InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Dhx58

Summary

InnateDB Protein

IDBP-211514.6

Last Modified

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

Gene Symbol

Dhx58

Protein Name

DEXH (Asp-Glu-X-His) box polypeptide 58

Synonyms

B430001I08Rik; D11Lgp2e; Lgp2; LPG2; RLR-3;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000017974

InnateDB Gene

IDBG-211512 (Dhx58)

Protein Structure

UniProt Annotation

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 also to the bacterial pathogen Listeria monocytogenes. 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. {ECO:0000269PubMed:17475874, ECO:0000269PubMed:20080593, ECO:0000269PubMed:21525357, ECO:0000269PubMed:21533147}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:11735219}.

Disease Associations

Tissue Specificity

Highly expressed in mammary tissues. Expressed in liver and testis. Expressed at lower level in spleen, embryo, mammary gland and breast tumors. {ECO:0000269PubMed:11735219}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.
They are also associated with 18 interaction(s) predicted by orthology.

Experimentally validated
Total	2 [view]
Protein-Protein	1 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	18 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003677	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

Biological Process

GO:0008152	metabolic process
GO:0009615	response to virus
GO:0032480	negative regulation of type I interferon production
GO:0032481	positive regulation of type I interferon production
GO:0039534	negative regulation of MDA-5 signaling pathway
GO:0039536	negative regulation of RIG-I signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0045088	regulation of innate immune response
GO:0045824	negative regulation of innate immune response
GO:0051607	defense response to virus
GO:1900245	positive regulation of MDA-5 signaling pathway
GO:1900246	positive regulation of RIG-I signaling pathway

Cellular Component

GO:0005737

cytoplasm

Protein Structure and Domains

PDB ID

MGI:1931560

InterPro

IPR001650 Helicase, C-terminal
IPR006935 Helicase/UvrB domain
IPR011545 DNA/RNA helicase, DEAD/DEAH box type, N-terminal
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

Q99J87