DDX58_MOUSE
ID DDX58_MOUSE Reviewed; 926 AA.
AC Q6Q899; A2AP28; Q8C320; Q8C5I3; Q8C7T2;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Antiviral innate immune response receptor RIG-I {ECO:0000305};
DE AltName: Full=ATP-dependent RNA helicase DDX58 {ECO:0000250|UniProtKB:O95786};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:O95786};
DE AltName: Full=DEAD box protein 58;
DE AltName: Full=RIG-I-like receptor 1;
DE Short=RLR-1;
DE AltName: Full=Retinoic acid-inducible gene 1 protein;
DE Short=RIG-1;
DE AltName: Full=Retinoic acid-inducible gene I protein;
DE Short=RIG-I;
GN Name=Ddx58 {ECO:0000312|MGI:MGI:2442858};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Wei J., Gu J.;
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP FUNCTION.
RX PubMed=16039576; DOI=10.1016/j.immuni.2005.04.010;
RA Kato H., Sato S., Yoneyama M., Yamamoto M., Uematsu S., Matsui K.,
RA Tsujimura T., Takeda K., Fujita T., Takeuchi O., Akira S.;
RT "Cell type-specific involvement of RIG-I in antiviral response.";
RL Immunity 23:19-28(2005).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16625202; DOI=10.1038/nature04734;
RA Kato H., Takeuchi O., Sato S., Yoneyama M., Yamamoto M., Matsui K.,
RA Uematsu S., Jung A., Kawai T., Ishii K.J., Yamaguchi O., Otsu K.,
RA Tsujimura T., Koh C.S., Reis e Sousa C., Matsuura Y., Fujita T., Akira S.;
RT "Differential roles of MDA5 and RIG-I helicases in the recognition of RNA
RT viruses.";
RL Nature 441:101-105(2006).
RN [7]
RP FUNCTION.
RX PubMed=17942531; DOI=10.1128/jvi.01080-07;
RA Loo Y.M., Fornek J., Crochet N., Bajwa G., Perwitasari O.,
RA Martinez-Sobrido L., Akira S., Gill M.A., Garcia-Sastre A., Katze M.G.,
RA Gale M. Jr.;
RT "Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity.";
RL J. Virol. 82:335-345(2008).
RN [8]
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 [9]
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 [10]
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
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 [13]
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 [14]
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 [15]
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 [16]
RP REVIEW ON FUNCTION.
RX PubMed=21496944; DOI=10.1016/j.ejcb.2011.01.015;
RA Schmidt A., Rothenfusser S., Hopfner K.P.;
RT "Sensing of viral nucleic acids by RIG-I: from translocation to
RT translation.";
RL Eur. J. Cell Biol. 91:78-85(2012).
RN [17]
RP INTERACTION WITH SIGLEC10; CBL AND PTPN11, UBIQUITINATION AT LYS-813, AND
RP MUTAGENESIS OF LYS-813.
RX PubMed=23374343; DOI=10.1016/j.cell.2013.01.011;
RA Chen W., Han C., Xie B., Hu X., Yu Q., Shi L., Wang Q., Li D., Wang J.,
RA Zheng P., Liu Y., Cao X.;
RT "Induction of Siglec-G by RNA viruses inhibits the innate immune response
RT by promoting RIG-I degradation.";
RL Cell 152:467-478(2013).
RN [18] {ECO:0007744|PDB:3TBK}
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 240-794 IN COMPLEX WITH ATP
RP ANALOG.
RX PubMed=21979817; DOI=10.1038/embor.2011.190;
RA Civril F., Bennett M., Moldt M., Deimling T., Witte G., Schiesser S.,
RA Carell T., Hopfner K.P.;
RT "The RIG-I ATPase domain structure reveals insights into ATP-dependent
RT antiviral signalling.";
RL EMBO Rep. 12:1127-1134(2011).
RN [19] {ECO:0007744|PDB:6BZH}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-189.
RX PubMed=29259080; DOI=10.1042/bcj20170427;
RA D'Cruz A.A., Kershaw N.J., Hayman T.J., Linossi E.M., Chiang J.J.,
RA Wang M.K., Dagley L.F., Kolesnik T.B., Zhang J.G., Masters S.L.,
RA Griffin M.D.W., Gack M.U., Murphy J.M., Nicola N.A., Babon J.J.,
RA Nicholson S.E.;
RT "Identification of a second binding site on the TRIM25 B30.2 domain.";
RL Biochem. J. 475:429-440(2018).
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. Forms
CC a ribonucleoprotein complex with viral RNAs on which it
CC homooligomerizes to form filaments. The homooligomerization allows the
CC recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and
CC amplifies the RIG-I-mediated antiviral signaling in an RNA length-
CC dependent manner through ubiquitination-dependent and -independent
CC mechanisms. Upon activation, associates with mitochondria antiviral
CC signaling protein (MAVS/IPS1) that activates the IKK-related kinases
CC TBK1 and IKBKE which in turn phosphorylate the interferon regulatory
CC factors IRF3 and IRF7, activating transcription of antiviral
CC immunological genes including the IFN-alpha and IFN-beta interferons.
CC Ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA
CC (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end
CC base pairing at the 5'-end of the RNA is very essential. Overhangs at
CC the non-triphosphorylated end of the dsRNA RNA have no major impact on
CC its activity. A 3'overhang at the 5'triphosphate end decreases and any
CC 5'overhang at the 5' triphosphate end abolishes its activity. Detects
CC both positive and negative strand RNA viruses including members of the
CC families Paramyxoviridae: Sendai virus (SeV), Rhabdoviridae and
CC Flaviviridae. It also detects rotavirus and orthoreovirus. Also
CC involved in antiviral signaling in response to viruses containing a
CC dsDNA genome. Detects dsRNA produced from non-self dsDNA by RNA
CC polymerase III. May play important roles in granulocyte production and
CC differentiation, bacterial phagocytosis and in the regulation of cell
CC migration. {ECO:0000269|PubMed:16039576, ECO:0000269|PubMed:16625202,
CC ECO:0000269|PubMed:17942531, ECO:0000269|PubMed:19576794,
CC ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370}.
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:0000250|UniProtKB:O95786};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:O95786};
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. Interacts (via tandem CARD
CC domain) with MAVS/IPS1 promoting its filamentation. Interacts with
CC DHX58/LGP2, IKBKE, TBK1 and STING1. Interacts (via CARD domain) with
CC TRIM25 (via SPRY domain). Interacts (double-stranded RNA-bound
CC oligomeric form) with RNF135 (homodimer); involved in RNA length-
CC dependent activation of the RIG-I signaling pathway. Interacts with
CC CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to
CC DDX58. Interacts with SRC. Interacts with DDX60. Interacts with ZC3HAV1
CC (via zinc-fingers) in an RNA-dependent manner. Interacts (via tandem
CC CARD domain) with SEC14L1; the interaction is direct and impairs the
CC interaction of DDX58 with MAVS/IPS1. Interacts with VCP/p97;
CC interaction is direct and allows the recruitment of RNF125 and
CC subsequent ubiquitination and degradation. Interacts with NOP53; may
CC regulate DDX58 through USP15-mediated 'Lys-63'-linked deubiquitination
CC (By similarity). Interacts with SIGLEC10, CBL and PTPN11; within a
CC negative feedback loop leading to DDX58 degradation (PubMed:23374343).
CC Interacts with LRRC25. Interacts with ZCCHC3; leading to activation of
CC DDX58/RIG-I. Interacts with RNF123 (By similarity). Interacts with
CC UBE2D3 and UBE2N; E2 ubiquitin ligases involved in RNF135-mediated
CC ubiquitination of DDX58 and activation of the RIG-I signaling pathway
CC (By similarity). Interacts with IFIT3 (By similarity). Interacts with
CC DDX3X (By similarity). Interacts with RTN3 (By similarity). Interacts
CC with ARL16; this interaction is GTP-dependent and induced upon viral
CC infection; this interaction suppresses the RNA sensing activity of
CC DDX58 (By similarity). {ECO:0000250|UniProtKB:O95786,
CC ECO:0000269|PubMed:23374343}.
CC -!- INTERACTION:
CC Q6Q899; P22682: Cbl; NbExp=3; IntAct=EBI-6841237, EBI-640919;
CC Q6Q899; Q80ZE3: Siglec10; NbExp=7; IntAct=EBI-6841237, EBI-6841023;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell projection, ruffle
CC membrane {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cell
CC junction, tight junction {ECO:0000250}. Note=Colocalized with TRIM25 at
CC cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton
CC at membrane ruffles. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6Q899-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6Q899-2; Sequence=VSP_016055, VSP_016060;
CC Name=3;
CC IsoId=Q6Q899-3; Sequence=VSP_016058, VSP_016059;
CC Name=4;
CC IsoId=Q6Q899-4; Sequence=VSP_016056, VSP_016057;
CC -!- INDUCTION: By interferon (IFN).
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:0000250|UniProtKB:O95786}.
CC -!- DOMAIN: The helicase domain is responsible for dsRNA recognition.
CC {ECO:0000250|UniProtKB:O95786}.
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. {ECO:0000250|UniProtKB:O95786}.
CC -!- DOMAIN: The second CARD domain is the primary site for 'Lys-63'-linked
CC ubiquitination. {ECO:0000250|UniProtKB:O95786}.
CC -!- PTM: Phosphorylated in resting cells and dephosphorylated in RNA virus-
CC infected cells. Phosphorylation at Thr-771 results in inhibition of its
CC activity while dephosphorylation at these sites results in its
CC activation. {ECO:0000250|UniProtKB:O95786}.
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:0000250|UniProtKB:O95786}.
CC -!- PTM: Sumoylated, probably by MUL1; inhibiting its polyubiquitination.
CC {ECO:0000250|UniProtKB:O95786}.
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. Also ubiquitinated by TRIM4.
CC Also undergoes 'Lys-48' ubiquitination by RNF125 that leads to
CC proteasomal degradation. 'Lys-48' ubiquitination follows viral
CC infection and is enhanced by 'Lys-63'-linked ubiquitination of the CARD
CC domains that promotes interaction with VCP/p97 and subsequent
CC recruitment of RNF125 (By similarity). Within a negative feedback loop
CC involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-813 by
CC CBL also elicits the proteasomal degradation of DDX58
CC (PubMed:23374343). Deubiquitinated by CYLD, a protease that selectively
CC cleaves 'Lys-63'-linked ubiquitin chains. Also probably deubiquitinated
CC by USP17L2/USP17 that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin
CC chains and positively regulates the receptor (By similarity).
CC Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to
CC proteasomal degradation (By similarity). Deubiquitinated by USP27X that
CC cleaves 'Lys-63'-linked ubiquitin chains and inhibits the innate immune
CC receptor activity (By similarity). {ECO:0000250|UniProtKB:O95786,
CC ECO:0000269|PubMed:23374343}.
CC -!- DISRUPTION PHENOTYPE: Death between 12.5 dpc and 14 dpc due to liver
CC apoptosis. Those who are born alive show growth retardation and die
CC within 3 weeks. {ECO:0000269|PubMed:16625202}.
CC -!- SIMILARITY: Belongs to the helicase family. RLR subfamily.
CC {ECO:0000305}.
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DR EMBL; AY553221; AAS59532.1; -; mRNA.
DR EMBL; AL831793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466538; EDL05445.1; -; Genomic_DNA.
DR EMBL; AK049305; BAC33670.1; -; mRNA.
DR EMBL; AK078287; BAC37205.1; -; mRNA.
DR EMBL; AK087261; BAC39830.1; -; mRNA.
DR CCDS; CCDS18043.1; -. [Q6Q899-1]
DR RefSeq; NP_766277.3; NM_172689.3. [Q6Q899-1]
DR PDB; 3TBK; X-ray; 2.14 A; A=240-794.
DR PDB; 6BZH; X-ray; 2.50 A; A/B/C/D/E=2-189.
DR PDBsum; 3TBK; -.
DR PDBsum; 6BZH; -.
DR AlphaFoldDB; Q6Q899; -.
DR SMR; Q6Q899; -.
DR BioGRID; 230926; 9.
DR DIP; DIP-61741N; -.
DR IntAct; Q6Q899; 4.
DR STRING; 10090.ENSMUSP00000042433; -.
DR iPTMnet; Q6Q899; -.
DR PhosphoSitePlus; Q6Q899; -.
DR SwissPalm; Q6Q899; -.
DR EPD; Q6Q899; -.
DR MaxQB; Q6Q899; -.
DR PaxDb; Q6Q899; -.
DR PeptideAtlas; Q6Q899; -.
DR PRIDE; Q6Q899; -.
DR ProteomicsDB; 279183; -. [Q6Q899-1]
DR ProteomicsDB; 279184; -. [Q6Q899-2]
DR ProteomicsDB; 279185; -. [Q6Q899-3]
DR ProteomicsDB; 279186; -. [Q6Q899-4]
DR DNASU; 230073; -.
DR Ensembl; ENSMUST00000037907; ENSMUSP00000042433; ENSMUSG00000040296. [Q6Q899-1]
DR GeneID; 230073; -.
DR KEGG; mmu:230073; -.
DR UCSC; uc008she.1; mouse. [Q6Q899-2]
DR UCSC; uc008shf.1; mouse. [Q6Q899-1]
DR UCSC; uc008shg.1; mouse. [Q6Q899-3]
DR UCSC; uc008shh.1; mouse. [Q6Q899-4]
DR CTD; 23586; -.
DR MGI; MGI:2442858; Ddx58.
DR VEuPathDB; HostDB:ENSMUSG00000040296; -.
DR eggNOG; KOG0354; Eukaryota.
DR GeneTree; ENSGT00940000153173; -.
DR InParanoid; Q6Q899; -.
DR OMA; IFCARQD; -.
DR PhylomeDB; Q6Q899; -.
DR TreeFam; TF330258; -.
DR Reactome; R-MMU-1169408; ISG15 antiviral mechanism.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8983711; OAS antiviral response.
DR Reactome; R-MMU-936440; Negative regulators of DDX58/IFIH1 signaling.
DR BioGRID-ORCS; 230073; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Ddx58; mouse.
DR EvolutionaryTrace; Q6Q899; -.
DR PRO; PR:Q6Q899; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q6Q899; protein.
DR Bgee; ENSMUSG00000040296; Expressed in granulocyte and 175 other tissues.
DR ExpressionAtlas; Q6Q899; baseline and differential.
DR Genevisible; Q6Q899; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003724; F:RNA helicase activity; ISS:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; ISS:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0009597; P:detection of virus; ISO:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0002735; P:positive regulation of myeloid dendritic cell cytokine production; IMP:UniProtKB.
DR GO; GO:0060760; P:positive regulation of response to cytokine stimulus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI.
DR GO; GO:0009615; P:response to virus; IMP:UniProtKB.
DR GO; GO:0039529; P:RIG-I signaling pathway; ISS:UniProtKB.
DR CDD; cd08817; CARD_RIG-I_r2; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR Gene3D; 2.170.150.30; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR031964; CARD_dom.
DR InterPro; IPR042145; CARD_RIG-I_r2.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR006935; Helicase/UvrB_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041204; RIG-I_C.
DR InterPro; IPR038557; RLR_C_sf.
DR InterPro; IPR021673; RLR_CTR.
DR Pfam; PF16739; CARD_2; 2.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF04851; ResIII; 1.
DR Pfam; PF18119; RIG-I_C; 1.
DR Pfam; PF11648; RIG-I_C-RD; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51789; RLR_CTR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Antiviral defense;
KW ATP-binding; Cell junction; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Helicase; Hydrolase; Immunity; Innate immunity;
KW Isopeptide bond; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; Tight junction;
KW Ubl conjugation; Zinc.
FT CHAIN 1..926
FT /note="Antiviral innate immune response receptor RIG-I"
FT /id="PRO_0000144094"
FT DOMAIN 1..87
FT /note="CARD 1"
FT DOMAIN 92..172
FT /note="CARD 2"
FT DOMAIN 252..431
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 611..777
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 791..926
FT /note="RLR CTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT REGION 219..926
FT /note="Interaction with ZC3HAV1"
FT /evidence="ECO:0000250"
FT REGION 736..926
FT /note="Mediates interaction with RNF135"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT MOTIF 373..376
FT /note="DECH box"
FT BINDING 243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:21979817"
FT BINDING 248
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:21979817"
FT BINDING 265..272
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541,
FT ECO:0000269|PubMed:21979817"
FT BINDING 811
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 814
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 865
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 870
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT MOD_RES 771
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT MOD_RES 859
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 48
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 154
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 164
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 181
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 190
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 193
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 813
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23374343"
FT VAR_SEQ 1..454
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016055"
FT VAR_SEQ 192..227
FT /note="FKRAESKADEDDGAEASSIQIFIQEEPECQNLSQNP -> GVLQERTLDPAA
FT LLPVLPTLLSIRGAVHFRYQRLYP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016056"
FT VAR_SEQ 228..926
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016057"
FT VAR_SEQ 407..410
FT /note="VGLT -> FPIF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016058"
FT VAR_SEQ 411..926
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016059"
FT VAR_SEQ 455..460
FT /note="YKPQKI -> MPLTPV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016060"
FT MUTAGEN 813
FT /note="K->R: Greatly decreases 'K-48'-linked
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:23374343"
FT CONFLICT 4
FT /note="E -> A (in Ref. 1; AAS59532)"
FT /evidence="ECO:0000305"
FT CONFLICT 282
FT /note="H -> R (in Ref. 1; AAS59532)"
FT /evidence="ECO:0000305"
FT CONFLICT 604
FT /note="D -> G (in Ref. 1; AAS59532)"
FT /evidence="ECO:0000305"
FT HELIX 2..11
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 13..19
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:6BZH"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 35..47
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 50..61
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 69..80
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 111..117
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 120..127
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 133..146
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 148..160
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 181..185
FT /evidence="ECO:0007829|PDB:6BZH"
FT HELIX 246..256
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 271..284
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 301..316
FT /evidence="ECO:0007829|PDB:3TBK"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:3TBK"
FT TURN 327..329
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 335..341
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 343..347
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 349..357
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 375..377
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 383..395
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 405..411
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 421..434
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 447..451
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 459..463
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 471..488
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 492..495
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 496..499
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 508..522
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 529..558
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 561..575
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 583..592
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 595..603
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 605..607
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 610..625
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 631..634
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 638..650
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 659..661
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 693..697
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 711..717
FT /evidence="ECO:0007829|PDB:3TBK"
FT TURN 733..735
FT /evidence="ECO:0007829|PDB:3TBK"
FT STRAND 738..744
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 746..771
FT /evidence="ECO:0007829|PDB:3TBK"
FT HELIX 774..793
FT /evidence="ECO:0007829|PDB:3TBK"
SQ SEQUENCE 926 AA; 105975 MW; 119FC0F88BC56957 CRC64;
MTAEQRQNLQ AFRDYIKKIL DPTYILSYMS SWLEDEEVQY IQAEKNNKGP MEAASLFLQY
LLKLQSEGWF QAFLDALYHA GYCGLCEAIE SWDFQKIEKL EEHRLLLRRL EPEFKATVDP
NDILSELSEC LINQECEEIR QIRDTKGRMA GAEKMAECLI RSDKENWPKV LQLALEKDNS
KFSELWIVDK GFKRAESKAD EDDGAEASSI QIFIQEEPEC QNLSQNPGPP SEASSNNLHS
PLKPRNYQLE LALPAKKGKN TIICAPTGCG KTFVSLLICE HHLKKFPCGQ KGKVVFFANQ
IPVYEQQATV FSRYFERLGY NIASISGATS DSVSVQHIIE DNDIIILTPQ ILVNNLNNGA
IPSLSVFTLM IFDECHNTSK NHPYNQIMFR YLDHKLGESR DPLPQVVGLT ASVGVGDAKT
AEEAMQHICK LCAALDASVI ATVRDNVAEL EQVVYKPQKI SRKVASRTSN TFKCIISQLM
KETEKLAKDV SEELGKLFQI QNREFGTQKY EQWIVGVHKA CSVFQMADKE EESRVCKALF
LYTSHLRKYN DALIISEDAQ MTDALNYLKA FFHDVREAAF DETERELTRR FEEKLEELEK
VSRDPSNENP KLRDLYLVLQ EEYHLKPETK TILFVKTRAL VDALKKWIEE NPALSFLKPG
ILTGRGRTNR ATGMTLPAQK CVLEAFRASG DNNILIATSV ADEGIDIAEC NLVILYEYVG
NVIKMIQTRG RGRARDSKCF LLTSSADVIE KEKANMIKEK IMNESILRLQ TWDEMKFGKT
VHRIQVNEKL LRDSQHKPQP VPDKENKKLL CGKCKNFACY TADIRVVETS HYTVLGDAFK
ERFVCKPHPK PKIYDNFEKK AKIFCAKQNC SHDWGIFVRY KTFEIPVIKI ESFVVEDIVS
GVQNRHSKWK DFHFERIQFD PAEMSV
