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Q9Y6K5 (OAS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
2'-5'-oligoadenylate synthase 3

Short name=(2-5')oligo(A) synthase 3
Short name=2-5A synthase 3
EC=2.7.7.84
Alternative name(s):
p100 OAS
Short name=p100OAS
Gene names
Name:OAS3
ORF Names:P/OKcl.4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1087 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 preferentially dimers 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. Displays antiviral activity against Chikungunya virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest virus (SFV). Ref.1 Ref.8 Ref.10

Catalytic activity

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

Cofactor

Magnesium Potential.

Enzyme regulation

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.

Subunit structure

Monomer.

Subcellular location

Cytoplasm. Nucleus Ref.1 Ref.8.

Tissue specificity

Present at high level in placenta trophoblast.

Induction

By type I interferon (IFN) and viruses.

Sequence similarities

Belongs to the 2-5A synthase family.

Sequence caution

The sequence AAD28543.1 differs from that shown. Reason: Frameshift at positions 394 and 398.

Ontologies

Keywords
   Biological processAntiviral defense
Immunity
Innate immunity
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
RNA-binding
   Molecular functionNucleotidyltransferase
Transferase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

defense response to virus

Inferred from direct assay Ref.8. Source: UniProtKB

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

negative regulation of viral genome replication

Inferred from direct assay Ref.10Ref.8. Source: UniProtKB

nucleobase-containing compound metabolic process

Traceable author statement PubMed 2440675. Source: ProtInc

regulation of ribonuclease activity

Inferred from direct assay Ref.8. Source: UniProtKB

response to virus

Inferred from direct assay Ref.10. Source: UniProtKB

type I interferon signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.8Ref.1. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 23580065. Source: UniProt

intracellular membrane-bounded organelle

Traceable author statement PubMed 2440675. Source: ProtInc

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_function2'-5'-oligoadenylate synthetase activity

Inferred from direct assay Ref.1. Source: UniProtKB

ATP binding

Inferred from direct assay Ref.1. Source: UniProtKB

double-stranded RNA binding

Inferred from direct assay Ref.1. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 21903422. Source: IntAct

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 108710872'-5'-oligoadenylate synthase 3
PRO_0000160265

Regions

Region6 – 343338OAS domain 1
Region344 – 41067Linker
Region411 – 742332OAS domain 2
Region750 – 1084335OAS domain 3

Sites

Metal binding8161Magnesium; catalytic Potential
Metal binding8181Magnesium; catalytic Potential
Metal binding8881Magnesium; catalytic Potential
Binding site9471Substrate By similarity
Binding site9501ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.6 Ref.13

Natural variations

Natural variant181R → K. Ref.2
Corresponds to variant rs1859330 [ dbSNP | Ensembl ].
VAR_060076
Natural variant181R → M.
Corresponds to variant rs1859330 [ dbSNP | Ensembl ].
VAR_060077
Natural variant181R → T.
Corresponds to variant rs1859330 [ dbSNP | Ensembl ].
VAR_060078
Natural variant651R → W.
Corresponds to variant rs12819767 [ dbSNP | Ensembl ].
VAR_057660
Natural variant3781R → K.
Corresponds to variant rs45519442 [ dbSNP | Ensembl ].
VAR_062127
Natural variant3811S → R. Ref.4
Corresponds to variant rs2285933 [ dbSNP | Ensembl ].
VAR_057661
Natural variant8691R → H.
Corresponds to variant rs16942374 [ dbSNP | Ensembl ].
VAR_057662

Experimental info

Sequence conflict1591G → A in AAD28543. Ref.1
Sequence conflict2491A → G in AAD28543. Ref.1
Sequence conflict287 – 2882QL → HV in AAD28543. Ref.1
Sequence conflict3161L → H in AAD28543. Ref.1
Sequence conflict3931G → A in AAD28543. Ref.1
Sequence conflict503 – 5042QL → HV in AAD28543. Ref.1
Sequence conflict503 – 5042QL → HV in BAB18647. Ref.2
Sequence conflict9841G → R in BAB18647. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Y6K5 [UniParc].

Last modified January 11, 2011. Version 3.
Checksum: 36DAADE4574DE961

FASTA1,087121,170
        10         20         30         40         50         60 
MDLYSTPAAA LDRFVARRLQ PRKEFVEKAR RALGALAAAL RERGGRLGAA APRVLKTVKG 

        70         80         90        100        110        120 
GSSGRGTALK GGCDSELVIF LDCFKSYVDQ RARRAEILSE MRASLESWWQ NPVPGLRLTF 

       130        140        150        160        170        180 
PEQSVPGALQ FRLTSVDLED WMDVSLVPAF NVLGQAGSGV KPKPQVYSTL LNSGCQGGEH 

       190        200        210        220        230        240 
AACFTELRRN FVNIRPAKLK NLILLVKHWY HQVCLQGLWK ETLPPVYALE LLTIFAWEQG 

       250        260        270        280        290        300 
CKKDAFSLAE GLRTVLGLIQ QHQHLCVFWT VNYGFEDPAV GQFLQRQLKR PRPVILDPAD 

       310        320        330        340        350        360 
PTWDLGNGAA WHWDLLAQEA ASCYDHPCFL RGMGDPVQSW KGPGLPRAGC SGLGHPIQLD 

       370        380        390        400        410        420 
PNQKTPENSK SLNAVYPRAG SKPPSCPAPG PTGAASIVPS VPGMALDLSQ IPTKELDRFI 

       430        440        450        460        470        480 
QDHLKPSPQF QEQVKKAIDI ILRCLHENCV HKASRVSKGG SFGRGTDLRD GCDVELIIFL 

       490        500        510        520        530        540 
NCFTDYKDQG PRRAEILDEM RAQLESWWQD QVPSLSLQFP EQNVPEALQF QLVSTALKSW 

       550        560        570        580        590        600 
TDVSLLPAFD AVGQLSSGTK PNPQVYSRLL TSGCQEGEHK ACFAELRRNF MNIRPVKLKN 

       610        620        630        640        650        660 
LILLVKHWYR QVAAQNKGKG PAPASLPPAY ALELLTIFAW EQGCRQDCFN MAQGFRTVLG 

       670        680        690        700        710        720 
LVQQHQQLCV YWTVNYSTED PAMRMHLLGQ LRKPRPLVLD PADPTWNVGH GSWELLAQEA 

       730        740        750        760        770        780 
AALGMQACFL SRDGTSVQPW DVMPALLYQT PAGDLDKFIS EFLQPNRQFL AQVNKAVDTI 

       790        800        810        820        830        840 
CSFLKENCFR NSPIKVIKVV KGGSSAKGTA LRGRSDADLV VFLSCFSQFT EQGNKRAEII 

       850        860        870        880        890        900 
SEIRAQLEAC QQERQFEVKF EVSKWENPRV LSFSLTSQTM LDQSVDFDVL PAFDALGQLV 

       910        920        930        940        950        960 
SGSRPSSQVY VDLIHSYSNA GEYSTCFTEL QRDFIISRPT KLKSLIRLVK HWYQQCTKIS 

       970        980        990       1000       1010       1020 
KGRGSLPPQH GLELLTVYAW EQGGKDSQFN MAEGFRTVLE LVTQYRQLCI YWTINYNAKD 

      1030       1040       1050       1060       1070       1080 
KTVGDFLKQQ LQKPRPIILD PADPTGNLGH NARWDLLAKE AAACTSALCC MGRNGIPIQP 


WPVKAAV 

« Hide

References

« Hide 'large scale' references
[1]"The 100-kDa 2',5'-oligoadenylate synthetase catalyzing preferentially the synthesis of dimeric pppA2'p5'A molecules is composed of three homologous domains."
Rebouillat D., Hovnanian A., Marie I., Hovanessian A.G.
J. Biol. Chem. 274:1557-1565(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION.
[2]"Molecular basis of T cell-mediated recognition of pancreatic cancer cells."
Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K.
Cancer Res. 61:2038-2046(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-18.
Tissue: Pancreatic cancer.
[3]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-381.
Tissue: Brain.
[5]"Characterization of the gene encoding the 100-kDa form of human 2', 5'oligoadenylate synthetase."
Rebouillat D., Hovnanian A., David G., Hovanessian A.G., Williams B.R.
Genomics 70:232-240(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-59.
Tissue: Monocyte.
[6]Bienvenut W.V., Gao M., Leug H.
Submitted (JUN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-17; 118-132; 244-253 AND 371-378, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Prostatic carcinoma.
[7]"The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation."
Hovanessian A.G., Justesen J.
Biochimie 89:779-788(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[8]"Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members against dengue virus infection."
Lin R.J., Yu H.P., Chang B.L., Tang W.C., Liao C.L., Lin Y.L.
J. Immunol. 183:8035-8043(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Evolution of the 2'-5'-oligoadenylate synthetase family in eukaryotes and bacteria."
Kjaer K.H., Poulsen J.B., Reintamm T., Saby E., Martensen P.M., Kelve M., Justesen J.
J. Mol. Evol. 69:612-624(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"The large form of human 2',5'-Oligoadenylate Synthetase (OAS3) exerts antiviral effect against Chikungunya virus."
Brehin A.C., Casademont I., Frenkiel M.P., Julier C., Sakuntabhai A., Despres P.
Virology 384:216-222(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities."
Kristiansen H., Gad H.H., Eskildsen-Larsen S., Despres P., Hartmann R.
J. Interferon Cytokine Res. 31:41-47(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF063613 mRNA. Translation: AAD28543.1. Frameshift.
AB044545 mRNA. Translation: BAB18647.1.
AC004551 Genomic DNA. No translation available.
BC113746 mRNA. Translation: AAI13747.1.
AF251351 Genomic DNA. No translation available.
CCDSCCDS44981.1.
RefSeqNP_006178.2. NM_006187.2.
UniGeneHs.528634.
Hs.744211.

3D structure databases

ProteinModelPortalQ9Y6K5.
SMRQ9Y6K5. Positions 407-740, 747-1081.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110994. 15 interactions.
IntActQ9Y6K5. 13 interactions.
MINTMINT-4991875.
STRING9606.ENSP00000228928.

PTM databases

PhosphoSiteQ9Y6K5.

Polymorphism databases

DMDM317373408.

Proteomic databases

MaxQBQ9Y6K5.
PaxDbQ9Y6K5.
PRIDEQ9Y6K5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000228928; ENSP00000228928; ENSG00000111331.
GeneID4940.
KEGGhsa:4940.
UCSCuc001tug.3. human.

Organism-specific databases

CTD4940.
GeneCardsGC12P113376.
H-InvDBHIX0201822.
HGNCHGNC:8088. OAS3.
HPAHPA041253.
HPA041372.
MIM603351. gene.
neXtProtNX_Q9Y6K5.
PharmGKBPA31877.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG124087.
HOGENOMHOG000013200.
HOVERGENHBG007856.
InParanoidQ9Y6K5.
KOK14216.
OMACQGGEHA.
OrthoDBEOG7WDN1R.
PhylomeDBQ9Y6K5.
TreeFamTF329749.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000111331-MONOMER.
ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9Y6K5.
BgeeQ9Y6K5.
CleanExHS_OAS3.
GenevestigatorQ9Y6K5.

Family and domain databases

Gene3D1.10.1410.20. 3 hits.
InterProIPR006117. 2-5-oligoadenylate_synth_CS.
IPR006116. 2-5-oligoadenylate_synth_N.
IPR018952. 2-5-oligoAdlate_synth_1_dom2/C.
IPR026774. 2-5A_synthase.
IPR002934. Nucleotidyltransferase.
[Graphical view]
PANTHERPTHR11258. PTHR11258. 1 hit.
PfamPF01909. NTP_transf_2. 1 hit.
PF10421. OAS1_C. 3 hits.
[Graphical view]
PROSITEPS00832. 25A_SYNTH_1. 3 hits.
PS00833. 25A_SYNTH_2. 2 hits.
PS50152. 25A_SYNTH_3. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSOAS3. human.
GeneWikiOAS3.
GenomeRNAi4940.
NextBio19035.
PROQ9Y6K5.
SOURCESearch...

Entry information

Entry nameOAS3_HUMAN
AccessionPrimary (citable) accession number: Q9Y6K5
Secondary accession number(s): Q2HJ14, Q9H3P5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM