DHX58 (DExH-box helicase 58)

Gene

• Entrez ID: 79132
• Gene name: DExH-box helicase 58
• Gene symbol: DHX58
• Synonyms: D11LGP2, D11lgp2e, LGP2, RLR-3
• Chromosome: 17
• Chromosome location: 17q21.2

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003677	Function	DNA binding	IEA
GO:0003724	Function	RNA helicase activity	IEA
GO:0003725	Function	Double-stranded RNA binding	IBA	21873635
GO:0003725	Function	Double-stranded RNA binding	IDA	18411269
GO:0003727	Function	Single-stranded RNA binding	IBA	21873635
GO:0003727	Function	Single-stranded RNA binding	IDA	18411269
GO:0005515	Function	Protein binding	IPI	17190814, 19403670, 21791617, 21903422, 25340845, 30833792
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0008270	Function	Zinc ion binding	IBA	21873635
GO:0008270	Function	Zinc ion binding	IDA	19278996
GO:0009615	Process	Response to virus	IBA	21873635
GO:0009615	Process	Response to virus	ISS
GO:0009617	Process	Response to bacterium	IEA
GO:0016032	Process	Viral process	IEA
GO:0032480	Process	Negative regulation of type I interferon production	IDA	21525357
GO:0032481	Process	Positive regulation of type I interferon production	ISS
GO:0032728	Process	Positive regulation of interferon-beta production	IBA	21873635
GO:0039534	Process	Negative regulation of MDA-5 signaling pathway	IMP	21187438
GO:0039536	Process	Negative regulation of RIG-I signaling pathway	IDA	18411269
GO:0039536	Process	Negative regulation of RIG-I signaling pathway	IMP	21187438
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0045088	Process	Regulation of innate immune response	IDA	18411269
GO:0045824	Process	Negative regulation of innate immune response	IDA	21525357
GO:0051607	Process	Defense response to virus	IEA
GO:1900245	Process	Positive regulation of MDA-5 signaling pathway	ISS
GO:1900246	Process	Positive regulation of RIG-I signaling pathway	ISS

Other IDs

• MIM: 608588
• HGNC: 29517
• e!Ensembl: ENSG00000108771

Protein

• UniProt ID: Q96C10
• Protein name: Probable ATP-dependent RNA helicase DHX58 (EC 3.6.4.13) (Probable ATP-dependent helicase LGP2) (Protein D11Lgp2 homolog) (RIG-I-like receptor 3) (RLR-3) (RIG-I-like receptor LGP2) (RLR)
• Protein function: Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: competition with DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses and coronavirus SARS-CoV-2, and also to the bacterial pathogen Listeria monocytogenes (PubMed:31256877). Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate.
• PDB: 2RQA, 2W4R, 3EQT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04851	ResIII	1 → 172	Type III restriction enzyme, res subunit	Family
  PF18119	RIG-I_C	215 → 343	RIG-I receptor C-terminal domain	Domain
  PF00271	Helicase_C	349 → 475	Helicase conserved C-terminal domain	Family
  PF11648	RIG-I_C-RD	552 → 667	C-terminal domain of RIG-I	Domain

• Sequence:

  MELRSYQWEVIMPALEGKNIIIWLPTGAGKTRAAAYVAKRHLETVDGAKVVVLVNRVHLV
  TQHGEEFRRMLDGRWTVTTLSGDMGPRAGFGHLARCHDLLICTAELLQMALTSPEEEEHV
  ELTVFSLIVVDECHHTHKDTVYNVIMSQYLELKLQRAQPLPQVLGLTASPGTGGASKLDG
  AINHVLQLCANLDTWCIMSPQNCCPQLQEHSQQPCKQYNLCHRRSQDPFGDLLKKLMDQI
  HDHLEMPELSRKFGTQMYEQQVVKLSEAAALAGLQEQRVYALHLRRYNDALLIHDTVRAV
  DALAALQDFYHREHVTKTQILCAERRLLALFDDRKNELAHLATHGPENPKLEMLEKILQR
  QFSSSNSPRGIIFTRTRQSAHSLLLWLQQQQGLQTVDIRAQLLIGAGNSSQSTHMTQRDQ
  QEVIQKFQDGTLNLLVATSVAEEGLDIPHCNVVVRYGLLTNEISMVQARGRARADQSVYA
  FVATEGSRELKRELINEALETLMEQAVAAVQKMDQAEYQAKIRDLQQAALTKRAAQAAQR
  ENQRQQFPVEHVQLLCINCMVAVGHGSDLRKVEGTHHVNVNPNFSNYYNVSRDPVVINKV
  FKDWKPGGVISCRNCGEVWGLQMIYKSVKLPVLKVRSMLLETPQGRIQAKKWSRVPFSVP
  DFDFLQHCAENLSDLSLD

• Sequence length: 678

Pathways

KEGG:

RIG-I-like receptor signaling pathway

Reactome:

DDX58/IFIH1-mediated induction of interferon-alpha/beta

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	29212778