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Q99J87 (DHX58_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Dhx58
Synonyms:D11lgp2e, Lgp2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length678 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.7 Ref.9 Ref.10

Catalytic activity

ATP + H2O = ADP + phosphate.

Cofactor

Zinc By similarity.

Subunit structure

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.

Subcellular location

Cytoplasm Ref.4.

Tissue specificity

Highly expressed in mammary tissues. Expressed in liver and testis. Expressed at lower level in spleen, embryo, mammary gland and breast tumors. Ref.4

Induction

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

Domain

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

Disruption phenotype

Embryonic lethality at a high frequency. Adult female that survive show an enlarged uterus filled with fluid resulting from vaginal atresia. Ref.7

Sequence similarities

Belongs to the helicase family. RLR subfamily.

Contains 1 helicase ATP-binding domain.

Contains 1 helicase C-terminal domain.

Ontologies

Keywords
   Biological processAntiviral defense
Immunity
Innate immunity
   Cellular componentCytoplasm
   DomainCoiled coil
   LigandATP-binding
Metal-binding
Nucleotide-binding
RNA-binding
Zinc
   Molecular functionHelicase
Hydrolase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of MDA-5 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of RIG-I signaling pathway

Inferred from mutant phenotype Ref.5. Source: UniProtKB

negative regulation of innate immune response

Inferred from mutant phenotype Ref.9. Source: UniProtKB

negative regulation of type I interferon production

Inferred from mutant phenotype Ref.9. Source: UniProtKB

positive regulation of MDA-5 signaling pathway

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of RIG-I signaling pathway

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of type I interferon production

Inferred from mutant phenotype Ref.7. Source: UniProtKB

response to virus

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.4. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: InterPro

double-stranded RNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

helicase activity

Inferred from electronic annotation. Source: UniProtKB-KW

single-stranded RNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 678678Probable ATP-dependent RNA helicase DHX58
PRO_0000102011

Regions

Domain11 – 188178Helicase ATP-binding
Domain353 – 514162Helicase C-terminal
Nucleotide binding24 – 318ATP Potential
Region476 – 678203Repressor domain
Region572 – 65584RNA-binding By similarity
Coiled coil489 – 54658 Potential
Motif131 – 1344DECH box

Sites

Metal binding5561Zinc By similarity
Metal binding5591Zinc By similarity
Metal binding6121Zinc By similarity
Metal binding6151Zinc By similarity

Experimental info

Mutagenesis301K → A: Abolishes IFNB1 production upon infection with various viruses. Ref.7
Sequence conflict6381I → M in AAK15474. Ref.1
Sequence conflict6381I → M in AAK15475. Ref.1
Sequence conflict6381I → M in AAH29209. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q99J87 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: D907A30E3AD376A8

FASTA67876,709
        10         20         30         40         50         60 
MELRPYQWEV ILPALEGKNI IIWLPTGAGK TRAAAFVAKR HLETVDRGKV VVLVNRVHLV 

        70         80         90        100        110        120 
SQHAEEFRRM LDKHWTVTTL SGDMGSRAGF GLMARSHDLL ICTAELLQLA LNSSEEDEHV 

       130        140        150        160        170        180 
ELREFSLIVV DECHHTHKDT VYNTILSRYL EQKLKKAEPL PQVLGLTASP GTGGATKLQG 

       190        200        210        220        230        240 
AIDHILQLCA NLDTCHIMSP KNCYSQLLMH NPKPCKQYDL CQRRAQDPFG DLIKKLMNQI 

       250        260        270        280        290        300 
HQQLEMPDLK QQFGTQMYEQ QVVQLCKDAA EAGLQEQRVY ALHLRRYNDA LFIHDTVRAR 

       310        320        330        340        350        360 
DALDMLQDFY DRERTTKTQM VRAESWLLKL FDDHKNVLGQ LAARGPENPK LEMLERILLK 

       370        380        390        400        410        420 
QFGSPGHTRG IIFTRTRQTA SSLLLWLRQQ PCLQTVGIKP QMLIGAGNTS QSTHMTQKDQ 

       430        440        450        460        470        480 
QEVIQEFRDG ILSLLVATSV AEEGLDIAQC NVVVRYGLLT NEISMVQARG RARAGQSVYS 

       490        500        510        520        530        540 
FLATEGSREM KRELTNEALE VLMEKAVAAV QKMDPDEFKA KIRDLQQASL VKRAARAAHR 

       550        560        570        580        590        600 
EIQQGQFLPE HVQLLCINCM VAVGYGSDLR KVEGTHHVNV NPNFSVYYTT SQNPVVINKV 

       610        620        630        640        650        660 
FKDWRPGGTI RCSNCGEVWG FQMIYKSVTL PVLKIGSILL ETPRGKIQAK KWSRVPFSIP 

       670 
VFDILQDCTQ SLSELSLD 

« Hide

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses."
Satoh T., Kato H., Kumagai Y., Yoneyama M., Sato S., Matsushita K., Tsujimura T., Fujita T., Akira S., Takeuchi O.
Proc. Natl. Acad. Sci. U.S.A. 107:1512-1517(2010) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF316999 mRNA. Translation: AAK15474.1.
AF317000 Genomic DNA. Translation: AAK15475.1.
AL591469 Genomic DNA. Translation: CAM22908.1.
BC029209 mRNA. Translation: AAH29209.1.
CCDSCCDS25431.1.
RefSeqNP_084426.2. NM_030150.2.
UniGeneMm.271830.

3D structure databases

ProteinModelPortalQ99J87.
SMRQ99J87. Positions 1-678.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid219822. 1 interaction.

PTM databases

PhosphoSiteQ99J87.

Proteomic databases

MaxQBQ99J87.
PaxDbQ99J87.
PRIDEQ99J87.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000017974; ENSMUSP00000017974; ENSMUSG00000017830.
GeneID80861.
KEGGmmu:80861.
UCSCuc007llx.1. mouse.

Organism-specific databases

CTD79132.
MGIMGI:1931560. Dhx58.

Phylogenomic databases

eggNOGCOG1111.
GeneTreeENSGT00510000046789.
HOGENOMHOG000230992.
HOVERGENHBG106019.
InParanoidA2A5E9.
KOK12649.
OMAENPKLEM.
OrthoDBEOG7RV9FC.
TreeFamTF330258.

Gene expression databases

BgeeQ99J87.
CleanExMM_DHX58.
GenevestigatorQ99J87.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
InterProIPR006935. Helicase/UvrB_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view]
PfamPF00271. Helicase_C. 1 hit.
PF04851. ResIII. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view]
SMARTSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 2 hits.
PROSITEPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio350167.
PROQ99J87.
SOURCESearch...

Entry information

Entry nameDHX58_MOUSE
AccessionPrimary (citable) accession number: Q99J87
Secondary accession number(s): A2A5E9, Q9D1X4
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot