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Protein

Histone deacetylase 5

Gene

Hdac5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity).By similarity

Catalytic activityi

Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi687 – 6871ZincBy similarity
Metal bindingi689 – 6891ZincBy similarity
Metal bindingi695 – 6951ZincBy similarity
Metal bindingi772 – 7721ZincBy similarity
Active sitei824 – 8241By similarity

GO - Molecular functioni

  • core promoter binding Source: MGI
  • core promoter sequence-specific DNA binding Source: UniProtKB
  • histone deacetylase activity Source: UniProtKB
  • histone deacetylase binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
  • protein deacetylase activity Source: MGI
  • protein kinase binding Source: UniProtKB
  • protein kinase C binding Source: MGI
  • repressing transcription factor binding Source: MGI
  • RNA polymerase III transcription factor binding Source: MGI
  • RNA polymerase II transcription corepressor binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: UniProtKB
  • transcription corepressor activity Source: MGI
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • B cell activation Source: UniProtKB
  • B cell differentiation Source: UniProtKB
  • cellular response to fluid shear stress Source: UniProtKB
  • chromatin modification Source: UniProtKB
  • heart development Source: MGI
  • histone deacetylation Source: MGI
  • inflammatory response Source: UniProtKB
  • multicellular organismal response to stress Source: MGI
  • negative regulation of cell migration involved in sprouting angiogenesis Source: MGI
  • negative regulation of gene expression Source: MGI
  • negative regulation of myotube differentiation Source: MGI
  • negative regulation of osteoblast differentiation Source: MGI
  • negative regulation of striated muscle tissue development Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • nervous system development Source: UniProtKB
  • osteoblast development Source: MGI
  • positive regulation of neural precursor cell proliferation Source: BHF-UCL
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • positive regulation of stem cell proliferation Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein deacetylation Source: MGI
  • regulation of gene expression, epigenetic Source: MGI
  • regulation of myotube differentiation Source: UniProtKB
  • regulation of protein binding Source: MGI
  • regulation of skeletal muscle fiber development Source: MGI
  • regulation of striated muscle cell differentiation Source: MGI
  • renal tubule morphogenesis Source: UniProtKB
  • response to cocaine Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 5 (EC:3.5.1.98)
Short name:
HD5
Alternative name(s):
Histone deacetylase mHDA1
Gene namesi
Name:Hdac5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1333784. Hdac5.

Subcellular locationi

  • Nucleus
  • Cytoplasm

  • Note: Shuttles between the nucleus and the cytoplasm. In muscle cells, it shuttles into the cytoplasm during myocyte differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-250 and Ser-488 by AMPK, CaMK1 and SIK1.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: MGI
  • Golgi apparatus Source: MGI
  • histone deacetylase complex Source: UniProtKB
  • nuclear body Source: MGI
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • RNA polymerase II transcription repressor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi250 – 2501S → A: Abolishes phosphorylation by SIK1 and fails to promote beta-catenin expression; when associated with A-488. 2 Publications
Mutagenesisi488 – 4881S → A: Abolishes phosphorylation by SIK1 and fails to promote beta-catenin expression; when associated with A-250. 2 Publications
Mutagenesisi824 – 8241H → A: Abolishes deacetylase activity. 1 Publication
Mutagenesisi884 – 8841H → F: Disrupts the dot-like nuclear pattern. 1 Publication

Chemistry

ChEMBLiCHEMBL2768.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11131113Histone deacetylase 5PRO_0000114702Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei250 – 2501Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD12 Publications
Modified residuei283 – 2831Phosphothreonine; by PKCBy similarity
Modified residuei488 – 4881Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD12 Publications
Modified residuei523 – 5231N6-acetyllysineBy similarity
Modified residuei600 – 6001PhosphoserineBy similarity
Modified residuei650 – 6501PhosphoserineBy similarity
Modified residuei1099 – 10991PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-250 and Ser-488. The phosphorylation is required for the export to the cytoplasm and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import (By similarity). Phosphorylated by GRK5, leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription.By similarity3 Publications
Ubiquitinated. Polyubiquitination however does not lead to its degradation (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9Z2V6.
PaxDbiQ9Z2V6.
PRIDEiQ9Z2V6.

PTM databases

iPTMnetiQ9Z2V6.
PhosphoSiteiQ9Z2V6.

Expressioni

Gene expression databases

CleanExiMM_HDAC5.

Interactioni

Subunit structurei

Interacts with AHRR, BAHD1, BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with BCL6, DDIT3/CHOP, GRK5, KDM5B and MYOCD. Interacts with EP300 in the presence of TFAP2C.8 Publications

GO - Molecular functioni

  • histone deacetylase binding Source: MGI
  • protein kinase binding Source: UniProtKB
  • protein kinase C binding Source: MGI
  • repressing transcription factor binding Source: MGI
  • RNA polymerase III transcription factor binding Source: MGI
  • RNA polymerase II transcription corepressor binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

DIPiDIP-40855N.
IntActiQ9Z2V6. 4 interactions.
MINTiMINT-125422.
STRINGi10090.ENSMUSP00000102770.

Chemistry

BindingDBiQ9Z2V6.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2V6.
SMRiQ9Z2V6. Positions 672-1052.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni675 – 1019345Histone deacetylaseAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1072 – 111342Nuclear export signalBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi47 – 526Poly-Gly
Compositional biasi85 – 928Poly-Gln
Compositional biasi577 – 58812Poly-GluAdd
BLAST

Domaini

The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
HOVERGENiHBG057100.
InParanoidiQ9Z2V6.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
IPR030703. Histone_deacetylase_5.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 2 hits.
PTHR10625:SF57. PTHR10625:SF57. 2 hits.
PfamiPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFiPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSiPR01270. HDASUPER.

Sequencei

Sequence statusi: Complete.

Q9Z2V6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSPNESDGM SGREPSLGIL PRTPLHSIPV AVEVKPVLPG AMPSSMGGGG
60 70 80 90 100
GGSPSPVELR GALAGPMDPA LREQQLQQEL LVLKQQQQLQ KQLLFAEFQK
110 120 130 140 150
QHDHLTRQHE VQLQKHLKQQ QEMLAAKRQQ ELEQQRQREQ QRQEELEKQR
160 170 180 190 200
LEQQLLILRN KEKSKESAIA STEVKLRLQE FLLSKSKEPT PGGLNHSLPQ
210 220 230 240 250
HPKCWGAHHA SLDQSSPPQS GPPGTPPSYK LPLLGPYDSR DDFPLRKTAS
260 270 280 290 300
EPNLKVRSRL KQKVAERRSS PLLRRKDGTV ISTFKKRAVE ITGTGPGVSS
310 320 330 340 350
VCNSAPGSGP SSPNSSHSTI AENGFTGSVP NIPTEMIPQH RALPLDSSPN
360 370 380 390 400
QFSLYTSPSL PNISLGLQAT VTVTNSHLTA SPKLSTQQEA ERQALQSLRQ
410 420 430 440 450
GGTLTGKFMS TSSIPGCLLG VALEGDTSPH GHASLLQHVC SWTGRQQSTL
460 470 480 490 500
IAVPLHGQSP LVTGERVATS MRTVGKLPRH RPLSRTQSSP LPQSPQALQQ
510 520 530 540 550
LVMQQQHQQF LEKQKQQQMQ LGKILTKTGE LSRQPTTHPE ETEEELTEQQ
560 570 580 590 600
EALLGEGALT IPREGSTESE STQEDLEEEE EEEEEEEEDC IQVKDEDGES
610 620 630 640 650
GPDEGPDLEE SSAGYKKLFA DAQQLQPLQV YQAPLSLATV PHQALGRTQS
660 670 680 690 700
SPAAPGSMKS PTDQPTVVKH LFTTGVVYDT FMLKHQCMCG NTHVHPEHAG
710 720 730 740 750
RIQSIWSRLQ ETGLLGKCER IRGRKATLDE IQTVHSEYHT LLYGTSPLNR
760 770 780 790 800
QKLDSKKLLG PISQKMYAML PCGGIGVDSD TVWNEMHSSS AVRMAVGCLV
810 820 830 840 850
ELAFKVAAGE LKNGFAIIRP PGHHAEESTA MGFCFFNSVA ITAKLLQQKL
860 870 880 890 900
SVGKVLIVDW DIHHGNGTQQ AFYNDPSVLY ISLHRYDNGN FFPGSGAPEE
910 920 930 940 950
VGGGPGVGYN VNVAWTGGVD PPIGDVEYLT AFRTVVMPIA QEFSPDVVLV
960 970 980 990 1000
SAGFDAVEGH LSPLGGYSVT ARCFGHLTRQ LMTLAGGRVV LALEGGHDLT
1010 1020 1030 1040 1050
AICDASEACV SALLSVELQP LDEAVLQQKP SVNAVATLEK VIEIQSKHWS
1060 1070 1080 1090 1100
CVQRFAAGLG CSLREAQTGE KEEAETVSAM ALLSVGAEQA QAVATQEHSP
1110
RPAEEPMEQE PAL
Length:1,113
Mass (Da):120,942
Last modified:May 1, 2000 - v2
Checksum:i63071AF45B87815A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71S → SA in AAF31418 (PubMed:10640276).Curated
Sequence conflicti18 – 181G → E in AAF31418 (PubMed:10640276).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF006602 mRNA. Translation: AAD09834.2.
AF207748 mRNA. Translation: AAF31418.1.
UniGeneiMm.22665.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF006602 mRNA. Translation: AAD09834.2.
AF207748 mRNA. Translation: AAF31418.1.
UniGeneiMm.22665.

3D structure databases

ProteinModelPortaliQ9Z2V6.
SMRiQ9Z2V6. Positions 672-1052.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-40855N.
IntActiQ9Z2V6. 4 interactions.
MINTiMINT-125422.
STRINGi10090.ENSMUSP00000102770.

Chemistry

BindingDBiQ9Z2V6.
ChEMBLiCHEMBL2768.

PTM databases

iPTMnetiQ9Z2V6.
PhosphoSiteiQ9Z2V6.

Proteomic databases

MaxQBiQ9Z2V6.
PaxDbiQ9Z2V6.
PRIDEiQ9Z2V6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1333784. Hdac5.

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
HOVERGENiHBG057100.
InParanoidiQ9Z2V6.

Miscellaneous databases

ChiTaRSiHdac5. mouse.
PROiQ9Z2V6.
SOURCEiSearch...

Gene expression databases

CleanExiMM_HDAC5.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
IPR030703. Histone_deacetylase_5.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 2 hits.
PTHR10625:SF57. PTHR10625:SF57. 2 hits.
PfamiPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFiPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSiPR01270. HDASUPER.
ProtoNetiSearch...

Entry informationi

Entry nameiHDAC5_MOUSE
AccessioniPrimary (citable) accession number: Q9Z2V6
Secondary accession number(s): Q9JL73
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: July 6, 2016
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.