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Lexique

Numbering according to the longest isoform of 441 AA (Nomemclature selon l'isoforme la plus longue (441 acides aminés))

1 M (Met) (N terminal)

2 A (Ala)

3 E (Glu)

4 P (Pro)

5 R (Arg)  Mutation reported (4R tau aggregates) Ann Neurol 2002 Apr;51(4):525-30                     R5L also

6 Q (Gln)

7 E (Glu)

8 F (Phe)

9 E (Glu)

10 V (Val)

11 M (Met)

12 E (Glu)

13 D (Asp)

14 H (His)

15 A (Ala)

16 G (Gly)

17 T (Thr)

18 Y (Tyr)

19 G (Gly)

20 L (Leu)

21 G (Gly)

22 D (Asp)

23 R (Arg)

24 K (Lys)

25 D (Asp)

26 Q (Gln)

27 G (Gly)

28 G (Gly)

29 Y (Tyr)

30 T (Thr)

31 M (Met)

32 H (His)

33 Q (Gln)

34 D (Asp)

35 Q (Gln)

36 E (Glu)

37 G (Gly)

38 D (Asp)

39 T (Thr)

40 D (Asp)

41 A (Ala)

42 G (Gly)

43 L (Leu)

44 K (Lys) END EXON 1

intron: gttagtggac..........................

45 E

46 S

47 P(Pro)

48 L

49 Q

50 T

51 P(Pro)

52 T

53 E

54 D

55 G

56 S

57 E

58 E

59 P(Pro)

60 G

61 S

62 E

63 T

64 S

65 D

66 A

67 K

68 S

69 T

70 P(Pro)

71 T

72 A

73 E End exon 2

74 D

75 V

76 T

77 A

78 P(Pro)

79 L

80 V

81 D

82 E

83 G

84 A

85 P(Pro)

86 G

87 K

88 Q (Gln)

89 A

90 A

91 A

92 Q (Gln)

93 P(Pro)

94 H

95 T

96 E

97 I

98 P(Pro)

99 E

100 G

101 T

102 T End EXON 3

103 A (Ala)

104 E (Glu)

105 E (Glu)

106 A (Ala)

107 G (Gly)

108 I (Ile)

109 G (Gly)

110 D (Asp)

111 T (Thr)

112 P (Pro)

113 S (Ser)

114 L (Leu)

115 E (Glu)

116 D (Asp)

117 E (Glu)

118 A (Ala)

119 A (Ala)

120 G (Gly)

121 H (His)

122 V (Val)

123 T (Thr)

124 Q (Gln) End exon 4

125 A (Ala)

126 R (Arg)

127 M (Met)

128 V (Val)

129 S (Ser)

130 K (Lys)

131 Ser

132 K (Lys)

133 D (Asp)

134 G (Gly)

135 T (Thr)

136 G (Gly)

137 Ser

138 D (Asp)

139 D (Asp)

140 K (Lys)

141 K (Lys)

142 A (Ala)

143 K (Lys) End exon5

144 G (Gly)

145 A (Ala)

146 D (Asp)

147 G (Gly)

148 K (Lys)

149 T (Thr)

150 K (Lys)

151 I (Ile)

152 A (Ala)

153 T (Thr)

154 P (Pro)**

155 R (Arg)

156 G (Gly)

157 A (Ala)

158 A (Ala)

159 P (Pro)

160 P (Pro

161 G (Gly)

162 Q (Gln)

163 K (Lys)

164 G (Gly)

165 E (Glu)

166 A (Ala)

167 N (Asn)

168 A (Ala)

169 T (Thr)

170 R (Arg)

171 I (Ile)

172 P (Pro)

173 A (Ala)

174 K (Lys)

175 T (Thr)

176 P (Pro)

177 P (Pro)

178 A (Ala)

179 P (Pro)

180 K (Lys)

181 T (Thr) 

182 P (Pro)

183 P (Pro)

184 Ser

185 Ser End exon7

186 G (Gly) start exon 9

187 E (Glu)

188 P (Pro)

189 P (Pro)

190 K (Lys)

191 Ser

192 G (Gly)

193 D (Asp)

194 R (Arg)

195 Ser

196 G (Gly)

197 Y (Tyr)

198 Ser

199 Ser

200 P (Pro)

201 G (Gly)

202 Ser

203 P (Pro)

204 G (Gly)

205 T (Thr)

206 P (Pro)

207 G (Gly)

208 Ser

209 R (Arg)

210 Ser

211 R (Arg)

212 T (Thr)

213 P (Pro)

214 Ser

215 L (Leu)

216 P (Pro)

217 T (Thr)

218 P (Pro)

219 P (Pro)

220 T (Thr)

221 R (Arg)

222 E (Glu)

223 P (Pro)

224 K (Lys)

225 K (Lys)

226 V (Val)

227 A (Ala)

228 V (Val)

229 V (Val)

230 R (Arg)

231 T (Thr)

232 P (Pro)

233 P (Pro)

234 K (Lys)

235 Ser

236 P (Pro)

237 Ser

238 Ser

Lesions with tau exon 10+ isoforms(Tau 64 et 69): Clark et al, PNAS, 1998,95:13103-13107. PSP phenotype

N279K: clinical pattern

280 K (Lys)Mutation deltaK280 deletion of lysine: decreases microtubules stability: Rizzu et al, Am J Human Genet, 1999, 64:414-421; Mutation acts first on exon 10 splicing: D'Souza et al, PNAS, 1999, 96:5598-5602

281 K (Lys)

282 L (Leu)

283 D (Asp)

L284 L (Leu) This mutation acts on exon 10 splicing: D'Souza et al, PNAS, 1999, 96:5598-5602. Amyloid deposits

285 Ser

286 N (Asn)

287 V (Val) Repeat 2

288 Q (Gln)

289 Ser

290 K (Lys)

291 C (Cys)

292 G (Gly)

293 Ser

294 K (Lys)

295 D (Asp)

296 N (Asn) mutation ; Delta N 296

297 I (Ile)

298 K (Lys)

299 H (His)

300 V (Val)

301 P (Pro) to Mutations Leu or Ser...strongly inhibits the polymerisation of microtubules. Families HFTD I (Seatle D,F ; Oregon E,L. Neuron and glial tangles. Twisted ribbons of tau,essentially E10+ (Tau 64 et 69): Spillantini et al, Am J Pathol 1998,153:1359-1363 ; Clark et al, PNAS, 1998,95:13103-13107 ; Mirra et al, JNEN, 1998,58:335-345

P301L: clinical pattern

This mutation provokes destabilisation of tau and its aggregation: Nacharaju et al, FEBS 1999,447:195-199 ; dicreases microtubule stability: Rizzu et al, Am J Human Genet, 1999,64:414-421; Hasegawa et al, 1998, FEBS Letters, 437:207-210; Nacharaju et al, FEBS Lett, 1999,447:195-199, suggesting that other factors modulate clinical and neuropathological expression (Bird et al, Brain 1999, 12:741-756

Patterns with the upper tau doublet in the frontal cortex and the triplet in the temporal and parietal cortex (van Swieten et al, Ann Neurol, 1999,46:617-626)

P301S: specificity: seizures; Lossos A et al J Neurol  2003 Jun;250(6):733-40

302 G (Gly)

303 G (Gly)

304 G (Gly)

305 Ser Mutation Ser305Asn: Iijima et al, Neuroreport 1999,10:497-501: Japonese family. Frontotemporal dementia, low Parkinsonism. Tangles in neurones made up of straight tubules , found mainly in cortical layer II. Tangles in astrocytes of the cortical ans subcortical white matter

This mutation does not modify tau-tubulin interaction, but acts on exon 10 splicing: Hasegawa et al, Febs Letters, 199, 443:93-96 .

Early memory loss

-------------------------End exon 10: intron 10------------------------

Intron that regulates splicing of exon 10: many mutations in this intronic region provoke FTDP-17.

Mutations +3,+12,+13,+14,+16, +33: modification of a stem loop of messager RNA that abnormally increases the expression of tau E10+ isoforms.

  +3: Early memory loss

+11: mental reatardation

Mutation +16: clinical picture

-----------------Exon 11

306 V (Val)

307 Q (Gln)

308 I (Ile)

309 V (Val)

310 Y (Tyr)

311 K (Lys)

312 P (Pro)** R2-R3 IR

313 V (Val)

314 D (Asp)

315 L (Leu)     L315R (van Herpen et al,2002; Van Herpen E, Variable phenotypic expression and extensive tau pathology in two families with the novel tau mutation L315R., Ann Neurol  2003 Nov;54(5):573-81)

316 Ser

317 K (Lys) K317M Zarranz JJ, A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease., Neurology  2005 May;64(9):1578-85

318 V (Val) R3

319 T (Thr)

320 Ser     S320F

:

Rosso SM, van Herpen E, Deelen W, Kamphorst W, Severijnen LA, Willemsen R, Ravid R, Niermeijer MF, Dooijes D, Smith MJ, Goedert M, Heutink P, van Swieten JC.

Related Articles, Links

321 K (Lys)

322 C (Cys)

323 G (Gly)

324 Ser

325 L (Leu)

326 G (Gly)

327 N (Asn)

328 I (Ile)

329 H (His)

330 H (His)

331 K (Lys)

332 P (Pro)* End exon 11

Exon 12

333 G (Gly)

334 G (Gly)

335 G (Gly)

336 Q (Gln) R3-R4 IR

337 V (Val) Mutation V337M GTG->ATG Families Seatle A, 6 isoforms. PHF

This mutation provokes microtubule destabilisation and tau aggregation: Nacharaju et al, FEBS 1999,447:195-199 ; dicreases microtubules stability: Hasegawa et al, 1998, FEBS Letters, 437:207-210; Nacharaju et al, FEBS Lett, 1999,447:195-199; Arawaka et al, 1999, Neuroreport, 10:993-997
This mutation provokes a loss of function of the tau isoforms without exon 10. It shows that mutations located on the six tau isoforms (because the mutation is located in a region common to all six isoforms) can have essentially a physiological defect on only 3 of the six isoforms. It explains the heterogeneous eeffet of tau mutation (Sahara et al, J Neurosci Res, 2000, 60:380-387).

339 V (Val)

340 K (Lys)

341 Ser

342 E (Glu) mutation Val: 4R tauopathy essentiall

343 K (Lys) R3-R4 IR

344 L (Leu) h

345 D (Asp)

346 F (Phe)

347 K (Lys)

348 D (Asp)

349 R (Arg)

350 V (Val) R4

351 Q (Gln)

352 Ser

353 K (Lys)

354 I (Ile)

355 G (Gly)

356 Ser

357 L (Leu)

358 D (Asp)

359 N (Asn)

360 I (Ile)

361 T (Thr)

362 H (His)

363 V (Val)

364 P (Pro)

365 G (Gly)

366 G (Gly)

367 G (Gly)

368 N (Asn)

369 K (Lys) mutation K369 I: Pick phenotype

370 K (Lys) fin exon 12

371 I (Ile)

372 E (Glu)

373 T (Thr)

374 H (His)

375 K (Lys)

376 L (Leu)

377 T (Thr)

378 F (Phe)

379 R (Arg)

380 E (Glu)

381 N (Asn)

382 A (Ala)

383 K (Lys)

384 A (Ala)

385 K (Lys)

386 T (Thr)

387 D (Asp)

388 H (His)

389 G (Gly) Mutation G389R

Murell et al, JNEN, 1999,58:1227_1233. Provokes a "Pick-like" pathology

390 A (Ala)

391 E (Glu)

392 I (Ile)

393 V (Val)

394 Y (Tyr)

395 K (Lys)

396 Ser         AD2 phosporylation site

397 P (Pro)**

398 V (Val)

399 V (Val)

400 Ser

401 G (Gly)

402 D (Asp)

403 T (Thr)

404 Ser  AD2 phosphorylation site

405 P (Pro)**

406 R (Arg)Mutation R406W: Iowa family. Mutation decreases microtubule stability: Rizzu et al, Am J Human Genet, 1999, 64:414-421 ; Hasegawa et al, 1998, FEBS Letters, 437:207-210; Nacharaju et al, FEBS Lett, 1999,447:195-199
.
Affects more specifically tau isoforms with 3R: Sahara et al, J. Neuroscience Research, 60:380-387, 2000.

PSP phenotype. Early memory loss

407 H (His)

408 L (Leu)

409 Ser

410 N (Asn)

411 V (Val)

412 Ser

413 Ser

414 T (Thr)

415 G (Gly)

416 Ser

417 I (Ile)

418 D (Asp)

419 M (Met)

420 V (Val)

421 D (Asp)

422 Ser

423 P (Pro)**

424 Q (Gln)

425 L (Leu)

426 A (Ala)

427 T (Thr)

428 L (Leu)

429 A (Ala)

430 D (Asp)

431 E (Glu)

432 V (Val)

433 Ser

434 A (Ala)

435 Ser

436 L (Leu)

437 A (Ala)

438 K (Lys)

439 Q (Gln)

440 G (Gly)

441 L (Leu)