Table 1.
Hsp90 post-translational modifications, identified modifying enzymes, and functional consequences
Identified modification sites in Hsp90 are shown. Conservation between α and β isoforms is highlighted. Further indication of other species in which residues were found as well as other modifications that particular sites are subject to is as follows: boldface type, identified in that isoform; *, identified in Hsp82; †, identified in zebrafish Hsp90a1; §, identified in Candida albicans; a, acetylation; n, nitration; p, phosphorylation; s, SUMOylation; sc, succinylation; u, ubiquitination; g, glycation; o, O-GlcNAcylation; m, methylation; c, citrullination; sn, S-nitrosylation; t, thiocarbamlyation; ↑, binding increased (increased ATPase or increased inhibitor binding or sensitivity); ↓, binding decreased (decreased ATPase or decreased inhibitor binding or sensitivity); nc, no change; NA, not applicable/not conserved; no entry provided in the table if not determined or examined.
| PTM | Residue |
Enzyme |
Small-molecule binding |
References | ||
|---|---|---|---|---|---|---|
| Hsp90α | Hsp90β | Compound | ATP | Inhibitors | ||
| Serine/threonine phosphorylation | T5 | NA | ATM, DNA-PK | 57–62 | ||
| T7 | NA | ATM, DNA-PK | 57–63 | |||
| T36 (*,†) | T31 | CK2 | ↓ | ↑ | 64–66 | |
| S63 | S58 | CK2 | 67–69 | |||
| T65 | T60 | CK2 | 68, 70 | |||
| S68 | S63 | CK2 | 68 | |||
| S72 | S67 | CK2 | 68 | |||
| T88 | T83 | PKA | 69, 71, 72 | |||
| T90 | T85 | PKA | ↓ | 72–76 | ||
| S113 | S108 (*) | HopBF1 | ↓ | 77 | ||
| T115 | T110 | Mps1, Cdc14, PKCγ | ↓ | ↑ | 78, 79 | |
| S164 | S159 | Cdc7-Dbf4 | 80, 81 | |||
| S211 | S206 | PKA/PKG | 82, 83 | |||
| S231 | S226 | CK2, PP5 | 55, 84–89 | |||
| S263 | S255 | CK2, B-Raf, PP5 | 55, 84–92 | |||
| N373 | S365 | CK2 | 83, 93 | |||
| S399 (*) | S391 | ↓ | ↑ | 67, 94–96 | ||
| T425 | S417 | PKCγ | ↓ | 79 | ||
| S460 (o) | S452 (o) | PKA | 82 | |||
| S505 (*) | S497 | ↓ | ↑ | 69, 94 | ||
| S595 | S587 | Mitogen-activated protein kinase 12 (p38γ) | 97–99 | |||
| T603 | T595 | PKCγ | nc | 79, 99 | ||
| S623 (*) | S615 | ↓ | 94, 100, 101 | |||
| T624 | T616 | 102, 103 | ||||
| M625 (*) | M617 | ↓ | 94 | |||
| T725 | A717 | CK2, CK1, GSK3β | 104, 105 | |||
| S726 | S718 | CK2, CK1, GSK3β | 104, 105 | |||
| Tyrosine phosphorylation | Y38 (*,n) | Y33 (n) | Swe1 | ↓ | ↓ | 99, 106 |
| Y197 | Y192 | v-Src, Yes | 107–112 | |||
| Y309 | Y301 | c-Src | 110, 113, 114 | |||
| Y313 | Y305 | ↑ | 42, 69, 107, 115 | |||
| Y627 (*) | Y619 | 69, 107, 116, 117 | ||||
| Acetylation | K41 (§,u) | K36 (u) | ↑ | 118–120 | ||
| K69 (u) | K64 (u) | HAT p300 | ↓ | ↑ | 101, 121–124 | |
| K74 (u,g) | K69 (u) | 97, 99 | ||||
| K100 (u,g) | K95 | HAT p300 | ↓ | ↑ | 121 | |
| K292 (u) | K284 (u) | HAT p300 | ↑ | 121, 124 | ||
| K294 (†,§,u) | K286 (u) | HDAC6 | ↑ | 65, 118, 119, 125–129 | ||
| K327 (u) | K319 (u) | HAT p300 | ↓ | ↑ | 99, 121 | |
| K407 (u) | K399 (u) | ↑ | 124, 130 | |||
| K419 (u) | K411 | ↑ | 130, 131 | |||
| K478 (u,g) | S470 | HAT p300 | ↓ | ↑ | 121 | |
| K546 (u,g,sc) | K538 (u,sc) | HAT p300 | ↓ | ↑ | 121, 131 | |
| K558 (u) | K550 | HAT p300 | ↓ | ↑ | 121 | |
| Monomethylation | K209 (†,u) | K204 | SMYD2 | 65, 132 | ||
| K539 | K531 (a,u) | SMYD2 | 133 | |||
| K582 | K574 (a,u) | SMYD2 | 133 | |||
| K615 (*,†,a,u) | K607 | SMYD2 | 65, 132, 134–136 | |||
| Thiocarbamylation | C529 | C521 | 6-HITC-ME | 137 | ||
| C597 (sn) | C589 (sn) | STCA | 138 | |||
| S-Nitrosylation | C597 (t) | C589 (t) | Nitric oxide | 139, 140 | ||
| SUMOylation | K191 (a,u) | K186 | SUMO-1 | ↑ | 141 | |
| K559 (u) | K551 | SUMO peptidase sentrin/SUMO-specific protease 2 (SENP2) | 142 | |||
| Ubiquitination | K112 (g) | K107 | CHIP | 143–145 | ||
| K209 (m) | K204 (a) | CHIP | 143, 144, 146 | |||
| K224 (a) | K219 (a) | CHIP | 143, 144, 146 | |||
| K283 (a,g) | K275 (a) | CHIP | 143, 144, 146 | |||
| K292 (a) | K284 (a) | CHIP | 143, 144, 146 | |||
| R355 | K347 (a,m,sc) | CHIP | 144 | |||
| K407 (a) | K399 (a) | CHIP | 143, 144, 146 | |||
| K485 (a) | K477 (a) | CHIP | 143, 144 | |||
| K489 (a,m,sc) | K481 (a,sc) | CHIP | 143, 144, 146 | |||
| K546 (a,g,sc) | K538 (a,sc) | CHIP | 143–145 | |||
| K558 (a) | K550 | CHIP | 143, 144 | |||
| K615 (a,m) | K607 (a) | CHIP | 143, 144, 147 | |||
| K631 (a,sc) | K623 (a,sc) | CHIP | 143, 144, 148 | |||
| Nitration | Y38 (p) | Y33 (p) | 149, 150 | |||
| Y61 (p) | Y56 (p) | 149 | ||||
| O-GlcNAcylation | S442 (p) | S434 (p) | 151 | |||
| S460 (p) | S452 (p) | 151 | ||||