Alternative titles; symbols
HGNC Approved Gene Symbol: OAS2
Cytogenetic location: 12q24.13 Genomic coordinates (GRCh38): 12:112,978,519-113,011,723 (from NCBI)
The 2-prime,5-prime oligoadenylate synthetases (OASs), such as OAS2, are interferon-induced proteins characterized by their capacity to catalyze the synthesis of 2-prime,5-prime oligomers of adenosine (2-5As) (Hovnanian et al., 1998). For further information on OASs, see OAS1 (164350).
Hovanessian et al. (1987) found that interferon-treated human cells contain several OASs corresponding to proteins of 40 (OAS1), 46 (OAS1), 69 (OAS2), and 100 (OAS3; 603351) kD. Marie et al. (1989) generated highly specific polyclonal antibodies against p69, the 69-kD OAS. By screening an interferon-treated human cell expression library with the anti-p69 antibodies, Marie and Hovanessian (1992) isolated a partial OAS2 cDNA. They screened additional libraries with the partial cDNA and recovered cDNAs encoding 2 OAS2 isoforms. The smaller isoform is encoded by 2 mRNAs that differ in the length of the 3-prime untranslated region. Northern blot analysis revealed that OAS2 is expressed as 4 interferon-induced mRNAs in human cells. The predicted OAS2 proteins have a common 683-amino acid sequence and different 3-prime termini. By SDS-PAGE of in vitro transcription/translation products, the authors showed that 2 isoforms have molecular masses of 69 and 71 kD. Sequence analysis indicated that OAS2 contains 2 OAS1-homologous domains separated by a proline-rich putative linker region. The N- and C-terminal domains are 41% and 53% identical to OAS1, respectively. Marie and Hovanessian (1992) suggested that the OAS2 gene derived from the fusion of 2 ancestral genes analogous to OAS1.
Marie and Hovanessian (1992) found that both isoforms of human OAS2 exhibited OAS activity in vitro.
By fluorescence in situ hybridization and by inclusion within mapped clones, Hovnanian et al. (1998) determined that the OAS1, OAS2, and OAS3 genes are clustered with a 130-kb region on chromosome 12q24.2.
In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen, Oakes et al. (2017) identified an ile450-to-asn (I405N) mutation in the catalytic domain of Oas2, a sensor of viral double-stranded RNA, as the underlying cause of lactation failure in mice. In I405N mutant mice, mammary development through puberty and pregnancy appeared normal, and the onset of milk protein synthesis showed no defects during pregnancy. However, activation of lactation failed in the immediate postpartum period, and no milk reached pups. Lactation failure was accompanied by greatly diminished milk protein synthesis, decreased epithelial cell proliferation, increased epithelial cell death, and a robust interferon response. The Oas2 mutant caused a 34-fold increase in the activity of RNase L (RNASEL; 180435), the most proximal effector of OAS2 action, in mammary glands of mice. Expression of the mutant mouse Oas2 in T47D human breast cancer cells or mouse mammary HC11 cells recapitulated the phenotypes observed in mutant mice, including the molecular phenotypes. Further analyses demonstrated that the Oas2 mutation caused activation of the viral signaling pathway, as knockdown of RNASEL or IRF7 (605047) in T47D cells prevented the effects produced by expression of mutant mouse Oas2, whereas knockdown of IRF3 (603734) had the opposite effect.
Hovanessian, A. G., Laurent, A. G., Chebath, J., Galabru, J., Robert, N., Svab, J. Identification of 69-kd and 100-kd forms of 2-5A synthetase in interferon-treated human cells by specific monoclonal antibodies. EMBO J. 6: 1273-1280, 1987. [PubMed: 2440675] [Full Text: https://doi.org/10.1002/j.1460-2075.1987.tb02364.x]
Hovnanian, A., Rebouillat, D., Mattei, M.-G., Levy, E. R., Marie, I., Monaco, A. P., Hovanessian, A. G. The human 2-prime,5-prime-oligoadenylate synthetase locus is composed of three distinct genes clustered on chromosome 12q24.2 encoding the 100-, 69-, and 40-kDa forms. Genomics 52: 267-277, 1998. [PubMed: 9790745] [Full Text: https://doi.org/10.1006/geno.1998.5443]
Marie, I., Galabru, J., Svab, J., Hovanessian, A. G. Preparation and characterization of polyclonal antibodies specific for the 69 and 100 k-dalton forms of human 2-5A synthetase. Biochem. Biophys. Res. Commun. 160: 580-587, 1989. [PubMed: 2470369] [Full Text: https://doi.org/10.1016/0006-291x(89)92472-8]
Marie, I., Hovanessian, A. G. The 69-kDa 2-5A synthetase is composed of two homologous and adjacent functional domains. J. Biol. Chem. 267: 9933-9939, 1992. [PubMed: 1577824]
Oakes, S. R., Gallego-Ortega, D., Stanford, P. M., Junankar, S., Au, W. W. Y., Kikhtyak, Z., von Korff, A., Sergio, C. M., Law, A. M. K., Castillo, L. E., Allerdice, S. L., Young, A. I. J., and 10 others. A mutation in the viral sensor 2-prime-5-prime-oligoadenylate synthetase 2 causes failure of lactation. PLoS Genet. 13: e1007072, 2017. Note: Electronic Article. [PubMed: 29117179] [Full Text: https://doi.org/10.1371/journal.pgen.1007072]