HDAC4
entrez
9759
canonical
uniprot
P56524
canonical
ensembl
ENSG00000068024
resolver
ensp
ENSP00000264606
resolver
ensp
ENSP00000440481
resolver
ensp
ENSP00000566827
resolver
ensp
ENSP00000566828
resolver
ensp
ENSP00000566829
resolver
ensp
ENSP00000566830
resolver
ensp
ENSP00000583721
resolver
ensp
ENSP00000583722
resolver
ensp
ENSP00000583723
resolver
ensp
ENSP00000583724
resolver
ensp
ENSP00000583725
resolver
ensp
ENSP00000583728
resolver
ensp
ENSP00000583731
resolver
ensp
ENSP00000785340
resolver
enst
ENST00000543185
resolver
enst
ENST00000896768
resolver
enst
ENST00000913664
resolver
enst
ENST00000913672
resolver
genesymbol
HDAC4
resolver
genesymbol_syn
KIAA0288
resolver
hgnc
HGNC:14063
resolver
uniprot
A0A7I2SVS4
resolver
uniprot
B7Z8G5
resolver
uniprot
E9PGB9
resolver
uniprot
F5GX36
resolver
uniprot
Q86YH7
resolver
uniprot
Q9UND6
resolver
uniprot_entry
A0A7I2SVS4_HUMAN
resolver
uniprot_entry
B7Z8G5_HUMAN
resolver
uniprot_entry
HDAC4_HUMAN
resolver
uniprot_sec
E9PGB9
resolver
uniprot_sec
F5GX36
resolver
uniprot_sec
Q86YH7
resolver
uniprot_sec
Q9UND6
resolver
amino_acid_sequence
MSSQSHPDGLSGRDQPVELLNPARVNHMPSTVDVATALPLQVAPSAVPMDLRLDHQFSLPVAEPALREQQLQQELLALKQKQQIQRQILIAEFQRQHEQLSRQHEAQLHEHIKQQQEMLAMKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVLNKKKALAHRNLNHCISSDPRYWYGKTQHSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFPLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPGSGPSSPNNSSGSVSAENGIAPAVPSIPAETSLAHRLVAREGSAAPLPLYTSPSLPNITLGLPATGPSAGTAGQQDAERLTLPALQQRLSLFPGTHLTPYLSTSPLERDGGAAHSPLLQHMVLLEQPPAQAPLVTGLGALPLHAQSLVGADRVSPSIHKLRQHRPLGRTQSAPLPQNAQALQHLVIQQQHQQFLEKHKQQFQQQQLQMNKIIPKPSEPARQPESHPEETEEELREHQALLDEPYLDRLPGQKEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQRIHQLRNYQASMEAAGIPVSFGGHRPLSRAQSSPASATFPVSVQEPPTKPRFTTGLVYDTLMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHTLLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVELVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKLLQQRLSVSKILIVDWDVHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDPPMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLQQRPNANAVRSMEKVMEIHSKYWRCLQRTTSTAGRSLIEAQTCENEEAETVTAMASLSVGVKPAEKRPDEEPMEEEPPL
uniprot
proteins
disease_involvement
DISEASE: Note=HDAC4 point mutations and chromosomal microdeletions encompassing this gene have been found in patients with brachydactyly and intellectual disability syndrome (PubMed:20691407, PubMed:23188045, PubMed:24715439). However, HDAC4 haploinsufficiency is not fully penetrant and multiple genes may contribute to manifestation of the full phenotypic spectrum (PubMed:23188045, PubMed:24715439). {ECO:0000269|PubMed:20691407, ECO:0000269|PubMed:23188045, ECO:0000269|PubMed:24715439}.; DISEASE: Neurodevelopmental disorder with central hypotonia and dysmorphic facies (NEDCHF) [MIM:619797]: An autosomal dominant disease characterized by global developmental delay, impaired intellectual development, seizures, distinctive facial features, scoliosis, delayed closure of the anterior fontanel, and non-specific brain abnormalities. {ECO:0000269|PubMed:33537682}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.5.1.98
uniprot
proteins
function
FUNCTION: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1 (PubMed:27708256). {ECO:0000269|PubMed:10523670, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:27708256}.
uniprot
proteins
mass_dalton
119040
uniprot
proteins
mutagenesis
MUTAGEN 246; /note="S->A: Reduces phosphorylation and its subsequent nuclear export."; /evidence="ECO:0000269|PubMed:10958686"; MUTAGEN 345; /note="L->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 346; /note="Y->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 347; /note="T->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 348; /note="S->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 349; /note="P->A: May affect interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097, ECO:0000269|PubMed:25752541"; MUTAGEN 349; /note="P->G: Decreased interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 350; /note="S->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 351; /note="L->A,G: Loss of interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 352; /note="P->A: Loss of interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 353; /note="N->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 354; /note="I->A: May affect interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097, ECO:0000269|PubMed:25752541"; MUTAGEN 354; /note="I->G: Loss of interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 355; /note="T->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 356; /note="L->A: No effect on interaction with ANKRA2."; /evidence="ECO:0000269|PubMed:22649097"; MUTAGEN 467; /note="S->A: Reduces phosphorylation and its subsequent nuclear export."; /evidence="ECO:0000269|PubMed:10958686, ECO:0000269|PubMed:11470791"; MUTAGEN 559; /note="K->R: Abolishes sumoylation and reduces the histone deacetylase activity."; /evidence="ECO:0000269|PubMed:12032081"; MUTAGEN 632; /note="S->A: Reduces phosphorylation and its subsequent nuclear export."; /evidence="ECO:0000269|PubMed:10958686, ECO:0000269|PubMed:11470791"; MUTAGEN 803; /note="H->L: Abolishes histone deacetylase activity."; /evidence="ECO:0000269|PubMed:10523670"; MUTAGEN 1056; /note="V->A: Reduces CaMK-dependent nuclear export."; /evidence="ECO:0000269|PubMed:11509672"; MUTAGEN 1062; /note="L->A: Reduces CaMK-dependent nuclear export."; /evidence="ECO:0000269|PubMed:11509672
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-350, within the PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3. {ECO:0000269|PubMed:10958686, ECO:0000269|PubMed:22649097}.; PTM: Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4. {ECO:0000269|PubMed:12032081}.
uniprot
proteins
protein_family
HD type 2 subfamily
uniprot
proteins
protein_family
Histone deacetylase family
uniprot
proteins
pubmed
10220385
uniprot
proteins
pubmed
10487761
uniprot
proteins
pubmed
10523670
uniprot
proteins
pubmed
10958686
uniprot
proteins
pubmed
11463856
uniprot
proteins
pubmed
11470791
uniprot
proteins
pubmed
11509672
uniprot
proteins
pubmed
12032081
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17179159
uniprot
proteins
pubmed
17373667
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20110259
uniprot
proteins
pubmed
20691407
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22649097
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23188045
uniprot
proteins
pubmed
24169519
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24413532
uniprot
proteins
pubmed
24715439
uniprot
proteins
pubmed
25752541
uniprot
proteins
pubmed
27708256
uniprot
proteins
pubmed
30487602
uniprot
proteins
pubmed
33537682
uniprot
proteins
pubmed
9179496
uniprot
proteins
sequence_length
1084
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation. Interaction with SIK3 leads to HDAC4 retention in the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q6NZM9}.
uniprot
proteins