Homo sapiens Gene: DDX58
Summary
InnateDB Gene IDBG-108556.1
Last Modified 2018-06-05 [Report errors or provide feedback]
Gene Symbol DDX58
Gene Name DExD/H-box helicase 58
Synonyms RIG-I; RIGI; RLR-1; SGMRT2;
Species Homo sapiens
Ensembl Gene ENSG00000107201
Encoded Proteins
DExD/H-box helicase 58
DExD/H-box helicase 58
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
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.
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.
DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses.
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.
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.
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.
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.
DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction.
DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD).
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)
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.
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.
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)
Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse)
DDX58 (RIG-I) stimulation with a synthetic ligand inhibits HIV replication in macrophages.
RNF135 is essential for the association of DDX58 (RIG-I) and TRIM25, resulting in the activation of RIG-I signalling.
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.
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.
The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
IFI16 transcriptionally regulates type I interferons and DDX58 (RIG-I) and controls the interferon response to both DNA and RNA viruses.
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.
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.
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.
Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
Hepatitis B virus-induced MIR146A attenuates cell-intrinsic anti-viral innate immunity through targeting DDX58 and IFIT3.
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.
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.
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.
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.
EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.
MIR136 exhibits potent antiviral activity against H5N1 influenza A virus and acts as an immune agonist of DDX58.
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
ENST00000379868 ENSP00000369197
ENST00000379883 ENSP00000369213
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 129 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.
Experimentally validated
Total 129 [view]
Protein-Protein 118 [view]
Protein-DNA 7 [view]
Protein-RNA 2 [view]
DNA-DNA 0
RNA-RNA 1 [view]
DNA-RNA 1 [view]
Predicted by orthology
Total 21 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0003676 nucleic acid binding
GO:0003690 double-stranded DNA binding
GO:0003723 RNA 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:0031625 ubiquitin protein ligase binding
GO:0042802 identical protein binding
GO:0046872 metal ion binding
Biological Process
GO:0002230 positive regulation of defense response to virus by host
GO:0002376 immune system process
GO:0009597 detection of virus
GO:0009615 response to virus
GO:0010628 positive regulation of gene expression
GO:0016032 viral process
GO:0016579 protein deubiquitination
GO:0030334 regulation of cell migration
GO:0032480 negative regulation of type I interferon production
GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0032755 positive regulation of interleukin-6 production
GO:0032757 positive regulation of interleukin-8 production
GO:0034344 regulation of type III interferon production
GO:0035549 positive regulation of interferon-beta secretion
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 DNA binding transcription factor activity
GO:0051607 defense response to virus
GO:0060760 positive regulation of response to cytokine stimulus
GO:0071360 cellular response to exogenous dsRNA
GO:1902741 positive regulation of interferon-alpha secretion
GO:1904469 positive regulation of tumor necrosis factor secretion
GO:2000778 positive regulation of interleukin-6 secretion
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0005923 bicellular tight junction
GO:0015629 actin cytoskeleton
GO:0016020 membrane
GO:0030054 cell junction
GO:0032587 ruffle membrane
GO:0042995 cell projection
Orthologs
No orthologs found for this gene
Pathways
NETPATH
REACTOME
TRAF3-dependent IRF activation pathway pathway
Post-translational protein modification pathway
Ovarian tumor domain proteases pathway
Negative regulators of DDX58/IFIH1 signaling pathway
Ub-specific processing proteases pathway
Metabolism of proteins pathway
Immune System pathway
Antiviral mechanism by IFN-stimulated genes pathway
ISG15 antiviral mechanism pathway
TRAF6 mediated NF-kB activation pathway
Interferon Signaling pathway
Innate Immune System pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
DDX58/IFIH1-mediated induction of interferon-alpha/beta pathway
Cytokine Signaling in Immune system pathway
Deubiquitination pathway
TRAF6 mediated IRF7 activation pathway
KEGG
NF-kappa B signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
Hepatitis B pathway
Measles pathway
Influenza A pathway
Herpes simplex infection pathway
Epstein-Barr virus infection pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt O95786
TrEMBL A2A376
UniProt Splice Variant
Entrez Gene 23586
UniGene
RefSeq NM_014314
HUGO HGNC:19102
OMIM 609631
CCDS CCDS6526
HPRD
IMGT
EMBL AF038963 AL137608 AL161783 AL353671 BC132786 BC136610 BX647917 CH471071
GenPept AAD19826 AAI32787 AAI36611 CAB70840 CAH71251 CAH72600 CAI46068 EAW58548
RNA Seq Atlas 23586