STING/TMEM173 Products

Description

STING (stimulator of interferon genes) is encoded by the TMEM173 gene and is an adaptor molecule involved in the activation of innate immune responses to PAMPS (pathogen-associated molecular patterns) and DAMPS (damage-associated molecular patterns). STING specifically recognizes cytosolic DNA products derived from pathogens (e.g., cytomegalovirus, vaccinia virus, Listeria monocytogenes) or dead cells (1, 2). In the STING pathway, dsDNA derived from pathogens or damaged cells serves as a substrate for the enzyme cGAS (cyclic GMP-AMP synthase) which produces the second messenger cyclic GMP-AMP (cGAMP) from ATP and GTP (3, 4). Under steady-state conditions STING (theoretical molecular weight 42 kDa), a protein localizes to the ER membrane. Upon activation by dsDNA derived second messenger (cGAMP), STING translocates to the Golgi apparatus as a homodimer. Once STING has trafficked to the perinuclear region, it activates TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3) and NF-kB leading to the production of cytokines (e.g., type I interferon) (2, 4). Mutations in the TMEM173 gene affecting STING expression are associated with the development of the auto-inflammatory disease SAVI (STING-associated vasculopathy with onset in infancy) (2). A novel SAVI dominant mutation in the TMEM173 human gene (V155M) leads to increased localization of STING to the Golgi and perinuclear region, indicative of an activated state (1). Hallmarks of SAVI, a rare inflammatory disease, include severe vasculitis in extremities and lung inflammation (7).

References

1. Patel, S., & Jin, L. (2019). TMEM173 variants and potential importance to human biology and disease. Genes and Immunity. https://doi.org/10.1038/s41435-018-0029-9

2. Jounai, N., Kobiyama, K., Takeshita, F., & Ishii, K. J. (2013). Recognition of damage-associated molecular patterns related to nucleic acids during inflammation and vaccination. Frontiers in Cellular and Infection Microbiology. https://doi.org/10.3389/fcimb.2012.00168

3. Xiao, T. S., & Fitzgerald, K. A. (2013). The cGAS-STING Pathway for DNA Sensing. Molecular Cell. https://doi.org/10.1016/j.molcel.2013.07.004

4. Kato, K., Omura, H., Ishitani, R., & Nureki, O. (2017). Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Annual Review of Biochemistry. https://doi.org/10.1146/annurev-biochem-061516-044813

5. Crowl, J. T., Gray, E. E., Pestal, K., Volkman, H. E., & Stetson, D. B. (2017). Intracellular Nucleic Acid Detection in Autoimmunity. Annual Review of Immunology. https://doi.org/10.1146/annurev-immunol-051116-052331

Bioinformatics

Entrez	340061 Human
Uniprot	NM_198282 Human NP_938023 Human Q86WV6 Human
Product By Gene ID	340061
Alternate Names	endoplasmic reticulum IFN stimulator Endoplasmic reticulum interferon stimulator ERIS FLJ38577 hMITA hSTING Mediator of IRF3 activation MITA mitochondrial mediator of IRF3 activation MPYS NET23 N-terminal methionine-proline-tyrosine-serine plasma membrane tetraspanner SAVI Stimulator of interferon genes protein stimulator of interferon protein sting STING-beta TMEM173 transmembrane protein 173

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STING in Innate Immunity and Cancer: What’s the Buzz About? STING (STimulator of INterferon Genes protein) acts as a sensor of cytosolic DNA. Bacteria/Virus or self-derived DNA in the cytosol activates the STING pathway and promotes the production of type I interferons (IFN-alpha and IFN-beta). STING also ...    Read more.

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