Thr523
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Home > Phosphorylation Site Page: > Thr523  -  Tau (mouse)

Site Information
KKVAVVRtPPKsPsA   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449079

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 4 ) , immunoprecipitation ( 3 ) , mass spectrometry ( 1 , 5 , 7 , 8 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 29 ) , microscopy-colocalization with upstream kinase ( 35 ) , mutation of modification site ( 3 ) , phospho-antibody ( 3 , 4 , 6 , 10 , 24 , 25 , 26 , 27 , 28 , 31 , 32 , 33 , 34 , 35 ) , western blotting ( 3 , 4 , 6 , 10 , 24 , 25 , 26 , 27 , 28 , 32 , 33 , 35 )
Disease tissue studied:
Alzheimer's disease ( 4 , 35 ) , brain cancer ( 12 , 13 , 14 , 15 ) , neuroblastoma ( 3 , 27 , 33 ) , neuroendocrine cancer ( 12 , 13 , 14 , 15 ) , melanoma skin cancer ( 18 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 7 ) , 'brain, cerebellum' ( 32 ) , 'brain, cerebral cortex' ( 6 , 10 , 26 ) , 'brain, cerebrum' ( 32 ) , 'brain, embryonic' ( 22 , 35 ) , 'brain, forebrain' ( 23 , 34 ) , 'brain, forebrain' [CDK5R1 (mouse), transgenic] ( 34 ) , 'brain, hippocampus' ( 25 , 35 ) , 'neuron, cortical' ( 28 ) , 'neuron, hippocampal, CA1 pyramidal'-brain ( 4 ) , 293 (epithelial) ( 3 ) , brain ( 11 , 12 , 13 , 14 , 15 , 17 , 19 , 20 , 21 , 24 , 29 , 35 ) , brain [CDK5R1 (mouse)] ( 24 ) , heart ( 8 ) , liver ( 1 ) , Neuro-2a (neuron) ( 27 , 33 ) , neuron-'brain, hippocampus' ( 3 ) , SH-SY5Y (neural crest) ( 3 ) , skin [mGluR1 (mouse), transgenic, TG mutant mice] ( 18 ) , stromal ( 5 )

Upstream Regulation
Regulatory protein:
APP (mouse) ( 27 ) , CDK5R1 (mouse) ( 24 ) , DVL1 (mouse) ( 33 ) , NMNAT2 (human) ( 10 ) , NPC1 (mouse) ( 32 )
Treatments:
antichymotrypsin ( 26 ) , beta-amyloid_42 ( 3 ) , cold_water_stress ( 25 ) , ether ( 25 ) , fasting ( 30 ) , food deprivation ( 25 ) , H2O2 ( 28 ) , insulin ( 7 , 31 ) , juglone ( 28 ) , lithium ( 27 ) , okadaic_acid ( 10 ) , seliciclib ( 4 , 27 ) , trichostatin_A ( 9 )

Downstream Regulation
Effects of modification on Tau:
intracellular localization ( 6 ) , phosphorylation ( 3 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 4 )

References 

1

Robles MS, Humphrey SJ, Mann M (2017) Phosphorylation Is a Central Mechanism for Circadian Control of Metabolism and Physiology. Cell Metab 25, 118-127
27818261   Curated Info

2

Sacco F, et al. (2016) Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. Nat Commun 7, 13250
27841257   Curated Info

3

Kam TI, et al. (2016) FcγRIIb-SHIP2 axis links Aβ to tau pathology by disrupting phosphoinositide metabolism in Alzheimer's disease model. Elife 5
27834631   Curated Info

4

Li K, et al. (2016) Olfactory Deprivation Hastens Alzheimer-Like Pathologies in a Human Tau-Overexpressed Mouse Model via Activation of cdk5. Mol Neurobiol 53, 391-401
25465240   Curated Info

5

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

6

Sahara N, et al. (2014) Biochemical Distribution of Tau Protein in Synaptosomal Fraction of Transgenic Mice Expressing Human P301L Tau. Front Neurol 5, 26
24653715   Curated Info

7

Humphrey SJ, et al. (2013) Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metab 17, 1009-20
23684622   Curated Info

8

Lundby A, et al. (2013) In vivo phosphoproteomics analysis reveals the cardiac targets of β-adrenergic receptor signaling. Sci Signal 6, rs11
23737553   Curated Info

9

Ando K, et al. (2013) Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker. Neurobiol Aging 34, 757-69
22926167   Curated Info

10

Cheng XS, et al. (2013) Nmnat2 attenuates Tau phosphorylation through activation of PP2A. J Alzheimers Dis 36, 185-95
23579329   Curated Info

11

Goswami T, et al. (2012) Comparative phosphoproteomic analysis of neonatal and adult murine brain. Proteomics 12, 2185-9
22807455   Curated Info

12

Guo A (2011) CST Curation Set: 12728; Year: 2011; Biosample/Treatment: tissue, brain/untreated; Disease: brain cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

13

Guo A (2011) CST Curation Set: 12729; Year: 2011; Biosample/Treatment: tissue, brain/untreated; Disease: brain cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

14

Guo A (2011) CST Curation Set: 12734; Year: 2011; Biosample/Treatment: tissue, brain/untreated; Disease: brain cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) CDKs Substrate Antibody Cat#: 2324, PTMScan(R) Phospho-CDK Substrate Motif (K/RS*PXK/R) Immunoaffinity Beads Cat#: 1981
Curated Info

15

Guo A (2011) CST Curation Set: 12739; Year: 2011; Biosample/Treatment: tissue, brain/untreated; Disease: brain cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: PXpSP, pSPX(K/R) Antibodies Used to Purify Peptides prior to LCMS: Phospho-MAPK/CDK Substrates (PXSP or SPXR/K) (34B2) Rabbit mAb Cat#: 2325, PTMScan(R) Phospho-MAPK/CDK Substrate Motif (PXS*P, S*PXK/R) Immunoaffinity Beads Cat#: 1982
Curated Info

16

Thornton C, et al. (2011) AMP-activated protein kinase (AMPK) is a tau kinase, activated in response to amyloid β-peptide exposure. Biochem J 434, 503-12
21204788   Curated Info

17

Wiśniewski JR, et al. (2010) Brain phosphoproteome obtained by a FASP-based method reveals plasma membrane protein topology. J Proteome Res 9, 3280-9
20415495   Curated Info

18

Zanivan S, et al. (2008) Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry. J Proteome Res 7, 5314-26
19367708   Curated Info

19

Guo A (2008) CST Curation Set: 5005; Year: 2008; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) CDKs Substrate Antibody Cat#: 2324, PTMScan(R) Phospho-CDK Substrate Motif (K/RS*PXK/R) Immunoaffinity Beads Cat#: 1981
Curated Info

20

Guo A (2008) CST Curation Set: 5007; Year: 2008; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) CDKs Substrate Antibody Cat#: 2324, PTMScan(R) Phospho-CDK Substrate Motif (K/RS*PXK/R) Immunoaffinity Beads Cat#: 1981
Curated Info

21

Zhou J (2008) CST Curation Set: 4863; Year: 2008; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-Thr-Pro Motif Antibody (polyAB) Cat#: 3003, PTMScan(R) Phospho-Thr-Pro Motif (T*P) Immunoaffinity Beads Cat#: 1996
Curated Info

22

Zhou J (2008) CST Curation Set: 4864; Year: 2008; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-Thr-Pro Motif Antibody (polyAB) Cat#: 3003, PTMScan(R) Phospho-Thr-Pro Motif (T*P) Immunoaffinity Beads Cat#: 1996
Curated Info

23

Collins MO, et al. (2008) Phosphoproteomic analysis of the mouse brain cytosol reveals a predominance of protein phosphorylation in regions of intrinsic sequence disorder. Mol Cell Proteomics 7, 1331-48
18388127   Curated Info

24

Wen Y, et al. (2008) Interplay between cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta mediated by neuregulin signaling leads to differential effects on tau phosphorylation and amyloid precursor protein processing. J Neurosci 28, 2624-32
18322105   Curated Info

25

Ikeda Y, Ishiguro K, Fujita SC (2007) Ether stress-induced Alzheimer-like tau phosphorylation in the normal mouse brain. FEBS Lett 581, 891-7
17289030   Curated Info

26

Padmanabhan J, Levy M, Dickson DW, Potter H (2006) Alpha1-antichymotrypsin, an inflammatory protein overexpressed in Alzheimer's disease brain, induces tau phosphorylation in neurons. Brain 129, 3020-34
16987932   Curated Info

27

Wang ZF, et al. (2006) Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture. J Neurochem 98, 1167-75
16762022   Curated Info

28

Galas MC, et al. (2006) The peptidylprolyl cis/trans-isomerase Pin1 modulates stress-induced dephosphorylation of Tau in neurons. Implication in a pathological mechanism related to Alzheimer disease. J Biol Chem 281, 19296-304
16675464   Curated Info

29

Trinidad JC, et al. (2006) Comprehensive identification of phosphorylation sites in postsynaptic density preparations. Mol Cell Proteomics 5, 914-22
16452087   Curated Info

30

Li X, Lu F, Wang JZ, Gong CX (2006) Concurrent alterations of O-GlcNAcylation and phosphorylation of tau in mouse brains during fasting. Eur J Neurosci 23, 2078-86
16630055   Curated Info

31

Freude S, et al. (2005) Peripheral hyperinsulinemia promotes tau phosphorylation in vivo. Diabetes 54, 3343-8
16306348   Curated Info

32

Yu W, Ko M, Yanagisawa K, Michikawa M (2005) Neurodegeneration in heterozygous Niemann-Pick type C1 (NPC1) mouse: implication of heterozygous NPC1 mutations being a risk for tauopathy. J Biol Chem 280, 27296-302
15919659   Curated Info

33

Wang HH, et al. (2005) Overexpression of dishevelled-1 attenuates wortmannin-induced hyperphosphorylation of cytoskeletal proteins in N2a cell. Acta Pharmacol Sin 26, 679-84
15916733   Curated Info

34

Cruz JC, et al. (2003) Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40, 471-83
14642273   Curated Info

35

Jicha GA, et al. (1999) cAMP-dependent protein kinase phosphorylations on tau in Alzheimer's disease. J Neurosci 19, 7486-94
10460255   Curated Info