P56524 · HDAC4_HUMAN
- ProteinHistone deacetylase 4
- GeneHDAC4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1084 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic activity
- H2O + N6-acetyl-L-lysyl-[histone] = acetate + L-lysyl-[histone]This reaction proceeds in the forward direction.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
The subsequence EHQALLDEPYLDRLPGQKEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQRIHQLRNYQA shows transcriptional repressor activity in a high-throughput recruitment assay.
Names & Taxonomy
Protein names
- Recommended nameHistone deacetylase 4
- EC number
- Short namesHD4
Gene names
- Community suggested namesHDAC4
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP56524
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Neurodevelopmental disorder with central hypotonia and dysmorphic facies (NEDCHF)
- Note
- DescriptionAn 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.
- See alsoMIM:619797
Natural variants in NEDCHF
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_087034 | 244 | T>K | in NEDCHF; decreased interaction with YWHAB; dbSNP:rs2042442594 | |
VAR_087035 | 247 | E>G | in NEDCHF; decreased interaction with YWHAB; dbSNP:rs2152917896 | |
VAR_087036 | 248 | P>A | in NEDCHF; dbSNP:rs2152917882 | |
VAR_087037 | 248 | P>L | in NEDCHF; dbSNP:rs1064797002 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_087034 | 244 | in NEDCHF; decreased interaction with YWHAB; dbSNP:rs2042442594 | |||
Sequence: T → K | ||||||
Mutagenesis | 246 | Reduces phosphorylation and its subsequent nuclear export. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_087035 | 247 | in NEDCHF; decreased interaction with YWHAB; dbSNP:rs2152917896 | |||
Sequence: E → G | ||||||
Natural variant | VAR_087036 | 248 | in NEDCHF; dbSNP:rs2152917882 | |||
Sequence: P → A | ||||||
Natural variant | VAR_087037 | 248 | in NEDCHF; dbSNP:rs1064797002 | |||
Sequence: P → L | ||||||
Mutagenesis | 345 | No effect on interaction with ANKRA2. | ||||
Sequence: L → A | ||||||
Mutagenesis | 346 | No effect on interaction with ANKRA2. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 347 | No effect on interaction with ANKRA2. | ||||
Sequence: T → A | ||||||
Mutagenesis | 348 | No effect on interaction with ANKRA2. | ||||
Sequence: S → A | ||||||
Mutagenesis | 349 | May affect interaction with ANKRA2. | ||||
Sequence: P → A | ||||||
Mutagenesis | 349 | Decreased interaction with ANKRA2. | ||||
Sequence: P → G | ||||||
Mutagenesis | 350 | No effect on interaction with ANKRA2. | ||||
Sequence: S → A | ||||||
Mutagenesis | 351 | Loss of interaction with ANKRA2. | ||||
Sequence: L → A or G | ||||||
Mutagenesis | 352 | Loss of interaction with ANKRA2. | ||||
Sequence: P → A | ||||||
Mutagenesis | 353 | No effect on interaction with ANKRA2. | ||||
Sequence: N → A | ||||||
Mutagenesis | 354 | May affect interaction with ANKRA2. | ||||
Sequence: I → A | ||||||
Mutagenesis | 354 | Loss of interaction with ANKRA2. | ||||
Sequence: I → G | ||||||
Mutagenesis | 355 | No effect on interaction with ANKRA2. | ||||
Sequence: T → A | ||||||
Mutagenesis | 356 | No effect on interaction with ANKRA2. | ||||
Sequence: L → A | ||||||
Mutagenesis | 467 | Reduces phosphorylation and its subsequent nuclear export. | ||||
Sequence: S → A | ||||||
Mutagenesis | 559 | Abolishes sumoylation and reduces the histone deacetylase activity. | ||||
Sequence: K → R | ||||||
Mutagenesis | 632 | Reduces phosphorylation and its subsequent nuclear export. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_036042 | 727 | in a breast cancer sample; somatic mutation | |||
Sequence: P → R | ||||||
Natural variant | VAR_071965 | 754 | in dbSNP:rs151043798 | |||
Sequence: V → I | ||||||
Mutagenesis | 803 | Abolishes histone deacetylase activity. | ||||
Sequence: H → L | ||||||
Mutagenesis | 1056 | Reduces CaMK-dependent nuclear export. | ||||
Sequence: V → A | ||||||
Mutagenesis | 1062 | Reduces CaMK-dependent nuclear export. | ||||
Sequence: L → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,495 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue, cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000114699 | 1-1084 | UniProt | Histone deacetylase 4 | |||
Sequence: MSSQSHPDGLSGRDQPVELLNPARVNHMPSTVDVATALPLQVAPSAVPMDLRLDHQFSLPVAEPALREQQLQQELLALKQKQQIQRQILIAEFQRQHEQLSRQHEAQLHEHIKQQQEMLAMKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVLNKKKALAHRNLNHCISSDPRYWYGKTQHSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFPLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPGSGPSSPNNSSGSVSAENGIAPAVPSIPAETSLAHRLVAREGSAAPLPLYTSPSLPNITLGLPATGPSAGTAGQQDAERLTLPALQQRLSLFPGTHLTPYLSTSPLERDGGAAHSPLLQHMVLLEQPPAQAPLVTGLGALPLHAQSLVGADRVSPSIHKLRQHRPLGRTQSAPLPQNAQALQHLVIQQQHQQFLEKHKQQFQQQQLQMNKIIPKPSEPARQPESHPEETEEELREHQALLDEPYLDRLPGQKEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQRIHQLRNYQASMEAAGIPVSFGGHRPLSRAQSSPASATFPVSVQEPPTKPRFTTGLVYDTLMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHTLLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVELVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKLLQQRLSVSKILIVDWDVHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDPPMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLQQRPNANAVRSMEKVMEIHSKYWRCLQRTTSTAGRSLIEAQTCENEEAETVTAMASLSVGVKPAEKRPDEEPMEEEPPL | |||||||
Modified residue (large scale data) | 2 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 3 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 196 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 206 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 210 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 210 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 214 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 215 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 246 | UniProt | Phosphoserine; by CaMK4 and SIK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 246 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 265 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 266 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 350 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 350 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 400 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 465 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 467 | UniProt | Phosphoserine; by CaMK4 and SIK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 467 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 559 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | |||||||
Modified residue | 565 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 565 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 611 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 628 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 632 | UniProt | Phosphoserine; by CaMK4 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 632 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 633 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 633 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 636 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with MEF2A (PubMed:10487761).
Interacts with MEF2C and MEF2D (PubMed:10523670).
Interacts with AHRR (By similarity).
Interacts with NR2C1 (PubMed:11463856).
Interacts with HDAC7 (By similarity).
Interacts with a 14-3-3 chaperone proteins in a phosphorylation dependent manner (PubMed:10958686).
Interacts with 14-3-3 protein YWHAB (PubMed:33537682).
Interacts with BTBD14B (By similarity).
Interacts with KDM5B (PubMed:17373667).
Interacts with MYOCD (By similarity).
Interacts with MORC2 (PubMed:20110259).
Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats). Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2 (PubMed:25752541).
Interacts with EP300 in the presence of TFAP2C (PubMed:24413532).
Interacts with HSPA1A and HSPA1B leading to their deacetylation at 'Lys-77' (PubMed:27708256).
Interacts with ZBTB7B; the interaction allows the recruitment of HDAC4 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression (By similarity).
Interacts with DHX36 (By similarity).
Interacts with SIK3; this interaction leads to HDAC4 retention in the cytoplasm (By similarity).
Interacts with ZNF638 (PubMed:30487602).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for coiled coil, region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Coiled coil | 67-177 | |||||
Sequence: REQQLQQELLALKQKQQIQRQILIAEFQRQHEQLSRQHEAQLHEHIKQQQEMLAMKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQE | ||||||
Region | 118-313 | Interaction with MEF2A | ||||
Sequence: MLAMKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVLNKKKALAHRNLNHCISSDPRYWYGKTQHSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFPLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPGSGPSSPNNSSGSVSAE | ||||||
Region | 133-166 | Disordered | ||||
Sequence: KLERHRQEQELEKQHREQKLQQLKNKEKGKESAV | ||||||
Region | 206-226 | Disordered | ||||
Sequence: TQHSSLDQSSPPQSGVSTSYN | ||||||
Compositional bias | 240-279 | Basic and acidic residues | ||||
Sequence: PLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTA | ||||||
Region | 240-315 | Disordered | ||||
Sequence: PLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPGSGPSSPNNSSGSVSAENG | ||||||
Compositional bias | 291-313 | Polar residues | ||||
Sequence: ACSSAPGSGPSSPNNSSGSVSAE | ||||||
Motif | 349-354 | PxLPxI/L motif; mediates interaction with ANKRA2 and 14-3-3 proteins | ||||
Sequence: PSLPNI | ||||||
Region | 509-531 | Disordered | ||||
Sequence: PKPSEPARQPESHPEETEEELRE | ||||||
Compositional bias | 516-531 | Basic and acidic residues | ||||
Sequence: RQPESHPEETEEELRE | ||||||
Region | 548-585 | Disordered | ||||
Sequence: KEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSE | ||||||
Region | 626-646 | Disordered | ||||
Sequence: PLSRAQSSPASATFPVSVQEP | ||||||
Region | 655-1084 | Histone deacetylase | ||||
Sequence: GLVYDTLMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHTLLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVELVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKLLQQRLSVSKILIVDWDVHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDPPMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLQQRPNANAVRSMEKVMEIHSKYWRCLQRTTSTAGRSLIEAQTCENEEAETVTAMASLSVGVKPAEKRPDEEPMEEEPPL | ||||||
Motif | 1051-1084 | Nuclear export signal | ||||
Sequence: EEAETVTAMASLSVGVKPAEKRPDEEPMEEEPPL | ||||||
Region | 1061-1084 | Disordered | ||||
Sequence: SLSVGVKPAEKRPDEEPMEEEPPL | ||||||
Compositional bias | 1068-1084 | Basic and acidic residues | ||||
Sequence: PAEKRPDEEPMEEEPPL |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P56524-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length1,084
- Mass (Da)119,040
- Last updated2009-09-22 v3
- ChecksumBB7FD37652D12398
P56524-2
- Name2
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9J481 | C9J481_HUMAN | HDAC4 | 162 | ||
C9J0X4 | C9J0X4_HUMAN | HDAC4 | 123 | ||
A0A7I2SVS4 | A0A7I2SVS4_HUMAN | HDAC4 | 1089 | ||
H7BZT3 | H7BZT3_HUMAN | HDAC4 | 148 | ||
H7C397 | H7C397_HUMAN | HDAC4 | 175 |
Sequence caution
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_057290 | 1-117 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 240-279 | Basic and acidic residues | ||||
Sequence: PLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTA | ||||||
Compositional bias | 291-313 | Polar residues | ||||
Sequence: ACSSAPGSGPSSPNNSSGSVSAE | ||||||
Sequence conflict | 373 | in Ref. 1; AAD29046 and 2; BAA22957 | ||||
Sequence: A → T | ||||||
Alternative sequence | VSP_057291 | 431 | in isoform 2 | |||
Sequence: T → TDWYLS | ||||||
Compositional bias | 516-531 | Basic and acidic residues | ||||
Sequence: RQPESHPEETEEELRE | ||||||
Compositional bias | 1068-1084 | Basic and acidic residues | ||||
Sequence: PAEKRPDEEPMEEEPPL |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF132607 EMBL· GenBank· DDBJ | AAD29046.1 EMBL· GenBank· DDBJ | mRNA | ||
AB006626 EMBL· GenBank· DDBJ | BAA22957.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AC017028 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC062017 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
KF510800 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
KF510801 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471063 EMBL· GenBank· DDBJ | EAW71165.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC039904 EMBL· GenBank· DDBJ | AAH39904.1 EMBL· GenBank· DDBJ | mRNA |