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Protein

Histone deacetylase 2

Gene

HDAC2

Organism
Homo sapiens (Human)
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. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A.2 Publications

Catalytic activityi

Hydrolysis of an N6-acetyl-lysine residue of a histone to yield a deacetylated histone.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei142By similarity1

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • core promoter binding Source: Ensembl
  • deacetylase activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • heat shock protein binding Source: Ensembl
  • histone deacetylase activity Source: BHF-UCL
  • histone deacetylase binding Source: UniProtKB
  • NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
  • NF-kappaB binding Source: UniProtKB
  • protein deacetylase activity Source: BHF-UCL
  • RNA binding Source: UniProtKB
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • sequence-specific DNA binding Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL

GO - Biological processi

  • ATP-dependent chromatin remodeling Source: UniProtKB
  • behavioral response to ethanol Source: Ensembl
  • blood coagulation Source: Reactome
  • cardiac muscle hypertrophy Source: Ensembl
  • cellular response to dopamine Source: Ensembl
  • cellular response to heat Source: Ensembl
  • cellular response to hydrogen peroxide Source: Ensembl
  • cellular response to retinoic acid Source: Ensembl
  • cellular response to transforming growth factor beta stimulus Source: Ensembl
  • chromatin remodeling Source: BHF-UCL
  • circadian regulation of gene expression Source: UniProtKB
  • dendrite development Source: UniProtKB
  • embryonic digit morphogenesis Source: BHF-UCL
  • epidermal cell differentiation Source: BHF-UCL
  • eyelid development in camera-type eye Source: BHF-UCL
  • fungiform papilla formation Source: BHF-UCL
  • hair follicle placode formation Source: BHF-UCL
  • histone deacetylation Source: BHF-UCL
  • histone H3 deacetylation Source: UniProtKB
  • histone H4 deacetylation Source: UniProtKB
  • maintenance of chromatin silencing Source: BHF-UCL
  • negative regulation of apoptotic process Source: BHF-UCL
  • negative regulation of dendritic spine development Source: Ensembl
  • negative regulation of DNA binding Source: Ensembl
  • negative regulation of MHC class II biosynthetic process Source: BHF-UCL
  • negative regulation of neuron projection development Source: BHF-UCL
  • negative regulation of peptidyl-lysine acetylation Source: Ensembl
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • odontogenesis of dentin-containing tooth Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of collagen biosynthetic process Source: BHF-UCL
  • positive regulation of epithelial to mesenchymal transition Source: Ensembl
  • positive regulation of interleukin-1 production Source: Ensembl
  • positive regulation of oligodendrocyte differentiation Source: Ensembl
  • positive regulation of proteolysis Source: BHF-UCL
  • positive regulation of receptor biosynthetic process Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of tumor necrosis factor production Source: Ensembl
  • positive regulation of tyrosine phosphorylation of STAT protein Source: Ensembl
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • response to amphetamine Source: Ensembl
  • response to caffeine Source: Ensembl
  • response to cocaine Source: Ensembl
  • response to drug Source: Ensembl
  • response to hyperoxia Source: Ensembl
  • response to lipopolysaccharide Source: Ensembl
  • response to nicotine Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionChromatin regulator, Hydrolase, Repressor
Biological processBiological rhythms, Transcription, Transcription regulation

Enzyme and pathway databases

BRENDAi3.5.1.98. 2681.
ReactomeiR-HSA-193670. p75NTR negatively regulates cell cycle via SC1.
R-HSA-2122947. NOTCH1 Intracellular Domain Regulates Transcription.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-3214815. HDACs deacetylate histones.
R-HSA-427389. ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression.
R-HSA-427413. NoRC negatively regulates rRNA expression.
R-HSA-4551638. SUMOylation of chromatin organization proteins.
R-HSA-6804758. Regulation of TP53 Activity through Acetylation.
R-HSA-73762. RNA Polymerase I Transcription Initiation.
R-HSA-8943724. Regulation of PTEN gene transcription.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SABIO-RKiQ92769.
SIGNORiQ92769.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 2 (EC:3.5.1.98)
Short name:
HD2
Gene namesi
Name:HDAC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000196591.11.
HGNCiHGNC:4853. HDAC2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi3066.
OpenTargetsiENSG00000196591.
PharmGKBiPA29227.

Chemistry databases

ChEMBLiCHEMBL1937.
DrugBankiDB01223. Aminophylline.
DB05015. Belinostat.
DB00227. Lovastatin.
DB05651. MGCD-0103.
DB01303. Oxtriphylline.
DB06603. Panobinostat.
DB06176. Romidepsin.
DB05223. SB939.
DB00277. Theophylline.
DB00313. Valproic Acid.
DB02546. Vorinostat.
GuidetoPHARMACOLOGYi2616.

Polymorphism and mutation databases

BioMutaiHDAC2.
DMDMi68068066.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001146931 – 488Histone deacetylase 2Add BLAST488

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei75N6-acetyllysine; alternateBy similarity1
Cross-linki75Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei221N6-acetyllysineBy similarity1
Modified residuei262S-nitrosocysteineBy similarity1
Modified residuei274S-nitrosocysteineBy similarity1
Modified residuei394PhosphoserineCombined sources1
Modified residuei407PhosphoserineCombined sources1
Modified residuei422PhosphoserineCombined sources1
Modified residuei424PhosphoserineCombined sources1
Cross-linki439Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki458Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki462Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki478Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki481Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

S-nitrosylated by GAPDH. In neurons, S-Nitrosylation at Cys-262 and Cys-274 does not affect the enzyme activity but abolishes chromatin-binding, leading to increases acetylation of histones and activate genes that are associated with neuronal development. In embryonic cortical neurons, S-Nitrosylation regulates dendritic growth and branching.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

EPDiQ92769.
MaxQBiQ92769.
PaxDbiQ92769.
PeptideAtlasiQ92769.
PRIDEiQ92769.

PTM databases

iPTMnetiQ92769.
PhosphoSitePlusiQ92769.

Expressioni

Tissue specificityi

Widely expressed; lower levels in brain and lung.

Gene expression databases

BgeeiENSG00000196591.
CleanExiHS_HDAC2.
ExpressionAtlasiQ92769. baseline and differential.
GenevisibleiQ92769. HS.

Organism-specific databases

HPAiCAB005054.
HPA011727.

Interactioni

Subunit structurei

Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core complex associates with MTA2, MBD3, MTA1L1, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylation (NuRD) complex, or with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex. Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B. Interacts with SNW1, HDAC7, PRDM6, SAP30, SETDB1 and SUV39H1. Interacts with the H2AFY (via the non-histone region). Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Part of a complex containing the core histones H2A, H2B, H3 and H4, DEK and unphosphorylated DAXX. Part of a complex containing ATR and CHD4. Forms a heterologous complex at least with YY1. Interacts with ATR, CBFA2T3, DNMT1, MINT, HDAC10, HCFC1, NRIP1, KDM4A and PELP1. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2. Interacts with CHFR and SAP30L. Interacts (CK2 phosphorylated form) with SP3. Interacts with TSHZ3 (via its N-terminus). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with PIMREG. Interacts with BCL6 (non-acetylated form). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. Interacts with CRY1, INSM1 and ZNF431. Interacts with NACC2. Interacts with MTA1, with a preference for sumoylated MTA1. Interacts with SIX3 (By similarity). Interacts with BEND3. Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2 (PubMed:21573134).By similarity29 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • heat shock protein binding Source: Ensembl
  • histone deacetylase binding Source: UniProtKB
  • NF-kappaB binding Source: UniProtKB
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109316. 329 interactors.
CORUMiQ92769.
DIPiDIP-24220N.
IntActiQ92769. 162 interactors.
MINTiMINT-90593.
STRINGi9606.ENSP00000430432.

Chemistry databases

BindingDBiQ92769.

Structurei

Secondary structure

1488
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi12 – 15Combined sources4
Helixi20 – 22Combined sources3
Helixi34 – 45Combined sources12
Helixi48 – 51Combined sources4
Beta strandi52 – 55Combined sources4
Helixi62 – 65Combined sources4
Turni66 – 68Combined sources3
Helixi71 – 79Combined sources9
Turni82 – 84Combined sources3
Helixi85 – 88Combined sources4
Helixi89 – 95Combined sources7
Beta strandi98 – 101Combined sources4
Helixi107 – 126Combined sources20
Beta strandi131 – 135Combined sources5
Beta strandi152 – 154Combined sources3
Helixi156 – 164Combined sources9
Turni165 – 167Combined sources3
Beta strandi171 – 175Combined sources5
Beta strandi177 – 179Combined sources3
Helixi182 – 187Combined sources6
Turni188 – 190Combined sources3
Beta strandi192 – 201Combined sources10
Helixi218 – 220Combined sources3
Beta strandi224 – 229Combined sources6
Helixi235 – 253Combined sources19
Beta strandi256 – 261Combined sources6
Helixi264 – 266Combined sources3
Helixi279 – 291Combined sources13
Beta strandi296 – 299Combined sources4
Helixi306 – 320Combined sources15
Helixi335 – 338Combined sources4
Turni339 – 341Combined sources3
Beta strandi343 – 345Combined sources3
Helixi357 – 371Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MAXX-ray2.05A/B/C9-374[»]
4LXZX-ray1.85A/B/C8-376[»]
4LY1X-ray1.57A/B/C8-376[»]
5IWGX-ray1.66A/B/C8-375[»]
5IX0X-ray1.72A/B/C7-375[»]
ProteinModelPortaliQ92769.
SMRiQ92769.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92769.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni9 – 322Histone deacetylaseAdd BLAST314

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi300 – 303Poly-Gly4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1342. Eukaryota.
COG0123. LUCA.
GeneTreeiENSGT00530000062889.
HOGENOMiHOG000225180.
HOVERGENiHBG057112.
InParanoidiQ92769.
KOiK06067.
OMAiKRVCYFF.
OrthoDBiEOG091G067J.
PhylomeDBiQ92769.
TreeFamiTF106171.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiView protein in InterPro
IPR000286. His_deacetylse.
IPR003084. His_deacetylse_1.
IPR023801. His_deacetylse_dom.
PANTHERiPTHR10625. PTHR10625. 1 hit.
PfamiView protein in Pfam
PF00850. Hist_deacetyl. 1 hit.
PIRSFiPIRSF037913. His_deacetylse_1. 1 hit.
PRINTSiPR01270. HDASUPER.
PR01271. HISDACETLASE.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92769-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAYSQGGGKK KVCYYYDGDI GNYYYGQGHP MKPHRIRMTH NLLLNYGLYR
60 70 80 90 100
KMEIYRPHKA TAEEMTKYHS DEYIKFLRSI RPDNMSEYSK QMQRFNVGED
110 120 130 140 150
CPVFDGLFEF CQLSTGGSVA GAVKLNRQQT DMAVNWAGGL HHAKKSEASG
160 170 180 190 200
FCYVNDIVLA ILELLKYHQR VLYIDIDIHH GDGVEEAFYT TDRVMTVSFH
210 220 230 240 250
KYGEYFPGTG DLRDIGAGKG KYYAVNFPMR DGIDDESYGQ IFKPIISKVM
260 270 280 290 300
EMYQPSAVVL QCGADSLSGD RLGCFNLTVK GHAKCVEVVK TFNLPLLMLG
310 320 330 340 350
GGGYTIRNVA RCWTYETAVA LDCEIPNELP YNDYFEYFGP DFKLHISPSN
360 370 380 390 400
MTNQNTPEYM EKIKQRLFEN LRMLPHAPGV QMQAIPEDAV HEDSGDEDGE
410 420 430 440 450
DPDKRISIRA SDKRIACDEE FSDSEDEGEG GRRNVADHKK GAKKARIEED
460 470 480
KKETEDKKTD VKEEDKSKDN SGEKTDTKGT KSEQLSNP
Length:488
Mass (Da):55,364
Last modified:June 21, 2005 - v2
Checksum:i775419CCCDAE07FA
GO
Isoform 2 (identifier: Q92769-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: Missing.

Note: No experimental confirmation available.
Show »
Length:458
Mass (Da):51,998
Checksum:i73BF368ACAA58819
GO

Sequence cautioni

The sequence AAH31055 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAG59420 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti93 – 94QR → HI in AAC50814 (PubMed:8917507).Curated2
Sequence conflicti103V → A in AAC50814 (PubMed:8917507).Curated1
Sequence conflicti146S → Y in AAC50814 (PubMed:8917507).Curated1
Sequence conflicti248K → M in BAG59420 (PubMed:14702039).Curated1
Sequence conflicti281G → D in BAG59420 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025311230R → C1 PublicationCorresponds to variant dbSNP:rs1042903Ensembl.1
Natural variantiVAR_025312315Y → H1 PublicationCorresponds to variant dbSNP:rs17852888Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561751 – 30Missing in isoform 2. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U31814 mRNA. Translation: AAC50814.1.
AK092156 mRNA. Translation: BAG52487.1.
AK296856 mRNA. Translation: BAG59420.1. Different initiation.
AL590398 Genomic DNA. No translation available.
AL671967 Genomic DNA. No translation available.
FO393415 Genomic DNA. No translation available.
CH471051 Genomic DNA. Translation: EAW48252.1.
CH471051 Genomic DNA. Translation: EAW48253.1.
CH471051 Genomic DNA. Translation: EAW48254.1.
CH471051 Genomic DNA. Translation: EAW48255.1.
BC031055 mRNA. Translation: AAH31055.2. Different initiation.
CCDSiCCDS43493.2. [Q92769-1]
RefSeqiNP_001518.3. NM_001527.3. [Q92769-1]
XP_011534090.1. XM_011535788.1. [Q92769-3]
XP_016866288.1. XM_017010799.1. [Q92769-3]
UniGeneiHs.3352.

Genome annotation databases

EnsembliENST00000368632; ENSP00000357621; ENSG00000196591. [Q92769-3]
ENST00000519065; ENSP00000430432; ENSG00000196591. [Q92769-1]
ENST00000519108; ENSP00000430008; ENSG00000196591. [Q92769-3]
GeneIDi3066.
KEGGihsa:3066.
UCSCiuc003pwc.3. human. [Q92769-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHDAC2_HUMAN
AccessioniPrimary (citable) accession number: Q92769
Secondary accession number(s): B3KRS5
, B4DL58, E1P561, Q5SRI8, Q5SZ86, Q8NEH4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 21, 2005
Last modified: September 27, 2017
This is version 196 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families