C/D=1-200.
DR PDB; 4ON9; X-ray; 2.71 A; A/B=230-793.
DR PDB; 4P4H; X-ray; 3.40 A; A/B/C/D/E/F/G/H=1-201.
DR PDB; 5E3H; X-ray; 2.70 A; A=232-925.
DR PDB; 5F98; X-ray; 3.28 A; A/C/E/G/I/K=232-925.
DR PDB; 5F9F; X-ray; 2.60 A; A/C/E/G/I/K=232-925.
DR PDB; 5F9H; X-ray; 3.10 A; A/C/E/G/I/K=232-925.
DR PDB; 6GPG; X-ray; 2.89 A; A=232-925.
DR PDB; 6KYV; X-ray; 3.00 A; B/D/F/H/J/L=242-922.
DR PDB; 7BAH; X-ray; 1.89 A; A/B=802-925.
DR PDB; 7BAI; X-ray; 3.40 A; A/B/E=802-925.
DR PDB; 7JL1; EM; 3.90 A; A=204-925.
DR PDB; 7JL3; EM; 4.20 A; A/C/E=204-925.
DR PDB; 7MK1; X-ray; 1.90 A; A/B=801-925.
DR PDBsum; 2LWD; -.
DR PDBsum; 2LWE; -.
DR PDBsum; 2QFB; -.
DR PDBsum; 2QFD; -.
DR PDBsum; 2RMJ; -.
DR PDBsum; 2YKG; -.
DR PDBsum; 3LRN; -.
DR PDBsum; 3LRR; -.
DR PDBsum; 3NCU; -.
DR PDBsum; 3OG8; -.
DR PDBsum; 3ZD6; -.
DR PDBsum; 3ZD7; -.
DR PDBsum; 4AY2; -.
DR PDBsum; 4BPB; -.
DR PDBsum; 4NQK; -.
DR PDBsum; 4ON9; -.
DR PDBsum; 4P4H; -.
DR PDBsum; 5E3H; -.
DR PDBsum; 5F98; -.
DR PDBsum; 5F9F; -.
DR PDBsum; 5F9H; -.
DR PDBsum; 6GPG; -.
DR PDBsum; 6KYV; -.
DR PDBsum; 7BAH; -.
DR PDBsum; 7BAI; -.
DR PDBsum; 7JL1; -.
DR PDBsum; 7JL3; -.
DR PDBsum; 7MK1; -.
DR AlphaFoldDB; O95786; -.
DR BMRB; O95786; -.
DR SASBDB; O95786; -.
DR SMR; O95786; -.
DR BioGRID; 117121; 1750.
DR CORUM; O95786; -.
DR DIP; DIP-35444N; -.
DR IntAct; O95786; 39.
DR MINT; O95786; -.
DR STRING; 9606.ENSP00000369213; -.
DR GlyGen; O95786; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; O95786; -.
DR PhosphoSitePlus; O95786; -.
DR BioMuta; DDX58; -.
DR EPD; O95786; -.
DR jPOST; O95786; -.
DR MassIVE; O95786; -.
DR MaxQB; O95786; -.
DR PaxDb; O95786; -.
DR PeptideAtlas; O95786; -.
DR PRIDE; O95786; -.
DR ProteomicsDB; 51047; -. [O95786-1]
DR ProteomicsDB; 51048; -. [O95786-2]
DR Antibodypedia; 3367; 665 antibodies from 43 providers.
DR DNASU; 23586; -.
DR Ensembl; ENST00000379868.6; ENSP00000369197.2; ENSG00000107201.11. [O95786-2]
DR Ensembl; ENST00000379883.3; ENSP00000369213.2; ENSG00000107201.11. [O95786-1]
DR GeneID; 23586; -.
DR KEGG; hsa:23586; -.
DR MANE-Select; ENST00000379883.3; ENSP00000369213.2; NM_014314.4; NP_055129.2.
DR UCSC; uc003zra.4; human. [O95786-1]
DR CTD; 23586; -.
DR DisGeNET; 23586; -.
DR GeneCards; DDX58; -.
DR HGNC; HGNC:19102; DDX58.
DR HPA; ENSG00000107201; Low tissue specificity.
DR MalaCards; DDX58; -.
DR MIM; 609631; gene.
DR MIM; 616298; phenotype.
DR neXtProt; NX_O95786; -.
DR OpenTargets; ENSG00000107201; -.
DR Orphanet; 85191; Singleton-Merten dysplasia.
DR PharmGKB; PA134994272; -.
DR VEuPathDB; HostDB:ENSG00000107201; -.
DR eggNOG; KOG0354; Eukaryota.
DR GeneTree; ENSGT00940000153173; -.
DR HOGENOM; CLU_006888_1_0_1; -.
DR InParanoid; O95786; -.
DR OMA; IFCARQD; -.
DR OrthoDB; 1337630at2759; -.
DR PhylomeDB; O95786; -.
DR TreeFam; TF330258; -.
DR BRENDA; 3.6.4.13; 2681.
DR PathwayCommons; O95786; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-8983711; OAS antiviral response.
DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway.
DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; O95786; -.
DR SIGNOR; O95786; -.
DR BioGRID-ORCS; 23586; 13 hits in 1073 CRISPR screens.
DR ChiTaRS; DDX58; human.
DR EvolutionaryTrace; O95786; -.
DR GeneWiki; RIG-I; -.
DR GenomeRNAi; 23586; -.
DR Pharos; O95786; Tbio.
DR PRO; PR:O95786; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O95786; protein.
DR Bgee; ENSG00000107201; Expressed in buccal mucosa cell and 197 other tissues.
DR ExpressionAtlas; O95786; baseline and differential.
DR Genevisible; O95786; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003724; F:RNA helicase activity; IMP:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; IMP:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IMP:UniProtKB.
DR GO; GO:0039528; P:cytoplasmic pattern recognition receptor signaling pathway in response to virus; TAS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0009597; P:detection of virus; IDA:BHF-UCL.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:CACAO.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IDA:CACAO.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:CACAO.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:CACAO.
DR GO; GO:0002735; P:positive regulation of myeloid dendritic cell cytokine production; ISS:UniProtKB.
DR GO; GO:0060760; P:positive regulation of response to cytokine stimulus; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0034344; P:regulation of type III interferon production; TAS:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; IBA:GO_Central.
DR GO; GO:0039529; P:RIG-I signaling pathway; IDA:UniProtKB.
DR CDD; cd08817; CARD_RIG-I_r2; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR Gene3D; 2.170.150.30; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR031964; CARD_dom.
DR InterPro; IPR042145; CARD_RIG-I_r2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041204; RIG-I_C.
DR InterPro; IPR038557; RLR_C_sf.
DR InterPro; IPR021673; RLR_CTR.
DR Pfam; PF16739; CARD_2; 2.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF18119; RIG-I_C; 1.
DR Pfam; PF11648; RIG-I_C-RD; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51789; RLR_CTR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Antiviral defense;
KW ATP-binding; Cell junction; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Disease variant; Helicase; Host-virus interaction; Hydrolase;
KW Immunity; Innate immunity; Isopeptide bond; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW RNA-binding; Tight junction; Ubl conjugation; Zinc.
FT CHAIN 1..925
FT /note="Antiviral innate immune response receptor RIG-I"
FT /id="PRO_0000144093"
FT DOMAIN 1..87
FT /note="CARD 1"
FT DOMAIN 92..172
FT /note="CARD 2"
FT DOMAIN 251..430
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 610..776
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 794..925
FT /note="RLR CTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT REGION 218..925
FT /note="Interaction with ZC3HAV1"
FT /evidence="ECO:0000269|PubMed:21102435"
FT REGION 735..925
FT /note="Mediates interaction with RNF135"
FT /evidence="ECO:0000269|PubMed:23950712"
FT MOTIF 372..375
FT /note="DECH box"
FT BINDING 264..271
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 810
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 813
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 864
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 869
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT MOD_RES 495
FT /note="(Microbial infection) Deamidated asparagine; by
FT herpes simplex virus 1/HHV-1 UL37"
FT /evidence="ECO:0000269|PubMed:27866900"
FT MOD_RES 549
FT /note="(Microbial infection) Deamidated asparagine; by
FT herpes simplex virus 1/HHV-1 UL37"
FT /evidence="ECO:0000269|PubMed:27866900"
FT MOD_RES 770
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:21068236"
FT MOD_RES 854
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:21068236"
FT MOD_RES 855
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:21068236"
FT MOD_RES 858
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 48
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:28469175"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:28469175"
FT CROSSLNK 154
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19484123,
FT ECO:0000269|PubMed:24755855"
FT CROSSLNK 164
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19484123,
FT ECO:0000269|PubMed:24755855"
FT CROSSLNK 172
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19484123,
FT ECO:0000269|PubMed:24755855, ECO:0000269|PubMed:28469175"
FT CROSSLNK 181
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26471729"
FT CROSSLNK 812
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q6Q899"
FT VAR_SEQ 36..80
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_016054"
FT VARIANT 7
FT /note="R -> C (in dbSNP:rs10813831)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_023747"
FT VARIANT 268
FT /note="C -> F (in SGMRT2; results in constitutive
FT activation and enhanced interferon-mediated signaling;
FT dbSNP:rs786204848)"
FT /evidence="ECO:0000269|PubMed:25620203"
FT /id="VAR_073667"
FT VARIANT 373
FT /note="E -> A (in SGMRT2; results in constitutive
FT activation and enhanced interferon-mediated signaling;
FT dbSNP:rs786204847)"
FT /evidence="ECO:0000269|PubMed:25620203"
FT /id="VAR_073668"
FT VARIANT 580
FT /note="D -> E (in dbSNP:rs17217280)"
FT /evidence="ECO:0000269|PubMed:11890704, ECO:0000269|Ref.1"
FT /id="VAR_023748"
FT MUTAGEN 55
FT /note="T->I: No IRF3 signaling activity. No effect on dsRNA
FT binding."
FT /evidence="ECO:0000269|PubMed:15708988"
FT MUTAGEN 99
FT /note="K->R: Little or no effect on ubiquitination of the 2
FT CARD domain. Abolishes ubiquitination by RNF125."
FT /evidence="ECO:0000269|PubMed:17392790,
FT ECO:0000269|PubMed:26471729"
FT MUTAGEN 154
FT /note="K->R: Reduction of ubiquitination. Reduction of INFB
FT induction."
FT /evidence="ECO:0000269|PubMed:19484123"
FT MUTAGEN 164
FT /note="K->R: Reduction of ubiquitination. Reduction of INFB
FT induction."
FT /evidence="ECO:0000269|PubMed:19484123"
FT MUTAGEN 169
FT /note="K->R: Little or no effect on ubiquitination of the 2
FT CARD domains."
FT /evidence="ECO:0000269|PubMed:17392790"
FT MUTAGEN 172
FT /note="K->R: Complete loss of ubiquitination. No
FT interaction with MAVS/IPS1. No induction of IFN-beta."
FT /evidence="ECO:0000269|PubMed:17392790,
FT ECO:0000269|PubMed:19484123"
FT MUTAGEN 181
FT /note="K->R: Little or no effect on ubiquitination of the 2
FT CARD domains."
FT /evidence="ECO:0000269|PubMed:17392790"
FT MUTAGEN 190
FT /note="K->R: Little or no effect on ubiquitination of the 2
FT CARD domains."
FT /evidence="ECO:0000269|PubMed:17392790"
FT MUTAGEN 193
FT /note="K->R: Little or no effect on ubiquitination of the 2
FT CARD domains."
FT /evidence="ECO:0000269|PubMed:17392790"
FT MUTAGEN 270
FT /note="K->A: No IRF3 signaling activity. Loss of dsRNA-
FT induced ATPase activity. No effect on ds-RNA binding.
FT Changed RIG-I signaling pathway."
FT /evidence="ECO:0000269|PubMed:15208624,
FT ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:19211564"
FT MUTAGEN 372..375
FT /note="DECH->AACA: Loss of dsRNA-induced ATPase activity.
FT No effect on ds-RNA binding. Changed RIG-I signaling
FT pathway."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 409..411
FT /note="TAS->AAA: Loss of dsRNA-induced ATPase activity. No
FT effect on ds-RNA binding. Changed RIG-I signaling pathway."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 495
FT /note="N->Q: Complete loss of herpes simplex virus 1 UL37-
FT mediated deamidation; when associated with Q-549."
FT /evidence="ECO:0000269|PubMed:27866900"
FT MUTAGEN 549
FT /note="N->Q: Complete loss of herpes simplex virus 1 UL37-
FT mediated deamidation; when associated with Q-495."
FT /evidence="ECO:0000269|PubMed:27866900"
FT MUTAGEN 633..636
FT /note="FVKT->AVKA: Loss of dsRNA-induced ATPase activity.
FT Changed RIG-I signaling pathway."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 697..701
FT /note="TSVAD->ASVAA: No effect on dsRNA-induced ATPase
FT activity. Changed RIG-I signaling pathway."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 726..730
FT /note="QTRGR->ATRGA: Loss of dsRNA-induced ATPase activity.
FT Changed RIG-I signaling pathway."
FT /evidence="ECO:0000269|PubMed:19211564"
FT MUTAGEN 788
FT /note="K->R: Decreased polyubiquitination. Loss of function
FT in RIG-I signaling pathway. Decreased ubiquitination and
FT function in RIG-I signaling pathway without effect on RNA-
FT binding; when associated with R-849, R-851, R-888, R-907
FT and R-909."
FT /evidence="ECO:0000269|PubMed:23950712"
FT MUTAGEN 849
FT /note="K->R: Decreased ubiquitination and function in RIG-I
FT signaling pathway without effect on RNA-binding; when
FT associated with R-788, R-851, R-888, R-907 and R-909."
FT /evidence="ECO:0000269|PubMed:23950712"
FT MUTAGEN 851
FT /note="K->R: Decreased ubiquitination and function in RIG-I
FT signaling pathway without effect on RNA-binding; when
FT associated with R-788, R-849, R-888, R-907 and R-909."
FT /evidence="ECO:0000269|PubMed:23950712"
FT MUTAGEN 888
FT /note="K->R: Decreased ubiquitination and function in RIG-I
FT signaling pathway without effect on RNA-binding; when
FT associated with R-788, R-849, R-851, R-907 and R-909."
FT /evidence="ECO:0000269|PubMed:23950712"
FT MUTAGEN 907
FT /note="K->R: Decreased ubiquitination and function in RIG-I
FT signaling pathway without effect on RNA-binding; when
FT associated with R-788, R-849, R-851, R-888 and R-909."
FT /evidence="ECO:0000269|PubMed:23950712"
FT MUTAGEN 909
FT /note="K->R: Decreased ubiquitination and function in RIG-I
FT signaling pathway without effect on RNA-binding; when
FT associated with R-788, R-849, R-851, R-888 and R-907."
FT /evidence="ECO:0000269|PubMed:23950712"
FT HELIX 2..11
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 13..19
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:4P4H"
FT TURN 26..32
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 35..48
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 50..63
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 69..80
FT /evidence="ECO:0007829|PDB:4P4H"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 86..91
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 95..99
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 101..117
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 120..127
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 133..146
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 148..160
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:4P4H"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:4P4H"
FT HELIX 245..255
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 270..284
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 300..313
FT /evidence="ECO:0007829|PDB:2YKG"
FT TURN 314..318
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 334..339
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 342..346
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 348..356
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 358..360
FT /evidence="ECO:0007829|PDB:5F9F"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 367..372
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:6GPG"
FT HELIX 382..395
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:4ON9"
FT STRAND 404..410
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 420..433
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:5F98"
FT HELIX 446..452
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 457..462
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 470..489
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 493..495
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 496..498
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 504..506
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 507..518
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:5F9F"
FT HELIX 531..557
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 560..575
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 581..591
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 594..602
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 604..606
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 609..622
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 630..633
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 637..649
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 651..653
FT /evidence="ECO:0007829|PDB:3ZD7"
FT STRAND 658..660
FT /evidence="ECO:0007829|PDB:3ZD7"
FT HELIX 675..683
FT /evidence="ECO:0007829|PDB:5F9F"
FT STRAND 686..690
FT /evidence="ECO:0007829|PDB:5F9F"
FT STRAND 694..700
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 701..703
FT /evidence="ECO:0007829|PDB:4ON9"
FT HELIX 706..708
FT /evidence="ECO:0007829|PDB:3ZD7"
FT STRAND 710..716
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 721..726
FT /evidence="ECO:0007829|PDB:5F9F"
FT HELIX 727..731
FT /evidence="ECO:0007829|PDB:5F9F"
FT STRAND 737..743
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 745..768
FT /evidence="ECO:0007829|PDB:2YKG"
FT HELIX 773..793
FT /evidence="ECO:0007829|PDB:2YKG"
FT STRAND 801..804
FT /evidence="ECO:0007829|PDB:2RMJ"
FT STRAND 806..810
FT /evidence="ECO:0007829|PDB:7BAH"
FT TURN 811..813
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 816..819
FT /evidence="ECO:0007829|PDB:7BAH"
FT HELIX 820..822
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 823..826
FT /evidence="ECO:0007829|PDB:7BAH"
FT TURN 827..829
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 830..833
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 835..837
FT /evidence="ECO:0007829|PDB:5F9F"
FT HELIX 838..840
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 842..846
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 856..865
FT /evidence="ECO:0007829|PDB:7BAH"
FT TURN 867..869
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 872..879
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 882..887
FT /evidence="ECO:0007829|PDB:7BAH"
FT HELIX 889..891
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 892..896
FT /evidence="ECO:0007829|PDB:7BAH"
FT TURN 897..899
FT /evidence="ECO:0007829|PDB:7BAH"
FT STRAND 902..904
FT /evidence="ECO:0007829|PDB:4BPB"
FT HELIX 908..910
FT /evidence="ECO:0007829|PDB:7BAH"
FT HELIX 920..922
FT /evidence="ECO:0007829|PDB:7MK1"
SQ SEQUENCE 925 AA; 106600 MW; BF0D501C395BAE25 CRC64;
MTTEQRRSLQ AFQDYIRKTL DPTYILSYMA PWFREEEVQY IQAEKNNKGP MEAATLFLKF
LLELQEEGWF RGFLDALDHA GYSGLYEAIE SWDFKKIEKL EEYRLLLKRL QPEFKTRIIP
TDIISDLSEC LINQECEEIL QICSTKGMMA GAEKLVECLL RSDKENWPKT LKLALEKERN
KFSELWIVEK GIKDVETEDL EDKMETSDIQ IFYQEDPECQ NLSENSCPPS EVSDTNLYSP
FKPRNYQLEL ALPAMKGKNT IICAPTGCGK TFVSLLICEH HLKKFPQGQK GKVVFFANQI
PVYEQQKSVF SKYFERHGYR VTGISGATAE NVPVEQIVEN NDIIILTPQI LVNNLKKGTI
PSLSIFTLMI FDECHNTSKQ HPYNMIMFNY LDQKLGGSSG PLPQVIGLTA SVGVGDAKNT
DEALDYICKL CASLDASVIA TVKHNLEELE QVVYKPQKFF RKVESRISDK FKYIIAQLMR
DTESLAKRIC KDLENLSQIQ NREFGTQKYE QWIVTVQKAC MVFQMPDKDE ESRICKALFL
YTSHLRKYND ALIISEHARM KDALDYLKDF FSNVRAAGFD EIEQDLTQRF EEKLQELESV
SRDPSNENPK LEDLCFILQE EYHLNPETIT ILFVKTRALV DALKNWIEGN PKLSFLKPGI
LTGRGKTNQN TGMTLPAQKC ILDAFKASGD HNILIATSVA DEGIDIAQCN LVILYEYVGN
VIKMIQTRGR GRARGSKCFL LTSNAGVIEK EQINMYKEKM MNDSILRLQT WDEAVFREKI
LHIQTHEKFI RDSQEKPKPV PDKENKKLLC RKCKALACYT ADVRVIEECH YTVLGDAFKE
CFVSRPHPKP KQFSSFEKRA KIFCARQNCS HDWGIHVKYK TFEIPVIKIE SFVVEDIATG
VQTLYSKWKD FHFEKIPFDP AEMSK
