TABLE 2.
PTMs in class III PI3K subunits
| Subunit | Position | Type | Enzyme | Region | Reference | Effect | Position in Yeast |
| VPS34 | K29 | Acet. | p300 | C2 | (25) | Inhibits VPS34-Beclin 1 association, enhances Rubicon interaction | H28 |
| T159 | Phos. | Cdk1/Cdk5 | C2HH | (19) | Inhibits interaction with Beclin 1 | NA | |
| T163, S165 | Phos. | AMPK | C2HH | (15) | Inhibits autophagic complex assembly | NA | |
| S249 | Phos. | Ulk1 | C2 | (60) | No effect | G237 | |
| D285 | Caspase-mediated cleavage | Caspase 8 | C2/helical linker | (20) | Abolishes kinase activity, decreases interaction with Beclin 1 | Q296 | |
| T668 | Phos. | Cdk5 | Kinase (N-lobe) | (19) | Inhibits lipid kinase activity | T656 | |
| T677 | Phos. | PDK | Kinase (N-lobe) | (105) | Activates autophagy | P665 | |
| K771 | Acet. | p300 | Kinase (C-lobe) | (25) | Disrupts VPS34-PtdIns interaction | K759 | |
| K781 | Acet. | Kinase (C-lobe) | (25) | K781Q mutation attenuates VPS34-PtdIns interaction | P769 | ||
| K840 | SUMO. | TRIM28/KAP1 | Kinase (C-lobe) | (106) | Enhances association with Beclin 1 | L828 | |
| Y231 | Phos. | Src | C2/helical linker | (107) | Stimulates VPS34 translocation to the plasma membrane induced by insulin, and activation there | E219 | |
| Y310 | Phos. | Helical | (107) | A321 | |||
| k348, k352 (C. elegans) | K63-poly-polyubiquitylation | UBC-13–UEV-1–CHN-1 | Helical | (21) | Stabilizes VPS-34 (C. elegans) | K339 K343 | |
| VPS15 | 2G | Myristoyl. | ? | N terminus | (46) | G2A single mutant is similar to WT, phenotypes are enhanced when G2A is combined with one C-terminal deletions (S. cerevisiae) | 2G |
| Beclin 1 | S15 | Phos. | ULK1 | IDR | (6) | Enhances activity of complex I | NA |
| S30 | Phos. | Acetylated PGK1 | IDR | (108) | Enhances the ability of VPS34 to bind to PtdIns thereby increasing complex I activity | S15 | |
| S90 | Phos. | CaMKII | IDR | (109) | Promotes activation of autophagy via Beclin 1 dissociation from Bcl-2 | D78 | |
| S90 | Phos. | MK2 and MK3 | IDR | (110) | Promotes autophagy | D78 | |
| S93, S96 | Phos. | AMPK | IDR | (15) | Activates the pro-autophagy Vps34 complex, and induces autophagy | L81, S85 | |
| S90,93 | Phos. | ? | IDR | (111) | Critical for maximally efficient autophagy | D78, L81 | |
| T108 | Phos. | Mst1 | BH3 | (112) | Inhibits the activity of complex I and suppresses autophagy | S154 | |
| K117 | K63-linked ubiquitination | TRAF6 | BH3 | (113) | Critical for TLR4-triggered autophagy in macrophages | N162 | |
| T119 | Phos. | DAPK | BH3 | (114) | Promotes the dissociation of Beclin 1 from Bcl-XL and the induction of autophagy | M164 | |
| TDVD133 and DQLD149 | Caspase-mediated cleavage | Casp-3, 7 and 8 | CC1 | (115) | Yields fragmentation of Beclin 1, which lacks the autophagy-inducing capacity | ||
| Y229, Y233 and/or Y352 | Phos. | EGFR | CC2 and/or BARA | (65) | Decreases Beclin 1-associated VPS34 kinase activity | K282, Q286 and/or Y419 | |
| S234, S295 | Phos. | Akt | CC2 (and possibly BARA) | (66) | Inhibits autophagy and promotes the formation of the Beclin 1/14-3-3/vimentin intermediate filament complex | N287 (and possibly E348) | |
| T388 | Phos. | AMPK | BARA | (116) | Causes a higher affinity for BCL2 | S459 | |
| K402 | K48-linked ubiquitination | ? | BARA | (117) | Causes proteasome-mediated degradation, de-ubiquitinated by ataxin3 | K498 | |
| K430, K437 | Acet. | p300 | BARA | (118) | Inhibits autophagosome maturation and endocytic trafficking by promoting the recruitment of Rubicon. | K520, K527 | |
| K437 | K63-linked ubiquitination | Ambra1 | BARA | (119) | Enhances the association with VPS34 to promote Vps34 activity | K527 | |
| ATG14L | S3 | Phos. | mTOR | N-ter to CXXC | (72) | Inhibits complex I activity | NA |
| S223 | Phos. | C-ter | NA | ||||
| S233 | Phos. | C-ter | NA | ||||
| T383 | Phos. | C-ter | V288 | ||||
| S440 | Phos. | BATS | NA | ||||
| R423, R442 | — | — | BATS | (75) | PtdIns(4,5)P2 binding, important for binding to the autophagosome | NA | |
| S29 | Phos. | Ulk1 | N-terminal before CXXC | (70) | Important for complex I activity | NA | |
| UVRAG | S493 | Phos. | mTOR | C-Ter | (89) | Not known | NA |
| S498 | Phos. | (13, 89, 120, 121) | Incrcases the association with Rubicon inhibits VPS34, decreased endosome maturation | NA | |||
| S508 | Phos. | (89) | Not known | NA | |||
| S518 | Phos. | (13, 120) | Not known | NA | |||
| S522 | Phos. | (89) | Not known | NA | |||
| S549 | Phos. | (89, 120) | Not known | NA | |||
| S550 | Phos. | (13, 89, 120) | Increases VPS34 complex II activity and promotes autophagosome-lysosome reformation | NA | |||
| S571 | Phos. | (13, 120) | Increases VPS34 complex II activity and promotes autophagosome-lysosome reformation | NA | |||
| S582 | Phos. | (89) | Not known | NA | |||
| S689 | Phos. | (13, 120) | Not known | NA |