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Protein

2'-5'-oligoadenylate synthase 2

Gene

OAS2

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

Functioni

Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:10464285, PubMed:9880569). Activated by detection of double stranded RNA (dsRNA): polymerizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNASEL) leading to its dimerization and subsequent activation (PubMed:10464285, PubMed:9880569, PubMed:11682059). Activation of RNASEL leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:10464285, PubMed:9880569). Can mediate the antiviral effect via the classical RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL (PubMed:21142819). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation (PubMed:21142819). May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates (By similarity). Non-infected lobules would not be affected, allowing efficient pup feeding during infection (By similarity).1 PublicationBy similarity4 Publications

Catalytic activityi

3 ATP = pppA2'p5'A2'p5'A + 2 diphosphate.4 Publications

Cofactori

Mg2+1 Publication

Enzyme regulationi

Produced as a latent enzyme which is activated by double stranded RNA (dsRNA) generated during the course of viral infection(PubMed:9880569). The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated (PubMed:9880569). ssRNA or dsDNA do not act as activators (PubMed:9880569). Strongly inhibited by copper, iron and zinc ions (PubMed:11682059). Partially inhibited by cobalt and nickel ions (PubMed:11682059).2 Publications

Kineticsi

  1. KM=2.1 mM for ATP3 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei396ATPBy similarity1
    Metal bindingi408Magnesium; catalyticSequence analysis1
    Metal bindingi410Magnesium; catalyticSequence analysis1
    Metal bindingi481Magnesium; catalyticSequence analysis1
    Binding sitei544ATP1 Publication1
    Binding sitei547ATP1 Publication1

    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

    GO - Biological processi

    Keywordsi

    Molecular functionNucleotidyltransferase, RNA-binding, Transferase
    Biological processAntiviral defense, Immunity, Innate immunity
    LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000111335-MONOMER
    ReactomeiR-HSA-877300 Interferon gamma signaling
    R-HSA-909733 Interferon alpha/beta signaling
    SABIO-RKiP29728

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    2'-5'-oligoadenylate synthase 2 (EC:2.7.7.843 Publications)
    Short name:
    (2-5')oligo(A) synthase 2
    Short name:
    2-5A synthase 2
    Alternative name(s):
    p69 OAS / p71 OAS1 Publication
    Short name:
    p69OAS / p71OAS1 Publication
    Gene namesi
    Name:OAS2Imported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000111335.12
    HGNCiHGNC:8087 OAS2
    MIMi603350 gene
    neXtProtiNX_P29728

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    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 methionineiRemoved1 Publication
    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.1 Publication

    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
    InterProiView protein in InterPro
    IPR006117 2-5-oligoadenylate_synth_CS
    IPR006116 2-5-oligoadenylate_synth_N
    IPR018952 2-5-oligoAdlate_synth_1_dom2/C
    IPR038121 2-5-oligoAdlate_synth_2_sf
    IPR026774 2-5A_synthase
    IPR002934 Polymerase_NTP_transf_dom
    PANTHERiPTHR11258 PTHR11258, 1 hit
    PfamiView protein in Pfam
    PF01909 NTP_transf_2, 1 hit
    PF10421 OAS1_C, 2 hits
    PROSITEiView protein in PROSITE
    PS00832 25A_SYNTH_1, 2 hits
    PS00833 25A_SYNTH_2, 2 hits
    PS50152 25A_SYNTH_3, 2 hits

    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 p711 Publication (identifier: P29728-1) [UniParc]FASTAAdd to basket
    Also known as: 71 kDa1 Publication

    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 p692 Publications (identifier: P29728-2) [UniParc]FASTAAdd to basket
    Also known as: 69 kDa2 Publications

    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

    Similar proteinsi

    Entry informationi

    Entry nameiOAS2_HUMAN
    AccessioniPrimary (citable) accession number: P29728
    Secondary accession number(s): A8K9T1, Q6PJ33, Q86XX8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: January 23, 2007
    Last modified: April 25, 2018
    This is version 160 of the entry and version 3 of the sequence. See 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

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