P70288 (HDAC2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	488 AA.
Sequence status	Complete.
Protein existence	Evidence 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 By similarity. 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 By similarity. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
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 process	Transcription Transcription regulation
Cellular component	Nucleus
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Acetylation Phosphoprotein S-nitrosylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle cell development Inferred from mutant phenotype PubMed 17322895. Source: MGI 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 H3 deacetylation Inferred from electronic annotation. Source: GOC histone H4 deacetylation Inferred from electronic annotation. Source: GOC maintenance of chromatin silencing Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL negative regulation of canonical Wnt receptor 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 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: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction PubMed 21093383. Source: BHF-UCL 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: Compara positive regulation of receptor biosynthetic process Inferred from electronic annotation. Source: Compara 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: Compara regulation of protein deacetylation Inferred from genetic interaction PubMed 20833366. Source: MGI regulation of protein kinase B signaling cascade Inferred from mutant phenotype PubMed 17322895. Source: MGI regulation of sarcomere organization Inferred from mutant phenotype PubMed 17322895. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	ESC/E(Z) complex Inferred from sequence or structural similarity. Source: UniProtKB NuRD complex Inferred from electronic annotation. Source: Compara Sin3 complex Inferred from electronic annotation. Source: Compara 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 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_function	NAD-dependent histone deacetylase activity (H3-K14 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K18 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K9 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H4-K16 specific) Inferred from electronic annotation. Source: EC chromatin DNA binding Inferred from direct assay PubMed 18458156. Source: MGI histone deacetylase activity Inferred from direct assay Ref.13. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: Compara 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 488	488	Histone deacetylase 2		PRO_0000114694
Regions
	Region	9 – 322	314	Histone deacetylase
	Compositional bias	300 – 303	4	Poly-Gly
Sites
	Active site	142	1	By similarity
Amino acid modifications
	Modified residue	262	1	S-nitrosocysteine Ref.13
	Modified residue	274	1	S-nitrosocysteine Ref.13
	Modified residue	394	1	Phosphoserine Ref.12 Ref.14 Ref.15
	Modified residue	422	1	Phosphoserine Ref.12 Ref.15
	Modified residue	424	1	Phosphoserine Ref.12 Ref.15
Experimental info
	Mutagenesis	152	1	C → A: Does not affect S-nitrosylation. Ref.13
	Mutagenesis	262	1	C → A: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with A-274. Ref.13
	Mutagenesis	274	1	C → A: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with A-262. Ref.13
	Sequence conflict	289	1	A → V in EDL04897. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P70288 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: B9843D24A775157C	FASTA	488	55,302
	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

References

	« Hide 'large scale' referencesShow '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]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND SER-424, MASS SPECTROMETRY. Tissue: Melanoma.
[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, MASS SPECTROMETRY. Tissue: Macrophage.
[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, MASS SPECTROMETRY. 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.
+	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.
IPI	IPI00137668.
RefSeq	NP_032255.2. NM_008229.2.
UniGene	Mm.19806.
3D structure databases
ProteinModelPortal	P70288.
SMR	P70288. Positions 9-374.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32854N.
IntAct	P70288. 15 interactions.
MINT	MINT-146936.
PTM databases
PhosphoSite	P70288.
Proteomic databases
PaxDb	P70288.
PRIDE	P70288.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000019911; ENSMUSP00000019911; ENSMUSG00000019777.
GeneID	15182.
KEGG	mmu:15182.
Organism-specific databases
CTD	3066.
MGI	MGI:1097691. Hdac2.
Phylogenomic databases
eggNOG	COG0123.
GeneTree	ENSGT00530000062889.
HOGENOM	HOG000225180.
HOVERGEN	HBG057112.
InParanoid	B2RRP3.
KO	K06067.
OrthoDB	EOG4868CH.
Gene expression databases
ArrayExpress	P70288.
Bgee	P70288.
CleanEx	MM_HDAC2.
Genevestigator	P70288.
GermOnline	ENSMUSG00000019777. Mus musculus.
Family and domain databases
Gene3D	3.40.800.20. 1 hit.
InterPro	IPR000286. His_deacetylse. IPR003084. His_deacetylse_1. IPR023801. His_deacetylse_dom. [Graphical view]
PANTHER	PTHR10625. PTHR10625. 1 hit.
Pfam	PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037913. His_deacetylse_1. 1 hit.
PRINTS	PR01270. HDASUPER. PR01271. HISDACETLASE.
ProtoNet	Search...
Other
BindingDB	P70288.
ChEMBL	CHEMBL4238.
NextBio	287693.
SOURCE	Search...

Entry information

Entry name

HDAC2_MOUSE

Accession

Primary (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 3, 2013
This is version 130 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program