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Protein

Microtubule-associated protein tau

Gene

MAPT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • apolipoprotein binding Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • lipoprotein particle binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB
  • structural constituent of cytoskeleton Source: ProtInc

GO - Biological processi

  • adult walking behavior Source: Ensembl
  • axo-dendritic transport Source: Ensembl
  • axon extension Source: Ensembl
  • generation of neurons Source: UniProtKB
  • microtubule cytoskeleton organization Source: UniProtKB
  • mitochondrion transport along microtubule Source: Ensembl
  • negative regulation of intracellular transport Source: Ensembl
  • neuron migration Source: Ensembl
  • positive regulation of axon extension Source: UniProtKB
  • positive regulation of microtubule polymerization Source: UniProtKB
  • regulation of autophagy Source: MGI
  • regulation of microtubule-based movement Source: Ensembl
  • regulation of microtubule polymerization Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006127-MONOMER.
ReactomeiR-HSA-264870. Caspase-mediated cleavage of cytoskeletal proteins.
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

HGNCiHGNC:6893. MAPT.

Subcellular locationi

GO - Cellular componenti

  • axon Source: UniProtKB
  • axoneme Source: Ensembl
  • cell body Source: ParkinsonsUK-UCL
  • cytoplasmic ribonucleoprotein granule Source: ParkinsonsUK-UCL
  • cytosol Source: Reactome
  • dendrite Source: ParkinsonsUK-UCL
  • growth cone Source: UniProtKB
  • microtubule Source: UniProtKB-KW
  • microtubule associated complex Source: ProtInc
  • neurofibrillary tangle Source: ParkinsonsUK-UCL
  • nuclear periphery Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: Ensembl
  • tubulin complex Source: UniProtKB
Complete GO annotation...

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.

Frontotemporal dementia (FTD)21 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 rs63750959dbSNPEnsembl.1
Natural variantiVAR_019662583L → V in FTD; less able to promote microtubule assembly than wild-type tau. 1 PublicationCorresponds to variant rs63750349dbSNPEnsembl.1
Natural variantiVAR_010345589G → V in FTD. 2 PublicationsCorresponds to variant rs63750376dbSNPEnsembl.1
Natural variantiVAR_010346596N → K in FTD; with parkinsonism. 5 PublicationsCorresponds to variant rs63750756dbSNPEnsembl.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 rs63750416dbSNPEnsembl.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 rs63751273dbSNPEnsembl.1
Natural variantiVAR_010349618P → S in FTD and CBD; reduction in the ability to promote microtubule assembly. 4 PublicationsCorresponds to variant rs63751438dbSNPEnsembl.1
Natural variantiVAR_010350622S → N in FTD; minimal parkinsonism; very early age of onset. 1 PublicationCorresponds to variant rs63751165dbSNPEnsembl.1
Natural variantiVAR_037440634K → M in FTD. 1 PublicationCorresponds to variant rs63750092dbSNPEnsembl.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 rs63750570dbSNPEnsembl.1
Natural variantiVAR_019666659E → V in FTD. 1 PublicationCorresponds to variant rs63750711dbSNPEnsembl.1
Natural variantiVAR_010353723R → W in FTD/Alzheimer disease; accelerates aggregation of tau into filaments; reduces tau phosphorylation in cells compared to both the wild-type and other mutant forms. 7 PublicationsCorresponds to variant rs63750424dbSNPEnsembl.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 rs63750129dbSNPEnsembl.1
Natural variantiVAR_019665637S → F in PIDB; markedly reduced ability of tau to promote microtubule assembly. 1 PublicationCorresponds to variant rs63750635dbSNPEnsembl.1
Natural variantiVAR_019668686K → I in PIDB; 90% reduction in the rate of microtubule assembly. 1 PublicationCorresponds to variant rs63751264dbSNPEnsembl.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 rs63750512dbSNPEnsembl.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 rs63750959dbSNPEnsembl.1
Natural variantiVAR_010340285D → N Risk factor for PSNP1. 2 PublicationsCorresponds to variant rs62063786dbSNPEnsembl.1
Natural variantiVAR_010341289V → A Risk factor for PSNP1. 2 PublicationsCorresponds to variant rs62063787dbSNPEnsembl.1
Natural variantiVAR_019664613Missing in PSNP1/atypical PSNP1; heterozygosity may be a risk factor for both a PSNP1-like syndrome and Parkinson disease; 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. 4 Publications1
Natural variantiVAR_037439620G → V in PSNP1. 1 PublicationCorresponds to variant rs63751391dbSNPEnsembl.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.
MalaCardsiMAPT.
MIMi157140. gene+phenotype.
172700. phenotype.
260540. phenotype.
600274. phenotype.
601104. phenotype.
OpenTargetsiENSG00000186868.
ENSG00000276155.
ENSG00000277956.
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); in PHF-tau; in vitro1 Publication1
Modified residuei111PhosphothreonineBy similarity1
Modified residuei214Phosphoserine; by SGK11 Publication1
Glycosylationi383N-linked (Glc) (glycation); in PHF-tau; in vitro1 Publication1
Modified residuei396Phosphoserine; in PHF-tau1 Publication1
Glycosylationi467N-linked (Glc) (glycation); 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); in PHF-tau; in vitro1 Publication1
Modified residuei484Deamidated asparagine; in tau and PHF-tau; partial1 Publication1
Modified residuei486PhosphothreonineBy similarity1
Glycosylationi491N-linked (Glc) (glycation); 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)1 Publication1
Modified residuei529Phosphothreonine; by BRSK1, BRSK2, DYRK2 and PDPK16 Publications1
Modified residuei531Phosphoserine; by PKA4 Publications1
Modified residuei534Phosphothreonine; by PDPK12 Publications1
Modified residuei542N6-acetyllysineBy similarity1
Glycosylationi542N-linked (Glc) (glycation); in PHF-tau; in vitro1 Publication1
Modified residuei548Phosphothreonine; by GSK3-beta and PDPK1Combined sources3 Publications1
Glycosylationi551N-linked (Glc) (glycation); in PHF-tau; in vitro1 Publication1
Modified residuei552Phosphoserine; by PDPK1Combined sources3 Publications1
Modified residuei554Phosphoserine; by PHK2 Publications1
Glycosylationi555O-linked (GlcNAc)1 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); in PHF-tau; in vitro1 Publication1
Cross-linki576Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei579Phosphoserine; by MARK1, MARK4, BRSK1, BRSK2 and PHK7 Publications1
Cross-linki584Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei596Deamidated asparagine; in tau and PHF-tau; partial1
Glycosylationi597N-linked (Glc) (glycation); in PHF-tau; in vitro1 Publication1
Modified residuei598N6-acetyllysine; alternateBy similarity1
Glycosylationi598N-linked (Glc) (glycation); 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 residuei606Phosphoserine; by PHK1 Publication1
Modified residuei607N6-acetyllysineBy similarity1
Disulfide bondi608 ↔ 639By similarity
Modified residuei610Phosphoserine; by MARK1; in PHF-tau1 Publication1
Modified residuei615N6-acetyllysine; alternateBy similarity1
Cross-linki615Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei622Phosphoserine; by MARK1; in PHF-tau1 Publication1
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 residuei641Phosphoserine; by MARK1; in PHF-tau1 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); 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); in PHF-tau; in vitro1 Publication1
Cross-linki670Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau1 Publication
Modified residuei673Phosphoserine; by MARK1; in PHF-tau1 Publication1
Modified residuei686N6-acetyllysine; alternateBy similarity1
Glycosylationi686N-linked (Glc) (glycation); 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); 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 or MARK2), causing detachment from microtubules, and their disassembly. 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. 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.11 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
Sitei44Not glycated1
Sitei67Not glycated1
Sitei381Not glycated1
Sitei391Not glycated1
Sitei392Not glycated1
Sitei394Not glycated1
Sitei465Not glycated1
Sitei497Not glycated1
Sitei507Not glycated1
Sitei541Not glycated1
Sitei557Not glycated1
Sitei571Not glycated1
Sitei574Not glycated1
Sitei584Not glycated1
Sitei591Not glycated1
Sitei607Not glycated1
Sitei611Not glycated1
Sitei615Not glycated1
Sitei628Not glycated1
Sitei634Not glycated1
Sitei638Not glycated1
Sitei648Not glycated1
Sitei657Not glycated1
Sitei660Not glycated1
Sitei687Not glycated1
Sitei692Not glycated1
Sitei700Not glycated1
Sitei702Not glycated1
Sitei712Not glycated1
Sitei755Not glycated1

Keywords - PTMi

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

Proteomic databases

MaxQBiP10636.
PaxDbiP10636.
PeptideAtlasiP10636.
PRIDEiP10636.
TopDownProteomicsiP10636-3. [P10636-3]

PTM databases

iPTMnetiP10636.
PhosphoSitePlusiP10636.

Miscellaneous databases

PMAP-CutDBP10636.

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.
HPA069524.
HPA069570.

Interactioni

Subunit structurei

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 similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APOEP026493EBI-366182,EBI-9209835
APPP050679EBI-366182,EBI-77613
BIN1O00499-15EBI-6926270,EBI-6926280
DCTN1Q142038EBI-366233,EBI-724352
GSK3BP498419EBI-366233,EBI-373586
HSP90AB1P082384EBI-366233,EBI-352572
LRRK2Q5S0079EBI-366233,EBI-5323863
MARK2Q7KZI72EBI-366233,EBI-516560
PRNPP041562EBI-366182,EBI-977302
SLC1A2P430044EBI-366182,EBI-3440986
SNCAP378403EBI-366233,EBI-985879
STUB1Q9UNE72EBI-366182,EBI-357085
YWHAZP631049EBI-7145070,EBI-347088

GO - Molecular functioni

  • apolipoprotein binding Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110308. 109 interactors.
DIPiDIP-29753N.
IntActiP10636. 52 interactors.
MINTiMINT-134394.
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
Helixi596 – 599Combined sources4
Helixi603 – 605Combined sources3
Beta strandi607 – 610Combined sources4
Helixi613 – 615Combined sources3
Turni620 – 622Combined sources3
Beta strandi625 – 627Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I8HNMR-A542-554[»]
2MZ7NMR-A584-629[»]
2ON9X-ray1.51A/B623-628[»]
3OVLX-ray1.81A623-628[»]
4E0MX-ray1.75A/B/C/D622-634[»]
4E0NX-ray1.65A/B/C/D622-634[»]
4E0OX-ray1.82A/B/C/D622-634[»]
4FL5X-ray1.90P/Q527-536[»]
4GLRX-ray1.90A/B541-557[»]
4NP8X-ray1.51A623-628[»]
4TQEX-ray1.60A532-547[»]
4Y32X-ray1.70C/D528-534[»]
4Y3BX-ray1.80C/D528-534[»]
4Y5IX-ray1.40F/G528-534[»]
5DMGX-ray2.50P/X/Z733-747[»]
5E2VX-ray1.64P511-528[»]
5E2WX-ray1.50P511-528[»]
5HF3X-ray1.80B528-534[»]
DisProtiDP00126.
ProteinModelPortaliP10636.
SMRiP10636.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10636.

Family & Domainsi

Domains and Repeats

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

Domaini

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

Sequence similaritiesi

Contains 4 Tau/MAP repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2418. Eukaryota.
ENOG4111J07. LUCA.
GeneTreeiENSGT00530000063491.
HOVERGENiHBG000991.
InParanoidiP10636.
KOiK04380.
OMAiMKVKGAD.
OrthoDBiEOG091G0AHK.
TreeFamiTF316358.

Family and domain databases

InterProiIPR027324. MAP2/MAP4/Tau.
IPR001084. MAP_tubulin-bd_rpt.
IPR002955. Tau.
[Graphical view]
PANTHERiPTHR11501. PTHR11501. 1 hit.
PfamiPF00418. Tubulin-binding. 4 hits.
[Graphical view]
PRINTSiPR01261. TAUPROTEIN.
PROSITEiPS00229. TAU_MAP_1. 4 hits.
PS51491. TAU_MAP_2. 4 hits.
[Graphical view]

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.

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        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.
     103-104: Missing.
     125-375: Missing.
     395-460: Missing.
     592-622: Missing.

Show »
Length:316
Mass (Da):32,944
Checksum:i4C86C95F53015575
GO
Isoform Tau-B (identifier: P10636-4) [UniParc]FASTAAdd to basket

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

Show »
Length:381
Mass (Da):39,720
Checksum:iEA206819FE73B67A
GO
Isoform Tau-C (identifier: P10636-5) [UniParc]FASTAAdd to basket
Also known as: Tau-3

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

Show »
Length:410
Mass (Da):42,603
Checksum:iA76B304E99E6A978
GO
Isoform Tau-D (identifier: P10636-6) [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.

Show »
Length:383
Mass (Da):40,007
Checksum:iF3256B0AB87B348D
GO
Isoform Tau-E (identifier: P10636-7) [UniParc]FASTAAdd to basket

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

Show »
Length:412
Mass (Da):42,967
Checksum:i0D4EABCA15179E7D
GO
Isoform Tau-F (identifier: P10636-8) [UniParc]FASTAAdd to basket
Also known as: Tau-4

The sequence of this isoform differs from the canonical sequence as follows:
     125-375: Missing.
     395-460: Missing.

Show »
Length:441
Mass (Da):45,850
Checksum:i835A8706D847A8CC
GO
Isoform Tau-G (identifier: P10636-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     502-502: S → SATKQVQRRPPPAGPRSER

Note: No experimental confirmation available.
Show »
Length:776
Mass (Da):80,941
Checksum:i13E913ACD1790C26
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48L → P in AAU45390 (Ref. 6) Curated1
Sequence conflicti414H → L in AAC04277 (PubMed:1420178).Curated1
Sequence conflicti557K → M in AAS17881 (Ref. 12) Curated1
Sequence conflicti591K → S in AAS17881 (Ref. 12) Curated1
Sequence conflicti617V → Q AA sequence (PubMed:1915258).Curated1
Sequence conflicti622S → K AA sequence (PubMed:1915258).Curated1

Natural variant

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 rs63750959dbSNPEnsembl.1
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 rs63750959dbSNPEnsembl.1
Natural variantiVAR_06462217T → M.1 PublicationCorresponds to variant rs144611688dbSNPEnsembl.1
Natural variantiVAR_06462330T → A.1 PublicationCorresponds to variant rs748728879dbSNPEnsembl.1
Natural variantiVAR_010340285D → N Risk factor for PSNP1. 2 PublicationsCorresponds to variant rs62063786dbSNPEnsembl.1
Natural variantiVAR_010341289V → A Risk factor for PSNP1. 2 PublicationsCorresponds to variant rs62063787dbSNPEnsembl.1
Natural variantiVAR_056121370R → W.Corresponds to variant rs17651549dbSNPEnsembl.1
Natural variantiVAR_010342441Y → H.3 PublicationsCorresponds to variant rs2258689dbSNPEnsembl.1
Natural variantiVAR_010343447S → P.1 PublicationCorresponds to variant rs10445337dbSNPEnsembl.1
Natural variantiVAR_010344574K → T in PIDB; reduces the ability to promote microtubule assembly by 70%. 2 PublicationsCorresponds to variant rs63750129dbSNPEnsembl.1
Natural variantiVAR_019662583L → V in FTD; less able to promote microtubule assembly than wild-type tau. 1 PublicationCorresponds to variant rs63750349dbSNPEnsembl.1
Natural variantiVAR_010345589G → V in FTD. 2 PublicationsCorresponds to variant rs63750376dbSNPEnsembl.1
Natural variantiVAR_010346596N → K in FTD; with parkinsonism. 5 PublicationsCorresponds to variant rs63750756dbSNPEnsembl.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 rs63750416dbSNPEnsembl.1
Natural variantiVAR_019664613Missing in PSNP1/atypical PSNP1; heterozygosity may be a risk factor for both a PSNP1-like syndrome and Parkinson disease; 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. 4 Publications1
Natural variantiVAR_064624617V → I.1 PublicationCorresponds to variant rs116733906dbSNPEnsembl.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 rs63751273dbSNPEnsembl.1
Natural variantiVAR_010349618P → S in FTD and CBD; reduction in the ability to promote microtubule assembly. 4 PublicationsCorresponds to variant rs63751438dbSNPEnsembl.1
Natural variantiVAR_037439620G → V in PSNP1. 1 PublicationCorresponds to variant rs63751391dbSNPEnsembl.1
Natural variantiVAR_010350622S → N in FTD; minimal parkinsonism; very early age of onset. 1 PublicationCorresponds to variant rs63751165dbSNPEnsembl.1
Natural variantiVAR_037440634K → M in FTD. 1 PublicationCorresponds to variant rs63750092dbSNPEnsembl.1
Natural variantiVAR_019665637S → F in PIDB; markedly reduced ability of tau to promote microtubule assembly. 1 PublicationCorresponds to variant rs63750635dbSNPEnsembl.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 rs63750570dbSNPEnsembl.1
Natural variantiVAR_019666659E → V in FTD. 1 PublicationCorresponds to variant rs63750711dbSNPEnsembl.1
Natural variantiVAR_019667669S → L in fatal respiratory hypoventilation; unusual apparent autosomal recessive inheritance; reduced binding to microtubules as well as increased fibrillization and aggregation. 1 PublicationCorresponds to variant rs63750425dbSNPEnsembl.1
Natural variantiVAR_019668686K → I in PIDB; 90% reduction in the rate of microtubule assembly. 1 PublicationCorresponds to variant rs63751264dbSNPEnsembl.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 rs63750512dbSNPEnsembl.1
Natural variantiVAR_010353723R → W in FTD/Alzheimer disease; accelerates aggregation of tau into filaments; reduces tau phosphorylation in cells compared to both the wild-type and other mutant forms. 7 PublicationsCorresponds to variant rs63750424dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0031751 – 44MAEPR…DAGLK → MLRALQQRKR in isoform Tau-A. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_00317645 – 73Missing in isoform Tau-A, isoform Tau-D and isoform Fetal-tau. 5 PublicationsAdd BLAST29
Alternative sequenceiVSP_00317774 – 102Missing in isoform Tau-A, isoform Tau-B, isoform Tau-D, isoform Tau-E and isoform Fetal-tau. 7 PublicationsAdd BLAST29
Alternative sequenceiVSP_003178103 – 104Missing in isoform Tau-A. 1 Publication2
Alternative sequenceiVSP_003179125 – 375Missing in isoform Tau-A, isoform Tau-B, isoform Tau-C, isoform Tau-D, isoform Tau-E, isoform Tau-F and isoform Fetal-tau. 7 Publications