InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ifih1

Summary

InnateDB Protein

IDBP-255962.6

Last Modified

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

Gene Symbol

Ifih1

Protein Name

interferon induced with helicase C domain 1

Synonyms

9130009C22Rik; Helicard; Hlcd; MDA5; RLR-2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000108078

InnateDB Gene

IDBG-174129 (Ifih1)

Protein Structure

UniProt Annotation

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 mRNA lacking 2'-O- methylation at their 5' cap and long-dsRNA (>1 kb in length). 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. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and theiler's murine encephalomyelitis virus (TMEV). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines. {ECO:0000269PubMed:12015121, ECO:0000269PubMed:16625202, ECO:0000269PubMed:17942531, ECO:0000269PubMed:19656871, ECO:0000269PubMed:21217758}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:12015121}. Nucleus {ECO:0000305}. Note=May be found in the nucleus, during apoptosis.

Disease Associations

Tissue Specificity

Expression is prominent in lung, liver, kidney, heart and spleen (at protein level). Widely expressed at low level. {ECO:0000269PubMed:12015121}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.

Experimentally validated
Total	7 [view]
Protein-Protein	3 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	23 [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
GO:0043021	ribonucleoprotein complex binding

Biological Process

GO:0009615	response to virus
GO:0016925	protein sumoylation
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0042981	regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0051607	defense response to virus

Cellular Component

GO:0005622	intracellular
GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

MGI:1918836

InterPro

IPR001315 CARD domain
IPR001650 Helicase, C-terminal
IPR006935 Helicase/UvrB domain
IPR011029 Death-like 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

PF00619
PF00271
PF04851
PF00270
PF11648

PRINTS

PIRSF

SMART

SM00114
SM00490
SM00487

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q8R5F7