Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P70288 (HDAC2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone deacetylase 2

Short name=HD2
EC=3.5.1.98
Alternative name(s):
YY1 transcription factor-binding protein
Gene names
Name:Hdac2
Synonyms:Yy1bp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length488 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. 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 By similarity. Ref.11

Catalytic activity

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

Subunit structure

Interacts with SNW1, PELP1, ATR, DNMT1, MINT, HDAC10, HCFC1, NRIP1, KDM4A, CHFR and SAP30L. 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. 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. 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. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2. Interacts with CBFA2T3, HDAC7, PRDM6, SAP30, SETDB1 and SUV39H1. Interacts with the H2AFY (via the non-histone region). Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with FAM64A. Interacts with BCL6 (non-acetylated form). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. Interacts with ZNF431. Interacts with INSM1. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.17 Ref.18 Ref.19

Subcellular location

Nucleus.

Post-translational modification

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.

Sequence similarities

Belongs to the histone deacetylase family. HD type 1 subfamily.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMAcetylation
Phosphoprotein
S-nitrosylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle cell development

Inferred from mutant phenotype PubMed 17322895. Source: MGI

cellular response to heat

Inferred from electronic annotation. Source: Ensembl

chromatin modification

Traceable author statement PubMed 12711221. Source: UniProtKB

dendrite development

Inferred from mutant phenotype Ref.13. Source: UniProtKB

embryonic digit morphogenesis

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

epidermal cell differentiation

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

eyelid development in camera-type eye

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

fungiform papilla formation

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

hair follicle placode formation

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

hippocampus development

Inferred from genetic interaction PubMed 19380719. Source: MGI

histone deacetylation

Inferred from genetic interaction PubMed 12975471. Source: MGI

maintenance of chromatin silencing

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

negative regulation of canonical Wnt signaling pathway

Inferred from genetic interaction PubMed 19503085. Source: MGI

negative regulation of cardiac muscle cell proliferation

Inferred from mutant phenotype PubMed 17322895. Source: MGI

negative regulation of intrinsic apoptotic signaling pathway

Inferred from genetic interaction PubMed 21093383. Source: MGI

negative regulation of neuron projection development

Inferred from direct assay Ref.13. Source: BHF-UCL

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.13. Source: BHF-UCL

neuron differentiation

Inferred from genetic interaction PubMed 19380719. Source: MGI

odontogenesis of dentin-containing tooth

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL

positive regulation of oligodendrocyte differentiation

Inferred from genetic interaction PubMed 19503085. Source: MGI

positive regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

positive regulation of receptor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 20833366. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein deacetylation

Inferred from direct assay Ref.13. Source: BHF-UCL

regulation of protein deacetylation

Inferred from genetic interaction PubMed 20833366. Source: MGI

regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 17322895. Source: MGI

regulation of sarcomere organization

Inferred from mutant phenotype PubMed 17322895. Source: MGI

response to cocaine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentESC/E(Z) complex

Inferred from sequence or structural similarity. Source: UniProtKB

NuRD complex

Inferred from electronic annotation. Source: Ensembl

Sin3 complex

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Traceable author statement PubMed 12711221. Source: UniProtKB

heterochromatin

Inferred from direct assay PubMed 14519686PubMed 14643676. Source: MGI

histone deacetylase complex

Traceable author statement PubMed 12711221. Source: UniProtKB

nuclear chromatin

Inferred from direct assay Ref.13. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 20720167. Source: MGI

replication fork

Inferred from direct assay PubMed 10888872. Source: MGI

transcription factor complex

Inferred from physical interaction PubMed 17182846. Source: MGI

transcriptional repressor complex

Inferred from physical interaction PubMed 17182846. Source: MGI

   Molecular_functionKrueppel-associated box domain binding

Inferred from physical interaction Ref.17Ref.18. Source: UniProtKB

NAD-dependent histone deacetylase activity (H3-K14 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K18 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K9 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H4-K16 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

chromatin DNA binding

Inferred from direct assay PubMed 18458156. Source: MGI

chromatin binding

Inferred from direct assay Ref.13. Source: UniProtKB

core promoter binding

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction Ref.16. Source: UniProtKB

histone deacetylase activity

Inferred from direct assay Ref.13. Source: UniProtKB

protein deacetylase activity

Inferred from direct assay Ref.13. Source: BHF-UCL

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 17392792. Source: MGI

transcription factor binding

Traceable author statement PubMed 12711221. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 488488Histone deacetylase 2
PRO_0000114694

Regions

Region9 – 322314Histone deacetylase
Compositional bias300 – 3034Poly-Gly

Sites

Active site1421 By similarity

Amino acid modifications

Modified residue2621S-nitrosocysteine Ref.13
Modified residue2741S-nitrosocysteine Ref.13
Modified residue3941Phosphoserine Ref.12 Ref.14 Ref.15
Modified residue4221Phosphoserine Ref.12 Ref.15
Modified residue4241Phosphoserine Ref.12 Ref.15

Experimental info

Mutagenesis1521C → A: Does not affect S-nitrosylation. Ref.13
Mutagenesis2621C → A: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with A-274. Ref.13
Mutagenesis2741C → A: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with A-262. Ref.13
Sequence conflict2891A → V in EDL04897. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P70288 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: B9843D24A775157C

FASTA48855,302
        10         20         30         40         50         60 
MAYSQGGGKK KVCYYYDGDI GNYYYGQGHP MKPHRIRMTH NLLLNYGLYR KMEIYRPHKA 

        70         80         90        100        110        120 
TAEEMTKYHS DEYIKFLRSI RPDNMSEYSK QMQRFNVGED CPVFDGLFEF CQLSTGGSVA 

       130        140        150        160        170        180 
GAVKLNRQQT DMAVNWAGGL HHAKKSEASG FCYVNDIVLA ILELLKYHQR VLYIDIDIHH 

       190        200        210        220        230        240 
GDGVEEAFYT TDRVMTVSFH KYGEYFPGTG DLRDIGAGKG KYYAVNFPMR DGIDDESYGQ 

       250        260        270        280        290        300 
IFKPIISKVM EMYQPSAVVL QCGADSLSGD RLGCFNLTVK GHAKCVEVAK TFNLPLLMLG 

       310        320        330        340        350        360 
GGGYTIRNVA RCWTYETAVA LDCEIPNELP YNDYFEYFGP DFKLHISPSN MTNQNTPEYM 

       370        380        390        400        410        420 
EKIKQRLFEN LRMLPHAPGV QMQAIPEDAV HEDSGDEDGE DPDKRISIRA SDKRIACDEE 

       430        440        450        460        470        480 
FSDSEDEGEG GRRNVADHKK GAKKARIEED KKETEDKKTD VKEEDKSKDN SGEKTDPKGA 


KSEQLSNP 

« Hide

References

« Hide 'large scale' references
[1]"Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3."
Yang W.-M., Inouye C.J., Zeng Y., Bearss D., Seto E.
Proc. Natl. Acad. Sci. U.S.A. 93:12845-12850(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lymphoma.
[2]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors."
Laherty C.D., Billin A.N., Lavinsky R.M., Yochum G.S., Bush A.C., Sun J.-M., Mullen T.-M., Davie J.R., Rose D.W., Glass C.K., Rosenfeld M.G., Ayer D.E., Eisenman R.N.
Mol. Cell 2:33-42(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SAP30.
[5]"Identification of a nuclear domain with deacetylase activity."
Downes M., Ordentlich P., Kao H.-Y., Alvarez J.G.A., Evans R.M.
Proc. Natl. Acad. Sci. U.S.A. 97:10330-10335(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC7.
[6]"ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain."
Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W.
Mol. Cell. Biol. 21:6470-6483(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBFA2T3.
[7]"Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases."
Vaute O., Nicolas E., Vandel L., Trouche D.
Nucleic Acids Res. 30:475-481(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUV39H1.
[8]"An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B."
Yang L., Mei Q., Zielinska-Kwiatkowska A., Matsui Y., Blackburn M.L., Benedetti D., Krumm A.A., Taborsky G.J. Jr., Chansky H.A.
Biochem. J. 369:651-657(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SETDB1.
[9]"Structural characterization of the histone variant macroH2A."
Chakravarthy S., Gundimella S.K., Caron C., Perche P.-Y., Pehrson J.R., Khochbin S., Luger K.
Mol. Cell. Biol. 25:7616-7624(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH H2AFY.
[10]"PRISM/PRDM6, a transcriptional repressor that promotes the proliferative gene program in smooth muscle cells."
Davis C.A., Haberland M., Arnold M.A., Sutherland L.B., McDonald O.G., Richardson J.A., Childs G., Harris S., Owens G.K., Olson E.N.
Mol. Cell. Biol. 26:2626-2636(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRDM6.
[11]"Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1."
Saleque S., Kim J., Rooke H.M., Orkin S.H.
Mol. Cell 27:562-572(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY AS A COMPONENT OF A GFI-RCOR-KDM1A-HDAC COMPLEX, INTERACTION WITH GFI1 AND GFI1B, FUNCTION.
[12]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND SER-424, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[13]"S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons."
Nott A., Watson P.M., Robinson J.D., Crepaldi L., Riccio A.
Nature 455:411-415(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION AT CYS-262 AND CYS-274, MUTAGENESIS OF CYS-152; CYS-262 AND CYS-274.
[14]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND SER-424, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[16]"GAPDH mediates nitrosylation of nuclear proteins."
Kornberg M.D., Sen N., Hara M.R., Juluri K.R., Nguyen J.V., Snowman A.M., Law L., Hester L.D., Snyder S.H.
Nat. Cell Biol. 12:1094-1100(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION BY GAPDH.
[17]"A novel KRAB domain-containing zinc finger transcription factor ZNF431 directly represses Patched1 transcription."
He Z., Cai J., Lim J.W., Kroll K., Ma L.
J. Biol. Chem. 286:7279-7289(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF431.
[18]"ZFP932 suppresses cellular Hedgehog response and Patched1 transcription."
Huang G.J., He Z., Ma L.
Vitam. Horm. 88:309-332(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF431.
[19]"Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors."
Welcker J.E., Hernandez-Miranda L.R., Paul F.E., Jia S., Ivanov A., Selbach M., Birchmeier C.
Development 140:4947-4958(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INSM1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U31758 mRNA. Translation: AAC52889.1.
CH466540 Genomic DNA. Translation: EDL04897.1.
BC138517 mRNA. Translation: AAI38518.1.
RefSeqNP_032255.2. NM_008229.2.
UniGeneMm.19806.

3D structure databases

ProteinModelPortalP70288.
SMRP70288. Positions 9-376.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200260. 47 interactions.
DIPDIP-32854N.
IntActP70288. 25 interactions.
MINTMINT-146936.

Chemistry

BindingDBP70288.

PTM databases

PhosphoSiteP70288.

Proteomic databases

PaxDbP70288.
PRIDEP70288.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000019911; ENSMUSP00000019911; ENSMUSG00000019777.
GeneID15182.
KEGGmmu:15182.
UCSCuc007evf.1. mouse.

Organism-specific databases

CTD3066.
MGIMGI:1097691. Hdac2.

Phylogenomic databases

eggNOGCOG0123.
GeneTreeENSGT00530000062889.
HOGENOMHOG000225180.
HOVERGENHBG057112.
InParanoidB2RRP3.
KOK06067.
OrthoDBEOG7DNNTW.
PhylomeDBP70288.
TreeFamTF106171.

Gene expression databases

ArrayExpressP70288.
BgeeP70288.
CleanExMM_HDAC2.
GenevestigatorP70288.

Family and domain databases

Gene3D3.40.800.20. 1 hit.
InterProIPR000286. His_deacetylse.
IPR003084. His_deacetylse_1.
IPR023801. His_deacetylse_dom.
[Graphical view]
PANTHERPTHR10625. PTHR10625. 1 hit.
PfamPF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFPIRSF037913. His_deacetylse_1. 1 hit.
PRINTSPR01270. HDASUPER.
PR01271. HISDACETLASE.
ProtoNetSearch...

Other

NextBio287693.
PROP70288.
SOURCESearch...

Entry information

Entry nameHDAC2_MOUSE
AccessionPrimary (citable) accession number: P70288
Secondary accession number(s): B2RRP3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 1, 1997
Last modified: April 16, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot