Stimulator of interferon genes
- interferon-beta production
- cellular response to interferon-beta
- immune system process
- regulation of type I interferon production
- defense response to virus
- cellular response to exogenous dsRNA
- activation of innate immune response
- positive regulation of protein binding
- positive regulation of transcription by RNA polymerase II
- positive regulation of defense response to virus by host
- apoptotic process
- innate immune response
- neutrophil degranulation
- cellular response to organic cyclic compound
- viral process
- positive regulation of DNA-binding transcription factor activity
- positive regulation of type I interferon production
- regulation of gene expression
- regulation of cellular metabolic process
- regulation of inflammatory response
- cytoplasmic pattern recognition receptor signaling pathway in response to virus
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| Location (UCSC) | Chr 5: 139.48 – 139.48 Mb | Chr 18: 35.87 – 35.87 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.[5]
STING plays an important role in
STING works as both a direct
Structure
Amino acids 1–379 of human STING include the 4
The STING forms a symmetrical dimer in the cell. STING dimer resembles a butterfly, with a deep cleft between the two protomers. The
Expression
STING is expressed in
Localization
The subcellular localization of STING has been elucidated as an
Function
STING mediates the
Antiviral immunity
STING elicits powerful
STING deficiency in mice led to lethal susceptibility to HSV-1 infection due to the lack of a successful type I interferon response.[16]
Point mutation of serine-358 dampens STING-IFN activation in bats and is suggested to give bats their ability to serve as reservoir hosts.[17]
Against intracellular bacteria
Intracellular bacteria,
Other
STING may be an important molecule for protective immunity against infectious organisms. For example, animals that cannot express STING are more susceptible to infection from
Role in host immunity
Although
STING signaling mechanisms
STING mediates
Several reports suggested that STING is associated with the activation of selective autophagy.
In summary, STING coordinates multiple immune responses to infection, including the induction of interferons and STAT6-dependent response and selective autophagy response.[8]
As a cytosolic DNA sensor
Cyclic dinucleotides-second-messenger signaling molecules produced by diverse bacterial species were detected in the cytosol of mammalian cells during intracellular pathogen infection; this leads to activation of TBK1-IRF3 and the downstream production of type I interferon.[8][25] STING has been shown to bind directly to
As a signaling adaptor
DDX41, a member of the DEXDc family of helicases, in myeloid dendritic cells recognizes intracellular DNA and mediates innate immune response through direct association with STING.[27] Other DNA sensors- DAI, RNA polymerase III, IFI16, have also been shown to activate STING through direct or indirect interactions.[15]
It has been proposed that intracellular calcium plays an important role in the response of the STING pathway.[30]
See also
- STING agonist– Component of the innate immune system
References
- ^ a b c ENSG00000288243 GRCh38: Ensembl release 89: ENSG00000184584, ENSG00000288243 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024349 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "STING1 stimulator of interferon response cGAMP interactor 1 [ Homo sapiens (human) ]".
- PMID 20022884.
- PMID 34347572.
- ^ S2CID 7968532.
- PMID 22728658.
- ^ "EST expression profile of TMEM173". biogps org. biogps.org.
- ^ "NCBI TMEM173 expression GEOprofile". NCBI. www.ncbi.nlm.nih.gov/geoprofiles.
- ^ PMID 18724357.
- ^ PMID 19926846.
- ^ PMID 21239155.
- ^ PMID 21940216.
- PMID 26867174.
- PMID 29478775.
- ^ PMID 23378430.
- PMID 20508090.
- PMID 19776740.
- ^ PMID 21820332.
- ^ PMID 22607800.
- PMID 22000020.
- PMID 22901810.
- PMID 19652017.
- PMID 21947006.
- PMID 21892174.
- PMID 23258412.
- PMID 23258413.
- bioRxiv 10.1101/145854.
Further reading
- Wang Y, Tong X, Omoregie ES, Liu W, Meng S, Ye X (Oct 2012). "Tetraspanin 6 (TSPAN6) negatively regulates retinoic acid-inducible gene I-like receptor-mediated immune signaling in a ubiquitination-dependent manner". The Journal of Biological Chemistry. 287 (41): 34626–34. PMID 22908223.
- Yin Q, Tian Y, Kabaleeswaran V, Jiang X, Tu D, Eck MJ, Chen ZJ, Wu H (Jun 2012). "Cyclic di-GMP sensing via the innate immune signaling protein STING". Molecular Cell. 46 (6): 735–45. PMID 22705373.
- Aguirre S, Maestre AM, Pagni S, Patel JR, Savage T, Gutman D, Maringer K, Bernal-Rubio D, Shabman RS, Simon V, Rodriguez-Madoz JR, Mulder LC, Barber GN, Fernandez-Sesma A (2012). "DENV inhibits type I IFN production in infected cells by cleaving human STING". PLOS Pathogens. 8 (10): e1002934. PMID 23055924.
- Li Y, Li C, Xue P, Zhong B, Mao AP, Ran Y, Chen H, Wang YY, Yang F, Shu HB (May 2009). "ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response". Proceedings of the National Academy of Sciences of the United States of America. 106 (19): 7945–50. PMID 19416887.
- Conlon J, Burdette DL, Sharma S, Bhat N, Thompson M, Jiang Z, Rathinam VA, Monks B, Jin T, Xiao TS, Vogel SN, Vance RE, Fitzgerald KA (May 2013). "Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid". Journal of Immunology. 190 (10): 5216–25. PMID 23585680.
- Abe T, Harashima A, Xia T, Konno H, Konno K, Morales A, Ahn J, Gutman D, Barber GN (Apr 2013). "STING recognition of cytoplasmic DNA instigates cellular defense". Molecular Cell. 50 (1): 5–15. PMID 23478444.
- Nazmi A, Mukhopadhyay R, Dutta K, Basu A (2012). "STING mediates neuronal innate immune response following Japanese encephalitis virus infection". Scientific Reports. 2: 347. PMID 22470840.
- Zhang J, Hu MM, Wang YY, Shu HB (Aug 2012). "TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination". The Journal of Biological Chemistry. 287 (34): 28646–55. PMID 22745133.
- Ishikawa H, Barber GN (Oct 2008). "STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling". Nature. 455 (7213): 674–8. PMID 18724357.