cGAS Protein, Human (His)

cGAS belongs to the nucleotidyltransferase family^[1]. cGAS is a cytoplasmic DNA sensor that can bind to double-stranded DNA (dsDNA) and catalyze the generation of cyclic guanosine-adenylate (cGAMP), which in turn activates the STING protein and initiates the type I interferon (IFN-I) pathway^[1][2]. After cGAS binds to cytoplasmic DNA, it undergoes a conformational change and catalyzes ATP and GTP to generate cGAMP with a 2′-5′/3′-5′ phosphodiester bond. cGAMP binds to and activates STING, ultimately inducing IRF3 dimerization and the expression of IFN-I and proinflammatory cytokines^[2][6]. cGAS is expressed in a variety of cells, including monocyte-derived dendritic cells (moDC), macrophages (MF), plasmacytoid dendritic cells (pDC), HEK293T cells, THP1 cells, etc., and its expression level in immune cells can be upregulated by viral infection or IFN-α induction^[5][6]. cGAS, Human and cGAS homologs from other species such as mice have sequence and structural homology in the catalytic domain, but there are species-specific differences. For example, the catalytic efficiency of human cGAS is lower than that of mice, and differences in some regulatory sites (such as K187 and L195) affect its binding to DNA and activation mode^[1][4]. cGAS, Human consists of an N-terminal disordered region (1-156 amino acids) and a C-terminal structured catalytic domain (157-522 amino acids). The catalytic domain contains a nucleotidyltransferase (NTase) domain and a Mab21 domain, which is the functional core that binds DNA and catalyzes the synthesis of cGAMP^[4]. The activity of cGAS, Human depends on DNA binding, and its efficiency in catalyzing the production of cGAMP is affected by DNA length, conformation, and histone binding status. For example, nucleosome binding reduces its activity. In addition, its activity can be specifically inhibited by small molecule inhibitors (such as RU.521)^[3][5].

cGAS Protein, Human can be activated by HCMV DNA to synthesize cGAMP^[6].