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   02-OCT-2024, entry version 200.
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}.
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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   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; 1768.
DR   CORUM; O95786; -.
DR   DIP; DIP-35444N; -.
DR   IntAct; O95786; 39.
DR   MINT; O95786; -.
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; 727 antibodies from 46 providers.
DR   DNASU; 23586; -.
DR   Ensembl; ENST00000379868.6; ENSP00000369197.2; ENSG00000107201.12. [O95786-2]
DR   Ensembl; ENST00000379883.3; ENSP00000369213.2; ENSG00000107201.12. [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; Proteomics identification;
KW   Reference proteome; Repeat; RNA-binding; Tight junction; Ubl conjugation;
KW   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
//