Any feedback?
Information on EC 2.7.7.84 - 2'-5' oligoadenylate synthase
for references in articles please use BRENDA:EC2.7.7.84Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.7.7.84 2'-5' oligoadenylate synthaseIUBMB Comments
The enzyme is activated by binding to double-stranded RNA. The resulting product binds to and activates RNase L, which subsequently degrades the RNA. Oligoadenylates of chain lengths 2, 4 and 5 are also produced. The dimer does not have any known biological activity .
Specify your search results
Word Map
- 2.7.7.84
-
interferon-induced
-
ifn-induced
- ifn-alpha
- viruses
- interferon-alpha
-
ifn-beta
- ifn-gamma
- synthetases
- dsrna
-
ifn-stimulated
-
antiproliferative
- stomatitis
- interferon-beta
-
interferon-stimulated
-
myxovirus
- stat1
- alpha-interferon
-
interferon-treated
-
encephalomyocarditis
- neopterin
-
2-microglobulin
- flavivirus
-
daudi
-
ifn-treated
-
dsrna-dependent
-
2'-5'oligoadenylate
-
endoribonuclease
-
ifn-mediated
-
ifn-alpha-induced
- isg15
-
2-5a-dependent
-
dsrna-activated
- cydonium
-
ifn-dependent
-
polyi
-
rnasel
-
polyinosinic-polycytidylic
- geodia
-
interferon-mediated
-
ifn-resistant
-
anticellular
- analysis
- medicine
The enzyme appears in viruses and cellular organisms
Synonyms
2-5a synthetase, 2',5'-oligoadenylate synthetase, 2'-5'-oligoadenylate synthetase, 2'-5' oligoadenylate synthetase, oas1b, oas1a, 2'-5'-oligoadenylate synthetase 1, 2'-5'oas, 2'5' oligoadenylate synthetase, oligoadenylate synthetase-like, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2',5'-oligoadenylate synthetase 1
2'-5' oligoadenylate synthetase
2'-5'-oligoadenylate synthetase
2'5' oligoadenylate synthetase
OAS
OAS-L
OAS1
OAS1A
OAS1b
OAS1c
OAS1d
OAS1e
OAS1f
OAS1g
OAS1h
OAS2
OAS3
OASL
2',5'-oligoadenylate synthetase 1
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3 ATP = pppA2'p5'A2'p5'A + 2 diphosphate
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
ATP:ATP adenylyltransferase (2'-5' linkages-forming)
The enzyme is activated by binding to double-stranded RNA. The resulting product binds to and activates RNase L, which subsequently degrades the RNA. Oligoadenylates of chain lengths 2, 4 and 5 are also produced. The dimer does not have any known biological activity [2].
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 ATP
pppA2'p5'A + diphosphate
-
synthesis of 2-5A dimer, trimer and tetramer with the prevalence of dimer among reaction products
-
?
3 ATP
pppA2'p5'A3'p5'A + 2 diphosphate
-
enzyme synthesizes triadenylates with the first linkage being a 2',5'-phosphodiester bond and the second one being a 3',5'-bond. The ratio of products containing 2',5'-linkage to the products with 3',5'-linkage is 2.4 in the presence of 100 mg/ml poly(I)poly(C)
-
?
NTP + pppA2'p5'A
pppA2'p5'Ap2'p5'N + 2 diphosphate
-
reaction of OAS2, broad spectrum of accepted donor substrates, including ATP, GTP, CTP, UTP, ITP, and their deoxy variants, overview
-
-
?
NTP + RpA
RpA2'p5'N + 2 diphosphate
-
reaction of OAS3, broad spectrum of accepted donor substrates, including ATP, GTP, CT, UTP, ITP, and their deoxy variants, and of acceptor substrates including tRNA, A5'ppp5''A, A5'pppp5''A, NAD+, and polyA, overview
-
-
?
3 ATP
pppA2'p5'A2'p5'A + 2 diphosphate
during the synthesis of 2-5A, one ATP, known as the donor, transfers its AMP moiety to a second ATP, known as the acceptor. For polymerization, the acceptor ATP is replaced by a growing chain of 2-5A
-
-
?
3 ATP
pppA2'p5'A2'p5'A + 2 diphosphate
-
-
-
?
additional information
?
-
enzyme duOASL possesses the enzymatic activity to convert the ATP to 2'-5'-A up to tetramer
-
-
-
additional information
?
-
-
enzyme duOASL possesses the enzymatic activity to convert the ATP to 2'-5'-A up to tetramer
-
-
-
additional information
?
-
enzyme goOASL possesses the enzymatic activity to convert the ATP to 2'-5'-A up to tetramer
-
-
-
additional information
?
-
-
the 2'5' oligoadenylate synthetase has a multifunctional 2',5' nucleotidyl-transferase activity
-
-
?
additional information
?
-
enzyme chOASL possesses the enzymatic activity to convert the ATP to 2'-5'-A up to tetramer
-
-
-
additional information
?
-
-
enzyme chOASL possesses the enzymatic activity to convert the ATP to 2'-5'-A up to tetramer
-
-
-
additional information
?
-
-
the 2'5' oligoadenylate synthetase has a multifunctional 2',5' nucleotidyl-transferase activity
-
-
?
additional information
?
-
-
whereas only two 2',5'-adenylates that inhibit protein synthesis (i.e., trimer and tetramer) are synthesized by normal peripheral blood mononuclear cells, trimer, tetramer, pentamer, and hexamer are synthesized by peripheral blood mononuclear cells from cutaneous T-cell lymphomas
-
-
?
additional information
?
-
-
addition of high concentrations of tRNA (2 mg/ml) does not relieve the absolute dependence on double stranded RNA for 2' adenylation activity and 2'5' oligoadenylate synthetase activity in an extract of human Wish cells
-
-
?
additional information
?
-
-
isozyme OAS1 is specific for ATP, but isozyme OAS2 shows broad substrate specificity accepting diverse nucleotide triphosphates as donor substrates that give several products, overview. Isozymes OAS1 and OAS2 produce 2-5A oligomers, while isozyme OAS3 produces 2-5A dimers. GTP is an alternative substrate for the 2'-5'OAS, as donor as well as acceptor molecule. Nevertheless, competition experiments of GTP versus ATP points out that GTP exhibits a much higher affinity for the donor site of OAS than for the acceptor one. A monomeric OAS-like protein, OASL, is catalytically inactive
-
-
?
additional information
?
-
catalytic activity of OAS proteins incubated with polyriboinosinic polyribocytidylic acid [poly (I:C)] in a buffered solution with ATP and MgCl2 at 37°C
-
-
-
additional information
?
-
catalytic activity of OAS proteins incubated with polyriboinosinic polyribocytidylic acid [poly (I:C)] in a buffered solution with ATP and MgCl2 at 37°C
-
-
-
additional information
?
-
-
catalytic activity of OAS proteins incubated with polyriboinosinic polyribocytidylic acid [poly (I:C)] in a buffered solution with ATP and MgCl2 at 37°C
-
-
-
additional information
?
-
-
the 2'5' oligoadenylate synthetase has a multifunctional 2',5' nucleotidyl-transferase activity
-
-
?
additional information
?
-
-
besides accepting AMP, the NAD+ molecule can accept UMP, CMP, GMP and dAMP and probably other NMP catalyzed by the rabbit reticulocyte synthetase, UMP, CMP, and dAMP as well as AMP are incorporated into NAD+ at about half the rate of AMP incorporation into 2'5'-oligoadenylates, overview. A natural RNA, tRNA, can also be used as a primer for the 2' adenylation by both the the mouse L-cell enzyme. NADP+ does not serve as substrate
-
-
?
additional information
?
-
-
substrate specificity and possible products, overview. Selected nucleoside 5'-triphosphates are converted to 2',5'-oligonucleotides with the following order of efficiency for the nucleoside: 8-azaadenosine > adenosine = 2-chloroadenosine > sangivamycin > toyocamycin > formycin > 3-ribosyladenine > ribavirin > tubercidin > adenosine 1-oxide > 2-beta-D-ribofuranosylthiazole-4-carboxamide > inosine = 1,N6-ethenoadenosine > guanosine > 8-bromoadenosine = uridine > cytidine. Adenosine 5'-(beta,gamma-imidotriphosphate) is no substrate
-
-
?
additional information
?
-
-
the 2'5' oligoadenylate synthase has a multifunctional 2',5'-nucleotidyl-transferase activity
-
-
?
additional information
?
-
-
besides accepting AMP, the NAD+ molecule can accept UMP, CMP, GMP, and dAMP and probably other NMP catalyzed by the rabbit reticulocyte synthetase, UMP, CMP, and dAMP as well as AMP are incorporated into NAD+ at about half the rate of AMP incorporation into 2'5' oligoadenylates, overview. A natural RNA, tRNA, can also be used as a primer for the 2' adenylation by both the rabbit reticulocyte enzyme. NADP+ does not serve as substrate
-
-
?
additional information
?
-
enzyme osOASL possesses the enzymatic activity to convert the ATP to 2'-5'-A up to tetramer, very low activity
-
-
-
additional information
?
-
enzyme polymerizes ATP into 2',5'-linked and 3'-5'-linked oligoadenylates in the presence of synthetic dsRNA poly(I)poly(C). The presence of dsRNA is required
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3 ATP
pppA2'p5'A2'p5'A + 2 diphosphate
-
-
-
?
additional information
?
-
-
the 2'5' oligoadenylate synthetase has a multifunctional 2',5' nucleotidyl-transferase activity
-
-
?
additional information
?
-
-
the 2'5' oligoadenylate synthetase has a multifunctional 2',5' nucleotidyl-transferase activity
-
-
?
additional information
?
-
-
whereas only two 2',5'-adenylates that inhibit protein synthesis (i.e., trimer and tetramer) are synthesized by normal peripheral blood mononuclear cells, trimer, tetramer, pentamer, and hexamer are synthesized by peripheral blood mononuclear cells from cutaneous T-cell lymphomas
-
-
?
additional information
?
-
-
the 2'5' oligoadenylate synthetase has a multifunctional 2',5' nucleotidyl-transferase activity
-
-
?
additional information
?
-
-
the 2'5' oligoadenylate synthase has a multifunctional 2',5'-nucleotidyl-transferase activity
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
activates, after stimulation with dsRNA, OAS requires two Mg2+ ions and two molecules of ATP to perform its enzymatic activity. Residues Ser396, Gln528, Lys547, Lys566, and Tyr567 are involved in positioning of the donor ATP, while residues Val412, Arg463, Leu483, Ser 521, Thr522, Thr525, and Gln528 are involved in positioning of the acceptor ATP
ATP
activates, after stimulation with dsRNA, OAS requires two Mg2+ ions and two molecules of ATP to perform its enzymatic activity. Residues Ser63, Gln194, Lys213, Gln229, and Tyr230 are involved in positioning of the donor ATP, while residues Val79, Arg130, Leu150, Ser 187, Thr188, Thr191, and Gln194 are involved in positioning of the acceptor ATP
ATP
activates, after stimulation with dsRNA, OAS requires two Mg2+ ions and two molecules of ATP to perform its enzymatic activity. Residues Ser804, Gln931, Lys950, Gln969, and His970 are involved in positioning of the donor ATP, while residues Val820, Arg869, Leu890, Ser924, Thr925, Thr928, and Gln931 are involved in positioning of the acceptor ATP
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
-
the catalysis of 2'-5'-oligoadenylate synthesis is strictly dependent on double-stranded RNA and magnesium ions
Mg2+
activates, after stimulation with dsRNA, OAS requires two Mg2+ ions and two molecules of ATP to perform its enzymatic activity. The Mg2+ ions play a critical role in positioning the substrates in an ideal geometry for the reaction, binding structure modeling, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Zn2+
-
strong inhibition, zinc ions can control the oligomerisation by enhancing the formation of tetrameric forms of OAS1p42
additional information
inhibitor screening and identification of 12 compounds exerting competitive inhibition in the ATP binding site1 of OAS1 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors; inhibitor screening and identification of 18 compounds exerting competitive inhibition in the ATP binding site of OAS2 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors; inhibitor screening and identification of 7 compounds exerting competitive inhibition in the ATP binding site of OAS3 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors
-
additional information
inhibitor screening and identification of 12 compounds exerting competitive inhibition in the ATP binding site1 of OAS1 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors; inhibitor screening and identification of 18 compounds exerting competitive inhibition in the ATP binding site of OAS2 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors; inhibitor screening and identification of 7 compounds exerting competitive inhibition in the ATP binding site of OAS3 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors
-
additional information
inhibitor screening and identification of 12 compounds exerting competitive inhibition in the ATP binding site1 of OAS1 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors; inhibitor screening and identification of 18 compounds exerting competitive inhibition in the ATP binding site of OAS2 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors; inhibitor screening and identification of 7 compounds exerting competitive inhibition in the ATP binding site of OAS3 protein, independently of the activation state of the enzyme, docking and interaction study. Although there is little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids are mainly promoted by heterocycles with Pi electrons and hydrogen bond acceptors
-
additional information
-
presence of a nucleoside triphosphate other than ATP also reduces the rate of 2'5' oligoadenylate formation indicating a competition between ATP and NTP for the donor site
-
additional information
-
presence of a nucleoside triphosphate other than ATP also reduces the rate of 2'5'-oligoadenylate formation indicating a competition between ATP and NTP for the donor site
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
viral dsRNA
-
2'-5'-oligoadenylate synthases are activated by viral double-stranded RNA in infected cells and initiate a cellular response by synthesizing 2'-5'-oligoadenylates, which in turn activate RNase L. All mammalian OAS proteins require dsRNA for activity ssRNA or DNA does not activate this class of enzymes. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. OAS1 RNA activation site structure, overview
-
viral RNA VAI
-
sequences and secondary structures of adenovirus VAI dsRNAs, overview. Highly structured RNA, VAI, positively regulates the activity of the interferon-induced 2'5'-oligoadenylate synthase, which typically represents a key mechanism whereby host-cell protein translation is attenuated in response to foreign dsRNA. In the contrary, with other cell proteins, RNA VAI, after processing by the RNA silencing machinery, inhibits the innate immune response via a series of interactions with specific protein partners. OAS1:VAI complex stoichiometry and kinetics, overview. The RNA 5'-end phosphorylation state is important in the activation or inhibition of OAS enzymes. While full-length VAI does indeed activate OAS1 in vitro, the Dicer-truncated molecule lacking the terminal stem has the opposite effect, and this is the physiologically important response, overview
-
dsRNA
-
the catalysis of 2'-5'-oligoadenylate synthesis is strictly dependent on double-stranded RNA and magnesium ions
-
dsRNA
-
the enzyme is dependent on dsRNA, activation of isozyme OAs3 by 0.001 mg/ml, and of isozymes AS1 and OAS2 by 0.1 mg/ml, at optimals pH values
-
dsRNA
OAS1 can be catalytically activated by dsRNA of any length greater than 19 bp. Highly structured viral RNAs are established OAS1 activators, but they are not able to activate OAS2 enzymatic activity based on the lack of extended stretches of dsRNA of greater than 35 bp. In-vitro transcribtion of WNV 5' TR, WNV 3' TR, VAI, VAIDELTATS, HIV-TAR, and EBER-1 from linearized plasmids using T7 polymerase, with the exceptions of HIV-TAR and EBER-1, all viral RNAs can activate OAS1 to some extent. Whereas 5'-TR and 3'-TR achieve potent activation, VAI and VAIDELTATS are only modestly above baseline
-
dsRNA
OAS2 shows a marked increase in activity with increasing dsRNA length with a minimum requirement of 35 bp. Activation of OAS2 is also more efficient when the dsRNA contained 3'-overhangs, despite no significant impact on binding affinity. The OAS2 activation potential is dependent on dsRNA length, kinetic analysis, overview. In-vitro transcribtion of WNV 5' TR, WNV 3' TR, VAI, VAIDELTATS, HIV-TAR, and EBER-1 from linearized plasmids using T7 polymerase, none of the RNAs can activate isozyme OAS2
-
dsRNA
-
double-stranded RNA, synthetic poly(I:C), an allosteric activator of the latent (2-5)A synthetase
-
dsRNA
2'-5'-oligoadenylate synthases are activated by viral double-stranded RNA in infected cells and initiate a cellular response by synthesizing 2'-5'-oligoadenylates, which in turn activate RNase L. All mammalian OAS proteins require dsRNA for activity ssRNA or DNA does not activate this class of enzymes. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. OAS1 RNA activation site structure, overview
-
additional information
highly structured viral RNAs that are established OAS1 activators are not able to activate OAS2 enzymatic activity based on the lack of extended stretches of dsRNA of greater than 35 bp. Phosphorylation state of the 5' end of dsRNA activators does not affect OAS2 activation
-
additional information
highly structured viral RNAs that are established OAS1 activators are not able to activate OAS2 enzymatic activity based on the lack of extended stretches of dsRNA of greater than 35 bp. Phosphorylation state of the 5' end of dsRNA activators does not affect OAS2 activation
-
additional information
-
highly structured viral RNAs that are established OAS1 activators are not able to activate OAS2 enzymatic activity based on the lack of extended stretches of dsRNA of greater than 35 bp. Phosphorylation state of the 5' end of dsRNA activators does not affect OAS2 activation
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00044
ATP
wild-type OAS1, with ATP as sole substrate, pH and temperature not specified in the publication
0.0017
ATP
OAS1 mutant K212A, with ATP as sole substrate, pH and temperature not specified in the publication
0.0011
NAD+
OAS1 mutant S62A, with ATP and NAD+ as substrates, pH and temperature not specified in the publication
0.0013
NAD+
wild-type OAS1, with ATP and NAD+ as substrates, pH and temperature not specified in the publication
0.0014
NAD+
OAS1 mutant S63A, with ATP and NAD+ as substrates, pH and temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.95
ATP
OAS1 mutant K212A, with ATP as sole substrate, pH and temperature not specified in the publication
8.1
ATP
wild-type OAS1, with ATP as sole substrate, pH and temperature not specified in the publication
0.99
NAD+
OAS1 mutant S62A, with ATP and NAD+ as substrates, pH and temperature not specified in the publication
3.6
NAD+
OAS1 mutant S63A, with ATP and NAD+ as substrates, pH and temperature not specified in the publication
3.6
NAD+
wild-type OAS1, with ATP and NAD+ as substrates, pH and temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0005
OAS1 mutant R38E/K41E/K59E/R194E/R198E, pH and temperature not specified in the publication
0.001
OAS1 mutant R194E/R198E, pH and temperature not specified in the publication
0.004
OAS1 mutant R198E, pH and temperature not specified in the publication
0.007
OAS1 mutant R198M, pH and temperature not specified in the publication
0.016
OAS1 mutant R38E/K41E, pH and temperature not specified in the publication
0.05
OAS1 mutant K203E, pH and temperature not specified in the publication
0.117
OAS1 mutant K59E, pH and temperature not specified in the publication
0.17
OAS1 mutant R194E, pH and temperature not specified in the publication
3.3
OAS1 mutant R245E/K246E, pH and temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
freshwater sponge, collected in Lake Baikal (Russia) from an unpolluted, natural site near the village of Listvianka, gene LB2-5OAS
-
-
brenda
Mus musculus C57BL/6J (B6)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
peripheral blood mononuclear cells from healthy persons, and obtained from cutaneous T-cell lymphomas
brenda
-
no appreciable difference in 2',5'-oligoadenylate synthetase activity is found between T-cells and non-T-cells from cutaneous T-cell lymphomas, increased activity of 2'5'-oligoadenylate synthetase in PBMC from cutaneous T-cell lymphomas forming tetramer, pentamer, and hexamer products
brenda
-
lymphoid cell of thymus, expression increases during inflammatory processes under ulcerogenic conditions caused by stress factors
brenda
additional information
-
highest expression of the gene occurs in cells surrounding the aquiferous canals
brenda
in the brain, only Oas1a, Oas1b, and Oas1g are expressed in the mice stimulated with poly I:C
brenda
Mus musculus C57BL/6J (B6)
-
in the brain, only Oas1a, Oas1b, and Oas1g are expressed in the mice stimulated with poly I:C
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
association of this form of OAS with membranes of the nuclear envelope and the rough endoplasmic reticulum
brenda
-
association of this form of OAS with membranes of the nuclear envelope and the rough endoplasmic reticulum
brenda
additional information
additional information
-
three distinct forms of 2'-5'OAS exist in human cells, that show distinct subcellular localizations
-
brenda
additional information
the CaaX motif (C = cysteine, a = aliphatic amino acid, X = terminal amino acid) in OAS1 is of key importance to the cellular localization, it is present in the C-terminal of only the p46 isoform, localization study, detailed overview. The wild-type OAS1 p42 isozyme is highly dispersed in the cytosol, but changes to a more organelle-associated protein when the CaaX motif is added. The same correlation between the CaaX motif and spatial distribution can be observed with endogenous OAS1 protein in IFN-beta treated HeLa cells (only p42) and HT-1080 cells (mainly p46)
-
brenda
additional information
-
the CaaX motif (C = cysteine, a = aliphatic amino acid, X = terminal amino acid) in OAS1 is of key importance to the cellular localization, it is present in the C-terminal of only the p46 isoform, localization study, detailed overview. The wild-type OAS1 p42 isozyme is highly dispersed in the cytosol, but changes to a more organelle-associated protein when the CaaX motif is added. The same correlation between the CaaX motif and spatial distribution can be observed with endogenous OAS1 protein in IFN-beta treated HeLa cells (only p42) and HT-1080 cells (mainly p46)
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
-
conserved catalytic mechanism for the 2'- and 3'-specific nucleotidyl transferases. specific nucleotidyl transferases. Comparison with structures of other superfamily members indicates that the donor substrates are bound by conserved active site features while the acceptor substrates are oriented by nonconserved regions
evolution
conserved catalytic mechanism for the 2'- and 3'-specific nucleotidyl transferases. specific nucleotidyl transferases. Comparison with structures of other superfamily members indicates that the donor substrates are bound by conserved active site features while the acceptor substrates are oriented by nonconserved regions
evolution
in mice, the OAS gene family locates on chromosome 5 and consists of eight genes of Oas1 (Oas1a through Oas1h), Oas2, Oas3, and two OasL genes (OasL1 and OasL2). Oas1a and Oas1g are only active to convert ATP into di- and tri-2,5A, whereas Oas1b, Oas1c, Oas1d, Oas1e, Oas1f, Oas1h and MSM-derived Oas1b are inactive
evolution
isozyme OAS1 belongs to the 2'-5'-oligoadenylate synthetases (OAS) family of interferon-inducible enzymes that act as pattern recognition receptors (PRR) to bind double-stranded RNA (dsRNA) during viral infection. The C-terminal catalytic domain of OAS2 (DII) shares strong sequence homology and catalytic aspartic acids (D408, D410, D481) with OAS1
evolution
isozyme OAS2 belongs to the 2'-5'-oligoadenylate synthetases (OAS) family of interferon-inducible enzymes that act as pattern recognition receptors (PRR) to bind double-stranded RNA (dsRNA) during viral infection. The C-terminal catalytic domain of OAS2 (DII) shares strong sequence homology and catalytic aspartic acids (D408, D410, D481) with OAS1iral infection
evolution
Mus musculus C57BL/6J (B6)
-
in mice, the OAS gene family locates on chromosome 5 and consists of eight genes of Oas1 (Oas1a through Oas1h), Oas2, Oas3, and two OasL genes (OasL1 and OasL2). Oas1a and Oas1g are only active to convert ATP into di- and tri-2,5A, whereas Oas1b, Oas1c, Oas1d, Oas1e, Oas1f, Oas1h and MSM-derived Oas1b are inactive
-
malfunction
-
cells transfected with 25 AS antisense oligonucleotides inhibit the antiviral effect of IFN-gamma
malfunction
-
mutation of the conserved Leu3 and Pro7 and of Cys330, Cys331, and Lys332 reduce enzyme activity
malfunction
mutation of the conserved Leu3 and Pro7 and of Cys330, Cys331, and Lys332 reduce enzyme activity. Mutants S62A and S63A display Michaelis-Menten kinetics toward NAD+, the kcat of the Ser62Ala mutant is approximately 3fold lower than the kcat for either the wild-type or the S63A mutant
malfunction
knockdown of endogenous OAS1 increases the PRRSV ORF7 mRNA level to 1.6 and 1.7times of that in control in 24 and 36 hours post-infection of PRRSV, respectively, and leads to approximate 5.5times increase of the frequency of fluorescence positive cells compared to negative control. Overexpression of OAS1 in Marc-145 cells can inhibit the replication of PRRSV
malfunction
OAS2 knockdown increases ZIKV replication. Overexpression of OAS2 modestly increases the IFN-induced p-STAT1 both with IFN treatment and without IFN treatment compared to control. OAS2 overexpression also increases ISRE activity and some classical ISGs expression including Myxovirus resistance-A (MxA) and interferon-induced protein 2 (IFIT2)
malfunction
the effects of OASL silencing on cytokine and chemokine (MCP-1) secretion in THP-1 macrophages can be summarised as follows: I. TNF-alpha and IL-1beta secretion is enhanced during mycobacterial infection in the presence of OASL, II. OASL enhances MCP-1 production in response to THP-1 infection by pathogenic mycobacteria only, and III. IL-10 production is unaffected by the presence/absence of OASL. Silencing of OASL promotes intracellular replication of pathogenic and non-pathogenic mycobacteria, OASL exerts a suppressive effect on intracellular mycobacterial replication
metabolism
only Oas1a and Oas1g show enzymatic activity. Although MSM-derived Oas1b shows antiviral activity in BHK-21 cells to both viruses, the two neurotropic flaviviruses, West Nile virus and tick-borne encephalitis virus, but all B6-derived OAS paralogues do not show antiviral activity. Paralogues Oas1a and Oas1g play a role in potentiating viral RNA-induced interferon response in the cell, whereas the paralogue Oas1b works as a specific anti-flavivirus factor unless it is mutated. The role of other paralogues (OAS1c, d, e, f, and h) is unknown to date
metabolism
only Oas1a and Oas1g show enzymatic activity. Although MSM-derived Oas1b shows antiviral activity to both viruses, the two neurotropic flaviviruses, West Nile virus and tick-borne encephalitis virus, but all B6-derived OAS paralogues do not show antiviral activity. Paralogues Oas1a and Oas1g play a role in potentiating viral RNA-induced interferon response in the cell, whereas the paralogue Oas1b works as a specific anti-flavivirus factor unless it is mutated. The role of other paralogues (OAS1c, d, e, f, and h) is unknown to date
metabolism
the human 2',5'-oligoadenylate synthetase (OAS) are IFN-induced genes that play an essential role in the antiviral activity of IFNs. The OAS family is composed of four gene members, including OAS1, OAS2, OAS3, and OAS-like protein (OASL), differing in numbers of OAS domain, type of synthesized 2-5A and oligomerization level
metabolism
Mus musculus C57BL/6J (B6)
-
only Oas1a and Oas1g show enzymatic activity. Although MSM-derived Oas1b shows antiviral activity in BHK-21 cells to both viruses, the two neurotropic flaviviruses, West Nile virus and tick-borne encephalitis virus, but all B6-derived OAS paralogues do not show antiviral activity. Paralogues Oas1a and Oas1g play a role in potentiating viral RNA-induced interferon response in the cell, whereas the paralogue Oas1b works as a specific anti-flavivirus factor unless it is mutated. The role of other paralogues (OAS1c, d, e, f, and h) is unknown to date
-
metabolism
Mus musculus C57BL/6J (B6)
-
only Oas1a and Oas1g show enzymatic activity. Although MSM-derived Oas1b shows antiviral activity to both viruses, the two neurotropic flaviviruses, West Nile virus and tick-borne encephalitis virus, but all B6-derived OAS paralogues do not show antiviral activity. Paralogues Oas1a and Oas1g play a role in potentiating viral RNA-induced interferon response in the cell, whereas the paralogue Oas1b works as a specific anti-flavivirus factor unless it is mutated. The role of other paralogues (OAS1c, d, e, f, and h) is unknown to date
-
physiological function
-
2'-5' oligoadenylate synthase plays a critical role in interferon-gamma inhibition of respiratory syncytial virus infection of human epithelial cells. Respiratory syncytial virus, RSV, associated with bronchiolitis and asthma, is resistant to the antiviral effects of type-I interferons, but not IFN-gamma, molecular mechanism involving the 2',5'-oligoadenylate synthetase, overview
physiological function
-
2'-5'-oligoadenylate synthases are interferon-induced, double-stranded RNA-activated antiviral enzymes which are the only proteins known to catalyze 2'-specific nucleotidyl transfer
physiological function
2'-5'-oligoadenylate synthases are interferon-induced, double-stranded RNA-activated antiviral enzymes which are the only proteins known to catalyze 2'-specific nucleotidyl transfer
physiological function
-
2'-5'OASs are initially described as important components of the antiviral action of interferon. But the structural and functional complexity of the human 2'-5'OAS family implying that these proteins may have distinct roles in the cell. 2'-5'OAS forms 2-5A molecules that activate the latent endoribonuclease. The RNAse L. OAS1 and OAS2 mediate resistance to virus infections, OAS3 appears to confer sensitivity to dsRNA-induced apoptosis via a mechanism that does not require the synthesis of 2-5A
physiological function
-
2'5' oligoadenylate synthase catalyzes the synthesis of a series of 2'5' heteronucleotides with the general structure of pppA(pA)nPN and NAD-NMP. NAD+ acts as an acceptor for 2'-adenylation by the enzyme isolated from interferon treated chicken cell. The requirement for the acceptor site is an AMP group linked in a RpA configuration where R stands for pyrophosphate, NAD+, oligomeric or polymeric primers. NAD+ tRNA may play a regulatory role in 2'5'-oligoadenylates synthesis in the cell
physiological function
-
2'5' oligoadenylate synthase catalyzes the synthesis of a series of 2'5' heteronucleotides with the general structure of pppA(pA)nPN and NAD-NMP. The enzyme also catalyzes the 2' adenylation of tRNA. The requirement for the acceptor site is an AMP group linked in a RpA configuration where R stands for pyrophosphate, NAD+, oligomeric or polymeric primers. NAD+ tRNA may play a regulatory role in 2'5'-oligoadenylates synthesis in the cell
physiological function
-
2'5' oligoadenylate synthase catalyzes the synthesis of a series of 2'5' heteronucleotides with the general structure of pppA(pA)nPN and NAD-NMP. The enzyme also catalyzes the 2' adenylation of tRNA. The requirement for the acceptor site is an AMP group linked in a RpA configuration where R stands for pyrophosphate, NAD+, oligomeric or polymeric primers. NAD+ tRNA may play a regulatory role in 2'5'-oligoadenylates synthesis in the cell
physiological function
-
2'5'-oligoadenylate synthase catalyzes the synthesis of a series of 2'5'-heteronucleotides with the general structure of pppA(pA)nPN and NAD-NMP. NAD+ acts as an acceptor for 2'-adenylation by the enzyme isolated from interferon treated chicken cell. The requirement for the acceptor site is an AMP group linked in a RpA configuration where R stands for pyrophosphate, NAD+, oligomeric or polymeric primers. NAD+ tRNA may play a regulatory role in 2'5'-oligoadenylates synthesis in the cell
physiological function
-
highly structured RNA, VAI, is able to positively regulate the activity of the interferon-induced 2'5'-oligoadenylate synthase, a processed version of VAI lacking the terminal stem behaves as a pseudo-inhibitor of OAS1. The RNA 5'-end phosphorylation state is important in the activation or inhibition of OAS enzymes. While full-length VAI activates OAS1 in vitro, the Dicer-truncated molecule lacking the terminal stem has the opposite effect, and this is the physiologically important response
physiological function
-
synthesis of higher molecular weight 2',5'-adenylates is that in vitro protein synthesis is inhibited 30% by a 2500fold dilution of the 2',5'-oligoadenylates synthesized by 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells cell-free extracts from cutaneous T-cell lymphoma, whereas a 2500fold dilution of the 2',5'-oligoadenylates from normal peripheral blood mononuclear cells is not inhibitory. No appreciable difference in 2',5'-oligoadenylate synthetase activity occurs between T-cells and non-T-cells from cutaneous T-cell lymphomas
physiological function
-
The 2,5'-oligoadenylate synthetase proteins associated with endoribonuclease RNase L are components of the interferon-regulated OAS/RNase L system, which is an RNA decay pathway known to play an important role in the innate antiviral immunity. Critical role for the 1b isoform of the mouse Oas1b gene in resistance to West Nile virus, WNV, infection in vivo, molecular basis for the sensitivity of WNVto the Oas1b antiviral pathway, overview. Antiviral action of Oas1b is essentially restricted to the early stages in virus life cycle. Inability of WNV to productively infect the Oas1b-expressing cells is attributable to a dramatic reduction in positive-stranded viral RNA level
physiological function
-
the enzyme is part of the (2-5)A synthetase antiviral protection system of the sponge
physiological function
2',5'-oligoadenylate synthetase 1 (OAS1) inhibits PRRSV replication in monkey Marc-145 cells. Antiviral activity of OAS1 has been demonstrated in mice and humans with infections of numerous RNA and DNA viruses, such as coxsackie virus, West Nile virus, Hepatitis C virus, cowpox virus, and SARS virus
physiological function
2',5'-oligoadenylate synthetase 2 (OAS2) inhibits Zika virus replication through activation of type I IFN signaling pathway. ZIKV infection induces OAS2 expression through a RIG-I-dependent pathway. OAS2 overexpression inhibits ZIKV replication, while OAS2 knockdown increases ZIKV replication. OAS2 inhibits ZIKV replication through enhanced IFNbeta expression, leading to the activation of the Jak/STAT signaling pathway
physiological function
as part of the type I IFN signaling, the 2'-5'-oligoadenylate synthetase (OAS) proteins are involved in the progression of several non-viral diseases. OAS is correlated with immune-modulatory functions that promote chronic inflammatory conditions, autoimmune disorders, cancer, and infectious diseases
physiological function
different dsRNA length requirement of OAS2 suggests non-overlapping biological functions
physiological function
enzyme ChOAS-L possesses enzymatic activity to convert ATP into 2'-5'-linked oligoadenylates and antiviral activity against West Nile virus (WNV) replicon, relationship between enzymatic and antiviral activities of the chicken oligoadenylate synthetase-like, overview. The ChOAS-L antiviral activity is independent of enzymatic activity. Analysis of the mechanism of antiviral activity against the flavivirus replication of ChOAS-L
physiological function
human 2'-5'-oligoadenylate synthetase-like protein inhibits intracellular Mycobacterium tuberculosis replication and promotes proinflammatory cytokine secretion
physiological function
mouse Oas1b provides resistance to flavivirus infection, and Oas1b is enzymatically inactive and independent of RNase L
physiological function
Oas1a, Oas1b, and Oas1g genes play a general role in various tissues in the stimulation of virus or interferon, whereas other paralogues work as somewhat specific factors in the respective tissues
physiological function
the enzyme shows inhibitory activity on WNV replicon replication
physiological function
the enzyme shows inhibitory activity on WNV replicon replication
physiological function
the enzyme shows inhibitory activity on WNV replicon replication
physiological function
the enzyme shows inhibitory activity on WNV replicon replication
physiological function
the observed differences in anti-viral activity between the human OAS1 p46 and p42 isoforms are not fully understood. The protein expression of these isoforms is determined by the SNP rs10774671, either being an A or a G allele resulting in expression of either the p42 or the p46 isoform. The rs10774671 SNP and in extension the discrepancy between the p42 and p46 isoforms have been directly associated with several viral diseases includingWest Nile Virus infections, susceptibility to hepatitis B virus (HBV) infections and Sjögren's syndrome development, liver fibrosis progression and response to interferon therapy during hepatitis C virus (HCV) infections as well as in tuberculosis. In all of these instances, it is the G allele (i.e. the OAS1 p46 isoform) that confers resistance, while the p42 variant is associated with a higher risk in these infectious diseases. It has also been shown that the p46 isoform, but not the p42 isoform, facilitate RNase L-dependent anti-viral activity against HCV in cultured Huh7 cells
physiological function
Mus musculus C57BL/6J (B6)
-
Oas1a, Oas1b, and Oas1g genes play a general role in various tissues in the stimulation of virus or interferon, whereas other paralogues work as somewhat specific factors in the respective tissues
-
physiological function
Mus musculus C57BL/6J (B6)
-
mouse Oas1b provides resistance to flavivirus infection, and Oas1b is enzymatically inactive and independent of RNase L
-
additional information
-
mechanism responsible for the inhibition of virus replication in interferon treated cells, overview
additional information
-
mechanism responsible for the inhibition of virus replication in interferon treated cells, overview
additional information
-
OAS active site structure with three conserved active site aspartic acid residues, overview
additional information
-
OAS active site structure with three conserved active site aspartic acid residues, overview
additional information
OAS active site structure with three conserved active site aspartic acid residues, overview
additional information
-
OAS1 is the small form and OAS2 is the medium form of the human interferon-induced 2'-5'-oligoadenylate synthases
additional information
-
the active site is composed of three aspartic acids, Asp76, Asp78, and Asp148, and two domains found right after the dsRNA binding regions constituting a catalytic groove on the opposite face of the protein, which has the form of an erythrocyte, where the two ends are close
additional information
-
the different isozymes may require different conditionss for catalytic reaction and are located in different subcelular locations
additional information
-
three major forms of OAS proteins in human cells: 40/46-kDa small isoforms, OAS1, 69/71-kDa medium isoforms, OAS2, and a 100-kDa large isoform, OAS3
additional information
enzyme structure homology modeling. The active site is formed by residues Asp408, Asp410, Asp481
additional information
enzyme structure homology modeling. The active site is formed by residues Asp408, Asp410, Asp481
additional information
enzyme structure homology modeling. The active site is formed by residues Asp408, Asp410, Asp481
additional information
enzyme structure homology modeling. The active site is formed by residues Asp75, Asp77, Asp148
additional information
enzyme structure homology modeling. The active site is formed by residues Asp75, Asp77, Asp148
additional information
enzyme structure homology modeling. The active site is formed by residues Asp75, Asp77, Asp148
additional information
enzyme structure homology modeling. The active site is formed by residues Asp816, Asp818, Asp888
additional information
enzyme structure homology modeling. The active site is formed by residues Asp816, Asp818, Asp888
additional information
enzyme structure homology modeling. The active site is formed by residues Asp816, Asp818, Asp888
Show AA Sequence and Transmembrane Helices (1297 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
x * 39200, recombinant FLAG-tagged OAS2 domain I, SDS-PAGE, x * 41500, FLAG-tagged OAS2 domain II, x * 69000, recombinant full-length FLAG-tagged OAS2, SDS-PAGE
additional information
-
three distinct forms of 2'-5'OAS exist in human cells, small, medium, and large, which contain one, two, and three OAS units, respectively, and are encoded by distinct genes clustered on the 2'-5OAS locus on human chromosome 12. The monomeric OAS-like protein, OASL, is catalytically inactive
additional information
-
three isozymes of different sizes, the core OAS unit adopts a bilobal conformation in which the catalytic core is located at the junction between the N- and C-terminal domains
additional information
-
zinc ions can control the oligomerisation by enhancing the formation of tetrameric forms of OAS1p42
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
OAS1, purified recombinant porcine OAS1, 1.5 mg/ml protein in 50 mM NaCl, 10 mM HEPES, pH 6.8, 0.5 mM EDTA, with 5 mM of iodoacetamide for 30 min at room temperature, then concentrated to 6 mg/ml for crystallization by vapor diffusion, best crystals grow at 20°C in 1:1 drops with a well solution of 30% PEG 2000 MME, 0.2 M ammonium sulfate, and 0.1 M sodium cacodylate at pH 6, X-ray diffraction structure determination and analysis at 2.2 A resolution, molecular replacement
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K203E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K212A
the mutant has strongly impaired catalytic activity, KM for ATP is increased by almost 4fold relative to that of the wild-type protein, and kcat is decreased by roughly 8fold
K41E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K59E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R194E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R194E/R198E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R198E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R198M
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R245E/K246E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R38E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R38E/K41E
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R38E/K41E/K59E/R194E/R198E
site-directed mutagenesis, the mutant is almost inactive
S62A
the mutant displays a strong substrate inhibition at higher ATP concentrations, more dramatic than that observed for wild-type OAS1
S63A
the mutant displays a strong substrate inhibition at higher ATP concentrations, more dramatic than that observed for wild-type OAS1
additional information
additional information
enzyme OAS1 knockdown by siRNA, or overexpression in Marc-145 cells. Three siRNAs are designed according to the published Macaque OAS1 mRNA sequence (Macaca mulatta, UniProt ID A4LAA0). Knockdown of OAS1 by siRNA significantly increases the frequency of CPE of PRRSV in Marc-145 cells
additional information
construction of enzyme mutants, ChOAS-L-A-FL, which is ChOAS-L-A conjugated with the Flag-Tag DYKDDDDK sequence, is used for generation of eight mutations: The DELTALxxxP domain, DELTAP-LooP domain, DELTAD-D box domain, 5 KR-RR-K193H (one AA substitution), DELTAKR-RR, and ChOAS-L-B (the other allele) are generated by site-directed mutagenesis. The other two mutations, DELTAUbL2 domain and DELTAUbL1/UbL2 domains, are generated in addition. All mutated variants are enzymatically inactive except for ChOAS-L-ADELTAUbL2, but all mutants shows antiviral activity to inhibit the replication of the WNV replicon except for the ChOAS-L-ADELTAUbL1/UbL2, which shows a partial inhibition compared to the wild-type ChOAS-L-A or the other mutant enzyme variants
additional information
-
construction of enzyme mutants, ChOAS-L-A-FL, which is ChOAS-L-A conjugated with the Flag-Tag DYKDDDDK sequence, is used for generation of eight mutations: The DELTALxxxP domain, DELTAP-LooP domain, DELTAD-D box domain, 5 KR-RR-K193H (one AA substitution), DELTAKR-RR, and ChOAS-L-B (the other allele) are generated by site-directed mutagenesis. The other two mutations, DELTAUbL2 domain and DELTAUbL1/UbL2 domains, are generated in addition. All mutated variants are enzymatically inactive except for ChOAS-L-ADELTAUbL2, but all mutants shows antiviral activity to inhibit the replication of the WNV replicon except for the ChOAS-L-ADELTAUbL1/UbL2, which shows a partial inhibition compared to the wild-type ChOAS-L-A or the other mutant enzyme variants
additional information
-
substitutions of amino acids in front of the P-loop of Lys42 and Lys60 as well as that of Arg195 reduce the 2'-5'OAS activity at least 50fold. Furthermore substitutions in the Lys199 and Lys204 reduce the activity more than a 1000fold
additional information
OAS2 knockdown increases ZIKV replication. Overexpression of OAS2 modestly increases the IFN-induced p-STAT1 both with IFN treatment and without IFN treatment compared to control. OAS2 overexpression also increases ISRE activity and some classical ISGs expression including Myxovirus resistance-A (MxA) and interferon-induced protein 2 (IFIT2)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant FLAG-tagged full-length enzyme and enzyme domains I and II from Escherichia coli by immunoaffinity chromatography using a anti-DYKDDDDK G1 affinity resin, followed by dialysis and gel filtration
recombinant His-tagged OAS1 p42 isoform from Escherichia coli strain BL21(DE3)RIL by nickel affinity chromatography, tag cleavage by TEV protease, and dialysis
recombinant myc- and His-tagged enzyme from Escherichhia coli by use of poly(I:C)-iron oxide nanoparticles
-
recombinant wild-type and mutant OAS1 from Escherichia coli strain BL21(DE3) by gel filtration, ammonium sulfate fractionation, heparin affinity chromatography and gel filtration
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in transgenic Solanum tuberosum plants using the Agrobacterium tumefaciens transfection system, the transformed plants show increased resistance against potato virus X, virus concentration is much lower in leaves and tubers compared to wild-type plants, the virus concentrations are almost that low in transgenic plants expressing the potato virus X coat protein
functional expression of p42 isoform of OAS1 and the p69 isoform of OAS2 in insect cells
-
gene LB2-5OAS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression of myc- and His-tagged enzyme in Escherichhia coli
-
gene N308_13623, DNA and amino acid sequence determination and analysis, sequence comparisons of avian OASL enzymes, phylogenetic analysis, recombinant expression of EGFP-tagged enzyme in HEK-293FT and BHK-21 cells
gene OAS-L, DNA and amino acid sequence determination and analysis, sequence comparisons of avian OASL enzymes, phylogenetic analysis, recombinant expression of EGFP-tagged enzyme in HEK-293FT and BHK-21 cells
gene OAS1, cloning of paralogues OAS1a-OAS1h, DNA and amino acid sequence determination and analysis, sequence comparisons, recombinant expression of EGFP-tagged isozyme paralogue in HEK-293T cell
gene OAS1, recombinant expression of His-tagged OAS1 p42 isoform in Escherichia coli strain BL21(DE3)RIL
gene OAS1, the gene is 25414 base pairs long and consists of eight exons. Of these exons, the first five exons from the 5' end are translated into the core protein while the latter three exons enable alternative splicing into the six known protein isoforms of OAS1. Two of these isoforms are the p42 and p46 variants named due to their theoretical size of about 42 and about 46 kDa, the expression pattern between these two variants is related to one single nucleotide polymorphism (SNP), the SNP rs10774671. The SNP is an A/G variation locates in the splice acceptor site of exon 7 which results in either the A allele expressing the p42 isoform or the G allele expressing the p46 isoform. Recombinant expression of C-terminally EGFP-tagged isozymes in HeLa cells, where the C-terminus of OAS1 p46 and its CaaX motif is in itself not enough for membrane translocation
gene OAS2, DNA and amino acid sequencing, RNA sequence library production, and complete transcriptome analysis of A549 cells with and without Zika virus (ZIKV) infection, quantitative real-time PCR expression analysis
gene OAS2, recombinant expression of N-terminally FLAG-tagged OAS1 p69 isoform in Escherichia coli, and of N-terminally FLAG-tagged OAS2 domain I (DI1-331) or domain II (DII332-687), recombinant expression of N-terminally FLAG-tagged OAS2 in HEK-293T cells
gene OASL, DNA and amino acid sequence determination and analysis, sequence comparisons of avian OASL enzymes, phylogenetic analysis, recombinant expression of EGFP-tagged enzyme in HEK-293FT and BHK-21 cells
gene OASL, wild-type and mutant enzymes are ectopically expressed in HEK 293FT cells to analyze the enzymatic activity, and in BHK-21 and BALB/3T3 cells to analyze the antiviral activity using WNV replicon
OAS1, expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
stable Oas1b protein overexpression under the control of the Tet-Off expression system in a mouse fibroblastic cell line, MEF/3T3.Tet-Off. The murine cells respond to Oas1b expression by efficiently inhibiting WNV viral replication
-
three distinct forms of 2'-5'OAS exist in human cells, small, medium, and large, which contain one, two, and three OAS units, respectively, and are encoded by distinct genes, clustering of the genes encoding OAS1, OAS2, OAS3 and OASL on human chromosome 12q24.2, genetic organization, expression of isozyme OAS3 and the two forms of OAS2 in HeLa cells, expression of recombinant OAS2 in insect cells
-
gene OAS-L, DNA and amino acid sequence determination and analysis, sequence comparisons of avian OASL enzymes, phylogenetic analysis, recombinant expression of EGFP-tagged enzyme in HEK-293FT and BHK-21 cells
gene OAS-L, DNA and amino acid sequence determination and analysis, sequence comparisons of avian OASL enzymes, phylogenetic analysis, recombinant expression of EGFP-tagged enzyme in HEK-293FT and BHK-21 cells
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of Oas1a, Oas1b, and Oas1g is much increased by the stimulation of poly I:C in all tissues, suggesting that these paralogues are expressed mainly in a virus- or interferon-stimulated manner, expression of other paralogues is restricted to the specific tissues and relatively independent of the poly I:C stimulation
induction by interferon
pathogenic Mycobacterium tuberulosis infection induces OASL expression in THP1 macrophages 24 h post-infection
porcine reproductive and respiratory syndrome virus (PRRSV) infection leads to induction of 2',5'-oligoadenylate synthetase gene 1 (OAS1), an important interferon-stimulated gene
the enzyme has to be induced, induction by NDV or phenylhydrazine enhances expression of different isozymes, overview
-
the expression of OAS1c is relatively independent of the poly I:C stimulation
expression of Oas1a, Oas1b, and Oas1g is much increased by the stimulation of poly I:C in all tissues, suggesting that these paralogues are expressed mainly in a virus- or interferon-stimulated manner, expression of other paralogues is restricted to the specific tissues and relatively independent of the poly I:C stimulation
expression of Oas1a, Oas1b, and Oas1g is much increased by the stimulation of poly I:C in all tissues, suggesting that these paralogues are expressed mainly in a virus- or interferon-stimulated manner, expression of other paralogues is restricted to the specific tissues and relatively independent of the poly I:C stimulation
Mus musculus C57BL/6J (B6)
-
-
the expression of OAS1c is relatively independent of the poly I:C stimulation
the expression of OAS1c is relatively independent of the poly I:C stimulation
Mus musculus C57BL/6J (B6)
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
modified coupled spectrophotometric assay to detect 2-5 oligoadenylate synthetase enzyme activity in prostate cell lines as a model system. The phosphates generated by the OAS enzymatic reaction are coupled with conversion of the substrate 2-amino-6-mercapto-7-methylpurine ribonucleoside to a purine base product, 2-amino-6-mercapto-7-methylpurine and ribose1-phosphate via a purine nucleoside phosphorylase
medicine
medicine
-
in lymphoid cell of thymus, expression increases during inflammatory processes under ulcerogenic conditions caused by stress factors. Omeprazole treatment leads to increase in enzymic activity in thymocytes under stress, but not in the absence of stress. Omeprazole treatment does not increase enzymic activity in lymphoid cells of spleen
medicine
isoforms OAS1 p46 and OAS3 p100 mediate the RNase L-dependent antiviral activity against hepatitis C virus. The expression of isoform p46 shows a notable inhibition for the protein expression from HCV JFH-1 in an RNase L-dependent manner, whereas no inhibitory effect is produced by the p42, p48 or p52 isoforms of OAS1
medicine
-
secreted OAS2 is capable of regulating T-cell receptor CD3-zeta chain expression. Incubation of T-cells with cell-free supernatants of oral tumours or recombinant human OAS2 induces caspase-3 activation, which results in CD3-zeta chain down-regulation
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hartmann, R.; Justesen, J.; Sarkar, S.N.; Sen, G.C.; Yee, V.C.
Crystal structure of the 2'-specific and double-stranded RNA-activated interferon-induced antiviral protein 2'-5'-oligoadenylate synthetase
Mol. Cell
12
1173-1185
2003
Homo sapiens, Sus scrofa, Sus scrofa (Q29599)
brenda
Feng, Y.; Yang, K.
A comparative study of different types of rabbit 2',5'-oligoadenylate synthetase
Acta Biochim. Biophys. Sin. (Shanghai)
29
249-250
1997
Oryctolagus cuniculus
-
brenda
Ferbus, D.; Justesen, J.; Besancon, F.; Thang, M.
The 2'5' oligoadenylate synthetase has a multifunctional 2',5' nucleotidyl-transferase activity
Biochem. Biophys. Res. Commun.
100
847-856
1981
Gallus gallus, Oryctolagus cuniculus, Homo sapiens, Mus musculus
brenda
Hughes, B.; Srivastava, P.; Muse, D.; Robins, R.
2',5'-Oligoadenylates and related 2',5'-oligonucleotide analogues. 1. Substrate specificity of the interferon-induced murine 2',5'-oligoadenylate synthetase and enzymatic synthesis of oligomers
Biochemistry
22
2116-2126
1983
Mus musculus
brenda
Suhadolnik, R.; Flick, M.; Mosca, J.; Sawada, Y.; Doetsch, P.; Vonderheid, E.
2',5'oligoadenylate synthetase from cutaneous T-cell lymphoma: biosynthesis, identification, quantitation, molecular size of the 2',5'oligoadenylates, and inhibition of protein synthesis
Biochemistry
22
4153-4158
1983
Homo sapiens
brenda
Hovanessian, A.; Justesen, J.
The human 2'-5' oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation
Biochimie
89
779-788
2007
Homo sapiens
brenda
Hartmann, R.; Walko, G.; Justesen, J.
Inhibition of 2'-5' oligoadenylate synthetase by divalent metal ions
FEBS Lett.
507
54-58
2001
Homo sapiens
brenda
Behera, A.; Kumar, M.; Lockey, R.; Mohapatra, S.
2'-5' oligoadenylate synthetase plays a critical role in interferon-gamma inhibition of respiratory syncytial virus infection of human epithelial cells
J. Biol. Chem.
277
25601-25608
2002
Homo sapiens
brenda
Kajaste-Rudnitski, A.; Mashimo, T.; Frenkiel, M.; Guenet, J.; Lucas, M.; Despres, P.
The 2',5'oligoadenylate synthetase 1b is a potent inhibitor of West Nile virus replication inside infected cells
J. Biol. Chem.
281
4624-4637
2006
Mus musculus
brenda
Meng, H.; Deo, S.; Xiong, S.; Dzananovic, E.; Donald, L.; Van Dijk, C.; McKenna, S.
Regulation of the interferon-inducible 2'-5'-oligoadenylate synthetases by adenovirus VAI RNA
J. Mol. Biol.
422
635-649
2012
Homo sapiens
brenda
Schroeder, H.; Natalio, F.; Wiens, M.; Tahir, M.; Shukoor, M.; Tremel, W.; Belikov, S.; Krasko, A.; Mueller, W.
The 2'-5'-oligoadenylate synthetase in the lowest metazoa: isolation, cloning, expression and functional activity in the sponge Lubomirskia baicalensis
Mol. Immunol.
45
945-953
2008
Lubomirskia baikalensis
brenda
Truve, E.; Aaspollu, A.; Honkanen, J.; Puska, R.; Mehto, M.; Hassi, A.; Teeri, T.; Kelve, M.; Seppaenen, P.; Saarma, M.
Transgenic potato plants expressing mammalian 2'-5' oligoadenylate synthetase are protected from potato virus X infection under field conditions
Nat. Biotechnol.
11
1048-1052
1993
Rattus norvegicus (Q05961)
brenda
Paeri, M.; Kuusksalu, A.; Lopp, A.; Kjaer, K.H.; Justesen, J.; Kelve, M.
Enzymatically active 2,5-oligoadenylate synthetases are widely distributed among Metazoa, including protostome lineage
Biochimie
97
200-209
2014
Tedania ignis (U5XFV4)
brenda
Bhosle, S.; Hunt, A.; Chaudhary, J.
A modified coupled spectrophotometric method to detect 2-5 oligoadenylate synthetase activity in prostate cell lines
Biol. Proced. Online
18
009
2016
Homo sapiens
brenda
Kwon, Y.; Kang, J.; Hwang, S.; Ahn, B.
The ribonuclease l-dependent antiviral roles of human 2',5'-oligoadenylate synthetase family members against hepatitis C virus
FEBS Lett.
587
156-164
2013
Homo sapiens (P00973)
brenda
Dar, A.A.; Pradhan, T.N.; Kulkarni, D.P.; Shah, S.U.; Rao, K.V.; Chaukar, D.A.; DCruz, A.K.; Chiplunkar, S.V.
Extracellular 2'5'-oligoadenylate synthetase 2 mediates T-cell receptor CD3-zeta chain down-regulation via caspase-3 activation in oral cancer
Immunology
147
251-264
2016
Homo sapiens
brenda
Kot, L.; Kompanets, I.; Ostapchenko, L.; Bogdanova, O.
2,5-oligoadenylate-synthetase activity in lymphoid cells of rats with experimental stress-induced gastric ulcer
Russ. J. Biopharm.
7
14-20
2015
Rattus norvegicus
-
brenda
Zhao, J.; Feng, N.; Li, Z.; Wang, P.; Qi, Z.; Liang, W.; Zhou, X.; Xu, X.; Liu, B.
2',5'-Oligoadenylate synthetase 1 (OAS1) inhibits PRRSV replication in Marc-145 cells
Antiviral Res.
132
268-273
2016
Chlorocebus sabaeus (A0A0D9S3Y6)
brenda
Koul, A.; Deo, S.; Booy, E.P.; Orriss, G.L.; Genung, M.; McKenna, S.A.
Impact of double-stranded RNA characteristics on the activation of human 2'-5'-oligoadenylate synthetase 2 (OAS2)
Biochem. Cell Biol.
98
70-82
2020
Homo sapiens (P00973), Homo sapiens (P29728), Homo sapiens
brenda
Gonzalez, K.J.; Moncada-Giraldo, D.M.; Gutierrez, J.B.
In silico identification of potential inhibitors against human 2'-5'-oligoadenylate synthetase (OAS) proteins
Comput. Biol. Chem.
85
107211
2020
Homo sapiens (P00973), Homo sapiens (P29728), Homo sapiens (Q9Y6K5)
brenda
Elkhateeb, E.; Tag-El-Din-Hassan, H.T.; Sasaki, N.; Torigoe, D.; Morimatsu, M.; Agui, T.
The role of mouse 2',5'-oligoadenylate synthetase 1 paralogs
Infect. Genet. Evol.
45
393-401
2016
Mus musculus (P11928), Mus musculus (Q14AZ4), Mus musculus (Q60856), Mus musculus (Q8C2W3), Mus musculus (Q8K469), Mus musculus (Q8VI95), Mus musculus (Q8VI97), Mus musculus (Q924S2), Mus musculus, Mus musculus C57BL/6J (B6) (P11928), Mus musculus C57BL/6J (B6) (Q14AZ4), Mus musculus C57BL/6J (B6) (Q60856), Mus musculus C57BL/6J (B6) (Q8C2W3), Mus musculus C57BL/6J (B6) (Q8K469), Mus musculus C57BL/6J (B6) (Q8VI95), Mus musculus C57BL/6J (B6) (Q8VI97), Mus musculus C57BL/6J (B6) (Q924S2)
brenda
Tag-El-Din-Hassan, H.T.; Morimatsu, M.; Agui, T.
Functional analysis of duck, goose, and ostrich 2'-5'-oligoadenylate synthetase
Infect. Genet. Evol.
62
220-232
2018
Struthio camelus australis (A0A093JNH5), Anser cygnoides (A0A1B1V537), Anas platyrhynchos (A0A1B1V538), Anas platyrhynchos, Gallus gallus (H9L0X6), Gallus gallus
brenda
Tag-El-Din-Hassan, H.T.; Sasaki, N.; Torigoe, D.; Morimatsu, M.; Agui, T.
Analysis of the relationship between enzymatic and antiviral activities of the chicken oligoadenylate synthetase-like
J. Interferon Cytokine Res.
37
71-80
2017
Gallus gallus (H9L0X6), Gallus gallus
brenda
Leisching, G.; Ali, A.; Cole, V.; Baker, B.
2'-5'-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion
Mol. Immunol.
118
73-78
2020
Homo sapiens (Q15646)
brenda
Skrivergaard, S.; Jensen, M.S.; Rolander, T.B.; Nguyen, T.B.N.; Bundgaard, A.; Nejsum, L.N.; Martensen, P.M.
The cellular localization of the p42 and p46 oligoadenylate synthetase 1 isoforms and their impact on mitochondrial respiration
Viruses
11
1122
2019
Homo sapiens (P00973), Homo sapiens
brenda
Liao, X.; Xie, H.; Li, S.; Ye, H.; Li, S.; Ren, K.; Li, Y.; Xu, M.; Lin, W.; Duan, X.; Yang, C.; Chen, L.
2',5'-Oligoadenylate synthetase 2 (OAS2) inhibits Zika virus replication through activation of type I IFN signaling pathway
Viruses
12
418
2020
Homo sapiens (P29728)
brenda
Select items on the left to see more content.
EXTERNAL LINKS (specific for EC-Number 2.7.7.84)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
