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O95786 (DDX58_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Probable ATP-dependent RNA helicase DDX58

EC=3.6.4.13
Alternative name(s):
DEAD box protein 58
RIG-I-like receptor 1
Short name=RLR-1
Retinoic acid-inducible gene 1 protein
Short name=RIG-1
Retinoic acid-inducible gene I protein
Short name=RIG-I
Gene names
Name:DDX58
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length925 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.17 Ref.18 Ref.21 Ref.22 Ref.24 Ref.25 Ref.28 Ref.38

Catalytic activity

ATP + H2O = ADP + phosphate.

Cofactor

Zinc.

Subunit structure

Monomer; maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift, homomultimerizes and interacts with MAVS/IPS1. Interacts with DHX58/LGP2, IKBKE, TBK1 and TMEM173/STING. Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts with RNF135. Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to DDX58. Interacts with SRC. Interacts with protein Z of Guanarito virus, Machupo virus, Junin arenavirus and Sabia virus. This interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 and NF-kappa-B activation and resulting in decreased IFN-beta induction. Interacts (via CARD domain) with Human respiratory syncytial virus A non-structural protein 2 (NS2) and this interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 activation. Interacts with Rotavirus A non-structural protein 1 (NSP1) and this interaction induces down-regulation of DDX58/RIG-I. Interacts with DDX60. Interacts with isoform 2 of ZC3HAV1 (via zinc-fingers) in an RNA-dependent manner. Ref.10 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.23 Ref.26 Ref.27 Ref.29 Ref.31 Ref.34 Ref.39 Ref.42 Ref.43 Ref.44

Subcellular location

Cytoplasm. Cell projectionruffle membrane. Cytoplasmcytoskeleton. Cell junctiontight junction. Note: Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles. Ref.7 Ref.8 Ref.9 Ref.16 Ref.24 Ref.43

Tissue specificity

Present in vascular smooth cells (at protein level). Ref.8

Induction

By bacterial lipopolysaccharides (LPS) in endothelial cells. By interferon (IFN). Ref.2 Ref.7 Ref.8 Ref.9 Ref.12

Domain

The repressor domain controls homomultimerization and interaction with MAVS/IPS1. In the absence of viral infection, the protein is maintained as a monomer in an autoinhibited state with the CARD domains masked through intramolecular interactions mediated by the repressor domain. Upon binding to viral RNA in the presence of ATP, the repressor domain induces a conformational change exposing the CARD domain and promotes dimerization and CARD interactions with the adapter protein MAVS/IPS1 leading to the induction of downstream signaling. Ref.17

The helicase domain is responsible for dsRNA recognition. Ref.17

The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association with the actin cytoskeleton. Ref.17

The second CARD domain is the primary site for 'Lys-63'-linked ubiquitination. Ref.17

Post-translational modification

Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-770, Ser-854 and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation. Ref.41

ISGylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation. ISGylation negatively regulates its function in antiviral signaling response. Ref.15 Ref.19

Sumoylated, probably by MUL1; inhibiting its polyubiquitination. Ref.46

Ubiquitinated. Undergoes 'Lys-48'- and 'Lys-63'-linked ubiquitination. Lys-172 is the critical site for TRIM25-mediated ubiquitination, for MAVS/IPS1 binding and to induce anti-viral signal transduction. Lys-154, Lys-164 and Lys-172 are critical sites for RNF135-mediated ubiquitination. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'-and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor. Ref.16 Ref.18 Ref.23 Ref.29 Ref.32

Sequence similarities

Belongs to the helicase family. RLR subfamily.

Contains 2 CARD domains.

Contains 1 helicase ATP-binding domain.

Contains 1 helicase C-terminal domain.

Ontologies

Keywords
   Biological processAntiviral defense
Host-virus interaction
Immunity
Innate immunity
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Tight junction
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandATP-binding
Metal-binding
Nucleotide-binding
RNA-binding
Zinc
   Molecular functionHelicase
Hydrolase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRIG-I signaling pathway

Inferred from mutant phenotype Ref.25. Source: UniProtKB

cytoplasmic pattern recognition receptor signaling pathway in response to virus

Traceable author statement Ref.36. Source: UniProtKB

detection of virus

Inferred from direct assay PubMed 17079289. Source: BHF-UCL

innate immune response

Inferred from mutant phenotype Ref.28Ref.21. Source: UniProtKB

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

positive regulation of defense response to virus by host

Inferred from mutant phenotype Ref.28. Source: UniProtKB

positive regulation of interferon-alpha production

Inferred from direct assay Ref.22. Source: UniProtKB

positive regulation of interferon-beta production

Inferred from mutant phenotype Ref.25Ref.28Ref.21. Source: UniProtKB

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred by curator PubMed 17079289. Source: BHF-UCL

positive regulation of transcription factor import into nucleus

Inferred from direct assay PubMed 17079289. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17079289. Source: BHF-UCL

regulation of cell migration

Inferred from direct assay Ref.24. Source: UniProtKB

regulation of type III interferon production

Traceable author statement Ref.36. Source: UniProtKB

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

response to virus

Traceable author statement Ref.36. Source: UniProtKB

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentactin cytoskeleton

Inferred from direct assay Ref.24. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.43. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

ruffle membrane

Inferred from direct assay Ref.24. Source: UniProtKB

tight junction

Inferred from direct assay Ref.24. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP-dependent helicase activity

Inferred from electronic annotation. Source: InterPro

double-stranded DNA binding

Inferred from electronic annotation. Source: Ensembl

double-stranded RNA binding

Inferred from direct assay Ref.22. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.43. Source: IntAct

protein binding

Inferred from physical interaction Ref.11Ref.17Ref.18Ref.20Ref.23Ref.26Ref.31Ref.42Ref.39Ref.44. Source: UniProtKB

single-stranded RNA binding

Inferred from mutant phenotype Ref.25. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.47. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-995350,EBI-995350
1BP045432EBI-995350,EBI-3648048From a different organism.
Casp12Q920D54EBI-995350,EBI-1374296From a different organism.
CYLDQ9NQC72EBI-995350,EBI-2117940
DDX3XO005712EBI-995350,EBI-353779
MAVSQ7Z43412EBI-995350,EBI-995373
NSSP216993EBI-995350,EBI-6693910From a different organism.
STAT1P422244EBI-995350,EBI-1057697
US11P044874EBI-995350,EBI-6150681From a different organism.
WRNIP1Q96S552EBI-995350,EBI-2513471
ZQ6IUF93EBI-995350,EBI-3647473From a different organism.
ZQ6IVU53EBI-995350,EBI-3647294From a different organism.
ZQ6UY622EBI-995350,EBI-3647496From a different organism.
ZQ6UY713EBI-995350,EBI-3647448From a different organism.
ZC3HAV1Q7Z2W43EBI-995350,EBI-922540
ZC3HAV1Q7Z2W4-24EBI-995350,EBI-922559

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95786-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O95786-2)

The sequence of this isoform differs from the canonical sequence as follows:
     36-80: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 925925Probable ATP-dependent RNA helicase DDX58
PRO_0000144093

Regions

Domain1 – 8787CARD 1
Domain92 – 17281CARD 2
Domain251 – 430180Helicase ATP-binding
Domain610 – 776167Helicase C-terminal
Nucleotide binding264 – 2718ATP Probable
Region218 – 925708Interaction with ZC3HAV1
Region735 – 925191Repressor domain
Motif372 – 3754DECH box

Sites

Metal binding8101Zinc
Metal binding8131Zinc
Metal binding8641Zinc
Metal binding8691Zinc

Amino acid modifications

Modified residue7701Phosphothreonine; by CK2 Ref.41
Modified residue8541Phosphoserine; by CK2 Ref.41
Modified residue8551Phosphoserine; by CK2 Ref.41
Modified residue8581N6-acetyllysine Ref.30
Cross-link154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
Cross-link164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
Cross-link172Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Natural variations

Alternative sequence36 – 8045Missing in isoform 2.
VSP_016054
Natural variant71R → C. Ref.6
Corresponds to variant rs10813831 [ dbSNP | Ensembl ].
VAR_023747
Natural variant5801D → E. Ref.1 Ref.2
Corresponds to variant rs17217280 [ dbSNP | Ensembl ].
VAR_023748

Experimental info

Mutagenesis551T → I: No IRF3 signaling activity; no effect on dsRNA binding. Ref.12
Mutagenesis991K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16
Mutagenesis1541K → R: Reduction of ubiquitination. Reduction of INFB induction. Ref.29
Mutagenesis1641K → R: Reduction of ubiquitination. Reduction of INFB induction. Ref.29
Mutagenesis1691K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16
Mutagenesis1721K → R: Complete loss of ubiquitination; No interaction with MAVS/IPS1; No induction of IFN-beta. Ref.16 Ref.29
Mutagenesis1811K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16
Mutagenesis1901K → R: Little or no effect on ubiquitination of the 2 CARD domains.
Mutagenesis1931K → R: Little or no effect on ubiquitination of the 2 CARD domains. Ref.16
Mutagenesis2701K → A: No IRF3 signaling activity. Ref.9 Ref.12

Secondary structure

.......................................................................................................................................... 925
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 8, 2005. Version 2.
Checksum: BF0D501C395BAE25

FASTA925106,600
        10         20         30         40         50         60 
MTTEQRRSLQ AFQDYIRKTL DPTYILSYMA PWFREEEVQY IQAEKNNKGP MEAATLFLKF 

        70         80         90        100        110        120 
LLELQEEGWF RGFLDALDHA GYSGLYEAIE SWDFKKIEKL EEYRLLLKRL QPEFKTRIIP 

       130        140        150        160        170        180 
TDIISDLSEC LINQECEEIL QICSTKGMMA GAEKLVECLL RSDKENWPKT LKLALEKERN 

       190        200        210        220        230        240 
KFSELWIVEK GIKDVETEDL EDKMETSDIQ IFYQEDPECQ NLSENSCPPS EVSDTNLYSP 

       250        260        270        280        290        300 
FKPRNYQLEL ALPAMKGKNT IICAPTGCGK TFVSLLICEH HLKKFPQGQK GKVVFFANQI 

       310        320        330        340        350        360 
PVYEQQKSVF SKYFERHGYR VTGISGATAE NVPVEQIVEN NDIIILTPQI LVNNLKKGTI 

       370        380        390        400        410        420 
PSLSIFTLMI FDECHNTSKQ HPYNMIMFNY LDQKLGGSSG PLPQVIGLTA SVGVGDAKNT 

       430        440        450        460        470        480 
DEALDYICKL CASLDASVIA TVKHNLEELE QVVYKPQKFF RKVESRISDK FKYIIAQLMR 

       490        500        510        520        530        540 
DTESLAKRIC KDLENLSQIQ NREFGTQKYE QWIVTVQKAC MVFQMPDKDE ESRICKALFL 

       550        560        570        580        590        600 
YTSHLRKYND ALIISEHARM KDALDYLKDF FSNVRAAGFD EIEQDLTQRF EEKLQELESV 

       610        620        630        640        650        660 
SRDPSNENPK LEDLCFILQE EYHLNPETIT ILFVKTRALV DALKNWIEGN PKLSFLKPGI 

       670        680        690        700        710        720 
LTGRGKTNQN TGMTLPAQKC ILDAFKASGD HNILIATSVA DEGIDIAQCN LVILYEYVGN 

       730        740        750        760        770        780 
VIKMIQTRGR GRARGSKCFL LTSNAGVIEK EQINMYKEKM MNDSILRLQT WDEAVFREKI 

       790        800        810        820        830        840 
LHIQTHEKFI RDSQEKPKPV PDKENKKLLC RKCKALACYT ADVRVIEECH YTVLGDAFKE 

       850        860        870        880        890        900 
CFVSRPHPKP KQFSSFEKRA KIFCARQNCS HDWGIHVKYK TFEIPVIKIE SFVVEDIATG 

       910        920 
VQTLYSKWKD FHFEKIPFDP AEMSK 

« Hide

Isoform 2 [UniParc].

Checksum: 4B1603B6F2F37A66
Show »

FASTA880101,377

References

« Hide 'large scale' references
[1]"RIG-I, a human homolog gene of RNA helicase, is induced by retinoic acid during the differentiation of acute promyelocytic leukemia cell."
Sun Y.-W.
Thesis (1997), Shanghai Institute of Hematology, China
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-580.
[2]"Retinoic acid-inducible gene-I is induced in endothelial cells by LPS and regulates expression of COX-2."
Imaizumi T., Aratani S., Nakajima T., Carlson M., Matsumiya T., Tanji K., Ookawa K., Yoshida H., Tsuchida S., McIntyre T.M., Prescott S.M., Zimmerman G.A., Satoh K.
Biochem. Biophys. Res. Commun. 292:274-279(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-580, INDUCTION.
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 1).
Tissue: Brain.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-748 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 528-925 (ISOFORMS 1/2), VARIANT CYS-7.
Tissue: Skin and Testis.
[7]"Retinoic acid-inducible gene-I is induced by interferon-gamma and regulates the expression of interferon-gamma stimulated gene 15 in MCF-7 cells."
Cui X.-F., Imaizumi T., Yoshida H., Borden E.C., Satoh K.
Biochem. Cell Biol. 82:401-405(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, SUBCELLULAR LOCATION.
[8]"Expression of retinoic acid-inducible gene-I in vascular smooth muscle cells stimulated with interferon-gamma."
Imaizumi T., Yagihashi N., Hatakeyama M., Yamashita K., Ishikawa A., Taima K., Yoshida H., Inoue I., Fujita T., Yagihashi S., Satoh K.
Life Sci. 75:1171-1180(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]"The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses."
Yoneyama M., Kikuchi M., Natsukawa T., Shinobu N., Imaizumi T., Miyagishi M., Taira K., Akira S., Fujita T.
Nat. Immunol. 5:730-737(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, MUTAGENESIS OF LYS-270, SUBCELLULAR LOCATION, BINDING TO DOUBLE-STRANDED RNA, FUNCTION.
[10]"Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3."
Seth R.B., Sun L., Ea C.-K., Chen Z.J.
Cell 122:669-682(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1.
[11]"SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways."
Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B.
EMBO J. 24:4018-4028(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IKBKE AND TBK1.
[12]"Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I."
Sumpter R. Jr., Loo Y.-M., Foy E., Li K., Yoneyama M., Fujita T., Lemon S.M., Gale M. Jr.
J. Virol. 79:2689-2699(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, MUTAGENESIS OF THR-55 AND LYS-270, BINDING TO DOUBLE-STRANDED RNA, FUNCTION.
[13]"VISA is an adapter protein required for virus-triggered IFN-beta Signaling."
Xu L.-G., Wang Y.-Y., Han K.-J., Li L.-Y., Zhai Z., Shu H.-B.
Mol. Cell 19:727-740(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1.
[14]"IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction."
Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., Takeuchi O., Akira S.
Nat. Immunol. 6:981-988(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAVS/IPS1.
[15]"Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways."
Zhao C., Denison C., Huibregtse J.M., Gygi S.P., Krug R.M.
Proc. Natl. Acad. Sci. U.S.A. 102:10200-10205(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, ISGYLATION.
[16]"TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity."
Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., Takeuchi O., Akira S., Chen Z., Inoue S., Jung J.U.
Nature 446:916-920(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM25, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF LYS-99; LYS-169; LYS-172; LYS-181 AND LYS-193.
[17]"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, SUBUNIT, REPRESSOR DOMAIN, INTERACTION WITH DHX58.
[18]"The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response."
Friedman C.S., O'Donnell M.A., Legarda-Addison D., Ng A., Cardenas W.B., Yount J.S., Moran T.M., Basler C.F., Komuro A., Horvath C.M., Xavier R., Ting A.T.
EMBO Rep. 9:930-936(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION, INTERACTION WITH CYLD.
[19]"Negative feedback regulation of RIG-I-mediated antiviral signaling by interferon-induced ISG15 conjugation."
Kim M.J., Hwang S.Y., Imaizumi T., Yoo J.Y.
J. Virol. 82:1474-1483(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION.
[20]"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling."
Ishikawa H., Barber G.N.
Nature 455:674-678(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TMEM173.
[21]"RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway."
Chiu Y.-H., Macmillan J.B., Chen Z.J.
Cell 138:576-591(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[22]"Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus."
Schlee M., Roth A., Hornung V., Hagmann C.A., Wimmenauer V., Barchet W., Coch C., Janke M., Mihailovic A., Wardle G., Juranek S., Kato H., Kawai T., Poeck H., Fitzgerald K.A., Takeuchi O., Akira S., Tuschl T. expand/collapse author list , Latz E., Ludwig J., Hartmann G.
Immunity 31:25-34(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection."
Oshiumi H., Matsumoto M., Hatakeyama S., Seya T.
J. Biol. Chem. 284:807-817(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH RNF135.
[24]"Retinoic acid-induced gene-1 (RIG-I) associates with the actin cytoskeleton via caspase activation and recruitment domain-dependent interactions."
Mukherjee A., Morosky S.A., Shen L., Weber C.R., Turner J.R., Kim K.S., Wang T., Coyne C.B.
J. Biol. Chem. 284:6486-6494(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[25]"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.
[26]"The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-elicited antiviral signaling."
Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., Anthonsen M.W.
J. Biol. Chem. 284:19122-19131(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SRC.
[27]"Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I."
Ling Z., Tran K.C., Teng M.N.
J. Virol. 83:3734-3742(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HRSV PROTEIN NS2.
[28]"RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate."
Ablasser A., Bauernfeind F., Hartmann G., Latz E., Fitzgerald K.A., Hornung V.
Nat. Immunol. 10:1065-1072(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[29]"REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I."
Gao D., Yang Y.K., Wang R.P., Zhou X., Diao F.C., Li M.D., Zhai Z.H., Jiang Z.F., Chen D.Y.
PLoS ONE 4:E5760-E5760(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-154; LYS-164 AND LYS-172, INTERACTION WITH RNF135, MUTAGENESIS OF LYS-154; LYS-164 AND LYS-172.
[30]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-858, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]"NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways."
Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P., Zheng S., Chen Z.J., Wang R.F.
Cell 141:483-496(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NLRC5.
[32]"The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling."
Chen R., Zhang L., Zhong B., Tan B., Liu Y., Shu H.B.
Cell Res. 20:802-811(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP17L2.
[33]"Function and regulation of retinoic acid-inducible gene-I."
Matsumiya T., Stafforini D.M.
Crit. Rev. Immunol. 30:489-513(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[34]"Z proteins of New World arenaviruses bind RIG-I and interfere with type I interferon induction."
Fan L., Briese T., Lipkin W.I.
J. Virol. 84:1785-1791(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEW WORLD ARENAVIRUSES PROTEIN Z.
[35]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]"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.
[37]"RIG-I-like receptors: cytoplasmic sensors for non-self RNA."
Kato H., Takahasi K., Fujita T.
Immunol. Rev. 243:91-98(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[38]"Innate immune responses in human monocyte-derived dendritic cells are highly dependent on the size and the 5' phosphorylation of RNA molecules."
Jiang M., Osterlund P., Sarin L.P., Poranen M.M., Bamford D.H., Guo D., Julkunen I.
J. Immunol. 187:1713-1721(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[39]"IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1."
Liu X.Y., Chen W., Wei B., Shan Y.F., Wang C.
J. Immunol. 187:2559-2568(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IFIT3.
[40]"Retinoic acid-inducible gene-I-like receptors."
Onoguchi K., Yoneyama M., Fujita T.
J. Interferon Cytokine Res. 31:27-31(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[41]"Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response."
Sun Z., Ren H., Liu Y., Teeling J.L., Gu J.
J. Virol. 85:1036-1047(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-770; SER-854 AND SER-855.
[42]"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.
[43]"ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses."
Hayakawa S., Shiratori S., Yamato H., Kameyama T., Kitatsuji C., Kashigi F., Goto S., Kameoka S., Fujikura D., Yamada T., Mizutani T., Kazumata M., Sato M., Tanaka J., Asaka M., Ohba Y., Miyazaki T., Imamura M., Takaoka A.
Nat. Immunol. 12:37-44(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZC3HAV1, SUBCELLULAR LOCATION.
[44]"Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I."
Qin L., Ren L., Zhou Z., Lei X., Chen L., Xue Q., Liu X., Wang J., Hung T.
Virol. J. 8:526-526(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ROTAVIRUS PROTEIN NSP1.
[45]"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.
[46]"Mitochondrially localised MUL1 is a novel modulator of antiviral signaling."
Jenkins K., Khoo J.J., Sadler A., Piganis R., Wang D., Borg N.A., Hjerrild K., Gould J., Thomas B.J., Nagley P., Hertzog P.J., Mansell A.
Immunol. Cell Biol. 91:321-330(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION BY MUL1.
[47]"The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I."
Cui S., Eisenaecher K., Kirchhofer A., Brzozka K., Lammens A., Lammens K., Fujita T., Conzelmann K.-K., Krug A., Hopfner K.-P.
Mol. Cell 29:169-179(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 802-925 IN COMPLEX WITH ZINC IONS.
[48]"Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses."
Takahasi K., Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita R., Gale M. Jr., Inagaki F., Fujita T.
Mol. Cell 29:428-440(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 792-925.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF038963 mRNA. Translation: AAD19826.1.
AL353671, AL161783 Genomic DNA. Translation: CAH71251.1.
AL161783, AL353671 Genomic DNA. Translation: CAH72600.1.
CH471071 Genomic DNA. Translation: EAW58548.1.
BC132786 mRNA. Translation: AAI32787.1.
BC136610 mRNA. Translation: AAI36611.1.
BX647917 mRNA. Translation: CAI46068.1.
AL137608 mRNA. Translation: CAB70840.1.
CCDSCCDS6526.1. [O95786-1]
PIRT46312.
RefSeqNP_055129.2. NM_014314.3. [O95786-1]
UniGeneHs.190622.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LWDNMR-A95-190[»]
2LWENMR-A95-190[»]
2QFBX-ray3.00A/B/C/D/E/F/G/H/I/J802-925[»]
2QFDX-ray2.70A/B/C/D/E/F/G/H/I/J802-925[»]
2RMJNMR-A792-925[»]
2YKGX-ray2.50A230-925[»]
3LRNX-ray2.60A/B803-923[»]
3LRRX-ray2.15A/B803-923[»]
3NCUX-ray2.55A/B792-925[»]
3OG8X-ray2.40A/B802-925[»]
3TMIX-ray2.90A232-925[»]
3ZD6X-ray2.80A230-925[»]
3ZD7X-ray2.50A230-925[»]
4AY2X-ray2.80A239-925[»]
4BPBX-ray2.58A230-925[»]
4NQKX-ray3.70A/B/C/D1-200[»]
ProteinModelPortalO95786.
SMRO95786. Positions 1-188, 240-925.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117121. 35 interactions.
DIPDIP-35444N.
IntActO95786. 19 interactions.
MINTMINT-2799116.
STRING9606.ENSP00000369213.

PTM databases

PhosphoSiteO95786.

Proteomic databases

MaxQBO95786.
PaxDbO95786.
PRIDEO95786.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379882; ENSP00000369212; ENSG00000107201. [O95786-2]
ENST00000379883; ENSP00000369213; ENSG00000107201. [O95786-1]
GeneID23586.
KEGGhsa:23586.
UCSCuc003zra.3. human. [O95786-1]
uc010mjk.1. human. [O95786-2]

Organism-specific databases

CTD23586.
GeneCardsGC09M032447.
HGNCHGNC:19102. DDX58.
HPACAB012643.
HPA047193.
MIM609631. gene.
neXtProtNX_O95786.
PharmGKBPA134994272.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1111.
HOGENOMHOG000230911.
HOVERGENHBG052325.
InParanoidO95786.
KOK12646.
OMAKCKAFAC.
PhylomeDBO95786.
TreeFamTF330258.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressO95786.
BgeeO95786.
CleanExHS_DDX58.
GenevestigatorO95786.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
3.40.50.300. 2 hits.
InterProIPR003593. AAA+_ATPase.
IPR011029. DEATH-like_dom.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view]
PfamPF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 3 hits.
PROSITEPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDDX58. human.
EvolutionaryTraceO95786.
GeneWikiRIG-I.
GenomeRNAi23586.
NextBio46208.
PROO95786.
SOURCESearch...

Entry information

Entry nameDDX58_HUMAN
AccessionPrimary (citable) accession number: O95786
Secondary accession number(s): A2RU81 expand/collapse secondary AC list , Q5HYE1, Q5VYT1, Q9NT04
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: November 8, 2005
Last modified: July 9, 2014
This is version 123 of the entry and version 2 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 9

Human chromosome 9: entries, gene names and cross-references to MIM