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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

DDX58 Gene

protein-coding GIFtS: 61
GCID: GC09M032447

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

Explore 35 diseases affiliated with
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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
DEAD (Asp-Glu-Ala-Asp) Box Polypeptide 58¹ ²		DKFZp434J1111¹
RIG-I¹ ² ³		FLJ13599¹
Retinoic Acid-Inducible Gene 1 Protein² ³		RIGI²
Retinoic Acid-Inducible Gene I Protein² ³		DEAD/H (Asp-Glu-Ala-Asp/His) Box Polypeptide²
RIG-1² ³		Probable ATP-Dependent RNA Helicase DDX58²
RLR-1² ³		Retinoic Acid Inducible Gene I²
DEAD Box Protein 58² ³		RNA Helicase RIG-I²
RIG-I-Like Receptor 1² ³		EC 3.6.4.13³

External Ids:	HGNC: 19102¹	Entrez Gene: 23586²	Ensembl: ENSG00000107201⁷	OMIM: 609631⁵	UniProtKB: O95786³

Export aliases for DDX58 gene to outside databases

Previous GC identifer: GC09M032446

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for DDX58:

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)

UniProtKB/Swiss-Prot: DDX58_HUMAN, O95786

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 Wiki entry for DDX58

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000009.11 NC_018920.1 NT_008413.18

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the DDX58 gene promoter:
TBP GR AP-1 GR-beta ATF-2 YY1 GATA-1 STAT3 c-Jun GR-alpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: DDX58 promoter sequence

Search SABiosciences Chromatin IP Primers for DDX58

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat DDX58

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 9p12 Ensembl cytogenetic band: 9p21.1 HGNC cytogenetic band: 9p12

DDX58 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DDX58 gene location

GeneLoc information about chromosome 9 GeneLoc Exon Structure

GeneLoc location for GC09M032447: view genomic region (about GC identifiers)

Start:	32,455,300 bp from pter	End:	32,526,322 bp from pter
Size:	71,023 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: DDX58_HUMAN, O95786 (See protein sequence)

Recommended Name: Probable ATP-dependent RNA helicase DDX58

Size: 925 amino acids; 106600 Da

Cofactor: Zinc

Subunit: Monomer; maintained as a monomer in an autoinhibited state. Upon viral dsRNA binding and conformation shift,

homomultimerizes and interacts with MAVS/IPS1. Interacts with DHX58/LGP2, IKBKE, TBK1 and TMEM173/STING. Interacts

(via CARD domain) with TRIM25 (via SPRY domain). Interacts with RNF135. Interacts with CYLD. Interacts with NLRC5;

blocks the interaction of MAVS/IPS1 to DDX58. Interacts with SRC. Interacts with protein Z of Guanarito virus, Machupo

virus, Junin arenavirus and Sabia virus. This interaction disrupts its interaction with MAVS/IPS1, impeding downstream

IRF3 and NF-kappa-B activation and resulting in decreased IFN-beta induction. Interacts (via CARD domain) with Human

respiratory syncytial virus A non-structural protein 2 (NS2) and this interaction disrupts its interaction with

MAVS/IPS1, impeding downstream IRF3 activation. Interacts with Rotavirus A non-structural protein 1 (NSP1) and this

interaction induces down-regulation of DDX58/RIG-I. Interacts with DDX60. Interacts with isoform 2 of ZC3HAV1 (via

zinc-fingers) in an RNA-dependent manner

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

6/12 PDB 3D structures from and Proteopedia for DDX58 (see all 12):

2LWD (3D)

2LWE (3D)

2QFB (3D)

2QFD (3D)

2RMJ (3D)

2YKG (3D)

Secondary accessions: A2RU81 Q5HYE1 Q5VYT1 Q9NT04

Alternative splicing: 2 isoforms: O95786-1 O95786-2 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for DDX58: NX_O95786

Post-translational modifications:

Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-770, Ser-854

and Ser-855 results in inhibition of its activity while dephosphorylation at these sites results in its activation¹

Isgylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation¹

Ubiquitinated. Undergoes 'Lys-48'- and 'Lys-63'-linked ubiquitination. Lys-172 is the critical site for TRIM25-mediated

ubiquitination, for MAVS/IPS1 binding and to induce anti-viral signal transduction. Lys-154, Lys-164 and Lys-172 are

critical sites for RNF135-mediated ubiquitination. Deubiquitinated by CYLD, a protease that selectively cleaves

'Lys-63'-linked ubiquitin chains. Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'-and

'Lys-63'-linked ubiquitin chains and positively regulates the receptor¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O95786

DDX58 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_055129.2

ENSEMBL proteins:

ENSP00000369213 ENSP00000369197 ENSP00000369212 ENSP00000442160 ENSP00000443055

Reactome Protein details: O95786
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: DDX58 OriGene Protein Over-expression Lysate: DDX58 OriGene Custom Protein Services for DDX58
	GenScript Custom Purified and Recombinant Proteins Services for DDX58
	Novus Biologicals DDX58 Protein Novus Biologicals DDX58 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Uscn

Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IDA	--
GO:0005829	cytosol	TAS	--
GO:0005923	tight junction	IDA	19122199
GO:0015629	actin cytoskeleton	IDA	19122199
GO:0032587	ruffle membrane	IDA	19122199

DDX58 for ontologies About GeneDecksing

DDX58 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of DDX58
	R&D Systems Antibodies for DDX58 (RIG-I)
	Cell Signaling Technology (CST) Antibodies for DDX58
	OriGene Antibodies (see all 3): DDX58 OriGene Custom Antibody Services for DDX58
	GenScript Custom Superior Antibodies Services for DDX58
	Novus Biologicals DDX58 Antibodies
	Search for Antibodies for DDX58 at Abcam
	Browse Antibodies at Uscn
	ThermoFisher Antibodies for DDX58

Assay Products for DDX58:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for DDX58
	Enzo Life Sciences assays for DDX58
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

DDX58 for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR003593 AAA+_ATPase

IPR011545 DNA/RNA_helicase_DEAD/DEAH_N

IPR021673 RIG-I_C-RD

IPR014001 Helicase_ATP-bd

IPR011029 DEATH-like_dom

Graphical View of Domain Structure for InterPro Entry O95786

ProtoNet protein and cluster: O95786

1 Blocks protein family: IPB001315 CARD interaction domain

UniProtKB/Swiss-Prot: DDX58_HUMAN, O95786

Domain: The repressor domain controls homomultimerization and interaction with MAVS/IPS1. In the absence of viral

infection, the protein is maintained as a monomer in an autoinhibited state with the CARD domains masked through

intramolecular interactions mediated by the repressor domain. Upon binding to viral RNA in the presence of ATP, the

repressor domain induces a conformational change exposing the CARD domain and promotes dimerization and CARD

interactions with the adapter protein MAVS/IPS1 leading to the induction of downstream signaling

Domain: The helicase domain is responsible for dsRNA recognition

Domain: The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association

with the actin cytoskeleton

Domain: The second CARD domain is the primary site for 'Lys-63'-linked ubiquitination

Similarity: Belongs to the helicase family. RLR subfamily

Similarity: Contains 2 CARD domains

Similarity: Contains 1 helicase ATP-binding domain

Similarity: Contains 1 helicase C-terminal domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: