STING A162 variant (human, recombinant)

STING A162 variant (human recombinant) contains amino acids 138-379 of the wild-type variant (R232) with an alanine substituted for serine at position 162. Stimulator of interferon genes (STING) is a component of the innate immune response that binds to cyclic dinucleotides, which are bacterial second messengers, leading to activation of NF-κB and transcription of immunomodulatory genes, including type I interferon (IFN).^1,2,3,4 The R232 variant of STING is the most common variant in the human population, found at a frequency of 57.9% in the 1000 Genome Project.⁵ The SNP variant H232 is found at a 13.7% frequency. The S162A point mutation is located in the cyclic dinucleotide binding site of the human STING variants R232 and H232 and allows human STING to bind to DMXAA, a compound previously known to bind mouse, but not human, STING.^6,7 When STING S162A is bound to DMXAA, it adopts the closed conformation, similar to the conformation it has when bound to the second messenger 2’3’-cGAMP (Item No. 19887), and activates the IFN pathway similarly to mouse STING.⁶

WARNING This product is not for human or veterinary use.

1. Sun, L., Wu, J., Du, F., et al. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339(6121), 786-791 (2013).

2. Wu, J., Sun, L., Chen, X., et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339(6121), 826-830 (2013).

3. Konno, H., Konno, K., and Barber, G.N. Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 155(3), 688-698 (2013).

4. Burdette, D.L., Monroe, K.M., Sotelo-Troha, K., et al. STING is a direct innate immune sensor of cyclic-di-GMP. Nature 478(7370), 515-518 (2011).

5. Yi, G., Brendel, V.P., Shu, C., et al. Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides. PLoS One 8(10), e77846 (2013).

6. Gao, P., Ascano, M., Zillinger, T., et al. Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] and targeting by antiviral DMXAA. Cell 154(4), 748-762 (2013).

7. Conlon, J., Burdette, D.L., Sharma, S., et al. Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid. J. Immunol. 190(10), 5216-5225 (2013).