InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DDX58

Summary

InnateDB Protein

IDBP-55856.6

Last Modified

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

Gene Symbol

DDX58

Protein Name

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

Synonyms

RIG-I; RIGI; RLR-1;

Species

Homo sapiens

Ensembl Protein

ENSP00000369213

InnateDB Gene

IDBG-55854 (DDX58)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:15208624, ECO:0000269PubMed:15708988, ECO:0000269PubMed:16125763, ECO:0000269PubMed:16127453, ECO:0000269PubMed:16153868, ECO:0000269PubMed:17190814, ECO:0000269PubMed:18636086, ECO:0000269PubMed:19122199, ECO:0000269PubMed:19211564, ECO:0000269PubMed:19576794, ECO:0000269PubMed:19609254, ECO:0000269PubMed:19631370, ECO:0000269PubMed:21742966}.

Subcellular Localization

Cytoplasm. Cell projection, ruffle membrane. Cytoplasm, cytoskeleton. Cell junction, tight junction. Note=Colocalized with TRIM25 at cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton at membrane ruffles.

Disease Associations

Tissue Specificity

Present in vascular smooth cells (at protein level). {ECO:0000269PubMed:15219805}.

Comments

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

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005923	tight junction
GO:0015629	actin cytoskeleton
GO:0032587	ruffle membrane

Protein Structure and Domains

PDB ID

InterPro

IPR001650 Helicase, C-terminal
IPR006935 Helicase/UvrB domain
IPR011029 Death-like domain
IPR011545 DEAD/DEAH box helicase domain
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR021673 C-terminal domain of RIG-I
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00271
PF04851
PF00270
PF11648

PRINTS

PIRSF

SMART

SM00490
SM00487

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

O95786