OAS1_PIG
ID OAS1_PIG Reviewed; 349 AA.
AC Q29599; O77734;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 116.
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;
DE AltName: Full=p42 OAS;
GN Name=OAS1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Small intestine;
RA Hartmann R.;
RL Thesis (1997), University of Aarhus, Denmark.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-128.
RC TISSUE=Small intestine;
RX PubMed=8672129; DOI=10.1007/s003359900153;
RA Winteroe A.K., Fredholm M., Davies W.;
RT "Evaluation and characterization of a porcine small intestine cDNA library:
RT analysis of 839 clones.";
RL Mamm. Genome 7:509-517(1996).
RN [3]
RP MUTAGENESIS OF LYS-65; ARG-209; TYR-230; GLU-233 AND ASP-300.
RX PubMed=18604630; DOI=10.1007/s00018-008-8164-5;
RA Torralba S., Sojat J., Hartmann R.;
RT "2'-5' oligoadenylate synthetase shares active site architecture with the
RT archaeal CCA-adding enzyme.";
RL Cell. Mol. Life Sci. 65:2613-2620(2008).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20844035; DOI=10.1128/jvi.01003-10;
RA Kristiansen H., Scherer C.A., McVean M., Iadonato S.P., Vends S.,
RA Thavachelvam K., Steffensen T.B., Horan K.A., Kuri T., Weber F.,
RA Paludan S.R., Hartmann R.;
RT "Extracellular 2'-5' oligoadenylate synthetase stimulates RNase L-
RT independent antiviral activity: a novel mechanism of virus-induced innate
RT immunity.";
RL J. Virol. 84:11898-11904(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 1-349, CATALYTIC ACTIVITY,
RP SUBUNIT, METAL BINDING, AND MUTAGENESIS OF LYS-212.
RX PubMed=14636576; DOI=10.1016/s1097-2765(03)00433-7;
RA Hartmann R., Justesen J., Sarkar S.N., Sen G.C., Yee V.C.;
RT "Crystal structure of the 2'-specific and double-stranded RNA-activated
RT interferon-induced antiviral protein 2'-5'-oligoadenylate synthetase.";
RL Mol. Cell 12:1173-1185(2003).
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 higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP
CC which then bind to the inactive monomeric form of ribonuclease L (RNase
CC L) leading to its dimerization and subsequent activation. Activation of
CC RNase L leads to degradation of cellular as well as viral RNA,
CC 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. The secreted form displays antiviral effect
CC against vesicular stomatitis virus (VSV), herpes simplex virus type 2
CC (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the
CC alternative antiviral pathway independent of RNase L.
CC {ECO:0000269|PubMed:20844035}.
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:14636576};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P00973};
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. ssRNA or dsDNA do not act as
CC activators (By similarity). {ECO:0000250|UniProtKB:P00973}.
CC -!- SUBUNIT: Monomer. Homotetramer (By similarity).
CC {ECO:0000250|UniProtKB:P00973}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P00973}.
CC Mitochondrion {ECO:0000250|UniProtKB:P00973}. Nucleus
CC {ECO:0000250|UniProtKB:P00973}. Microsome
CC {ECO:0000250|UniProtKB:P00973}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P00973}. Secreted {ECO:0000269|PubMed:20844035}.
CC Note=Associated with different subcellular fractions such as
CC mitochondrial, nuclear, and rough/smooth microsomal fractions.
CC {ECO:0000250|UniProtKB:P00973}.
CC -!- SIMILARITY: Belongs to the 2-5A synthase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA23153.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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; AJ225090; CAA12397.1; -; mRNA.
DR EMBL; F14610; CAA23153.1; ALT_INIT; mRNA.
DR RefSeq; NP_999468.1; NM_214303.1.
DR PDB; 1PX5; X-ray; 1.74 A; A/B=1-349.
DR PDB; 4RWN; X-ray; 2.00 A; A=1-349.
DR PDB; 4RWO; X-ray; 2.20 A; A=1-349.
DR PDB; 4RWP; X-ray; 2.25 A; A=1-349.
DR PDB; 4RWQ; X-ray; 3.10 A; A/B=1-349.
DR PDBsum; 1PX5; -.
DR PDBsum; 4RWN; -.
DR PDBsum; 4RWO; -.
DR PDBsum; 4RWP; -.
DR PDBsum; 4RWQ; -.
DR AlphaFoldDB; Q29599; -.
DR SMR; Q29599; -.
DR STRING; 9823.ENSSSCP00000010549; -.
DR PeptideAtlas; Q29599; -.
DR PRIDE; Q29599; -.
DR GeneID; 397570; -.
DR CTD; 4938; -.
DR eggNOG; ENOG502RH25; Eukaryota.
DR InParanoid; Q29599; -.
DR OrthoDB; 611234at2759; -.
DR BRENDA; 2.7.7.84; 6170.
DR EvolutionaryTrace; Q29599; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0001730; F:2'-5'-oligoadenylate synthetase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0060700; P:regulation of ribonuclease activity; IDA:UniProtKB.
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; Antiviral defense; ATP-binding; Cytoplasm;
KW Endoplasmic reticulum; Immunity; Innate immunity; Magnesium; Metal-binding;
KW Microsome; Mitochondrion; Nucleotide-binding; Nucleotidyltransferase;
KW Nucleus; Reference proteome; RNA-binding; Secreted; Transferase.
FT CHAIN 1..349
FT /note="2'-5'-oligoadenylate synthase 1"
FT /id="PRO_0000160262"
FT REGION 12..59
FT /note="Interaction with dsRNA"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT REGION 199..209
FT /note="Interaction with dsRNA"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT BINDING 62
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT BINDING 74
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT BINDING 76
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT BINDING 147
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT BINDING 209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:18604630"
FT BINDING 212
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:14636576"
FT BINDING 229
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT SITE 157
FT /note="Interaction with dsRNA"
FT /evidence="ECO:0000250|UniProtKB:P00973"
FT MUTAGEN 65
FT /note="K->A: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:18604630"
FT MUTAGEN 209
FT /note="R->A: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:18604630"
FT MUTAGEN 212
FT /note="K->A: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:14636576"
FT MUTAGEN 230
FT /note="Y->A: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:18604630"
FT MUTAGEN 233
FT /note="E->A: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:18604630"
FT MUTAGEN 300
FT /note="D->A: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:18604630"
FT CONFLICT 54
FT /note="V -> F (in Ref. 2; CAA23153)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="S -> R (in Ref. 2; CAA23153)"
FT /evidence="ECO:0000305"
FT HELIX 3..5
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 11..18
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 23..43
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:4RWQ"
FT STRAND 53..62
FT /evidence="ECO:0007829|PDB:1PX5"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:4RWN"
FT STRAND 73..83
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 94..111
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:4RWP"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:4RWP"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:1PX5"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 143..152
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 166..179
FT /evidence="ECO:0007829|PDB:1PX5"
FT TURN 182..185
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 190..198
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 202..219
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:4RWQ"
FT HELIX 229..243
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:4RWN"
FT HELIX 251..263
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 264..267
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 281..291
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:1PX5"
FT TURN 308..311
FT /evidence="ECO:0007829|PDB:4RWO"
FT HELIX 313..326
FT /evidence="ECO:0007829|PDB:1PX5"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:1PX5"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:4RWQ"
SQ SEQUENCE 349 AA; 40246 MW; 06949A35BFCF7710 CRC64;
MELRHTPARD LDKFIEDHLL PNTCFRTQVK EAIDIVCRFL KERCFQGTAD PVRVSKVVKG
GSSGKGTTLR GRSDADLVVF LTKLTSFEDQ LRRRGEFIQE IRRQLEACQR EQKFKVTFEV
QSPRRENPRA LSFVLSSPQL QQEVEFDVLP AFDALGQWTP GYKPNPEIYV QLIKECKSRG
KEGEFSTCFT ELQRDFLRNR PTKLKSLIRL VKHWYQTCKK THGNKLPPQY ALELLTVYAW
EQGSRKTDFS TAQGFQTVLE LVLKHQKLCI FWEAYYDFTN PVVGRCMLQQ LKKPRPVILD
PADPTGNVGG GDTHSWQRLA QEARVWLGYP CCKNLDGSLV GAWTMLQKI
