OAS1
Function
Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:34581622). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:34145065, PubMed:34581622). Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.
Isoform p46
When prenylated at C-terminal, acts as a double-stranded RNA (dsRNA) sensor specifically targeted to membranous replicative organelles in SARS coronavirus-2/SARS-CoV-2 infected cells where it binds to dsRNA structures in the SARS-CoV-2 5'-UTR and initiates a potent block to SARS-CoV-2 replication. Recognizes short stretches of dsRNA and activates RNase L. The binding is remarkably specific, with two conserved stem loops in the SARS-CoV-2 5'- untranslated region (UTR) constituting the principal viral target (PubMed:34581622). The same mechanism is necessary to initiate a block to cardiovirus EMCV (PubMed:34581622).
Isoform p42
Not prenylated at C-terminal, is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.
Involvement in disease
Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia
IMD100
An autosomal dominant disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis in the first months of life. Disease development appears to be influenced or triggered by viral infection. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Isoform p46
Prenylated at C-terminal. C-terminal prenylation is necessary to initiate a block to SARS-CoV-2 and is associated with protection from severe COVID-1. The prenylated form is targeted to perinuclear structures rich in viral dsRNA, whereas the non-prenylated form is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication (Probable). C-terminal prenylation is also necessary to initiate a block to cardiovirus EMCV (Probable).
Isoform p42
Not prenylated at C-terminal. The non-prenylated form is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.
Sequence Similarities
Belongs to the 2-5A synthase family.
Tissue Specificity
Expressed in lungs.
Cellular localization
- Cytoplasm
- Mitochondrion
- Nucleus
- Microsome
- Endoplasmic reticulum
- Secreted
- Associated with different subcellular fractions such as mitochondrial, nuclear, and rough/smooth microsomal fractions.
- Isoform p46
- (Microbial infection) In SARS coronavirus-2/SARS-CoV-2 infected cells, prenylated form localizes to membranous perinuclear structures reminiscent of the endoplasmic reticulum rich in viral dsRNA which are SARS-CoV-2 replicative organelles.
- Isoform p42
- (Microbial infection) In SARS coronavirus-2/SARS-CoV-2 infected cells, since its not prenylated, is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.
Alternative names
OIAS, OAS1, 2'-5'-oligoadenylate synthase 1, (2-5')oligo(A) synthase 1, 2-5A synthase 1, E18/E16, p46/p42 OAS