Part:BBa_K4165009
Tau (0N4R)
This basic part encodes the human tau protein isoform 0N4R.
Usage and Biology
Alzheimer's disease (AD), which is considered the most common neurodegenerative disease to cause dementia, is characterized by 2 main accumulations that are amyloid plaques from amyloid beta and NFTs aggregates resulting from hyperphosphorylated or abnormally-phosphorylated tau protein accumulation [1]. Our part Tau, microtubule-associated protein (MAP) is a phosphoprotein that is prevalently found in cytosol and neuron axons [2]. It is determined to be significantly expressed in neurons of the central nervous system (CNS) and the ocular tissues. [3]. It has a crucial role both under normal physiological conditions and also in the pathology of Alzheimer's disease.
In the normal brain, It can stabilize the neuronal microtubules that are essential for the establishment of cell polarity, the development of cell processes, and intracellular signal transduction. Six molecular tau isoforms are coded by a single gene on chromosome 17 resulting from alternative splicing of tau pre-mRNA AND characterized to be significantly hydrophilic, heat stable, and soluble. These six isoforms differ in their binding repeats either 3R taus or 4R taus microtubule-binding repeats and the extra 4R repeat comes from the second (R2) repeat found in 4R. Tau biological activity is affected by 2 main processes that are alternative splicing and its phosphorylation process. For tau's interaction with tubulin and the enhancement of microtubule assembly, normal brain tau appears to require 2-3 moles of phosphate per mole of the protein [4]. Specifically, tau is phosphorylated at Ser262 and Ser214 in AD, which causes tau to separate from microtubules.
In the AD brain, Tau Hyperphosphorylation is considered the main cause of AD progression. It may alter the protein's shape and charge, which in turn causes the microtubule-binding domain to become exposed and allow tau to self-assemble and form oligomers characterized to be neurofibrillary tangles [[5-9], and [10]]. According to several studies, the polymerized tau into neurofibrillary tangles is inert since it does not bind to tubulin or encourage its assembly into microtubules [11-15]. In the AD brain, up to 40% of the abnormally hyperphosphorylated tau is found in the cytosol and has not formed into paired helical filaments or neurofibrillary tangles [4,16,17] Instead of binding to tubulin and promoting microtubule assembly, the AD cytosolic abnormally hyperphosphorylated tau (AD P-tau) opposes assembly and causes microtubule disruption.
Before the development of NFTs, all six forms of tau are self-assembled into paired helical filaments as a result of hyperphosphorylation at the C-terminus of tau (PHFs). The aggregated tau protein assumes this shape, which impairs axonal transit and continuously promotes microtubule instability [18, 11]. AD patients have an aberrant or hyperphosphorylated tau protein concentration that is four times higher than that of normal controls. These misfolded tau proteins are also discovered to be potential neurotoxins and lose their basic function of MT stability along with enhanced aggregation effects. [19-23]. In the AD brain, the shortest isoform, 3R0N, is the only one present.
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25INCOMPATIBLE WITH RFC[25]Illegal NgoMIV site found at 43
Illegal AgeI site found at 229 - 1000INCOMPATIBLE WITH RFC[1000]Illegal BsaI site found at 207
Illegal BsaI site found at 1119
Illegal SapI.rc site found at 393
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