UniProtKB - Q99P99 (HDAC4_RAT)
Histone deacetylase 4
Hdac4
Functioni
Catalytic activityi
- EC:3.5.1.98
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 665 | ZincBy similarity | 1 | |
Metal bindingi | 667 | ZincBy similarity | 1 | |
Metal bindingi | 673 | ZincBy similarity | 1 | |
Metal bindingi | 744 | ZincBy similarity | 1 | |
Active sitei | 796 | By similarity | 1 |
GO - Molecular functioni
- activating transcription factor binding Source: RGD
- chromatin binding Source: RGD
- DNA binding Source: RGD
- histone deacetylase activity Source: RGD
- histone deacetylase binding Source: RGD
- identical protein binding Source: RGD
- NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
- potassium ion binding Source: RGD
- promoter-specific chromatin binding Source: RGD
- protein deacetylase activity Source: RGD
- protein kinase binding Source: RGD
- repressing transcription factor binding Source: RGD
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: RGD
- RNA polymerase II transcription factor binding Source: RGD
- SUMO transferase activity Source: RGD
- transcription corepressor activity Source: RGD
- transcription factor binding Source: RGD
- zinc ion binding Source: RGD
GO - Biological processi
- cellular response to mechanical stimulus Source: RGD
- cellular response to parathyroid hormone stimulus Source: RGD
- cellular response to tumor necrosis factor Source: RGD
- chromatin remodeling Source: RGD
- histone deacetylation Source: RGD
- histone H3 deacetylation Source: RGD
- histone H4 deacetylation Source: RGD
- negative regulation of cell population proliferation Source: RGD
- negative regulation of DNA-binding transcription factor activity Source: RGD
- negative regulation of glycolytic process Source: RGD
- negative regulation of myotube differentiation Source: RGD
- negative regulation of osteoblast differentiation Source: RGD
- negative regulation of pri-miRNA transcription by RNA polymerase II Source: RGD
- negative regulation of transcription, DNA-templated Source: RGD
- negative regulation of transcription by RNA polymerase II Source: RGD
- osteoblast development Source: RGD
- peptidyl-lysine deacetylation Source: RGD
- positive regulation of cell population proliferation Source: RGD
- positive regulation of DNA-binding transcription factor activity Source: RGD
- positive regulation of lamellipodium assembly Source: RGD
- positive regulation of male mating behavior Source: RGD
- positive regulation of neuron apoptotic process Source: RGD
- positive regulation of protein sumoylation Source: RGD
- positive regulation of reactive oxygen species biosynthetic process Source: RGD
- positive regulation of smooth muscle cell migration Source: RGD
- positive regulation of smooth muscle cell proliferation Source: RGD
- positive regulation of transcription, DNA-templated Source: RGD
- positive regulation of transcription by RNA polymerase II Source: RGD
- protein deacetylation Source: RGD
- regulation of cardiac muscle contraction by calcium ion signaling Source: RGD
- regulation of gene expression, epigenetic Source: RGD
- regulation of protein binding Source: RGD
- regulation of skeletal muscle fiber development Source: RGD
- regulation of striated muscle cell differentiation Source: RGD
- response to denervation involved in regulation of muscle adaptation Source: RGD
- response to drug Source: RGD
- response to interleukin-1 Source: RGD
- skeletal system development Source: RGD
Keywordsi
Molecular function | Chromatin regulator, Hydrolase, Repressor |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-RNO-350054, Notch-HLH transcription pathway R-RNO-4090294, SUMOylation of intracellular receptors R-RNO-4551638, SUMOylation of chromatin organization proteins R-RNO-8951936, RUNX3 regulates p14-ARF |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Hdac4 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 619979, Hdac4 |
Subcellular locationi
Nucleus
Other locations
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-245, Ser-466 and Ser-630 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation (By similarity). Interaction with SIK3 leads to HDAC4 retention in the cytoplasm (By similarity). Interacts with ZNF638 (By similarity).By similarity
Cytoskeleton
- actomyosin Source: RGD
Cytosol
- cytosol Source: RGD
Nucleus
- histone deacetylase complex Source: RGD
- nuclear speck Source: Ensembl
- nucleus Source: RGD
Other locations
- A band Source: MGI
- cytoplasm Source: RGD
- neuromuscular junction Source: RGD
- protein-containing complex Source: RGD
- sarcomere Source: MGI
- transcription repressor complex Source: RGD
- Z disc Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000281034 | 1 – 1077 | Histone deacetylase 4Add BLAST | 1077 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 209 | PhosphoserineBy similarity | 1 | |
Modified residuei | 245 | Phosphoserine; by CaMK4 and SIK1By similarity | 1 | |
Modified residuei | 349 | PhosphoserineBy similarity | 1 | |
Modified residuei | 466 | Phosphoserine; by CaMK4 and SIK1By similarity | 1 | |
Cross-linki | 557 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Modified residuei | 563 | PhosphoserineCombined sources | 1 | |
Modified residuei | 630 | PhosphoserineCombined sources | 1 | |
Modified residuei | 631 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q99P99 |
PRIDEi | Q99P99 |
PTM databases
iPTMneti | Q99P99 |
PhosphoSitePlusi | Q99P99 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000020372, Expressed in frontal cortex and 21 other tissues |
Genevisiblei | Q99P99, RN |
Interactioni
Subunit structurei
Homodimer. Homodimerization via its N-terminal domain.
Interacts with HDAC7.
Interacts with MEF2A, MEF2C, MEF2D, MORC2 and NR2C1.
Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner.
Interacts with KDM5B and AHRR (By similarity).
Interacts with BTBD14B (PubMed:16033423).
Interacts with MYOCD.
Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats).
Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2.
Interacts with EP300 in the presence of TFAP2C.
Interacts with HSPA1A and HSPA1B leading to their deacetylation at 'Lys-77' (By similarity).
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).
By similarity1 PublicationGO - Molecular functioni
- activating transcription factor binding Source: RGD
- histone deacetylase binding Source: RGD
- identical protein binding Source: RGD
- protein kinase binding Source: RGD
- repressing transcription factor binding Source: RGD
- RNA polymerase II transcription factor binding Source: RGD
- transcription factor binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 264106, 4 interactors |
CORUMi | Q99P99 |
STRINGi | 10116.ENSRNOP00000027622 |
Chemistry databases
BindingDBi | Q99P99 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 117 – 312 | Interaction with MEF2ABy similarityAdd BLAST | 196 | |
Regioni | 653 – 1077 | Histone deacetylaseBy similarityAdd BLAST | 425 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 66 – 169 | Sequence analysisAdd BLAST | 104 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 348 – 353 | PxLPxI/L motif; mediates interaction with ANKRA2 and 14-3-3 proteinsBy similarity | 6 | |
Motifi | 1044 – 1077 | Nuclear export signalBy similarityAdd BLAST | 34 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 465 – 500 | Gln-richAdd BLAST | 36 | |
Compositional biasi | 562 – 569 | Poly-Glu | 8 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG1343, Eukaryota |
GeneTreei | ENSGT00940000157440 |
HOGENOMi | CLU_006530_2_0_1 |
InParanoidi | Q99P99 |
OMAi | HSHGAFQ |
OrthoDBi | 1484694at2759 |
PhylomeDBi | Q99P99 |
TreeFami | TF106174 |
Family and domain databases
Gene3Di | 3.40.800.20, 1 hit |
InterProi | View protein in InterPro IPR033660, HDAC4 IPR000286, His_deacetylse IPR023801, His_deacetylse_dom IPR037138, His_deacetylse_dom_sf IPR024643, Hist_deacetylase_Gln_rich_N IPR017320, Histone_deAcase_II_euk IPR023696, Ureohydrolase_dom_sf |
PANTHERi | PTHR45364, PTHR45364, 1 hit PTHR45364:SF3, PTHR45364:SF3, 1 hit |
Pfami | View protein in Pfam PF12203, HDAC4_Gln, 1 hit PF00850, Hist_deacetyl, 1 hit |
PIRSFi | PIRSF037911, HDAC_II_euk, 1 hit |
PRINTSi | PR01270, HDASUPER |
SUPFAMi | SSF52768, SSF52768, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPAAVPMD
60 70 80 90 100
LRLDHQFSLP LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS
110 120 130 140 150
RQHEAQLHEH IKQQQEMLAM KHQQELLEHQ RKLERHRQEQ ELEKQHREQK
160 170 180 190 200
LQQLKNKEKG KESAVASTEV KMKLQEFVLN KKKALAHRNL NHCMSSDPRY
210 220 230 240 250
WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL RKTASEPNLK
260 270 280 290 300
LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS
310 320 330 340 350
SPNSSSGNVS TENGIAPTVP STPAETSLAH RLVTREGSVA PLPLYTSPSL
360 370 380 390 400
PNITLGLPAT GPAAGAAGQQ DAERLALPAL QQRISLFPGT HLTPYLSTSP
410 420 430 440 450
LERDGGAAHN PLLQHMVLLE QPPTQTPLVT GLGALPLHTQ SLVGADRVSP
460 470 480 490 500
SIHKLRQHRP LGRTQSAPLP QNAQALQHLV IQQQHQQFLE KHKQQFQQQQ
510 520 530 540 550
LHLSKMISKP SEPPRQPESH PEETEEELRE HQALLDEPYL DRLPGQKEPS
560 570 580 590 600
LAGVQVKQEP IESEEEEVEA TREAEPSQRP ATEQELLFRQ QALLLEQQRI
610 620 630 640 650
HQLRNYQASM EAAGIPVSFG SHRPLSRAQS SPASATFPMS VQEPPTKPRF
660 670 680 690 700
TTGLVYDTLM LKHQCTCGNT NSHPEHAGRI QSIWSRLQET GLRGKCECIR
710 720 730 740 750
GRKATLEELQ TVHSEAHTLL YGTNPLNRQK LDSSLTSVFV RLPCGGVGVD
760 770 780 790 800
SDTIWNEVHS SGAARLAVGC VVELVFKVAT GELKNGFAVV RPPGHHAEES
810 820 830 840 850
TPMGFCYFNS VAIAAKLLQQ RLNVSKILIV DWDVHHGNGT QQAFYNDPNV
860 870 880 890 900
LYMSLHRYDD GNFFPGSGAP DEVGTGPGVG FNVNMAFTGG LDPPMGDAEY
910 920 930 940 950
LAAFRTVVMP IANEFAPDVV LVSSGFDAVE GHPTPLGGYN LSAKCFGYLT
960 970 980 990 1000
KQLMGLAGGR IVLALEGGHD LTAICDASEA CVSALLGNEL EPLPEKVLHQ
1010 1020 1030 1040 1050
RPNANAVHSM EKVMGIHSEY WRCLQRLSPT VGHSLIEAQK CENEEAETVT
1060 1070
AMASLSVGVK PAEKRSEEEP MEEEPPL
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AABR03067902 Genomic DNA No translation available. AABR03068091 Genomic DNA No translation available. AABR03070452 Genomic DNA No translation available. AF321132 mRNA Translation: AAK11185.1 |
RefSeqi | NP_445901.1, NM_053449.1 |
Genome annotation databases
Ensembli | ENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372 |
GeneIDi | 363287 |
KEGGi | rno:363287 |
UCSCi | RGD:619979, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AABR03067902 Genomic DNA No translation available. AABR03068091 Genomic DNA No translation available. AABR03070452 Genomic DNA No translation available. AF321132 mRNA Translation: AAK11185.1 |
RefSeqi | NP_445901.1, NM_053449.1 |
3D structure databases
SMRi | Q99P99 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 264106, 4 interactors |
CORUMi | Q99P99 |
STRINGi | 10116.ENSRNOP00000027622 |
Chemistry databases
BindingDBi | Q99P99 |
ChEMBLi | CHEMBL2095943 |
DrugCentrali | Q99P99 |
PTM databases
iPTMneti | Q99P99 |
PhosphoSitePlusi | Q99P99 |
Proteomic databases
PaxDbi | Q99P99 |
PRIDEi | Q99P99 |
Genome annotation databases
Ensembli | ENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372 |
GeneIDi | 363287 |
KEGGi | rno:363287 |
UCSCi | RGD:619979, rat |
Organism-specific databases
CTDi | 9759 |
RGDi | 619979, Hdac4 |
Phylogenomic databases
eggNOGi | KOG1343, Eukaryota |
GeneTreei | ENSGT00940000157440 |
HOGENOMi | CLU_006530_2_0_1 |
InParanoidi | Q99P99 |
OMAi | HSHGAFQ |
OrthoDBi | 1484694at2759 |
PhylomeDBi | Q99P99 |
TreeFami | TF106174 |
Enzyme and pathway databases
Reactomei | R-RNO-350054, Notch-HLH transcription pathway R-RNO-4090294, SUMOylation of intracellular receptors R-RNO-4551638, SUMOylation of chromatin organization proteins R-RNO-8951936, RUNX3 regulates p14-ARF |
Miscellaneous databases
PROi | PR:Q99P99 |
Gene expression databases
Bgeei | ENSRNOG00000020372, Expressed in frontal cortex and 21 other tissues |
Genevisiblei | Q99P99, RN |
Family and domain databases
Gene3Di | 3.40.800.20, 1 hit |
InterProi | View protein in InterPro IPR033660, HDAC4 IPR000286, His_deacetylse IPR023801, His_deacetylse_dom IPR037138, His_deacetylse_dom_sf IPR024643, Hist_deacetylase_Gln_rich_N IPR017320, Histone_deAcase_II_euk IPR023696, Ureohydrolase_dom_sf |
PANTHERi | PTHR45364, PTHR45364, 1 hit PTHR45364:SF3, PTHR45364:SF3, 1 hit |
Pfami | View protein in Pfam PF12203, HDAC4_Gln, 1 hit PF00850, Hist_deacetyl, 1 hit |
PIRSFi | PIRSF037911, HDAC_II_euk, 1 hit |
PRINTSi | PR01270, HDASUPER |
SUPFAMi | SSF52768, SSF52768, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HDAC4_RAT | |
Accessioni | Q99P99Primary (citable) accession number: Q99P99 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 20, 2007 |
Last sequence update: | March 20, 2007 | |
Last modified: | December 2, 2020 | |
This is version 125 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families