InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAPT

Summary

InnateDB Protein

IDBP-55169.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAPT

Protein Name

microtubule-associated protein tau

Synonyms

DDPAC; FTDP-17; MAPTL; MSTD; MTBT1; MTBT2; PPND; PPP1R103; TAU;

Species

Homo sapiens

Ensembl Protein

ENSP00000303214

InnateDB Gene

IDBG-55163 (MAPT)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:21985311}.

Subcellular Localization

Cytoplasm, cytosol {ECO:0000269PubMed:10747907}. Cell membrane {ECO:0000269PubMed:10747907}; Peripheral membrane protein {ECO:0000269PubMed:10747907}; Cytoplasmic side {ECO:0000269PubMed:10747907}. Cytoplasm, cytoskeleton {ECO:0000269PubMed:10747907}. Cell projection, axon {ECO:0000269PubMed:10747907}. Note=Mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components.

Disease Associations

Note=In Alzheimer disease, the neuronal cytoskeleton in the brain is progressively disrupted and replaced by tangles of paired helical filaments (PHF) and straight filaments, mainly composed of hyperphosphorylated forms of TAU (PHF-TAU or AD P- TAU). O-GlcNAcylation is greatly reduced in Alzheimer disease brain cerebral cortex leading to an increase in TAU/MAPT phosphorylations. {ECO:0000269PubMed:14517953}.Frontotemporal dementia (FTD) [MIM:600274]: 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. {ECO:0000269PubMed:10208578, ECO:0000269PubMed:10214944, ECO:0000269PubMed:10489057, ECO:0000269PubMed:10553987, ECO:0000269PubMed:10802785, ECO:0000269PubMed:11071507, ECO:0000269PubMed:11117541, ECO:0000269PubMed:11585254, ECO:0000269PubMed:11889249, ECO:0000269PubMed:11921059, ECO:0000269PubMed:12473774, ECO:0000269PubMed:12509859, ECO:0000269PubMed:15883319, ECO:0000269PubMed:16240366, ECO:0000269PubMed:9629852, ECO:0000269PubMed:9641683, ECO:0000269PubMed:9736786, ECO:0000269PubMed:9789048, ECO:0000269PubMed:9973279}. Note=The disease is caused by mutations affecting the gene represented in this entry.Pick disease of the brain (PIDB) [MIM:172700]: 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. {ECO:0000269PubMed:10604746, ECO:0000269PubMed:11089577, ECO:0000269PubMed:11117542, ECO:0000269PubMed:11601501, ECO:0000269PubMed:11891833}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in MAPT are a cause of corticobasal degeneration (CBD). It is marked by extrapyramidal signs and apraxia and can be associated with memory loss. Neuropathologic features may overlap Alzheimer disease, progressive supranuclear palsy, and Parkinson disease.Progressive supranuclear palsy 1 (PSNP1) [MIM:601104]: 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. {ECO:0000269PubMed:10534245, ECO:0000269PubMed:11220749, ECO:0000269PubMed:12325083, ECO:0000269PubMed:14991828, ECO:0000269PubMed:14991829, ECO:0000269PubMed:16157753}. Note=The disease is caused by mutations affecting the gene represented in this entry.Parkinson-dementia syndrome (PARDE) [MIM:260540]: A syndrome characterized by parkinsonism, tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei. Note=The disease is caused by mutations affecting the gene represented in this entry.

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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 129 experimentally validated interaction(s) in this database.
They are also associated with 10 interaction(s) predicted by orthology.

Experimentally validated
Total	129 [view]
Protein-Protein	128 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	10 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005200	structural constituent of cytoskeleton
GO:0005515	protein binding
GO:0008017	microtubule binding
GO:0015631	tubulin binding
GO:0017124	SH3 domain binding
GO:0019899	enzyme binding
GO:0034185	apolipoprotein binding
GO:0071813	lipoprotein particle binding

Biological Process

GO:0000226	microtubule cytoskeleton organization
GO:0006915	apoptotic process
GO:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0010506	regulation of autophagy
GO:0031113	regulation of microtubule polymerization
GO:0031116	positive regulation of microtubule polymerization
GO:0045773	positive regulation of axon extension
GO:0048699	generation of neurons

Cellular Component

GO:0005829	cytosol
GO:0005875	microtubule associated complex
GO:0005886	plasma membrane
GO:0030424	axon
GO:0030426	growth cone
GO:0034399	nuclear periphery
GO:0036464	cytoplasmic ribonucleoprotein granule
GO:0045298	tubulin complex