OAS2_MOUSE
ID OAS2_MOUSE Reviewed; 742 AA.
AC E9Q9A9; Q8K4E5; Q8VI92;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=2'-5'-oligoadenylate synthase 2;
DE Short=(2-5')oligo(A) synthase 2;
DE Short=2-5A synthase 2;
DE EC=2.7.7.84 {ECO:0000269|PubMed:15865429, ECO:0000269|PubMed:29117179};
DE AltName: Full=2',5'-oligoadenylate synthetase-like 11 {ECO:0000303|PubMed:12396720};
GN Name=Oas2 {ECO:0000312|MGI:MGI:2180852};
GN Synonyms=oasl11 {ECO:0000303|PubMed:12396720};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Colon;
RX PubMed=12396720; DOI=10.1089/10799900260286696;
RA Kakuta S., Shibata S., Iwakura Y.;
RT "Genomic structure of the mouse 2',5'-oligoadenylate synthetase gene
RT family.";
RL J. Interferon Cytokine Res. 22:981-993(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT ARG-232.
RC STRAIN=C3H/He;
RX PubMed=12080145; DOI=10.1073/pnas.142287799;
RA Perelygin A.A., Scherbik S.V., Zhulin I.B., Stockman B.M., Li Y.,
RA Brinton M.A.;
RT "Positional cloning of the murine flavivirus resistance gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:9322-9327(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-232.
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP REVIEW.
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF LYS-444; SER-509 AND PRO-538.
RX PubMed=15865429; DOI=10.1021/bi0502893;
RA Sarkar S.N., Kessler S.P., Rowe T.M., Pandey M., Ghosh A., Elco C.P.,
RA Hartmann R., Pal S., Sen G.C.;
RT "Natural mutations in a 2'-5' oligoadenylate synthetase transgene revealed
RT residues essential for enzyme activity.";
RL Biochemistry 44:6837-6843(2005).
RN [7]
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF ILE-405.
RX PubMed=29117179; DOI=10.1371/journal.pgen.1007072;
RA Oakes S.R., Gallego-Ortega D., Stanford P.M., Junankar S., Au W.W.Y.,
RA Kikhtyak Z., von Korff A., Sergio C.M., Law A.M.K., Castillo L.E.,
RA Allerdice S.L., Young A.I.J., Piggin C., Whittle B., Bertram E.,
RA Naylor M.J., Roden D.L., Donovan J., Korennykh A., Goodnow C.C.,
RA O'Bryan M.K., Ormandy C.J.;
RT "A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes
RT failure of lactation.";
RL PLoS Genet. 13:E1007072-E1007072(2017).
CC -!- FUNCTION: Interferon-induced, dsRNA-activated antiviral enzyme which
CC plays a critical role in cellular innate antiviral response
CC (PubMed:12396720, PubMed:29117179). Activated by detection of double
CC stranded RNA (dsRNA): polymerizes higher oligomers of 2'-5'-
CC oligoadenylates (2-5A) from ATP which then bind to the inactive
CC monomeric form of ribonuclease L (RNASEL) leading to its dimerization
CC and subsequent activation (PubMed:29117179). Activation of RNASEL leads
CC to degradation of cellular as well as viral RNA, resulting in the
CC inhibition of protein synthesis, thus terminating viral replication
CC (PubMed:21142819). Can mediate the antiviral effect via the classical
CC RNASEL-dependent pathway or an alternative antiviral pathway
CC independent of RNASEL (PubMed:21142819). In addition, it may also play
CC a role in other cellular processes such as apoptosis, cell growth,
CC differentiation and gene regulation (PubMed:21142819). May act as a
CC negative regulator of lactation, stopping lactation in virally infected
CC mammary gland lobules, thereby preventing transmission of viruses to
CC neonates (PubMed:29117179). Non-infected lobules would not be affected,
CC allowing efficient pup feeding during infection (PubMed:29117179).
CC {ECO:0000269|PubMed:12396720, ECO:0000269|PubMed:15865429,
CC ECO:0000269|PubMed:29117179, ECO:0000303|PubMed:21142819}.
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:15865429, ECO:0000269|PubMed:29117179};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P29728};
CC -!- ACTIVITY REGULATION: Produced as a latent enzyme which is activated by
CC double stranded RNA (dsRNA) generated during the course of viral
CC infection (PubMed:29117179). The dsRNA activator must be at least 15
CC nucleotides long, and no modification of the 2'-hydroxyl group is
CC tolerated (By similarity). ssRNA or dsDNA do not act as activators (By
CC similarity). Strongly inhibited by copper, iron and zinc ions (By
CC similarity). Partially inhibited by cobalt and nickel ions (By
CC similarity). {ECO:0000250|UniProtKB:P29728,
CC ECO:0000269|PubMed:29117179}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.9 mM for ATP {ECO:0000269|PubMed:15865429};
CC Note=kcat is 6.4 sec(-1) for ATP. {ECO:0000269|PubMed:15865429};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P29728}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P29728}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P29728}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=E9Q9A9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=E9Q9A9-2; Sequence=VSP_044068;
CC -!- TISSUE SPECIFICITY: Expressed in the uterus (PubMed:12396720).
CC Expressed in mammary glands: expressed at low level before the
CC establishment of lactation, then expression strongly increases, and
CC subsequently decreases during early involution (PubMed:29117179).
CC {ECO:0000269|PubMed:12396720, ECO:0000269|PubMed:29117179}.
CC -!- PTM: Myristoylation is not essential for its activity.
CC {ECO:0000250|UniProtKB:P29728}.
CC -!- PTM: Glycosylated. Glycosylation is essential for its activity.
CC {ECO:0000250|UniProtKB:P29728}.
CC -!- SIMILARITY: Belongs to the 2-5A synthase family. {ECO:0000305}.
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DR EMBL; AB067535; BAB84135.1; -; mRNA.
DR EMBL; AF418010; AAM54499.1; -; mRNA.
DR EMBL; AC115937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466529; EDL19753.1; -; Genomic_DNA.
DR CCDS; CCDS19625.2; -. [E9Q9A9-1]
DR CCDS; CCDS84949.1; -. [E9Q9A9-2]
DR RefSeq; NP_001334377.1; NM_001347448.1. [E9Q9A9-2]
DR RefSeq; NP_660262.2; NM_145227.3. [E9Q9A9-1]
DR AlphaFoldDB; E9Q9A9; -.
DR SMR; E9Q9A9; -.
DR BioGRID; 232936; 10.
DR STRING; 10090.ENSMUSP00000060082; -.
DR iPTMnet; E9Q9A9; -.
DR PhosphoSitePlus; E9Q9A9; -.
DR SwissPalm; E9Q9A9; -.
DR EPD; E9Q9A9; -.
DR jPOST; E9Q9A9; -.
DR MaxQB; E9Q9A9; -.
DR PaxDb; E9Q9A9; -.
DR PeptideAtlas; E9Q9A9; -.
DR PRIDE; E9Q9A9; -.
DR ProteomicsDB; 289956; -. [E9Q9A9-1]
DR ProteomicsDB; 289957; -. [E9Q9A9-2]
DR Antibodypedia; 31214; 441 antibodies from 31 providers.
DR DNASU; 246728; -.
DR Ensembl; ENSMUST00000053909; ENSMUSP00000060082; ENSMUSG00000032690. [E9Q9A9-1]
DR Ensembl; ENSMUST00000081491; ENSMUSP00000080209; ENSMUSG00000032690. [E9Q9A9-2]
DR GeneID; 246728; -.
DR KEGG; mmu:246728; -.
DR UCSC; uc008zhw.2; mouse. [E9Q9A9-2]
DR UCSC; uc008zhx.2; mouse. [E9Q9A9-1]
DR CTD; 4939; -.
DR MGI; MGI:2180852; Oas2.
DR VEuPathDB; HostDB:ENSMUSG00000032690; -.
DR eggNOG; ENOG502S649; Eukaryota.
DR GeneTree; ENSGT00510000046406; -.
DR HOGENOM; CLU_026275_0_0_1; -.
DR InParanoid; E9Q9A9; -.
DR OMA; WMKDSFE; -.
DR OrthoDB; 611234at2759; -.
DR TreeFam; TF329749; -.
DR BioGRID-ORCS; 246728; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Oas2; mouse.
DR PRO; PR:E9Q9A9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; E9Q9A9; protein.
DR Bgee; ENSMUSG00000032690; Expressed in mucous cell of stomach and 95 other tissues.
DR ExpressionAtlas; E9Q9A9; baseline and differential.
DR Genevisible; E9Q9A9; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0001730; F:2'-5'-oligoadenylate synthetase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0070106; P:interleukin-27-mediated signaling pathway; IEP:ARUK-UCL.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IBA:GO_Central.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:1903487; P:regulation of lactation; IMP:UniProtKB.
DR GO; GO:0060700; P:regulation of ribonuclease activity; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0009615; P:response to virus; TAS:UniProtKB.
DR GO; GO:0006401; P:RNA catabolic process; IDA:MGI.
DR GO; GO:0060337; P:type I interferon signaling pathway; IDA:UniProtKB.
DR CDD; cd05400; NT_2-5OAS_ClassI-CCAase; 2.
DR Gene3D; 3.30.460.10; -; 2.
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; 2.
DR SUPFAM; SSF81301; SSF81301; 2.
DR PROSITE; PS00832; 25A_SYNTH_1; 1.
DR PROSITE; PS00833; 25A_SYNTH_2; 2.
DR PROSITE; PS50152; 25A_SYNTH_3; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Antiviral defense; ATP-binding;
KW Cytoplasm; Glycoprotein; Immunity; Innate immunity; Lipoprotein; Magnesium;
KW Metal-binding; Myristate; Nucleotide-binding; Nucleotidyltransferase;
KW Reference proteome; Repeat; RNA-binding; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P29728"
FT CHAIN 2..742
FT /note="2'-5'-oligoadenylate synthase 2"
FT /id="PRO_0000418628"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 60..374
FT /note="OAS domain 1"
FT REGION 382..721
FT /note="OAS domain 2"
FT COMPBIAS 1..26
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 436
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT BINDING 448
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 450
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 519
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 582
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT BINDING 585
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT MOD_RES 417
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P29728"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P29728"
FT VAR_SEQ 723..742
FT /note="MQTPGSCGGQIYPTVGGVTK -> PRDLKTSDMVGVFTTGGILWQDQGFLSF
FT V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12080145"
FT /id="VSP_044068"
FT VARIANT 232
FT /note="Q -> R (in strain: C3H/He)"
FT /evidence="ECO:0000269|PubMed:12080145, ECO:0000269|Ref.4"
FT MUTAGEN 405
FT /note="I->N: Mice display postpartum failure of lactation
FT and strongly reduced milk protein synthesis. Otherwise,
FT mice develop normally and mammary glands are normal. The
FT mutation causes an activation of the OAS2 pathway,
FT characterized by a strong increase of Ribonuclease L
FT (RNASEL) activity."
FT /evidence="ECO:0000269|PubMed:29117179"
FT MUTAGEN 444
FT /note="K->A,G: Strongly reduced 2'-5'-oligoadenylate
FT synthase activity."
FT /evidence="ECO:0000269|PubMed:15865429"
FT MUTAGEN 509
FT /note="S->L: Abolished 2'-5'-oligoadenylate synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:15865429"
FT MUTAGEN 538
FT /note="P->L: Strongly reduced 2'-5'-oligoadenylate synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:15865429"
FT CONFLICT 270
FT /note="Y -> C (in Ref. 1; BAB84135)"
FT /evidence="ECO:0000305"
FT CONFLICT 630
FT /note="F -> L (in Ref. 1; BAB84135)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 742 AA; 85051 MW; F8F21FB4BEF90C58 CRC64;
MGNWLTGNWS SDRSSGYSSG WSPGGSSGVP SGPVHKLEKS IQANLTPNEN CLKQIAVSSV
PSQKLEGYIQ ENLKPNRESL KQIDQAVDAI WDLLRSQIPV KEVAKGGSYG RETALRGCSD
GTLVLFMDCF QQFQDQIKYQ DAYLDVIELW LKIHEKKSVK HEHALVVQVS VPGQRILLQL
LPVFNPLRSN ENPSSCVYVD LKKSMDQVRA SPGEFSDCFT TLQQRFFKKY PQRLKDLILL
VKHWYEQCQE KWKTPPPQPL LYALELLTVY AWEQGCQAED FDMAQGVRTV LRLIQRPTEL
CVYWTVNYNF EDETVRNILL HQLRSQRPVI LDPTDPTNNV GKDDGFWELL TEEAMAWLYS
PSLNTESPAP YWDVLPMPLF VTPSHLLNKF IKDFLQPNKL FLKQIKEAVD IICSFLKNVC
FLNSDTKVLK TVKGGSTAKG TALKRGSDAD IVVFLSSLES YDSLKTNRSQ FVQEIQKQLE
EFVQAQEWEV TFEISKWKAP RVLSFTLKSK TLNESVEFDV LPAYDALGQL RSDFTLRPEA
YKDLIELCAS QDIKEGEFSI CFTELQRNFI QTRPTKLKSL LRLIKHWYKQ YERKMKPKAS
LPPKYALELL TVYAWEQGSG TDDFDIAEGF RTVLDLVIKY RQLCIFWTVN YNFEEEYMRK
FLLTQIQKKR PVILDPADPT GDVGGGDRWC WHLLAEEAKE WLSSPCFQVE QKGLVQPWKV
PVMQTPGSCG GQIYPTVGGV TK
