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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, PubMed:40010341). Involved in intercellular immune signaling that limits local spread of RNA virus infection and protects against tumorigenesis (PubMed:40010341). Can generate high levels of 2',5'-oligoadenylates in transformed cells, targeting them to innate and adaptive immunesurveillance mechanisms (PubMed:40010341). 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.FUNCTION 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).FUNCTION Not prenylated at C-terminal, is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.CATALYTIC ACTIVITY 3 ATP = 5'-triphosphoadenylyl-(2'->5')-adenylyl-(2'->5')-adenosine + 2 diphosphateCOFACTOR Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated (PubMed:34581622). ssRNA or dsDNA do not act as activators.BIOPHYSICOCHEMICAL PROPERTIES Monomer (PubMed:9407111). Homotetramer (PubMed:23319625, PubMed:9407111).INTERACTION Associated with different subcellular fractions such as mitochondrial, nuclear, and rough/smooth microsomal fractions.SUBCELLULAR LOCATION (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.SUBCELLULAR LOCATION (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 PRODUCTS Expressed in lungs.INDUCTION By type I interferon (IFN) and viruses.PTM 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).PTM Not prenylated at C-terminal. The non-prenylated form is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.POLYMORPHISM Polymorphism dbSNP:rs10774671 is associated with protection against severe COVID-19 disease (PubMed:33633408, PubMed:34581622). In humans, the OAS1 protein is expressed as two major forms designated p46 and p42. The longer p46 isoform is generated by alternative splicing to an exon downstream of the terminal exon used by the p42 isoform. Although all human genotypes contain the exon that completes the transcript encoding p46, an intronic SNP (rs10774671) determines OAS1 exon usage. Alleles with a G at this SNP (G alleles) specify expression of the p46 isoform and some p42, whereas alleles with A at this position predominantly encode the p42 isoform and cannot express the p46 isoform (PubMed:34581622). The p42 isoform, which is the most common isoform in humans (~61% of alleles), has no detectable anti-SARS-CoV-2 activity. The p46 isoform has anti-SARS-CoV-2 activity (PubMed:34581622).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the 2-5A synthase family.CAUTION PubMed:1651324 sequence was originally thought to originate from mouse.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Luck of the draw - Issue 246 of April 2022
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