TISIDB

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

[ TOP ]

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
Symbol	DDX58
Name	DEAD (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 Location	9p12
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

[ TOP ]

Literatures describing the relation between DDX58 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24574393	Non-Small Cell Lung Carcinoma	Promote immunity	We 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.
28468914	Melanoma	Promote 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.
24360797	Hepatocellular Carcinoma	Promote immunity	We 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.
20551064	Ovarian Carcinoma	Promote immunity	Here, 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
Symbol	DDX58
Name	DEAD (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 Location	9p12
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.173	0.625
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.042	0.97
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.324	0.676
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.133	0.73
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.073	0.969
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.395	0.869
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.227	0.633
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.335	0.811
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.091	0.954
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.629	0.586
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.27	0.882
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.153	0.209

> Mutation difference between responders and non-responders

[ TOP ]

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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
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 [ TOP ]

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DDX58 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DDX58 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DDX58
Name	DEAD (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 Location	9p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DDX58 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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