Cyclic GMP-AMP synthase

Cyclic GMP-AMP synthase (cGAS, cGAMP synthase), belonging to the nucleotidyltransferase family, is a cytosolic DNA sensor that activates a type-I interferon response. It is part of the cGAS-STING DNA sensing pathway. It binds to microbial DNA as well as self DNA that invades the cytoplasm, and catalyzes cGAMP synthesis.[1] cGAMP then functions as a second messenger that binds to and activates the endoplasmic reticulum protein STING to trigger type-I IFNs production.[2][3][4] Mice lacking cGAS are more vulnerable to lethal infection by DNA viruses and RNA viruses.[5][6] In addition, cGAS has been shown to be an innate immune sensor of retroviruses including HIV.[7][8] The human gene encoding cGAS is MB21D1 on chromosome 6.

cGAS complexed with dsDNA (based on PDB 4O6A)
Identifiers
EC no.2.7.7.86
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins
cGAS dimer, human
cGAS-cGAMP-STING pathway

References
  1. Sun L, Wu J, Du F, Chen X, Chen ZJ (February 2013). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway". Science. 339 (6121): 786–91. Bibcode:2013Sci...339..786S. doi:10.1126/science.1232458. PMC 3863629. PMID 23258413.
  2. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ (February 2013). "Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA". Science. 339 (6121): 826–30. Bibcode:2013Sci...339..826W. doi:10.1126/science.1229963. PMC 3855410. PMID 23258412.
  3. Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, et al. (May 2013). "Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase". Cell. 153 (5): 1094–107. doi:10.1016/j.cell.2013.04.046. PMC 4382009. PMID 23647843.
  4. Zhang X, Shi H, Wu J, Zhang X, Sun L, Chen C, Chen ZJ (July 2013). "Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING". Molecular Cell. 51 (2): 226–35. doi:10.1016/j.molcel.2013.05.022. PMC 3808999. PMID 23747010.
  5. Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ (September 2013). "Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects". Science. 341 (6152): 1390–4. Bibcode:2013Sci...341.1390L. doi:10.1126/science.1244040. PMC 3863637. PMID 23989956.
  6. Yu P, Miao Z, Li Y, Bansal R, Peppelenbosch MP, Pan Q (January 2021). "cGAS-STING effectively restricts murine norovirus infection but antagonizes the antiviral action of N-terminus of RIG-I in mouse macrophages". Gut Microbes. 13 (1): 1959839. doi:10.1080/19490976.2021.1959839. PMC 8344765. PMID 34347572.
  7. Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, et al. (August 2013). "Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses". Science. 341 (6148): 903–6. Bibcode:2013Sci...341..903G. doi:10.1126/science.1240933. PMC 3860819. PMID 23929945.
  8. Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C, Hurbain I, et al. (December 2013). "The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells". Immunity. 39 (6): 1132–42. doi:10.1016/j.immuni.2013.11.002. PMID 24269171.
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