CGAS

Summary

Gene Symbol: CGAS
Description: cyclic GMP-AMP synthase
Alias: C6orf150, MB21D1, h-cGAS, cyclic GMP-AMP synthase, 2'3'-cGAMP synthase, Mab-21 domain containing 1, cGAMP synthase, mab-21 domain-containing protein 1, protein MB21D1
Species: human
Products:     CGAS

Top Publications

  1. Sun L, Wu J, Du F, Chen X, Chen Z. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339:786-91 pubmed publisher
    ..Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltransferase family...
  2. Zhang X, Wu J, Du F, Xu H, Sun L, Chen Z, et al. The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop. Cell Rep. 2014;6:421-30 pubmed publisher
    ..Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP...
  3. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339:826-30 pubmed publisher
    ..cGAMP bound to STING, leading to the activation of IRF3 and induction of interferon-?. Thus, cGAMP functions as an endogenous second messenger in metazoans and triggers interferon production in response to cytosolic DNA...
  4. Gao D, Wu J, Wu Y, Du F, Aroh C, Yan N, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science. 2013;341:903-6 pubmed publisher
    ..Here we show that HIV infection activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other ..
  5. Civril F, Deimling T, de Oliveira Mann C, Ablasser A, Moldt M, Witte G, et al. Structural mechanism of cytosolic DNA sensing by cGAS. Nature. 2013;498:332-7 pubmed publisher
    ..Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING)...
  6. Diner E, Burdette D, Wilson S, Monroe K, Kellenberger C, Hyodo M, et al. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep. 2013;3:1355-61 pubmed publisher
    ..cytosolic DNA was proposed to induce the synthesis of cyclic GMP-AMP (cGAMP) upon binding to an enzyme called cGAMP synthase (cGAS). cGAMP activates an interferon response by binding to a downstream receptor called STING...
  7. Kranzusch P, Lee A, Berger J, Doudna J. Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity. Cell Rep. 2013;3:1362-8 pubmed publisher
    ..Detection of cytosolic DNA triggers downstream immune signaling through activation of cyclic GMP-AMP synthase (cGAS)...
  8. Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C, Hurbain I, et al. The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity. 2013;39:1132-42 pubmed publisher
    ..Finally, we found that DC sensing of HIV-1 and HIV-2 required the DNA sensor cGAS. Thus, the HIV capsid is a determinant of innate sensing of the viral cDNA by cGAS in dendritic cells...
  9. Fang R, Wang C, Jiang Q, Lv M, Gao P, Yu X, et al. NEMO-IKK? Are Essential for IRF3 and NF-?B Activation in the cGAS-STING Pathway. J Immunol. 2017;199:3222-3233 pubmed publisher
    Cytosolic dsDNA activates the cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway to produce cytokines, including type I IFNs...

More Information

Publications56

  1. Yoh S, Schneider M, Seifried J, Soonthornvacharin S, Akleh R, Olivieri K, et al. PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1. Cell. 2015;161:1293-1305 pubmed publisher
    ..of DCs triggers an IRF3-dependent innate immune response, which requires the activity of cyclic GAMP synthase (cGAS)...
  2. Cox A, Siliciano R. Making sense of HIV innate sensing. Immunity. 2013;39:998-1000 pubmed publisher
    ..In this issue of Immunity, Lahaye et al. (2013) demonstrate that HIV capsid-cyclophilin A interactions affect viral cDNA sensing by the DNA sensor cCAS and contribute to differential pathogenesis of HIV-1 and HIV-2. ..
  3. Tao J, Zhou X, Jiang Z. cGAS-cGAMP-STING: The three musketeers of cytosolic DNA sensing and signaling. IUBMB Life. 2016;68:858-870 pubmed publisher
    ..Host- or pathogen-derived cytosolic DNA binds and activates the DNA sensor cGAS, which synthesizes the second messenger 2'3'-cGAMP and triggers STING-dependent downstream signaling...
  4. Ma Z, Damania B. The cGAS-STING Defense Pathway and Its Counteraction by Viruses. Cell Host Microbe. 2016;19:150-8 pubmed publisher
    ..Recently, cGAS and STING have been identified as intracellular sensors that activate the interferon pathway in response to virus ..
  5. Andrade W, Agarwal S, Mo S, Shaffer S, Dillard J, Schmidt T, et al. Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4. Cell Rep. 2016;15:2438-48 pubmed publisher
    ..Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression...
  6. Watkinson R, McEwan W, Tam J, Vaysburd M, James L. TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus. PLoS Pathog. 2015;11:e1005253 pubmed publisher
    ..In this second response, TRIM21-induced exposure of the viral genome promotes sensing of DNA and RNA viruses by cGAS and RIG-I...
  7. Lio C, McDonald B, Takahashi M, Dhanwani R, Sharma N, Huang J, et al. cGAS-STING Signaling Regulates Initial Innate Control of Cytomegalovirus Infection. J Virol. 2016;90:7789-97 pubmed publisher
    ..human endothelial cells mount robust IFN-I responses to human CMV that are dependent upon cyclic GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3) signaling...
  8. Orzalli M, Broekema N, Diner B, Hancks D, Elde N, Cristea I, et al. cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection. Proc Natl Acad Sci U S A. 2015;112:E1773-81 pubmed publisher
    Interferon γ-inducible protein 16 (IFI16) and cGMP-AMP synthase (cGAS) have both been proposed to detect herpesviral DNA directly in herpes simplex virus (HSV)-infected cells and initiate interferon regulatory factor-3 signaling, but ..
  9. Xiao D, Huang W, Ou M, Guo C, Ye X, Liu Y, et al. Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population. Oncotarget. 2016;7:84228-84238 pubmed publisher
    ..Nevertheless, only some infected individuals actually develop cervical cancer. The cGAS-STING pathway in innate immunity plays an important role in protecting against HPV infection. Chen et al...
  10. Ma Z, Jacobs S, West J, Stopford C, Zhang Z, Davis Z, et al. Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proc Natl Acad Sci U S A. 2015;112:E4306-15 pubmed publisher
    Infection of cells with DNA viruses triggers innate immune responses mediated by DNA sensors. cGMP-AMP synthase (cGAS) is a key DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which binds to and ..
  11. Wassermann R, Gulen M, Sala C, Perin S, Lou Y, Rybniker J, et al. Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1. Cell Host Microbe. 2015;17:799-810 pubmed publisher
    ..We demonstrate that the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) is essential for initiating an IFN response to Mtb infection...
  12. Lee A, Park E, Lee J, Choi B, Kang S. The N terminus of cGAS de-oligomerizes the cGAS:DNA complex and lifts the DNA size restriction of core-cGAS activity. FEBS Lett. 2017;591:954-961 pubmed publisher
    Cyclic GMP-AMP synthase (cGAS) is a DNA-sensing enzyme in the innate immune system...
  13. Kato K, Ishii R, Goto E, Ishitani R, Tokunaga F, Nureki O. Structural and functional analyses of DNA-sensing and immune activation by human cGAS. PLoS ONE. 2013;8:e76983 pubmed publisher
    ..Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of ..
  14. Zhang Y, Yeruva L, Marinov A, Prantner D, Wyrick P, Lupashin V, et al. The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-? during Chlamydia trachomatis infection. J Immunol. 2014;193:2394-404 pubmed publisher
    ..The DNA sensor cyclic GMP-AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP-AMP, which binds to the signaling adaptor stimulator ..
  15. Ablasser A, Hemmerling I, Schmid Burgk J, Behrendt R, Roers A, Hornung V. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. J Immunol. 2014;192:5993-7 pubmed publisher
    ..These findings indicate a key role of cyclic GMP-AMP synthase for the initiation of self-DNA-induced autoimmune disorders, thus providing important implications for novel therapeutic approaches. ..
  16. Vermeire J, Roesch F, Sauter D, Rua R, Hotter D, Van Nuffel A, et al. HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4+ T Cells. Cell Rep. 2016;17:413-424 pubmed publisher
    ..Here, we show that activated CD4+ T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response...
  17. Xia P, Wang S, Gao P, Gao G, Fan Z. DNA sensor cGAS-mediated immune recognition. Protein Cell. 2016;7:777-791 pubmed publisher
    ..DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types...
  18. Liu F, Niu Q, Fan X, Liu C, Zhang J, Wei Z, et al. Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16-STING-Type I IFN Pathway and AIM2 Sensor. J Immunol. 2017;199:3293-3305 pubmed publisher
    ..Microarray and comprehensive gene-knockout analyses (CRISPR/Cas9) identified that ALVAC stimulated the cGAS/IFI16-STING-type I IFN pathway to prime AIM2, which was functionally required for ALVAC-induced inflammasome ..
  19. Su C, Zheng C. Herpes Simplex Virus 1 Abrogates the cGAS/STING-Mediated Cytosolic DNA-Sensing Pathway via Its Virion Host Shutoff Protein, UL41. J Virol. 2017;91: pubmed publisher
    Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor capable of detecting microbial DNA and activating the adaptor protein stimulator of interferon genes (STING), leading to interferon (IFN) production and host antiviral responses...
  20. Kranzusch P, Wilson S, Lee A, Berger J, Doudna J, Vance R. Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling. Mol Cell. 2015;59:891-903 pubmed publisher
    In humans, the cGAS-STING immunity pathway signals in response to cytosolic DNA via 2',3' cGAMP, a cyclic dinucleotide (CDN) second messenger containing mixed 2'-5' and 3'-5' phosphodiester bonds...
  21. Langereis M, Rabouw H, Holwerda M, Visser L, van Kuppeveld F. Knockout of cGAS and STING Rescues Virus Infection of Plasmid DNA-Transfected Cells. J Virol. 2015;89:11169-73 pubmed publisher
    ..Here, we show that cytosolic plasmid DNA activates the cGAS/STING signaling pathway, which ultimately leads to the induction of an antiviral state of the cells...
  22. Maelfait J, Seiradake E, Rehwinkel J. Keeping your armour intact: how HIV-1 evades detection by the innate immune system: HIV-1 capsid controls detection of reverse transcription products by the cytosolic DNA sensor cGAS. Bioessays. 2014;36:649-57 pubmed publisher
    ..its affinity for CypA results in reduced virus infectivity and facilitates access of the cytosolic DNA sensor cGAS to reverse transcribed DNA. This in turn induces a strong host response...
  23. Bode C, Fox M, Tewary P, Steinhagen A, Ellerkmann R, Klinman D, et al. Human plasmacytoid dentritic cells elicit a Type I Interferon response by sensing DNA via the cGAS-STING signaling pathway. Eur J Immunol. 2016;46:1615-21 pubmed publisher
    ..Increasing evidence suggests that the cytosolic DNA receptor cyclic GMP-AMP (cGAMP) synthase (cGAS) is a critical component in the detection of pathogens and contributes to autoimmune diseases...
  24. He J, Hao R, Liu D, Liu X, Wu S, Guo S, et al. Inhibition of hepatitis B virus replication by activation of the cGAS-STING pathway. J Gen Virol. 2016;97:3368-3378 pubmed publisher
    Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyses synthesis of the second messenger cGAMP, which activates the downstream signalling adaptor protein STING, leading to the expression of type I interferons...
  25. Wu J, Li W, Shao Y, Avey D, Fu B, Gillen J, et al. Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein. Cell Host Microbe. 2015;18:333-44 pubmed publisher
    Invading viral DNA can be recognized by the host cytosolic DNA sensor, cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in production of the second messenger cGAMP, which directs the adaptor protein STING to stimulate production of type ..
  26. Collins A, Cai H, Li T, Franco L, Li X, Nair V, et al. Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis. Cell Host Microbe. 2015;17:820-8 pubmed publisher
    ..tuberculosis activated cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) in macrophages to produce cGAMP, a second messenger that activates the adaptor protein stimulator of interferon ..
  27. Tao J, Zhang X, Jin J, Du X, Lian T, Yang J, et al. Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation. J Immunol. 2017;198:3627-3636 pubmed publisher
    The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) mediates innate immune responses against invading pathogens, or against self-dsDNA, which causes autoimmune disorders...
  28. Cui Y, Yu H, Zheng X, Peng R, Wang Q, Zhou Y, et al. SENP7 Potentiates cGAS Activation by Relieving SUMO-Mediated Inhibition of Cytosolic DNA Sensing. PLoS Pathog. 2017;13:e1006156 pubmed publisher
    Cyclic GMP-AMP (cGAMP) synthase (cGAS, a.k.a. MB21D1), a cytosolic DNA sensor, catalyzes formation of the second messenger 2'3'-cGAMP that activates the stimulator of interferon genes (STING) signaling...
  29. Seo G, Kim C, Shin W, Sklan E, Eoh H, Jung J. TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing. Nat Commun. 2018;9:613 pubmed publisher
    ..Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (..
  30. Mankan A, Schmidt T, Chauhan D, Goldeck M, Höning K, Gaidt M, et al. Cytosolic RNA:DNA hybrids activate the cGAS-STING axis. EMBO J. 2014;33:2937-46 pubmed publisher
    ..Most recently, cGAS was shown to be critical for the recognition of cytoplasmic dsDNA...
  31. Ma F, Li B, Liu S, Iyer S, Yu Y, Wu A, et al. Positive feedback regulation of type I IFN production by the IFN-inducible DNA sensor cGAS. J Immunol. 2015;194:1545-54 pubmed publisher
    ..It has been well demonstrated that cyclic GMP-AMP (cGAMP) synthase (cGAS) plays an important role in sensing cytosolic DNA and triggering STING dependent signaling to induce IFN-I...
  32. Wang Z, Liu Y, Mi N, Duan D. Intracellular DNA sensing pathway of cGAS-cGAMP is decreased in human newborns and young children. Mol Immunol. 2017;87:76-85 pubmed publisher
    ..Both mRNA and protein expression of cGAS, an intracellular DNA sensor, were shown to be significantly reduced in neonatal peripheral blood mononuclear cells ..
  33. Ablasser A, Schmid Burgk J, Hemmerling I, Horvath G, Schmidt T, Latz E, et al. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature. 2013;503:530-4 pubmed publisher
    ..Cytosolic DNA is sensed by the receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), which catalyses the synthesis of the second messenger cGAMP(2'-5')...
  34. Wang Y, Su G, Zhang F, Chu J, Wang Y. Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes. Mediators Inflamm. 2015;2015:192329 pubmed publisher
    ..Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation...
  35. Ablasser A, Gulen M. The role of cGAS in innate immunity and beyond. J Mol Med (Berl). 2016;94:1085-1093 pubmed
    ..In the cytosol the enzyme cyclic GMP-AMP synthase (cGAS) is critical for the recognition of pathogen-derived DNA and provides key signals that initiate immune responses...
  36. Hall J, Ralph E, Shanker S, Wang H, Byrnes L, Horst R, et al. The catalytic mechanism of cyclic GMP-AMP synthase (cGAS) and implications for innate immunity and inhibition. Protein Sci. 2017;26:2367-2380 pubmed publisher
    Cyclic GMP-AMP synthase (cGAS) is activated by ds-DNA binding to produce the secondary messenger 2',3'-cGAMP...
  37. Holm C, Rahbek S, Gad H, Bak R, Jakobsen M, Jiang Z, et al. Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses. Nat Commun. 2016;7:10680 pubmed publisher
    ..During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon...
  38. Diner B, Lum K, Toettcher J, Cristea I. Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection. MBio. 2016;7: pubmed publisher
    ..dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS)...
  39. Lam E, Falck Pedersen E. Unabated adenovirus replication following activation of the cGAS/STING-dependent antiviral response in human cells. J Virol. 2014;88:14426-39 pubmed publisher
    The cGAS/STING DNA sensing complex has recently been established as a predominant pathogen recognition receptor (PRR) for DNA-directed type I interferon (IFN) innate immune activation...
  40. Mackenzie K, Carroll P, Martin C, Murina O, Fluteau A, Simpson D, et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature. 2017;548:461-465 pubmed publisher
    DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage...
  41. Liang Q, Seo G, Choi Y, Kwak M, Ge J, Rodgers M, et al. Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host Microbe. 2014;15:228-38 pubmed publisher
    ..Upon recognition of microbial DNA, the cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) produces the second messenger cGAMP to initiate the stimulator of interferon genes (STING) pathway and subsequent ..
  42. Wu M, Cheng W, Chen S, Nieh S, O Connor C, Liu C, et al. miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS. Nat Cell Biol. 2017;19:1286-1296 pubmed publisher
    ..for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, ..
  43. Zhang G, Chan B, Samarina N, Abere B, Weidner Glunde M, Buch A, et al. Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS. Proc Natl Acad Sci U S A. 2016;113:E1034-43 pubmed publisher
    ..Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms...
  44. Wang Q, Huang L, Hong Z, Lv Z, Mao Z, Tang Y, et al. The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response. PLoS Pathog. 2017;13:e1006264 pubmed publisher
    The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2'3'-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling...
  45. Andreeva L, Hiller B, Kostrewa D, Lässig C, de Oliveira Mann C, Jan Drexler D, et al. cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein-DNA ladders. Nature. 2017;549:394-398 pubmed publisher
    ..It is sensed by cyclic GMP-AMP synthase (cGAS), which elicits the production of type I interferons by generating the second messenger 2'3'-cyclic-GMP-AMP (cGAMP)...
  46. Shu C, Li X, Li P. The mechanism of double-stranded DNA sensing through the cGAS-STING pathway. Cytokine Growth Factor Rev. 2014;25:641-8 pubmed publisher
    ..Cyclic GMP-AMP synthase (cGAS) is a cytosolic dsDNA sensor mediating the innate immunity to microbial DNA...
  47. Biolatti M, Dell Oste V, Pautasso S, Gugliesi F, von Einem J, Krapp C, et al. Human Cytomegalovirus Tegument Protein pp65 (pUL83) Dampens Type I Interferon Production by Inactivating the DNA Sensor cGAS without Affecting STING. J Virol. 2018;92: pubmed publisher
    ..To clarify the mechanisms through which pp65 inhibits IFN-? production, we analyzed the activation of the cGAS/STING/IRF3 axis in HFFs infected with either the wild type, the revertant v65Rev, or the pp65-deficient mutant ..