| General information | | DisProt: | DP00126 | | Name: | Microtubule-associated protein tau [Isoform Tau-F] | | Synonym(s): | TAU_HUMAN
Neurofibrillary tangle protein
Paired helical filament-tau
PHF-tau
Tau-4
| | First appeared in release: | Release 1.0 (08/01/2003) | | UniProt: | P10636-8 | | UniGene: | Hs.101174 | | SwissProt: | TAU_HUMAN | | TrEMBL: | | | NCBI (GI): | 13124806 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 441 | | Percent disordered: | 100% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG - 60
SETSDAKSTP TAEDVTAPLV DEGAPGKQAA AQPHTEIPEG TTAEEAGIGD TPSLEDEAAG - 120
HVTQARMVSK SKDGTGSDDK KAKGADGKTK IATPRGAAPP GQKGQANATR IPAKTPPAPK - 180
TPPSSGEPPK SGDRSGYSSP GSPGTPGSRS RTPSLPTPPT REPKKVAVVR TPPKSPSSAK - 240
SRLQTAPVPM PDLKNVKSKI GSTENLKHQP GGGKVQIINK KLDLSNVQSK CGSKDNIKHV - 300
PGGGSVQIVY KPVDLSKVTS KCGSLGNIHH KPGGGQVEVK SEKLDFKDRV QSKIGSLDNI - 360
THVPGGGNKK IETHKLTFRE NAKAKTDHGA EIVYKSPVVS GDTSPRHLSN VSSTGSIDMV - 420
DSPQLATLAD EVSASLAKQG L
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| Functional narrative |
Microtubule-associated protein tau isoform Tau-F interacts with alpha and beta tubulin, as well as other microtubule-associated protein tau isoforms to promote microtubule assembly and stability. This isoform is generally found in the cytosol, axons of neurons, or involved with the plasma membrane. Microtubule-associated protein tau isoform F is associated with many forms of dementia including Alzheimer’s disease. This isoform forms paired helical filaments (PHFs) leading to the formation of neurofibrillary tangles, a characteristic symptom of this disease. Also, if point mutations occur in the repeat region of this protein, its function is lost and may lead to other forms of dementia. This entry is a characterization of the 441 residue isoform (Tau-F). The sequence is from Geodert (1989) and is an alternatively spliced isoform of Swiss-Prot TAU_HUMAN (P10636).
Microtubule-associated protein tau isoform Tau-F is an intrinsically disordered protein. It has the ability to form dimers, trimers, etc. During dimerization the area characterized by four pseudo repeats becomes ordered to form a more stable multimer.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered - Extended | | Name: | | | Location: | 1 - 243 | | Length: | 243 | | Region sequence: |
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPG
SETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAG
HVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPK
TPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAK
SRL | | Modification type: | Engineered
Isoform
| | PDB: | | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, near-UV (295 K; pH: 7; )
- Fourier transform infrared spectroscopy (FTIR), aka infrared spectroscopy)
- Small-angle X-ray scattering (SAXS)
- Stability at thermal extremes
- Rotory shadowing electron microscopy
| References:
- Barghorn S, Davies P, Mandelkow E. "Tau paired helical filaments from Alzheimer's disease brain and assembled in vitro are based on beta-structure in the core domain." Biochemistry. 2004; 43(6): 1694-703. PubMed: 14769047
- 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; 3(4): 519-526. PubMed: 2484340
- Santarella RA, Skiniotis G, Goldie KN, Tittmann P, Gross H, Mandelkow EM, Mandelkow E, Hoenger A. "Surface-decoration of microtubules by human tau." J Mol Biol. 2004; 339(3): 539-553. PubMed: 15147841
- Schweers O, Schonbrunn-Hanebeck E, Marx A, Mandelkow E. "Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure." J Biol Chem. 1994; 269(39): 24290-24297. PubMed: 7929085
| Comments:
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| Region 2 | | Type: | Disordered - Extended | | Name: | Core Domain/Binding Domain | | Location: | 244 - 368 | | Length: | 125 | | Region sequence: |
QTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGG
GSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHV
PGGGN | | Modification type: | Engineered
Isoform
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Stability at thermal extremes
- Rotory shadowing electron microscopy
| References:
- 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; 3(4): 519-526. PubMed: 2484340
- Santarella RA, Skiniotis G, Goldie KN, Tittmann P, Gross H, Mandelkow EM, Mandelkow E, Hoenger A. "Surface-decoration of microtubules by human tau." J Mol Biol. 2004; 339(3): 539-553. PubMed: 15147841
- Schweers O, Schonbrunn-Hanebeck E, Marx A, Mandelkow E. "Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure." J Biol Chem. 1994; 269(39): 24290-24297. PubMed: 7929085
| Comments:
|
| Region 3 | | Type: | Disordered - Extended | | Name: | Core Domain/Binding Domain | | Location: | 244 - 369 | | Length: | 126 | | Region sequence: |
QTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGG
GSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHV
PGGGNK | | Modification type: | Engineered
Isoform
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, near-UV (295 K; pH: 7; )
- Rotory shadowing electron microscopy
- Fourier transform infrared spectroscopy (FTIR), aka infrared spectroscopy)
- Small-angle X-ray scattering (SAXS)
- Stability at thermal extremes
| References:
- Barghorn S, Davies P, Mandelkow E. "Tau paired helical filaments from Alzheimer's disease brain and assembled in vitro are based on beta-structure in the core domain." Biochemistry. 2004; 43(6): 1694-703. PubMed: 14769047
- 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; 3(4): 519-526. PubMed: 2484340
- Schweers O, Schonbrunn-Hanebeck E, Marx A, Mandelkow E. "Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure." J Biol Chem. 1994; 269(39): 24290-24297. PubMed: 7929085
| Comments:This the microtubule binding domain.
|
| Region 4 | | Type: | Disordered - Extended | | Name: | | | Location: | 369 - 441 | | Length: | 73 | | Region sequence: |
KKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATL
ADEVSASLAKQGL | | Modification type: | Engineered
Isoform
| | PDB: | | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Rotory shadowing electron microscopy
- Stability at thermal extremes
| References:
- 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; 3(4): 519-526. PubMed: 2484340
- Santarella RA, Skiniotis G, Goldie KN, Tittmann P, Gross H, Mandelkow EM, Mandelkow E, Hoenger A. "Surface-decoration of microtubules by human tau." J Mol Biol. 2004; 339(3): 539-553. PubMed: 15147841
- Schweers O, Schonbrunn-Hanebeck E, Marx A, Mandelkow E. "Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure." J Biol Chem. 1994; 269(39): 24290-24297. PubMed: 7929085
| Comments:
|
| Region 5 | | Type: | Disordered - Extended | | Name: | | | Location: | 370 - 441 | | Length: | 72 | | Region sequence: |
KIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLA
DEVSASLAKQGL | | Modification type: | Engineered
Isoform
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, near-UV (295 K; pH: 7; )
- Rotory shadowing electron microscopy
- Fourier transform infrared spectroscopy (FTIR), aka infrared spectroscopy)
- Small-angle X-ray scattering (SAXS)
- Stability at thermal extremes
| References:
- Barghorn S, Davies P, Mandelkow E. "Tau paired helical filaments from Alzheimer's disease brain and assembled in vitro are based on beta-structure in the core domain." Biochemistry. 2004; 43(6): 1694-703. PubMed: 14769047
- 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; 3(4): 519-526. PubMed: 2484340
- Schweers O, Schonbrunn-Hanebeck E, Marx A, Mandelkow E. "Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure." J Biol Chem. 1994; 269(39): 24290-24297. PubMed: 7929085
| Comments:
|
| Region 6 | | Type: | Disordered | | Name: | K19 | | Location: | 244 - 372 | | Length: | 129 | | Region sequence: |
QTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGG
GSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHV
PGGGNKKIE | | Modification type: | Fragment
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (283 K; pH: 7.4; H2O/D2O (90%/10%); Na2HPO4 10 mM; NaCl 100 mM)
| References:
- Eliezer D, Barre P, Kobaslija M, Chan D, Li X, Heend L. "Residual structure in the repeat domain of tau: echoes of microtubule binding and paired helical filament formation." Biochemistry. 2005; 44(3): 1026-36. PubMed: 15654759
| Comments:
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| References |
- Mo ZY, Zhu YZ, Zhu HL, Fan JB, Chen J, Liang Y. "Low micromolar zinc accelerates the fibrillization of human tau via bridging of Cys-291 and Cys-322." J Biol Chem. 2009; 284(50): 34648-57. PubMed: 19826005
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| Comments |
PHF-tau is generally found as dimers but can also form larger complexes.
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