ID OAS1_HUMAN Reviewed; 400 AA. AC P00973; A8K4N8; F8VXY3; P04820; P29080; P29081; P78485; P78486; Q16700; AC Q16701; Q1PG42; Q3ZM01; Q53GC5; Q53YA4; Q6A1Z3; Q6IPC6; Q6P7N9; Q96J61; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 4. DT 24-JAN-2024, entry version 229. DE RecName: Full=2'-5'-oligoadenylate synthase 1; DE Short=(2-5')oligo(A) synthase 1; DE Short=2-5A synthase 1; DE EC=2.7.7.84 {ECO:0000269|PubMed:10464285, ECO:0000269|PubMed:12799444, ECO:0000269|PubMed:23319625, ECO:0000269|PubMed:25775560, ECO:0000269|PubMed:3753689, ECO:0000269|PubMed:3754863, ECO:0000269|PubMed:9407111}; DE AltName: Full=E18/E16; DE AltName: Full=p46/p42 OAS; GN Name=OAS1; Synonyms=OIAS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS P42 AND P46), AND RP VARIANTS ASP-31; SER-162; THR-352 AND THR-361. RC TISSUE=Fetal blood; RX PubMed=2416561; DOI=10.1002/j.1460-2075.1985.tb03922.x; RA Benech P., Mory Y., Revel M., Chebath J.; RT "Structure of two forms of the interferon-induced (2'-5') oligo A RT synthetase of human cells based on cDNAs and gene sequences."; RL EMBO J. 4:2249-2256(1985). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P42), CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, AND VARIANT SER-162. RX PubMed=3753689; DOI=10.1016/0014-5793(86)80224-1; RA Wathelet M.G., Moutschen S., Cravador A., Dewit L., Defilippi P., RA Huez G.A., Content J.; RT "Full-length sequence and expression of the 42 kDa 2-5A synthetase induced RT by human interferon."; RL FEBS Lett. 196:113-120(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P42), CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, AND VARIANT SER-162. RX PubMed=3754863; DOI=10.1093/oxfordjournals.jbchem.a135615; RA Shiojiri S., Fukunaga R., Ichii Y., Sokawa Y.; RT "Structure and expression of a cloned cDNA for human (2'-5')oligoadenylate RT synthetase."; RL J. Biochem. 99:1455-1464(1986). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS P48 AND P42), AND VARIANT RP SER-162. RX PubMed=1651324; DOI=10.1016/s0021-9258(18)98615-1; RA Ghosh S.K., Kusari J., Bandyopadhyay S.K., Samanta H., Kumar R., Sen G.C.; RT "Cloning, sequencing, and expression of two murine 2'-5'-oligoadenylate RT synthetases. Structure-function relationships."; RL J. Biol. Chem. 266:15293-15299(1991). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P44). RA Andersen J.B., Strandbygaard D.J., Larsen S.E., Justesen J.; RT "OAS1p44, a splice variant of the interferon induced human 2'-5' RT oligoadenylate synthetase."; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P48), AND VARIANTS SER-162; THR-352 AND RP THR-361. RX PubMed=17024523; DOI=10.1007/s00239-006-0073-3; RA Perelygin A.A., Zharkikh A.A., Scherbik S.V., Brinton M.A.; RT "The mammalian 2'-5' oligoadenylate synthetase gene family: evidence for RT concerted evolution of paralogous Oas1 genes in Rodentia and RT Artiodactyla."; RL J. Mol. Evol. 63:562-576(2006). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM P46), AND VARIANTS THR-352 AND RP THR-361. RA Lee M.-K., Morshed M.G., Jorgensen D.R., Hasselback P., Goh S.-H.; RT "Susceptibility to infection by West Nile Virus: OAS1 (OAS1 2'-5' RT oligoadenylate synthetase gene) stop codon detected in exon 1 of a normal RT individual heterozygous for the gene."; RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P42), AND VARIANT SER-162. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P42), AND VARIANT SER-162. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P42), AND VARIANT SER-162. RC TISSUE=Small intestine; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P42), AND VARIANT SER-162. RC TISSUE=Brain, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28. RX PubMed=3121313; DOI=10.1111/j.1432-1033.1987.tb13614.x; RA Wathelet M.G., Clauss I.M., Nols C.B., Content J., Huez G.A.; RT "New inducers revealed by the promoter sequence analysis of two interferon- RT activated human genes."; RL Eur. J. Biochem. 169:313-321(1987). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28. RC TISSUE=Liver; RX PubMed=2830497; DOI=10.1128/mcb.7.12.4498-4504.1987; RA Benech P., Vigneron M., Peretz D., Revel M., Chebath J.; RT "Interferon-responsive regulatory elements in the promoter of the human RT 2',5'-oligo(A) synthetase gene."; RL Mol. Cell. Biol. 7:4498-4504(1987). RN [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28. RC TISSUE=Liver; RX PubMed=2456211; DOI=10.1002/j.1460-2075.1988.tb02872.x; RA Rutherford M.N., Hannigan G.E., Williams B.R.G.; RT "Interferon-induced binding of nuclear factors to promoter elements of the RT 2-5A synthetase gene."; RL EMBO J. 7:751-759(1988). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 231-400 (ISOFORM P48), AND INDUCTION. RC TISSUE=Lymphoblast; RX PubMed=2411547; DOI=10.1002/j.1460-2075.1985.tb03848.x; RA Saunders M.E., Gewert D.R., Tugwell M.E., McMahon M., Williams B.R.G.; RT "Human 2-5A synthetase: characterization of a novel cDNA and corresponding RT gene structure."; RL EMBO J. 4:1761-1768(1985). RN [17] RP NUCLEOTIDE SEQUENCE [MRNA] OF 255-364 (ISOFORM P42). RX PubMed=6348777; DOI=10.1073/pnas.80.16.4904; RA Merlin G., Chebath J., Benech P., Metz R., Revel M.; RT "Molecular cloning and sequence of partial cDNA for interferon-induced (2'- RT 5')oligo(A) synthetase mRNA from human cells."; RL Proc. Natl. Acad. Sci. U.S.A. 80:4904-4908(1983). RN [18] RP CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF CYS-331; PHE-332 AND RP LYS-333. RX PubMed=9407111; DOI=10.1074/jbc.272.52.33220; RA Ghosh A., Sarkar S.N., Guo W., Bandyopadhyay S., Sen G.C.; RT "Enzymatic activity of 2'-5'-oligoadenylate synthetase is impaired by RT specific mutations that affect oligomerization of the protein."; RL J. Biol. Chem. 272:33220-33226(1997). RN [19] RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-75 AND ASP-77. RX PubMed=10464285; DOI=10.1074/jbc.274.36.25535; RA Sarkar S.N., Ghosh A., Wang H.W., Sung S.S., Sen G.C.; RT "The nature of the catalytic domain of 2'-5'-oligoadenylate synthetases."; RL J. Biol. Chem. 274:25535-25542(1999). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY RP REGULATION. RX PubMed=12799444; DOI=10.1093/nar/gkg427; RA Eskildsen S., Justesen J., Schierup M.H., Hartmann R.; RT "Characterization of the 2'-5'-oligoadenylate synthetase ubiquitin-like RT family."; RL Nucleic Acids Res. 31:3166-3173(2003). RN [21] RP REVIEW ON FUNCTION. RX PubMed=17408844; DOI=10.1016/j.biochi.2007.02.003; RA Hovanessian A.G., Justesen J.; RT "The human 2'-5'oligoadenylate synthetase family: unique interferon- RT inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond RT formation."; RL Biochimie 89:779-788(2007). RN [22] RP FUNCTION. RX PubMed=18931074; DOI=10.1099/vir.0.2008/003558-0; RA Marques J., Anwar J., Eskildsen-Larsen S., Rebouillat D., Paludan S.R., RA Sen G., Williams B.R., Hartmann R.; RT "The p59 oligoadenylate synthetase-like protein possesses antiviral RT activity that requires the C-terminal ubiquitin-like domain."; RL J. Gen. Virol. 89:2767-2772(2008). RN [23] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19923450; DOI=10.4049/jimmunol.0902728; RA Lin R.J., Yu H.P., Chang B.L., Tang W.C., Liao C.L., Lin Y.L.; RT "Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family RT members against dengue virus infection."; RL J. Immunol. 183:8035-8043(2009). RN [24] RP INDUCTION. RX PubMed=19203244; DOI=10.1089/jir.2008.0050; RA Melchjorsen J., Kristiansen H., Christiansen R., Rintahaka J., RA Matikainen S., Paludan S.R., Hartmann R.; RT "Differential regulation of the OASL and OAS1 genes in response to viral RT infections."; RL J. Interferon Cytokine Res. 29:199-207(2009). RN [25] RP REVIEW. RX PubMed=19904482; DOI=10.1007/s00239-009-9299-1; RA Kjaer K.H., Poulsen J.B., Reintamm T., Saby E., Martensen P.M., Kelve M., RA Justesen J.; RT "Evolution of the 2'-5'-oligoadenylate synthetase family in eukaryotes and RT bacteria."; RL J. Mol. Evol. 69:612-624(2009). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [27] RP REVIEW ON FUNCTION. RX PubMed=21142819; DOI=10.1089/jir.2010.0107; RA Kristiansen H., Gad H.H., Eskildsen-Larsen S., Despres P., Hartmann R.; RT "The oligoadenylate synthetase family: an ancient protein family with RT multiple antiviral activities."; RL J. Interferon Cytokine Res. 31:41-47(2011). RN [28] RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-75 AND ASP-77. RX PubMed=25775560; DOI=10.1073/pnas.1419409112; RA Donovan J., Whitney G., Rath S., Korennykh A.; RT "Structural mechanism of sensing long dsRNA via a noncatalytic domain in RT human oligoadenylate synthetase 3."; RL Proc. Natl. Acad. Sci. U.S.A. 112:3949-3954(2015). RN [29] RP POLYMORPHISM, AND ALTERNATIVE SPLICING. RX PubMed=33633408; DOI=10.1038/s41591-021-01281-1; RA Zhou S., Butler-Laporte G., Nakanishi T., Morrison D.R., Afilalo J., RA Afilalo M., Laurent L., Pietzner M., Kerrison N., Zhao K., RA Brunet-Ratnasingham E., Henry D., Kimchi N., Afrasiabi Z., Rezk N., RA Bouab M., Petitjean L., Guzman C., Xue X., Tselios C., Vulesevic B., RA Adeleye O., Abdullah T., Almamlouk N., Chen Y., Chasse M., Durand M., RA Paterson C., Normark J., Frithiof R., Lipcsey M., Hultstroem M., RA Greenwood C.M.T., Zeberg H., Langenberg C., Thysell E., Pollak M., RA Mooser V., Forgetta V., Kaufmann D.E., Richards J.B.; RT "A Neanderthal OAS1 isoform protects individuals of European ancestry RT against COVID-19 susceptibility and severity."; RL Nat. Med. 27:659-667(2021). RN [30] RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY IFN AND VIRUSES, SUBCELLULAR RP LOCATION, ISOPRENYLATION AT CYS-397, MUTAGENESIS OF CYS-397, POLYMORPHISM, RP AND ALTERNATIVE SPLICING. RX PubMed=34581622; DOI=10.1126/science.abj3624; RG ISARIC4C Investigators; RA Wickenhagen A., Sugrue E., Lytras S., Kuchi S., Noerenberg M., RA Turnbull M.L., Loney C., Herder V., Allan J., Jarmson I., Cameron-Ruiz N., RA Varjak M., Pinto R.M., Lee J.Y., Iselin L., Palmalux N., Stewart D.G., RA Swingler S., Greenwood E.J.D., Crozier T.W.M., Gu Q., Davies E.L., RA Clohisey S., Wang B., Trindade Maranhao Costa F., Freire Santana M., RA de Lima Ferreira L.C., Murphy L., Fawkes A., Meynert A., Grimes G., RA Da Silva Filho J.L., Marti M., Hughes J., Stanton R.J., Wang E.C.Y., Ho A., RA Davis I., Jarrett R.F., Castello A., Robertson D.L., Semple M.G., RA Openshaw P.J.M., Palmarini M., Lehner P.J., Baillie J.K., Rihn S.J., RA Wilson S.J.; RT "A prenylated dsRNA sensor protects against severe COVID-19."; RL Science 374:eabj3624-eabj3624(2021). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-347 IN COMPLEX WITH DSRNA; RP MAGNESIUM IONS AND ATP, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY RP REGULATION, AND MUTAGENESIS OF LYS-66; ASP-148 AND GLU-233. RX PubMed=23319625; DOI=10.1073/pnas.1218528110; RA Donovan J., Dufner M., Korennykh A.; RT "Structural basis for cytosolic double-stranded RNA surveillance by human RT oligoadenylate synthetase 1."; RL Proc. Natl. Acad. Sci. U.S.A. 110:1652-1657(2013). RN [32] RP VARIANTS IMD100 VAL-76; TYR-109 AND VAL-198, AND INVOLVEMENT IN IMD100. RX PubMed=29455859; DOI=10.1016/j.ajhg.2018.01.019; RA Cho K., Yamada M., Agematsu K., Kanegane H., Miyake N., Ueki M., RA Akimoto T., Kobayashi N., Ikemoto S., Tanino M., Fujita A., Hayasaka I., RA Miyamoto S., Tanaka-Kubota M., Nakata K., Shiina M., Ogata K., Minakami H., RA Matsumoto N., Ariga T.; RT "Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar RT Proteinosis with Hypogammaglobulinemia."; RL Am. J. Hum. Genet. 102:480-486(2018). RN [33] RP VARIANTS IMD100 VAL-76; TYR-109; GLY-121 AND VAL-198, CHARACTERIZATION OF RP VARIANTS IMD100 VAL-76; TYR-109; GLY-121 AND VAL-198, INVOLVEMENT IN RP IMD100, AND FUNCTION. RX PubMed=34145065; DOI=10.1126/sciimmunol.abf9564; RA Magg T., Okano T., Koenig L.M., Boehmer D.F.R., Schwartz S.L., Inoue K., RA Heimall J., Licciardi F., Ley-Zaporozhan J., Ferdman R.M., RA Caballero-Oteyza A., Park E.N., Calderon B.M., Dey D., Kanegane H., Cho K., RA Montin D., Reiter K., Griese M., Albert M.H., Rohlfs M., Gray P., Walz C., RA Conn G.L., Sullivan K.E., Klein C., Morio T., Hauck F.; RT "Heterozygous OAS1 gain-of-function variants cause an autoinflammatory RT immunodeficiency."; RL Sci. Immunol. 6:0-0(2021). CC -!- FUNCTION: Interferon-induced, dsRNA-activated antiviral enzyme which CC plays a critical role in cellular innate antiviral response CC (PubMed:34581622). In addition, it may also play a role in other CC cellular processes such as apoptosis, cell growth, differentiation and CC gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates CC (2-5A) from ATP which then bind to the inactive monomeric form of CC ribonuclease L (RNase L) leading to its dimerization and subsequent CC activation. Activation of RNase L leads to degradation of cellular as CC well as viral RNA, resulting in the inhibition of protein synthesis, CC thus terminating viral replication (PubMed:34581622, PubMed:34145065). CC Can mediate the antiviral effect via the classical RNase L-dependent CC pathway or an alternative antiviral pathway independent of RNase L. The CC secreted form displays antiviral effect against vesicular stomatitis CC virus (VSV), herpes simplex virus type 2 (HSV-2), and CC encephalomyocarditis virus (EMCV) and stimulates the alternative CC antiviral pathway independent of RNase L. {ECO:0000269|PubMed:12799444, CC ECO:0000269|PubMed:18931074, ECO:0000269|PubMed:19923450, CC ECO:0000269|PubMed:23319625, ECO:0000269|PubMed:34145065, CC ECO:0000269|PubMed:34581622}. CC -!- FUNCTION: [Isoform p46]: When prenylated at C-terminal, acts as a CC double-stranded RNA (dsRNA) sensor specifically targeted to membranous CC replicative organelles in SARS coronavirus-2/SARS-CoV-2 infected cells CC where it binds to dsRNA structures in the SARS-CoV-2 5'-UTR and CC initiates a potent block to SARS-CoV-2 replication. Recognizes short CC stretches of dsRNA and activates RNase L. The binding is remarkably CC specific, with two conserved stem loops in the SARS-CoV-2 CC 5'- untranslated region (UTR) constituting the principal viral target CC (PubMed:34581622). The same mechanism is necessary to initiate a block CC to cardiovirus EMCV (PubMed:34581622). {ECO:0000269|PubMed:34581622}. CC -!- FUNCTION: [Isoform p42]: Not prenylated at C-terminal, is diffusely CC localized and unable to initiate a detectable block to SARS-CoV-2 CC replication. {ECO:0000269|PubMed:34581622}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3 ATP = 5'-triphosphoadenylyl-(2'->5')-adenylyl-(2'->5')- CC adenosine + 2 diphosphate; Xref=Rhea:RHEA:34407, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:67143; EC=2.7.7.84; CC Evidence={ECO:0000269|PubMed:10464285, ECO:0000269|PubMed:12799444, CC ECO:0000269|PubMed:23319625, ECO:0000269|PubMed:25775560, CC ECO:0000269|PubMed:3753689, ECO:0000269|PubMed:3754863, CC ECO:0000269|PubMed:9407111}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:23319625}; CC -!- ACTIVITY REGULATION: Produced as a latent enzyme which is activated by CC dsRNA generated during the course of viral infection. The dsRNA CC activator must be at least 15 nucleotides long, and no modification of CC the 2'-hydroxyl group is tolerated (PubMed:34581622). ssRNA or dsDNA do CC not act as activators. {ECO:0000269|PubMed:12799444, CC ECO:0000269|PubMed:23319625, ECO:0000269|PubMed:34581622}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.31 mM for ATP {ECO:0000269|PubMed:12799444}; CC -!- SUBUNIT: Monomer (PubMed:9407111). Homotetramer (PubMed:9407111, CC PubMed:23319625). {ECO:0000269|PubMed:23319625, CC ECO:0000269|PubMed:9407111}. CC -!- INTERACTION: CC P00973; P12814: ACTN1; NbExp=4; IntAct=EBI-3932815, EBI-351710; CC P00973; O00471: EXOC5; NbExp=3; IntAct=EBI-3932815, EBI-949824; CC P00973; Q96LA8: PRMT6; NbExp=2; IntAct=EBI-3932815, EBI-912440; CC P00973; P14373: TRIM27; NbExp=5; IntAct=EBI-3932815, EBI-719493; CC P00973-2; P12814: ACTN1; NbExp=3; IntAct=EBI-12081862, EBI-351710; CC P00973-2; Q96RK4: BBS4; NbExp=5; IntAct=EBI-12081862, EBI-1805814; CC P00973-2; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-12081862, EBI-3866319; CC P00973-2; O00471: EXOC5; NbExp=6; IntAct=EBI-12081862, EBI-949824; CC P00973-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12081862, EBI-618309; CC P00973-2; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-12081862, EBI-10961706; CC P00973-2; Q96T51-2: RUFY1; NbExp=3; IntAct=EBI-12081862, EBI-12192715; CC P00973-2; P14373: TRIM27; NbExp=6; IntAct=EBI-12081862, EBI-719493; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19923450, CC ECO:0000269|PubMed:3753689, ECO:0000269|PubMed:3754863}. Mitochondrion CC {ECO:0000269|PubMed:19923450}. Nucleus {ECO:0000269|PubMed:19923450, CC ECO:0000269|PubMed:3753689}. Microsome {ECO:0000269|PubMed:19923450}. CC Endoplasmic reticulum {ECO:0000269|PubMed:19923450}. Secreted CC {ECO:0000250|UniProtKB:Q29599}. Note=Associated with different CC subcellular fractions such as mitochondrial, nuclear, and rough/smooth CC microsomal fractions. {ECO:0000269|PubMed:19923450}. CC -!- SUBCELLULAR LOCATION: [Isoform p46]: Note=(Microbial infection) In SARS CC coronavirus-2/SARS-CoV-2 infected cells, prenylated form localizes to CC membranous perinuclear structures reminiscent of the endoplasmic CC reticulum rich in viral dsRNA which are SARS-CoV-2 replicative CC organelles. {ECO:0000269|PubMed:34581622}. CC -!- SUBCELLULAR LOCATION: [Isoform p42]: Note=(Microbial infection) In SARS CC coronavirus-2/SARS-CoV-2 infected cells, since its not prenylated, is CC diffusely localized and unable to initiate a detectable block to SARS- CC CoV-2 replication. {ECO:0000269|PubMed:34581622}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=p46 {ECO:0000303|PubMed:33633408, ECO:0000303|PubMed:34581622}; CC Synonyms=46 kDa, E18; CC IsoId=P00973-1; Sequence=Displayed; CC Name=p42 {ECO:0000303|PubMed:33633408, ECO:0000303|PubMed:34581622}; CC Synonyms=41 kDa, E16, 3-9, p41; CC IsoId=P00973-2; Sequence=VSP_003738, VSP_003739; CC Name=p48; Synonyms=9-2; CC IsoId=P00973-3; Sequence=VSP_003740; CC Name=p44; CC IsoId=P00973-4; Sequence=VSP_060747, VSP_060748; CC -!- TISSUE SPECIFICITY: Expressed in lungs. {ECO:0000269|PubMed:34581622}. CC -!- INDUCTION: By type I interferon (IFN) and viruses. CC {ECO:0000269|PubMed:19203244, ECO:0000269|PubMed:2411547, CC ECO:0000269|PubMed:34581622}. CC -!- PTM: [Isoform p46]: Prenylated at C-terminal. C-terminal prenylation is CC necessary to initiate a block to SARS-CoV-2 and is associated with CC protection from severe COVID-1. The prenylated form is targeted to CC perinuclear structures rich in viral dsRNA, whereas the non-prenylated CC form is diffusely localized and unable to initiate a detectable block CC to SARS-CoV-2 replication (Probable). C-terminal prenylation is also CC necessary to initiate a block to cardiovirus EMCV (Probable). CC {ECO:0000305|PubMed:34581622}. CC -!- PTM: [Isoform p42]: Not prenylated at C-terminal. The non-prenylated CC form is diffusely localized and unable to initiate a detectable block CC to SARS-CoV-2 replication. {ECO:0000269|PubMed:34581622}. CC -!- POLYMORPHISM: Polymorphism dbSNP:rs10774671 is associated with CC protection against severe COVID-19 disease (PubMed:34581622, CC PubMed:33633408). In humans, the OAS1 protein is expressed as two major CC forms designated p46 and p42. The longer p46 isoform is generated by CC alternative splicing to an exon downstream of the terminal exon used by CC the p42 isoform. Although all human genotypes contain the exon that CC completes the transcript encoding p46, an intronic SNP (rs10774671) CC determines OAS1 exon usage. Alleles with a G at this SNP (G alleles) CC specify expression of the p46 isoform and some p42, whereas alleles CC with A at this position predominantly encode the p42 isoform and cannot CC express the p46 isoform (PubMed:34581622). The p42 isoform, which is CC the most common isoform in humans (~61% of alleles), has no detectable CC anti-SARS-CoV-2 activity. The p46 isoform has anti-SARS-CoV-2 activity CC (PubMed:34581622). {ECO:0000269|PubMed:34581622, CC ECO:0000303|PubMed:33633408}. CC -!- DISEASE: Immunodeficiency 100 with pulmonary alveolar proteinosis and CC hypogammaglobulinemia (IMD100) [MIM:618042]: An autosomal dominant CC disorder characterized by onset of respiratory insufficiency due to CC pulmonary alveolar proteinosis in the first months of life. Disease CC development appears to be influenced or triggered by viral infection. CC Patients also have hypogammaglobulinemia, leukocytosis, and CC splenomegaly. {ECO:0000269|PubMed:29455859, CC ECO:0000269|PubMed:34145065}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the 2-5A synthase family. {ECO:0000305}. CC -!- CAUTION: PubMed:1651324 sequence was originally thought to originate CC from mouse. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA39857.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA39858.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA59955.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAD96726.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA26497.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=CAA30164.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAF33358.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Luck of the draw - Issue 246 CC of April 2022; CC URL="https://web.expasy.org/spotlight/back_issues/246/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M11809; AAB59552.1; -; Genomic_DNA. DR EMBL; M11805; AAB59552.1; JOINED; Genomic_DNA. DR EMBL; M11806; AAB59552.1; JOINED; Genomic_DNA. DR EMBL; M11807; AAB59552.1; JOINED; Genomic_DNA. DR EMBL; M11808; AAB59552.1; JOINED; Genomic_DNA. DR EMBL; M11810; AAB59553.1; -; Genomic_DNA. DR EMBL; X02874; CAA26633.1; -; mRNA. DR EMBL; X02875; CAA26634.1; -; mRNA. DR EMBL; X04371; CAB51602.1; -; mRNA. DR EMBL; D00068; BAA00047.1; -; mRNA. DR EMBL; M63849; AAA39857.1; ALT_INIT; Genomic_DNA. DR EMBL; M63850; AAA39858.1; ALT_INIT; Genomic_DNA. DR EMBL; AJ629455; CAF33358.1; ALT_FRAME; mRNA. DR EMBL; AY730628; AAW63050.1; -; mRNA. DR EMBL; DQ445949; ABE27977.1; -; Genomic_DNA. DR EMBL; AK291003; BAF83692.1; -; mRNA. DR EMBL; BT006785; AAP35431.1; -; mRNA. DR EMBL; AK223006; BAD96726.1; ALT_INIT; mRNA. DR EMBL; AC004551; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000562; AAH00562.4; -; mRNA. DR EMBL; BC061587; AAH61587.1; -; mRNA. DR EMBL; BC071981; AAH71981.3; -; mRNA. DR EMBL; X06560; CAA29803.1; -; Genomic_DNA. DR EMBL; M18099; AAA59955.1; ALT_INIT; Genomic_DNA. DR EMBL; X07179; CAA30164.1; ALT_INIT; Genomic_DNA. DR EMBL; X02661; CAA26497.1; ALT_SEQ; mRNA. DR CCDS; CCDS31905.1; -. [P00973-3] DR CCDS; CCDS41838.1; -. [P00973-1] DR CCDS; CCDS44980.1; -. [P00973-2] DR CCDS; CCDS81742.1; -. [P00973-4] DR PIR; A39417; SYMSO2. DR PIR; A91013; SYHU16. DR PIR; B24359; SYHU18. DR PIR; B39417; SYMSO3. DR RefSeq; NP_001027581.1; NM_001032409.2. [P00973-3] DR RefSeq; NP_001307080.1; NM_001320151.1. [P00973-4] DR RefSeq; NP_002525.2; NM_002534.3. [P00973-2] DR RefSeq; NP_058132.2; NM_016816.3. [P00973-1] DR PDB; 4IG8; X-ray; 2.70 A; A=1-347. DR PDBsum; 4IG8; -. DR AlphaFoldDB; P00973; -. DR SMR; P00973; -. DR BioGRID; 110992; 19. DR IntAct; P00973; 15. DR MINT; P00973; -. DR STRING; 9606.ENSP00000388001; -. DR DrugBank; DB02987; Cysteine-S-acetamide. DR iPTMnet; P00973; -. DR PhosphoSitePlus; P00973; -. DR BioMuta; OAS1; -. DR DMDM; 296439492; -. DR EPD; P00973; -. DR jPOST; P00973; -. DR MassIVE; P00973; -. DR MaxQB; P00973; -. DR PaxDb; 9606-ENSP00000388001; -. DR PeptideAtlas; P00973; -. DR ProteomicsDB; 29167; -. DR ProteomicsDB; 51294; -. [P00973-1] DR ProteomicsDB; 51295; -. [P00973-2] DR ProteomicsDB; 51296; -. [P00973-3] DR ProteomicsDB; 51297; -. [P00973-4] DR Pumba; P00973; -. DR Antibodypedia; 1275; 357 antibodies from 34 providers. DR DNASU; 4938; -. DR Ensembl; ENST00000202917.10; ENSP00000202917.5; ENSG00000089127.15. [P00973-1] DR Ensembl; ENST00000445409.7; ENSP00000388001.2; ENSG00000089127.15. [P00973-3] DR Ensembl; ENST00000452357.7; ENSP00000415721.2; ENSG00000089127.15. [P00973-2] DR Ensembl; ENST00000551241.6; ENSP00000448790.1; ENSG00000089127.15. [P00973-4] DR Ensembl; ENST00000680189.1; ENSP00000505572.1; ENSG00000089127.15. [P00973-1] DR Ensembl; ENST00000681934.1; ENSP00000505482.1; ENSG00000089127.15. [P00973-1] DR GeneID; 4938; -. DR KEGG; hsa:4938; -. DR MANE-Select; ENST00000202917.10; ENSP00000202917.5; NM_016816.4; NP_058132.2. DR UCSC; uc001tub.4; human. [P00973-1] DR AGR; HGNC:8086; -. DR CTD; 4938; -. DR DisGeNET; 4938; -. DR GeneCards; OAS1; -. DR HGNC; HGNC:8086; OAS1. DR HPA; ENSG00000089127; Tissue enhanced (salivary gland, urinary bladder). DR MalaCards; OAS1; -. DR MIM; 164350; gene. DR MIM; 618042; phenotype. DR neXtProt; NX_P00973; -. DR OpenTargets; ENSG00000089127; -. DR Orphanet; 572428; Infantile-onset pulmonary alveolar proteinosis-hypogammaglobulinemia. DR PharmGKB; PA31875; -. DR VEuPathDB; HostDB:ENSG00000089127; -. DR eggNOG; ENOG502RH25; Eukaryota. DR GeneTree; ENSGT00510000046406; -. DR InParanoid; P00973; -. DR OMA; VHIISTF; -. DR OrthoDB; 4638494at2759; -. DR PhylomeDB; P00973; -. DR TreeFam; TF329749; -. DR BioCyc; MetaCyc:ENSG00000089127-MONOMER; -. DR BRENDA; 2.7.7.84; 2681. DR PathwayCommons; P00973; -. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-8983711; OAS antiviral response. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR SABIO-RK; P00973; -. DR SignaLink; P00973; -. DR BioGRID-ORCS; 4938; 17 hits in 1157 CRISPR screens. DR ChiTaRS; OAS1; human. DR GeneWiki; OAS1; -. DR GenomeRNAi; 4938; -. DR Pharos; P00973; Tbio. DR PRO; PR:P00973; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P00973; Protein. DR Bgee; ENSG00000089127; Expressed in monocyte and 165 other cell types or tissues. DR ExpressionAtlas; P00973; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:ARUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; IDA:ARUK-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL. DR GO; GO:0005840; C:ribosome; IDA:ARUK-UCL. DR GO; GO:0001730; F:2'-5'-oligoadenylate synthetase activity; IDA:ARUK-UCL. DR GO; GO:0005524; F:ATP binding; TAS:UniProtKB. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProtKB. DR GO; GO:0035457; P:cellular response to interferon-alpha; IDA:UniProtKB. DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:ARUK-UCL. DR GO; GO:0098586; P:cellular response to virus; IEP:ARUK-UCL. DR GO; GO:0042742; P:defense response to bacterium; IMP:ARUK-UCL. DR GO; GO:0051607; P:defense response to virus; IDA:ARUK-UCL. DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; IMP:UniProtKB. DR GO; GO:0070106; P:interleukin-27-mediated signaling pathway; IEP:ARUK-UCL. DR GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; IMP:ARUK-UCL. DR GO; GO:0071659; P:negative regulation of IP-10 production; IMP:ARUK-UCL. DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:ARUK-UCL. DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB. DR GO; GO:1901857; P:positive regulation of cellular respiration; IDA:ARUK-UCL. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:ARUK-UCL. DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IMP:ARUK-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR GO; GO:0060700; P:regulation of ribonuclease activity; IDA:ARUK-UCL. DR GO; GO:0009615; P:response to virus; IDA:UniProtKB. DR GO; GO:0043129; P:surfactant homeostasis; IMP:ARUK-UCL. DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IMP:ARUK-UCL. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IMP:ARUK-UCL. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IMP:ARUK-UCL. DR CDD; cd05400; NT_2-5OAS_ClassI-CCAase; 1. DR Gene3D; 1.10.1410.20; 2'-5'-oligoadenylate synthetase 1, domain 2; 1. DR Gene3D; 3.30.460.10; Beta Polymerase, domain 2; 1. DR InterPro; IPR018952; 2-5-oligoAdlate_synth_1_dom2/C. DR InterPro; IPR006117; 2-5OAS_C_CS. DR InterPro; IPR043518; 2-5OAS_N_CS. DR InterPro; IPR006116; NT_2-5OAS_ClassI-CCAase. DR InterPro; IPR043519; NT_sf. DR InterPro; IPR002934; Polymerase_NTP_transf_dom. DR PANTHER; PTHR11258:SF13; 2'-5'-OLIGOADENYLATE SYNTHASE 1; 1. DR PANTHER; PTHR11258; 2-5 OLIGOADENYLATE SYNTHETASE; 1. DR Pfam; PF01909; NTP_transf_2; 1. DR Pfam; PF10421; OAS1_C; 1. DR SUPFAM; SSF81301; Nucleotidyltransferase; 1. DR SUPFAM; SSF81631; PAP/OAS1 substrate-binding domain; 1. DR PROSITE; PS00832; 25A_SYNTH_1; 1. DR PROSITE; PS00833; 25A_SYNTH_2; 1. DR PROSITE; PS50152; 25A_SYNTH_3; 1. DR Genevisible; P00973; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Antiviral defense; ATP-binding; KW Cytoplasm; Disease variant; Endoplasmic reticulum; Host-virus interaction; KW Immunity; Innate immunity; Lipoprotein; Magnesium; Metal-binding; KW Microsome; Mitochondrion; Nucleotide-binding; Nucleotidyltransferase; KW Nucleus; Prenylation; Reference proteome; RNA-binding; Secreted; KW Transferase. FT CHAIN 1..400 FT /note="2'-5'-oligoadenylate synthase 1" FT /id="PRO_0000160259" FT REGION 13..60 FT /note="Interaction with dsRNA" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT REGION 200..210 FT /note="Interaction with dsRNA" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT BINDING 63 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT BINDING 75 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT BINDING 77 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT BINDING 148 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT BINDING 210 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P29728" FT BINDING 213 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT BINDING 229 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:23319625, FT ECO:0007744|PDB:4IG8" FT SITE 158 FT /note="Interaction with dsRNA" FT /evidence="ECO:0007744|PDB:4IG8" FT LIPID 397 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000305|PubMed:34581622" FT VAR_SEQ 347..400 FT /note="AESNSADDETDDPRRYQKYGYIGTHEYPHFSHRPSTLQAASTPQAEEDWTCT FT IL -> TQHTPGSIHPTGRRGLDLHHPLNASASWGKGLQCYLDQFLHFQVGLLIQRGQS FT SSVSWCIIQDRTQVS (in isoform p48)" FT /evidence="ECO:0000303|PubMed:17024523, FT ECO:0000303|PubMed:2411547" FT /id="VSP_003740" FT VAR_SEQ 347..364 FT /note="AESNSADDETDDPRRYQK -> VRPPASSLPFIPAPLHEA (in isoform FT p42)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:2416561, FT ECO:0000303|PubMed:3753689, ECO:0000303|PubMed:3754863, FT ECO:0000303|PubMed:6348777, ECO:0000303|Ref.10, FT ECO:0000303|Ref.9" FT /id="VSP_003738" FT VAR_SEQ 347..360 FT /note="AESNSADDETDDPR -> VNLTLVGRRNYTNN (in isoform p44)" FT /id="VSP_060747" FT VAR_SEQ 361..400 FT /note="Missing (in isoform p44)" FT /id="VSP_060748" FT VAR_SEQ 365..400 FT /note="Missing (in isoform p42)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:2416561, FT ECO:0000303|PubMed:3753689, ECO:0000303|PubMed:3754863, FT ECO:0000303|PubMed:6348777, ECO:0000303|Ref.10, FT ECO:0000303|Ref.9" FT /id="VSP_003739" FT VARIANT 31 FT /note="N -> D (in dbSNP:rs1050994)" FT /evidence="ECO:0000269|PubMed:2416561" FT /id="VAR_060471" FT VARIANT 76 FT /note="A -> V (in IMD100; results in increased FT 2'-5'-oligoadenylate synthetase activity leading to FT increased RNase L-mediated cellular RNA degradation, FT translational arrest and apoptosis)" FT /evidence="ECO:0000269|PubMed:29455859, FT ECO:0000269|PubMed:34145065" FT /id="VAR_087200" FT VARIANT 109 FT /note="C -> Y (in IMD100; results in increased FT 2'-5'-oligoadenylate synthetase activity leading to FT increased RNase L-mediated cellular RNA degradation, FT translational arrest and apoptosis)" FT /evidence="ECO:0000269|PubMed:29455859, FT ECO:0000269|PubMed:34145065" FT /id="VAR_087201" FT VARIANT 121 FT /note="V -> G (in IMD100; results in increased FT 2'-5'-oligoadenylate synthetase activity leading to FT increased RNase L-mediated cellular RNA degradation, FT translational arrest and apoptosis)" FT /evidence="ECO:0000269|PubMed:34145065" FT /id="VAR_087202" FT VARIANT 127 FT /note="G -> R (in dbSNP:rs4767022)" FT /id="VAR_060472" FT VARIANT 162 FT /note="G -> S (in dbSNP:rs1131454)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1651324, FT ECO:0000269|PubMed:17024523, ECO:0000269|PubMed:2416561, FT ECO:0000269|PubMed:3753689, ECO:0000269|PubMed:3754863, FT ECO:0000269|Ref.10, ECO:0000269|Ref.9" FT /id="VAR_034872" FT VARIANT 198 FT /note="L -> V (in IMD100; results in increased FT 2'-5'-oligoadenylate synthetase activity leading to FT increased RNase L-mediated cellular RNA degradation, FT translational arrest and apoptosis)" FT /evidence="ECO:0000269|PubMed:29455859, FT ECO:0000269|PubMed:34145065" FT /id="VAR_087203" FT VARIANT 352 FT /note="A -> T (in dbSNP:rs1131476)" FT /evidence="ECO:0000269|PubMed:17024523, FT ECO:0000269|PubMed:2416561, ECO:0000269|Ref.7" FT /id="VAR_060473" FT VARIANT 354 FT /note="D -> G (in dbSNP:rs35919998)" FT /id="VAR_057658" FT VARIANT 361 FT /note="R -> T (in dbSNP:rs1051042)" FT /evidence="ECO:0000269|PubMed:17024523, FT ECO:0000269|PubMed:2416561, ECO:0000269|Ref.7" FT /id="VAR_057659" FT MUTAGEN 66 FT /note="K->A: Decreased enzyme activity." FT /evidence="ECO:0000269|PubMed:23319625" FT MUTAGEN 75 FT /note="D->A: Loss of activity; when associated with A-77." FT /evidence="ECO:0000269|PubMed:10464285, FT ECO:0000269|PubMed:25775560" FT MUTAGEN 77 FT /note="D->A: Loss of activity; when associated with A-75." FT /evidence="ECO:0000269|PubMed:10464285, FT ECO:0000269|PubMed:25775560" FT MUTAGEN 148 FT /note="D->A: Strongly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:23319625" FT MUTAGEN 233 FT /note="E->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:23319625" FT MUTAGEN 331 FT /note="C->A: Loss of activity; when associated with A-332 FT and A-333." FT /evidence="ECO:0000269|PubMed:9407111" FT MUTAGEN 332 FT /note="F->A: Loss of activity; when associated with A-331 FT and A-333." FT /evidence="ECO:0000269|PubMed:9407111" FT MUTAGEN 333 FT /note="K->A: Loss of activity; when associated with A-331 FT and A-332." FT /evidence="ECO:0000269|PubMed:9407111" FT MUTAGEN 397 FT /note="C->A: Not prenylated and diffusely distributed. Loss FT of antiviral activity." FT /evidence="ECO:0000269|PubMed:34581622" FT CONFLICT 18 FT /note="D -> E (in Ref. 4; AAA39857)" FT /evidence="ECO:0000305" FT CONFLICT 111 FT /note="R -> S (in Ref. 12; AAH71981)" FT /evidence="ECO:0000305" FT CONFLICT 115 FT /note="F -> L (in Ref. 1; AAB59552/AAB59553/CAA26633)" FT /evidence="ECO:0000305" FT CONFLICT 120 FT /note="E -> V (in Ref. 10; BAD96726)" FT /evidence="ECO:0000305" FT CONFLICT 122 FT /note="Q -> QE (in Ref. 4; AAA39858)" FT /evidence="ECO:0000305" FT CONFLICT 157 FT /note="G -> D (in Ref. 4; AAA39857)" FT /evidence="ECO:0000305" FT CONFLICT 176 FT /note="E -> D (in Ref. 4; AAA39858)" FT /evidence="ECO:0000305" FT CONFLICT 295 FT /note="R -> T (in Ref. 2; CAB51602)" FT /evidence="ECO:0000305" FT CONFLICT 315 FT /note="G -> R (in Ref. 2; CAB51602)" FT /evidence="ECO:0000305" FT TURN 4..6 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 9..11 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 12..19 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 24..43 FT /evidence="ECO:0007829|PDB:4IG8" FT TURN 44..46 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 55..61 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 62..66 FT /evidence="ECO:0007829|PDB:4IG8" FT TURN 71..73 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 76..84 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 88..111 FT /evidence="ECO:0007829|PDB:4IG8" FT TURN 112..114 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 132..137 FT /evidence="ECO:0007829|PDB:4IG8" FT TURN 139..141 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 145..152 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 167..179 FT /evidence="ECO:0007829|PDB:4IG8" FT TURN 183..186 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 187..190 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 191..195 FT /evidence="ECO:0007829|PDB:4IG8" FT TURN 196..200 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 203..223 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 229..243 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 251..263 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 265..267 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 278..280 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 281..290 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 297..300 FT /evidence="ECO:0007829|PDB:4IG8" FT STRAND 303..308 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 313..326 FT /evidence="ECO:0007829|PDB:4IG8" FT HELIX 330..332 FT /evidence="ECO:0007829|PDB:4IG8" FT CONFLICT P00973-3:397 FT /note="G -> R (in Ref. 4; AAA39858, 6; AAW63050 and 16; FT CAA26497)" FT /evidence="ECO:0000305" SQ SEQUENCE 400 AA; 46029 MW; 03F0A3AA17DAD4E4 CRC64; MMDLRNTPAK SLDKFIEDYL LPDTCFRMQI NHAIDIICGF LKERCFRGSS YPVCVSKVVK GGSSGKGTTL RGRSDADLVV FLSPLTTFQD QLNRRGEFIQ EIRRQLEACQ RERAFSVKFE VQAPRWGNPR ALSFVLSSLQ LGEGVEFDVL PAFDALGQLT GGYKPNPQIY VKLIEECTDL QKEGEFSTCF TELQRDFLKQ RPTKLKSLIR LVKHWYQNCK KKLGKLPPQY ALELLTVYAW ERGSMKTHFN TAQGFRTVLE LVINYQQLCI YWTKYYDFKN PIIEKYLRRQ LTKPRPVILD PADPTGNLGG GDPKGWRQLA QEAEAWLNYP CFKNWDGSPV SSWILLAESN SADDETDDPR RYQKYGYIGT HEYPHFSHRP STLQAASTPQ AEEDWTCTIL //