Ser498
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Home > Phosphorylation Site Page: > Ser498  -  HDAC5 (human)

Site Information
RPLSRtQsSPLPQsP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447996

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 2 , 21 ) , mass spectrometry ( 3 , 7 , 9 , 11 , 15 , 16 ) , mutation of modification site ( 4 , 5 , 8 , 11 , 17 , 20 , 21 , 24 ) , phospho-antibody ( 1 , 2 , 5 , 8 , 10 , 13 , 18 , 19 , 20 , 21 , 23 ) , western blotting ( 1 , 2 , 5 , 8 , 10 , 11 , 13 , 18 , 19 , 20 , 21 )
Disease tissue studied:
bone cancer ( 4 , 11 ) , colorectal cancer ( 5 ) , colorectal carcinoma ( 5 ) , neuroblastoma ( 3 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' ( 21 ) , 'neuron, striatal' ( 10 ) , 293 (epithelial) ( 1 , 11 , 17 , 18 ) , ARVM (myocyte) ( 2 ) , BAEC (endothelial) ( 20 ) , C3H10T1/2 (fibroblast) ( 24 ) , COS (fibroblast) ( 1 , 13 , 21 , 24 ) , H9c2 (myoblast) ( 1 ) , HAEC (endothelial) ( 19 ) , HCT116 (intestinal) ( 5 ) , HeLa (cervical) ( 16 , 23 ) , Jurkat (T lymphocyte) ( 7 ) , K562 (erythroid) ( 9 ) , myocyte ( 1 ) , myocyte-heart ( 8 ) , NCI-H1650 (pulmonary) ( 15 ) , SK-N-BE(2) (neural crest) ( 3 ) , U2OS (bone cell) ( 11 ) , UMR106 (bone cell) ( 4 )

Upstream Regulation
Putative in vivo kinases:
AMPKA1 (human) ( 21 ) , AMPKA2 (human) ( 21 ) , CAMK1A (human) ( 24 ) , CAMK2A (human) ( 6 ) , CAMK4 (human) ( 24 ) , PRKD1 (human) ( 20 )
Kinases, in vitro:
AMPKA1 (human) ( 21 ) , CAMK4 (human) ( 24 ) , PRKD1 (human) ( 12 , 22 ) , PRKD2 (human) ( 22 ) , PRKD3 (human) ( 22 )
Treatments:
6-Bnz cAMP ( 1 ) , 8-Rp-cAMP ( 1 ) , acadesine ( 21 ) , bpkdi ( 1 ) , cAMP_analog ( 1 ) , CGP_20712A ( 2 ) , colforsin ( 8 , 10 ) , endothelin ( 8 ) , etoposide ( 5 ) , GF109203X ( 18 , 20 ) , Go_6976 ( 19 , 20 ) , Go_6983 ( 18 ) , IBMX ( 1 ) , isoproterenol ( 1 , 2 , 8 ) , KN-92 ( 5 ) , KN-93 ( 5 , 19 ) , LY294002 ( 20 ) , N6-benzoyl-cAMP ( 2 ) , NKH_477 ( 1 ) , okadaic_acid ( 2 ) , phenylephrine ( 8 ) , phorbol_ester ( 8 , 13 , 23 ) , Ro31-8220 ( 18 ) , Ro31-8425 ( 20 ) , tiron ( 5 ) , U73122 ( 20 ) , VEGF ( 19 , 20 )

Downstream Regulation
Effects of modification on HDAC5:
activity, induced ( 1 ) , enzymatic activity, inhibited ( 11 ) , intracellular localization ( 1 , 2 , 4 , 5 , 10 , 17 , 20 , 21 , 24 ) , molecular association, regulation ( 11 , 21 )
Effects of modification on biological processes:
apoptosis, induced ( 5 ) , cell cycle regulation ( 5 ) , cell differentiation, altered ( 24 ) , cell motility, altered ( 20 ) , chromatin organization, altered ( 21 ) , transcription, altered ( 20 ) , transcription, induced ( 5 , 21 )
Induce interaction with:
14-3-3 beta (human) ( 17 , 21 ) , 14-3-3 epsilon (human) ( 11 ) , N-CoR1 (human) ( 11 )
Inhibit interaction with:
GPS2 (human) ( 11 ) , HDAC3 (human) ( 11 ) , PRKD1 (human) ( 11 ) , PRKD2 (human) ( 11 ) , PRKD3 (human) ( 11 ) , SMRT (human) ( 11 ) , TBL1X (human) ( 11 ) , TBL1XR1 (human) ( 11 )

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

Palacios-Moreno J, et al. (2015) Neuroblastoma Tyrosine Kinase Signaling Networks Involve FYN and LYN in Endosomes and Lipid Rafts. PLoS Comput Biol 11, e1004130
25884760   Curated Info

4

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

5

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

6

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

7

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

8

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

9

Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71
23186163   Curated Info

10

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

11

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

12

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

13

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

14

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

15

Possemato A (2009) CST Curation Set: 8049; Year: 2009; Biosample/Treatment: cell line, NCI-H1650/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST]
Curated Info

16

Zhou J (2009) CST Curation Set: 7616; Year: 2009; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) PKD Substrate Antibody Cat#: 4381, PTMScan(R) Phospho-PKD Substrate Motif (LXRXXpS/pT) Immunoaffinity Beads Cat#: 1986
Curated Info

17

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

18

Papazyan R, et al. (2008) Protein kinase D isozymes activation and localization during mitosis. Exp Cell Res 314, 3057-68
18692497   Curated Info

19

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

20

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

21

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

22

Huynh QK, McKinsey TA (2006) Protein kinase D directly phosphorylates histone deacetylase 5 via a random sequential kinetic mechanism. Arch Biochem Biophys 450, 141-8
16584705   Curated Info

23

Döppler H, et al. (2005) A phosphorylation state-specific antibody recognizes Hsp27, a novel substrate of protein kinase D. J Biol Chem 280, 15013-9
15728188   Curated Info

24

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