Table 2.
Endogenous tau modifications in wildtype and hAPP mice.
| Modification site(s) | PTM | No. of PTMs | Modified residue (mouse 430 isoform) | Homologous residue (human 441 isoform) |
|---|---|---|---|---|
| DHGLKESPP | GlyGly | 1 | 33a | 44 |
| DHGLKAEEA | GlyGly | 1 | 33b | 44 |
| PGSETSDAK | Phospho | 1 | 50|52|53a | 61|63|64 |
| SDAKSTPTAE | Phospho | 1 | 57|58a | 68|69 |
| DAKSTPTAE | Phospho | 1 | 58a | 69 |
| GIGDTPNQE | Phospho | 1 | 100c | 111 |
| VTQARVASK | Methyl | 1 | 115c | 126 |
| IATPRGAAS | Methyl | 1 | 144 | 155 |
| RGAASPAQK | Phospho | 1 | 148 | – d |
| RGAASPAQKGTSNATRIPA | Phospho | 2 | 148,158e | –d,169 |
| SPAQKGTSN | Acetyl | 1 | 152 | 163 |
| SPAQKGTSN | Dimethyl | 1 | 152 | 163 |
| IPAKTTPSPKTP | Phospho | 2 | 164|165, 167 | 175|–,–d |
| IPAKTTPSPKTPPGS | Phospho | 3 | 164, 167, 170 | 175,–d,181 |
| KTTPSPKTP | Phospho | 1 | 167 | – d |
| KTTPSPKTPPGS | Phospho | 2 | 167, 170 | –d,181 |
| PSPKTPPGS | Phospho | 1 | 170 | 181 |
| PSPKTPPGSGEPPKSGERS | Phospho | 2 | 170, 180 | 181, 191 |
| RSGYSSPGSPGTP | Phospho | 2 | 187, 191 | 198, 202 |
| RSGYSSPGSPGTPGSRSRTPS | Phospho | 3 | 187|188|191|194|199 | 198|199|202|205|210 |
| SGYSSPGSP | Phospho | 1 | 188 | 199 |
| SGYSSPGSPGTP | Phospho | 2 | 188, 191 | 199,202 |
| SSPGSPGTP | Phospho | 1 | 191 | 202 |
| SSPGSPGTPGSR | Phospho | 2 | 191, 194 | 202, 205 |
| GSPGTPGSR | Phospho | 1 | 194 | 205 |
| PGSRSRTPSLPTPPTR | Phospho | 2 | 199|201|203|206 | 210|212|214|217 |
| SRSRTPSLP | Phospho | 1 | 201 | 212 |
| SRTPSLPTP | Phospho | 1 | 203 | 214 |
| PSLPTPPTR | Phospho | 1 | 206 | 217 |
| REPKKVAVV | Acetyl | 1 | 214 | 225 |
| AVVRTPPKS | Phospho | 1 | 220 | 231 |
| AWRTPPKSPSASKSRL | Phospho | 2 | 220|224|226|228 | 231|235|237|239 |
| AVVRTPPKSPSAS | Phospho | 2 | 220, 224 | 231, 235 |
| AVVRTPPKSPSASKSRL | Phospho | 2 | 220, 228f | 231, –d |
| PKSPSASKS | Phospho | 1 | 226 | 237 |
| NVRSKIGST | Acetyl | 1 | 248 | 259 |
| NVRSKIGST | GlyGly | 1 | 248 | 259 |
| NVRSKIGST | Methyl | 1 | 248 | 259 |
| SKIGSTENL | Phospho | 1 | 251 | 262 |
| TENLKHQPG | GlyGly | 1 | 256 | 267 |
| IINKKLDLS | Acetyl | 1 | 270 | 281 |
| IINKKLDLS | GlyGly | 1 | 270 | 281 |
| IINKKLDLS | Methyl | 1 | 270g | 281 |
| NVQSKCGSK | Acetyl | 1 | 279 | 290 |
| NVQSKCGSK | GlyGly | 1 | 279g | 290 |
| KDNIKHVPG | Acetyl | 1 | 287 | 298 |
| KDNIKHVPG | GlyGly | 1 | 287 | 298 |
| QIVYKPVDL | Acetyl | 1 | 300 | 311 |
| QIVYKPVDL | Dimethyl | 1 | 300 | 311 |
| QIVYKPVDL | GlyGly | 1 | 300 | 311 |
| VDLSKVTSK | Acetyl | 1 | 306 | 317 |
| VDLSKVTSK | GlyGly | 1 | 306 | 317 |
| KVTSKCGSL | Acetyl | 1 | 310 | 321 |
| KVTSKCGSL | GlyGly | 1 | 310 | 321 |
| SKCGSLGNI | Phospho | 1 | 313g | 324 |
| NIHHKPGGG | Acetyl | 1 | 320 | 331 |
| NIHHKPGGG | GlyGly | 1 | 320 | 331 |
| NIHHKPGGG | Methyl | 1 | 320g | 331 |
| VKSEKLDFK | Acetyl | 1 | 332 | 343 |
| VKSEKLDFK | GlyGly | 1 | 332 | 343 |
| KLDFKDRVQ | Acetyl | 1 | 336 | 347 |
| KLDFKDRVQ | GlyGly | 1 | 336 | 347 |
| DFKDRVQSK | Methyl | 1 | 338 | 349 |
| RVQSKIGSL | GlyGly | 1 | 342 | 353 |
| SKIGSLDNI | Phospho | 1 | 345 | 356 |
| GGGNKKIET | Acetyl | 1 | 358 | 369 |
| GGGNKKIET | GlyGly | 1 | 358 | 369 |
| KKIETHKLTFREN | Phospho | 1 | 362|366 | 373|377 |
| IETHKLTFR | GlyGly | 1 | 364 | 375 |
| NAKAKTDHG | Acetyl | 1 | 374 | 385 |
| NAKAKTDHG | GlyGly | 1 | 374 | 385 |
| AKAKTDHGAEIVYKSPVVS | Phospho | 2 | 375, 385g | 386, 396 |
| AKAKTDHGAEIVYKSPVVSGDTSPRHL | Phospho | 3 | 375, 385, 392|393 | 386, 396, 403|404 |
| AEIVYKSPVVS | Phospho | 2 | 383, 385g | 394, 396 |
| AEIVYKSPVVSGDTSPRHL | Phospho | 3 | 383, 389, 392|393 | 394, 400, 403|404 |
| AEIVYKSPVVSGDTSPRHL | Phospho | 3 | 383, 385, 392|393g | 394, 396, 403|404 |
| IVYKSPVVS | Phospho | 1 | 385 | 396 |
| IVYKSPVVSGDTS | Phospho | 2 | 385, 389 | 396, 400 |
| IVYKSPVV SGDTSPRHL | Phospho | 2 | 385, 392|393 | 396, 403|404 |
| IVYKSPVVSGDTSPRHL | Phospho | 3 | 385, 389, 393 | 396, 400, 404 |
| IVYKSPVVSGDTSPRHL | Phospho | 3 | 385, 389, 392|393 | 396, 400, 403|404 |
| SPVVSGDTS | HexNAc | 1 | 389 | 400 |
| SPVVSGDTS | Phospho | 1 | 389 | 400 |
| SPVVSGDTSPRHL | Phospho | 2 | 389, 392|393 | 400, 403|404 |
| SGDTSPRHL | Phospho | 1 | 393g | 404 |
| PRHLSNVSSTGSIDMV | Phospho | 2 | 398|401|402|403|405 | 409|412|413|414|416 |
| PRHLSNVSSTGSIDMV | Phospho | 3 | 398|401|402|403|405g | 409|412|413|414|416 |
| SSTGSIDMV | Phospho | 1 | 405h | 416 |
Endogenous PTM sites identified in this study are numbered according to the mouse 430 isoform (unless otherwise indicated). Identified sites conserved in mice and humans are also numbered according to the human 441 isoform and are indicated in Fig. 1. Novel modification sites found in wildtype mice are in bold and red font and are highlighted in Fig. 1b. Confirmed modification sites previously identified only by in vitro studies are in bold and blue. Sequences for PTM sites found only in hAPP mice are italicized and gray; these PTMs were excluded from Fig. 1. Site numberings for which unambiguous assignment was not possible are indicated with a vertical bar between alternative assignments. References for previously identified PTMs are provided in Supplementary Table 9.
Mouse tau isoform A peptide. Because this site and modification occurred in alternate isoforms, it was counted only once.
Mouse tau isoform B, C, or D peptide.
Mouse tau isoform A, B, C, or D peptide.
Not conserved in human tau.
Site identified in PSD experiments.
This site was previously reported only in mouse lung.
Modified species was observed only in hAPP samples.
Peptide site was unambiguously assigned with AspN digestion.