Ser235
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Home > Phosphorylation Site Page: > Ser235  -  Tau iso8 (human)

Site Information
VVRtPPKsPssAKsR   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449080

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 20 , 24 , 27 ) , immunoprecipitation ( 4 ) , mass spectrometry ( 4 , 7 , 14 , 15 , 24 ) , mutation of modification site ( 1 , 3 , 9 , 11 , 12 , 18 , 20 , 25 ) , phospho-antibody ( 1 , 4 , 5 , 6 , 10 , 11 , 12 , 13 , 14 , 16 , 18 , 20 , 26 ) , western blotting ( 1 , 4 , 5 , 6 , 10 , 11 , 12 , 16 , 18 , 20 , 24 , 26 )
Disease tissue studied:
Alzheimer's disease ( 7 , 11 , 13 , 15 , 24 ) , adrenal cancer ( 9 , 12 ) , pheochromocytoma ( 9 , 12 ) , neuroblastoma ( 16 , 26 , 27 ) , PSP ( 14 )
Relevant cell line - cell type - tissue:
'neuron, cortical' ( 4 ) , 'neuron, cortical'-brain ( 5 , 20 ) , 'neuron, striatal'-brain ( 5 ) , 293 (epithelial) ( 18 ) , brain ( 1 , 6 , 7 , 14 , 15 , 24 ) , cerebrospinal fluid ( 13 ) , CHO (fibroblast) [Tau (human), transfection] ( 27 ) , CHO (fibroblast) ( 9 , 16 ) , COS (fibroblast) ( 20 ) , COS7 (fibroblast) ( 1 ) , E.coli (bacterial) ( 1 , 25 ) , LAN-5 (neural crest) ( 26 , 27 ) , lung ( 4 ) , Neuro-2a (neuron) ( 26 ) , neuron-'brain, hippocampus' ( 10 , 11 ) , PC-12 (chromaffin) ( 9 , 12 ) , SH-SY5Y (neural crest) ( 16 )

Upstream Regulation
Regulatory protein:
Tau iso8 (human) ( 11 , 16 )
Putative in vivo kinases:
CDK5 (human) ( 1 , 4 , 20 )
Kinases, in vitro:
CAMK2A (rat) ( 28 ) , CDK1 (human) ( 27 ) , CDK5 (human) ( 1 , 4 , 17 , 20 , 22 , 27 ) , ERK1 (human) ( 23 , 27 ) , ERK2 (human) ( 2 , 27 ) , GSK3A (cow) ( 28 ) , GSK3A (human) ( 25 ) , GSK3B (human) ( 23 ) , PKCA (rat) ( 28 )
Putative upstream phosphatases:
PPP2CA (rat) ( 10 )
Treatments:
MK-591 ( 6 ) , mutation ( 21 ) , okadaic_acid ( 10 )

Downstream Regulation
Effects of modification on Tau iso8:
intracellular localization ( 10 ) , molecular association, regulation ( 18 , 19 , 21 ) , phosphorylation ( 18 )
Effects of modification on biological processes:
cytoskeletal reorganization ( 18 )
Induce interaction with:
Tau iso8 (human) ( 21 )
Inhibit interaction with:
Fyn (human) ( 19 ) , TUBA4A (human) ( 18 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 5 , 7 , 13 , 24 ) , Parkinson's disease ( 5 ) , PSP ( 14 )

References 

1

Kimura T, et al. (2016) Quantitative and combinatory determination of in situ phosphorylation of tau and its FTDP-17 mutants. Sci Rep 6, 33479
27641626   Curated Info

2

Qi H, et al. (2016) Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase. J Biol Chem 291, 7742-53
26858248   Curated Info

3

Moszczynski AJ, et al. (2015) Thr(175)-phosphorylated tau induces pathologic fibril formation via GSK3β-mediated phosphorylation of Thr(231) in vitro. Neurobiol Aging 36, 1590-9
25573097   Curated Info

4

Grant NJ, et al. (2015) Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis. BMC Cancer 15, 885
26555036   Curated Info

5

Duka V, et al. (2013) Identification of the sites of tau hyperphosphorylation and activation of tau kinases in synucleinopathies and Alzheimer's diseases. PLoS One 8, e75025
24073234   Curated Info

6

Chu J, Lauretti E, Di Meco A, Praticò D (2013) FLAP pharmacological blockade modulates metabolism of endogenous tau in vivo . Transl Psychiatry 3, e333
24301651   Curated Info

7

Rudrabhatla P, Jaffe H, Pant HC (2011) Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs. FASEB J 25, 3896-905
21828286   Curated Info

8

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

9

Alonso AD, et al. (2010) Phosphorylation of tau at Thr212, Thr231, and Ser262 combined causes neurodegeneration. J Biol Chem 285, 30851-60
20663882   Curated Info

10

Bertrand J, et al. (2010) The formation of tau pathological phospho-epitopes in the axon is prevented by the dephosphorylation of selective sites in primary hippocampal neurons over-expressing human tau. J Neurochem 114, 1353-67
20550628   Curated Info

11

Bertrand J, Plouffe V, Sénéchal P, Leclerc N (2010) The pattern of human tau phosphorylation is the result of priming and feedback events in primary hippocampal neurons. Neuroscience 168, 323-34
20394726   Curated Info

12

Leugers CJ, Lee G (2010) Tau potentiates nerve growth factor-induced mitogen-activated protein kinase signaling and neurite initiation without a requirement for microtubule binding. J Biol Chem 285, 19125-34
20375017   Curated Info

13

Singer D, Soininen H, Alafuzoff I, Hoffmann R (2009) Immuno-PCR-based quantification of multiple phosphorylated tau-epitopes linked to Alzheimer's disease. Anal Bioanal Chem 395, 2263-7
19821112   Curated Info

14

Wray S, Saxton M, Anderton BH, Hanger DP (2008) Direct analysis of tau from PSP brain identifies new phosphorylation sites and a major fragment of N-terminally cleaved tau containing four microtubule-binding repeats. J Neurochem 105, 2343-52
18315566   Curated Info

15

Hanger DP, et al. (2007) Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J Biol Chem 282, 23645-54
17562708   Curated Info

16

Iliev AI, Ganesan S, Bunt G, Wouters FS (2006) Removal of pattern-breaking sequences in microtubule binding repeats produces instantaneous tau aggregation and toxicity. J Biol Chem 281, 37195-204
17008320   Curated Info

17

Sengupta A, Novak M, Grundke-Iqbal I, Iqbal K (2006) Regulation of phosphorylation of tau by cyclin-dependent kinase 5 and glycogen synthase kinase-3 at substrate level. FEBS Lett 580, 5925-33
17045592   Curated Info

18

Ding H, Matthews TA, Johnson GV (2006) Site-specific phosphorylation and caspase cleavage differentially impact tau-microtubule interactions and tau aggregation. J Biol Chem 281, 19107-14
16687396   Curated Info

19

Bhaskar K, Yen SH, Lee G (2005) Disease-related modifications in tau affect the interaction between Fyn and Tau. J Biol Chem 280, 35119-25
16115884   Curated Info

20

Sakaue F, et al. (2005) Phosphorylation of FTDP-17 mutant tau by cyclin-dependent kinase 5 complexed with p35, p25, or p39. J Biol Chem 280, 31522-9
15994305   Curated Info

21

Alonso Adel C, et al. (2004) Promotion of hyperphosphorylation by frontotemporal dementia tau mutations. J Biol Chem 279, 34873-81
15190058   Curated Info

22

Liu F, Iqbal K, Grundke-Iqbal I, Gong CX (2002) Involvement of aberrant glycosylation in phosphorylation of tau by cdk5 and GSK-3beta. FEBS Lett 530, 209-14
12387894   Curated Info

23

Schneider A, et al. (1999) Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry 38, 3549-58
10090741   Curated Info

24

Hanger DP, et al. (1998) New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry. J Neurochem 71, 2465-76
9832145   Curated Info

25

Sengupta A, et al. (1998) Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules. Arch Biochem Biophys 357, 299-309
9735171   Curated Info

26

Preuss U, Mandelkow EM (1998) Mitotic phosphorylation of tau protein in neuronal cell lines resembles phosphorylation in Alzheimer's disease. Eur J Cell Biol 76, 176-84
9716264   Curated Info

27

Illenberger S, et al. (1998) The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells: implications for Alzheimer's disease. Mol Biol Cell 9, 1495-512
9614189   Curated Info

28

Singh TJ, et al. (1997) Protein kinase C and calcium/calmodulin-dependent protein kinase II phosphorylate three-repeat and four-repeat tau isoforms at different rates. Mol Cell Biochem 168, 141-8
9062903   Curated Info