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.
Subunit structure: Interacts with SQSTM1 when polyubiquitinated. Interacts with PSMC2 through SQSTM1. Binds to CSNK1D
By similarity. Interacts with FKBP4. Interacts with SGK1
By similarity. Ref.9
Subcellular location: Cytoplasm › cytosol. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm › cytoskeleton. Cell projection › axon. Note: Mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components.
Tissue specificity: Expressed in neurons. The larger forms (isoform tau-Aand isoform tau-B)are preferentially expressed in the peripheral nervous system while the other are expressed in the central nervous system. Low amounts of the larger forms are also found in limited areas of the CNS.
Developmental stage: During the immediate postnatal period, the dorsal root ganglia express all isoforms whereas only the larger forms persist in the adults.
Domain: The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.
Post-translational modification: Polyubiquitinated. Requires functional TRAF6 and may provoke SQSTM1-dependent degradation by the proteasome
By similarity.Phosphorylated 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 or MARK2), causing detachment from microtubules, and their disassembly. Fetal Tau is much more phosphorylated than adult Tau. Phosphorylation at Ser-573 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. Phosphorylation at Ser-204 by SGK1 mediates microtubule depolymerization and neurite formation in hippocampal neurons
By similarity. Ref.7
Sequence similarities: Contains 4 Tau/MAP repeats.
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