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Details on Person UniProt:P10636 MAPT
| Class:Id | ReferenceGeneProduct:69947 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:2-758 added on Sat February 7 2015;initiator methionine:1 for 69947 removed on Fri Nov 03 2023;initiator methionine: for 69947 added on Fri Nov 03 2023;initiator methionine: for 69947 removed on Fri Aug 15 2025;initiator methionine:1 for 69947 added on Fri Aug 15 2025 |
| _displayName | UniProt:P10636 MAPT |
| _timestamp | 2025-08-15 21:03:57 |
| chain | initiator methionine:1 chain:2-758 |
| checksum | D46C66CDBCD196E8 |
| comment | FUNCTION Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). 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 (PubMed:21985311, PubMed:32961270). 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.SUBUNIT Interacts with MARK1, MARK2, MARK3 and MARK4 (PubMed:23666762). Interacts with PSMC2 through SQSTM1 (By similarity). Interacts with SQSTM1 when polyubiquitinated (PubMed:15953362). Interacts with FKBP4 (By similarity). Binds to CSNK1D (PubMed:14761950). Interacts with SGK1 (PubMed:16982696). Interacts with EPM2A; the interaction dephosphorylates MAPT at Ser-396 (PubMed:19542233). Interacts with PIN1 (PubMed:11313338). Interacts with LRRK2 (PubMed:26014385). Interacts with LRP1, leading to endocytosis; this interaction is reduced in the presence of LRPAP1/RAP (PubMed:32296178).INTERACTION Mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components (PubMed:10747907). 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 (PubMed:32272059).ALTERNATIVE PRODUCTS Additional isoforms seem to exist. Isoforms differ from each other by the presence or absence of up to 5 of the 15 exons. One of these optional exons contains the additional tau/MAP repeat.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.DEVELOPMENTAL STAGE Four-repeat (type II) TAU/MAPT is expressed in an adult-specific manner and is not found in fetal brain, whereas three-repeat (type I) TAU/MAPT is found in both adult and fetal brain.DOMAIN The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.PTM 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, MARK2, MARK3 or MARK4), causing detachment from microtubules, and their disassembly (PubMed:23666762, PubMed:7706316). 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 (PubMed:7706316). 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.PTM 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.PTM 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%.PTM 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.DISEASE 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.ONLINE INFORMATION MAPT mutationsONLINE INFORMATION Vita minima - Issue 68 of March 2006ONLINE INFORMATION Tau protein entry |
| description | recommendedName: fullName evidence="80"Microtubule-associated protein tau alternativeName: Neurofibrillary tangle protein alternativeName: Paired helical filament-tau shortName: PHF-tau |
| geneName | MAPT MAPTL MTBT1 TAU |
| identifier | P10636 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Alzheimer disease Cell membrane Cell projection Cytoplasm Cytoskeleton Direct protein sequencing Disease variant Disulfide bond Glycation Glycoprotein Isopeptide bond Membrane Methylation Microtubule Neurodegeneration Parkinsonism Phosphoprotein Proteomics identification Reference proteome Repeat Secreted Ubl conjugation |
| modified | [InstanceEdit:84067] Schmidt, EE, 2003-12-18 04:29:09 [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:4341137] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8934940] Weiser, JD [InstanceEdit:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9698430] Weiser, JD [InstanceEdit:9706439] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9819394] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | MAPT |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9004423] ENSEMBL:ENSG00000186868 MAPT [Homo sapiens] |
| secondaryIdentifier | TAU_HUMAN P18518 Q14799 Q15549 Q15550 Q15551 Q1RMF6 Q53YB1 Q5CZI7 Q5XWF0 Q6QT54 Q9UDJ3 Q9UMH0 Q9UQ96 |
| sequenceLength | 758 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:154706] UniProt:P10636-2 MAPT [Homo sapiens] [ReferenceIsoform:154707] UniProt:P10636-3 MAPT [Homo sapiens] [ReferenceIsoform:154708] UniProt:P10636-4 MAPT [Homo sapiens] [ReferenceIsoform:154709] UniProt:P10636-5 MAPT [Homo sapiens] [ReferenceIsoform:154710] UniProt:P10636-6 MAPT [Homo sapiens] [ReferenceIsoform:154711] UniProt:P10636-7 MAPT [Homo sapiens] [ReferenceIsoform:154712] UniProt:P10636-8 MAPT [Homo sapiens] [ReferenceIsoform:250570] UniProt:P10636-9 MAPT [Homo sapiens] [ReferenceIsoform:402759] UniProt:P10636-1 MAPT [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:201574] MAPT [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:350628] MAPT(2-421) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:350642] MAPT(422-758) [cytosol] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P10636 MAPT (69947)
