Table 1 Post-translational modifications of cGAS and STING
From: The interactions between cGAS-STING pathway and pathogens
Protein | Modification | Residues | Enzyme | Occurring contexts | Functions | Refs |
|---|---|---|---|---|---|---|
cGAS | Monoubiquitination | K335 | TRIM56 | Stimulated cells | Promotes cGAS dimerization and DNA-binding activity. | |
| Â | K27-linked polyubiquitination | K173/K384 | RNF185 | Stimulated cells | Promotes enzymatic activity of cGAS | |
| Â | K48-linked polyubiquitination | At least at K285/K479 | N.D. | Resting cells and stimulated cells | Facilitates degradation of cGAS in a proteasome pathway | |
| Â | Removal of K48-linked polyubiquitination | K414 | USP14 | Stimulated cells | Stabilizes cGAS | |
| Â | Phosphorylation | S305 | AKT | Stimulated cells | Impairs enzymatic activity of cGAS | |
| Â | Polyglutamylation | E272 | TTLL6 | Resting cells | Impairs DNA-binding ability of cGAS | |
| Â | Removal of polyglutamylation | E272 | CCP6 | Stimulated cells | Reverse inhibitory modification | |
| Â | Monoglutamylation | E302 | TTLL4 | Resting cells | Impairs enzymatic activity of cGAS | |
| Â | Removal of monoglutamylation | E302 | CCP5 | Stimulated cells | Reverse inhibitory modification | |
| Â | Acetylation | K384/K394/K414 | N.D. | Resting cells | Keeps cGAS in inactive states | |
| Â | Removal of acetylation | K384 | HDAC3 | Stimulated cells | Reverse inhibitory modification | |
| Â | Sumoylation | K231 | TRIM38 | Resting cells | Stablizes cGAS and impairs DNA-binding ability of cGAS | |
| Â | Sumoylation | K479 | TRIM38 | Stimulated cells | Stabilizes cGAS | |
| Â | Removal of sumoylation | K479 | SENP2 | Stimulated cells | Facilitates degradation of cGAS | |
STING | K11-linked polyubiquitination | K150 | RNF26 | Stimulated cells | Stabilizes STING | |
| Â | K27-linked polyubiquitination | K137/K150/K224/K236 | AMFR | Stimulated cells | Promotes recruitment of TBK1 | |
| Â | Removal of K27-linked polyubiquitination | N.D. | USP13 | Resting cells and stimulated cells | Prevents recruitment of TBK1 | |
|  | Removal of K27-linked polyubiquitination | N.D. | USP21 | Stimulated cells | Inhibits the formation of STING –TBK1-IRF3 complex | |
| Â | K63-linked polyubiquitination | K20/K150/K224/K236 | TRIM32 | Stimulated cells | Promotes interaction with TBK1 | |
| Â | K63-linked polyubiquitination | K224/K236/K289/K338 | MUL1 | Stimulated cells | Promotes dimerization and trafficking of STING | |
| Â | K63-linked polyubiquitination | K150 | TRIM56 | Stimulated cells | Promotes dimerization of STING and recruitment of TBK1 | |
| Â | Removal of K63-linked polyubiquitination | N.D. | USP21 | Stimulated cells | Inhibits the formation of STING-TBK1-RF3 complex | |
|  | K48-linked polyubiquitination | K275 | TRIM30α | Stimulated cells | Promotes degradation of STING in a proteasome pathway | |
| Â | K48-linked polyubiquitination | K150 | RNF5 | Stimulated cells | Promotes degradation of STING in a proteasome pathway | |
| Â | Removal of K48-linked polyubiquitination | N.D. | USP20 | Stimulated cells | Stabilizes STING | |
| Â | Removal of K48-linked polyubiquitination | N.D. | CYLD | Stimulated cells | Stabilizes STING | |
| Â | Removal of K48-linked polyubiquitination | N.D. | EIF3S5 | Stimulated cells | Stabilizes STING | |
| Â | Phosphorylation | Y245 | SRC | Stimulated cells | Enhances the activation of STING | |
| Â | Phosphorylation | S358 | TBK1 | Stimulated cells | Facilitates aggregation of STING | |
| Â | Phosphorylation | S366 | TBK1 | Stimulated cells | Facilitates recruitment of IRF3 | |
| Â | Phosphorylation | S366 | ULK1 | Stimulated cells | Facilitates degradation of STING | |
| Â | Dephosphorylation | Y245 | PTPN1/2 | Stimulated cells | Promotes degradation of STING in a proteasome pathway | |
| Â | Dephosphorylation | S358 | PPM1A | Stimulated cells | Impairs STING aggregation | |
| Â | Palmitoylation | C88/91 | DHHC | Stimulated cells | Enhances type I Interferon responses | |
| Â | Nitro-alkylation | C88/C91/H16 | N.D. | Stimulated cells | Antagonizes palmitoylation and impairs STING signaling | |
| Â | Sumoylation | K338 | TRIM38 | Stimulated cells | Promotes oligomerization and prevents degradation of STING | |
| Â | Removal of sumoylation | K338 | SENP2 | Stimulated cells | Facilitates degradation of STING |
