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Database: UniProt
Entry: Q99J87
LinkDB: Q99J87
Original site: Q99J87 
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   18-SEP-2019, entry version 140.
DE   RecName: Full=Probable ATP-dependent RNA helicase DHX58;
DE            EC=3.6.4.13;
DE   AltName: Full=Probable ATP-dependent helicase LGP2;
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; Synonyms=D11lgp2e, Lgp2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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.,
RA   She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA   Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA   Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA   Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA   Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of
RT   the 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
RT   project: 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-
RT   like proteins that are preferentially expressed in normal and
RT   neoplastic mammary 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
RT   self-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
RT   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
RT   Listeria monocytogenes and vaccinia virus in the absence of the murine
RT   LGP2 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
CC       mediated antiviral signaling. Cannot initiate antiviral signaling
CC       as it lacks the CARD domain required for activating MAVS/IPS1-
CC       dependent signaling events. Can have both negative and positive
CC       regulatory functions related to DDX58/RIG-I and IFIH1/MDA5
CC       signaling and this role in regulating signaling may be complex and
CC       could probably depend on characteristics of the infecting virus or
CC       target cells, or both. Its inhibitory action on DDX58/RIG-I
CC       signaling may involve the following mechanisms: competition with
CC       DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I
CC       and inhibiting its dimerization and interaction with MAVS/IPS1,
CC       competing with IKBKE in its binding to MAVS/IPS1 thereby
CC       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
CC       by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune
CC       response to various RNA viruses and some DNA viruses such as
CC       poxviruses, and also to the bacterial pathogen Listeria
CC       monocytogenes. Can bind both ssRNA and dsRNA, with a higher
CC       affinity for dsRNA. Shows a preference to 5'-triphosphorylated
CC       RNA, although it can recognize RNA lacking a 5'-triphosphate.
CC       {ECO:0000269|PubMed:17475874, ECO:0000269|PubMed:20080593,
CC       ECO:0000269|PubMed:21525357, 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   -!- SUBUNIT: Monomer in the absence of dsRNA. Homodimer in the
CC       presence of dsRNA. Interacts with DDX58/RIG-I (via CARD domain),
CC       MAVS/IPS1 and DDX60. Found in a complex with DDX58/RIG-I and
CC       IFIH1/MDA5. Interacts with ANKRD17. Directly interacts with ATG5
CC       and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5
CC       conjugates (By similarity). {ECO:0000250|UniProtKB:Q96C10}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11735219}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in mammary tissues. Expressed
CC       in liver and testis. Expressed at lower level in spleen, embryo,
CC       mammary 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
CC       and signaling of DDX58/RIG-I and also facilitates binding of
CC       dsRNA.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality at a high frequency.
CC       Adult female that survive show an enlarged uterus filled with
CC       fluid resulting from vaginal atresia.
CC       {ECO:0000269|PubMed:20080593}.
CC   -!- SIMILARITY: Belongs to the helicase family. RLR subfamily.
CC       {ECO:0000305}.
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   SMR; Q99J87; -.
DR   BioGrid; 219822; 1.
DR   STRING; 10090.ENSMUSP00000017974; -.
DR   iPTMnet; Q99J87; -.
DR   PhosphoSitePlus; Q99J87; -.
DR   EPD; Q99J87; -.
DR   MaxQB; Q99J87; -.
DR   PaxDb; Q99J87; -.
DR   PRIDE; Q99J87; -.
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   eggNOG; KOG0354; Eukaryota.
DR   eggNOG; COG1111; LUCA.
DR   GeneTree; ENSGT00940000153173; -.
DR   HOGENOM; HOG000230992; -.
DR   InParanoid; Q99J87; -.
DR   KO; K12649; -.
DR   OMA; HRAVGNY; -.
DR   OrthoDB; 1337630at2759; -.
DR   TreeFam; TF330258; -.
DR   PRO; PR:Q99J87; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   Bgee; ENSMUSG00000017830; Expressed in 107 organ(s), highest expression level in bone marrow macrophage.
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: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; IEA:UniProtKB-EC.
DR   GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
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: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   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; Complete proteome;
KW   Cytoplasm; Helicase; Hydrolase; Immunity; Innate immunity;
KW   Metal-binding; Nucleotide-binding; Reference proteome; RNA-binding;
KW   Zinc.
FT   CHAIN         1    678       Probable ATP-dependent RNA helicase
FT                                DHX58.
FT                                /FTId=PRO_0000102011.
FT   DOMAIN       11    188       Helicase ATP-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00541}.
FT   DOMAIN      353    514       Helicase C-terminal.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00542}.
FT   DOMAIN      542    669       RLR CTR. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01125}.
FT   NP_BIND      24     31       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00541}.
FT   REGION      572    655       RNA-binding. {ECO:0000250}.
FT   COILED      489    546       {ECO:0000255}.
FT   MOTIF       131    134       DECH box.
FT   METAL       556    556       Zinc. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01125}.
FT   METAL       559    559       Zinc. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01125}.
FT   METAL       612    612       Zinc. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01125}.
FT   METAL       615    615       Zinc. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01125}.
FT   MUTAGEN      30     30       K->A: Abolishes IFNB1 production upon
FT                                infection with various viruses.
FT                                {ECO:0000269|PubMed:20080593}.
FT   CONFLICT    638    638       I -> M (in Ref. 1; AAK15474/AAK15475 and
FT                                3; AAH29209). {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
//
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