DHX58_MOUSE
ID DHX58_MOUSE Reviewed; 678 AA.
AC Q99J87; A2A5E9; Q9D1X4;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=ATP-dependent RNA helicase DHX58 {ECO:0000250|UniProtKB:Q96C10};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q96C10};
DE AltName: Full=ATP-dependent helicase LGP2 {ECO:0000250|UniProtKB:Q96C10};
DE AltName: Full=Protein D11Lgp2;
DE AltName: Full=RIG-I-like receptor 3;
DE Short=RLR-3;
DE AltName: Full=RIG-I-like receptor Lgp2;
DE Short=RLR;
GN Name=Dhx58 {ECO:0000312|MGI:MGI:1931560}; Synonyms=D11lgp2e, Lgp2;
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 [GENOMIC DNA / MRNA].
RX PubMed=11161808; DOI=10.1006/geno.2000.6433;
RA Miyoshi K., Cui Y., Riedlinger G., Robinson P., Lehoczky J., Zon L.,
RA Oka T., Dewar K., Hennighausen L.;
RT "Structure of the mouse Stat 3/5 locus: evolution from Drosophila to
RT zebrafish to mouse.";
RL Genomics 71:150-155(2001).
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 MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11735219; DOI=10.1006/geno.2001.6661;
RA Cui Y., Li M., Walton K.D., Sun K., Hanover J.A., Furth P.A.,
RA Hennighausen L.;
RT "The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like
RT proteins that are preferentially expressed in normal and neoplastic mammary
RT tissue.";
RL Genomics 78:129-134(2001).
RN [5]
RP FUNCTION.
RX PubMed=17475874; DOI=10.4049/jimmunol.178.10.6444;
RA Venkataraman T., Valdes M., Elsby R., Kakuta S., Caceres G., Saijo S.,
RA Iwakura Y., Barber G.N.;
RT "Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral
RT responses.";
RL J. Immunol. 178:6444-6455(2007).
RN [6]
RP REVIEW ON FUNCTION.
RX PubMed=17473309; DOI=10.1126/stke.3842007pe20;
RA Vitour D., Meurs E.F.;
RT "Regulation of interferon production by RIG-I and LGP2: a lesson in self-
RT control.";
RL Sci. STKE 2007:PE20-PE20(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [8]
RP FUNCTION, MUTAGENESIS OF LYS-30, AND DISRUPTION PHENOTYPE.
RX PubMed=20080593; DOI=10.1073/pnas.0912986107;
RA Satoh T., Kato H., Kumagai Y., Yoneyama M., Sato S., Matsushita K.,
RA Tsujimura T., Fujita T., Akira S., Takeuchi O.;
RT "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral
RT responses.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:1512-1517(2010).
RN [9]
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 [10]
RP FUNCTION.
RX PubMed=21525357; DOI=10.1128/jvi.00302-11;
RA Chopy D., Pothlichet J., Lafage M., Megret F., Fiette L., Si-Tahar M.,
RA Lafon M.;
RT "Ambivalent role of the innate immune response in rabies virus
RT pathogenesis.";
RL J. Virol. 85:6657-6668(2011).
RN [11]
RP FUNCTION.
RX PubMed=21533147; DOI=10.1371/journal.pone.0018842;
RA Pollpeter D., Komuro A., Barber G.N., Horvath C.M.;
RT "Impaired cellular responses to cytosolic DNA or infection with Listeria
RT monocytogenes and vaccinia virus in the absence of the murine LGP2
RT protein.";
RL PLoS ONE 6:E18842-E18842(2011).
RN [12]
RP REVIEW ON FUNCTION.
RX PubMed=21481967; DOI=10.1016/j.ejcb.2011.01.011;
RA Eisenaecher K., Krug A.;
RT "Regulation of RLR-mediated innate immune signaling--it is all about
RT keeping the balance.";
RL Eur. J. Cell Biol. 91:36-47(2012).
RN [13]
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).
CC -!- FUNCTION: Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated
CC antiviral signaling. Cannot initiate antiviral signaling as it lacks
CC the CARD domain required for activating MAVS/IPS1-dependent signaling
CC events. Can have both negative and positive regulatory functions
CC related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in
CC regulating signaling may be complex and could probably depend on
CC characteristics of the infecting virus or target cells, or both. Its
CC inhibitory action on DDX58/RIG-I signaling may involve the following
CC mechanisms: competition with DDX58/RIG-I for binding to the viral RNA,
CC binding to DDX58/RIG-I and inhibiting its dimerization and interaction
CC with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1
CC thereby inhibiting activation of interferon regulatory factor 3 (IRF3).
CC Its positive regulatory role may involve unwinding or stripping
CC nucleoproteins of viral RNA thereby facilitating their recognition by
CC DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to
CC various RNA viruses and some DNA viruses such as poxviruses, and also
CC to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA
CC and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-
CC triphosphorylated RNA, although it can recognize RNA lacking a 5'-
CC triphosphate. {ECO:0000269|PubMed:17475874,
CC ECO:0000269|PubMed:20080593, ECO:0000269|PubMed:21525357,
CC ECO:0000269|PubMed:21533147}.
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:Q96C10};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:Q96C10};
CC -!- SUBUNIT: Monomer in the absence of dsRNA. Homodimer in the presence of
CC dsRNA. Interacts with DDX58/RIG-I (via CARD domain), MAVS/IPS1 and
CC DDX60. Found in a complex with DDX58/RIG-I and IFIH1/MDA5. Interacts
CC with ANKRD17. Directly interacts with ATG5 and ATG12, either as ATG5
CC and ATG12 monomers or as ATG12-ATG5 conjugates (By similarity).
CC {ECO:0000250|UniProtKB:Q96C10}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11735219}.
CC -!- TISSUE SPECIFICITY: Highly expressed in mammary tissues. Expressed in
CC liver and testis. Expressed at lower level in spleen, embryo, mammary
CC gland and breast tumors. {ECO:0000269|PubMed:11735219}.
CC -!- INDUCTION: By interferon (IFN), virus infection, or intracellular
CC dsRNA.
CC -!- DOMAIN: The RLR CTR domain is capable of inhibiting dimerization and
CC signaling of DDX58/RIG-I and also facilitates binding of dsRNA.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality at a high frequency. Adult
CC female that survive show an enlarged uterus filled with fluid resulting
CC from vaginal atresia. {ECO:0000269|PubMed:20080593}.
CC -!- SIMILARITY: Belongs to the helicase family. RLR subfamily.
CC {ECO:0000305}.
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DR EMBL; AF316999; AAK15474.1; -; mRNA.
DR EMBL; AF317000; AAK15475.1; -; Genomic_DNA.
DR EMBL; AL591469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029209; AAH29209.1; -; mRNA.
DR CCDS; CCDS25431.1; -.
DR RefSeq; NP_084426.2; NM_030150.2.
DR AlphaFoldDB; Q99J87; -.
DR SMR; Q99J87; -.
DR BioGRID; 219822; 2.
DR STRING; 10090.ENSMUSP00000017974; -.
DR iPTMnet; Q99J87; -.
DR PhosphoSitePlus; Q99J87; -.
DR EPD; Q99J87; -.
DR MaxQB; Q99J87; -.
DR PaxDb; Q99J87; -.
DR PRIDE; Q99J87; -.
DR ProteomicsDB; 279533; -.
DR Antibodypedia; 16840; 377 antibodies from 36 providers.
DR DNASU; 80861; -.
DR Ensembl; ENSMUST00000017974; ENSMUSP00000017974; ENSMUSG00000017830.
DR GeneID; 80861; -.
DR KEGG; mmu:80861; -.
DR UCSC; uc007llx.1; mouse.
DR CTD; 79132; -.
DR MGI; MGI:1931560; Dhx58.
DR VEuPathDB; HostDB:ENSMUSG00000017830; -.
DR eggNOG; KOG0354; Eukaryota.
DR GeneTree; ENSGT00940000153173; -.
DR HOGENOM; CLU_006888_2_1_1; -.
DR InParanoid; Q99J87; -.
DR OMA; HRAVGNY; -.
DR OrthoDB; 1337630at2759; -.
DR PhylomeDB; Q99J87; -.
DR TreeFam; TF330258; -.
DR BioGRID-ORCS; 80861; 4 hits in 75 CRISPR screens.
DR PRO; PR:Q99J87; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q99J87; protein.
DR Bgee; ENSMUSG00000017830; Expressed in granulocyte and 104 other tissues.
DR Genevisible; Q99J87; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0003724; F:RNA helicase activity; ISS:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0039528; P:cytoplasmic pattern recognition receptor signaling pathway in response to virus; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0039534; P:negative regulation of MDA-5 signaling pathway; ISS:UniProtKB.
DR GO; GO:0039536; P:negative regulation of RIG-I signaling pathway; IMP:UniProtKB.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IMP:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IBA:GO_Central.
DR GO; GO:1900245; P:positive regulation of MDA-5 signaling pathway; IMP:UniProtKB.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IMP:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0009615; P:response to virus; IMP:UniProtKB.
DR Gene3D; 2.170.150.30; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
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; 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; 1.
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 Antiviral defense; ATP-binding; Coiled coil; Cytoplasm; Helicase;
KW Hydrolase; Immunity; Innate immunity; Metal-binding; Nucleotide-binding;
KW Reference proteome; RNA-binding; Zinc.
FT CHAIN 1..678
FT /note="ATP-dependent RNA helicase DHX58"
FT /id="PRO_0000102011"
FT DOMAIN 11..188
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 353..514
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 542..669
FT /note="RLR CTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT REGION 572..655
FT /note="RNA-binding"
FT /evidence="ECO:0000250"
FT COILED 489..546
FT /evidence="ECO:0000255"
FT MOTIF 131..134
FT /note="DECH box"
FT BINDING 24..31
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 556
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 559
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 612
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 615
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT MUTAGEN 30
FT /note="K->A: Abolishes IFNB1 production upon infection with
FT various viruses."
FT /evidence="ECO:0000269|PubMed:20080593"
FT CONFLICT 638
FT /note="I -> M (in Ref. 1; AAK15474/AAK15475 and 3;
FT AAH29209)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 678 AA; 76709 MW; D907A30E3AD376A8 CRC64;
MELRPYQWEV ILPALEGKNI IIWLPTGAGK TRAAAFVAKR HLETVDRGKV VVLVNRVHLV
SQHAEEFRRM LDKHWTVTTL SGDMGSRAGF GLMARSHDLL ICTAELLQLA LNSSEEDEHV
ELREFSLIVV DECHHTHKDT VYNTILSRYL EQKLKKAEPL PQVLGLTASP GTGGATKLQG
AIDHILQLCA NLDTCHIMSP KNCYSQLLMH NPKPCKQYDL CQRRAQDPFG DLIKKLMNQI
HQQLEMPDLK QQFGTQMYEQ QVVQLCKDAA EAGLQEQRVY ALHLRRYNDA LFIHDTVRAR
DALDMLQDFY DRERTTKTQM VRAESWLLKL FDDHKNVLGQ LAARGPENPK LEMLERILLK
QFGSPGHTRG IIFTRTRQTA SSLLLWLRQQ PCLQTVGIKP QMLIGAGNTS QSTHMTQKDQ
QEVIQEFRDG ILSLLVATSV AEEGLDIAQC NVVVRYGLLT NEISMVQARG RARAGQSVYS
FLATEGSREM KRELTNEALE VLMEKAVAAV QKMDPDEFKA KIRDLQQASL VKRAARAAHR
EIQQGQFLPE HVQLLCINCM VAVGYGSDLR KVEGTHHVNV NPNFSVYYTT SQNPVVINKV
FKDWRPGGTI RCSNCGEVWG FQMIYKSVTL PVLKIGSILL ETPRGKIQAK KWSRVPFSIP
VFDILQDCTQ SLSELSLD
