Browse DDX58

Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location 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.
Domain PF16739 Caspase recruitment domain
PF00270 DEAD/DEAH box helicase
PF00271 Helicase conserved C-terminal domain
PF11648 C-terminal domain of RIG-I
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.

> Gene Ontology
 
Biological Process GO:0001818 negative regulation of cytokine production
GO:0001819 positive regulation of cytokine production
GO:0002218 activation of innate immune response
GO:0002221 pattern recognition receptor signaling pathway
GO:0002230 positive regulation of defense response to virus by host
GO:0002697 regulation of immune effector process
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002831 regulation of response to biotic stimulus
GO:0006606 protein import into nucleus
GO:0006913 nucleocytoplasmic transport
GO:0009597 detection of virus
GO:0009615 response to virus
GO:0017038 protein import
GO:0030522 intracellular receptor signaling pathway
GO:0031349 positive regulation of defense response
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032479 regulation of type I interferon production
GO:0032480 negative regulation of type I interferon production
GO:0032481 positive regulation of type I interferon production
GO:0032604 granulocyte macrophage colony-stimulating factor production
GO:0032606 type I interferon production
GO:0032607 interferon-alpha production
GO:0032608 interferon-beta production
GO:0032635 interleukin-6 production
GO:0032637 interleukin-8 production
GO:0032645 regulation of granulocyte macrophage colony-stimulating factor production
GO:0032647 regulation of interferon-alpha production
GO:0032648 regulation of interferon-beta production
GO:0032675 regulation of interleukin-6 production
GO:0032677 regulation of interleukin-8 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:0033157 regulation of intracellular protein transport
GO:0034343 type III interferon production
GO:0034344 regulation of type III interferon production
GO:0034504 protein localization to nucleus
GO:0039528 cytoplasmic pattern recognition receptor signaling pathway in response to virus
GO:0039529 RIG-I signaling pathway
GO:0042306 regulation of protein import into nucleus
GO:0042307 positive regulation of protein import into nucleus
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042993 positive regulation of transcription factor import into nucleus
GO:0043330 response to exogenous dsRNA
GO:0043331 response to dsRNA
GO:0043900 regulation of multi-organism process
GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism
GO:0044744 protein targeting to nucleus
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0050688 regulation of defense response to virus
GO:0050691 regulation of defense response to virus by host
GO:0050792 regulation of viral process
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051222 positive regulation of protein transport
GO:0051607 defense response to virus
GO:0090316 positive regulation of intracellular protein transport
GO:0098542 defense response to other organism
GO:0098586 cellular response to virus
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1902593 single-organism nuclear import
GO:1903533 regulation of protein targeting
GO:1903829 positive regulation of cellular protein localization
GO:1904589 regulation of protein import
GO:1904591 positive regulation of protein import
GO:1904951 positive regulation of establishment of protein localization
Molecular Function GO:0003725 double-stranded RNA binding
GO:0003727 single-stranded RNA binding
GO:0004386 helicase activity
Cellular Component GO:0001726 ruffle
GO:0005923 bicellular tight junction
GO:0015629 actin cytoskeleton
GO:0031252 cell leading edge
GO:0031253 cell projection membrane
GO:0031256 leading edge membrane
GO:0032587 ruffle membrane
GO:0043296 apical junction complex
GO:0070160 occluding junction
> KEGG and Reactome Pathway
 
KEGG hsa04064 NF-kappa B signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04623 Cytosolic DNA-sensing pathway
Reactome R-HSA-1169410: Antiviral mechanism by IFN-stimulated genes
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-5688426: Deubiquitination
R-HSA-1169408: ISG15 antiviral mechanism
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-913531: Interferon Signaling
R-HSA-392499: Metabolism of proteins
R-HSA-933543: NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-936440: Negative regulators of RIG-I/MDA5 signaling
R-HSA-5689896: Ovarian tumor domain proteases
R-HSA-597592: Post-translational protein modification
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-918233: TRAF3-dependent IRF activation pathway
R-HSA-933541: TRAF6 mediated IRF7 activation
R-HSA-933542: TRAF6 mediated NF-kB activation
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between DDX58 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between DDX58 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24574393Non-Small Cell Lung CarcinomaPromote immunityWe report that MV-Edm exploits selective autophagy to mitigate the innate immune response mediated by DDX58/RIG-I like receptors (RLRs) in non-small cell lung cancer (NSCLC) cells.
28468914MelanomaPromote immunity (T cell function)Scavenging of hypoxia-induced reactive oxygen species by vitamin C restored the inducible expression of RIG-I under hypoxiain vitro, boostedin vitroanti-melanoma NK- and CD8+T-cell attack, and augmented 3pRNA antitumor efficacyin vivoThese results demonstrate that RIG-I remains operational under hypoxia and that RIG-I function is largely insensitive to lower cell surface expression of the IFNα receptor.
24360797Hepatocellular CarcinomaPromote immunityWe found that expression of retinoic acid-inducible gene-I (RIG-I), an IFN-stimulated gene, was significantly downregulated in human HCC tissues. Mechanistically, RIG-I enhances IFN-α response by amplifying IFN-α effector signaling via strengthening STAT1 activation. Furthermore, we found that RIG-I deficiency promotes HCC carcinogenesis and that hepatic RIG-I expression is lower in men than in women.
20551064Ovarian CarcinomaPromote immunityHere, we show that targeted delivery of RIG-I agonists induced ovarian cancer cells to upregulate HLA class I and to secrete the proinflammatory cytokines CXCL10, CCL5, interleukin-6, tumor necrosis factor-alpha, and IFN-beta. Ovarian cancer cells stimulated via RIG-I became apoptotic and were readily phagocytosed by monocytes and monocyte-derived dendritic cells, which in turn upregulated HLA class I/II and costimulatory molecules and released CXCL10 and IFN-alpha.
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of DDX58 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of DDX58 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1730.625
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0420.97
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3240.676
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1330.73
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0730.969
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3950.869
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2270.633
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3350.811
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0910.954
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6290.586
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.270.882
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1530.209
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of DDX58 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.4015.40.482
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DDX58. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DDX58. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DDX58.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DDX58. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of DDX58 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between DDX58 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolDDX58
NameDEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Aliases RIG-I; FLJ13599; DKFZp434J1111; RNA helicase RIG-I; retinoic acid inducible gene I; RIGI; RLR-1; SGMRT2; DEA ......
Chromosomal Location9p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting DDX58 collected from DrugBank database.
> Drugs from DrugBank database
 

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