Summary

Name CGAS
Full Name Cyclic GMP-AMP synthase
Synonyms cGAMP synthase, cGAS, h-cGAS, 2'3'-cGAMP synthase, Mab-21 domain-containing protein 1 | C6orf150, MB21D1
Primary ID Q8N884
Links - -
Type protein
Relations 5
Function Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990, PubMed:29976794, PubMed:30799039). Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed:28363908, PubMed:28214358). Acts as a key cytosolic DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed:28363908). Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production (PubMed:28363908, PubMed:28314590). Preferentially recognizes and binds curved long DNAs (PubMed:30007416). In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less cyclic GMP-AMP (cGAMP), allowing a more fine-tuned response to pathogens (PubMed:30007416). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:28363908). Also acts as an innate immune sensor of infection by retroviruses, such as HIV-1, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:23929945). Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA (PubMed:26046437). Also detects the presence of DNA from bacteria, such as M.tuberculosis (PubMed:26048138). cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote TMEM173/STING activation and convey immune response to connecting cells (PubMed:24077100). cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but TMEM173/STING-dependent manner (PubMed:26229115). In addition to antiviral activity, also involved in the response to cellular stresses, such as senescence, DNA damage or genome instability (PubMed:28738408, PubMed:28759889). Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via TMEM173/STING and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ CDK1down-regulates activity img/direct_inhibition.png phosphorylation CGAS 0.2
Publications: 1
+ PPP6Cdown-regulates activity img/direct_inhibition.png dephosphorylation CGAS 0.2
Publications: 1 Organism: Homo Sapiens
+ BLKdown-regulates activity img/direct_inhibition.png phosphorylation CGAS 0.2
Publications: 1
+ CGASup-regulates quantity img/direct-activation.png chemical modification 2'-3'-cGAMP(2-) 0.8
Publications: 1
+ CGASdown-regulates activity img/indirect_inhibition.png DNA_repair 0.7
Publications: 1 Organism: Homo Sapiens