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Q99J87

- DHX58_MOUSE

UniProt

Q99J87 - DHX58_MOUSE

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Protein

Probable ATP-dependent RNA helicase DHX58

Gene
Dhx58, D11lgp2e, Lgp2
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 – 5561Zinc By similarity
Metal bindingi559 – 5591Zinc By similarity
Metal bindingi612 – 6121Zinc By similarity
Metal bindingi615 – 6151Zinc By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi24 – 318ATP Reviewed prediction

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
Complete GO annotation...

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
Complete GO annotation...

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.

Protein-protein interaction databases

BioGridi219822. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ99J87.
SMRiQ99J87. Positions 1-678.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini11 – 188178Helicase ATP-bindingAdd
BLAST
Domaini353 – 514162Helicase C-terminalAdd
BLAST

Region

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

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili489 – 54658 Reviewed predictionAdd
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

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti638 – 6381I → M in AAK15474. 1 Publication
Sequence conflicti638 – 6381I → M in AAK15475. 1 Publication
Sequence conflicti638 – 6381I → M in AAH29209. 1 Publication

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 107 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

Similar proteinsi