MAPT
Domain
The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.
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 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.
Post-translational modifications
Polyubiquitinated. Requires functional TRAF6 and may provoke SQSTM1-dependent degradation by the proteasome (By similarity).
Phosphorylation at various serine and threonine residues in S-P or T-P motifs by proline-directed protein kinases (PDPK1, CDK1, CDK5, GSK3, MAPK) (a few sites per protein in interphase, more in mitosis), and at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1, MARK2, MARK3, MARK4), causing detachment from microtubules, and their disassembly (By similarity). Phosphorylation at Ser-269 by BRSK1 and BRSK2 in neurons affects ability to bind microtubules and plays a role in neuron polarization. Phosphorylated by PHK. Dephosphorylation at several serine and threonine residues by the serine/threonine phosphatase PPP5C (By similarity).
O-glycosylated; contains at least 4 GlcNAc. Site-specific or stoichiometric changes in glycosylation may modulate tau function and also play a role in PHF's formation.
Tissue Specificity
Expressed in neurons.
Cellular localization
- Cytoplasm
- Cytosol
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasm
- Cytoskeleton
- Cell projection
- Axon
- Cytoplasm
- Cell projection
- Dendrite
- Secreted
- Mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components. Can be secreted; the secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion.
Alternative names
TAU, MAPT, Microtubule-associated protein tau, Neurofibrillary tangle protein, Paired helical filament-tau, PHF-tau