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Literature summary for 2.7.7.84 extracted from

  • 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 (2007), Biochimie, 89, 779-788.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
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 Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
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 Homo sapiens

Protein Variants

Protein Variants Comment Organism
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 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
additional information three distinct forms of 2'-5'OAS exist in human cells, that show distinct subcellular localizations Homo sapiens
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nucleus association of this form of OAS with membranes of the nuclear envelope and the rough endoplasmic reticulum Homo sapiens 5634
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ribosome OAS3 is mainly associated with the ribosomal fraction Homo sapiens 5840
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rough endoplasmic reticulum association of this form of OAS with membranes of the nuclear envelope and the rough endoplasmic reticulum Homo sapiens 5791
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Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
160000
-
dimeric isozyme OAS2, gel filtration Homo sapiens
180000
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tetrameric isozyme OAS1, gel filtration Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
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isozyme OAS1, two forms of isozyme OAS2, and isozyme OAS3
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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 Homo sapiens ?
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?
n ATP reaction of OAS1 Homo sapiens pppA(2'p5'A)n + 2 diphosphate
-
?
NTP + pppA2'p5'A reaction of OAS2, broad spectrum of accepted donor substrates, including ATP, GTP, CTP, UTP, ITP, and their deoxy variants, overview Homo sapiens pppA2'p5'Ap2'p5'N + 2 diphosphate
-
?
NTP + RpA 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 Homo sapiens RpA2'p5'N + 2 diphosphate
-
?

Subunits

Subunits Comment Organism
dimer 2 * 56000-59000, isozyme OAS2, two dimers form a tetramer, SDS-PAGE Homo sapiens
homotetramer 4 * 56000-59000, isozyme OAS1, SDS-PAGE Homo sapiens
More 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 Homo sapiens
trimer 3 * 56000-59000, isozyme OAS3, SDS-PAGE Homo sapiens

Synonyms

Synonyms Comment Organism
2'-5' oligoadenylate synthetase
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Homo sapiens
2'-5'OAS
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Homo sapiens
OAS1
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Homo sapiens
OAS2
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Homo sapiens
OAS3
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Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.6
-
isozyme OAS2 Homo sapiens
7.5
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isozyme OAS3 Homo sapiens

Expression

Organism Comment Expression
Homo sapiens induction by interferon up

General Information

General Information Comment Organism
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 Homo sapiens
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 Homo sapiens