Non-Fucosylated Anti-Human Tau protein (IPN007) Therapeutic Antibody (CAT#: BioBet-1209ZP) Datasheet

MAPT

microtubule-associated protein tau

This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimers disease, Picks disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy.

MAPT; microtubule-associated protein tau; TAU; MSTD; PPND; DDPAC; MAPTL; MTBT1; MTBT2; FTDP-17; PPP1R103; PHF-tau; paired helical filament-tau; neurofibrillary tangle protein; microtubule-associated protein tau, isoform 4; protein phosphatase 1, regulatory subunit 103; G protein beta1/gamma2 subunit-interacting factor 1

Plasma membrane, Cytosol, Cytoskeleton

Diseases associated with MAPT include Frontotemporal Dementia and Supranuclear Palsy, Progressive, 1.

Its related pathways are Neuroscience and Development Slit-Robo signaling.

Promote the assembly and stability of microtubules, and may participate in the establishment and maintenance of neuronal polarity. The c-terminus is bound to axon microtubules, and the n-terminus is bound to the neuroplasmic membrane components, suggesting that tau protein is the connecting protein between the two. Axon polarity is determined by the TAU/MAPT location (in neuronal cells) of the cell body region defined by the centrosome. The short subtype allows plasticity of the cytoskeleton, while the long subtype may preferentially play a role in stabilization.

Neuroscience antibody; Signaling Transduction antibody; Neuron Development Study antibody

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. Polyubiquitinated. Requires functional TRAF6 and may provoke SQSTM1-dependent degradation by the proteasome (By similarity). PHF-tau can be modified by three different forms of polyubiquitination. 'Lys-48'-linked polyubiquitination is the major form, 'Lys-6'-linked and 'Lys-11'-linked polyubiquitination also occur. O-glycosylated. O-GlcNAcylation content is around 8.2%. There is 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 O-GlcNAcylation by a factor of 2 and 4 respectively. O-GlcNAcylation on Ser-717 decreases the phosphorylation on Ser-721 by about 41.5%. Glycation of PHF-tau, but not normal brain TAU/MAPT. Glycation is a non-enzymatic post-translational modification that involves a covalent linkage between a sugar and an amino group of a protein molecule forming ketoamine. Subsequent oxidation, fragmentation and/or cross-linking of ketoamine leads to the production of advanced glycation endproducts (AGES). Glycation may play a role in stabilizing PHF aggregation leading to tangle formation in AD.

Protein Based Therapies
Monoclonal antibody (mAb)

IgG

IPN007

Humanized

Human

IPN007 is a preclinical monoclonal antibody that uses a new approach to treat progressive supranuclear palsy (PSP), a rare brain disease with Tau dysfunction that presents as an atypical parkinsonian disorder.

Alzheimer's Disease

Alzheimer's Disease