InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IFIH1

Summary

InnateDB Protein

IDBP-73752.6

Last Modified

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

Gene Symbol

IFIH1

Protein Name

interferon induced with helicase C domain 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000263642

InnateDB Gene

IDBG-73750 (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) and mengo encephalomyocarditis virus (ENMG). 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:14645903, ECO:0000269PubMed:19211564, ECO:0000269PubMed:19656871, ECO:0000269PubMed:21217758, ECO:0000269PubMed:21742966}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:11805321, ECO:0000269PubMed:14645903}. Nucleus {ECO:0000305}. Note=May be found in the nucleus, during apoptosis.

Disease Associations

Diabetes mellitus, insulin-dependent, 19 (IDDM19) [MIM:610155]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.Note=IFIH1 is the CADM-140 autoantigen, involved in clinically amyopathic dermatomyositis (CADM). This is a chronic inflammatory disorder that shows typical skin manifestations of dermatomyositis but has no or little evidence of clinical myositis. Anti-CADM-140 antibodies appear to be specific to dermatomyositis, especially CADM. Patients with anti-CADM-140 antibodies frequently develop life-threatening acute progressive interstitial lung disease (ILD).

Tissue Specificity

Widely expressed, at a low level. Expression is detected at slightly highest levels in placenta, pancreas and spleen and at barely levels in detectable brain, testis and lung. {ECO:0000269PubMed:11805321, ECO:0000269PubMed:12015121, ECO:0000269PubMed:14645903}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	44 [view]
Protein-Protein	42 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [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:0005488	binding
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:0009597	detection of virus
GO:0009615	response to virus
GO:0016032	viral process
GO:0016925	protein sumoylation
GO:0032480	negative regulation of type I interferon production
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0034344	regulation of type III interferon production
GO:0039528	cytoplasmic pattern recognition receptor signaling pathway in response to virus
GO:0042981	regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)

Cellular Component

GO:0005634	nucleus
GO:0005829	cytosol

Protein Structure and Domains

PDB ID

InterPro

IPR001315 CARD domain
IPR001650 Helicase, C-terminal
IPR006935 Helicase/UvrB domain
IPR011029 Death-like domain
IPR011545 DEAD/DEAH box helicase domain
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR016024 Armadillo-type fold
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

Q9BYX4