CGAS report

I. Expression across cell types

II. Expression across tissues

sc-RNAseq data

Insufficient scRNA-seq data for expression of CGAS at tissue level.

III. Associated gene sets

GO_0019934Biological processcGMP-mediated signaling
GO_0006281Biological processDNA repair
GO_0002221Biological processpattern recognition receptor signaling pathway
GO_2000774Biological processpositive regulation of cellular senescence
GO_0045087Biological processinnate immune response
GO_0008340Biological processdetermination of adult lifespan
GO_0051607Biological processdefense response to virus
GO_0006974Biological processDNA damage response
GO_0038001Biological processparacrine signaling
GO_0019933Biological processcAMP-mediated signaling
GO_0160049Biological processnegative regulation of cGAS/STING signaling pathway
GO_0032481Biological processpositive regulation of type I interferon production
GO_0002637Biological processregulation of immunoglobulin production
GO_2000042Biological processnegative regulation of double-strand break repair via homologous recombination
GO_0140896Biological processcGAS/STING signaling pathway
GO_0050863Biological processregulation of T cell activation
GO_0002218Biological processactivation of innate immune response
GO_0071360Biological processcellular response to exogenous dsRNA
GO_0002230Biological processpositive regulation of defense response to virus by host
GO_0002753Biological processcytoplasmic pattern recognition receptor signaling pathway
GO_0005886Cellular componentplasma membrane
GO_0005654Cellular componentnucleoplasm
GO_0016604Cellular componentnuclear body
GO_0005829Cellular componentcytosol
GO_0005737Cellular componentcytoplasm
GO_0035861Cellular componentsite of double-strand break
GO_0005634Cellular componentnucleus
GO_0003677Molecular functionDNA binding
GO_0042803Molecular functionprotein homodimerization activity
GO_0160004Molecular functionpoly-ADP-D-ribose modification-dependent protein binding
GO_0003682Molecular functionchromatin binding
GO_0003690Molecular functiondouble-stranded DNA binding
GO_0005546Molecular functionphosphatidylinositol-4,5-bisphosphate binding
GO_0005525Molecular functionGTP binding
GO_0140693Molecular functionmolecular condensate scaffold activity
GO_0046872Molecular functionmetal ion binding
GO_0005524Molecular functionATP binding
GO_0061501Molecular function2',3'-cyclic GMP-AMP synthase activity
GO_0031491Molecular functionnucleosome binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameCGAS
Protein nameCyclic GMP-AMP synthase
Cyclic GMP-AMP synthase (cGAMP synthase) (cGAS) (h-cGAS) (EC 2.7.7.86) (2'3'-cGAMP synthase) (Mab-21 domain-containing protein 1)
SynonymsC6orf150
MB21D1
DescriptionFUNCTION: Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity . 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] . Acts as a key DNA sensor: directly binds double-stranded DNA (dsDNA), inducing the formation of liquid-like droplets in which CGAS is activated, leading to synthesis of 2',3'-cGAMP, a second messenger that binds to and activates STING1, thereby triggering type-I interferon production . Preferentially recognizes and binds curved long dsDNAs of a minimal length of 40 bp . Acts as a key foreign DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses . Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm . Also acts as an innate immune sensor of infection by retroviruses, such as HIV-2, by detecting the presence of reverse-transcribed DNA in the cytosol . In contrast, HIV-1 is poorly sensed by CGAS, due to its capsid that cloaks viral DNA from CGAS detection . 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 . Also detects the presence of DNA from bacteria, such as M.tuberculosis . 2',3'-cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote STING1 activation and convey immune response to connecting cells . 2',3'-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 STING1-dependent manner . Also senses the presence of neutrophil extracellular traps (NETs) that are translocated to the cytosol following phagocytosis, leading to synthesis of 2',3'-cGAMP . In addition to foreign DNA, can also be activated by endogenous nuclear or mitochondrial DNA . When self-DNA leaks into the cytosol during cellular stress (such as mitochondrial stress, SARS-CoV-2 infection causing severe COVID-19 disease, DNA damage, mitotic arrest or senescence), or is present in form of cytosolic micronuclei, CGAS is activated leading to a state of sterile inflammation . 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 STING1 and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability . Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to 2',3'-cGAMP synthesis and subsequent activation of STING1 and type-I interferon production . Activated in response to prolonged mitotic arrest, promoting mitotic cell death . In a healthy cell, CGAS is however kept inactive even in cellular events that directly expose it to self-DNA, such as mitosis, when cGAS associates with chromatin directly after nuclear envelope breakdown or remains in the form of postmitotic persistent nuclear cGAS pools bound to chromatin . Nuclear CGAS is inactivated by chromatin via direct interaction with nucleosomes, which block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity . Also acts as a suppressor of DNA repair in response to DNA damage: inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex . In addition to DNA, also sense translation stress: in response to translation stress, translocates to the cytosol and associates with collided ribosomes, promoting its activation and triggering type-I interferon production . In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less 2',3'-cGAMP, allowing a more fine-tuned response to pathogens . .

AccessionsQ8N884
ENST00000370318.5 [Q8N884-2]
ENST00000370315.4 [Q8N884-1]
ENST00000680833.1
A0A7P0TBQ3