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Q99J87

- DHX58_MOUSE

UniProt

Q99J87 - DHX58_MOUSE

Protein

Probable ATP-dependent RNA helicase DHX58

Gene

Dhx58

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 108 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: competition with DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses, and also to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate.4 Publications

    Catalytic activityi

    ATP + H2O = ADP + phosphate.

    Cofactori

    Zinc.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi556 – 5561ZincBy similarity
    Metal bindingi559 – 5591ZincBy similarity
    Metal bindingi612 – 6121ZincBy similarity
    Metal bindingi615 – 6151ZincBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi24 – 318ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. DNA binding Source: InterPro
    3. double-stranded RNA binding Source: UniProtKB
    4. helicase activity Source: UniProtKB-KW
    5. single-stranded RNA binding Source: UniProtKB
    6. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. defense response to virus Source: UniProtKB-KW
    2. innate immune response Source: UniProtKB-KW
    3. negative regulation of innate immune response Source: UniProtKB
    4. negative regulation of MDA-5 signaling pathway Source: UniProtKB
    5. negative regulation of RIG-I signaling pathway Source: UniProtKB
    6. negative regulation of type I interferon production Source: UniProtKB
    7. positive regulation of MDA-5 signaling pathway Source: UniProtKB
    8. positive regulation of RIG-I signaling pathway Source: UniProtKB
    9. positive regulation of type I interferon production Source: UniProtKB
    10. response to virus Source: UniProtKB

    Keywords - Molecular functioni

    Helicase, Hydrolase

    Keywords - Biological processi

    Antiviral defense, Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Probable ATP-dependent RNA helicase DHX58 (EC:3.6.4.13)
    Alternative name(s):
    Probable ATP-dependent helicase LGP2
    Protein D11Lgp2
    RIG-I-like receptor 3
    Short name:
    RLR-3
    RIG-I-like receptor Lgp2
    Short name:
    RLR
    Gene namesi
    Name:Dhx58
    Synonyms:D11lgp2e, Lgp2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:1931560. Dhx58.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: MGI

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Embryonic lethality at a high frequency. Adult female that survive show an enlarged uterus filled with fluid resulting from vaginal atresia.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi30 – 301K → A: Abolishes IFNB1 production upon infection with various viruses. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 678678Probable ATP-dependent RNA helicase DHX58PRO_0000102011Add
    BLAST

    Proteomic databases

    MaxQBiQ99J87.
    PaxDbiQ99J87.
    PRIDEiQ99J87.

    PTM databases

    PhosphoSiteiQ99J87.

    Expressioni

    Tissue specificityi

    Highly expressed in mammary tissues. Expressed in liver and testis. Expressed at lower level in spleen, embryo, mammary gland and breast tumors.1 Publication

    Inductioni

    By interferon (IFN), virus infection, or intracellular dsRNA.

    Gene expression databases

    BgeeiQ99J87.
    CleanExiMM_DHX58.
    GenevestigatoriQ99J87.

    Interactioni

    Subunit structurei

    Monomer in the absence of dsRNA. Homodimer in the presence of dsRNA. Interacts with DDX58/RIG-I (via CARD domain), MAVS/IPS1 and DDX60. Found in a complex with DDX58/RIG-I and IFIH1/MDA5 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi219822. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ99J87.
    SMRiQ99J87. Positions 1-678.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini11 – 188178Helicase ATP-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini353 – 514162Helicase C-terminalPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni476 – 678203Repressor domainAdd
    BLAST
    Regioni572 – 65584RNA-bindingBy similarityAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili489 – 54658Sequence AnalysisAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi131 – 1344DECH box

    Domaini

    The repressor domain is capable of inhibiting dimerization and signaling of DDX58/RIG-I and also facilitates binding of dsRNA.

    Sequence similaritiesi

    Belongs to the helicase family. RLR subfamily.Curated
    Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
    Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiCOG1111.
    GeneTreeiENSGT00510000046789.
    HOGENOMiHOG000230992.
    HOVERGENiHBG106019.
    InParanoidiA2A5E9.
    KOiK12649.
    OMAiENPKLEM.
    OrthoDBiEOG7RV9FC.
    TreeFamiTF330258.

    Family and domain databases

    Gene3Di3.40.50.300. 2 hits.
    InterProiIPR006935. Helicase/UvrB_dom.
    IPR014001. Helicase_ATP-bd.
    IPR001650. Helicase_C.
    IPR027417. P-loop_NTPase.
    IPR021673. RIG-I_C-RD.
    [Graphical view]
    PfamiPF00271. Helicase_C. 1 hit.
    PF04851. ResIII. 1 hit.
    PF11648. RIG-I_C-RD. 1 hit.
    [Graphical view]
    SMARTiSM00487. DEXDc. 1 hit.
    SM00490. HELICc. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 2 hits.
    PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
    PS51194. HELICASE_CTER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q99J87-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELRPYQWEV ILPALEGKNI IIWLPTGAGK TRAAAFVAKR HLETVDRGKV    50
    VVLVNRVHLV SQHAEEFRRM LDKHWTVTTL SGDMGSRAGF GLMARSHDLL 100
    ICTAELLQLA LNSSEEDEHV ELREFSLIVV DECHHTHKDT VYNTILSRYL 150
    EQKLKKAEPL PQVLGLTASP GTGGATKLQG AIDHILQLCA NLDTCHIMSP 200
    KNCYSQLLMH NPKPCKQYDL CQRRAQDPFG DLIKKLMNQI HQQLEMPDLK 250
    QQFGTQMYEQ QVVQLCKDAA EAGLQEQRVY ALHLRRYNDA LFIHDTVRAR 300
    DALDMLQDFY DRERTTKTQM VRAESWLLKL FDDHKNVLGQ LAARGPENPK 350
    LEMLERILLK QFGSPGHTRG IIFTRTRQTA SSLLLWLRQQ PCLQTVGIKP 400
    QMLIGAGNTS QSTHMTQKDQ QEVIQEFRDG ILSLLVATSV AEEGLDIAQC 450
    NVVVRYGLLT NEISMVQARG RARAGQSVYS FLATEGSREM KRELTNEALE 500
    VLMEKAVAAV QKMDPDEFKA KIRDLQQASL VKRAARAAHR EIQQGQFLPE 550
    HVQLLCINCM VAVGYGSDLR KVEGTHHVNV NPNFSVYYTT SQNPVVINKV 600
    FKDWRPGGTI RCSNCGEVWG FQMIYKSVTL PVLKIGSILL ETPRGKIQAK 650
    KWSRVPFSIP VFDILQDCTQ SLSELSLD 678
    Length:678
    Mass (Da):76,709
    Last modified:July 27, 2011 - v2
    Checksum:iD907A30E3AD376A8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti638 – 6381I → M in AAK15474. (PubMed:11161808)Curated
    Sequence conflicti638 – 6381I → M in AAK15475. (PubMed:11161808)Curated
    Sequence conflicti638 – 6381I → M in AAH29209. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF316999 mRNA. Translation: AAK15474.1.
    AF317000 Genomic DNA. Translation: AAK15475.1.
    AL591469 Genomic DNA. Translation: CAM22908.1.
    BC029209 mRNA. Translation: AAH29209.1.
    CCDSiCCDS25431.1.
    RefSeqiNP_084426.2. NM_030150.2.
    UniGeneiMm.271830.

    Genome annotation databases

    EnsembliENSMUST00000017974; ENSMUSP00000017974; ENSMUSG00000017830.
    GeneIDi80861.
    KEGGimmu:80861.
    UCSCiuc007llx.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF316999 mRNA. Translation: AAK15474.1 .
    AF317000 Genomic DNA. Translation: AAK15475.1 .
    AL591469 Genomic DNA. Translation: CAM22908.1 .
    BC029209 mRNA. Translation: AAH29209.1 .
    CCDSi CCDS25431.1.
    RefSeqi NP_084426.2. NM_030150.2.
    UniGenei Mm.271830.

    3D structure databases

    ProteinModelPortali Q99J87.
    SMRi Q99J87. Positions 1-678.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 219822. 1 interaction.

    PTM databases

    PhosphoSitei Q99J87.

    Proteomic databases

    MaxQBi Q99J87.
    PaxDbi Q99J87.
    PRIDEi Q99J87.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000017974 ; ENSMUSP00000017974 ; ENSMUSG00000017830 .
    GeneIDi 80861.
    KEGGi mmu:80861.
    UCSCi uc007llx.1. mouse.

    Organism-specific databases

    CTDi 79132.
    MGIi MGI:1931560. Dhx58.

    Phylogenomic databases

    eggNOGi COG1111.
    GeneTreei ENSGT00510000046789.
    HOGENOMi HOG000230992.
    HOVERGENi HBG106019.
    InParanoidi A2A5E9.
    KOi K12649.
    OMAi ENPKLEM.
    OrthoDBi EOG7RV9FC.
    TreeFami TF330258.

    Miscellaneous databases

    NextBioi 350167.
    PROi Q99J87.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q99J87.
    CleanExi MM_DHX58.
    Genevestigatori Q99J87.

    Family and domain databases

    Gene3Di 3.40.50.300. 2 hits.
    InterProi IPR006935. Helicase/UvrB_dom.
    IPR014001. Helicase_ATP-bd.
    IPR001650. Helicase_C.
    IPR027417. P-loop_NTPase.
    IPR021673. RIG-I_C-RD.
    [Graphical view ]
    Pfami PF00271. Helicase_C. 1 hit.
    PF04851. ResIII. 1 hit.
    PF11648. RIG-I_C-RD. 1 hit.
    [Graphical view ]
    SMARTi SM00487. DEXDc. 1 hit.
    SM00490. HELICc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 2 hits.
    PROSITEi PS51192. HELICASE_ATP_BIND_1. 1 hit.
    PS51194. HELICASE_CTER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Structure of the mouse Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse."
      Miyoshi K., Cui Y., Riedlinger G., Robinson P., Lehoczky J., Zon L., Oka T., Dewar K., Hennighausen L.
      Genomics 71:150-155(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: Czech II.
      Tissue: Mammary gland.
    4. "The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like proteins that are preferentially expressed in normal and neoplastic mammary tissue."
      Cui Y., Li M., Walton K.D., Sun K., Hanover J.A., Furth P.A., Hennighausen L.
      Genomics 78:129-134(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    5. "Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses."
      Venkataraman T., Valdes M., Elsby R., Kakuta S., Caceres G., Saijo S., Iwakura Y., Barber G.N.
      J. Immunol. 178:6444-6455(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Regulation of interferon production by RIG-I and LGP2: a lesson in self-control."
      Vitour D., Meurs E.F.
      Sci. STKE 2007:PE20-PE20(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    7. Cited for: FUNCTION, MUTAGENESIS OF LYS-30, DISRUPTION PHENOTYPE.
    8. "Immune signaling by RIG-I-like receptors."
      Loo Y.M., Gale M. Jr.
      Immunity 34:680-692(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    9. "Ambivalent role of the innate immune response in rabies virus pathogenesis."
      Chopy D., Pothlichet J., Lafage M., Megret F., Fiette L., Si-Tahar M., Lafon M.
      J. Virol. 85:6657-6668(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Impaired cellular responses to cytosolic DNA or infection with Listeria monocytogenes and vaccinia virus in the absence of the murine LGP2 protein."
      Pollpeter D., Komuro A., Barber G.N., Horvath C.M.
      PLoS ONE 6:E18842-E18842(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Regulation of RLR-mediated innate immune signaling--it is all about keeping the balance."
      Eisenaecher K., Krug A.
      Eur. J. Cell Biol. 91:36-47(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    12. "Sensing of viral nucleic acids by RIG-I: from translocation to translation."
      Schmidt A., Rothenfusser S., Hopfner K.P.
      Eur. J. Cell Biol. 91:78-85(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.

    Entry informationi

    Entry nameiDHX58_MOUSE
    AccessioniPrimary (citable) accession number: Q99J87
    Secondary accession number(s): A2A5E9, Q9D1X4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 108 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3