OAS1_HUMAN
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 03-AUG-2022, entry version 221.
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).
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). Can mediate the
CC antiviral effect via the classical RNase L-dependent pathway or an
CC alternative antiviral pathway independent of RNase L. The secreted form
CC displays antiviral effect against vesicular stomatitis virus (VSV),
CC herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus
CC (EMCV) and stimulates the alternative antiviral pathway independent of
CC RNase L. {ECO:0000269|PubMed:12799444, ECO:0000269|PubMed:18931074,
CC ECO:0000269|PubMed:19923450, ECO:0000269|PubMed:23319625,
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 -!- 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 ---------------------------------------------------------------------------
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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; P00973; -.
DR PeptideAtlas; P00973; -.
DR PRIDE; 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 Antibodypedia; 1275; 330 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 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 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 OMA; VGRRHYT; -.
DR OrthoDB; 866189at2759; -.
DR PhylomeDB; P00973; -.
DR TreeFam; TF329749; -.
DR BioCyc; MetaCyc:ENSG00000089127-MON; -.
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 1076 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 164 other tissues.
DR ExpressionAtlas; P00973; baseline and differential.
DR Genevisible; P00973; HS.
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; IEP:ARUK-UCL.
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:UniProtKB.
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 signaling pathway; IMP:ARUK-UCL.
DR CDD; cd05400; NT_2-5OAS_ClassI-CCAase; 1.
DR Gene3D; 3.30.460.10; -; 1.
DR InterPro; IPR018952; 2-5-oligoAdlate_synth_1_dom2/C.
DR InterPro; IPR026774; 2-5A_synthase.
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; PTHR11258; 1.
DR Pfam; PF01909; NTP_transf_2; 1.
DR Pfam; PF10421; OAS1_C; 1.
DR SUPFAM; SSF81301; SSF81301; 1.
DR PROSITE; PS00832; 25A_SYNTH_1; 1.
DR PROSITE; PS00833; 25A_SYNTH_2; 1.
DR PROSITE; PS50152; 25A_SYNTH_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antiviral defense; ATP-binding;
KW Cytoplasm; Endoplasmic reticulum; Host-virus interaction; Immunity;
KW Innate immunity; Lipoprotein; Magnesium; Metal-binding; Microsome;
KW Mitochondrion; Nucleotide-binding; Nucleotidyltransferase; Nucleus;
KW Prenylation; Reference proteome; RNA-binding; Secreted; 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 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 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
