Mouse Anti-CGAS Recombinant Antibody (CBWJC-2566) (CBMAB-C3649WJ)

Mouse

Human

CBWJC-2566

IgG2a

WB, IP, IF

Full length human recombinant protein.

Mouse

Human

IgG2a

Monoclonal Antibody

The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Liquid

PBS, pH 7.2, 50% glycerol

0.02% sodium azide

Batch dependent

Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

Cyclic GMP-AMP Synthase

CGAS (Cyclic GMP-AMP Synthase) is a Protein Coding gene. Diseases associated with CGAS include Aicardi-Goutieres Syndrome and Renpenning Syndrome 1. Among its related pathways are Innate Immune System and Cytosolic sensors of pathogen-associated DNA.

Cyclic GMP-AMP Synthase; Mab-21 Domain-Containing Protein 1; Mab-21 Domain Containing 1; 23-CGAMP Synthase; CGAMP Synthase; C6orf150; MB21D1;

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: acts by localizing to micronuclei arising from genome instability (PubMed:28738408, PubMed:28759889).
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 cGAMP synthesis and subsequent activation of TMEM173/STING and type-I interferon production (PubMed:28738408, PubMed:28759889).
Acts as a suppressor of DNA repair in response to DNA damage: translocates to the nucleus following dephosphorylation at Tyr-215 and inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed:30356214).

Activation of innate immune response Source: UniProtKB
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to exogenous dsRNA Source: UniProtKB
Defense response to virus Source: UniProtKB
Determination of adult lifespan Source: Ensembl
DNA repair Source: UniProtKB-KW
Innate immune response Source: UniProtKB-KW
Negative regulation of double-strand break repair via homologous recombination Source: UniProtKB
Paracrine signaling Source: UniProtKB
Positive regulation of cAMP-mediated signaling Source: UniProtKB
Positive regulation of cellular senescence Source: UniProtKB
Positive regulation of cGMP-mediated signaling Source: UniProtKB
Positive regulation of defense response to virus by host Source: UniProtKB
Positive regulation of type I interferon production Source: UniProtKB
Regulation of immunoglobulin production Source: Ensembl
Regulation of T cell activation Source: Ensembl
Viral process Source: UniProtKB-KW

Nucleus; Cytosol; Cell membrane. In resting conditions, localizes at the cell membrane as a peripheral membrane protein by binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:30827685). Localization at the cell membrane is required to limit the recognition of self-DNA (PubMed:30827685). Following detection of double-stranded DNA (dsDNA), released from the cell membrane into the cytosol in order to signal (PubMed:30827685). Upon transfection with dsDNA forms punctate structures that co-localize with DNA and Beclin-1 (BECN1) (PubMed:26048138). Phosphorylation at Tyr-215 promotes cytosolic retention; translocates into the nucleus following dephosphorylation (PubMed:30356214).
(Microbial infection) Upon infection with virulent M.tuberculosis forms aggregates with dsDNA, non-virulent bacteria (without the ESX-1 locus) do not form these aggregates (PubMed:26048138).

Phosphorylation at Tyr-215 by BLK promotes cytosolic retention (PubMed:30356214). Translocates into the nucleus following dephosphorylation at Tyr-215 (PubMed:30356214).
(Microbial infection) Deamidated on 'Asn-210' by herpes simplex virus 1 protein UL37. This modification significantly reduces CGAS-dependent cGAMP production and innate immune signaling induced by dsDNA.
Polyglutamylated by TTLL6 at Glu-286, leading to impair DNA-binding activity. Monoglutamylated at Glu-314 by TTLL4, leading to impair the nucleotidyltransferase activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6.
Cleaved by CASP1 at Asp-140 and Asp-157 upon DNA virus infection; the cleavage impairs cGAMP production (PubMed:28314590). Also cleaved by the pyroptotic CASP4 and CASP5 during non-canonical inflammasome activation; they don't cut at the same sites than CASP1 (PubMed:28314590).
Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity (PubMed:30799039). Deacetylated upon cytosolic DNA challenge such as viral infections (PubMed:30799039). Acetylation can be mediated by aspirin (acetylsalicylate) drug, which directly acetylates CGAS (PubMed:30799039). Acetylation by aspirin efficiently inhibits CGAS-mediated immune responses and is able to suppress self-DNA-induced autoimmunity (PubMed:30799039).