Cyclic GMP-AMP synthase explained

Cyclic GMP-AMP synthase
Ec Number:	2.7.7.86

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.

Notes and References

1. Sun L, Wu J, Du F, Chen X, Chen ZJ . Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway . Science . 339 . 6121 . 786–91 . February 2013 . 23258413 . 3863629 . 10.1126/science.1232458 . 2013Sci...339..786S .
2. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ . Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA . Science . 339 . 6121 . 826–30 . February 2013 . 23258412 . 3855410 . 10.1126/science.1229963 . 2013Sci...339..826W .
3. Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, Serganov AA, Liu Y, Jones RA, Hartmann G, Tuschl T, Patel DJ . 6 . 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 . May 2013 . 23647843 . 4382009 . 10.1016/j.cell.2013.04.046 .
4. Zhang X, Shi H, Wu J, Zhang X, Sun L, Chen C, Chen ZJ . Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING . Molecular Cell . 51 . 2 . 226–35 . July 2013 . 23747010 . 3808999 . 10.1016/j.molcel.2013.05.022 .
5. Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ . Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects . Science . 341 . 6152 . 1390–4 . September 2013 . 23989956 . 3863637 . 10.1126/science.1244040 . 2013Sci...341.1390L .
6. Yu P, Miao Z, Li Y, Bansal R, Peppelenbosch MP, Pan Q. 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. January 2021 . 34347572 . 8344765 . 10.1080/19490976.2021.1959839 .
7. Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, Sun L, Chen ZJ . 6 . Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses . Science . 341 . 6148 . 903–6 . August 2013 . 23929945 . 3860819 . 10.1126/science.1240933 . 2013Sci...341..903G .
8. Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C, Hurbain I, El Marjou A, Lacabaratz C, Lelièvre JD, Manel N . 6 . 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 . December 2013 . 24269171 . 10.1016/j.immuni.2013.11.002 . free .