Ser422
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.5.8
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Ser422  -  Tau iso8 (human)

Site Information
GsIDMVDsPQLAtLA   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449083

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 25 ) , electrophoretic mobility shift ( 15 ) , mass spectrometry ( 3 , 12 , 15 ) , mutation of modification site ( 7 ) , phospho-antibody ( 2 , 3 , 5 , 7 , 8 , 9 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 23 , 26 ) , western blotting ( 2 , 3 , 5 , 7 , 8 , 9 , 13 , 16 , 19 , 20 , 26 )
Disease tissue studied:
Alzheimer's disease ( 7 , 8 , 9 , 12 , 17 ) , brain cancer ( 3 ) , glioma ( 3 ) , neuroblastoma ( 13 , 25 ) , diabetes mellitus ( 8 ) , type 2 diabetes ( 8 ) , PSP ( 19 )
Relevant cell line - cell type - tissue:
'brain, caudate-putamen' ( 19 ) , 'brain, cerebellum' ( 9 ) , 'brain, cerebral cortex' ( 19 , 23 ) , 'brain, embryonic' ( 26 ) , 'brain, hippocampus' ( 23 ) , 'brain, striatum' ( 19 ) , 'neuron, cerebellar granule'-brain ( 18 ) , 'neuron, cortical'-brain ( 5 ) , 'neuron, striatal'-brain ( 5 ) , brain ( 8 , 12 , 17 , 20 , 26 ) , brain [Tau iso8 (human)] ( 16 ) , CHO (fibroblast) [Tau (human), transfection] ( 25 ) , CHO (fibroblast) ( 13 ) , COS (fibroblast) ( 15 ) , H4 (glial) ( 3 ) , HEK293T (epithelial) ( 2 ) , LAN-5 (neural crest) ( 25 ) , neuron-'brain, hippocampus' ( 7 ) , SH-SY5Y (neural crest) ( 13 , 15 , 18 )

Upstream Regulation
Regulatory protein:
Tau iso8 (human) ( 7 , 13 , 16 )
Putative in vivo kinases:
DYRK1A (human) ( 2 ) , TTBK1 (human) ( 15 )
Kinases, in vitro:
AMPKA1 (human) ( 6 ) , CDK5 (human) ( 14 ) , DYRK1A (human) ( 2 ) , DYRK1A (rat) ( 11 ) , ERK1 (human) ( 24 , 25 ) , ERK2 (human) ( 1 , 25 ) , GSK3B (human) ( 14 ) , MARK1 (human) ( 6 ) , TTBK1 (human) ( 15 )
Putative upstream phosphatases:
PPP2R2A (human) ( 3 ) , PPP2R5D (human) ( 3 )
Treatments:
mutation ( 21 ) , okadaic_acid ( 3 , 18 ) , salicylate ( 18 )

Downstream Regulation
Effects of modification on Tau iso8:
molecular association, regulation ( 15 , 21 ) , O-GlcNAc glycosylation ( 9 ) , protein processing ( 17 )
Effects of modification on biological processes:
cytoskeletal reorganization ( 20 )
Induce interaction with:
Tau (human) ( 15 ) , Tau iso8 (human) ( 21 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 3 , 5 , 8 , 9 , 17 ) , ALS ( 26 ) , DLB ( 5 ) , type 2 diabetes ( 8 ) , Parkinson's disease ( 5 , 26 )

References 

1

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

2

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

3

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

4

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

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

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

7

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

8

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

9

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

10

Eun Jeoung L, et al. (2008) Regulation of glycogen synthase kinase 3beta functions by modification of the small ubiquitin-like modifier. Open Biochem J 2, 67-76
18949077   Curated Info

11

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

12

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

13

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

14

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

15

Sato S, Cerny RL, Buescher JL, Ikezu T (2006) Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation. J Neurochem 98, 1573-84
16923168   Curated Info

16

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

17

Guillozet-Bongaarts AL, et al. (2006) Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: in vitro evidence and implications for tangle formation in vivo. J Neurochem 97, 1005-14
16606369   Curated Info

18

Tortosa E, Avila J, Pérez M (2006) Acetylsalicylic acid decreases tau phosphorylation at serine 422. Neurosci Lett 396, 77-80
16386371   Curated Info

19

Puig B, Rey MJ, Ferrer I (2005) Individual and regional variations of phospho-tau species in progressive supranuclear palsy. Acta Neuropathol (Berl) 110, 261-8
15973541   Curated Info

20

Pérez M, et al. (2005) Characterization of a double (amyloid precursor protein-tau) transgenic: tau phosphorylation and aggregation. Neuroscience 130, 339-47
15664690   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, 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

23

Götz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293, 1491-5
11520988   Curated Info

24

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

25

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

26

Mawal-Dewan M, et al. (1996) Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex. J Neuropathol Exp Neurol 55, 1051-9
8858002   Curated Info