InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: DDX58

Summary

InnateDB Gene

IDBG-55854.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DDX58

Gene Name

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

Synonyms

RIG-I; RIGI; RLR-1

Species

Homo sapiens

Ensembl Gene

ENSG00000107201

Encoded Proteins

IDBP-55856

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

IDBP-55860

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

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 15208624

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

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

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

PMID 19683681

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

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

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

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

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

PMID 20511549

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

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

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

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

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

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

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

PMID 23950712

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

PMID 24448099

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

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

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

PMID 25002588

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

PMID 25520509

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

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

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

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

PMID 27210312

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

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.

PMID 26608320

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

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

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

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

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

InnateDB Annotation from Orthologs

Summary

PMID 19936053

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

PMID 21690088

[Mus musculus] 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

[Mus musculus] 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

[Mus musculus] 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

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

PMID 23064150

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

PMID 23553835

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

PMID 23966395

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

PMID 24692634

[Mus musculus] 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

[Mus musculus] 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

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

PMID 26645583

[Mus musculus] 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.

Entrez Gene

Summary

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 9:32455705-32526324

Strand

Reverse strand

Band

p21.1

Transcripts

ENST00000379883	ENSP00000369213
ENST00000379868	ENSP00000369197

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 119 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	119 [view]
Protein-Protein	108 [view]
Protein-DNA	7 [view]
Protein-RNA	2 [view]
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	1 [view]

Predicted by orthology
Total	19 [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:0016032	viral process
GO:0030334	regulation of cell migration
GO:0032480	negative regulation of type I interferon production
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0034344	regulation of type III interferon production
GO:0039528	cytoplasmic pattern recognition receptor signaling pathway in response to virus
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
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity