Ser246
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Home > Phosphorylation Site Page: > Ser246  -  HDAC4 (human)

Site Information
FPLRkTAsEPNLKLR   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448488
Available spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 1 ) , mass spectrometry ( 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ) , mutation of modification site ( 1 , 3 , 42 ) , phospho-antibody ( 1 , 2 , 4 , 8 , 40 , 41 ) , western blotting ( 1 , 2 , 4 , 8 , 40 )
Disease tissue studied:
bone cancer ( 8 ) , breast cancer ( 9 ) , breast ductal carcinoma ( 9 ) , HER2 positive breast cancer ( 5 ) , luminal A breast cancer ( 5 ) , luminal B breast cancer ( 5 ) , breast cancer, surrounding tissue ( 5 ) , breast cancer, triple negative ( 5 , 9 ) , cervical cancer ( 39 ) , cervical adenocarcinoma ( 39 ) , gastric cancer ( 20 , 30 , 38 ) , gastric carcinoma ( 30 , 38 ) , lung cancer ( 16 , 25 , 26 , 27 , 32 , 33 , 34 , 36 , 37 ) , non-small cell lung cancer ( 19 , 25 , 26 , 27 , 33 , 34 , 37 ) , non-small cell lung adenocarcinoma ( 16 , 25 ) , non-small cell squamous cell lung carcinoma ( 26 , 27 ) , ovarian cancer ( 4 , 9 ) , pancreatic ductal adenocarcinoma ( 11 ) , melanoma skin cancer ( 6 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
NAC1 (human) ( 4 )
Putative in vivo kinases:
MARK2 (human) ( 1 , 41 ) , TAK1 (human) ( 41 )
Kinases, in vitro:
MARK2 (human) ( 1 )
Treatments:
cAMP_analog ( 2 ) , Go_6976 ( 40 ) , hypoxia ( 4 ) , KN-93 ( 40 ) , okadaic_acid ( 8 ) , PTH ( 8 ) , siRNA ( 1 ) , staurosporine ( 41 ) , VEGF ( 40 )

Downstream Regulation
Effects of modification on HDAC4:
intracellular localization ( 4 , 41 , 42 , 43 ) , molecular association, regulation ( 1 , 42 , 43 ) , protein degradation ( 4 ) , protein stabilization ( 8 )
Effects of modification on biological processes:
apoptosis, inhibited ( 1 ) , carcinogenesis, induced ( 1 ) , cell cycle regulation ( 1 ) , transcription, altered ( 42 ) , transcription, induced ( 1 )
Induce interaction with:
14-3-3 beta (human) ( 42 , 43 ) , 14-3-3 epsilon (human) ( 43 ) , YAP1 (human) ( 1 )
Inhibit interaction with:
LATS2 (human) ( 1 )

References 

1

Zeng Y, et al. (2022) MARK2 regulates chemotherapeutic responses through class IIa HDAC-YAP axis in pancreatic cancer. Oncogene
35780183   Curated Info

2

He T, et al. (2020) Cyclic AMP represses pathological MEF2 activation by myocyte-specific hypo-phosphorylation of HDAC5. J Mol Cell Cardiol 145, 88-98
32485181   Curated Info

3

Gomis-Coloma C, et al. (2018) Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional program of Schwann cells. J Cell Biol
29472387   Curated Info

4

Zhang Y, et al. (2017) Nucleus accumbens-associated protein-1 promotes glycolysis and survival of hypoxic tumor cells via the HDAC4-HIF-1α axis. Oncogene 36, 4171-4181
28319066   Curated Info

5

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

6

Stuart SA, et al. (2015) A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells. Mol Cell Proteomics 14, 1599-615
25850435   Curated Info

7

Sharma K, et al. (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8, 1583-94
25159151   Curated Info

8

Shimizu E, Nakatani T, He Z, Partridge NC (2014) Parathyroid Hormone Regulates Histone Deacetylase (HDAC) 4 through Protein Kinase A-mediated Phosphorylation and Dephosphorylation in Osteoblastic Cells. J Biol Chem 289, 21340-50
24904057   Curated Info

9

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

10

Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62
24275569   Curated Info

11

Britton D, et al. (2014) Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. PLoS One 9, e90948
24670416   Curated Info

12

Rikova K, Hall B (2013) CST Curation Set: 20734, 21161, 30112, 30153, 30154; Year: 2013; Biosample/Treatment: cell line, H1417, DMS79, H128, H209, H524; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

13

Rikova K, Hall B (2013) CST Curation Set: 20737, 21164, 30161, 30162, 30163; Year: 2013; Biosample/Treatment: cell line, H1299, H1944, H358, H1734, H460; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

14

Rikova K, Hall B (2013) CST Curation Set: 20738, 21165, 30164, 30165, 30166; Year: 2013; Biosample/Treatment: cell line, H1650, HCC827, H1975, Calu-3, H2106; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

15

Masui K, et al. (2013) mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc. Cell Metab 18, 726-39
24140020   Curated Info

16

Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96
23911959   Curated Info

17

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
23749302   Curated Info

18

Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21
23312004   Curated Info

19

Rikova K (2013) CST Curation Set: 18857; Year: 2013; Biosample/Treatment: cell line, H3122/crizotinib, geldanamycin; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST](PSD)
Curated Info

20

Rikova K (2012) CST Curation Set: 15872; Year: 2012; Biosample/Treatment: cell line, MKN45/crizotinib; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST](PSD)
Curated Info

21

Mulhern D (2012) CST Curation Set: 13112; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

22

Mulhern D (2011) CST Curation Set: 13106; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

23

Rikova K (2011) CST Curation Set: 13122; Year: 2011; Biosample/Treatment: cell line, MGH-10/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

24

Mulhern D (2011) CST Curation Set: 12711; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]XP
Curated Info

25

Rikova K (2011) CST Curation Set: 10885; Year: 2011; Biosample/Treatment: cell line, NCI-H2342/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

26

Rikova K (2011) CST Curation Set: 10891; Year: 2011; Biosample/Treatment: cell line, LOU-NH91/untreated; Disease: non-small cell squamous cell lung carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

27

Rikova K (2011) CST Curation Set: 10911; Year: 2011; Biosample/Treatment: cell line, NCI-H520/untreated; Disease: non-small cell squamous cell lung carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

28

Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3
21406692   Curated Info

29

Rikova K (2010) CST Curation Set: 10047; Year: 2010; Biosample/Treatment: cell line, Jurkat A/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

30

Rikova K (2010) CST Curation Set: 10046; Year: 2010; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

31

Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53
20363803   Curated Info

32

Rikova K (2010) CST Curation Set: 9755; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

33

Rikova K (2010) CST Curation Set: 9765; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

34

Rikova K (2010) CST Curation Set: 9751; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

35

Rikova K (2010) CST Curation Set: 9774; Year: 2010; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

36

Rikova K (2010) CST Curation Set: 9770; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

37

Rikova K (2010) CST Curation Set: 9758; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

38

Rikova K (2010) CST Curation Set: 9773; Year: 2010; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

39

Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3
20068231   Curated Info

40

Wang S, et al. (2008) Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7. Proc Natl Acad Sci U S A 105, 7738-43
18509061   Curated Info

41

Dequiedt F, et al. (2006) New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases. Mol Cell Biol 26, 7086-102
16980613   Curated Info

42

Wang AH, et al. (2000) Regulation of histone deacetylase 4 by binding of 14-3-3 proteins. Mol Cell Biol 20, 6904-12
10958686   Curated Info

43

Grozinger CM, Schreiber SL (2000) Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization. Proc Natl Acad Sci U S A 97, 7835-40
10869435   Curated Info