| Function: |
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. |
| Tissue Specificity: |
Expressed in neurons. Isoform PNS-tau is expressed in the peripheral nervous system while the others are expressed in the central nervous system. |
| Involvement in Disease: |
Frontotemporal dementia: A 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.
Pick disease of the brain: A 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.
Progressive supranuclear palsy 1: Characterized 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.
Parkinson-dementia syndrome: A syndrome characterized by parkinsonism, tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei. |
| Post-Translational Modification: |
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. |
| Cellular Location: |
Cytoplasm > Cytosol. Cell membrane. Cytoplasm > Cytoskeleton. Cell projection > Axon.
Mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components. |
| Database Links: |
Entrez Gene: 4137?HumanEntrez Gene: 17762?MouseEntrez Gene: 29477?RatOmim: 157140?HumanSwissProt: P10636?HumanSwissProt: P10637?MouseSwissProt: P19332?RatUnigene: 101174?HumanUnigene: 1287?MouseUnigene: 2455?Rat |
| Synonyms: |
AI413597 AntibodyAW045860 AntibodyDDPAC AntibodyFLJ31424 AntibodyFTDP 17 AntibodyG protein beta1/gamma2 subunit interacting factor 1 AntibodyMAPT AntibodyMAPTL AntibodyMGC134287 AntibodyMGC138549 AntibodyMGC156663 AntibodyMicrotubule associated protein tau AntibodyMicrotubule associated protein tau isoform 4 AntibodyMicrotubule-associated protein tau AntibodyMSTD AntibodyMtapt AntibodyMTBT1 AntibodyMTBT2 AntibodyNeurofibrillary tangle protein AntibodyPaired helical filament tau AntibodyPaired helical filament-tau AntibodyPHF tau AntibodyPHF-tau AntibodyPPND AntibodyPPP1R103 AntibodyProtein phosphatase 1, regulatory subunit 103 AntibodypTau AntibodyRNPTAU AntibodyTau AntibodyTauopathy and respiratory failure, included AntibodyTAU_HUMAN Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
