Table 2.
STING post-translational modifications
| Type of PTMs | Residues | Enzyme | Types of regulation | Functions | Ref. |
|---|---|---|---|---|---|
| Polyubiquitination(K6) | K20 | TRIM13 | + | Promotes STING degradation through ERAD pathway. | 272 |
| Polyubiquitination(K11) | K150 | RNF26 | + | Stabilizes STING through K11-linked polyubiquitination | 273 |
| Polyubiquitination(K27) | K137/K150/K224/K236 | AMFR | + | Promotes recruitment of TBK1 | 274 |
| Polyubiquitination(K48) | K150 | RNF5 | − | Promotes degradation of STING in a proteasome pathway | 275 |
| Polyubiquitination(K48) | K275 | TRIM30α | − | Promotes K48-linked ubiquitination of STING and its degradation | 150 |
| Polyubiquitination(K48) | K370 | TRIM29 | − | Promotes K48-linked ubiquitination of STING and its degradation | 151 |
| Polyubiquitination(K48) | K288/K337 | TRIM29 | − | Promotes proteasome-dependent degradation of STING | 276 |
| Polyubiquitination(K63) | K150 | TRIM56 | + | Promotes dimerization of STING and recruitment of TBK1 | 152 |
| Polyubiquitination(K63) | K20/K150/K224/K236 | TRIM32 | + | Promotes interaction with TBK1 | 153 |
| Polyubiquitination(K63) | K224/K236/K289/K338 | MUL1 | + | Promotes dimerization and trafficking of STING | 277 |
| Polyubiquitination(K63) | K20/224/289 | RNF115 | + | Promotes the oligmerization of STING and the recruitment of TBK1 | 278 |
| Polyubiquitination(K63) | N.D. | LMO7 | + | Promotes K63-linked STING poly-ubiquitination and STING–TBK1 interaction | 266 |
| Polyubiquitination(K63) | N.D. | TRIP12 | + | Promotes K63-linked STING poly-ubiquitination and STING–TBK1 interaction | 266 |
| Deubiquitylation (K63) | K150 | MYSM1 | − | Interacts with STING to cleave STING ubiquitination and attenuate the pathway | 279 |
| Deubiquitylation (K27) | N.D. | USP13 | − | Prevents recruitment of TBK1 | 280 |
| Deubiquitylation (K27) | N.D. | USP21 | − | Inhibits the formation of STING-TBK1-IRF3 complex | 281 |
| Deubiquitylation (K48) | N.D. | USP20 | + | Deploited by USP18 to Stabilize STING | 282 |
| Deubiquitylation (K48) | N.D. | CYLD | + | Stabilizes STING by removing the K48-linked polyubiquitin chains | 283 |
| Deubiquitylation (K48) | N.D. | EIF3S5 | + | Stabilizes STING by removing the K48-linked polyubiquitin chains | 255 |
| Deubiquitylation (K48) | K347 | OTUD5 | + | Stabilizes STING stability | 284 |
| Deubiquitylation (K48) | N.D. | USP35 | + | Removes K6-, K11-, K27-, K29- or K63-linked polyubiquitin chains from STING | 285 |
| Deubiquitylation (K63) | N.D. | USP21 | − | Inhibits the formation of STING–TBK1–RF3 complex | 281 |
| Phosphorylation | Y245 | Src | + | Enhances the activation of STING | 286 |
| Phosphorylation | Y245 | EGFR | + | Promotes STING relocation to late endosome for IRF3 activation and stabilizes STING | 287 |
| Phosphorylation | S358 | TBK1 | + | Facilitates recruitment and activation of IRF3 | 7,288 |
| Phosphorylation | S366 | TBK1 | + | Provides docking site for IRF3 | 7 |
| Phosphorylation | S366 | ULK1 | − | Facilitates degradation of STING | 127 |
| Dephosphorylation | Y245 | PTPN1/2 | − | Promotes degradation of STING in a proteasome pathway | 289 |
| Dephosphorylation | S358 | PPM1A | − | Dephosphorylates both STING and TBK1 and Impairs STING aggregation | 290 |
| Dephosphorylation | N.D. | PPM1G | − | Dephosphorylates STING but not TBK1 | 291 |
| SUMOylation | K338 | TRIM38 | + | Promotes oligomerization and recruitment of IRF3 and stabilizes STING | 292 |
| De-SUMOylation | K338 | SENP2 | − | Facilitates degradation of STING | 292 |
| Palmitoylation | C88/91 | ZDHHC3/7/15 | + | Promotes polymerization and type I Interferon production | 293 |
| Nitro-alkylation | C88/C91/H16 | N.D. | + | Antagonizes palmitoylation and impairs STING signaling | 179 |
| Disulfide bond | C148 | − | + | Promotes polymerization and activation of STING | 177 |
| Oxidation | C148 | − | − | Prevents polymerization and activation of STING | 175 |
| Carbonylation | C88 | GPX4 | − | Inhibits its trafficking from the endoplasmic reticulum to the Golgi complex | 180 |
AMFR autocrine motility factor receptor, also known as gp75, RNF45, CYLD CYLD Lysine 63 deubiquitinase, ZDHHC3/7/15 zinc finger DHHC domain-containing protein 3/7/15, EGFR epidermal growth factor receptor, EIF3S5 eukaryotic translation initiation factor 3 subunit F, ERAD ER-associated protein degradation, IRF3 interferon regulatory factor 3, GPX4 glutathione peroxidase 4, LOM7 LIM domain only protein 7, MUL1 mitochondrial E3 ubiquitin protein ligase 1, MYSM1 Myb like, SWIRM and MPN domains 1, N.D. not determined, OTUD5 OTU deubiquitinase 5, PPM1A protein phosphatase magnesium-dependent 1 delta, PPM1G protein phosphatase magnesium-dependent 1 gamma, PTPN1/2 tyrosine-protein phosphatase non-receptor type 1/2, RNF ring finger protein, SENP2 sentrin-specific protease 2, STING stimulator of interferon genes, TBK1 TANK-binding kinase 1, TRIM tripartite motif containing-containing protein, TRIP12 thyroid hormone receptor interactor 12, ULK1 Unc-51 like autophagy activating kinase 1, USP ubiquitin-specific-processing protease.