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Protein

Microtubule-associated protein tau

Gene

MAPT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Promotes 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.1 Publication

GO - Molecular functioni

  • actin binding Source: ParkinsonsUK-UCL
  • apolipoprotein binding Source: BHF-UCL
  • AT DNA binding Source: ARUK-UCL
  • chaperone binding Source: ARUK-UCL
  • DNA binding Source: ParkinsonsUK-UCL
  • double-stranded DNA binding Source: ARUK-UCL
  • dynactin binding Source: ParkinsonsUK-UCL
  • enzyme binding Source: UniProtKB
  • histone-dependent DNA binding Source: ARUK-UCL
  • Hsp90 protein binding Source: ARUK-UCL
  • identical protein binding Source: CAFA
  • lipoprotein particle binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • microtubule lateral binding Source: CAFA
  • phosphatidylinositol binding Source: ARUK-UCL
  • phosphatidylinositol bisphosphate binding Source: ARUK-UCL
  • protein binding, bridging Source: ARUK-UCL
  • protein homodimerization activity Source: CAFA
  • protein kinase binding Source: ARUK-UCL
  • protein phosphatase 2A binding Source: ParkinsonsUK-UCL
  • receptor ligand activity Source: ARUK-UCL
  • RNA binding Source: ARUK-UCL
  • sequence-specific DNA binding Source: ARUK-UCL
  • SH3 domain binding Source: UniProtKB
  • single-stranded DNA binding Source: ARUK-UCL

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: ParkinsonsUK-UCL
  • amyloid fibril formation Source: CAFA
  • astrocyte activation Source: ParkinsonsUK-UCL
  • axonal transport Source: ParkinsonsUK-UCL
  • axonal transport of mitochondrion Source: ParkinsonsUK-UCL
  • axon development Source: ARUK-UCL
  • cell-cell signaling Source: ARUK-UCL
  • cellular response to brain-derived neurotrophic factor stimulus Source: ARUK-UCL
  • cellular response to heat Source: ParkinsonsUK-UCL
  • cellular response to nerve growth factor stimulus Source: ARUK-UCL
  • cellular response to reactive oxygen species Source: ARUK-UCL
  • central nervous system neuron development Source: ARUK-UCL
  • cytoplasmic microtubule organization Source: ParkinsonsUK-UCL
  • generation of neurons Source: UniProtKB
  • internal protein amino acid acetylation Source: ARUK-UCL
  • intracellular distribution of mitochondria Source: ParkinsonsUK-UCL
  • learning or memory Source: ARUK-UCL
  • memory Source: ParkinsonsUK-UCL
  • microglial cell activation Source: ParkinsonsUK-UCL
  • microtubule cytoskeleton organization Source: UniProtKB
  • microtubule polymerization Source: ARUK-UCL
  • negative regulation of establishment of protein localization to mitochondrion Source: ParkinsonsUK-UCL
  • negative regulation of gene expression Source: ARUK-UCL
  • negative regulation of kinase activity Source: ParkinsonsUK-UCL
  • negative regulation of mitochondrial fission Source: ParkinsonsUK-UCL
  • negative regulation of mitochondrial membrane potential Source: ParkinsonsUK-UCL
  • negative regulation of tubulin deacetylation Source: ARUK-UCL
  • neurofibrillary tangle assembly Source: ParkinsonsUK-UCL
  • neuron projection development Source: ParkinsonsUK-UCL
  • plus-end-directed organelle transport along microtubule Source: ParkinsonsUK-UCL
  • positive regulation of axon extension Source: UniProtKB
  • positive regulation of cellular protein localization Source: CAFA
  • positive regulation of diacylglycerol kinase activity Source: ParkinsonsUK-UCL
  • positive regulation of microtubule polymerization Source: UniProtKB
  • positive regulation of neuron death Source: ParkinsonsUK-UCL
  • positive regulation of protein localization to synapse Source: ParkinsonsUK-UCL
  • positive regulation of superoxide anion generation Source: ParkinsonsUK-UCL
  • protein complex oligomerization Source: ParkinsonsUK-UCL
  • protein homooligomerization Source: ARUK-UCL
  • regulation of autophagy Source: MGI
  • regulation of calcium-mediated signaling Source: ARUK-UCL
  • regulation of cellular response to heat Source: ParkinsonsUK-UCL
  • regulation of chromosome organization Source: ARUK-UCL
  • regulation of long term synaptic depression Source: ARUK-UCL
  • regulation of microtubule cytoskeleton organization Source: CAFA
  • regulation of microtubule polymerization Source: ARUK-UCL
  • regulation of microtubule polymerization or depolymerization Source: CAFA
  • regulation of mitochondrial fission Source: ParkinsonsUK-UCL
  • regulation of response to DNA damage stimulus Source: ParkinsonsUK-UCL
  • regulation of synaptic plasticity Source: ARUK-UCL
  • response to lead ion Source: ARUK-UCL
  • rRNA metabolic process Source: ARUK-UCL
  • stress granule assembly Source: ARUK-UCL
  • supramolecular fiber organization Source: CAFA
  • synapse assembly Source: ARUK-UCL
  • synapse organization Source: ParkinsonsUK-UCL

Enzyme and pathway databases

ReactomeiR-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins
SABIO-RKiP10636
SIGNORiP10636

Names & Taxonomyi

Protein namesi
Recommended name:
Microtubule-associated protein tau
Alternative name(s):
Neurofibrillary tangle protein
Paired helical filament-tau
Short name:
PHF-tau
Gene namesi
Name:MAPT
Synonyms:MAPTL, MTBT1, TAU
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000186868.15
HGNCiHGNC:6893 MAPT
MIMi157140 gene+phenotype
neXtProtiNX_P10636

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Microtubule

Pathology & Biotechi

Involvement in diseasei

In Alzheimer disease, the neuronal cytoskeleton in the brain is progressively disrupted and replaced by tangles of paired helical filaments (PHF) and straight filaments, mainly composed of hyperphosphorylated forms of TAU (PHF-TAU or AD P-TAU). O-GlcNAcylation is greatly reduced in Alzheimer disease brain cerebral cortex leading to an increase in TAU/MAPT phosphorylations.2 Publications
Frontotemporal dementia (FTD)24 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons.
See also OMIM:600274
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0196605R → H in FTD; reduces the ability of tau to promote microtubule assembly and promotes fibril formation in vitro. 1 PublicationCorresponds to variant dbSNP:rs63750959EnsemblClinVar.1
Natural variantiVAR_019662583L → V in FTD; less able to promote microtubule assembly than wild-type tau. 1 PublicationCorresponds to variant dbSNP:rs63750349EnsemblClinVar.1
Natural variantiVAR_010345589G → V in FTD. 2 PublicationsCorresponds to variant dbSNP:rs63750376EnsemblClinVar.1
Natural variantiVAR_010346596N → K in FTD; with parkinsonism. 5 PublicationsCorresponds to variant dbSNP:rs63750756EnsemblClinVar.1
Natural variantiVAR_010347597Missing in FTD. 1 Publication1
Natural variantiVAR_019663613N → H in FTD; reduced the ability of tau to promote microtubule assembly without having a significant effect on tau filament formation; effects at both the RNA and the protein level. 2 PublicationsCorresponds to variant dbSNP:rs63750416EnsemblClinVar.1
Natural variantiVAR_010348618P → L in FTD; most common mutation; reduction in the ability to promote microtubule assembly; accelerates aggregation of tau into filaments. 5 PublicationsCorresponds to variant dbSNP:rs63751273Ensembl.1
Natural variantiVAR_010350622S → N in FTD; minimal parkinsonism; very early age of onset. 1 PublicationCorresponds to variant dbSNP:rs63751165EnsemblClinVar.1
Natural variantiVAR_037440634K → M in FTD. 1 PublicationCorresponds to variant dbSNP:rs63750092EnsemblClinVar.1
Natural variantiVAR_010351654V → M in FTD; ultrastructural and biochemical characteristics indistinguishable from Alzheimer disease; accelerates aggregation of tau into filaments. 2 PublicationsCorresponds to variant dbSNP:rs63750570EnsemblClinVar.1
Natural variantiVAR_019666659E → V in FTD. 1 PublicationCorresponds to variant dbSNP:rs63750711EnsemblClinVar.1
Pick disease of the brain (PIDB)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration.
See also OMIM:172700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010344574K → T in PIDB; reduces the ability to promote microtubule assembly by 70%. 2 PublicationsCorresponds to variant dbSNP:rs63750129EnsemblClinVar.1
Natural variantiVAR_019665637S → F in PIDB; markedly reduced ability of tau to promote microtubule assembly. 1 PublicationCorresponds to variant dbSNP:rs63750635EnsemblClinVar.1
Natural variantiVAR_019668686K → I in PIDB; 90% reduction in the rate of microtubule assembly. 1 PublicationCorresponds to variant dbSNP:rs63751264EnsemblClinVar.1
Natural variantiVAR_010352706G → R in PIDB; in vitro the mutation reduces the ability of tau to promote microtubule assembly by 25 to 30%. 2 PublicationsCorresponds to variant dbSNP:rs63750512EnsemblClinVar.1
Defects in MAPT are a cause of corticobasal degeneration (CBD). It is marked by extrapyramidal signs and apraxia and can be associated with memory loss. Neuropathologic features may overlap Alzheimer disease, progressive supranuclear palsy, and Parkinson disease.
Progressive supranuclear palsy 1 (PSNP1)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613.
See also OMIM:601104
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0196615R → L in PSNP1; delays assembly initiation and lowers the mass of microtubules formed; but the assembly rate is increased compared to normal tau. 1 PublicationCorresponds to variant dbSNP:rs63750959EnsemblClinVar.1
Natural variantiVAR_037439620G → V in PSNP1. 1 PublicationCorresponds to variant dbSNP:rs63751391EnsemblClinVar.1
Parkinson-dementia syndrome (PARDE)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by parkinsonism, tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei.
See also OMIM:260540

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi515S → E: No association with plasma membrane. 1
Mutagenesisi516S → E: No association with plasma membrane. 1
Mutagenesisi519S → E: No association with plasma membrane. 1
Mutagenesisi531S → A: No decrease in microtubule-binding and nucleation activity after in vitro phosphorylation of mutant protein. 1
Mutagenesisi548T → A: 50% Decrease in microtubule-binding after in vitro phosphorylation of mutant protein. 1
Mutagenesisi548T → E: No association with plasma membrane. 1
Mutagenesisi552S → A: 70% decrease in microtubule-binding after in vitro phosphorylation of mutant protein. 1
Mutagenesisi552S → E: No association with plasma membrane. 1
Mutagenesisi579S → A: 8% decrease in microtubule-binding after in vitro phosphorylation of mutant protein. 1
Mutagenesisi713S → E: No association with plasma membrane. 1
Mutagenesisi721S → E: No association with plasma membrane. 1
Mutagenesisi726S → E: No association with plasma membrane. 1
Mutagenesisi730S → E: No association with plasma membrane. 1
Mutagenesisi739S → E: No association with plasma membrane. 1

Keywords - Diseasei

Alzheimer disease, Disease mutation, Neurodegeneration, Parkinsonism

Organism-specific databases

DisGeNETi4137
GeneReviewsiMAPT
MalaCardsiMAPT
MIMi157140 gene+phenotype
172700 phenotype
260540 phenotype
600274 phenotype
601104 phenotype
OpenTargetsiENSG00000186868
Orphaneti275864 Behavioral variant of frontotemporal dementia
240071 Classical progressive supranuclear palsy
100070 Progressive non-fluent aphasia
240103 Progressive supranuclear palsy - corticobasal syndrome
240085 Progressive supranuclear palsy - parkinsonism
240112 Progressive supranuclear palsy - progressive non fluent aphasia
240094 Progressive supranuclear palsy - pure akinesia with gait freezing
100069 Semantic dementia
PharmGKBiPA238

Chemistry databases

ChEMBLiCHEMBL1293224
DrugBankiDB01248 Docetaxel
DB01229 Paclitaxel

Polymorphism and mutation databases

BioMutaiMAPT
DMDMi334302961

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000727392 – 758Microtubule-associated protein tauAdd BLAST757

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei18Phosphotyrosine; by FYN1 Publication1
Modified residuei29PhosphotyrosineBy similarity1
Cross-linki44Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei46PhosphoserineBy similarity1
Modified residuei61PhosphoserineBy similarity1
Modified residuei69PhosphothreonineBy similarity1
Modified residuei71PhosphothreonineBy similarity1
Glycosylationi87N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei111PhosphothreonineBy similarity1
Modified residuei214Phosphoserine; by SGK11 Publication1
Glycosylationi383N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei396Phosphoserine; in PHF-tau1 Publication1
Glycosylationi467N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei470Phosphothreonine; by PDPK11 Publication1
Modified residuei472Omega-N-methylarginineBy similarity1
Modified residuei480N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei480N6-acetyllysine; alternateBy similarity1
Glycosylationi480N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei484Deamidated asparagine; in tau and PHF-tau; partial1 Publication1
Modified residuei486PhosphothreonineBy similarity1
Glycosylationi491N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei492PhosphothreonineBy similarity1
Modified residuei498Phosphothreonine; by PDPK11 Publication1
Modified residuei502PhosphoserineBy similarity1
Modified residuei508PhosphoserineBy similarity1
Modified residuei512PhosphoserineBy similarity1
Modified residuei514Phosphotyrosine; by TTBK11 Publication1
Modified residuei515Phosphoserine; by PDPK1 and TTBK11 Publication1
Modified residuei516Phosphoserine; by PDPK1 and TTBK14 Publications1
Modified residuei519Phosphoserine; by CK1, PDPK1 and TTBK1Combined sources6 Publications1
Modified residuei522Phosphothreonine; by CK1 and PDPK13 Publications1
Glycosylationi525O-linked (GlcNAc) serine1 Publication1
Modified residuei529Phosphothreonine; by BRSK1, BRSK2, DYRK2 and PDPK15 Publications1
Modified residuei531Phosphoserine; by PKA4 Publications1
Modified residuei534Phosphothreonine; by PDPK12 Publications1
Modified residuei542N6-acetyllysineBy similarity1
Glycosylationi542N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei548Phosphothreonine; by GSK3-beta and PDPK1Combined sources3 Publications1
Glycosylationi551N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei552Phosphoserine; by PDPK1Combined sources3 Publications1
Modified residuei554Phosphoserine; by PHK2 Publications1
Glycosylationi555O-linked (GlcNAc) serine1 Publication1
Cross-linki571Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau1 Publication
Modified residuei576N6-acetyllysine; alternateBy similarity1
Modified residuei576N6-methyllysine; alternateBy similarity1
Glycosylationi576N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Cross-linki576Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei579Phosphoserine; by MARK1, MARK2, MARK3, MARK4, BRSK1, BRSK2 and PHK8 Publications1
Cross-linki584Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei596Deamidated asparagine; in tau and PHF-tau; partial1 Publication1
Glycosylationi597N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Modified residuei598N6-acetyllysine; alternateBy similarity1
Glycosylationi598N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Cross-linki598Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei602Phosphoserine; by PHK1 Publication1
Modified residuei607N6-acetyllysineBy similarity1
Disulfide bondi608 ↔ 639By similarity
Modified residuei610Phosphoserine1 Publication1
Modified residuei615N6-acetyllysine; alternateBy similarity1
Cross-linki615Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei622Phosphoserine; by PHK2 Publications1
Modified residuei628N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei628N6-acetyllysine; alternateBy similarity1
Cross-linki628Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau1 Publication
Modified residuei634N6-acetyllysine; alternateBy similarity1
Cross-linki634Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei638N6-acetyllysine; alternateBy similarity1
Cross-linki638Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei641Phosphoserine1 Publication1
Modified residuei648N6-acetyllysine; alternateBy similarity1
Cross-linki648Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei660N6-acetyllysine; alternateBy similarity1
Cross-linki660Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei664N6-acetyllysine; alternateBy similarity1
Glycosylationi664N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Cross-linki664Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei666Omega-N-methylarginineBy similarity1
Modified residuei669Phosphoserine; by PHK1 Publication1
Glycosylationi670N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Cross-linki670Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau1 Publication
Modified residuei673Phosphoserine1 Publication1
Modified residuei686N6-acetyllysine; alternateBy similarity1
Glycosylationi686N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro1 Publication1
Cross-linki686Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki692Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei702N6-acetyllysine; alternateBy similarity1
Cross-linki702Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei711PhosphotyrosineBy similarity1
Modified residuei713Phosphoserine; by CK1 and PDPK1Combined sources6 Publications1
Modified residuei717Phosphoserine; alternateCombined sources1
Glycosylationi717O-linked (GlcNAc) serine; alternate1 Publication1
Modified residuei720PhosphothreonineBy similarity1
Modified residuei721Phosphoserine; by CK1 and PDPK1Combined sources5 Publications1
Modified residuei726PhosphoserineCombined sources1 Publication1
Modified residuei733Phosphoserine; by CaMK2 and TTBK11 Publication1
Modified residuei739Phosphoserine; by PDPK1 and TTBK14 Publications1
Modified residuei744Phosphothreonine; by TTBK11 Publication1

Post-translational modificationi

Phosphorylation at serine and threonine residues in S-P or T-P motifs by proline-directed protein kinases (PDPK1, CDK1, CDK5, GSK3, MAPK) (only 2-3 sites per protein in interphase, seven-fold increase in mitosis, and in the form associated with paired helical filaments (PHF-tau)), and at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1, MARK2, MARK3 or MARK4), causing detachment from microtubules, and their disassembly (PubMed:7706316, PubMed:23666762). Phosphorylation decreases with age. Phosphorylation within tau/MAP's repeat domain or in flanking regions seems to reduce tau/MAP's interaction with, respectively, microtubules or plasma membrane components (PubMed:7706316). Phosphorylation on Ser-610, Ser-622, Ser-641 and Ser-673 in several isoforms during mitosis. Phosphorylation at Ser-548 by GSK3B reduces ability to bind and stabilize microtubules. Phosphorylation at Ser-579 by BRSK1 and BRSK2 in neurons affects ability to bind microtubules and plays a role in neuron polarization. Phosphorylated at Ser-554, Ser-579, Ser-602, Ser-606 and Ser-669 by PHK. Phosphorylation at Ser-214 by SGK1 mediates microtubule depolymerization and neurite formation in hippocampal neurons. There is a reciprocal down-regulation of phosphorylation and O-GlcNAcylation. Phosphorylation on Ser-717 completely abolishes the O-GlcNAcylation on this site, while phosphorylation on Ser-713 and Ser-721 reduces glycosylation by a factor of 2 and 4 respectively. Phosphorylation on Ser-721 is reduced by about 41.5% by GlcNAcylation on Ser-717. Dephosphorylated at several serine and threonine residues by the serine/threonine phosphatase PPP5C.12 Publications
Polyubiquitinated. Requires functional TRAF6 and may provoke SQSTM1-dependent degradation by the proteasome (By similarity). PHF-tau can be modified by three different forms of polyubiquitination. 'Lys-48'-linked polyubiquitination is the major form, 'Lys-6'-linked and 'Lys-11'-linked polyubiquitination also occur.By similarity2 Publications
O-glycosylated. O-GlcNAcylation content is around 8.2%. There is reciprocal down-regulation of phosphorylation and O-GlcNAcylation. Phosphorylation on Ser-717 completely abolishes the O-GlcNAcylation on this site, while phosphorylation on Ser-713 and Ser-721 reduces O-GlcNAcylation by a factor of 2 and 4 respectively. O-GlcNAcylation on Ser-717 decreases the phosphorylation on Ser-721 by about 41.5%.6 Publications
Glycation of PHF-tau, but not normal brain TAU/MAPT. Glycation is a non-enzymatic post-translational modification that involves a covalent linkage between a sugar and an amino group of a protein molecule forming ketoamine. Subsequent oxidation, fragmentation and/or cross-linking of ketoamine leads to the production of advanced glycation endproducts (AGES). Glycation may play a role in stabilizing PHF aggregation leading to tangle formation in AD.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei24Not glycated1 Publication1
Sitei44Not glycated1 Publication1
Sitei67Not glycated1 Publication1
Sitei381Not glycated1 Publication1
Sitei391Not glycated1 Publication1
Sitei392Not glycated1 Publication1
Sitei394Not glycated1 Publication1
Sitei465Not glycated1 Publication1
Sitei497Not glycated1 Publication1
Sitei507Not glycated1 Publication1
Sitei541Not glycated1 Publication1
Sitei557Not glycated1 Publication1
Sitei571Not glycated1 Publication1
Sitei574Not glycated1 Publication1
Sitei584Not glycated1 Publication1
Sitei591Not glycated1 Publication1
Sitei607Not glycated1 Publication1
Sitei611Not glycated1 Publication1
Sitei615Not glycated1 Publication1
Sitei628Not glycated1 Publication1
Sitei634Not glycated1 Publication1
Sitei638Not glycated1 Publication1
Sitei648Not glycated1 Publication1
Sitei657Not glycated1 Publication1
Sitei660Not glycated1 Publication1
Sitei687Not glycated1 Publication1
Sitei692Not glycated1 Publication1
Sitei700Not glycated1 Publication1
Sitei702Not glycated1 Publication1
Sitei712Not glycated1 Publication1
Sitei755Not glycated1 Publication1

Keywords - PTMi

Acetylation, Disulfide bond, Glycation, Glycoprotein, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP10636
MaxQBiP10636
PaxDbiP10636
PeptideAtlasiP10636
PRIDEiP10636
ProteomicsDBi12705 [P10636-9]
52624
52625 [P10636-2]
52626 [P10636-3]
52627 [P10636-4]
52628 [P10636-5]
52629 [P10636-6]
52630 [P10636-7]
52631 [P10636-8]
52632 [P10636-9]
TopDownProteomicsiP10636-3 [P10636-3]

PTM databases

iPTMnetiP10636
PhosphoSitePlusiP10636

Miscellaneous databases

PMAP-CutDBiP10636

Expressioni

Tissue specificityi

Expressed in neurons. Isoform PNS-tau is expressed in the peripheral nervous system while the others are expressed in the central nervous system.

Developmental stagei

Four-repeat (type II) TAU/MAPT is expressed in an adult-specific manner and is not found in fetal brain, whereas three-repeat (type I) TAU/MAPT is found in both adult and fetal brain.

Gene expression databases

BgeeiENSG00000186868
ExpressionAtlasiP10636 baseline and differential
GenevisibleiP10636 HS

Organism-specific databases

HPAiCAB000151
CAB072344
HPA048895
HPA069524
HPA069570

Interactioni

Subunit structurei

Interacts with MARK1, MARK2, MARK3 AND MARK4 (PubMed:23666762). Interacts with PSMC2 through SQSTM1 (By similarity). Interacts with SQSTM1 when polyubiquitinated (PubMed:15953362). Interacts with FKBP4 (By similarity). Binds to CSNK1D (PubMed:14761950). Interacts with SGK1 (PubMed:16982696). Interacts with EPM2A; the interaction dephosphorylates MAPT at Ser-396 (PubMed:19542233).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin binding Source: ParkinsonsUK-UCL
  • apolipoprotein binding Source: BHF-UCL
  • chaperone binding Source: ARUK-UCL
  • dynactin binding Source: ParkinsonsUK-UCL
  • enzyme binding Source: UniProtKB
  • Hsp90 protein binding Source: ARUK-UCL
  • identical protein binding Source: CAFA
  • microtubule binding Source: UniProtKB
  • microtubule lateral binding Source: CAFA
  • protein binding, bridging Source: ARUK-UCL
  • protein homodimerization activity Source: CAFA
  • protein kinase binding Source: ARUK-UCL
  • protein phosphatase 2A binding Source: ParkinsonsUK-UCL
  • receptor ligand activity Source: ARUK-UCL
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110308, 117 interactors
CORUMiP10636
DIPiDIP-29753N
ELMiP10636
IntActiP10636, 58 interactors
MINTiP10636
STRINGi9606.ENSP00000340820

Chemistry databases

BindingDBiP10636

Structurei

Secondary structure

1758
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi578 – 584Combined sources7
Beta strandi587 – 590Combined sources4
Helixi596 – 599Combined sources4
Helixi603 – 605Combined sources3
Beta strandi607 – 610Combined sources4
Helixi613 – 615Combined sources3
Beta strandi618 – 620Combined sources3
Turni622 – 624Combined sources3
Beta strandi625 – 627Combined sources3
Beta strandi634 – 640Combined sources7
Beta strandi653 – 657Combined sources5
Beta strandi665 – 667Combined sources3
Beta strandi670 – 673Combined sources4
Beta strandi677 – 679Combined sources3
Beta strandi682 – 688Combined sources7

3D structure databases

DisProtiDP01100
ProteinModelPortaliP10636
SMRiP10636
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10636

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati561 – 591Tau/MAP 1PROSITE-ProRule annotation1 PublicationAdd BLAST31
Repeati592 – 622Tau/MAP 2PROSITE-ProRule annotation1 PublicationAdd BLAST31
Repeati623 – 653Tau/MAP 3PROSITE-ProRule annotation1 PublicationAdd BLAST31
Repeati654 – 685Tau/MAP 4PROSITE-ProRule annotation1 PublicationAdd BLAST32

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni561 – 685Microtubule-binding domain1 PublicationAdd BLAST125

Domaini

The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2418 Eukaryota
ENOG4111J07 LUCA
GeneTreeiENSGT00530000063491
HOVERGENiHBG000991
InParanoidiP10636
KOiK04380
OMAiPPEFTFH
OrthoDBiEOG091G0AHK
TreeFamiTF316358

Family and domain databases

InterProiView protein in InterPro
IPR001084 MAP_tubulin-bd_rpt
IPR002955 Tau
PfamiView protein in Pfam
PF00418 Tubulin-binding, 4 hits
PRINTSiPR01261 TAUPROTEIN
PROSITEiView protein in PROSITE
PS00229 TAU_MAP_1, 4 hits
PS51491 TAU_MAP_2, 4 hits

Sequences (9)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. Isoforms differ from each other by the presence or absence of up to 5 of the 15 exons. One of these optional exons contains the additional tau/MAP repeat.
Isoform PNS-tau (identifier: P10636-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT
60 70 80 90 100
PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQAA AQPHTEIPEG
110 120 130 140 150
TTAEEAGIGD TPSLEDEAAG HVTQEPESGK VVQEGFLREP GPPGLSHQLM
160 170 180 190 200
SGMPGAPLLP EGPREATRQP SGTGPEDTEG GRHAPELLKH QLLGDLHQEG
210 220 230 240 250
PPLKGAGGKE RPGSKEEVDE DRDVDESSPQ DSPPSKASPA QDGRPPQTAA
260 270 280 290 300
REATSIPGFP AEGAIPLPVD FLSKVSTEIP ASEPDGPSVG RAKGQDAPLE
310 320 330 340 350
FTFHVEITPN VQKEQAHSEE HLGRAAFPGA PGEGPEARGP SLGEDTKEAD
360 370 380 390 400
LPEPSEKQPA AAPRGKPVSR VPQLKARMVS KSKDGTGSDD KKAKTSTRSS
410 420 430 440 450
AKTLKNRPCL SPKHPTPGSS DPLIQPSSPA VCPEPPSSPK YVSSVTSRTG
460 470 480 490 500
SSGAKEMKLK GADGKTKIAT PRGAAPPGQK GQANATRIPA KTPPAPKTPP
510 520 530 540 550
SSGEPPKSGD RSGYSSPGSP GTPGSRSRTP SLPTPPTREP KKVAVVRTPP
560 570 580 590 600
KSPSSAKSRL QTAPVPMPDL KNVKSKIGST ENLKHQPGGG KVQIINKKLD
610 620 630 640 650
LSNVQSKCGS KDNIKHVPGG GSVQIVYKPV DLSKVTSKCG SLGNIHHKPG
660 670 680 690 700
GGQVEVKSEK LDFKDRVQSK IGSLDNITHV PGGGNKKIET HKLTFRENAK
710 720 730 740 750
AKTDHGAEIV YKSPVVSGDT SPRHLSNVSS TGSIDMVDSP QLATLADEVS

ASLAKQGL
Length:758
Mass (Da):78,928
Last modified:May 31, 2011 - v5
Checksum:iD46C66CDBCD196E8
GO
Isoform Fetal-tau (identifier: P10636-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     45-73: Missing.
     74-102: Missing.
     125-375: Missing.
     395-460: Missing.
     592-622: Missing.

Show »
Length:352
Mass (Da):36,760
Checksum:i9B26AEDFF4D2677C
GO
Isoform Tau-A (identifier: P10636-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLK → MLRALQQRKR
     45-73: Missing.
     74-102: Missing.
     103-