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Information on EC 2.7.7.84 - 2'-5' oligoadenylate synthase and Organism(s) Homo sapiens and UniProt Accession P00973
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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 .
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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 taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
2-5a synthetase, 2',5'-oligoadenylate synthetase, 2'-5'-oligoadenylate synthetase, 2'-5' oligoadenylate synthetase, oas1b, oas1a, 2'-5'oas, 2'-5'-oligoadenylate synthetase 1, 2'5' oligoadenylate synthetase, oligoadenylate synthetase-like, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2'-5'-oligoadenylate synthetase
OAS
OAS2
OAS3
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].
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
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
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
-
-
?
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
?
-
-
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
-
-
-
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
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
-
-
?
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 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 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 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
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
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
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
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
-
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
-
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
-
additional information
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
-
additional information
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
-
additional information
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
-
additional information
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 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 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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
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
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
-
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
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
peripheral blood mononuclear cells from healthy persons, and obtained from cutaneous T-cell lymphomas
-
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
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
-
association of this form of OAS with membranes of the nuclear envelope and the rough endoplasmic reticulum
additional information
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)
-
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)
-
additional information
-
three distinct forms of 2'-5'OAS exist in human cells, that show distinct subcellular localizations
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
physiological function
evolution
malfunction
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
physiological function
additional information
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
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
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
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
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
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
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'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. 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
-
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
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
human 2'-5'-oligoadenylate synthetase-like protein inhibits intracellular Mycobacterium tuberculosis replication and promotes proinflammatory cytokine secretion
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
-
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
-
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
-
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 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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). OAS1_HUMAN
400
0
46029
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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)
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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 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
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
functional expression of p42 isoform of OAS1 and the p69 isoform of OAS2 in insect cells
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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
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
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
pathogenic Mycobacterium tuberulosis infection induces OASL expression in THP1 macrophages 24 h post-infection
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
-
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
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)
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
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1981
Gallus gallus, Oryctolagus cuniculus, Homo sapiens, Mus musculus
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
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
Hartmann, R.; Walko, G.; Justesen, J.
Inhibition of 2'-5' oligoadenylate synthetase by divalent metal ions
FEBS Lett.
507
54-58
2001
Homo sapiens
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
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
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
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)
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
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
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)
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)
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
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