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Symbol MAPT contributors: mct/pgu - updated : 26-01-2017
HGNC name microtubule-associated protein tau
HGNC id 6893
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 - 6762 78.88 758 nervous system, mainly in axons 2008 18940799
  • full length
  • also called PNS-tau
  • 4-repeat Tau
  • 12 splicing 5811 45.72 441 nervous system, mainly in axons 2008 18940799
  • exons 2+, 3+, 10+
  • lacking 4a & 6
  • 4-repeat Tau
  • 10 splicing 5637 39.87 383 nervous system, mainly in axons 2008 18940799
  • exon 10+
  • lacking 2, 3, 4a & 6
  • 4-repeat Tau
  • encodes the second microtubule-binding repeat, and is regulated by alternative splicing
  • 9 splicing 5464 36.63 352 nervous system, mainly in axons 2008 18940799
  • lacking 2, 3, 4a, 6 & 10
  • 3-repeat Tau
  • 15 - 6816 - 776 nervous system, mainly in axons 2008 18940799
    11 - 5724 - 412 nervous system, mainly in axons 2008 18940799
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Endocrinepancreas   moderately
    Nervousbrain   highly
     nerve   highly
    Reproductivemale systemtestis  moderately
    Respiratorylung   moderately
    Urinarykidney   moderately
    Visualeye   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • four conserved imperfect 18 AA repeats (microtubule binding motifs)
  • a proline rich region
  • another microtubule binding motif alternatively spliced in the C terminal region (exon 10)
  • fibril-forming motifs with a key role in the fibrillization of MAPT protein and determinants of amyloidogenic proteins tending to misfold, thereby causing the initiation and development of neurodegenerative diseases
    interspecies ortholog to MAPT, Pan troglodytes
    ortholog to Mapt, Rattus norvegicus
    ortholog to Mapt, Mus musculus
    CATEGORY structural protein , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • essential for microtubule assembly
  • necessary for the establishment of neuronal cell polarity, axonal outgrowth, and axonal transport and the maintenance of axonal morphology regulating the transport of vesicles or organelles along microtubules and maintenance of neuron polarity
  • toxicity of intracellular tau to neuronal cells
  • may regulate the subcellular localization and function of calmodulin in neurons
  • strongly implicated as a dosage-sensitive gene in this locus involved in intellectual disability
  • acts as an independent genetic risk factor in pathologically proven Parkinson disease
  • may alter the glucocorticoids -mediated regulation of PKA activity and CREB phosphorylation
  • loss of axonal mitochondria may play an important role in MAPT phosphorylation and toxicity in the pathogenesis of Alzheimer disease
    a component
  • primary constituent of paired helical filaments
    small molecule
  • phosphorylated by Akt/PKB kinase
  • protein
  • SFRS10 (target gene for the alternative splicing regulator SFRS10)
  • Rb binding protein Che-1 (AATF)
  • apolipoprotein E3 (ApoE3)
  • calmodulin 1 (phosphorylase kinase, delta) (CALM1)
  • Fyn kinase (FYN)
  • prolyl isomerase Pin1
  • Presenilin 1 (PSEN1)
  • S100 calcium binding protein B (S100B)
  • alpha-synuclein (SNCA)
  • spectrin (SPTB)
  • alpha and beta tubulin
  • ubiquitin
  • 14-3-3zeta protein
  • beta PP peptide
  • BCL2-associated athanogene 1 (BAG-1)
  • Amyloid-beta protein (Abeta)
  • interacting with CALM1 (the lack of MAPT in neurons changes the subcellular localization of CALM1 and that it correlates with a change in the expression of calbindin)
  • SRSF4 binds to the proximal downstream intron of MAPT exon 10 at the FTDP-17 hotspot region and interacts with RBMX and PCBP2 (increased exon 10 inclusion in FTDP mutants may arise from weakened SRSF4 binding)
  • YWHAZ monomeric form interacts with MAPT and with the HSPB6 protein
  • GSK3B activity regulates mitochondrial axonal trafficking largely in a MAPT-dependent manner
  • HTRA1 degrades MAPT aggregates and is induced by its substrates
  • CDC37 is essential for the stability of TARDBP and can be affected by MAPT accumulation
  • MAPT mRNA is a physiological splicing target of FUS
  • SRSF6 promoted MAPT exon 10 inclusion, and the promotion of MAPT exon 10 inclusion by SRSF6 required the arginine/serine-rich region, which was responsible for the subnucleic speckle localization
  • interaction of endogenous MAPT protein with synaptic proteins is regulated by N-methyl-D-aspartate receptor-dependent MAPT phosphorylation
  • NUB1 interacted with both MAPT and GSK3B to disrupt their interaction, and abolished recruitment of GSK3B to MAPT inclusions
  • ER stress reduced the binding between MAPT and STUB1, ubiquitin E3 ligase for MAPT (STUB1 binds to MAPT and is thought to promote the degradation of MAPT by its ubiquitination through ubiquitin–proteasome system)
  • NMNAT2 affects MAPT phosphorylation by regulating PPP2CA activity
  • novel function for PSEN1 in modulating NUP62 expression to control the proteostasis of MAPT
  • YWHAZ has a role in the fibrillization of MAPT in Alzheimer brain, and MAPT phosphorylation does not affect YWHAZ-induced MAPT aggregation
  • EFHD2 co-aggregates and interacts with known neuropathological proteins, such as MAPT, C9orf72, and LRRK2
  • regulatory role of DYRK1A in controlling MAPT and SNCA
  • CX3CR1 is a novel target for the clearance of extracellular MAPT
  • CX3CR1/CX3CL1 axis plays a key role in the phagocytosis of MAPT by microglia and that it is affected as Alzheimer disease progresses
  • DNAJA2 levels were correlated with MAPT pathology in human brains, supporting the idea that it is an important regulator of MAPT homeostasis
  • DNAJA2 is an unexpected, but potent, inhibitor of MAPT aggregation
  • cell & other
    Phosphorylated by CDC37 that is able to regulate phosphorylation of MAPT and ultimately its stability
    Other phosphorylated by CDK5 and other kinases with decrease of affinity for microtubules
    caspase cleavage of tau may be a molecular mechanism through wihch lysosomal dysfunction and neurodegeneration are causally linked in Alzeihmer's disease
    tau phosphorylation can regulate its association with motor machinery suggesting that signaling deregulation events can lead to tau mislocalization (
    regulated by CDC37 in two ways: by directly stabilizing it via HSP90 and by regulating the stability of distinct MAPT kinases
    increase in MAPT phosphorylation at Ser262 through MARK2 contributes to MAPT-mediated neurodegeneration under a pathological condition in which axonal mitochondria is depleted
    corresponding disease(s) FTDP17 , PSRP , DEL17Q21 , DUP17Q21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in extraskeletal myxoid chondrosarcoma and chordoma
    constitutional       loss of function
    forming tangles of paired helical filaments (PHF) consisting of hyperphosphorylated tau protein in Alzheimer disease
    constitutional   insertion    
    inclusion of exon 6c decreases in DM1 (myotonic dystrophy 1) brains compared to control brains whereas inclusion of 6d increases
    constitutional       gain of function
    and KLC1 axonal transport defects can initiate neurodegeneration and/or exacerbate human tau-dependent disease pathways in AD and other neurodegenerative tauopathies
    constitutional     --other  
    splicing misregulation of adult-specific exon 10, which codes for a microtubule binding domain, results in expression of abnormal ratios of tau isoforms, leading to FTDP17
    constitutional     --other  
    loss of axonal mitochondria may play an important role in tau phosphorylation and toxicity in the pathogenesis of AD
    constitutional     --over  
    increased levels of neuronal MAPT are an important factor in the progression of tauopathy, and ER stress-induced increase in total MAPT protein is due to a delay in its degradation
  • to progressive supranuclear palsy and to corticobasal degeneration
  • to Parkinson disease
  • to amyotrophic lateral sclerosis-parkinsonsim/dementia complex of Guam
  • Variant & Polymorphism SNP , other
  • over-representation of the soluble four repeats tau isoforms which may need a genetic defect in tau and a mitochondrial defect either genetic or toxic leading to tau aggregation
  • SNP H1 preferentially associated with Parkinson disease and H1C with Alzheimer disease
  • SNP 14 and 21 increasing the risk of progressive supranuclear palsy and corticobasal degeneration
  • genotypes at SNP9 interact with SNP6 genotypes to increase risk of amyotrophic lateral sclerosis-parkinsonsim/dementia complex of Guam
  • H1 haplotype increased in neurodegenerative disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and Parkinson's disease (PD)
  • H2 haplotype has been found to be related to familial FTD
  • ; H1 haplotype is associated with a particular cerebral morphology that may increase the susceptibility of the healthy carriers to develop neurodegenerative diseases such as sporadic tauopathies
    Candidate gene
  • salivary MAPT species could be ideal biomarkers for AD diagnosis, especially at early stages of the disease or even screening asymptomatic subjects
  • Therapy target
  • mice overexpress the 4R human tau isoform develop axonal degeneration in brain and spinal cord
  • mice expressing mutant (P301L) tau protein exhibit neurofibrillary tangles amyotrophy and progressive motor disturbance
  • double mutant (tau/APP (beta-amyloid precursor protein)) mice develop Abeta deposits and exhibit neurofibrillary tangle pathology enhanced in the limbic system and olfactory cortex
  • mice expressing a repressible human tau variant developed progressive age-related neurofibrillary tangles, neuronal loss, and behavioral impairments