Ser259
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Home > Phosphorylation Site Page: > Ser259  -  HDAC5 (human)

Site Information
FPLRkTAsEPNLKVR   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447995
Available spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 1 , 49 ) , mass spectrometry ( 2 , 4 , 5 , 8 , 9 , 10 , 11 , 12 , 16 , 18 , 21 , 22 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 45 ) , mutation of modification site ( 13 , 27 , 46 , 48 , 49 , 51 ) , phospho-antibody ( 1 , 13 , 20 , 33 , 47 , 48 , 49 , 50 ) , western blotting ( 1 , 13 , 20 , 27 , 33 , 47 , 48 , 49 )
Disease tissue studied:
bone cancer ( 27 ) , breast cancer ( 8 ) , HER2 positive breast cancer ( 2 ) , luminal A breast cancer ( 2 ) , luminal B breast cancer ( 2 ) , breast cancer, surrounding tissue ( 2 ) , breast cancer, triple negative ( 2 , 8 ) , cervical cancer ( 45 ) , cervical adenocarcinoma ( 45 ) , colorectal cancer ( 13 ) , colorectal carcinoma ( 13 ) , gastric cancer ( 21 , 35 , 43 ) , gastric carcinoma ( 35 , 43 ) , lung cancer ( 29 , 30 , 31 , 37 , 38 , 39 , 41 , 42 ) , non-small cell lung cancer ( 18 , 29 , 30 , 31 , 38 , 39 , 42 ) , non-small cell lung adenocarcinoma ( 29 ) , non-small cell squamous cell lung carcinoma ( 30 , 31 ) , melanoma skin cancer ( 4 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' ( 49 ) , 'neuron, cortical' ( 20 ) , 10T1/2 (fibroblast) ( 51 ) , 293 (epithelial) ( 27 , 46 , 50 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 36 ) , ARVM (myocyte) ( 1 ) , BAEC (endothelial) ( 48 ) , breast ( 2 , 8 ) , Calu-3 (pulmonary) ( 12 ) , COS (fibroblast) ( 33 , 49 , 51 ) , DMS79 (pulmonary) ( 10 ) , HAEC (endothelial) ( 47 ) , HCC827 (pulmonary) ( 12 ) , HCT116 (intestinal) ( 13 ) , HeLa (cervical) ( 5 ) , HeLa S3 (cervical) ( 45 ) , HUES-9 ('stem, embryonic') ( 32 ) , Jurkat (T lymphocyte) ( 16 , 22 , 24 , 26 , 34 , 40 ) , liver ( 9 ) , LOU-NH91 (squamous) ( 30 ) , lung ( 10 , 11 , 12 , 37 , 38 , 39 , 41 , 42 ) , MKN-45 (gastric) ( 21 , 35 , 43 ) , NCI-H128 (pulmonary) ( 10 ) , NCI-H1299 (pulmonary) ( 11 ) , NCI-H1417 (pulmonary) ( 10 ) , NCI-H1650 (pulmonary) ( 12 ) , NCI-H1734 (pulmonary) ( 11 ) , NCI-H1944 (pulmonary) ( 11 ) , NCI-H1975 (pulmonary) ( 12 ) , NCI-H209 (pulmonary) ( 10 ) , NCI-H2106 (pulmonary) ( 12 ) , NCI-H2342 (pulmonary) ( 29 ) , NCI-H3122 (pulmonary) ( 18 ) , NCI-H358 (pulmonary) ( 11 ) , NCI-H460 (pulmonary) ( 11 ) , NCI-H520 (squamous) ( 31 ) , NCI-H524 (pulmonary) ( 10 ) , U2OS (bone cell) ( 27 ) , WM239A (epidermal) ( 4 )

Upstream Regulation
Putative in vivo kinases:
AMPKA1 (human) ( 49 ) , AMPKA2 (human) ( 49 ) , CAMK1A (human) ( 51 ) , CAMK2A (human) ( 14 ) , CAMK4 (human) ( 51 ) , MARK2 (human) ( 50 ) , PRKD1 (human) ( 48 ) , TAK1 (human) ( 50 )
Kinases, in vitro:
AMPKA1 (human) ( 49 ) , CAMK4 (human) ( 51 ) , PKCD (human) ( 28 )
Putative upstream phosphatases:
PPP2R2A (human) ( 1 )
Treatments:
acadesine ( 49 ) , BDNF ( 20 ) , CGP_20712A ( 1 ) , etoposide ( 13 ) , GF109203X ( 48 ) , Go_6976 ( 47 , 48 ) , isoproterenol ( 1 ) , KN-92 ( 13 ) , KN-93 ( 13 , 47 ) , LY294002 ( 48 ) , N6-benzoyl-cAMP ( 1 ) , okadaic_acid ( 1 ) , phorbol_ester ( 33 ) , Ro31-8425 ( 48 ) , staurosporine ( 50 ) , tiron ( 13 ) , U73122 ( 48 ) , VEGF ( 47 , 48 )

Downstream Regulation
Effects of modification on HDAC5:
enzymatic activity, inhibited ( 27 ) , intracellular localization ( 1 , 13 , 48 , 49 , 50 , 51 ) , molecular association, regulation ( 27 , 49 )
Effects of modification on biological processes:
apoptosis, induced ( 13 ) , cell cycle regulation ( 13 ) , cell differentiation, altered ( 51 ) , cell motility, altered ( 48 ) , chromatin organization, altered ( 49 ) , transcription, altered ( 48 ) , transcription, induced ( 13 , 49 )
Induce interaction with:
14-3-3 beta (human) ( 46 , 49 ) , 14-3-3 epsilon (human) ( 27 ) , N-CoR1 (human) ( 27 )
Inhibit interaction with:
GPS2 (human) ( 27 ) , HDAC3 (human) ( 27 ) , PRKD1 (human) ( 27 ) , PRKD2 (human) ( 27 ) , PRKD3 (human) ( 27 ) , SMRT (human) ( 27 ) , TBL1X (human) ( 27 ) , TBL1XR1 (human) ( 27 )

References 

1

Weeks KL, et al. (2017) β-Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α-PP2A-Mediated Dephosphorylation. J Am Heart Assoc 6
28343149   Curated Info

2

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

3

Masui K, et al. (2015) Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance. Proc Natl Acad Sci U S A 112, 9406-11
26170313   Curated Info

4

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

5

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

6

Baertschi S, et al. (2014) Class I and IIa Histone Deacetylases Have Opposite Effects on Sclerostin Gene Regulation. J Biol Chem 289, 24995-5009
25012661   Curated Info

7

Lee CW, et al. (2014) Interaction between Salt-inducible Kinase 2 and Protein Phosphatase 2A Regulates the Activity of Calcium/Calmodulin-dependent Protein Kinase I and Protein Phosphatase Methylesterase-1. J Biol Chem 289, 21108-21119
24841198   Curated Info

8

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

9

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

10

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

11

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

12

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

13

Sen N, Kumari R, Singh MI, Das S (2013) HDAC5, a key component in temporal regulation of p53-mediated transactivation in response to genotoxic stress. Mol Cell 52, 406-20
24120667   Curated Info

14

Kim SS, Benchimol S (2013) HDAC5--a critical player in the p53 acetylation network. Mol Cell 52, 289-90
24207022   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

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

17

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

18

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

19

Chang CW, et al. (2013) Acute β-Adrenergic Activation Triggers Nuclear Import of Histone Deacetylase 5 and Delays Gq-induced Transcriptional Activation. J Biol Chem 288, 192-204
23161540   Curated Info

20

Finsterwald C, Carrard A, Martin JL (2013) Role of salt-inducible kinase 1 in the activation of MEF2-dependent transcription by BDNF. PLoS One 8, e54545
23349925   Curated Info

21

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

22

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

23

Taniguchi M, et al. (2012) Histone deacetylase 5 limits cocaine reward through cAMP-induced nuclear import. Neuron 73, 108-20
22243750   Curated Info

24

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

25

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

26

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

27

Greco TM, Yu F, Guise AJ, Cristea IM (2011) Nuclear import of histone deacetylase 5 by requisite nuclear localization signal phosphorylation. Mol Cell Proteomics 10, M110.004317
21081666   Curated Info

28

Huynh QK (2011) Evidence for the phosphorylation of serine259 of histone deacetylase 5 by protein kinase Cδ. Arch Biochem Biophys 506, 173-80
21146494   Curated Info

29

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

30

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

31

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

32

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

33

Ha CH, et al. (2010) PKA phosphorylates histone deacetylase 5 and prevents its nuclear export, leading to the inhibition of gene transcription and cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 107, 15467-72
20716686   Curated Info

34

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

35

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

36

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

37

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

38

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

39

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

40

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

41

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

42

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

43

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

44

Harrison BC, et al. (2010) Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. FEBS Lett 584, 1103-10
20188095   Curated Info

45

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

46

Carnegie GK, et al. (2008) AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway. Mol Cell 32, 169-79
18951085   Curated Info

47

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

48

Ha CH, et al. (2008) Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J Biol Chem 283, 14590-9
18332134   Curated Info

49

McGee SL, et al. (2008) AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5. Diabetes 57, 860-7
18184930   Curated Info

50

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

51

McKinsey TA, Zhang CL, Lu J, Olson EN (2000) Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408, 106-11
11081517   Curated Info