9h1z

Structural highlights

Function

OAS2_HUMAN Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:10464285, PubMed:9880569). Activated by detection of double stranded RNA (dsRNA): polymerizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNASEL) leading to its dimerization and subsequent activation (PubMed:10464285, PubMed:11682059, PubMed:9880569). Activation of RNASEL leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:10464285, PubMed:9880569). Can mediate the antiviral effect via the classical RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL (PubMed:21142819). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation (PubMed:21142819). May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates (By similarity). Non-infected lobules would not be affected, allowing efficient pup feeding during infection (By similarity).[UniProtKB:E9Q9A9]^{[1] [2] [3] [4] [5]}

References

1. ↑ Sarkar SN, Ghosh A, Wang HW, Sung SS, Sen GC. The nature of the catalytic domain of 2'-5'-oligoadenylate synthetases. J Biol Chem. 1999 Sep 3;274(36):25535-42. PMID:10464285 doi:10.1074/jbc.274.36.25535
2. ↑ Hartmann R, Walko G, Justesen J. Inhibition of 2'-5' oligoadenylate synthetase by divalent metal ions. FEBS Lett. 2001 Oct 19;507(1):54-8. PMID:11682059 doi:10.1016/s0014-5793(01)02918-0
3. ↑ Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL. Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members against dengue virus infection. J Immunol. 2009 Dec 15;183(12):8035-43. doi: 10.4049/jimmunol.0902728. Epub . PMID:19923450 doi:http://dx.doi.org/10.4049/jimmunol.0902728
4. ↑ Sarkar SN, Bandyopadhyay S, Ghosh A, Sen GC. Enzymatic characteristics of recombinant medium isozyme of 2'-5' oligoadenylate synthetase. J Biol Chem. 1999 Jan 15;274(3):1848-55. PMID:9880569 doi:10.1074/jbc.274.3.1848
5. ↑ Kristiansen H, Gad HH, Eskildsen-Larsen S, Despres P, Hartmann R. The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities. J Interferon Cytokine Res. 2011 Jan;31(1):41-7. PMID:21142819 doi:10.1089/jir.2010.0107