Q9Y6K5 (OAS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1087 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Antiviral defense Immunity Innate immunity
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding RNA-binding
Molecular function	Nucleotidyltransferase Transferase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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 type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome intracellular membrane-bounded organelle Traceable author statement PubMed 2440675. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	2'-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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DHX30	Q7L2E3	2	EBI-6115729,EBI-1211456
EIF6	P56537	2	EBI-6115729,EBI-372243
FTSJ3	Q8IY81	2	EBI-6115729,EBI-744088
IFRD2	Q12894	2	EBI-6115729,EBI-6115935
MAVS	Q7Z434	2	EBI-6115729,EBI-995373

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1087	1087	2'-5'-oligoadenylate synthase 3		PRO_0000160265
Regions
	Region	6 – 343	338	OAS domain 1
	Region	344 – 410	67	Linker
	Region	411 – 742	332	OAS domain 2
	Region	750 – 1084	335	OAS domain 3
Sites
	Metal binding	816	1	Magnesium; catalytic Potential
	Metal binding	818	1	Magnesium; catalytic Potential
	Metal binding	888	1	Magnesium; catalytic Potential
	Binding site	947	1	Substrate By similarity
	Binding site	950	1	ATP By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.6
Natural variations
	Natural variant	18	1	R → K. Ref.2 Corresponds to variant rs1859330 [ dbSNP | Ensembl ].		VAR_060076
	Natural variant	18	1	R → M. Corresponds to variant rs1859330 [ dbSNP | Ensembl ].		VAR_060077
	Natural variant	18	1	R → T. Corresponds to variant rs1859330 [ dbSNP | Ensembl ].		VAR_060078
	Natural variant	65	1	R → W. Corresponds to variant rs12819767 [ dbSNP | Ensembl ].		VAR_057660
	Natural variant	378	1	R → K. Corresponds to variant rs45519442 [ dbSNP | Ensembl ].		VAR_062127
	Natural variant	381	1	S → R. Ref.4 Corresponds to variant rs2285933 [ dbSNP | Ensembl ].		VAR_057661
	Natural variant	869	1	R → H. Corresponds to variant rs16942374 [ dbSNP | Ensembl ].		VAR_057662
Experimental info
	Sequence conflict	159	1	G → A in AAD28543. Ref.1
	Sequence conflict	249	1	A → G in AAD28543. Ref.1
	Sequence conflict	287 – 288	2	QL → HV in AAD28543. Ref.1
	Sequence conflict	316	1	L → H in AAD28543. Ref.1
	Sequence conflict	393	1	G → A in AAD28543. Ref.1
	Sequence conflict	503 – 504	2	QL → HV in AAD28543. Ref.1
	Sequence conflict	503 – 504	2	QL → HV in BAB18647. Ref.2
	Sequence conflict	984	1	G → R in BAB18647. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6K5 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 36DAADE4574DE961	FASTA	1,087	121,170
	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

References

	« Hide 'large scale' referencesShow '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. , 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, 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.
+	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.
IPI	IPI00002405.
RefSeq	NP_006178.2. NM_006187.2.
UniGene	Hs.528634. Hs.737661.
3D structure databases
ProteinModelPortal	Q9Y6K5.
SMR	Q9Y6K5. Positions 406-743, 747-1081.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6K5. 13 interactions.
STRING	9606.ENSP00000228928.
PTM databases
PhosphoSite	Q9Y6K5.
Polymorphism databases
DMDM	32470620.
Proteomic databases
PaxDb	Q9Y6K5.
PRIDE	Q9Y6K5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000228928; ENSP00000228928; ENSG00000111331.
GeneID	4940.
KEGG	hsa:4940.
UCSC	uc001tug.3. human.
Organism-specific databases
CTD	4940.
GeneCards	GC12P113376.
H-InvDB	HIX0201822.
HGNC	HGNC:8088. OAS3.
HPA	HPA041253. HPA041372.
MIM	603351. gene.
neXtProt	NX_Q9Y6K5.
PharmGKB	PA31877.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG124087.
HOGENOM	HOG000013200.
HOVERGEN	HBG007856.
InParanoid	Q9Y6K5.
KO	K14216.
OMA	YAWEQGG.
OrthoDB	EOG4GTKD5.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000111331-MONOMER.
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9Y6K5.
Bgee	Q9Y6K5.
CleanEx	HS_OAS3.
Genevestigator	Q9Y6K5.
GermOnline	ENSG00000111331. Homo sapiens.
Family and domain databases
Gene3D	1.10.1410.20. 3 hits.
InterPro	IPR006117. 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]
PANTHER	PTHR11258. PTHR11258. 1 hit.
Pfam	PF01909. NTP_transf_2. 1 hit. PF10421. OAS1_C. 3 hits. [Graphical view]
PROSITE	PS00832. 25A_SYNTH_1. 3 hits. PS00833. 25A_SYNTH_2. 2 hits. PS50152. 25A_SYNTH_3. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	OAS3. human.
GenomeRNAi	4940.
NextBio	19035.
SOURCE	Search...

Entry information

Entry name

OAS3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 105 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.