Cyclic GMP-AMP synthase
{{Short description|Cytosolic DNA sensor}}
{{Infobox enzyme
| Name = Cyclic GMP-AMP synthase
| EC_number = 2.7.7.86
| CAS_number =
| GO_code =
| image = CGAS complexed with dsDNA.png
| caption = cGAS complexed with dsDNA (based on PDB 4O6A)
|name=}}
File:cGAS-cGAMP-STING pathway.jpg
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.{{cite journal | vauthors = Sun L, Wu J, Du F, Chen X, Chen ZJ | title = Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway | journal = Science | volume = 339 | issue = 6121 | pages = 786–91 | date = February 2013 | pmid = 23258413 | pmc = 3863629 | doi = 10.1126/science.1232458 | bibcode = 2013Sci...339..786S }} cGAMP then functions as a second messenger that binds to and activates the endoplasmic reticulum protein STING to trigger type-I IFNs production.{{cite journal | vauthors = Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ | title = Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA | journal = Science | volume = 339 | issue = 6121 | pages = 826–30 | date = February 2013 | pmid = 23258412 | pmc = 3855410 | doi = 10.1126/science.1229963 | bibcode = 2013Sci...339..826W }}{{cite journal | vauthors = Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, Serganov AA, Liu Y, Jones RA, Hartmann G, Tuschl T, Patel DJ | display-authors = 6 | title = Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase | journal = Cell | volume = 153 | issue = 5 | pages = 1094–107 | date = May 2013 | pmid = 23647843 | pmc = 4382009 | doi = 10.1016/j.cell.2013.04.046 }}{{cite journal | vauthors = Zhang X, Shi H, Wu J, Zhang X, Sun L, Chen C, Chen ZJ | title = Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING | journal = Molecular Cell | volume = 51 | issue = 2 | pages = 226–35 | date = July 2013 | pmid = 23747010 | pmc = 3808999 | doi = 10.1016/j.molcel.2013.05.022 }} Mice lacking cGAS are more vulnerable to lethal infection by DNA viruses and RNA viruses.{{cite journal | vauthors = Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ | title = Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects | journal = Science | volume = 341 | issue = 6152 | pages = 1390–4 | date = September 2013 | pmid = 23989956 | pmc = 3863637 | doi = 10.1126/science.1244040 | bibcode = 2013Sci...341.1390L }}{{cite journal | vauthors =Yu P, Miao Z, Li Y, Bansal R, Peppelenbosch MP, Pan Q| title = cGAS-STING effectively restricts murine norovirus infection but antagonizes the antiviral action of N-terminus of RIG-I in mouse macrophages.| journal = Gut Microbes | volume = 13 | issue= 1 | pages = 1959839| date = January 2021 | pmid = 34347572 | pmc = 8344765 | doi = 10.1080/19490976.2021.1959839 }} In addition, cGAS has been shown to be an innate immune sensor of retroviruses including HIV.{{cite journal | vauthors = Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, Sun L, Chen ZJ | display-authors = 6 | title = Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses | journal = Science | volume = 341 | issue = 6148 | pages = 903–6 | date = August 2013 | pmid = 23929945 | pmc = 3860819 | doi = 10.1126/science.1240933 | bibcode = 2013Sci...341..903G }}{{cite journal | vauthors = Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C, Hurbain I, El Marjou A, Lacabaratz C, Lelièvre JD, Manel N | display-authors = 6 | title = The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells | journal = Immunity | volume = 39 | issue = 6 | pages = 1132–42 | date = December 2013 | pmid = 24269171 | doi = 10.1016/j.immuni.2013.11.002 | doi-access = free }} The human gene encoding cGAS is MB21D1 on chromosome 6.