The human 2′,5′-oligoadenylate synthetase family:: Interferon-induced proteins with unique enzymatic properties

2',5'-Oligoadenylate synthetase (2',5'-OAS) was discovered and characterized as an interferon (IFN)-induced enzyme that in the presence of double-stranded (ds) RNA converts ATP into 2',5'-linked oligomers of adenosine with the general formula pppA(2'p'A)(n), n greater than or equal to 1. The product is pppG2'p5'G when GTP is used as a substrate. Now, 20 years later, this activity is attributed to several well-characterized, homologous, and IFN-induced proteins in human cells. Three distinct forms of 2',5'-OAS exist, small, medium, and large, which contain 1, 2, and 3 OAS units, respectively, and are encoded by distinct genes clustered on the 2',5'-OAS locus on human chromosome 12, Recently, other IFN-induced proteins homologous to the OAS unit but devoid of the typical 2',5'-OAS catalytic activity have been described, These GAS-related proteins are encoded by a gene located at the proximity of the 2',5'-OAS locus. These findings illustrate the apparent structural and functional complexity of the human 2',5'-OAS family.