cGAS 蛋白, Human (His)

cGAS is a cytosolic DNA sensor. cGAS binds double-stranded DNA (dsDNA) and catalyzes the generation of cyclic guanosine-adenylate (cGAMP), which in turn activates the STING protein. cGAS induces the production of type I interferon (IFN-I) and pro-inflammatory cytokines. cGAS Protein, Human (His) is a recombinant cGAS protein expressed in E. coli with a C-6*His tag.

cGAS 属于核苷酸转移酶 (nucleotidyltransferase) 家族^[1]。cGAS 是一种胞质 DNA 传感器，能结合双链 DNA (dsDNA) 并催化生成环化鸟苷酸-腺苷酸 (cGAMP)，进而激活 STING 蛋白，启动 I 型干扰素 (IFN-I) 通路^[1][2]。cGAS 结合胞质 DNA 后发生构象变化，催化 ATP 和 GTP 生成具有 2′-5′/3′-5′ 磷酸二酯键的 cGAMP，cGAMP 结合并激活 STING，最终诱导 IRF3 二聚化及 IFN-I 和促炎细胞因子表达^[2][6]。cGAS 在多种细胞中表达，包括单核细胞衍生的树突状细胞 (moDC)、巨噬细胞 (MF)、plasmacytoid 树突状细胞 (pDC)、HEK293T 细胞、THP1 细胞等，且在免疫细胞中的表达水平可受病毒感染或 IFN-α 诱导上调^[5][6]。cGAS, Human 与小鼠等其他种属的 cGAS 同源物在催化结构域具有序列和结构同源性，但存在种属特异性差异，例如人类 cGAS 的催化效率低于小鼠，且部分调控位点 (如 K187、L195) 的差异影响其与 DNA 的结合及激活方式^[1][4]。cGAS, Human 由 N 端无序区 (1-156 氨基酸) 和 C 端结构化的催化结构域 (157-522 氨基酸) 构成，其中催化结构域包含核苷酸转移酶 (NTase) 结构域和 Mab21 结构域，是结合 DNA 和催化 cGAMP 合成的功能核心^[4]。cGAS, Human 的活性依赖于 DNA 结合，其催化生成 cGAMP 的效率受 DNA 长度、构象及组蛋白结合状态影响，例如核小体结合会降低其活性；此外，其活性还可被小分子抑制剂 (如 RU.521) 特异性抑制^[3][5]。

cGAS Protein, Human 可被 HCMV DNA 激活合成 cGAMP^[6]。

Enzyme activity has been tested in vitro.

Human

E. coli

C-6*His

Q8N884-1 (M1-F522)

115004  [NCBI]

Full Length of Isoform-1

MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPSDATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTYFLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF

Approximately 58.9 kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE.

溶液.

Supplied as a 0.22 μm filtered solution of 20 mM Tris HCl, 100 mM NaCl, 1 mM DTT, 5% Glycerol, pH 7.5.
Note: For SPR assay, please replace the buffer. Primary amine components (e.g., Tris, imidazole) can affect protein-coupled chips.

<1 EU/μg, determined by LAL method.

N/A.

Stored at -80°C for 1 year from date of receipt. It is stable at -20°C for 3 months after opening. It is recommended to freeze aliquots at -80°C for extended storage. Avoid repeated freeze-thaw cycles.

Shipping with dry ice.

• [1]. Sun L, et al. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013 Feb 15;339(6121):786-91.  [Content Brief]

  [2]. Ablasser A, et al. cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature. 2013 Jun 20;498(7454):380-4.  [Content Brief]

  [3]. Wiser C, et al. Small molecule inhibition of human cGAS reduces total cGAMP output and cytokine expression in cells. Sci Rep. 2020 May 5;10(1):7604.  [Content Brief]

  [4]. Zhou W, et al. Analysis of human cGAS activity and structure. Methods Enzymol. 2019;625:13-40. doi: 10.1016/bs.mie.2019.04.012. Epub 2019 May 2.  [Content Brief]

  [5]. Wang H, et al. Cellular uptake of extracellular nucleosomes induces innate immune responses by binding and activating cGMP-AMP synthase (cGAS). Sci Rep. 2020 Sep 21;10(1):15385.  [Content Brief]

  [6]. Paijo J, et al. cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells. PLoS Pathog. 2016 Apr 8;12(4):e1005546.  [Content Brief]