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{{Short description|Cytosolic DNA sensor}}
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[[File:CGAS complexed with dsDNA.png|thumbnail|cGAS complexed with dsDNA (Based on PDB 4O6A)]]
{{Infobox enzyme
| Name = Cyclic GMP-AMP synthase
| EC_number = 2.7.7.86
| CAS_number =
| GO_code =
| image = CGAS complexed with dsDNA.png
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| caption = cGAS complexed with dsDNA (based on PDB 4O6A)
|name=}}
[[File:5v8j.jpg|thumbnail|cGAS dimer, human]]
[[File:cGAS-cGAMP-STING pathway.jpg|thumb|cGAS-cGAMP-STING pathway]]
[[File:cGAS-cGAMP-STING pathway.jpg|thumb|cGAS-cGAMP-STING pathway]]
'''Cyclic GMP-AMP synthase''' (cGAS, [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthase), belonging to the [[nucleotidyltransferase]] family, is a [[The cGAS – STING cytosolic DNA sensing pathway|cytosolic DNA sensor]] that activates the [[Interferon type I|type-I interferon]] pathway. It binds to microbial [[DNA]] as well as self DNA that invades the [[cytoplasm]], and catalyzes [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthesis.<ref name="pmid23258413">{{cite journal|last=Sun|first=L|author2=Wu, J |author3=Du, F |author4=Chen, X |author5= Chen, ZJ |title=Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=786–91|pmid=23258413|doi=10.1126/science.1232458}}</ref> [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] then functions as a [[second messenger]] that binds to and activates the [[endoplasmic reticulum]] protein STING to trigger type-I IFNs production.<ref name="pmid23258412">{{cite journal|last=Wu|first=J|author2=Sun, L |author3=Chen, X |author4=Du, F |author5=Shi, H |author6=Chen, C |author7= Chen, ZJ |title=Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=826–30|pmid=23258412|doi=10.1126/science.1229963}}</ref><ref name="GaoAscano2013">{{cite journal|last1=Gao|first1=Pu|last2=Ascano|first2=Manuel|last3=Wu|first3=Yang|last4=Barchet|first4=Winfried|last5=Gaffney|first5=Barbara L.|last6=Zillinger|first6=Thomas|last7=Serganov|first7=Artem A.|last8=Liu|first8=Yizhou|last9=Jones|first9=Roger A.|last10=Hartmann|first10=Gunther|last11=Tuschl|first11=Thomas|last12=Patel|first12=Dinshaw J.|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|year=2013|pages=1094–1107|issn=00928674|doi=10.1016/j.cell.2013.04.046}}</ref>
'''Cyclic GMP-AMP synthase''' (cGAS, [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthase), belonging to the [[nucleotidyltransferase]] family, is a [[The cGAS – STING cytosolic DNA sensing pathway|cytosolic DNA sensor]] that activates a [[Interferon type I|type-I interferon]] response. It is part of the [[CGAS–STING cytosolic DNA sensing pathway|cGAS-STING DNA sensing pathway]]. It binds to microbial [[DNA]] as well as self DNA that invades the [[cytoplasm]], and catalyzes [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] synthesis.<ref name="pmid23258413">{{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 }}</ref> [[Cyclic guanosine monophosphate–adenosine monophosphate|cGAMP]] then functions as a [[second messenger]] that binds to and activates the [[endoplasmic reticulum]] protein [[Stimulator of interferon genes|STING]] to trigger [[Interferon type I|type-I IFNs]] production.<ref name="pmid23258412">{{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 }}</ref><ref name="GaoAscano2013">{{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 }}</ref><ref name=Zhang>{{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 }}</ref> Mice lacking cGAS are more vulnerable to lethal infection by [[DNA virus]]es and [[RNA virus]]es.<ref name=Li>{{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 }}</ref><ref>{{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 }}</ref> In addition, cGAS has been shown to be an innate immune sensor of retroviruses including [[HIV]].<ref name=Gao>{{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 }}</ref><ref name=Lahaye>{{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 }}</ref> The human gene encoding cGAS is [[MB21D1]] on chromosome 6.
<ref name=Zhang>{{cite journal|last=Zhang|first=X|author2=Shi, H |author3=Wu, J |author4=Zhang, X |author5=Sun, L |author6=Chen, C |author7= Chen, ZJ |title=Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING|journal=Molecular Cell|date=Jun 3, 2013|volume=51|issue=2|pages=226–235|doi=10.1016/j.molcel.2013.05.022}}</ref> Mice lacking cGAS were more vulnerable to lethal infection by DNA viruses.<ref name=Li>{{cite journal|last=Li|first=XD|author2=Wu, J |author3=Gao, D |author4=Wang, H |author5=Sun, L |author6= Chen, ZJ |title=Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects|journal=Science|date=Sep 20, 2013|volume=341|issue=6152|pages=1390–4|doi=10.1126/science.1244040 |pmid=23989956 |pmc=3863637}}</ref> In addition, cGAS has been shown to be an innate immune sensor of retroviruses including [[HIV]].<ref name=Gao>{{cite journal|last=Gao|first=D|author2=Wu, J |author3=Wu, YT |author4=Du, F |author5=Aroh, C |author6=Yan, N |author7=Sun, L |author8= Chen, ZJ |title=Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses|journal=Science|date=Aug 23, 2013|volume=341|issue=6148|pages=903–6|doi=10.1126/science.1240933 |pmid=23929945 |pmc=3860819}}</ref><ref name=Lahaye>{{cite journal|last=Lahaye|first=X|author2=Satoh, T |author3=Gentili, M |author4=Cerboni, S |author5=Conrad, C |author6=Hurbain, I |author7=El Marjou, A |author8=Lacabaratz, C |author9=Lelièvre, JD |author10=Manel, N |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|date=Dec 12, 2013|volume=39|issue=6|pages=1132–42|doi=10.1016/j.immuni.2013.11.002}}</ref>


== References ==
== References ==
{{Reflist}}
{{Reflist}}


{{Kinases|state=collapsed}}
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[[Category:Transferases]]


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[[Category:Transferases]]


{{transferase-stub}}
{{transferase-stub}}

Latest revision as of 18:35, 23 January 2024

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

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.

References

[edit]
  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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