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Protein

2'-5'-oligoadenylate synthase 2

Gene

OAS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L.3 Publications

Catalytic activityi

3 ATP = pppA2'p5'A2'p5'A + 2 diphosphate.

Cofactori

Mg2+Curated

Enzyme regulationi

Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. ssRNA or dsDNA do not act as activators.1 Publication

Kineticsi

  1. KM=2.1 mM for ATP3 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi408Magnesium; catalyticSequence analysis1
    Metal bindingi410Magnesium; catalyticSequence analysis1
    Metal bindingi481Magnesium; catalyticSequence analysis1
    Binding sitei544Substrate1
    Binding sitei547ATP1

    GO - Molecular functioni

    • 2'-5'-oligoadenylate synthetase activity Source: UniProtKB
    • ATP binding Source: UniProtKB
    • double-stranded RNA binding Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • defense response to virus Source: UniProtKB-KW
    • interferon-gamma-mediated signaling pathway Source: Reactome
    • nucleobase-containing compound metabolic process Source: ProtInc
    • protein glycosylation Source: UniProtKB
    • protein myristoylation Source: UniProtKB
    • purine nucleotide biosynthetic process Source: UniProtKB
    • response to virus Source: UniProtKB
    • RNA catabolic process Source: Ensembl
    • type I interferon signaling pathway Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Nucleotidyltransferase, Transferase

    Keywords - Biological processi

    Antiviral defense, Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, RNA-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000111335-MONOMER.
    ZFISH:ENSG00000111335-MONOMER.
    ReactomeiR-HSA-877300. Interferon gamma signaling.
    R-HSA-909733. Interferon alpha/beta signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    2'-5'-oligoadenylate synthase 2 (EC:2.7.7.84)
    Short name:
    (2-5')oligo(A) synthase 2
    Short name:
    2-5A synthase 2
    Alternative name(s):
    p69 OAS / p71 OAS
    Short name:
    p69OAS / p71OAS
    Gene namesi
    Name:OAS2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:8087. OAS2.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • endoplasmic reticulum Source: UniProtKB-SubCell
    • intracellular membrane-bounded organelle Source: ProtInc
    • membrane Source: UniProtKB
    • mitochondrion Source: UniProtKB-SubCell
    • nucleus Source: UniProtKB-SubCell
    • perinuclear region of cytoplasm Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Microsome, Mitochondrion, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi2G → A or D: No loss of activity. 1 Publication1
    Mutagenesisi408D → A: Loss of activity; when associated with A-410. 1 Publication1
    Mutagenesisi410D → A: Loss of activity; when associated with A-408. 1 Publication1
    Mutagenesisi421Y → P or A: Significant loss of activity. 1 Publication1
    Mutagenesisi481D → A: Loss of activity. 1 Publication1
    Mutagenesisi544R → A or Y: Significant loss of activity. 1 Publication1
    Mutagenesisi547K → A: Partial loss of activity. 1 Publication1
    Mutagenesisi668C → A: Loss of activity; when associated with A-669 and A-670. 1 Publication1
    Mutagenesisi669F → A: Loss of activity; when associated with A-668 and A-670. 1 Publication1
    Mutagenesisi670K → A: Loss of activity; when associated with A-668 and A-669. 1 Publication1

    Organism-specific databases

    DisGeNETi4939.
    OpenTargetsiENSG00000111335.
    PharmGKBiPA31876.

    Polymorphism and mutation databases

    BioMutaiOAS2.
    DMDMi116242687.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved
    ChainiPRO_00001602642 – 7192'-5'-oligoadenylate synthase 2Add BLAST718

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Lipidationi2N-myristoyl glycine1 Publication1
    Modified residuei378N6-acetyllysineCombined sources1

    Post-translational modificationi

    Myristoylation is not essential for its activity.2 Publications
    Glycosylated. Glycosylation is essential for its activity.1 Publication

    Keywords - PTMi

    Acetylation, Glycoprotein, Lipoprotein, Myristate

    Proteomic databases

    MaxQBiP29728.
    PaxDbiP29728.
    PeptideAtlasiP29728.
    PRIDEiP29728.

    PTM databases

    iPTMnetiP29728.
    PhosphoSitePlusiP29728.

    Expressioni

    Inductioni

    By type I interferon (IFN) and viruses.

    Gene expression databases

    BgeeiENSG00000111335.
    CleanExiHS_OAS2.
    ExpressionAtlasiP29728. baseline and differential.
    GenevisibleiP29728. HS.

    Organism-specific databases

    HPAiCAB024984.
    HPA045947.

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CLK3P497613EBI-10211452,EBI-745579

    Protein-protein interaction databases

    BioGridi110993. 5 interactors.
    IntActiP29728. 1 interactor.
    STRINGi9606.ENSP00000342278.

    Structurei

    3D structure databases

    ProteinModelPortaliP29728.
    SMRiP29728.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni11 – 335OAS domain 1Add BLAST325
    Regioni343 – 683OAS domain 2Add BLAST341

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi326 – 346Pro-rich (linker)Add BLAST21

    Sequence similaritiesi

    Belongs to the 2-5A synthase family.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiKOG0001. Eukaryota.
    COG5272. LUCA.
    GeneTreeiENSGT00510000046406.
    HOGENOMiHOG000013200.
    HOVERGENiHBG007855.
    KOiK14216.
    PhylomeDBiP29728.
    TreeFamiTF329749.

    Family and domain databases

    Gene3Di1.10.1410.20. 2 hits.
    InterProiIPR006117. 2-5-oligoadenylate_synth_CS.
    IPR006116. 2-5-oligoadenylate_synth_N.
    IPR018952. 2-5-oligoAdlate_synth_1_dom2/C.
    IPR026774. 2-5A_synthase.
    IPR002934. Polymerase_NTP_transf_dom.
    [Graphical view]
    PANTHERiPTHR11258. PTHR11258. 1 hit.
    PfamiPF01909. NTP_transf_2. 1 hit.
    PF10421. OAS1_C. 2 hits.
    [Graphical view]
    PROSITEiPS00832. 25A_SYNTH_1. 2 hits.
    PS00833. 25A_SYNTH_2. 2 hits.
    PS50152. 25A_SYNTH_3. 2 hits.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform p71 (identifier: P29728-1) [UniParc]FASTAAdd to basket
    Also known as: 71 kDa

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MGNGESQLSS VPAQKLGWFI QEYLKPYEEC QTLIDEMVNT ICDVLQEPEQ
    60 70 80 90 100
    FPLVQGVAIG GSYGRKTVLR GNSDGTLVLF FSDLKQFQDQ KRSQRDILDK
    110 120 130 140 150
    TGDKLKFCLF TKWLKNNFEI QKSLDGFTIQ VFTKNQRISF EVLAAFNALS
    160 170 180 190 200
    LNDNPSPWIY RELKRSLDKT NASPGEFAVC FTELQQKFFD NRPGKLKDLI
    210 220 230 240 250
    LLIKHWHQQC QKKIKDLPSL SPYALELLTV YAWEQGCRKD NFDIAEGVRT
    260 270 280 290 300
    VLELIKCQEK LCIYWMVNYN FEDETIRNIL LHQLQSARPV ILDPVDPTNN
    310 320 330 340 350
    VSGDKICWQW LKKEAQTWLT SPNLDNELPA PSWNVLPAPL FTTPGHLLDK
    360 370 380 390 400
    FIKEFLQPNK CFLEQIDSAV NIIRTFLKEN CFRQSTAKIQ IVRGGSTAKG
    410 420 430 440 450
    TALKTGSDAD LVVFHNSLKS YTSQKNERHK IVKEIHEQLK AFWREKEEEL
    460 470 480 490 500
    EVSFEPPKWK APRVLSFSLK SKVLNESVSF DVLPAFNALG QLSSGSTPSP
    510 520 530 540 550
    EVYAGLIDLY KSSDLPGGEF STCFTVLQRN FIRSRPTKLK DLIRLVKHWY
    560 570 580 590 600
    KECERKLKPK GSLPPKYALE LLTIYAWEQG SGVPDFDTAE GFRTVLELVT
    610 620 630 640 650
    QYQQLCIFWK VNYNFEDETV RKFLLSQLQK TRPVILDPAE PTGDVGGGDR
    660 670 680 690 700
    WCWHLLAKEA KEWLSSPCFK DGTGNPIPPW KVPTMQTPGS CGARIHPIVN
    710
    EMFSSRSHRI LNNNSKRNF
    Length:719
    Mass (Da):82,431
    Last modified:January 23, 2007 - v3
    Checksum:i1B680D397D5EDB78
    GO
    Isoform p69 (identifier: P29728-2) [UniParc]FASTAAdd to basket
    Also known as: 69 kDa

    The sequence of this isoform differs from the canonical sequence as follows:
         684-687: TMQT → VKVI
         688-719: Missing.

    Show »
    Length:687
    Mass (Da):78,787
    Checksum:i34729B5A88A38B2D
    GO
    Isoform 3 (identifier: P29728-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         151-172: LNDNPSPWIYRELKRSLDKTNA → KHCWVSGEKSQRSGCQTALCNL
         173-719: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:172
    Mass (Da):19,517
    Checksum:i8CF5C0C9EE9850A9
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti45 – 47LQE → CRN in AAA60607 (PubMed:1577824).Curated3
    Sequence conflicti45 – 47LQE → CRN in AAA60606 (PubMed:1577824).Curated3
    Sequence conflicti127F → S in AAA60607 (PubMed:1577824).Curated1
    Sequence conflicti127F → S in AAA60606 (PubMed:1577824).Curated1
    Sequence conflicti606C → G in AAA60607 (PubMed:1577824).Curated1
    Sequence conflicti606C → G in AAA60606 (PubMed:1577824).Curated1
    Sequence conflicti639A → G in AAA60607 (PubMed:1577824).Curated1
    Sequence conflicti639A → G in AAA60606 (PubMed:1577824).Curated1
    Sequence conflicti657A → D in AAA60607 (PubMed:1577824).Curated1
    Sequence conflicti657A → D in AAA60606 (PubMed:1577824).Curated1
    Sequence conflicti662 – 663EW → VR in AAA60607 (PubMed:1577824).Curated2
    Sequence conflicti662 – 663EW → VR in AAA60606 (PubMed:1577824).Curated2
    Sequence conflicti719F → FWRSSGNRF in AAA60607 (PubMed:1577824).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_043354151 – 172LNDNP…DKTNA → KHCWVSGEKSQRSGCQTALC NL in isoform 3. 1 PublicationAdd BLAST22
    Alternative sequenceiVSP_043355173 – 719Missing in isoform 3. 1 PublicationAdd BLAST547
    Alternative sequenceiVSP_003741684 – 687TMQT → VKVI in isoform p69. 3 Publications4
    Alternative sequenceiVSP_003742688 – 719Missing in isoform p69. 3 PublicationsAdd BLAST32

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M87434 mRNA. Translation: AAA60607.1.
    M87284 mRNA. Translation: AAA60606.1.
    AK292796 mRNA. Translation: BAF85485.1.
    AC004551 Genomic DNA. No translation available.
    CH471054 Genomic DNA. Translation: EAW98027.1.
    BC023637 mRNA. Translation: AAH23637.1.
    BC049215 mRNA. Translation: AAH49215.1.
    CCDSiCCDS31906.1. [P29728-1]
    CCDS41839.1. [P29728-2]
    CCDS44982.1. [P29728-3]
    PIRiB42665.
    RefSeqiNP_001027903.1. NM_001032731.1. [P29728-3]
    NP_002526.2. NM_002535.2. [P29728-2]
    NP_058197.2. NM_016817.2. [P29728-1]
    UniGeneiHs.414332.

    Genome annotation databases

    EnsembliENST00000342315; ENSP00000342278; ENSG00000111335. [P29728-1]
    ENST00000392583; ENSP00000376362; ENSG00000111335. [P29728-2]
    ENST00000449768; ENSP00000411763; ENSG00000111335. [P29728-3]
    GeneIDi4939.
    KEGGihsa:4939.
    UCSCiuc001tuh.4. human. [P29728-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M87434 mRNA. Translation: AAA60607.1.
    M87284 mRNA. Translation: AAA60606.1.
    AK292796 mRNA. Translation: BAF85485.1.
    AC004551 Genomic DNA. No translation available.
    CH471054 Genomic DNA. Translation: EAW98027.1.
    BC023637 mRNA. Translation: AAH23637.1.
    BC049215 mRNA. Translation: AAH49215.1.
    CCDSiCCDS31906.1. [P29728-1]
    CCDS41839.1. [P29728-2]
    CCDS44982.1. [P29728-3]
    PIRiB42665.
    RefSeqiNP_001027903.1. NM_001032731.1. [P29728-3]
    NP_002526.2. NM_002535.2. [P29728-2]
    NP_058197.2. NM_016817.2. [P29728-1]
    UniGeneiHs.414332.

    3D structure databases

    ProteinModelPortaliP29728.
    SMRiP29728.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi110993. 5 interactors.
    IntActiP29728. 1 interactor.
    STRINGi9606.ENSP00000342278.

    PTM databases

    iPTMnetiP29728.
    PhosphoSitePlusiP29728.

    Polymorphism and mutation databases

    BioMutaiOAS2.
    DMDMi116242687.

    Proteomic databases

    MaxQBiP29728.
    PaxDbiP29728.
    PeptideAtlasiP29728.
    PRIDEiP29728.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000342315; ENSP00000342278; ENSG00000111335. [P29728-1]
    ENST00000392583; ENSP00000376362; ENSG00000111335. [P29728-2]
    ENST00000449768; ENSP00000411763; ENSG00000111335. [P29728-3]
    GeneIDi4939.
    KEGGihsa:4939.
    UCSCiuc001tuh.4. human. [P29728-1]

    Organism-specific databases

    CTDi4939.
    DisGeNETi4939.
    GeneCardsiOAS2.
    H-InvDBHIX0129679.
    HGNCiHGNC:8087. OAS2.
    HPAiCAB024984.
    HPA045947.
    MIMi603350. gene.
    neXtProtiNX_P29728.
    OpenTargetsiENSG00000111335.
    PharmGKBiPA31876.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0001. Eukaryota.
    COG5272. LUCA.
    GeneTreeiENSGT00510000046406.
    HOGENOMiHOG000013200.
    HOVERGENiHBG007855.
    KOiK14216.
    PhylomeDBiP29728.
    TreeFamiTF329749.

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000111335-MONOMER.
    ZFISH:ENSG00000111335-MONOMER.
    ReactomeiR-HSA-877300. Interferon gamma signaling.
    R-HSA-909733. Interferon alpha/beta signaling.

    Miscellaneous databases

    GeneWikiiOAS2.
    GenomeRNAii4939.
    PROiP29728.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000111335.
    CleanExiHS_OAS2.
    ExpressionAtlasiP29728. baseline and differential.
    GenevisibleiP29728. HS.

    Family and domain databases

    Gene3Di1.10.1410.20. 2 hits.
    InterProiIPR006117. 2-5-oligoadenylate_synth_CS.
    IPR006116. 2-5-oligoadenylate_synth_N.
    IPR018952. 2-5-oligoAdlate_synth_1_dom2/C.
    IPR026774. 2-5A_synthase.
    IPR002934. Polymerase_NTP_transf_dom.
    [Graphical view]
    PANTHERiPTHR11258. PTHR11258. 1 hit.
    PfamiPF01909. NTP_transf_2. 1 hit.
    PF10421. OAS1_C. 2 hits.
    [Graphical view]
    PROSITEiPS00832. 25A_SYNTH_1. 2 hits.
    PS00833. 25A_SYNTH_2. 2 hits.
    PS50152. 25A_SYNTH_3. 2 hits.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiOAS2_HUMAN
    AccessioniPrimary (citable) accession number: P29728
    Secondary accession number(s): A8K9T1, Q6PJ33, Q86XX8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: January 23, 2007
    Last modified: November 2, 2016
    This is version 153 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.