Thr205
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Home > Phosphorylation Site Page: > Thr205  -  Tau iso8 (human)

Site Information
ssPGsPGtPGsRsRt   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447933

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 38 , 50 ) , immunoprecipitation ( 8 ) , mass spectrometry ( 8 , 10 , 30 ) , microscopy-colocalization with upstream kinase ( 45 ) , mutation of modification site ( 2 , 21 , 22 , 38 , 47 ) , peptide sequencing ( 43 ) , phospho-antibody ( 2 , 5 , 6 , 7 , 8 , 10 , 13 , 17 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 41 , 42 , 45 , 47 , 49 ) , western blotting ( 2 , 5 , 6 , 8 , 10 , 17 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 31 , 32 , 34 , 35 , 36 , 38 , 43 , 45 , 47 , 49 )
Disease tissue studied:
Alzheimer's disease ( 7 , 13 , 22 , 23 , 25 , 26 , 30 , 35 , 45 ) , adrenal cancer ( 41 ) , pheochromocytoma ( 41 ) , brain cancer ( 10 , 45 ) , glioma ( 10 , 45 ) , neuroblastoma ( 32 , 47 , 49 , 50 ) , diabetes mellitus ( 25 ) , type 2 diabetes ( 25 )
Relevant cell line - cell type - tissue:
'brain, cerebellum' ( 26 ) , 'brain, cerebral cortex' ( 2 , 35 ) , 'brain, hippocampus' ( 2 , 37 ) , 'neuron, cortical' ( 8 , 28 ) , 'neuron, cortical'-brain ( 38 ) , 293 (epithelial) ( 2 , 5 , 42 ) , 293T (epithelial) ( 6 ) , brain ( 5 , 7 , 17 , 25 , 30 ) , brain [Tau iso8 (human)] ( 31 , 34 ) , CHO (fibroblast) ( 23 , 32 , 36 , 43 , 47 ) , CHO (fibroblast) [Tau (human), transfection] ( 50 ) , COS (fibroblast) ( 35 , 38 ) , H4 (glial) ( 10 , 45 ) , HeLa (cervical) ( 24 ) , LAN-5 (neural crest) ( 49 , 50 ) , lung ( 8 ) , Neuro-2a (neuron) ( 49 ) , neuron-'brain, cerebral cortex' ( 13 ) , neuron-'brain, hippocampus' ( 2 , 21 , 22 ) , PC-12 (chromaffin) ( 41 ) , SH-SY5Y (neural crest) ( 32 ) , SK-N-MC (neural crest) ( 47 )

Upstream Regulation
Regulatory protein:
OGT (human) ( 26 ) , PKN1 (human) ( 47 ) , PTEN (human) ( 35 ) , RPS23 (mouse) ( 24 ) , SET (mouse) ( 2 ) , Tau iso8 (human) ( 22 , 32 , 34 )
Putative in vivo kinases:
CDK5 (human) ( 8 , 38 ) , CK1D (human) ( 42 ) , DYRK1A (human) ( 6 ) , GSK3B (human) ( 23 ) , LRRK2 (human) ( 12 )
Kinases, in vitro:
CDK1 (human) ( 50 ) , CDK2 (human) ( 19 ) , CDK5 (human) ( 3 , 8 , 33 , 38 , 44 , 46 , 50 ) , CK1D (human) ( 42 ) , DYRK1A (human) ( 6 ) , DYRK1A (rat) ( 29 ) , ERK1 (human) ( 48 , 50 ) , ERK2 (human) ( 4 , 50 ) , GSK3B (human) ( 20 , 29 , 33 , 46 )
Putative upstream phosphatases:
PPP2CA (rat) ( 21 ) , PPP2R2A (human) ( 10 ) , PPP2R5D (human) ( 10 )
Phosphatases, in vitro:
PPP2CA (human) ( 19 , 23 )
Treatments:
acadesine ( 28 ) , arsenite ( 43 ) , chloroquine ( 36 ) , doxycycline ( 45 ) , FK506 ( 31 ) , IC261 ( 42 ) , insulin ( 28 ) , kenpaullone ( 43 ) , lithium ( 28 , 43 ) , low_glucose ( 41 ) , LY294002 ( 28 , 35 ) , MG132 ( 36 ) , mutation ( 40 ) , okadaic_acid ( 10 , 21 , 28 , 41 , 43 ) , olomoucine ( 43 ) , PUGNAc ( 41 ) , purvalanol ( 8 ) , rolipram ( 5 ) , SB203580 ( 43 ) , seliciclib ( 43 ) , siRNA ( 26 ) , streptozotocin ( 41 ) , tanespimycin ( 36 ) , U0126 ( 43 )

Downstream Regulation
Effects of modification on Tau iso8:
intracellular localization ( 7 , 21 , 45 ) , molecular association, regulation ( 12 , 40 , 42 ) , O-GlcNAc glycosylation ( 26 ) , protein conformation ( 27 )
Effects of modification on biological processes:
cytoskeletal reorganization ( 39 , 45 )
Induce interaction with:
Tau iso8 (human) ( 12 , 40 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 10 , 26 , 27 )

References 

1

Park J, et al. (2018) A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer's disease. Nat Neurosci 21, 941-951
29950669   Curated Info

2

Zhang Q, et al. (2018) CK2 Phosphorylating I/SET Mediates Tau Pathology and Cognitive Impairment. Front Mol Neurosci 11, 146
29760653   Curated Info

3

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

4

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

5

Myeku N, et al. (2016) Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. Nat Med 22, 46-53
26692334   Curated Info

6

Jin N, et al. (2015) Truncation and Activation of Dual Specificity Tyrosine Phosphorylation-regulated Kinase 1A by Calpain I: A MOLECULAR MECHANISM LINKED TO TAU PATHOLOGY IN ALZHEIMER DISEASE. J Biol Chem 290, 15219-37
25918155   Curated Info

7

Day RJ, et al. (2015) Caspase-Cleaved Tau Co-Localizes with Early Tangle Markers in the Human Vascular Dementia Brain. PLoS One 10, e0132637
26161867   Curated Info

8

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

9

Luo HB, et al. (2014) SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination. Proc Natl Acad Sci U S A 111, 16586-91
25378699   Curated Info

10

Yu UY, Yoo BC, Ahn JH (2014) Regulatory B Subunits of Protein Phosphatase 2A Are Involved in Site-specific Regulation of Tau Protein Phosphorylation. Korean J Physiol Pharmacol 18, 155-61
24757378   Curated Info

11

Mondragón-Rodríguez S, et al. (2014) Phosphorylation of tau protein at sites Ser(396-404) is one of the earliest events in Alzheimer's disease and Down syndrome. Neuropathol Appl Neurobiol 40, 121-35
24033439   Curated Info

12

Bailey RM, et al. (2013) LRRK2 phosphorylates novel tau epitopes and promotes tauopathy. Acta Neuropathol 126, 809-27
24113872   Curated Info

13

Yanamandra K, et al. (2013) Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80, 402-14
24075978   Curated Info

14

Yu G, et al. (2013) Ser9 phosphorylation causes cytoplasmic detention of I2PP2A/SET in Alzheimer disease. Neurobiol Aging 34, 1748-58
23374587   Curated Info

15

Luo Y, et al. (2013) PTPA activates protein phosphatase-2A through reducing its phosphorylation at tyrosine-307 with upregulation of protein tyrosine phosphatase 1B. Biochim Biophys Acta 1833, 1235-43
23428800   Curated Info

16

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

17

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

18

Smet-Nocca C, et al. (2011) Identification of O-GlcNAc sites within peptides of the Tau protein and their impact on phosphorylation. Mol Biosyst 7, 1420-9
21327254   Curated Info

19

Landrieu I, et al. (2011) Molecular implication of PP2A and Pin1 in the Alzheimer's disease specific hyperphosphorylation of Tau. PLoS One 6, e21521
21731772   Curated Info

20

Leroy A, et al. (2010) Spectroscopic studies of GSK3{beta} phosphorylation of the neuronal tau protein and its interaction with the N-terminal domain of apolipoprotein E. J Biol Chem 285, 33435-44
20679343   Curated Info

21

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

22

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

23

Qian W, et al. (2010) PP2A regulates tau phosphorylation directly and also indirectly via activating GSK-3beta. J Alzheimers Dis 19, 1221-9
20308788   Curated Info

24

Zhang YW, et al. (2009) A functional mouse retroposed gene Rps23r1 reduces Alzheimer's beta-amyloid levels and tau phosphorylation. Neuron 64, 328-40
19914182   Curated Info

25

Liu Y, et al. (2009) Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease. J Neurochem 111, 242-9
19659459   Curated Info

26

Liu F, et al. (2009) Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease. Brain 132, 1820-32
19451179   Curated Info

27

Jeganathan S, et al. (2008) Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of Tau and generates a pathological (MC-1) conformation. J Biol Chem 283, 32066-76
18725412   Curated Info

28

Meske V, Albert F, Ohm TG (2008) Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3 -dependent phosphorylation of Tau. J Biol Chem 283, 100-9
17971449   Curated Info

29

Liu F, et al. (2007) Site-specific effects of tau phosphorylation on its microtubule assembly activity and self-aggregation. Eur J Neurosci 26, 3429-36
18052981   Curated Info

30

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

31

Yoshiyama Y, et al. (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337-51
17270732   Curated Info

32

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

33

Liu F, et al. (2006) PKA modulates GSK-3beta- and cdk5-catalyzed phosphorylation of tau in site- and kinase-specific manners. FEBS Lett 580, 6269-74
17078951   Curated Info

34

Schindowski K, et al. (2006) Alzheimer's disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am J Pathol 169, 599-616
16877359   Curated Info

35

Zhang X, et al. (2006) Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules. FASEB J 20, 1272-4
16645045   Curated Info

36

Dickey CA, et al. (2006) HSP induction mediates selective clearance of tau phosphorylated at proline-directed Ser/Thr sites but not KXGS (MARK) sites. FASEB J 20, 753-5
16464956   Curated Info

37

Härtig W, et al. (2005) Phosphorylation of the tau protein sequence 199-205 in the hippocampal CA3 region of Syrian hamsters in adulthood and during aging. Brain Res 1056, 100-4
16095576   Curated Info

38

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

39

Necula M, Kuret J (2004) Pseudophosphorylation and glycation of tau protein enhance but do not trigger fibrillization in vitro. J Biol Chem 279, 49694-703
15364924   Curated Info

40

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

41

Liu F, et al. (2004) O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. Proc Natl Acad Sci U S A 101, 10804-9
15249677   Curated Info

42

Li G, Yin H, Kuret J (2004) Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J Biol Chem 279, 15938-45
14761950   Curated Info

43

Giasson BI, et al. (2002) The environmental toxin arsenite induces tau hyperphosphorylation. Biochemistry 41, 15376-87
12484777   Curated Info

44

Hashiguchi M, Saito T, Hisanaga S, Hashiguchi T (2002) Truncation of CDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau. J Biol Chem 277, 44525-30
12226093   Curated Info

45

DeTure M, Ko LW, Easson C, Yen SH (2002) Tau assembly in inducible transfectants expressing wild-type or FTDP-17 tau. Am J Pathol 161, 1711-22
12414518   Curated Info

46

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

47

Taniguchi T, et al. (2001) Phosphorylation of tau is regulated by PKN. J Biol Chem 276, 10025-31
11104762   Curated Info

48

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

49

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

50

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
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