InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-135959

DEAD (Asp-Glu-Ala-Asp) box polypeptide 58

IDBP-536590

DEAD (Asp-Glu-Ala-Asp) box polypeptide 58

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 19936053

Ddx58 (Rig-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response.

PMID 21690088

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)

PMID 21695051

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)

PMID 22072774

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.

PMID 22912779

Antiviral stress granules containing Ddx58 (RIG-I) and Eif2ak2 (PKR) have a critical role in viral detection and innate immunity.

PMID 23064150

DDX58 (RIG-I) detects cytosolic Listeria monocytogenes infections by sensing secreted bacterial nucleic acids.

PMID 23553835

Ddx58 (RIG-I) is a positive regulator of NF-kB signalling via binding to Nfkb1 mRNA.

PMID 23966395

Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.

PMID 24692634

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.

PMID 26074083

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.

PMID 26146945

Ddx58 acts in parallel with Zbp1 in an RNA polymerase III-dependent manner to initiate glial responses to herpes simplex virus-1.

PMID 26645583

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

PMID 15208624

[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.

PMID 18948594

[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.

PMID 19074283

[Homo sapiens] DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses.

PMID 19683681

[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.

PMID 18523264

[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.

PMID 19915568

[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.

PMID 20403326

[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.

PMID 20406818

[Homo sapiens] DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction.

PMID 20511549

[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).

PMID 19936053

[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)

PMID 21690088

[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.

PMID 21695051

[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.

PMID 22072774

[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)

PMID 22912779

[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)

PMID 23744645

[Homo sapiens] DDX58 (RIG-I) stimulation with a synthetic ligand inhibits HIV replication in macrophages.

PMID 23950712

[Homo sapiens] RNF135 is essential for the association of DDX58 (RIG-I) and TRIM25, resulting in the activation of RIG-I signalling.

PMID 24448099

[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.

PMID 24448099

[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.

PMID 24550253

[Homo sapiens] The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.

PMID 25002588

[Homo sapiens] IFI16 transcriptionally regulates type I interferons and DDX58 (RIG-I) and controls the interferon response to both DNA and RNA viruses.

PMID 25520509

[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.

PMID 25557055

[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.

PMID 26074083

[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.

PMID 25880109

[Homo sapiens] Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.

PMID 27210312

[Homo sapiens] Hepatitis B virus-induced MIR146A attenuates cell-intrinsic anti-viral innate immunity through targeting DDX58 and IFIT3.

PMID 26645583

[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.

PMID 26608320

[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.

PMID 26371557

[Homo sapiens] ATP binding is required for DDX58 signalling on viral RNA. ATP hydrolysis provides an important function by recycling DDX58 and promoting its dissociation from non-pathogenic RNA.

PMID 26378160

[Homo sapiens] Influenza B virus induces IRF3 activation and IL29 (IFNL1) gene expression without a requirement for viral protein synthesis or replication and DDX58 is the critical pattern recognition receptor needed for IRF3 activation.

PMID 25878102

[Homo sapiens] EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.

PMID 26450567

[Homo sapiens] MIR136 exhibits potent antiviral activity against H5N1 influenza A virus and acts as an immune agonist of DDX58.

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

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