2'-5'-oligoadenylate synthase 1

Details

Name
2'-5'-oligoadenylate synthase 1
Synonyms
  • (2-5')oligo(A) synthase 1
  • 2.7.7.84
  • E18/E16
  • OIAS
  • p46/p42 OAS
Gene Name
OAS1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009506|2'-5'-oligoadenylate synthase 1
MMDLRNTPAKSLDKFIEDYLLPDTCFRMQINHAIDIICGFLKERCFRGSSYPVCVSKVVK
GGSSGKGTTLRGRSDADLVVFLSPLTTFQDQLNRRGEFIQEIRRQLEACQRERAFSVKFE
VQAPRWGNPRALSFVLSSLQLGEGVEFDVLPAFDALGQLTGGYKPNPQIYVKLIEECTDL
QKEGEFSTCFTELQRDFLKQRPTKLKSLIRLVKHWYQNCKKKLGKLPPQYALELLTVYAW
ERGSMKTHFNTAQGFRTVLELVINYQQLCIYWTKYYDFKNPIIEKYLRRQLTKPRPVILD
PADPTGNLGGGDPKGWRQLAQEAEAWLNYPCFKNWDGSPVSSWILLAESNSADDETDDPR
RYQKYGYIGTHEYPHFSHRPSTLQAASTPQAEEDWTCTIL
Number of residues
400
Molecular Weight
46028.165
Theoretical pI
Not Available
GO Classification
Functions
2'-5'-oligoadenylate synthetase activity / ATP binding / double-stranded RNA binding / metal ion binding / zinc ion binding
Processes
cellular response to interferon-alpha / cytokine-mediated signaling pathway / defense response to virus / glucose homeostasis / glucose metabolic process / interferon-gamma-mediated signaling pathway / negative regulation of viral genome replication / protein oligomerization / purine nucleotide biosynthetic process / regulation of ribonuclease activity / response to virus / type I interferon signaling pathway
Components
cytoplasm / cytosol / endoplasmic reticulum / extracellular region / mitochondrion / nucleus
General Function
Zinc ion binding
Specific Function
Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0017479|2'-5'-oligoadenylate synthase 1 (OAS1)
ATGATGGATCTCAGAAATACCCCAGCCAAATCTCTGGACAAGTTCATTGAAGACTATCTC
TTGCCAGACACGTGTTTCCGCATGCAAATCAACCATGCCATTGACATCATCTGTGGGTTC
CTGAAGGAAAGGTGCTTCCGAGGTAGCTCCTACCCTGTGTGTGTGTCCAAGGTGGTAAAG
GGTGGCTCCTCAGGCAAGGGCACCACCCTCAGAGGCCGATCTGACGCTGACCTGGTTGTC
TTCCTCAGTCCTCTCACCACTTTTCAGGATCAGTTAAATCGCCGGGGAGAGTTCATCCAG
GAAATTAGGAGACAGCTGGAAGCCTGTCAAAGAGAGAGAGCATTTTCCGTGAAGTTTGAG
GTCCAGGCTCCACGCTGGGGCAACCCCCGTGCGCTCAGCTTCGTACTGAGTTCGCTCCAG
CTCGGGGAGGGGGTGGAGTTCGATGTGCTGCCTGCCTTTGATGCCCTGGGTCAGTTGACT
GGCGGCTATAAACCTAACCCCCAAATCTATGTCAAGCTCATCGAGGAGTGCACCGACCTG
CAGAAAGAGGGCGAGTTCTCCACCTGCTTCACAGAACTACAGAGAGACTTCCTGAAGCAG
CGCCCCACCAAGCTCAAGAGCCTCATCCGCCTAGTCAAGCACTGGTACCAAAATTGTAAG
AAGAAGCTTGGGAAGCTGCCACCTCAGTATGCCCTGGAGCTCCTGACGGTCTATGCTTGG
GAGCGAGGGAGCATGAAAACACATTTCAACACAGCCCAGGGATTTCGGACGGTCTTGGAA
TTAGTCATAAACTACCAGCAACTCTGCATCTACTGGACAAAGTATTATGACTTTAAAAAC
CCCATTATTGAAAAGTACCTGAGAAGGCAGCTCACGAAACCCAGGCCTGTGATCCTGGAC
CCGGCGGACCCTACAGGAAACTTGGGTGGTGGAGACCCAAAGGGTTGGAGGCAGCTGGCA
CAAGAGGCTGAGGCCTGGCTGAATTACCCATGCTTTAAGAATTGGGATGGGTCCCCAGTG
AGCTCCTGGATTCTGCTGACCCAGCACACTCCAGGCAGCATCCACCCCACAGGCAGAAGA
GGACTGGACCTGCACCATCCTCTGAATGCCAGTGCATCTTGGGGGAAAGGGCTCCAGTGT
TATCTGGACCAGTTCCTTCATTTTCAGGTGGGACTCTTGATCCAGAGAGGACAAAGCTCC
TCAGTGAGCTGGTGTATAATCCAGGACAGAACCCAGGTCTCCTGA
Chromosome Location
12
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP00973
UniProtKB Entry NameOAS1_HUMAN
HGNC IDHGNC:8086
General References
  1. Benech P, Mory Y, Revel M, Chebath J: Structure of two forms of the interferon-induced (2'-5') oligo A synthetase of human cells based on cDNAs and gene sequences. EMBO J. 1985 Sep;4(9):2249-56. [Article]
  2. Wathelet M, Moutschen S, Cravador A, DeWit L, Defilippi P, Huez G, Content J: Full-length sequence and expression of the 42 kDa 2-5A synthetase induced by human interferon. FEBS Lett. 1986 Feb 3;196(1):113-20. [Article]
  3. Shiojiri S, Fukunaga R, Ichii Y, Sokawa Y: Structure and expression of a cloned cDNA for human (2'-5')oligoadenylate synthetase. J Biochem. 1986 May;99(5):1455-64. [Article]
  4. Ghosh SK, Kusari J, Bandyopadhyay SK, Samanta H, Kumar R, Sen GC: Cloning, sequencing, and expression of two murine 2'-5'-oligoadenylate synthetases. Structure-function relationships. J Biol Chem. 1991 Aug 15;266(23):15293-9. [Article]
  5. Perelygin AA, Zharkikh AA, Scherbik SV, Brinton MA: The mammalian 2'-5' oligoadenylate synthetase gene family: evidence for concerted evolution of paralogous Oas1 genes in Rodentia and Artiodactyla. J Mol Evol. 2006 Oct;63(4):562-76. Epub 2006 Oct 5. [Article]
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  9. Wathelet MG, Clauss IM, Nols CB, Content J, Huez GA: New inducers revealed by the promoter sequence analysis of two interferon-activated human genes. Eur J Biochem. 1987 Dec 1;169(2):313-21. [Article]
  10. Benech P, Vigneron M, Peretz D, Revel M, Chebath J: Interferon-responsive regulatory elements in the promoter of the human 2',5'-oligo(A) synthetase gene. Mol Cell Biol. 1987 Dec;7(12):4498-504. [Article]
  11. Rutherford MN, Hannigan GE, Williams BR: Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene. EMBO J. 1988 Mar;7(3):751-9. [Article]
  12. Saunders ME, Gewert DR, Tugwell ME, McMahon M, Williams BR: Human 2-5A synthetase: characterization of a novel cDNA and corresponding gene structure. EMBO J. 1985 Jul;4(7):1761-8. [Article]
  13. Merlin G, Chebath J, Benech P, Metz R, Revel M: Molecular cloning and sequence of partial cDNA for interferon-induced (2'-5')oligo(A) synthetase mRNA from human cells. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4904-8. [Article]
  14. Ghosh A, Sarkar SN, Guo W, Bandyopadhyay S, Sen GC: Enzymatic activity of 2'-5'-oligoadenylate synthetase is impaired by specific mutations that affect oligomerization of the protein. J Biol Chem. 1997 Dec 26;272(52):33220-6. [Article]
  15. Sarkar SN, Ghosh A, Wang HW, Sung SS, Sen GC: The nature of the catalytic domain of 2'-5'-oligoadenylate synthetases. J Biol Chem. 1999 Sep 3;274(36):25535-42. [Article]
  16. Eskildsen S, Justesen J, Schierup MH, Hartmann R: Characterization of the 2'-5'-oligoadenylate synthetase ubiquitin-like family. Nucleic Acids Res. 2003 Jun 15;31(12):3166-73. [Article]
  17. Hovanessian AG, Justesen J: The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation. Biochimie. 2007 Jun-Jul;89(6-7):779-88. Epub 2007 Feb 20. [Article]
  18. Marques J, Anwar J, Eskildsen-Larsen S, Rebouillat D, Paludan SR, Sen G, Williams BR, Hartmann R: The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domain. J Gen Virol. 2008 Nov;89(Pt 11):2767-72. doi: 10.1099/vir.0.2008/003558-0. [Article]
  19. Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL: Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members against dengue virus infection. J Immunol. 2009 Dec 15;183(12):8035-43. doi: 10.4049/jimmunol.0902728. Epub . [Article]
  20. Melchjorsen J, Kristiansen H, Christiansen R, Rintahaka J, Matikainen S, Paludan SR, Hartmann R: Differential regulation of the OASL and OAS1 genes in response to viral infections. J Interferon Cytokine Res. 2009 Apr;29(4):199-207. doi: 10.1089/jir.2008.0050. [Article]
  21. Kjaer KH, Poulsen JB, Reintamm T, Saby E, Martensen PM, Kelve M, Justesen J: Evolution of the 2'-5'-oligoadenylate synthetase family in eukaryotes and bacteria. J Mol Evol. 2009 Dec;69(6):612-24. doi: 10.1007/s00239-009-9299-1. Epub 2009 Nov 11. [Article]
  22. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  23. Kristiansen H, Gad HH, Eskildsen-Larsen S, Despres P, Hartmann R: The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities. J Interferon Cytokine Res. 2011 Jan;31(1):41-7. doi: 10.1089/jir.2010.0107. Epub 2010 Dec 12. [Article]
  24. Donovan J, Dufner M, Korennykh A: Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1. Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1652-7. doi: 10.1073/pnas.1218528110. Epub 2013 Jan 14. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02987Cysteine-S-acetamideexperimentalunknownDetails