PROSITE documentation PDOC00653

2'-5'-oligoadenylate synthases signatures and profile

2'-5'-oligoadenylate synthases [1] constitute a family of interferon-induced enzymes that bind double-stranded RNA (dsRNA) and polymerizes ATP into 2'-5' linked oligomers of adenosine (pppA(2'p5'A)n) (2-5A) of various lengths. The 2-5A molecules activate a latent ribonuclease (Rnase L) that then cleaves single-stranded RNAs; as a result protein synthesis and virus growth are inhibited. Thus 2-5A synthases play an important role in the antiviral action of interferons.

Three distinct classes of 2-5A synthases have been described that correspond to proteins of 40-46 Kd, 69-71 Kd, and 100 Kd. The 40 and 46 Kd forms are produced by alternative splicing of the same gene. The 69 and 71 Kd forms are also produced by alternative splicing of a gene and consist of two adjacent homologous domains whose sequences are highly similar to that of the 40/46 Kd forms. The sequence of the 100 Kd form is not yet known.

We developed two signature patterns for these enzymes. The first spans a region rich in glycine residues which has been proposed [2] to be part of the ATP-binding site. The second signature corresponds to a highly conserved region located in the C-terminal part of 2-5A synthases proteins or domains.