Mus musculus Gene: Ddx58
Summary
InnateDB Gene IDBG-135957.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Ddx58
Gene Name DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Synonyms
Species Mus musculus
Ensembl Gene ENSMUSG00000040296
Encoded Proteins
DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Ddx58 (Rig-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response.
Ddx58 and Nod2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. Ddx58 negatively regulates ligand-induced NFkB signalling mediated by Nod2, and conversely, Nod2 negatively regulates type I interferon induction by Ddx58. (Demonstrated in human)
Ddx58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of Ddx58. (Demonstrated in human)
Ddx58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling.
Antiviral stress granules containing Ddx58 (RIG-I) and Eif2ak2 (PKR) have a critical role in viral detection and innate immunity.
DDX58 (RIG-I) detects cytosolic Listeria monocytogenes infections by sensing secreted bacterial nucleic acids.
Ddx58 (RIG-I) is a positive regulator of NF-kB signalling via binding to Nfkb1 mRNA.
Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.
Ddx58 preferentially binds to coding RNA from S. Typhimurium during infection leading to the expression of IFN beta andthis immunostimulatory activity depends on 5? triphosphorylation of RNA.
Ddx58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but Ifih1 is a significant contributor to the cellular defense against IAV.
Ddx58 acts in parallel with Zbp1 in an RNA polymerase III-dependent manner to initiate glial responses to herpes simplex virus-1.
Mir485 exhibits bispecificity, targeting Ddx58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
InnateDB Annotation from Orthologs
Summary
[Homo sapiens] DDX58 (RIG-I) is a cytoplasmic RNA helicase that functions as an intracellular sensor of dsRNA leading to the induction of Interferon (IFN) production independently of TLR signalling.
[Homo sapiens] DDX58 (RIG-I) first and second caspase recruitment domains (CARDs) have distinct roles in TRIM25-mediated RIG-I ubiquitination, which leads to initiation of an antiviral signalling cascade.
[Homo sapiens] DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses.
[Homo sapiens] DDX58 plays an essential role in Toll-like receptor (TLR)-stimulated phagocytosis, demonstrating that DDX58 plays a role not only in antiviral responses but in antibacterial responses as well.
[Homo sapiens] DDX58 plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha.
[Homo sapiens] DDX58 is a sensor able to activate the inflammasome in response to certain RNA viruses by binding to the adaptor PYCARD to trigger the caspase-1 (CASP1)-dependent inflammasome activation and IL-1-beta production.
[Homo sapiens] DDX58 binds specifically to K63-polyubiquitin chains through its tandem caspase recruitment domains (CARDs) that act as a ubiquitin sensor in a manner that depends on RNA and ATP, demonstrate that un-anchored K63-polyubiquitin chains are signalling molecules in antiviral innate immunity.
[Homo sapiens] DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction.
[Homo sapiens] DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD).
[Homo sapiens] DDX58 (RIG-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model)
[Homo sapiens] DDX58 and NOD2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. DDX58 negatively regulates ligand-induced NFkB signalling mediated by NOD2, and conversely, NOD2 negatively regulates type I interferon induction by DDX58.
[Homo sapiens] DDX58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus to suppress viral replication. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of DDX58.
[Homo sapiens] DDX58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling. (Demonstrated in mice)
[Homo sapiens] Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse)
[Homo sapiens] DDX58 (RIG-I) stimulation with a synthetic ligand inhibits HIV replication in macrophages.
[Homo sapiens] RNF135 is essential for the association of DDX58 (RIG-I) and TRIM25, resulting in the activation of RIG-I signalling.
[Homo sapiens] ISG15 does not directly alter human rhinovirus replication but modulates immune signalling via the viral sensor protein DDX58 to impact production of CXCL10, which has been linked to innate immunity to viruses.
[Homo sapiens] Human rhinovirus infection of epithelial cells induces the expression and secretion of ISG15, which modulates immune responses via effects on DDX58, and by regulating CXCL10 production.
[Homo sapiens] The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
[Homo sapiens] IFI16 transcriptionally regulates type I interferons and DDX58 (RIG-I) and controls the interferon response to both DNA and RNA viruses.
[Homo sapiens] Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
[Homo sapiens] DDX58 dually functions as an hepatitis B virus sensor activating innate signalling and as a direct antiviral factor by counteracting the viral polymerase in hepatocytes.
[Homo sapiens] DDX58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but IFIH1 is a significant contributor to the cellular defense against IAV.
[Homo sapiens] Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
[Homo sapiens] Hepatitis B virus-induced MIR146A attenuates cell-intrinsic anti-viral innate immunity through targeting DDX58 and IFIT3.
[Homo sapiens] MIR485 exhibits bispecificity, targeting DDX58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
[Homo sapiens] A defective interfering RNA isolated from the Hu-191 vaccine strain of measles virus is sensed by PRKRA and DDX58 to initiate an innate antiviral response.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000107201:
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular processes involving RNA binding and alteration of RNA secondary structure. This gene encodes a protein containing RNA helicase-DEAD box protein motifs and a caspase recruitment domain (CARD). It is involved in viral double-stranded (ds) RNA recognition and the regulation of immune response. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 4:40203773-40239828
Strand Reverse strand
Band A5
Transcripts
ENSMUST00000037907 ENSMUSP00000042433
ENSMUST00000136435
ENSMUST00000137903
ENSMUST00000140616
ENSMUST00000135966
ENSMUST00000142055 ENSMUSP00000115052
ENSMUST00000139583
ENSMUST00000127026
ENSMUST00000139110
ENSMUST00000149539
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 33 experimentally validated interaction(s) in this database.
They are also associated with 52 interaction(s) predicted by orthology.
Experimentally validated
Total 33 [view]
Protein-Protein 20 [view]
Protein-DNA 2 [view]
Protein-RNA 11 [view]
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 52 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003690 double-stranded DNA binding
GO:0003725 double-stranded RNA binding
GO:0003727 single-stranded RNA binding
GO:0004386 helicase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0016817 hydrolase activity, acting on acid anhydrides
GO:0042802 identical protein binding
Biological Process
GO:0002230 positive regulation of defense response to virus by host
GO:0008152 metabolic process
GO:0009597 detection of virus
GO:0009615 response to virus
GO:0030334 regulation of cell migration
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0039529 RIG-I signaling pathway
GO:0042993 positive regulation of transcription factor import into nucleus
GO:0043330 response to exogenous dsRNA
GO:0045087 innate immune response (InnateDB)
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005923 tight junction
GO:0015629 actin cytoskeleton
GO:0032587 ruffle membrane
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
TRAF6 mediated NF-kB activation pathway
Innate Immune System pathway
Negative regulators of RIG-I/MDA5 signaling pathway
Immune System pathway
TRAF6 mediated IRF7 activation pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
TRAF3-dependent IRF activation pathway pathway
KEGG
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
INOH
PID BIOCARTA
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
REACTOME
Antiviral mechanism by IFN-stimulated genes pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
TRAF6 mediated IRF7 activation pathway
TRAF6 mediated NF-kB activation pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Interferon Signaling pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
Immune System pathway
TRAF3-dependent IRF activation pathway pathway
ISG15 antiviral mechanism pathway
Negative regulators of RIG-I/MDA5 signaling pathway
KEGG
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt Q6Q899
TrEMBL A2AP29
UniProt Splice Variant
Entrez Gene 230073
UniGene Mm.86382
RefSeq NM_172689
OMIM
CCDS CCDS18043
HPRD
IMGT
MGI ID MGI:2442858
MGI Symbol Ddx58
EMBL AK049305 AK078287 AK087261 AL831793 AY553221 CH466538
GenPept AAS59532 BAC33670 BAC37205 BAC39830 CAM27574 EDL05445
RNA Seq Atlas 230073