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 .

Q8N884

115004

Cyclic GMP-AMP synthase, cGAMP synthase, cGAS, h-cGAS, Mab-21 domain-containing protein 1, MB21D1, C6orf150

Human

WB,FC

WB 1:1000
FC 1:25

59 kD

Rabbit

Polyclonal

Rabbit IgG

This antibody is purified by peptide affinity purification.

PBS (pH7.4) with 0.09% (W/V) sodium azide.

Store at -20°C. Stable for 12 months from date of receipt.Do not aliquot the antibody.Avoid freeze / thaw cycle.