Ser259

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:	immunoassay ( 4 ) , immunoprecipitation ( 2 , 8 , 15 , 50 ) , mass spectrometry ( 3 , 5 , 6 , 9 , 10 , 11 , 12 , 13 , 15 , 17 , 19 , 22 , 23 , 25 , 26 , 27 , 28 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 46 ) , mutation of modification site ( 7 , 14 , 15 , 20 , 28 , 47 , 49 , 50 , 52 ) , phospho-antibody ( 1 , 2 , 4 , 8 , 14 , 21 , 24 , 34 , 48 , 49 , 50 , 51 ) , western blotting ( 1 , 2 , 4 , 8 , 14 , 15 , 21 , 24 , 28 , 34 , 48 , 49 , 50 )
Disease tissue studied:	bone cancer ( 7 , 15 , 28 ) , brain cancer ( 4 ) , glioblastoma ( 4 ) , glioma ( 4 ) , breast cancer ( 9 ) , HER2 positive breast cancer ( 3 ) , luminal A breast cancer ( 3 ) , luminal B breast cancer ( 3 ) , breast cancer, surrounding tissue ( 3 ) , breast cancer, triple negative ( 3 , 9 ) , cervical cancer ( 46 ) , cervical adenocarcinoma ( 46 ) , colorectal cancer ( 14 , 15 ) , colorectal carcinoma ( 14 , 15 ) , gastric cancer ( 22 , 36 , 44 ) , gastric carcinoma ( 36 , 44 ) , lung cancer ( 15 , 30 , 31 , 32 , 38 , 39 , 40 , 42 , 43 ) , non-small cell lung cancer ( 15 , 19 , 30 , 31 , 32 , 39 , 40 , 43 ) , non-small cell lung adenocarcinoma ( 30 ) , non-small cell squamous cell lung carcinoma ( 31 , 32 ) , melanoma skin cancer ( 5 )
Relevant cell line - cell type - tissue:	'muscle, skeletal' ( 50 ) , 'neuron, cortical' ( 21 ) , 'neuron, striatal' ( 24 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 37 ) , 293 (epithelial) ( 28 , 47 , 51 ) , ARVM (myocyte) ( 2 ) , BAEC (endothelial) ( 49 ) , brain ( 4 ) , breast ( 3 , 9 ) , C3H10T1/2 (fibroblast) ( 52 ) , Calu-3 (pulmonary) ( 13 ) , COS (fibroblast) ( 34 , 50 , 52 ) , DMS79 (pulmonary) ( 11 ) , HAEC (endothelial) ( 48 ) , HCC827 (pulmonary) ( 13 ) , HCT116 (intestinal) ( 14 , 15 ) , HEK293T (epithelial) ( 8 ) , HeLa (cervical) ( 6 ) , HeLa S3 (cervical) ( 46 ) , HUES-9 ('stem, embryonic') ( 33 ) , Jurkat (T lymphocyte) ( 17 , 23 , 25 , 27 , 35 , 41 ) , liver ( 10 ) , LOU-NH91 (squamous) ( 31 ) , lung ( 11 , 12 , 13 , 38 , 39 , 40 , 42 , 43 ) , MKN-45 (gastric) ( 22 , 36 , 44 ) , myocyte ( 1 ) , myocyte-heart ( 20 ) , NCI-H128 (pulmonary) ( 11 ) , NCI-H1299 (pulmonary) ( 12 , 15 ) , NCI-H1417 (pulmonary) ( 11 ) , NCI-H1650 (pulmonary) ( 13 ) , NCI-H1734 (pulmonary) ( 12 ) , NCI-H1944 (pulmonary) ( 12 ) , NCI-H1975 (pulmonary) ( 13 ) , NCI-H209 (pulmonary) ( 11 ) , NCI-H2106 (pulmonary) ( 13 ) , NCI-H2342 (pulmonary) ( 30 ) , NCI-H3122 (pulmonary) ( 19 ) , NCI-H358 (pulmonary) ( 12 ) , NCI-H460 (pulmonary) ( 12 ) , NCI-H520 (squamous) ( 32 ) , NCI-H524 (pulmonary) ( 11 ) , U2OS (bone cell) ( 15 , 28 ) , U87MG (glial) ( 4 ) , UMR106 (bone cell) ( 7 ) , WM239A (melanocyte) ( 5 )

Upstream Regulation
Regulatory protein:	PKD1 (human) ( 4 )
Putative in vivo kinases:	AMPKA1 (human) ( 50 ) , AMPKA2 (human) ( 50 ) , CAMK1A (human) ( 52 ) , CAMK2A (human) ( 15 ) , CAMK4 (human) ( 52 ) , MARK2 (human) ( 51 ) , PKCA (human) ( 4 ) , PRKD1 (human) ( 49 ) , QIK (human) ( 8 ) , TAK1 (human) ( 51 )
Kinases, in vitro:	AMPKA1 (human) ( 50 ) , CAMK4 (human) ( 52 ) , PKCD (human) ( 29 )
Putative upstream phosphatases:	PPP2R2A (human) ( 2 )
Treatments:	acadesine ( 50 ) , BDNF ( 21 ) , bpkdi ( 1 ) , cAMP_analog ( 1 ) , CGP_20712A ( 2 ) , colforsin ( 24 ) , etoposide ( 14 ) , GF109203X ( 49 ) , Go_6976 ( 48 , 49 ) , isoproterenol ( 2 ) , KN-92 ( 14 ) , KN-93 ( 14 , 48 ) , LY294002 ( 49 ) , N6-benzoyl-cAMP ( 2 ) , okadaic_acid ( 2 ) , phorbol_ester ( 34 ) , Ro31-8425 ( 49 ) , staurosporine ( 51 ) , tiron ( 14 ) , U73122 ( 49 ) , VEGF ( 48 , 49 )

Downstream Regulation
Effects of modification on HDAC5:	activity, induced ( 1 ) , enzymatic activity, inhibited ( 28 ) , intracellular localization ( 1 , 2 , 7 , 8 , 14 , 24 , 49 , 50 , 51 , 52 ) , molecular association, regulation ( 8 , 28 , 50 )
Effects of modification on biological processes:	apoptosis, induced ( 14 ) , cell cycle regulation ( 14 ) , cell differentiation, altered ( 52 ) , cell growth, induced ( 15 ) , cell motility, altered ( 49 ) , chromatin organization, altered ( 50 ) , transcription, altered ( 49 ) , transcription, induced ( 8 , 14 , 50 )
Induce interaction with:	14-3-3 beta (human) ( 47 , 50 ) , 14-3-3 epsilon (human) ( 28 ) , N-CoR1 (human) ( 28 )
Inhibit interaction with:	14-3-3 beta (human) ( 8 ) , GPS2 (human) ( 28 ) , HDAC3 (human) ( 28 ) , PRKD1 (human) ( 28 ) , PRKD2 (human) ( 28 ) , PRKD3 (human) ( 28 ) , SMRT (human) ( 28 ) , TBL1X (human) ( 28 ) , TBL1XR1 (human) ( 28 )

References
1	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
2	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
3	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
4	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
5	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
6	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
7	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
8	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
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	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
12	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
13	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
14	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
15	Kim SS, Benchimol S (2013) HDAC5--a critical player in the p53 acetylation network. Mol Cell 52, 289-90 24207022 Curated Info
16	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
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	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
21	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
22	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
23	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
24	Taniguchi M, et al. (2012) Histone deacetylase 5 limits cocaine reward through cAMP-induced nuclear import. Neuron 73, 108-20 22243750 Curated Info
25	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
26	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
27	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
28	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
29	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
30	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
31	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
32	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
33	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
34	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
35	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
36	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
37	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
38	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
39	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
40	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
41	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
42	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
43	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
44	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
45	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
46	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
47	Carnegie GK, et al. (2008) AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway. Mol Cell 32, 169-79 18951085 Curated Info
48	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
49	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
50	McGee SL, et al. (2008) AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5. Diabetes 57, 860-7 18184930 Curated Info
51	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
52	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