ID RIGI_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 24-JUL-2024, entry version 199. 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=RNA sensor RIG-I {ECO:0000312|HGNC:HGNC:19102}; 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=RIGI {ECO:0000312|HGNC:HGNC:19102}; Synonyms=DDX58; 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 INTERACTION WITH YWHAE. RX PubMed=22607805; DOI=10.1016/j.chom.2012.04.006; RA Liu H.M., Loo Y.M., Horner S.M., Zornetzer G.A., Katze M.G., Gale M. Jr.; RT "The mitochondrial targeting chaperone 14-3-3epsilon regulates a RIG-I RT translocon that mediates membrane association and innate antiviral RT immunity."; RL Cell Host Microbe 11:528-537(2012). RN [50] 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 [51] 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 [52] 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 [53] 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 [54] 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 [55] RP FUNCTION, AND DEUBIQUITINATION BY USP3. RX PubMed=24366338; DOI=10.1038/cr.2013.170; RA Cui J., Song Y., Li Y., Zhu Q., Tan P., Qin Y., Wang H.Y., Wang R.F.; RT "USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like RT receptors."; RL Cell Res. 24:400-416(2014). RN [56] 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 [57] 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 [58] RP INTERACTION WITH ECSIT. RX PubMed=25228397; DOI=10.1159/000365971; RA Lei C.Q., Zhang Y., Li M., Jiang L.Q., Zhong B., Kim Y.H., Shu H.B.; RT "ECSIT bridges RIG-I-like receptors to VISA in signaling events of innate RT antiviral responses."; RL J. Innate Immun. 7:153-164(2015). RN [59] 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 [60] 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 [61] 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 [62] 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 [63] 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 [64] 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 [65] 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 [66] 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 [67] 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 [68] RP INTERACTION WITH IRGM, AND PROTEIN DEGRADATION. RX PubMed=32715615; DOI=10.15252/embr.202050051; RA Jena K.K., Mehto S., Nath P., Chauhan N.R., Sahu R., Dhar K., Das S.K., RA Kolapalli S.P., Murmu K.C., Jain A., Krishna S., Sahoo B.S., RA Chattopadhyay S., Rusten T.E., Prasad P., Chauhan S., Chauhan S.; RT "Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to RT control interferon response."; RL EMBO Rep. 21:e50051-e50051(2020). RN [69] 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 [70] 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 [71] 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 [72] RP FUNCTION, AND PHOSPHORYLATION AT SER-8 (MICROBIAL INFECTION). RX PubMed=34935440; DOI=10.1128/jvi.01510-21; RA van Gent M., Chiang J.J., Muppala S., Chiang C., Azab W., Kattenhorn L., RA Knipe D.M., Osterrieder N., Gack M.U.; RT "The US3 Kinase of Herpes Simplex Virus Phosphorylates the RNA Sensor RIG-I RT To Suppress Innate Immunity."; RL J. Virol. 96:e0151021-e0151021(2022). RN [73] RP FUNCTION, AND INTERACTION WITH DHX16. RX PubMed=35263596; DOI=10.1016/j.celrep.2022.110434; RA Hage A., Bharaj P., van Tol S., Giraldo M.I., Gonzalez-Orozco M., RA Valerdi K.M., Warren A.N., Aguilera-Aguirre L., Xie X., Widen S.G., RA Moulton H.M., Lee B., Johnson J.R., Krogan N.J., Garcia-Sastre A., RA Shi P.Y., Freiberg A.N., Rajsbaum R.; RT "The RNA helicase DHX16 recognizes specific viral RNA to trigger RIG-I- RT dependent innate antiviral immunity."; RL Cell Rep. 38:110434-110434(2022). RN [74] RP FUNCTION, AND INTERACTION WITH IFI6. RX PubMed=36793726; DOI=10.3389/fimmu.2023.1105309; RA Villamayor L., Rivero V., Lopez-Garcia D., Topham D.J., RA Martinez-Sobrido L., Nogales A., DeDiego M.L.; RT "Interferon alpha inducible protein 6 is a negative regulator of innate RT immune responses by modulating RIG-I activation."; RL Front. Immunol. 14:1105309-1105309(2023). RN [75] 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 [76] 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 [77] 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:15708988, PubMed:16125763, PubMed:16127453, CC PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, CC PubMed:19211564, PubMed:24366338, PubMed:28469175, PubMed:29117565, CC PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726). 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.70). 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:24366338, ECO:0000269|PubMed:28469175, CC ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:31006531, CC ECO:0000269|PubMed:34935440, ECO:0000269|PubMed:35263596, CC ECO:0000269|PubMed:36793726, ECO:0000269|Ref.70, 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 RIGI. 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 RIGI 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 RIGI 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 RIGI degradation (By similarity). Interacts with LRRC25 CC (PubMed:29288164). Interacts with ZCCHC3; leading to activation of RIGI CC (PubMed:30193849). Interacts with RNF123 (PubMed:27312109). Interacts CC with UBE2D3 and UBE2N; E2 ubiquitin ligases involved in RNF135-mediated CC ubiquitination of RIGI and activation of the RIG-I signaling pathway CC (PubMed:28469175). Interacts with IFIT3 (PubMed:21813773). Interacts CC with DDX3X (PubMed:20127681). Interacts with RTN3 (PubMed:34313226). CC Interacts with ARL16; this interaction is GTP-dependent and induced CC upon viral infection; this interaction suppresses the RNA sensing CC activity of RIGI (PubMed:21233210). Interacts with DHX16; this CC interaction enhances RIGI-mediated antiviral response CC (PubMed:35263596). Interacts with IRGM; promoting RIGI degradation CC (PubMed:32715615). Interacts with IFI6; this interaction inhibits RIGI CC activation (PubMed:36793726). Interacts with ECSIT; this interaction CC bridges RIGI to the MAVS complex at the mitochondrion CC (PubMed:25228397). Interacts with YWHAE; this interaction drives RIGI CC at the mitochondrion (PubMed:22607805). {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:22607805, ECO:0000269|PubMed:23843640, CC ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:25018021, CC ECO:0000269|PubMed:25228397, 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:32715615, ECO:0000269|PubMed:34313226, CC ECO:0000269|PubMed:35263596, ECO:0000269|PubMed:36793726}. 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 RIGI (PubMed:22152002). {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 RIGI (PubMed:22301138). {ECO:0000269|PubMed:22301138}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1 CC protein UL37; this interaction deaminates RIGI 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 RIGI 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; Q7Z434: MAVS; NbExp=19; IntAct=EBI-995350, EBI-995373; CC O95786; Q9NZM5: NOP53; NbExp=2; IntAct=EBI-995350, EBI-720156; CC O95786; Q8TAT6: NPLOC4; NbExp=6; IntAct=EBI-995350, EBI-1994109; CC O95786; O75569: PRKRA; NbExp=5; IntAct=EBI-995350, EBI-713955; CC O95786; O95786: RIGI; NbExp=3; IntAct=EBI-995350, EBI-995350; CC O95786; Q96EQ8: RNF125; NbExp=4; IntAct=EBI-995350, EBI-2339208; CC O95786; P42224: STAT1; NbExp=4; IntAct=EBI-995350, EBI-1057697; CC O95786; Q14258: TRIM25; NbExp=9; 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=15; IntAct=EBI-995350, EBI-25475856; CC O95786; A0A0B5AC19: NSS; Xeno; NbExp=5; IntAct=EBI-995350, EBI-9687469; CC O95786; P21699: NSS; Xeno; NbExp=3; IntAct=EBI-995350, EBI-6693910; CC O95786; PRO_0000449623 [P0DTD1]: rep; Xeno; NbExp=6; 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 O95786-1; Q9H1Y0: ATG5; NbExp=4; IntAct=EBI-15577823, EBI-1047414; CC O95786-1; Q7Z434-1: MAVS; NbExp=8; IntAct=EBI-15577823, EBI-15577799; CC O95786-1; O95786-1: RIGI; NbExp=4; IntAct=EBI-15577823, EBI-15577823; 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 RIGI (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). Deubiquitinated by USP3 CC that also cleaves 'Lys-63'-linked ubiquitin chains and inhibits the CC innate immune receptor activity (PubMed:24366338). 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:24366338, ECO:0000269|PubMed:24755855, CC ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:29117565, CC ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:31006531, CC 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 herpes CC simplex virus 1 protein UL37. These modifications eliminate RIGI CC detection of viral RNA and restriction of viral replication. CC {ECO:0000269|PubMed:27866900}. CC -!- PTM: Degraded via selective autophagy following interaction with IRGM CC (PubMed:32715615). IRGM promotes RIGI recruitment to autophagosome CC membranes, promoting its SQSTM1/p62-dependent autophagic degradation CC (PubMed:32715615). {ECO:0000269|PubMed:32715615}. 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 -!- PTM: (Microbial infection) Phosphorylated at Ser-8 by herpes simplex CC virus 1 protein US3 leading to inhibition of critical RIGI activation CC steps. {ECO:0000269|PubMed:34935440}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7TNX; EM; 3.54 A; A=1-925. DR PDB; 7TNY; EM; 3.20 A; A=1-925. DR PDB; 7TNZ; EM; 3.54 A; A=1-925. DR PDB; 7TO0; EM; 3.50 A; A=1-925. DR PDB; 7TO1; EM; 3.66 A; A=1-925. DR PDB; 7TO2; EM; 3.20 A; A=1-925. DR PDB; 8DVR; EM; 3.30 A; A=1-925. DR PDB; 8DVS; EM; 3.00 A; A=1-925. DR PDB; 8DVU; EM; 2.90 A; A=1-925. DR PDB; 8G7T; EM; 3.20 A; A/C=1-925. DR PDB; 8G7U; EM; 4.00 A; A/C=1-925. DR PDB; 8G7V; EM; 3.90 A; A/C=1-925. DR PDB; 8SCZ; EM; 3.40 A; A=1-925. DR PDB; 8SD0; EM; 3.80 A; A=1-925. 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 PDBsum; 7TNX; -. DR PDBsum; 7TNY; -. DR PDBsum; 7TNZ; -. DR PDBsum; 7TO0; -. DR PDBsum; 7TO1; -. DR PDBsum; 7TO2; -. DR PDBsum; 8DVR; -. DR PDBsum; 8DVS; -. DR PDBsum; 8DVU; -. DR PDBsum; 8G7T; -. DR PDBsum; 8G7U; -. DR PDBsum; 8G7V; -. DR PDBsum; 8SCZ; -. DR PDBsum; 8SD0; -. DR AlphaFoldDB; O95786; -. DR BMRB; O95786; -. DR EMDB; EMD-22369; -. DR EMDB; EMD-22371; -. DR EMDB; EMD-26022; -. DR EMDB; EMD-26023; -. DR EMDB; EMD-26024; -. DR EMDB; EMD-26025; -. DR EMDB; EMD-26026; -. DR EMDB; EMD-26027; -. DR EMDB; EMD-27743; -. DR EMDB; EMD-27744; -. DR EMDB; EMD-27745; -. DR EMDB; EMD-29823; -. DR EMDB; EMD-29824; -. DR EMDB; EMD-29825; -. DR EMDB; EMD-40347; -. DR EMDB; EMD-40348; -. DR SASBDB; O95786; -. DR SMR; O95786; -. DR BioGRID; 117121; 1765. DR CORUM; O95786; -. DR DIP; DIP-35444N; -. DR IntAct; O95786; 39. DR STRING; 9606.ENSP00000369213; -. DR GlyCosmos; O95786; 1 site, 2 glycans. DR GlyGen; O95786; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; O95786; -. DR MetOSite; O95786; -. DR PhosphoSitePlus; O95786; -. DR BioMuta; DDX58; -. DR jPOST; O95786; -. DR MassIVE; O95786; -. DR PaxDb; 9606-ENSP00000369213; -. DR PeptideAtlas; O95786; -. DR ProteomicsDB; 51047; -. [O95786-1] DR ProteomicsDB; 51048; -. [O95786-2] DR Pumba; O95786; -. DR Antibodypedia; 3367; 688 antibodies from 46 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 AGR; HGNC:19102; -. DR CTD; 23586; -. DR DisGeNET; 23586; -. DR GeneCards; RIGI; -. DR HGNC; HGNC:19102; RIGI. DR HPA; ENSG00000107201; Low tissue specificity. DR MalaCards; RIGI; -. 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; FFANHVP; -. DR OrthoDB; 342391at2759; -. 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-9692916; SARS-CoV-1 activates/modulates innate immune responses. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-9833109; Evasion by RSV of host interferon responses. DR Reactome; R-HSA-9833110; RSV-host interactions. DR SignaLink; O95786; -. DR SIGNOR; O95786; -. DR BioGRID-ORCS; 23586; 13 hits in 1151 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 199 other cell types or tissues. DR ExpressionAtlas; O95786; baseline and differential. 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:0038187; F:pattern recognition receptor activity; IDA:UniProt. 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:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProt. 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: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; TAS:UniProtKB. DR GO; GO:0039529; P:RIG-I signaling pathway; IDA:UniProtKB. DR CDD; cd08817; CARD_RIG-I_r2; 1. DR CDD; cd18073; DEXHc_RIG-I_DDX58; 1. DR CDD; cd12090; MDA5_ID; 1. DR CDD; cd15805; RIG-I_C; 1. DR CDD; cd18802; SF2_C_dicer; 1. DR Gene3D; 1.20.1320.30; -; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR Gene3D; 2.170.150.30; RIG-I-like receptor, C-terminal regulatory domain; 1. 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-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR041204; RIG-I-like_C. DR InterPro; IPR038557; RLR_C_sf. DR InterPro; IPR021673; RLR_CTR. DR InterPro; IPR051363; RLR_Helicase. DR PANTHER; PTHR14074:SF16; ANTIVIRAL INNATE IMMUNE RESPONSE RECEPTOR RIG-I; 1. DR PANTHER; PTHR14074; HELICASE WITH DEATH DOMAIN-RELATED; 1. 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; P-loop containing nucleoside triphosphate hydrolases; 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 8 FT /note="(Microbial infection) Phosphoserine" FT /evidence="ECO:0000269|PubMed:34935440" 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:8DVU" 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 STRAND 667..670 FT /evidence="ECO:0007829|PDB:7TO0" 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 733..735 FT /evidence="ECO:0007829|PDB:8DVS" 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 853..855 FT /evidence="ECO:0007829|PDB:8DVS" 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 //