Mb21d1

Summary

Gene Symbol: Mb21d1
Description: Mab-21 domain containing 1
Alias: E330016A19Rik, cGAS, cyclic GMP-AMP synthase, 2'3'-cGAMP synthase, cGAMP synthase, mab-21 domain-containing protein 1
Species: mouse
Products:     Mb21d1

Top Publications

  1. Gao P, Ascano M, Wu Y, Barchet W, Gaffney B, Zillinger T, et al. Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell. 2013;153:1094-107 pubmed publisher
    ..cGAMP is generated from GTP and ATP by cytoplasmic dsDNA sensor cGAMP synthase (cGAS)...
  2. 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...
  3. Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, Röhl I, et al. cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature. 2013;498:380-4 pubmed publisher
    ..in an indirect fashion that depends on a recently characterized cytoplasmic nucleotidyl transferase, termed cGAMP synthase (cGAS), which upon interaction with DNA synthesizes a dinucleotide molecule that in turn binds to and ..
  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. Li X, Wu J, Gao D, Wang H, Sun L, Chen Z. Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science. 2013;341:1390-4 pubmed publisher
    ..approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses...
  6. 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...
  7. 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. ..
  8. Hasan M, Fermaintt C, Gao N, Sakai T, Miyazaki T, Jiang S, et al. Cytosolic Nuclease TREX1 Regulates Oligosaccharyltransferase Activity Independent of Nuclease Activity to Suppress Immune Activation. Immunity. 2015;43:463-74 pubmed publisher
    ..This function of the TREX1 C terminus suggests a potential therapeutic option for TREX1-fs mutant-associated diseases. ..
  9. 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 ..

More Information

Publications51

  1. Watson R, Bell S, MacDuff D, Kimmey J, Diner E, Olivas J, et al. The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy. Cell Host Microbe. 2015;17:811-819 pubmed publisher
    ..We report that the cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), is required for activating IFN production via the STING/TBK1/IRF3 pathway during M. tuberculosis and L...
  2. 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...
  3. STOREK K, Gertsvolf N, Ohlson M, Monack D. cGAS and Ifi204 cooperate to produce type I IFNs in response to Francisella infection. J Immunol. 2015;194:3236-45 pubmed publisher
    ..novicida infection is cytosolic. In this study, we report that the cytosolic DNA sensors, cyclic GMP-AMP synthase (cGAS) and Ifi204, are both required for the STING-dependent type I IFN response to F...
  4. Yockey L, Varela L, Rakib T, Khoury Hanold W, Fink S, Stutz B, et al. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection. Cell. 2016;166:1247-1256.e4 pubmed publisher
    ..This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy. ..
  5. Glück S, Guey B, Gulen M, Wolter K, Kang T, Schmacke N, et al. Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat Cell Biol. 2017;19:1061-1070 pubmed publisher
    ..We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells...
  6. 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 ..
  7. 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 ..
  8. 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')...
  9. Mackenzie K, Carroll P, Lettice L, TarnauskaitÄ— Å, Reddy K, Dix F, et al. Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response. EMBO J. 2016;35:831-44 pubmed publisher
    ..The inflammatory response is dependent on the nucleic acid sensor cyclicGMP-AMPsynthase (cGAS) and its adaptorSTINGand is associated with reduced cellular ribonucleotide excision repair activity and ..
  10. Chen M, Meng Q, Qin Y, Liang P, Tan P, He L, et al. TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses. Mol Cell. 2016;64:105-119 pubmed publisher
    Cyclic GMP-AMP synthase (cGAS) is an essential DNA virus sensor that triggers type I interferon (IFN) signaling by producing cGAMP to initiate antiviral immunity. However, post-translational regulation of cGAS remains largely unknown...
  11. Xu M, Pu Y, Han D, Shi Y, Cao X, Liang H, et al. Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein ? Signaling. Immunity. 2017;47:363-373.e5 pubmed publisher
    ..mtDNA was recognized by cyclic-GMP-AMP synthase (cGAS) in the DC cytosol, contributing to type I interferon (IFN) production and antitumor adaptive immunity...
  12. Harding S, Benci J, Irianto J, Discher D, Minn A, Greenberg R. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature. 2017;548:466-470 pubmed publisher
    ..of inflammatory signalling and are a repository for the pattern-recognition receptor cyclic GMP-AMP synthase (cGAS)...
  13. Anghelina D, Lam E, Falck Pedersen E. Diminished Innate Antiviral Response to Adenovirus Vectors in cGAS/STING-Deficient Mice Minimally Impacts Adaptive Immunity. J Virol. 2016;90:5915-27 pubmed publisher
    ..murine cell lines using short hairpin RNA (shRNA) knockdown strategies identified cyclic guanine adenine synthase (cGAS) as a pattern recognition receptor (PRR) that contributes to the antiadenovirus response...
  14. Carroll E, Jin L, Mori A, Muñoz Wolf N, Oleszycka E, Moran H, et al. The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons. Immunity. 2016;44:597-608 pubmed publisher
    ..of type I IFNs, IFN-stimulated genes and dendritic cell maturation by chitosan required the cytoplasmic DNA sensor cGAS and STING, implicating this pathway in dendritic cell activation...
  15. King K, Aguirre A, Ye Y, Sun Y, Roh J, Ng R, et al. IRF3 and type I interferons fuel a fatal response to myocardial infarction. Nat Med. 2017;23:1481-1487 pubmed publisher
    ..Mice genetically deficient in cyclic GMP-AMP synthase (cGAS), its adaptor STING, IRF3, or the type I IFN receptor IFNAR exhibited impaired interferon-stimulated gene (ISG) ..
  16. Schoggins J, MacDuff D, Imanaka N, Gainey M, Shrestha B, Eitson J, et al. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature. 2014;505:691-5 pubmed publisher
    ..Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses...
  17. Reinert L, Lopušná K, Winther H, Sun C, Thomsen M, Nandakumar R, et al. Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS. Nat Commun. 2016;7:13348 pubmed publisher
    ..are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE...
  18. Kerur N, Fukuda S, Banerjee D, Kim Y, Fu D, Apicella I, et al. cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. Nat Med. 2018;24:50-61 pubmed publisher
    ..pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-? production and gasdermin D-dependent interleukin-18 secretion...
  19. Liu T, Yang Q, Li M, Zhong B, Ran Y, Liu L, et al. LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner. J Immunol. 2016;196:5101-11 pubmed publisher
    ..Our findings reveal a nuclear mRNA precursor processing and cell-specific regulatory mechanism of antiviral immune responses. ..
  20. Xia P, Ye B, Wang S, Zhu X, Du Y, Xiong Z, et al. Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity. Nat Immunol. 2016;17:369-78 pubmed publisher
    Cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA during viral infection and catalyzes synthesis of the dinucleotide cGAMP, which activates the adaptor STING to initiate antiviral responses...
  21. Pokatayev V, Hasin N, Chon H, Cerritelli S, Sakhuja K, Ward J, et al. RNase H2 catalytic core Aicardi-Goutières syndrome-related mutant invokes cGAS-STING innate immune-sensing pathway in mice. J Exp Med. 2016;213:329-36 pubmed publisher
    ..we found that the G37S mutation led to increased expression of interferon-stimulated genes dependent on the cGAS-STING signaling pathway...
  22. Li X, Shu C, Yi G, Chaton C, Shelton C, Diao J, et al. Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity. 2013;39:1019-31 pubmed publisher
    Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity...
  23. 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...
  24. 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...
  25. Dai P, Wang W, Cao H, Avogadri F, Dai L, Drexler I, et al. Modified vaccinia virus Ankara triggers type I IFN production in murine conventional dendritic cells via a cGAS/STING-mediated cytosolic DNA-sensing pathway. PLoS Pathog. 2014;10:e1003989 pubmed publisher
    ..of type I IFN is fully dependent on STING (stimulator of IFN genes) and the newly discovered cytosolic DNA sensor cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase)...
  26. Suschak J, Wang S, Fitzgerald K, Lu S. A cGAS-Independent STING/IRF7 Pathway Mediates the Immunogenicity of DNA Vaccines. J Immunol. 2016;196:310-6 pubmed publisher
    ..In the present study, we investigated the roles of the putative DNA sensor cyclic GMP-AMP synthase (cGas), as well as the downstream IFN regulatory factors (IRF) 3 and 7 in type I IFN induction and Ag-specific immune ..
  27. Gao D, Li T, Li X, Chen X, Li Q, Wight Carter M, et al. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. Proc Natl Acad Sci U S A. 2015;112:E5699-705 pubmed publisher
    ..Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates the IFN pathway...
  28. Wang H, Hu S, Chen X, Shi H, Chen C, Sun L, et al. cGAS is essential for the antitumor effect of immune checkpoint blockade. Proc Natl Acad Sci U S A. 2017;114:1637-1642 pubmed publisher
    cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses...
  29. 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...
  30. Scumpia P, Botten G, Norman J, Kelly Scumpia K, Spreafico R, Ruccia A, et al. Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense. PLoS Pathog. 2017;13:e1006496 pubmed publisher
    ..aureus. This STING response was largely dependent on the cytosolic DNA sensor cyclic guanosine-adenosine synthase (cGAS)...
  31. 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...
  32. Lam E, Stein S, Falck Pedersen E. Adenovirus detection by the cGAS/STING/TBK1 DNA sensing cascade. J Virol. 2014;88:974-81 pubmed publisher
    ..Cyclic GMP-AMP synthase (cGAS), a DNA sensor that produces a cyclic guanine-adenine dinucleotide (cGAMP) inducer of STING, has been examined to ..
  33. 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...
  34. 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, ..
  35. Rongvaux A, Jackson R, Harman C, Li T, West A, de Zoete M, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159:1563-77 pubmed publisher
    ..This induction is mediated by mitochondrial DNA-dependent activation of the cGAS/STING pathway and results in the establishment of a potent state of viral resistance...
  36. 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)...
  37. Gray E, Treuting P, Woodward J, Stetson D. Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi-Goutières Syndrome. J Immunol. 2015;195:1939-43 pubmed publisher
    ..Multiple DNA sensors have been proposed to activate the ISD pathway, including cyclic GMP-AMP synthase (cGAS)...
  38. Yang H, Wang H, Ren J, Chen Q, Chen Z. cGAS is essential for cellular senescence. Proc Natl Acad Sci U S A. 2017;114:E4612-E4620 pubmed publisher
    ..Here we show that cGMP-AMP (cGAMP) synthase (cGAS), a cytosolic DNA sensor that activates innate immunity, is essential for senescence...
  39. Swanson K, Junkins R, Kurkjian C, Holley Guthrie E, Pendse A, El Morabiti R, et al. A noncanonical function of cGAMP in inflammasome priming and activation. J Exp Med. 2017;214:3611-3626 pubmed publisher
    ..The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon genes (STING) to activate IFN-I...
  40. Gray E, Winship D, Snyder J, Child S, Geballe A, Stetson D. The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA. Immunity. 2016;45:255-66 pubmed publisher
    ..Our findings indicate that ALRs are dispensable for the ISD response and suggest that alternative functions for these receptors should be explored. ..
  41. Di Micco A, Frera G, Lugrin J, Jamilloux Y, Hsu E, Tardivel A, et al. AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity. Proc Natl Acad Sci U S A. 2016;113:E4671-80 pubmed publisher
    ..These findings identify a pharmacologic activator of inflammasome and demonstrate the role of AIM2 in detecting endogenous DNA release upon perturbation of nuclear envelope integrity. ..
  42. 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...