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Q96C10 (DHX58_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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 homolog
RIG-I-like receptor 3
Short name=RLR-3
RIG-I-like receptor LGP2
Short name=RLR
Gene names
Name:DHX58
Synonyms:D11LGP2E, LGP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.11 Ref.12 Ref.16 Ref.17 Ref.18

Catalytic activity

ATP + H2O = ADP + phosphate.

Cofactor

Zinc.

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. Interacts (via helicase C-terminal domain) with non-structural protein V of Human parainfluenza 2 virus, Human parainfluenza 5 virus, measles virus, mumps virus, hendra virus and nipah virus. Ref.4 Ref.5 Ref.7 Ref.9 Ref.13 Ref.16 Ref.18

Subcellular location

Cytoplasm Ref.17.

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.

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
Host-virus interaction
Immunity
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DomainCoiled coil
   LigandATP-binding
Metal-binding
Nucleotide-binding
RNA-binding
Zinc
   Molecular functionHelicase
Hydrolase
   Technical term3D-structure
Complete 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 mutant phenotype Ref.11. Source: UniProtKB

negative regulation of RIG-I signaling pathway

Inferred from direct assay Ref.7. Source: UniProtKB

negative regulation of innate immune response

Inferred from direct assay Ref.12. Source: UniProtKB

negative regulation of type I interferon production

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of MDA-5 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of RIG-I signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of type I interferon production

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of innate immune response

Inferred from direct assay Ref.7. Source: UniProtKB

response to virus

Inferred from sequence or structural similarity. Source: UniProtKB

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: InterPro

double-stranded RNA binding

Inferred from direct assay Ref.7. Source: UniProtKB

helicase activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.5Ref.13. Source: UniProtKB

single-stranded RNA binding

Inferred from direct assay Ref.7. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.16. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 678678Probable ATP-dependent RNA helicase DHX58
PRO_0000102010

Regions

Domain11 – 188178Helicase ATP-binding
Domain350 – 514165Helicase C-terminal
Nucleotide binding24 – 318ATP Potential
Region476 – 678203Repressor domain
Region572 – 65584RNA-binding
Coiled coil489 – 54658 Potential
Motif131 – 1344DECH box

Sites

Metal binding5561Zinc
Metal binding5591Zinc
Metal binding6121Zinc
Metal binding6151Zinc

Natural variations

Natural variant761T → A.
Corresponds to variant rs34891485 [ dbSNP | Ensembl ].
VAR_049336
Natural variant951R → Q.
Corresponds to variant rs35118457 [ dbSNP | Ensembl ].
VAR_049337
Natural variant4251Q → R.
Corresponds to variant rs2074158 [ dbSNP | Ensembl ].
VAR_019394
Natural variant5231R → Q.
Corresponds to variant rs2074160 [ dbSNP | Ensembl ].
VAR_019395

Experimental info

Mutagenesis6341K → E: Abolishes RNA binding. Ref.16 Ref.18
Mutagenesis6511K → E: Abolishes RNA binding. Ref.16
Sequence conflict4731R → W in BAB13818. Ref.1

Secondary structure

.................................... 678
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96C10 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 859E1749C7313D06

FASTA67876,613
        10         20         30         40         50         60 
MELRSYQWEV IMPALEGKNI IIWLPTGAGK TRAAAYVAKR HLETVDGAKV VVLVNRVHLV 

        70         80         90        100        110        120 
TQHGEEFRRM LDGRWTVTTL SGDMGPRAGF GHLARCHDLL ICTAELLQMA LTSPEEEEHV 

       130        140        150        160        170        180 
ELTVFSLIVV DECHHTHKDT VYNVIMSQYL ELKLQRAQPL PQVLGLTASP GTGGASKLDG 

       190        200        210        220        230        240 
AINHVLQLCA NLDTWCIMSP QNCCPQLQEH SQQPCKQYNL CHRRSQDPFG DLLKKLMDQI 

       250        260        270        280        290        300 
HDHLEMPELS RKFGTQMYEQ QVVKLSEAAA LAGLQEQRVY ALHLRRYNDA LLIHDTVRAV 

       310        320        330        340        350        360 
DALAALQDFY HREHVTKTQI LCAERRLLAL FDDRKNELAH LATHGPENPK LEMLEKILQR 

       370        380        390        400        410        420 
QFSSSNSPRG IIFTRTRQSA HSLLLWLQQQ QGLQTVDIRA QLLIGAGNSS QSTHMTQRDQ 

       430        440        450        460        470        480 
QEVIQKFQDG TLNLLVATSV AEEGLDIPHC NVVVRYGLLT NEISMVQARG RARADQSVYA 

       490        500        510        520        530        540 
FVATEGSREL KRELINEALE TLMEQAVAAV QKMDQAEYQA KIRDLQQAAL TKRAAQAAQR 

       550        560        570        580        590        600 
ENQRQQFPVE HVQLLCINCM VAVGHGSDLR KVEGTHHVNV NPNFSNYYNV SRDPVVINKV 

       610        620        630        640        650        660 
FKDWKPGGVI SCRNCGEVWG LQMIYKSVKL PVLKVRSMLL ETPQGRIQAK KWSRVPFSVP 

       670 
DFDFLQHCAE NLSDLSLD 

« Hide

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Embryo.
[2]"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].
Tissue: Colon.
[3]"Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity."
Yoneyama M., Kikuchi M., Matsumoto K., Imaizumi T., Miyagishi M., Taira K., Foy E., Loo Y.-M., Gale M. Jr., Akira S., Yonehara S., Kato A., Fujita T.
J. Immunol. 175:2851-2858(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2."
Komuro A., Horvath C.M.
J. Virol. 80:12332-12342(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1 AND DDX58/RIG-I.
[5]"Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2."
Saito T., Hirai R., Loo Y.-M., Owen D., Johnson C.L., Sinha S.C., Akira S., Fujita T., Gale M. Jr.
Proc. Natl. Acad. Sci. U.S.A. 104:582-587(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DDX58/RIG-I.
[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]"Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response."
Murali A., Li X., Ranjith-Kumar C.T., Bhardwaj K., Holzenburg A., Li P., Kao C.C.
J. Biol. Chem. 283:15825-15833(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT.
[8]"Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2."
Bamming D., Horvath C.M.
J. Biol. Chem. 284:9700-9712(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2."
Parisien J.P., Bamming D., Komuro A., Ramachandran A., Rodriguez J.J., Barber G., Wojahn R.D., Horvath C.M.
J. Virol. 83:7252-7260(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARAMYXOVIRUSES NON-STRUCTURAL PROTEIN V.
[10]"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.
[11]"RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium."
Broquet A.H., Hirata Y., McAllister C.S., Kagnoff M.F.
J. Immunol. 186:1618-1626(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"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.
[13]"DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling."
Miyashita M., Oshiumi H., Matsumoto M., Seya T.
Mol. Cell. Biol. 31:3802-3819(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX60.
[14]"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.
[15]"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.
[16]"The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA."
Li X., Ranjith-Kumar C.T., Brooks M.T., Dharmaiah S., Herr A.B., Kao C., Li P.
J. Biol. Chem. 284:13881-13891(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 541-678 IN COMPLEX WITH RNA, FUNCTION, SUBUNIT, MUTAGENESIS OF LYS-634 AND LYS-651, ZINC-BINDING SITES.
[17]"Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors."
Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R., Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F.
J. Biol. Chem. 284:17465-17474(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 546-678, FUNCTION, SUBCELLULAR LOCATION.
[18]"The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA."
Pippig D.A., Hellmuth J.C., Cui S., Kirchhofer A., Lammens K., Lammens A., Schmidt A., Rothenfusser S., Hopfner K.-P.
Nucleic Acids Res. 37:2014-2025(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 537-678, FUNCTION, SUBUNIT, MUTAGENESIS OF LYS-634, ZINC-BINDING SITES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK021416 mRNA. Translation: BAB13818.1.
BC014949 mRNA. Translation: AAH14949.1.
CCDSCCDS11416.1.
RefSeqNP_077024.2. NM_024119.2.
UniGeneHs.55918.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2RQANMR-A546-678[»]
2W4RX-ray2.60A/B/C/D537-678[»]
3EQTX-ray2.00A/B541-678[»]
ProteinModelPortalQ96C10.
SMRQ96C10. Positions 1-678.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122553. 14 interactions.
DIPDIP-60792N.
IntActQ96C10. 18 interactions.
MINTMINT-1460040.
STRING9606.ENSP00000251642.

PTM databases

PhosphoSiteQ96C10.

Polymorphism databases

DMDM50401123.

Proteomic databases

MaxQBQ96C10.
PaxDbQ96C10.
PRIDEQ96C10.

Protocols and materials databases

DNASU79132.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000251642; ENSP00000251642; ENSG00000108771.
ENST00000563880; ENSP00000455290; ENSG00000260178.
GeneID79132.
KEGGhsa:79132.
UCSCuc002hyw.3. human.

Organism-specific databases

CTD79132.
GeneCardsGC17M040255.
HGNCHGNC:29517. DHX58.
HPAHPA018670.
HPA019570.
MIM608588. gene.
neXtProtNX_Q96C10.
PharmGKBPA162383566.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1111.
HOGENOMHOG000230992.
HOVERGENHBG106019.
InParanoidQ96C10.
KOK12649.
OMAENPKLEM.
PhylomeDBQ96C10.
TreeFamTF330258.

Gene expression databases

ArrayExpressQ96C10.
BgeeQ96C10.
CleanExHS_DHX58.
GenevestigatorQ96C10.

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

ChiTaRSDHX58. human.
EvolutionaryTraceQ96C10.
GeneWikiLGP2.
GenomeRNAi79132.
NextBio67993.
PROQ96C10.
SOURCESearch...

Entry information

Entry nameDHX58_HUMAN
AccessionPrimary (citable) accession number: Q96C10
Secondary accession number(s): Q9HAM6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM