NameMicrotubule-associated protein tau
Synonyms
  • MAPTL
  • MTBT1
  • Neurofibrillary tangle protein
  • Paired helical filament-tau
  • PHF-tau
  • TAU
Gene NameMAPT
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037237|Microtubule-associated protein tau
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPG
SETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAG
HVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEG
GRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPA
QDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLE
FTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPA
AAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSS
DPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQK
GQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREP
KKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLD
LSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEK
LDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDT
SPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL
Number of residues758
Molecular Weight78927.025
Theoretical pI6.69
GO Classification
Functions
  • SH3 domain binding
  • microtubule binding
  • apolipoprotein binding
  • lipoprotein particle binding
  • structural constituent of cytoskeleton
  • enzyme binding
Processes
  • response to organic substance
  • positive regulation of microtubule polymerization
  • cellular component disassembly involved in execution phase of apoptosis
  • regulation of autophagy
  • regulation of microtubule-based movement
  • microtubule cytoskeleton organization
  • regulation of microtubule polymerization
  • apoptotic process
  • intrinsic apoptotic signaling pathway in response to oxidative stress
  • female pregnancy
  • programmed cell death
  • axon cargo transport
  • brain development
  • axon extension
  • response to nutrient
  • generation of neurons
  • adult walking behavior
  • mitochondrion transport along microtubule
  • negative regulation of intracellular transport
  • neuron migration
  • positive regulation of axon extension
Components
  • nuclear periphery
  • dendrite
  • postsynaptic density
  • axoneme
  • neurofibrillary tangle
  • tubulin complex
  • cell body
  • microtubule
  • cytoplasmic ribonucleoprotein granule
  • growth cone
  • plasma membrane
  • microtubule associated complex
  • axon
  • cytosol
General FunctionStructural constituent of cytoskeleton
Specific FunctionPromotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP10636
UniProtKB Entry NameTAU_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0012425|Microtubule-associated protein tau (MAPT)
ATGGCTGAGCCCCGCCAGGAGTTCGAAGTGATGGAAGATCACGCTGGGACGTACGGGTTG
GGGGACAGGAAAGATCAGGGGGGCTACACCATGCACCAAGACCAAGAGGGTGACACGGAC
GCTGGCCTGAAAGAATCTCCCCTGCAGACCCCCACTGAGGACGGATCTGAGGAACCGGGC
TCTGAAACCTCTGATGCTAAGAGCACTCCAACAGCGGAAGATGTGACAGCACCCTTAGTG
GATGAGGGAGCTCCCGGCAAGCAGGCTGCCGCGCAGCCCCACACGGAGATCCCAGAAGGA
ACCACAGCTGAAGAAGCAGGCATTGGAGACACCCCCAGCCTGGAAGACGAAGCTGCTGGT
CACGTGACCCAAGAGCCTGAAAGTGGTAAGGTGGTCCAGGAAGGCTTCCTCCGAGAGCCA
GGCCCCCCAGGTCTGAGCCACCAGCTCATGTCCGGCATGCCTGGGGCTCCCCTCCTGCCT
GAGGGCCCCAGAGAGGCCACACGCCAACCTTCGGGGACAGGACCTGAGGACACAGAGGGC
GGCCGCCACGCCCCTGAGCTGCTCAAGCACCAGCTTCTAGGAGACCTGCACCAGGAGGGG
CCGCCGCTGAAGGGGGCAGGGGGCAAAGAGAGGCCGGGGAGCAAGGAGGAGGTGGATGAA
GACCGCGACGTCGATGAGTCCTCCCCCCAAGACTCCCCTCCCTCCAAGGCCTCCCCAGCC
CAAGATGGGCGGCCTCCCCAGACAGCCGCCAGAGAAGCCACCAGCATCCCAGGCTTCCCA
GCGGAGGGTGCCATCCCCCTCCCTGTGGATTTCCTCTCCAAAGTTTCCACAGAGATCCCA
GCCTCAGAGCCCGACGGGCCCAGTGTAGGGCGGGCCAAAGGGCAGGATGCCCCCCTGGAG
TTCACGTTTCACGTGGAAATCACACCCAACGTGCAGAAGGAGCAGGCGCACTCGGAGGAG
CATTTGGGAAGGGCTGCATTTCCAGGGGCCCCTGGAGAGGGGCCAGAGGCCCGGGGCCCC
TCTTTGGGAGAGGACACAAAAGAGGCTGACCTTCCAGAGCCCTCTGAAAAGCAGCCTGCT
GCTGCTCCGCGGGGGAAGCCCGTCAGCCGGGTCCCTCAACTCAAAGCTCGCATGGTCAGT
AAAAGCAAAGACGGGACTGGAAGCGATGACAAAAAAGCCAAGACATCCACACGTTCCTCT
GCTAAAACCTTGAAAAATAGGCCTTGCCTTAGCCCCAAACACCCCACTCCTGGTAGCTCA
GACCCTCTGATCCAACCCTCCAGCCCTGCTGTGTGCCCAGAGCCACCTTCCTCTCCTAAA
TACGTCTCTTCTGTCACTTCCCGAACTGGCAGTTCTGGAGCAAAGGAGATGAAACTCAAG
GGGGCTGATGGTAAAACGAAGATCGCCACACCGCGGGGAGCAGCCCCTCCAGGCCAGAAG
GGCCAGGCCAACGCCACCAGGATTCCAGCAAAAACCCCGCCCGCTCCAAAGACACCACCC
AGCTCTGCGACTAAGCAAGTCCAGAGAAGACCACCCCCTGCAGGGCCCAGATCTGAGAGA
GGTGAACCTCCAAAATCAGGGGATCGCAGCGGCTACAGCAGCCCCGGCTCCCCAGGCACT
CCCGGCAGCCGCTCCCGCACCCCGTCCCTTCCAACCCCACCCACCCGGGAGCCCAAGAAG
GTGGCAGTGGTCCGTACTCCACCCAAGTCGCCGTCTTCCGCCAAGAGCCGCCTGCAGACA
GCCCCCGTGCCCATGCCAGACCTGAAGAATGTCAAGTCCAAGATCGGCTCCACTGAGAAC
CTGAAGCACCAGCCGGGAGGCGGGAAGGTGCAGATAATTAATAAGAAGCTGGATCTTAGC
AACGTCCAGTCCAAGTGTGGCTCAAAGGATAATATCAAACACGTCCCGGGAGGCGGCAGT
GTGCAAATAGTCTACAAACCAGTTGACCTGAGCAAGGTGACCTCCAAGTGTGGCTCATTA
GGCAACATCCATCATAAACCAGGAGGTGGCCAGGTGGAAGTAAAATCTGAGAAGCTTGAC
TTCAAGGACAGAGTCCAGTCGAAGATTGGGTCCCTGGACAATATCACCCACGTCCCTGGC
GGAGGAAATAAAAAGATTGAAACCCACAAGCTGACCTTCCGCGAGAACGCCAAAGCCAAG
ACAGACCACGGGGCGGAGATCGTGTACAAGTCGCCAGTGGTGTCTGGGGACACGTCTCCA
CGGCATCTCAGCAATGTCTCCTCCACCGGCAGCATCGACATGGTAGACTCGCCCCAGCTC
GCCACGCTAGCTGACGAGGTGTCTGCCTCCCTGGCCAAGCAGGGTTTGTGA
GenBank Gene IDBN000503
GeneCard IDNot Available
GenAtlas IDMAPT
HGNC IDHGNC:6893
Chromosome Location17
LocusNot Available
References
  1. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A: Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051-5. 3131773
  2. Goedert M, Spillantini MG, Potier MC, Ulrich J, Crowther RA: Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. EMBO J. 1989 Feb;8(2):393-9. 2498079
  3. Lee G, Neve RL, Kosik KS: The microtubule binding domain of tau protein. Neuron. 1989 Jun;2(6):1615-24. 2516729
  4. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA: Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989 Oct;3(4):519-26. 2484340
  5. Andreadis A, Brown WM, Kosik KS: Structure and novel exons of the human tau gene. Biochemistry. 1992 Nov 3;31(43):10626-33. 1420178
  6. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. 16625196
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Hasegawa M, Morishima-Kawashima M, Takio K, Suzuki M, Titani K, Ihara Y: Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain. J Biol Chem. 1992 Aug 25;267(24):17047-54. 1512244
  9. Cripps D, Thomas SN, Jeng Y, Yang F, Davies P, Yang AJ: Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-Tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation. J Biol Chem. 2006 Apr 21;281(16):10825-38. Epub 2006 Jan 27. 16443603
  10. Drewes G, Trinczek B, Illenberger S, Biernat J, Schmitt-Ulms G, Meyer HE, Mandelkow EM, Mandelkow E: Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262. J Biol Chem. 1995 Mar 31;270(13):7679-88. 7706316
  11. Mori H, Hamada Y, Kawaguchi M, Honda T, Kondo J, Ihara Y: A distinct form of tau is selectively incorporated into Alzheimer's paired helical filaments. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1221-6. 2495000
  12. Lee VM, Balin BJ, Otvos L Jr, Trojanowski JQ: A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science. 1991 Feb 8;251(4994):675-8. 1899488
  13. Jakes R, Novak M, Davison M, Wischik CM: Identification of 3- and 4-repeat tau isoforms within the PHF in Alzheimer's disease. EMBO J. 1991 Oct;10(10):2725-9. 1915258
  14. Rademakers R, Cruts M, van Broeckhoven C: The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat. 2004 Oct;24(4):277-95. 15365985
  15. Goedert M, Crowther RA, Garner CC: Molecular characterization of microtubule-associated proteins tau and MAP2. Trends Neurosci. 1991 May;14(5):193-9. 1713721
  16. Paudel HK: The regulatory Ser262 of microtubule-associated protein tau is phosphorylated by phosphorylase kinase. J Biol Chem. 1997 Jan 17;272(3):1777-85. 8999860
  17. Nacharaju P, Ko L, Yen SH: Characterization of in vitro glycation sites of tau. J Neurochem. 1997 Oct;69(4):1709-19. 9326300
  18. Sengupta A, Kabat J, Novak M, Wu Q, Grundke-Iqbal I, Iqbal K: Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules. Arch Biochem Biophys. 1998 Sep 15;357(2):299-309. 9735171
  19. Illenberger S, Zheng-Fischhofer Q, Preuss U, Stamer K, Baumann K, Trinczek B, Biernat J, Godemann R, Mandelkow EM, Mandelkow E: The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells: implications for Alzheimer's disease. Mol Biol Cell. 1998 Jun;9(6):1495-512. 9614189
  20. Maas T, Eidenmuller J, Brandt R: Interaction of tau with the neural membrane cortex is regulated by phosphorylation at sites that are modified in paired helical filaments. J Biol Chem. 2000 May 26;275(21):15733-40. 10747907
  21. Li G, Yin H, Kuret J: Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J Biol Chem. 2004 Apr 16;279(16):15938-45. Epub 2004 Feb 2. 14761950
  22. Cho JH, Johnson GV: Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta (GSK3beta) plays a critical role in regulating tau's ability to bind and stabilize microtubules. J Neurochem. 2004 Jan;88(2):349-58. 14690523
  23. Lee G, Thangavel R, Sharma VM, Litersky JM, Bhaskar K, Fang SM, Do LH, Andreadis A, Van Hoesen G, Ksiezak-Reding H: Phosphorylation of tau by fyn: implications for Alzheimer's disease. J Neurosci. 2004 Mar 3;24(9):2304-12. 14999081
  24. Babu JR, Geetha T, Wooten MW: Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation. J Neurochem. 2005 Jul;94(1):192-203. 15953362
  25. Liu F, Iqbal K, Grundke-Iqbal I, Rossie S, Gong CX: Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease. J Biol Chem. 2005 Jan 21;280(3):1790-6. Epub 2004 Nov 15. 15546861
  26. Sato S, Cerny RL, Buescher JL, Ikezu T: Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation. J Neurochem. 2006 Sep;98(5):1573-84. 16923168
  27. Yang YC, Lin CH, Lee EH: Serum- and glucocorticoid-inducible kinase 1 (SGK1) increases neurite formation through microtubule depolymerization by SGK1 and by SGK1 phosphorylation of tau. Mol Cell Biol. 2006 Nov;26(22):8357-70. Epub 2006 Sep 18. 16982696
  28. Hanger DP, Byers HL, Wray S, Leung KY, Saxton MJ, Seereeram A, Reynolds CH, Ward MA, Anderton BH: Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J Biol Chem. 2007 Aug 10;282(32):23645-54. Epub 2007 Jun 11. 17562708
  29. Yoshida K: Role for DYRK family kinases on regulation of apoptosis. Biochem Pharmacol. 2008 Dec 1;76(11):1389-94. doi: 10.1016/j.bcp.2008.05.021. Epub 2008 Jul 2. 18599021
  30. Liu F, Shi J, Tanimukai H, Gu J, Gu J, Grundke-Iqbal I, Iqbal K, Gong CX: Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease. Brain. 2009 Jul;132(Pt 7):1820-32. doi: 10.1093/brain/awp099. Epub 2009 May 18. 19451179
  31. Puri R, Suzuki T, Yamakawa K, Ganesh S: Hyperphosphorylation and aggregation of Tau in laforin-deficient mice, an animal model for Lafora disease. J Biol Chem. 2009 Aug 21;284(34):22657-63. doi: 10.1074/jbc.M109.009688. Epub 2009 Jun 19. 19542233
  32. Smet-Nocca C, Broncel M, Wieruszeski JM, Tokarski C, Hanoulle X, Leroy A, Landrieu I, Rolando C, Lippens G, Hackenberger CP: Identification of O-GlcNAc sites within peptides of the Tau protein and their impact on phosphorylation. Mol Biosyst. 2011 May;7(5):1420-9. doi: 10.1039/c0mb00337a. Epub 2011 Feb 16. 21327254
  33. Yoshida H, Goedert M: Phosphorylation of microtubule-associated protein tau by AMPK-related kinases. J Neurochem. 2012 Jan;120(1):165-76. doi: 10.1111/j.1471-4159.2011.07523.x. Epub 2011 Nov 11. 21985311
  34. Wintjens R, Wieruszeski JM, Drobecq H, Rousselot-Pailley P, Buee L, Lippens G, Landrieu I: 1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine peptides. J Biol Chem. 2001 Jul 6;276(27):25150-6. Epub 2001 Apr 19. 11313338
  35. Goedert M, Spillantini MG: Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer's disease. Biochim Biophys Acta. 2000 Jul 26;1502(1):110-21. 10899436
  36. Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD: Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998 Jun;43(6):815-25. 9629852
  37. Dumanchin C, Camuzat A, Campion D, Verpillat P, Hannequin D, Dubois B, Saugier-Veber P, Martin C, Penet C, Charbonnier F, Agid Y, Frebourg T, Brice A: Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism. Hum Mol Genet. 1998 Oct;7(11):1825-9. 9736786
  38. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P: Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998 Jun 18;393(6686):702-5. 9641683
  39. Clark LN, Poorkaj P, Wszolek Z, Geschwind DH, Nasreddine ZS, Miller B, Li D, Payami H, Awert F, Markopoulou K, Andreadis A, D'Souza I, Lee VM, Reed L, Trojanowski JQ, Zhukareva V, Bird T, Schellenberg G, Wilhelmsen KC: Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13103-7. 9789048
  40. Delisle MB, Murrell JR, Richardson R, Trofatter JA, Rascol O, Soulages X, Mohr M, Calvas P, Ghetti B: A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy. Acta Neuropathol. 1999 Jul;98(1):62-77. 10412802
  41. Rizzu P, Van Swieten JC, Joosse M, Hasegawa M, Stevens M, Tibben A, Niermeijer MF, Hillebrand M, Ravid R, Oostra BA, Goedert M, van Duijn CM, Heutink P: High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am J Hum Genet. 1999 Feb;64(2):414-21. 9973279
  42. Sperfeld AD, Collatz MB, Baier H, Palmbach M, Storch A, Schwarz J, Tatsch K, Reske S, Joosse M, Heutink P, Ludolph AC: FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann Neurol. 1999 Nov;46(5):708-15. 10553987
  43. Nacharaju P, Lewis J, Easson C, Yen S, Hackett J, Hutton M, Yen SH: Accelerated filament formation from tau protein with specific FTDP-17 missense mutations. FEBS Lett. 1999 Mar 26;447(2-3):195-9. 10214944
  44. Bugiani O, Murrell JR, Giaccone G, Hasegawa M, Ghigo G, Tabaton M, Morbin M, Primavera A, Carella F, Solaro C, Grisoli M, Savoiardo M, Spillantini MG, Tagliavini F, Goedert M, Ghetti B: Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J Neuropathol Exp Neurol. 1999 Jun;58(6):667-77. 10374757
  45. Murrell JR, Spillantini MG, Zolo P, Guazzelli M, Smith MJ, Hasegawa M, Redi F, Crowther RA, Pietrini P, Ghetti B, Goedert M: Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits. J Neuropathol Exp Neurol. 1999 Dec;58(12):1207-26. 10604746
  46. Yasuda M, Kawamata T, Komure O, Kuno S, D'Souza I, Poorkaj P, Kawai J, Tanimukai S, Yamamoto Y, Hasegawa H, Sasahara M, Hazama F, Schellenberg GD, Tanaka C: A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration. Neurology. 1999 Sep 11;53(4):864-8. 10489057
  47. Higgins JJ, Adler RL, Loveless JM: Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology. 1999 Oct 22;53(7):1421-4. 10534245
  48. Iijima M, Tabira T, Poorkaj P, Schellenberg GD, Trojanowski JQ, Lee VM, Schmidt ML, Takahashi K, Nabika T, Matsumoto T, Yamashita Y, Yoshioka S, Ishino H: A distinct familial presenile dementia with a novel missense mutation in the tau gene. Neuroreport. 1999 Feb 25;10(3):497-501. 10208578
  49. Lippa CF, Zhukareva V, Kawarai T, Uryu K, Shafiq M, Nee LE, Grafman J, Liang Y, St George-Hyslop PH, Trojanowski JQ, Lee VM: Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutation. Ann Neurol. 2000 Dec;48(6):850-8. 11117541
  50. Pickering-Brown S, Baker M, Yen SH, Liu WK, Hasegawa M, Cairns N, Lantos PL, Rossor M, Iwatsubo T, Davies Y, Allsop D, Furlong R, Owen F, Hardy J, Mann D, Hutton M: Pick's disease is associated with mutations in the tau gene. Ann Neurol. 2000 Dec;48(6):859-67. 11117542
  51. Rizzini C, Goedert M, Hodges JR, Smith MJ, Jakes R, Hills R, Xuereb JH, Crowther RA, Spillantini MG: Tau gene mutation K257T causes a tauopathy similar to Pick's disease. J Neuropathol Exp Neurol. 2000 Nov;59(11):990-1001. 11089577
  52. Arima K, Kowalska A, Hasegawa M, Mukoyama M, Watanabe R, Kawai M, Takahashi K, Iwatsubo T, Tabira T, Sunohara N: Two brothers with frontotemporal dementia and parkinsonism with an N279K mutation of the tau gene. Neurology. 2000 May 9;54(9):1787-95. 10802785
  53. Yasuda M, Yokoyama K, Nakayasu T, Nishimura Y, Matsui M, Yokoyama T, Miyoshi K, Tanaka C: A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation. Neurology. 2000 Oct 24;55(8):1224-7. 11071507
  54. Iseki E, Matsumura T, Marui W, Hino H, Odawara T, Sugiyama N, Suzuki K, Sawada H, Arai T, Kosaka K: Familial frontotemporal dementia and parkinsonism with a novel N296H mutation in exon 10 of the tau gene and a widespread tau accumulation in the glial cells. Acta Neuropathol. 2001 Sep;102(3):285-92. 11585254
  55. Pastor P, Pastor E, Carnero C, Vela R, Garcia T, Amer G, Tolosa E, Oliva R: Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene. Ann Neurol. 2001 Feb;49(2):263-7. 11220749
  56. Neumann M, Schulz-Schaeffer W, Crowther RA, Smith MJ, Spillantini MG, Goedert M, Kretzschmar HA: Pick's disease associated with the novel Tau gene mutation K369I. Ann Neurol. 2001 Oct;50(4):503-13. 11601501
  57. Connell JW, Gibb GM, Betts JC, Blackstock WP, Gallo J, Lovestone S, Hutton M, Anderton BH: Effects of FTDP-17 mutations on the in vitro phosphorylation of tau by glycogen synthase kinase 3beta identified by mass spectrometry demonstrate certain mutations exert long-range conformational changes. FEBS Lett. 2001 Mar 23;493(1):40-4. 11278002
  58. Tsuboi Y, Baker M, Hutton ML, Uitti RJ, Rascol O, Delisle MB, Soulages X, Murrell JR, Ghetti B, Yasuda M, Komure O, Kuno S, Arima K, Sunohara N, Kobayashi T, Mizuno Y, Wszolek ZK: Clinical and genetic studies of families with the tau N279K mutation (FTDP-17). Neurology. 2002 Dec 10;59(11):1791-3. 12473774
  59. 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: A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease. Ann Neurol. 2002 Mar;51(3):373-6. 11891833
  60. Hayashi S, Toyoshima Y, Hasegawa M, Umeda Y, Wakabayashi K, Tokiguchi S, Iwatsubo T, Takahashi H: Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation. Ann Neurol. 2002 Apr;51(4):525-30. 11921059
  61. Poorkaj P, Muma NA, Zhukareva V, Cochran EJ, Shannon KM, Hurtig H, Koller WC, Bird TD, Trojanowski JQ, Lee VM, Schellenberg GD: An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann Neurol. 2002 Oct;52(4):511-6. 12325083
  62. Yoshida H, Crowther RA, Goedert M: Functional effects of tau gene mutations deltaN296 and N296H. J Neurochem. 2002 Feb;80(3):548-51. 11906000
  63. Saito Y, Geyer A, Sasaki R, Kuzuhara S, Nanba E, Miyasaka T, Suzuki K, Murayama S: Early-onset, rapidly progressive familial tauopathy with R406W mutation. Neurology. 2002 Mar 12;58(5):811-3. 11889249
  64. Kobayashi T, Ota S, Tanaka K, Ito Y, Hasegawa M, Umeda Y, Motoi Y, Takanashi M, Yasuhara M, Anno M, Mizuno Y, Mori H: A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology. Ann Neurol. 2003 Jan;53(1):133-7. 12509859
  65. Nicholl DJ, Greenstone MA, Clarke CE, Rizzu P, Crooks D, Crowe A, Trojanowski JQ, Lee VM, Heutink P: An English kindred with a novel recessive tauopathy and respiratory failure. Ann Neurol. 2003 Nov;54(5):682-6. 14595660
  66. Rademakers R, Dermaut B, Peeters K, Cruts M, Heutink P, Goate A, Van Broeckhoven C: Tau (MAPT) mutation Arg406Trp presenting clinically with Alzheimer disease does not share a common founder in Western Europe. Hum Mutat. 2003 Nov;22(5):409-11. 14517953
  67. Rossi G, Gasparoli E, Pasquali C, Di Fede G, Testa D, Albanese A, Bracco F, Tagliavini F: Progressive supranuclear palsy and Parkinson's disease in a family with a new mutation in the tau gene. Ann Neurol. 2004 Mar;55(3):448. 14991829
  68. Oliva R, Pastor P: Tau gene delN296 mutation, Parkinson's disease, and atypical supranuclear palsy. Ann Neurol. 2004 Mar;55(3):448-9. 14991828
  69. Yasuda M, Nakamura Y, Kawamata T, Kaneyuki H, Maeda K, Komure O: Phenotypic heterogeneity within a new family with the MAPT p301s mutation. Ann Neurol. 2005 Dec;58(6):920-8. 16240366
  70. Ros R, Thobois S, Streichenberger N, Kopp N, Sanchez MP, Perez M, Hoenicka J, Avila J, Honnorat J, de Yebenes JG: A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy. Arch Neurol. 2005 Sep;62(9):1444-50. 16157753
  71. Zarranz JJ, Ferrer I, Lezcano E, Forcadas MI, Eizaguirre B, Atares B, Puig B, Gomez-Esteban JC, Fernandez-Maiztegui C, Rouco I, Perez-Concha T, Fernandez M, Rodriguez O, Rodriguez-Martinez AB, de Pancorbo MM, Pastor P, Perez-Tur J: A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease. Neurology. 2005 May 10;64(9):1578-85. 15883319
  72. Guerreiro RJ, Washecka N, Hardy J, Singleton A: A thorough assessment of benign genetic variability in GRN and MAPT. Hum Mutat. 2010 Feb;31(2):E1126-40. doi: 10.1002/humu.21152. 20020531