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UniProtKB - P10636 (TAU_HUMAN)

Entry version 259 (31 Jul 2019)
Sequence version 5 (31 May 2011)
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins
R-HSA-9619483 Activation of AMPK downstream of NMDARs

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		P10636

SIGNOR Signaling Network Open Resource

More...SIGNORi		P10636

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Microtubule-associated protein tau
Alternative name(s):
Neurofibrillary tangle protein
Paired helical filament-tau
Short name:
PHF-tau
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MAPT
Synonyms:MAPTL, MTBT1, TAU
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 17

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:6893 MAPT

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		157140 gene+phenotype

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P10636

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Cellular componenti

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

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>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:rs63750756Ensembl.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_010349618P → S in FTD and CBD; reduction in the ability to promote microtubule assembly. 4 PublicationsCorresponds to variant dbSNP:rs63751438EnsemblClinVar.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.
Related information in OMIM
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.
Related information in OMIM
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.
Related information in OMIM

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

DisGeNET

More...DisGeNETi		4137

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		MAPT

MalaCards human disease database

More...MalaCardsi		MAPT
MIMi157140 gene+phenotype
172700 phenotype
260540 phenotype
600274 phenotype
601104 phenotype

NIAGADS Genomics Database

More...NIAGADSi		ENSG00000186868

Open Targets

More...OpenTargetsi		ENSG00000186868

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		275864 Behavioral variant of frontotemporal dementia
240071 Classic progressive supranuclear palsy syndrome
100070 Progressive non-fluent aphasia
240103 Progressive supranuclear palsy-corticobasal syndrome
240085 Progressive supranuclear palsy-parkinsonism syndrome
240112 Progressive supranuclear palsy-progressive non-fluent aphasia syndrome
240094 Progressive supranuclear palsy-pure akinesia with gait freezing syndrome
100069 Semantic dementia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA238

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1293224

Drug and drug target database

More...DrugBanki		DB01248 Docetaxel
DB01229 Paclitaxel

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		MAPT

Domain mapping of disease mutations (DMDM)

More...DMDMi		334302961

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemoved1 Publication
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000727392 – 758Microtubule-associated protein tauAdd BLAST757

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylalanine1 Publication1
Modified residuei18Phosphotyrosine; by FYN1 Publication1
Modified residuei29PhosphotyrosineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>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
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>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

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>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

Encyclopedia of Proteome Dynamics

More...EPDi		P10636

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P10636

MaxQB - The MaxQuant DataBase

More...MaxQBi		P10636

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P10636

PeptideAtlas

More...PeptideAtlasi		P10636

PRoteomics IDEntifications database

More...PRIDEi		P10636

ProteomicsDB human proteome resource

More...ProteomicsDBi		12705 [P10636-9]
52624 [P10636-1]
52625 [P10636-2]
52626 [P10636-3]
52627 [P10636-4]
52628 [P10636-5]
52629 [P10636-6]
52630 [P10636-7]
52631 [P10636-8]
52632 [P10636-9]

Consortium for Top Down Proteomics

More...TopDownProteomicsi		P10636-3 [P10636-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P10636

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P10636

Miscellaneous databases

CutDB - Proteolytic event database

More...PMAP-CutDBi		P10636

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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.

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000186868 Expressed in 217 organ(s), highest expression level in parietal lobe

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P10636 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P10636 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		CAB000151
CAB072344
HPA048895
HPA069524
HPA069570

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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).

Interacts with PIN1 (PubMed:11313338).

Interacts with LRRK2 (PubMed:26014385).

By similarity7 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		110308, 120 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P10636

Database of interacting proteins

More...DIPi		DIP-29753N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		P10636

Protein interaction database and analysis system

More...IntActi		P10636, 562 interactors

Molecular INTeraction database

More...MINTi		P10636

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000340820

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P10636

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1758
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P10636

Database of comparative protein structure models

More...ModBasei		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P10636

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>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
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni561 – 685Microtubule-binding domain1 PublicationAdd BLAST125

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>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

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG2418 Eukaryota
ENOG4111J07 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000155494

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P10636

KEGG Orthology (KO)

More...KOi		K04380

Identification of Orthologs from Complete Genome Data

More...OMAi		EPRQEFN

Database of Orthologous Groups

More...OrthoDBi		716848at2759

TreeFam database of animal gene trees

More...TreeFami		TF316358

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR027324 MAP2/MAP4/Tau
IPR001084 MAP_tubulin-bd_rpt
IPR002955 Tau

The PANTHER Classification System

More...PANTHERi		PTHR11501 PTHR11501, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00418 Tubulin-binding, 4 hits

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR01261 TAUPROTEIN

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00229 TAU_MAP_1, 4 hits
PS51491 TAU_MAP_2, 4 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (9+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 9 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> 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.

This entry has 9 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform PNS-tau (identifier: P10636-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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.