ID   OAS3_HUMAN              Reviewed;        1087 AA.
AC   Q9Y6K5; Q2HJ14; Q9H3P5;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 3.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=2'-5'-oligoadenylate synthase 3;
DE            Short=(2-5')oligo(A) synthase 3;
DE            Short=2-5A synthase 3;
DE            EC=2.7.7.84 {ECO:0000269|PubMed:25775560, ECO:0000269|PubMed:9880533};
DE   AltName: Full=p100 OAS;
DE            Short=p100OAS;
GN   Name=OAS3; ORFNames=P/OKcl.4;
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 [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP   ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION.
RX   PubMed=9880533; DOI=10.1074/jbc.274.3.1557;
RA   Rebouillat D., Hovnanian A., Marie I., Hovanessian A.G.;
RT   "The 100-kDa 2',5'-oligoadenylate synthetase catalyzing preferentially the
RT   synthesis of dimeric pppA2'p5'A molecules is composed of three homologous
RT   domains.";
RL   J. Biol. Chem. 274:1557-1565(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LYS-18.
RC   TISSUE=Pancreatic cancer;
RX   PubMed=11280764;
RA   Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K.;
RT   "Molecular basis of T cell-mediated recognition of pancreatic cancer
RT   cells.";
RL   Cancer Res. 61:2038-2046(2001).
RN   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-381.
RC   TISSUE=Brain;
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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-59.
RC   TISSUE=Monocyte;
RX   PubMed=11112351; DOI=10.1006/geno.2000.6382;
RA   Rebouillat D., Hovnanian A., David G., Hovanessian A.G., Williams B.R.;
RT   "Characterization of the gene encoding the 100-kDa form of human 2',
RT   5'oligoadenylate synthetase.";
RL   Genomics 70:232-240(2000).
RN   [6]
RP   PROTEIN SEQUENCE OF 1-17; 118-132; 244-253 AND 371-378, ACETYLATION AT
RP   MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Prostatic carcinoma;
RA   Bienvenut W.V., Gao M., Leug H.;
RL   Submitted (JUN-2009) to UniProtKB.
RN   [7]
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   [8]
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   [9]
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   [10]
RP   FUNCTION.
RX   PubMed=19056102; DOI=10.1016/j.virol.2008.10.021;
RA   Brehin A.C., Casademont I., Frenkiel M.P., Julier C., Sakuntabhai A.,
RA   Despres P.;
RT   "The large form of human 2',5'-Oligoadenylate Synthetase (OAS3) exerts
RT   antiviral effect against Chikungunya virus.";
RL   Virology 384:216-222(2009).
RN   [11]
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   [12]
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   [13]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-365, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-371 IN COMPLEX WITH DSRNA,
RP   CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ARG-30; ARG-41;
RP   GLU-76; SER-145 AND 816-ASP--ASP-818.
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).
CC   -!- FUNCTION: Interferon-induced, dsRNA-activated antiviral enzyme which
CC       plays a critical role in cellular innate antiviral response. In
CC       addition, it may also play a role in other cellular processes such as
CC       apoptosis, cell growth, differentiation and gene regulation.
CC       Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from
CC       ATP which then bind to the inactive monomeric form of ribonuclease L
CC       (RNase L) leading to its dimerization and subsequent activation.
CC       Activation of RNase L leads to degradation of cellular as well as viral
CC       RNA, resulting in the inhibition of protein synthesis, thus terminating
CC       viral replication. Can mediate the antiviral effect via the classical
CC       RNase L-dependent pathway or an alternative antiviral pathway
CC       independent of RNase L. Displays antiviral activity against Chikungunya
CC       virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest
CC       virus (SFV). {ECO:0000269|PubMed:19056102, ECO:0000269|PubMed:19923450,
CC       ECO:0000269|PubMed:9880533}.
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:25775560, ECO:0000269|PubMed:9880533};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000305|PubMed:9880533};
CC   -!- ACTIVITY REGULATION: Produced as a latent enzyme which is activated by
CC       dsRNA generated during the course of viral infection (Probable).
CC       Strongly activated by long dsRNAs at least 50 nucleotides in length
CC       (PubMed:25775560). ssRNA does not activate the enzyme
CC       (PubMed:25775560). {ECO:0000269|PubMed:25775560, ECO:0000305}.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:25775560}.
CC   -!- INTERACTION:
CC       Q9Y6K5; Q7L2E3: DHX30; NbExp=2; IntAct=EBI-6115729, EBI-1211456;
CC       Q9Y6K5; P56537: EIF6; NbExp=2; IntAct=EBI-6115729, EBI-372243;
CC       Q9Y6K5; Q8IY81: FTSJ3; NbExp=2; IntAct=EBI-6115729, EBI-744088;
CC       Q9Y6K5; Q12894: IFRD2; NbExp=2; IntAct=EBI-6115729, EBI-2512448;
CC       Q9Y6K5; Q7Z434: MAVS; NbExp=2; IntAct=EBI-6115729, EBI-995373;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC   -!- TISSUE SPECIFICITY: Present at high level in placenta trophoblast.
CC   -!- INDUCTION: By type I interferon (IFN) and viruses.
CC   -!- DOMAIN: OAS domain 3 is catalytically active. OAS domain 1 has no
CC       catalytic activity but is essential for recognition of long dsRNAs.
CC       {ECO:0000269|PubMed:25775560}.
CC   -!- SIMILARITY: Belongs to the 2-5A synthase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD28543.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF063613; AAD28543.1; ALT_FRAME; mRNA.
DR   EMBL; AB044545; BAB18647.1; -; mRNA.
DR   EMBL; AC004551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC113746; AAI13747.1; -; mRNA.
DR   EMBL; AF251351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS44981.1; -.
DR   RefSeq; NP_006178.2; NM_006187.3.
DR   PDB; 4S3N; X-ray; 2.00 A; A=1-371.
DR   PDBsum; 4S3N; -.
DR   AlphaFoldDB; Q9Y6K5; -.
DR   SMR; Q9Y6K5; -.
DR   BioGRID; 110994; 63.
DR   IntAct; Q9Y6K5; 43.
DR   MINT; Q9Y6K5; -.
DR   STRING; 9606.ENSP00000228928; -.
DR   GlyGen; Q9Y6K5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Y6K5; -.
DR   PhosphoSitePlus; Q9Y6K5; -.
DR   SwissPalm; Q9Y6K5; -.
DR   BioMuta; OAS3; -.
DR   DMDM; 317373408; -.
DR   EPD; Q9Y6K5; -.
DR   jPOST; Q9Y6K5; -.
DR   MassIVE; Q9Y6K5; -.
DR   MaxQB; Q9Y6K5; -.
DR   PaxDb; 9606-ENSP00000228928; -.
DR   PeptideAtlas; Q9Y6K5; -.
DR   ProteomicsDB; 86712; -.
DR   Pumba; Q9Y6K5; -.
DR   Antibodypedia; 31208; 227 antibodies from 32 providers.
DR   DNASU; 4940; -.
DR   Ensembl; ENST00000228928.12; ENSP00000228928.7; ENSG00000111331.14.
DR   GeneID; 4940; -.
DR   KEGG; hsa:4940; -.
DR   MANE-Select; ENST00000228928.12; ENSP00000228928.7; NM_006187.4; NP_006178.2.
DR   UCSC; uc001tug.4; human.
DR   AGR; HGNC:8088; -.
DR   CTD; 4940; -.
DR   DisGeNET; 4940; -.
DR   GeneCards; OAS3; -.
DR   HGNC; HGNC:8088; OAS3.
DR   HPA; ENSG00000111331; Low tissue specificity.
DR   MIM; 603351; gene.
DR   neXtProt; NX_Q9Y6K5; -.
DR   OpenTargets; ENSG00000111331; -.
DR   PharmGKB; PA31877; -.
DR   VEuPathDB; HostDB:ENSG00000111331; -.
DR   eggNOG; ENOG502S649; Eukaryota.
DR   GeneTree; ENSGT00510000046406; -.
DR   HOGENOM; CLU_287245_0_0_1; -.
DR   InParanoid; Q9Y6K5; -.
DR   OMA; WQDPVPG; -.
DR   OrthoDB; 4638494at2759; -.
DR   PhylomeDB; Q9Y6K5; -.
DR   TreeFam; TF329749; -.
DR   BioCyc; MetaCyc:ENSG00000111331-MONOMER; -.
DR   BRENDA; 2.7.7.84; 2681.
DR   PathwayCommons; Q9Y6K5; -.
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   SignaLink; Q9Y6K5; -.
DR   BioGRID-ORCS; 4940; 8 hits in 1170 CRISPR screens.
DR   ChiTaRS; OAS3; human.
DR   GeneWiki; OAS3; -.
DR   GenomeRNAi; 4940; -.
DR   Pharos; Q9Y6K5; Tbio.
DR   PRO; PR:Q9Y6K5; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q9Y6K5; Protein.
DR   Bgee; ENSG00000111331; Expressed in monocyte and 157 other cell types or tissues.
DR   ExpressionAtlas; Q9Y6K5; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:ProtInc.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0001730; F:2'-5'-oligoadenylate synthetase activity; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IDA: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:0042742; P:defense response to bacterium; IMP:ARUK-UCL.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0039530; P:MDA-5 signaling pathway; IMP:ARUK-UCL.
DR   GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; IMP:ARUK-UCL.
DR   GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; IMP:ARUK-UCL.
DR   GO; GO:0035395; P:negative regulation of chemokine (C-X-C motif) ligand 9 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:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
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:0060700; P:regulation of ribonuclease activity; IDA:UniProtKB.
DR   GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR   GO; GO:0039529; P:RIG-I signaling pathway; IMP:ARUK-UCL.
DR   CDD; cd05400; NT_2-5OAS_ClassI-CCAase; 3.
DR   Gene3D; 1.10.1410.20; 2'-5'-oligoadenylate synthetase 1, domain 2; 3.
DR   Gene3D; 3.30.460.10; Beta Polymerase, domain 2; 3.
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:SF7; 2'-5'-OLIGOADENYLATE SYNTHASE-LIKE PROTEIN 2; 1.
DR   PANTHER; PTHR11258; 2-5 OLIGOADENYLATE SYNTHETASE; 1.
DR   Pfam; PF01909; NTP_transf_2; 1.
DR   Pfam; PF10421; OAS1_C; 3.
DR   SUPFAM; SSF81301; Nucleotidyltransferase; 3.
DR   SUPFAM; SSF81631; PAP/OAS1 substrate-binding domain; 3.
DR   PROSITE; PS00832; 25A_SYNTH_1; 3.
DR   PROSITE; PS00833; 25A_SYNTH_2; 2.
DR   PROSITE; PS50152; 25A_SYNTH_3; 3.
DR   Genevisible; Q9Y6K5; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Antiviral defense; ATP-binding; Cytoplasm;
KW   Direct protein sequencing; Immunity; Innate immunity; Magnesium;
KW   Metal-binding; Nucleotide-binding; Nucleotidyltransferase; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; RNA-binding; Transferase.
FT   CHAIN           1..1087
FT                   /note="2'-5'-oligoadenylate synthase 3"
FT                   /id="PRO_0000160265"
FT   REGION          6..343
FT                   /note="OAS domain 1"
FT                   /evidence="ECO:0000305"
FT   REGION          12..57
FT                   /note="Interaction with dsRNA"
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   REGION          186..200
FT                   /note="Interaction with dsRNA"
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   REGION          344..410
FT                   /note="Linker"
FT                   /evidence="ECO:0000305"
FT   REGION          411..742
FT                   /note="OAS domain 2"
FT                   /evidence="ECO:0000305"
FT   REGION          750..1084
FT                   /note="OAS domain 3"
FT                   /evidence="ECO:0000305"
FT   BINDING         804
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P00973"
FT   BINDING         816
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000305|PubMed:25775560"
FT   BINDING         818
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000305|PubMed:25775560"
FT   BINDING         888
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00973"
FT   BINDING         947
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P29728"
FT   BINDING         950
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P00973"
FT   BINDING         969
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P00973"
FT   SITE            155
FT                   /note="Interaction with dsRNA"
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   SITE            244
FT                   /note="Interaction with dsRNA"
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:22814378"
FT   MOD_RES         365
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         18
FT                   /note="R -> K (in dbSNP:rs1859330)"
FT                   /evidence="ECO:0000269|PubMed:11280764"
FT                   /id="VAR_060076"
FT   VARIANT         18
FT                   /note="R -> M (in dbSNP:rs1859330)"
FT                   /id="VAR_060077"
FT   VARIANT         18
FT                   /note="R -> T (in dbSNP:rs1859330)"
FT                   /id="VAR_060078"
FT   VARIANT         65
FT                   /note="R -> W (in dbSNP:rs12819767)"
FT                   /id="VAR_057660"
FT   VARIANT         378
FT                   /note="R -> K (in dbSNP:rs45519442)"
FT                   /id="VAR_062127"
FT   VARIANT         381
FT                   /note="S -> R (in dbSNP:rs2285933)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_057661"
FT   VARIANT         869
FT                   /note="R -> H (in dbSNP:rs16942374)"
FT                   /id="VAR_057662"
FT   MUTAGEN         30
FT                   /note="R->A: Impaired dsRNA binding."
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   MUTAGEN         41
FT                   /note="R->A: Impaired dsRNA binding."
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   MUTAGEN         76
FT                   /note="E->D: No effect on catalytic activity; when
FT                   associated with D-145."
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   MUTAGEN         145
FT                   /note="S->D: No effect on catalytic activity. No effect on
FT                   catalytic activity; when associated with D-76."
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   MUTAGEN         816..818
FT                   /note="DAD->AAA: Abolishes catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:25775560"
FT   CONFLICT        159
FT                   /note="G -> A (in Ref. 1; AAD28543)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        249
FT                   /note="A -> G (in Ref. 1; AAD28543)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        287..288
FT                   /note="QL -> HV (in Ref. 1; AAD28543)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        316
FT                   /note="L -> H (in Ref. 1; AAD28543)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        393
FT                   /note="G -> A (in Ref. 1; AAD28543)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        503..504
FT                   /note="QL -> HV (in Ref. 1; AAD28543 and 2; BAB18647)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        984
FT                   /note="G -> R (in Ref. 2; BAB18647)"
FT                   /evidence="ECO:0000305"
FT   HELIX           2..5
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           8..10
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           11..18
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           23..41
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          54..60
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           61..65
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          73..81
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           89..92
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           95..108
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          116..119
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          129..139
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          141..149
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           165..172
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   TURN            177..180
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           181..184
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           185..193
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           197..215
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           226..240
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           248..260
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           262..264
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          275..277
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           278..288
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          290..292
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          294..296
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   STRAND          304..306
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           313..322
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   HELIX           327..329
FT                   /evidence="ECO:0007829|PDB:4S3N"
FT   TURN            332..334
FT                   /evidence="ECO:0007829|PDB:4S3N"
SQ   SEQUENCE   1087 AA;  121170 MW;  36DAADE4574DE961 CRC64;
     MDLYSTPAAA LDRFVARRLQ PRKEFVEKAR RALGALAAAL RERGGRLGAA APRVLKTVKG
     GSSGRGTALK GGCDSELVIF LDCFKSYVDQ RARRAEILSE MRASLESWWQ NPVPGLRLTF
     PEQSVPGALQ FRLTSVDLED WMDVSLVPAF NVLGQAGSGV KPKPQVYSTL LNSGCQGGEH
     AACFTELRRN FVNIRPAKLK NLILLVKHWY HQVCLQGLWK ETLPPVYALE LLTIFAWEQG
     CKKDAFSLAE GLRTVLGLIQ QHQHLCVFWT VNYGFEDPAV GQFLQRQLKR PRPVILDPAD
     PTWDLGNGAA WHWDLLAQEA ASCYDHPCFL RGMGDPVQSW KGPGLPRAGC SGLGHPIQLD
     PNQKTPENSK SLNAVYPRAG SKPPSCPAPG PTGAASIVPS VPGMALDLSQ IPTKELDRFI
     QDHLKPSPQF QEQVKKAIDI ILRCLHENCV HKASRVSKGG SFGRGTDLRD GCDVELIIFL
     NCFTDYKDQG PRRAEILDEM RAQLESWWQD QVPSLSLQFP EQNVPEALQF QLVSTALKSW
     TDVSLLPAFD AVGQLSSGTK PNPQVYSRLL TSGCQEGEHK ACFAELRRNF MNIRPVKLKN
     LILLVKHWYR QVAAQNKGKG PAPASLPPAY ALELLTIFAW EQGCRQDCFN MAQGFRTVLG
     LVQQHQQLCV YWTVNYSTED PAMRMHLLGQ LRKPRPLVLD PADPTWNVGH GSWELLAQEA
     AALGMQACFL SRDGTSVQPW DVMPALLYQT PAGDLDKFIS EFLQPNRQFL AQVNKAVDTI
     CSFLKENCFR NSPIKVIKVV KGGSSAKGTA LRGRSDADLV VFLSCFSQFT EQGNKRAEII
     SEIRAQLEAC QQERQFEVKF EVSKWENPRV LSFSLTSQTM LDQSVDFDVL PAFDALGQLV
     SGSRPSSQVY VDLIHSYSNA GEYSTCFTEL QRDFIISRPT KLKSLIRLVK HWYQQCTKIS
     KGRGSLPPQH GLELLTVYAW EQGGKDSQFN MAEGFRTVLE LVTQYRQLCI YWTINYNAKD
     KTVGDFLKQQ LQKPRPIILD PADPTGNLGH NARWDLLAKE AAACTSALCC MGRNGIPIQP
     WPVKAAV
//