Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP 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[GpAp] . Acts as a key DNA sensor: directly binds double-stranded DNA , 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 binds long dsDNA and forms ladder-like networks that function cooperatively to stabilize individual cGAS-dsDNA complexes . Acts as a key foreign DNA sensor, the presence of double-stranded DNA 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 by detecting the presence of reverse-transcribed DNA in the cytosol . 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 . 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 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 , 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 . 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 as frequently found in cancer cells, consist of chromatin surrounded by its 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 . 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 .

Cyclic GMP-AMP synthase (cGAMP synthase) (cGAS) (m-cGAS) (EC 2.7.7.86) (2'3'-cGAMP synthase) (Mab-21 domain-containing protein 1)

q8c6l5

Mouse

WB,IP

WB 1:1000
IP 1:20-1:50

~59 kD

Rabbit

50mM Tris-Glycine(pH 7.4), 0.15M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.

Store at -20°C. Stable for 12 months from date of receipt.