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. | |
Polyubiquitination(K11) | K150 | RNF26 | + | Stabilizes STING through K11-linked polyubiquitination | |
Polyubiquitination(K27) | K137/K150/K224/K236 | AMFR | + | Promotes recruitment of TBK1 | |
Polyubiquitination(K48) | K150 | RNF5 | − | Promotes degradation of STING in a proteasome pathway | |
Polyubiquitination(K48) | K275 | TRIM30α | − | Promotes K48-linked ubiquitination of STING and its degradation | |
Polyubiquitination(K48) | K370 | TRIM29 | − | Promotes K48-linked ubiquitination of STING and its degradation | |
Polyubiquitination(K48) | K288/K337 | TRIM29 | − | Promotes proteasome-dependent degradation of STING | |
Polyubiquitination(K63) | K150 | TRIM56 | + | Promotes dimerization of STING and recruitment of TBK1 | |
Polyubiquitination(K63) | K20/K150/K224/K236 | TRIM32 | + | Promotes interaction with TBK1 | |
Polyubiquitination(K63) | K224/K236/K289/K338 | MUL1 | + | Promotes dimerization and trafficking of STING | |
Polyubiquitination(K63) | K20/224/289 | RNF115 | + | Promotes the oligmerization of STING and the recruitment of TBK1 | |
Polyubiquitination(K63) | N.D. | LMO7 | + | Promotes K63-linked STING poly-ubiquitination and STING–TBK1 interaction | |
Polyubiquitination(K63) | N.D. | TRIP12 | + | Promotes K63-linked STING poly-ubiquitination and STING–TBK1 interaction | |
Deubiquitylation (K63) | K150 | MYSM1 | − | Interacts with STING to cleave STING ubiquitination and attenuate the pathway | |
Deubiquitylation (K27) | N.D. | USP13 | − | Prevents recruitment of TBK1 | |
Deubiquitylation (K27) | N.D. | USP21 | − | Inhibits the formation of STING-TBK1-IRF3 complex | |
Deubiquitylation (K48) | N.D. | USP20 | + | Deploited by USP18 to Stabilize STING | |
Deubiquitylation (K48) | N.D. | CYLD | + | Stabilizes STING by removing the K48-linked polyubiquitin chains | |
Deubiquitylation (K48) | N.D. | EIF3S5 | + | Stabilizes STING by removing the K48-linked polyubiquitin chains | |
Deubiquitylation (K48) | K347 | OTUD5 | + | Stabilizes STING stability | |
Deubiquitylation (K48) | N.D. | USP35 | + | Removes K6-, K11-, K27-, K29- or K63-linked polyubiquitin chains from STING | |
Deubiquitylation (K63) | N.D. | USP21 | − | Inhibits the formation of STING–TBK1–RF3 complex | |
Phosphorylation | Y245 | Src | + | Enhances the activation of STING | |
Phosphorylation | Y245 | EGFR | + | Promotes STING relocation to late endosome for IRF3 activation and stabilizes STING | |
Phosphorylation | S358 | TBK1 | + | Facilitates recruitment and activation of IRF3 | |
Phosphorylation | S366 | TBK1 | + | Provides docking site for IRF3 | |
Phosphorylation | S366 | ULK1 | − | Facilitates degradation of STING | |
Dephosphorylation | Y245 | PTPN1/2 | − | Promotes degradation of STING in a proteasome pathway | |
Dephosphorylation | S358 | PPM1A | − | Dephosphorylates both STING and TBK1 and Impairs STING aggregation | |
Dephosphorylation | N.D. | PPM1G | − | Dephosphorylates STING but not TBK1 | |
SUMOylation | K338 | TRIM38 | + | Promotes oligomerization and recruitment of IRF3 and stabilizes STING | |
De-SUMOylation | K338 | SENP2 | − | Facilitates degradation of STING | |
Palmitoylation | C88/91 | ZDHHC3/7/15 | + | Promotes polymerization and type I Interferon production | |
Nitro-alkylation | C88/C91/H16 | N.D. | + | Antagonizes palmitoylation and impairs STING signaling | |
Disulfide bond | C148 | − | + | Promotes polymerization and activation of STING | |
Oxidation | C148 | − | − | Prevents polymerization and activation of STING | |
Carbonylation | C88 | GPX4 | − | Inhibits its trafficking from the endoplasmic reticulum to the Golgi complex |
