| + |
CAMK2D | up-regulates 
phosphorylation
|
HDAC4 |
0.365 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151418 |
Ser210 |
YGKTQHSsLDQSSPP |
Homo sapiens |
|
| pmid |
sentence |
| 17179159 |
These results demonstrate that camkiideltab preferentially targets hdac4, and this involves serine 210overexpression of camkiideltab in primary neonatal cardiomyocytes increases the activity of the mef2 transcription factor and completely rescues hdac4-mediated repression of mef2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AURKB | down-regulates 
phosphorylation
|
HDAC4 |
0.268 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-198646 |
Ser265 |
QKVAERRsSPLLRRK |
Homo sapiens |
|
| pmid |
sentence |
| 22865920 |
We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B | down-regulates
phosphorylation
|
HDAC4 |
0.371 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-170144 |
Ser298 |
ACSSAPGsGPSSPNN |
Homo sapiens |
|
| pmid |
sentence |
| 21118993 |
The double mutation of serines 298/302 into alanines, but also the sole mutation of serine 302, abolishes hdac4 phosphorylation by gsk3_we have shown that cells lacking gsk3_ are unable to degrade hdac4 after serum starvation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-170148 |
Ser302 |
APGSGPSsPNNSSGS |
Homo sapiens |
|
| pmid |
sentence |
| 21118993 |
The double mutation of serines 298/302 into alanines, but also the sole mutation of serine 302, abolishes hdac4 phosphorylation by gsk3_we have shown that cells lacking gsk3_ are unable to degrade hdac4 after serum starvation |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | IGF and Myogenesis |
| + |
PPP2CA | up-regulates
dephosphorylation
|
HDAC4 |
0.357 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-159492 |
Ser298 |
ACSSAPGsGPSSPNN |
Homo sapiens |
|
| pmid |
sentence |
| 18045992 |
Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CAMK4 | down-regulates activity
phosphorylation
|
HDAC4 |
0.603 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250711 |
Ser467 |
RPLGRTQsAPLPQNA |
|
U2-OS Cell |
| pmid |
sentence |
| 11470791 |
CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. | Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. | Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250712 |
Ser632 |
RPLSRAQsSPASATF |
|
|
| pmid |
sentence |
| 11470791 |
CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. | Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. | Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus. |
|
| Publications: |
2 |
| Pathways: | IGF and Myogenesis |
| + |
PKA | up-regulates activity
phosphorylation
|
HDAC4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277423 |
Ser584 |
EPGQRQPsEQELLFR |
in vitro |
|
| pmid |
sentence |
| 30661366 |
In vitro kinase assays have established that Ser584 and Ser265/266 are phosphorylated by protein kinase A (PKA). Overexpression of site-specific HDAC4 mutants (S584A, S265/266A) in HEK 293T cells, followed by HDAC activity assays, revealed the mutants to be less active than the wild-type protein. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277424 |
|
|
in vitro |
|
| pmid |
sentence |
| 30661366 |
In vitro kinase assays have established that Ser584 and Ser265/266 are phosphorylated by protein kinase A (PKA). Overexpression of site-specific HDAC4 mutants (S584A, S265/266A) in HEK 293T cells, followed by HDAC activity assays, revealed the mutants to be less active than the wild-type protein. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277425 |
|
|
in vitro |
|
| pmid |
sentence |
| 30661366 |
In vitro kinase assays have established that Ser584 and Ser265/266 are phosphorylated by protein kinase A (PKA). Overexpression of site-specific HDAC4 mutants (S584A, S265/266A) in HEK 293T cells, followed by HDAC activity assays, revealed the mutants to be less active than the wild-type protein. |
|
| Publications: |
3 |
Organism: |
In Vitro |
| + |
belinostat | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257743 |
|
|
in vitro |
|
| pmid |
sentence |
| 17868033 |
Our findings suggest that hydroxamic acid-derived compounds such as TSA, NVP-LAQ824, panobinostat, ITF2357, vorinostat and belinostat act as potent pan-HDAC isoform inhibitors. A notable observation was the similarity between belinostat and vorinostat in the biochemical isoform assays; both compounds exhibit similar EC50 values in all but the HDAC8 assay. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257957 |
|
|
in vitro |
|
| pmid |
sentence |
| 20139990 |
Collaboratively, we synthesized and assembled a panel of structurally-diverse small-molecule HDACi 1, 2, 7-20 that comprise most of the relevant literature-reported tool compounds and pharmaceutically developed clinical candidates (Supplementary Fig 3). We next conducted a high-throughput, precise profiling of HDACi potency against all Class I and II enzymes, in a miniaturized dose-ranging format (Supplementary Table 1). |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
vorinostat | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257922 |
|
|
in vitro |
|
| pmid |
sentence |
| 17868033 |
Our findings suggest that hydroxamic acid-derived compounds such as TSA, NVP-LAQ824, panobinostat, ITF2357, vorinostat and belinostat act as potent pan-HDAC isoform inhibitors. A notable observation was the similarity between belinostat and vorinostat in the biochemical isoform assays; both compounds exhibit similar EC50 values in all but the HDAC8 assay. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
6-(1,3-dioxo-2-benzo[de]isoquinolinyl)-N-hydroxyhexanamide | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257998 |
|
|
in vitro |
|
| pmid |
sentence |
| 20139990 |
Collaboratively, we synthesized and assembled a panel of structurally-diverse small-molecule HDACi 1, 2, 7-20 that comprise most of the relevant literature-reported tool compounds and pharmaceutically developed clinical candidates (Supplementary Fig 3). We next conducted a high-throughput, precise profiling of HDACi potency against all Class I and II enzymes, in a miniaturized dose-ranging format (Supplementary Table 1). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
RELA | up-regulates
binding
|
HDAC4 |
0.322 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-138368 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15988006 |
P65 and histone deacetylases 4 cooperate to inhibit the ability of mef2 factors to induce the klf2 promoter |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HDAC4 | down-regulates quantity by repression 
transcriptional regulation
|
HOXB13 |
0.264 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254232 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19013255 |
Recruitment of HDAC4 by transcription factor YY1 represses HOXB13 to affect cell growth in AR-negative prostate cancers. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HDAC4 | down-regulates
binding
|
MEF2D |
0.679 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-76237 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10737771 |
We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IGF and Myogenesis |
| + |
AMPK | down-regulates
phosphorylation
|
HDAC4 |
0.275 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216658 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 21565617 |
We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
HDAC4 | down-regulates
deacetylation
|
RUNX2 |
0.54 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146122 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16613856 |
Hdac4 and hdac5 deacetylate runx2 and lead to a smurf-mediated degradation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-195603 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22298955 |
Hdac4 and hdac5 deacetylate runx2 and lead to a smurf-mediated degradation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CAMK4 | down-regulates
phosphorylation
|
HDAC4 |
0.603 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-83837 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11062529 |
Mckinsey et al. report that calcium/calmodulin-dependent kinase (camk), stimulates myogenesis and prevents formation of mef2/hdac complexes by inducing phosphorylation and nuclear export of hdacs 4 and 5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IGF and Myogenesis |
| + |
CUDC-101 | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262260 |
|
|
in vitro |
|
| pmid |
sentence |
| 20143778 |
By incorporating histone deacetylase (HDAC) inhibitory functionality into the pharmacophore of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors, we synthesized a novel series of compounds with potent, multiacting HDAC, EGFR, and HER2 inhibition and identified 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide 8 (CUDC-101) as a drug candidate, which is now in clinical development. 8 displays potent in vitro inhibitory activity against HDAC, EGFR, and HER2 with an IC(50) of 4.4, 2.4, and 15.7 nM, respectively. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
BCORL1 | up-regulates activity
binding
|
HDAC4 |
0.438 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259112 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17379597 |
BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HDAC4 | down-regulates
binding
|
MEF2A |
0.581 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-76231 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10737771 |
We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| Pathways: | IGF and Myogenesis |
| + |
romidepsin | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257991 |
|
|
in vitro |
|
| pmid |
sentence |
| 20139990 |
Collaboratively, we synthesized and assembled a panel of structurally-diverse small-molecule HDACi 1, 2, 7-20 that comprise most of the relevant literature-reported tool compounds and pharmaceutically developed clinical candidates (Supplementary Fig 3). We next conducted a high-throughput, precise profiling of HDACi potency against all Class I and II enzymes, in a miniaturized dose-ranging format (Supplementary Table 1). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
trichostatin A | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258017 |
|
|
in vitro |
|
| pmid |
sentence |
| 20139990 |
Collaboratively, we synthesized and assembled a panel of structurally-diverse small-molecule HDACi 1, 2, 7-20 that comprise most of the relevant literature-reported tool compounds and pharmaceutically developed clinical candidates (Supplementary Fig 3). We next conducted a high-throughput, precise profiling of HDACi potency against all Class I and II enzymes, in a miniaturized dose-ranging format (Supplementary Table 1). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257941 |
|
|
in vitro |
|
| pmid |
sentence |
| 17868033 |
Our findings suggest that hydroxamic acid-derived compounds such as TSA, NVP-LAQ824, panobinostat, ITF2357, vorinostat and belinostat act as potent pan-HDAC isoform inhibitors. A notable observation was the similarity between belinostat and vorinostat in the biochemical isoform assays; both compounds exhibit similar EC50 values in all but the HDAC8 assay. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
HDAC4 | down-regulates quantity by repression
transcriptional regulation
|
CDH1 |
0.292 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275663 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 25726523 |
GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
panobinostat | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257755 |
|
|
in vitro |
|
| pmid |
sentence |
| 17868033 |
Our findings suggest that hydroxamic acid-derived compounds such as TSA, NVP-LAQ824, panobinostat, ITF2357, vorinostat and belinostat act as potent pan-HDAC isoform inhibitors. A notable observation was the similarity between belinostat and vorinostat in the biochemical isoform assays; both compounds exhibit similar EC50 values in all but the HDAC8 assay. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257968 |
|
|
in vitro |
|
| pmid |
sentence |
| 20139990 |
Collaboratively, we synthesized and assembled a panel of structurally-diverse small-molecule HDACi 1, 2, 7-20 that comprise most of the relevant literature-reported tool compounds and pharmaceutically developed clinical candidates (Supplementary Fig 3). We next conducted a high-throughput, precise profiling of HDACi potency against all Class I and II enzymes, in a miniaturized dose-ranging format (Supplementary Table 1). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257911 |
|
|
in vitro |
|
| pmid |
sentence |
| 17868033 |
Our findings suggest that hydroxamic acid-derived compounds such as TSA, NVP-LAQ824, panobinostat, ITF2357, vorinostat and belinostat act as potent pan-HDAC isoform inhibitors. A notable observation was the similarity between belinostat and vorinostat in the biochemical isoform assays; both compounds exhibit similar EC50 values in all but the HDAC8 assay. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
HDAC4 | down-regulates activity
deacetylation, binding
|
RUNX2 |
0.54 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227547 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16613856 |
HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-226680 |
|
|
Chlorocebus aethiops |
|
| pmid |
sentence |
| 15537544 |
Here we report that HDAC4, which is expressed in prehypertrophic chondrocytes, regulates chondrocyte hypertrophy and endochondral bone formation by interacting with and inhibiting the activity of Runx2, a transcription factor necessary for chondrocyte hypertrophy.PDPK1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Chlorocebus Aethiops |
| + |
N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide | down-regulates activity
chemical inhibition
|
HDAC4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257986 |
|
|
in vitro |
|
| pmid |
sentence |
| 20139990 |
Collaboratively, we synthesized and assembled a panel of structurally-diverse small-molecule HDACi 1, 2, 7-20 that comprise most of the relevant literature-reported tool compounds and pharmaceutically developed clinical candidates (Supplementary Fig 3). We next conducted a high-throughput, precise profiling of HDACi potency against all Class I and II enzymes, in a miniaturized dose-ranging format (Supplementary Table 1). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257930 |
|
|
in vitro |
|
| pmid |
sentence |
| 17868033 |
Our findings suggest that hydroxamic acid-derived compounds such as TSA, NVP-LAQ824, panobinostat, ITF2357, vorinostat and belinostat act as potent pan-HDAC isoform inhibitors. A notable observation was the similarity between belinostat and vorinostat in the biochemical isoform assays; both compounds exhibit similar EC50 values in all but the HDAC8 assay. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
GATA1 | up-regulates activity
relocalization
|
HDAC4 |
0.566 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275665 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 25726523 |
GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKAA1 | down-regulates
phosphorylation
|
HDAC4 |
0.275 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-173689 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 21565617 |
We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
HDAC4 | down-regulates quantity by repression
transcriptional regulation
|
MMP13 |
0.332 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254235 |
|
|
Homo sapiens |
UMR-106-01 Cell |
| pmid |
sentence |
| 17656568 |
We have hypothesized that histone deacetylases (HDACs) are involved with PTH-induced MMP-13 gene expression in the osteoblastic cell line, UMR 106-01. We have shown that PTH profoundly regulates HDAC4 in UMR 106-01 cells through a PKA-dependent pathway, leading to removal of HDAC4 from the MMP-13 promoter and its enhanced transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HDAC4 | down-regulates
binding
|
MEF2C |
0.701 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-76234 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10737771 |
We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| Pathways: | IGF and Myogenesis |
3.0
HDAC4
- 
- 