Recombinant Human CGAS Protein, His-tagged

• Cat.No.: CGAS-132H
• Product Overview: Active recombinant N-terminal His-tagged full length human CGAS protein (2-522) was expressed in E. coli.

Specification

• Description: 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).
• Source: E. coli
• Species: Human
• Tag: His
• Molecular Mass: 61 kDa
• Protein length: 2-522
• Purity: ≥90% as determined by SDS-PAGE
• Unit Definition: One unit of cGAS produces 1 pmole of cGAMP per minute at 37 centigrade in 80 mM Tris-HCL, pH 7.5, containing 200 mM NaCl, 20 μM ZnCL2, and 20 mM MgCl2, with 4 μg circular DNA (3623 bp) and 0.25 mM each of GTP and ATP.
• Stability: ≥ 9 months
• Storage: At -80 centigrade.
• Storage Buffer: 50 mM HEPES, pH 8.0, with 300 mM sodium chloride, and 10% glycerol

Gene Information

• Gene Name: CGAS cyclic GMP-AMP synthase [ Homo sapiens (human) ]
• Official Symbol: CGAS
• Synonyms: CGAS; cyclic GMP-AMP synthase; MB21D1; h-cGAS; C6orf150; cyclic GMP-AMP synthase; 2'3'-cGAMP synthase; Mab-21 domain containing 1; cGAMP synthase; mab-21 domain-containing protein 1; protein MB21D1; EC 2.7.7.86
• Gene ID: 115004
• mRNA Refseq: NM_138441
• Protein Refseq: NP_612450
• MIM: 613973
• UniProt ID: Q8N884