ID HDAC2_MOUSE Reviewed; 488 AA. AC P70288; B2RRP3; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 220. DE RecName: Full=Histone deacetylase 2 {ECO:0000305}; DE Short=HD2; DE EC=3.5.1.98 {ECO:0000269|PubMed:18754010, ECO:0000305|PubMed:30279482}; DE AltName: Full=Protein deacylase HDAC2 {ECO:0000305}; DE EC=3.5.1.- {ECO:0000269|PubMed:30279482}; DE AltName: Full=YY1 transcription factor-binding protein; GN Name=Hdac2 {ECO:0000312|MGI:MGI:1097691}; Synonyms=Yy1bp; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lymphoma; RX PubMed=8917507; DOI=10.1073/pnas.93.23.12845; RA Yang W.-M., Inouye C.J., Zeng Y., Bearss D., Seto E.; RT "Transcriptional repression by YY1 is mediated by interaction with a RT mammalian homolog of the yeast global regulator RPD3."; RL Proc. Natl. Acad. Sci. U.S.A. 93:12845-12850(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH SAP30. RX PubMed=9702189; DOI=10.1016/s1097-2765(00)80111-2; RA Laherty C.D., Billin A.N., Lavinsky R.M., Yochum G.S., Bush A.C., RA Sun J.-M., Mullen T.-M., Davie J.R., Rose D.W., Glass C.K., Rosenfeld M.G., RA Ayer D.E., Eisenman R.N.; RT "SAP30, a component of the mSin3 corepressor complex involved in N-CoR- RT mediated repression by specific transcription factors."; RL Mol. Cell 2:33-42(1998). RN [5] RP INTERACTION WITH HDAC7. RX PubMed=10984530; DOI=10.1073/pnas.97.19.10330; RA Downes M., Ordentlich P., Kao H.-Y., Alvarez J.G.A., Evans R.M.; RT "Identification of a nuclear domain with deacetylase activity."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10330-10335(2000). RN [6] RP INTERACTION WITH CBFA2T3. RX PubMed=11533236; DOI=10.1128/mcb.21.19.6470-6483.2001; RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., RA Downing J.R., Meyers S., Hiebert S.W.; RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with RT multiple histone deacetylases and binds mSin3A through its oligomerization RT domain."; RL Mol. Cell. Biol. 21:6470-6483(2001). RN [7] RP INTERACTION WITH SUV39H1. RX PubMed=11788710; DOI=10.1093/nar/30.2.475; RA Vaute O., Nicolas E., Vandel L., Trouche D.; RT "Functional and physical interaction between the histone methyl transferase RT Suv39H1 and histone deacetylases."; RL Nucleic Acids Res. 30:475-481(2002). RN [8] RP INTERACTION WITH SETDB1. RX PubMed=12398767; DOI=10.1042/bj20020854; RA Yang L., Mei Q., Zielinska-Kwiatkowska A., Matsui Y., Blackburn M.L., RA Benedetti D., Krumm A.A., Taborsky G.J. Jr., Chansky H.A.; RT "An ERG (ets-related gene)-associated histone methyltransferase interacts RT with histone deacetylases 1/2 and transcription co-repressors mSin3A/B."; RL Biochem. J. 369:651-657(2003). RN [9] RP FUNCTION IN CIRCADIAN CLOCK, AND INTERACTION WITH CRY1. RX PubMed=15226430; DOI=10.1128/mcb.24.14.6278-6287.2004; RA Naruse Y., Oh-hashi K., Iijima N., Naruse M., Yoshioka H., Tanaka M.; RT "Circadian and light-induced transcription of clock gene Per1 depends on RT histone acetylation and deacetylation."; RL Mol. Cell. Biol. 24:6278-6287(2004). RN [10] RP INTERACTION WITH MACROH2A1. RX PubMed=16107708; DOI=10.1128/mcb.25.17.7616-7624.2005; RA Chakravarthy S., Gundimella S.K., Caron C., Perche P.-Y., Pehrson J.R., RA Khochbin S., Luger K.; RT "Structural characterization of the histone variant macroH2A."; RL Mol. Cell. Biol. 25:7616-7624(2005). RN [11] RP INTERACTION WITH PRDM6. RX PubMed=16537907; DOI=10.1128/mcb.26.7.2626-2636.2006; RA Davis C.A., Haberland M., Arnold M.A., Sutherland L.B., McDonald O.G., RA Richardson J.A., Childs G., Harris S., Owens G.K., Olson E.N.; RT "PRISM/PRDM6, a transcriptional repressor that promotes the proliferative RT gene program in smooth muscle cells."; RL Mol. Cell. Biol. 26:2626-2636(2006). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY AS A COMPONENT OF A GFI-RCOR-KDM1A-HDAC RP COMPLEX, INTERACTION WITH GFI1 AND GFI1B, AND FUNCTION. RX PubMed=17707228; DOI=10.1016/j.molcel.2007.06.039; RA Saleque S., Kim J., Rooke H.M., Orkin S.H.; RT "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b RT is mediated by the cofactors CoREST and LSD1."; RL Mol. Cell 27:562-572(2007). RN [13] RP INTERACTION WITH SIX3. RX PubMed=17666527; DOI=10.1073/pnas.0705878104; RA Manavathi B., Peng S., Rayala S.K., Talukder A.H., Wang M.H., Wang R.A., RA Balasenthil S., Agarwal N., Frishman L.J., Kumar R.; RT "Repression of Six3 by a corepressor regulates rhodopsin expression."; RL Proc. Natl. Acad. Sci. U.S.A. 104:13128-13133(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394 AND SER-422, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [15] RP S-NITROSYLATION AT CYS-262 AND CYS-274, FUNCTION, CATALYTIC ACTIVITY, AND RP MUTAGENESIS OF CYS-152; CYS-262 AND CYS-274. RX PubMed=18754010; DOI=10.1038/nature07238; RA Nott A., Watson P.M., Robinson J.D., Crepaldi L., Riccio A.; RT "S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in RT neurons."; RL Nature 455:411-415(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND SER-424, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394 AND SER-422, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [19] RP FUNCTION. RX PubMed=20071335; DOI=10.1074/jbc.m109.079095; RA Li D.Q., Pakala S.B., Reddy S.D., Ohshiro K., Peng S.H., Lian Y., Fu S.W., RA Kumar R.; RT "Revelation of p53-independent function of MTA1 in DNA damage response via RT modulation of the p21 WAF1-proliferating cell nuclear antigen pathway."; RL J. Biol. Chem. 285:10044-10052(2010). RN [20] RP RETRACTED PAPER. RX PubMed=20519513; DOI=10.1074/jbc.m110.139469; RA Pakala S.B., Bui-Nguyen T.M., Reddy S.D., Li D.Q., Peng S., Rayala S.K., RA Behringer R.R., Kumar R.; RT "Regulation of NF-kappaB circuitry by a component of the nucleosome RT remodeling and deacetylase complex controls inflammatory response RT homeostasis."; RL J. Biol. Chem. 285:23590-23597(2010). RN [21] RP CAUTION, AND RETRACTION NOTICE OF PUBMED:20519513. RX PubMed=28314777; DOI=10.1074/jbc.a117.139469; RA Pakala S.B., Bui-Nguyen T.M., Reddy S.D., Li D.Q., Peng S., Rayala S.K., RA Behringer R.R., Kumar R.; RL J. Biol. Chem. 292:4764-4764(2017). RN [22] RP S-NITROSYLATION BY GAPDH. RX PubMed=20972425; DOI=10.1038/ncb2114; RA Kornberg M.D., Sen N., Hara M.R., Juluri K.R., Nguyen J.V., Snowman A.M., RA Law L., Hester L.D., Snyder S.H.; RT "GAPDH mediates nitrosylation of nuclear proteins."; RL Nat. Cell Biol. 12:1094-1100(2010). RN [23] RP INTERACTION WITH ZNF431. RX PubMed=21177534; DOI=10.1074/jbc.m110.178780; RA He Z., Cai J., Lim J.W., Kroll K., Ma L.; RT "A novel KRAB domain-containing zinc finger transcription factor ZNF431 RT directly represses Patched1 transcription."; RL J. Biol. Chem. 286:7279-7289(2011). RN [24] RP INTERACTION WITH ZNF431. RX PubMed=22391310; DOI=10.1016/b978-0-12-394622-5.00014-6; RA Huang G.J., He Z., Ma L.; RT "ZFP932 suppresses cellular Hedgehog response and Patched1 transcription."; RL Vitam. Horm. 88:309-332(2012). RN [25] RP INTERACTION WITH INSM1. RX PubMed=24227653; DOI=10.1242/dev.097642; RA Welcker J.E., Hernandez-Miranda L.R., Paul F.E., Jia S., Ivanov A., RA Selbach M., Birchmeier C.; RT "Insm1 controls development of pituitary endocrine cells and requires a RT SNAG domain for function and for recruitment of histone-modifying RT factors."; RL Development 140:4947-4958(2013). RN [26] RP IDENTIFICATION IN THE NURD COMPLEX, INTERACTION WITH CHD4 AND CHD5, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=27806305; DOI=10.1016/j.celrep.2016.10.022; RA Nitarska J., Smith J.G., Sherlock W.T., Hillege M.M., Nott A., RA Barshop W.D., Vashisht A.A., Wohlschlegel J.A., Mitter R., Riccio A.; RT "A Functional Switch of NuRD Chromatin Remodeling Complex Subunits RT Regulates Mouse Cortical Development."; RL Cell Rep. 17:1683-1698(2016). RN [27] RP INTERACTION WITH PWWP2B. RX PubMed=34180153; DOI=10.1002/advs.202102060; RA Yan L., Jin W., Zhao Q., Cui X., Shi T., Xu Y., Li F., Jin W., Zhang Z., RA Zhang Z., Tang Q.Q., Pan D.; RT "PWWP2B Fine-Tunes Adipose Thermogenesis by Stabilizing HDACs in a NuRD RT Subcomplex."; RL Adv. Sci. 8:e2102060-e2102060(2021). RN [28] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30279482; DOI=10.1038/s41598-018-32927-9; RA Kelly R.D.W., Chandru A., Watson P.J., Song Y., Blades M., Robertson N.S., RA Jamieson A.G., Schwabe J.W.R., Cowley S.M.; RT "Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone RT acetylation and crotonylation in vivo."; RL Sci. Rep. 8:14690-14690(2018). RN [29] RP IDENTIFICATION IN A COMPLEX WITH HDAC1; KCTD19; DNTTIP1 AND ZNF541. RX PubMed=34075040; DOI=10.1038/s41467-021-23378-4; RA Horisawa-Takada Y., Kodera C., Takemoto K., Sakashita A., Horisawa K., RA Maeda R., Shimada R., Usuki S., Fujimura S., Tani N., Matsuura K., RA Akiyama T., Suzuki A., Niwa H., Tachibana M., Ohba T., Katabuchi H., RA Namekawa S.H., Araki K., Ishiguro K.I.; RT "Meiosis-specific ZFP541 repressor complex promotes developmental RT progression of meiotic prophase towards completion during mouse RT spermatogenesis."; RL Nat. Commun. 12:3184-3184(2021). RN [30] RP IDENTIFICATION IN A COMPLEX WITH HDAC1; KCTD19; DNTTIP1 AND ZNF541. RX PubMed=35341968; DOI=10.1016/j.jgg.2022.03.005; RA Li Y., Meng R., Li S., Gu B., Xu X., Zhang H., Tan X., Shao T., Wang J., RA Xu D., Wang F.; RT "The ZFP541-KCTD19 complex is essential for pachytene progression by RT activating meiotic genes during mouse spermatogenesis."; RL J. Genet. Genomics 49:1029-1041(2022). CC -!- FUNCTION: Histone deacetylase that catalyzes the deacetylation of CC lysine residues on the N-terminal part of the core histones (H2A, H2B, CC H3 and H4) (PubMed:18754010). Histone deacetylation gives a tag for CC epigenetic repression and plays an important role in transcriptional CC regulation, cell cycle progression and developmental events CC (PubMed:18754010). Histone deacetylases act via the formation of large CC multiprotein complexes (PubMed:18754010). Forms transcriptional CC repressor complexes by associating with MAD, SIN3, YY1 and N-COR (By CC similarity). Component of a RCOR/GFI/KDM1A/HDAC complex that CC suppresses, via histone deacetylase (HDAC) recruitment, a number of CC genes implicated in multilineage blood cell development CC (PubMed:17707228). Acts as a component of the histone deacetylase NuRD CC complex which participates in the remodeling of chromatin (By CC similarity). Component of the SIN3B complex that represses CC transcription and counteracts the histone acetyltransferase activity of CC EP300 through the recognition H3K27ac marks by PHF12 and the activity CC of the histone deacetylase HDAC2 (By similarity). Also deacetylates CC non-histone targets: deacetylates TSHZ3, thereby regulating its CC transcriptional repressor activity (By similarity). May be involved in CC the transcriptional repression of circadian target genes, such as PER1, CC mediated by CRY1 through histone deacetylation (PubMed:15226430). CC Involved in MTA1-mediated transcriptional corepression of TFF1 and CC CDKN1A (PubMed:20071335). In addition to protein deacetylase activity, CC also acts as a protein-lysine deacylase by recognizing other acyl CC groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2- CC hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine CC residues, leading to protein decrotonylation and de-2- CC hydroxyisobutyrylation, respectively (PubMed:30279482). CC {ECO:0000250|UniProtKB:Q92769, ECO:0000269|PubMed:15226430, CC ECO:0000269|PubMed:17707228, ECO:0000269|PubMed:18754010, CC ECO:0000269|PubMed:20071335, ECO:0000269|PubMed:30279482}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl- CC [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA- CC COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089, CC ChEBI:CHEBI:61930; EC=3.5.1.98; CC Evidence={ECO:0000269|PubMed:18754010, ECO:0000305|PubMed:30279482}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197; CC Evidence={ECO:0000269|PubMed:18754010, ECO:0000305|PubMed:30279482}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] = acetate + L-lysyl- CC [protein]; Xref=Rhea:RHEA:58108, Rhea:RHEA-COMP:9752, Rhea:RHEA- CC COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089, CC ChEBI:CHEBI:61930; Evidence={ECO:0000250|UniProtKB:Q92769}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58109; CC Evidence={ECO:0000250|UniProtKB:Q92769}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] = (2E)-2-butenoate CC + L-lysyl-[protein]; Xref=Rhea:RHEA:69172, Rhea:RHEA-COMP:9752, CC Rhea:RHEA-COMP:13707, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:35899, ChEBI:CHEBI:137954; CC Evidence={ECO:0000269|PubMed:30279482}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69173; CC Evidence={ECO:0000269|PubMed:30279482}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] = 2- CC hydroxy-2-methylpropanoate + L-lysyl-[protein]; Xref=Rhea:RHEA:69176, CC Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:15921, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:19641, ChEBI:CHEBI:29969, ChEBI:CHEBI:144968; CC Evidence={ECO:0000250|UniProtKB:Q92769}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69177; CC Evidence={ECO:0000250|UniProtKB:Q92769}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:Q92769}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:Q92769}; CC Note=Binds 2 Ca(2+) ions per subunit. {ECO:0000250|UniProtKB:Q92769}; CC -!- SUBUNIT: Part of the core histone deacetylase (HDAC) complex composed CC of HDAC1, HDAC2, RBBP4 and RBBP7, the core complex associates with CC SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex (By similarity). CC Component of the nucleosome remodeling and deacetylase (NuRD) repressor CC complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, CC HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CC CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:27806305). The CC exact stoichiometry of the NuRD complex is unknown, and some subunits CC such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 CC define mutually exclusive NuRD complexes (PubMed:27806305). Component CC of a RCOR/GFI/KDM1A/HDAC complex (PubMed:17707228). Component of a BHC CC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, CC RCOR1 and PHF21A (By similarity). The BHC complex may also contain CC ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I (By similarity). Part of a complex CC containing the core histones H2A, H2B, H3 and H4, DEK and CC unphosphorylated DAXX (By similarity). Part of a complex containing ATR CC and CHD4 (By similarity). Forms a heterologous complex at least with CC YY1 (By similarity). Interacts in the late S-phase of DNA-replication CC with DNMT1 in the other transcriptional repressor complex composed of CC DNMT1, DMAP1, PCNA, CAF1 (By similarity). Component of a mSin3A CC corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 CC and HDAC2 (By similarity). Part of a complex composed of TRIM28, HDAC1, CC HDAC2 and EHMT2 (By similarity). Part of a complex containing at least CC CDYL, MIER1, MIER2, HDAC1 and HDAC2 (By similarity). Component of a CC histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2 CC (By similarity). Forms a complex comprising APPL1, RUVBL2, APPL2, CC CTNNB1 and HDAC1 (By similarity). Interacts directly with GFI1 (By CC similarity). Interacts directly with GFI1B (By similarity). Interacts CC with APEX1; the interaction is not dependent on the acetylated status CC of APEX1 (By similarity). Interacts with ATR (By similarity). Interacts CC with BCL6 (non-acetylated form) (By similarity). Interacts with BEND3 CC (By similarity). Interacts with CBFA2T3 (PubMed:11533236). Interacts CC with CDK2AP1 (By similarity). Interacts with CHD4 (PubMed:27806305). CC Interacts with CHD5 (PubMed:27806305). Interacts with CHFR (By CC similarity). Interacts with CRY1 (PubMed:15226430). Interacts with CC DNMT1 (By similarity). Interacts with GATAD2A (By similarity). CC Interacts with HCFC1 (By similarity). Interacts with HDAC7 CC (PubMed:10984530). Interacts with HDAC10 (By similarity). Interacts CC with INSM1 (PubMed:24227653). Interacts with KDM4A (By similarity). CC Interacts with MACROH2A1 (via the non-histone region) CC (PubMed:16107708). Interacts with MBD3L2 (By similarity). Interacts CC with MTA1, with a preference for sumoylated MTA1 (By similarity). CC Interacts with NACC2 (By similarity). Interacts with NRIP1 (By CC similarity). Interacts with PELP1 (By similarity). Interacts with CC PIMREG (By similarity). Interacts with PRDM6 (PubMed:16537907). CC Interacts with PWWP2B (PubMed:34180153) Interacts with SAP30 CC (PubMed:9702189). Interacts with SAP30L (By similarity). Interacts with CC SETDB1 (PubMed:12398767). Interacts with SIX3 (PubMed:17666527). CC Interacts with SMARCAD1 (By similarity). Interacts with SNW1 (By CC similarity). Interacts with SPHK2 (By similarity). Interacts with CC SPEN/MINT (By similarity). Interacts (CK2 phosphorylated form) with SP3 CC (By similarity). Interacts with SUV39H1 (PubMed:11788710). Interacts CC with TSHZ3 (via its N-terminus) (By similarity). Interacts with ZMYND8 CC (By similarity). Interacts with ZNF431 (PubMed:21177534, CC PubMed:22391310). Interacts with ZNF263; recruited to the SIX3 promoter CC along with other proteins involved in chromatin modification and CC transcriptional corepression where it contributes to transcriptional CC repression (By similarity). Identified in a complex with HDAC1, KCTD19, CC DNTTIP1 and ZNF541 (PubMed:34075040, PubMed:35341968). Component of the CC SIN3B complex, which includes SIN3B, HDAC2, PHF12 and MORF4L1; CC interacts directly with all subunits (By similarity). CC {ECO:0000250|UniProtKB:Q92769, ECO:0000269|PubMed:10984530, CC ECO:0000269|PubMed:11533236, ECO:0000269|PubMed:11788710, CC ECO:0000269|PubMed:12398767, ECO:0000269|PubMed:15226430, CC ECO:0000269|PubMed:16107708, ECO:0000269|PubMed:16537907, CC ECO:0000269|PubMed:17666527, ECO:0000269|PubMed:17707228, CC ECO:0000269|PubMed:21177534, ECO:0000269|PubMed:22391310, CC ECO:0000269|PubMed:24227653, ECO:0000269|PubMed:27806305, CC ECO:0000269|PubMed:34075040, ECO:0000269|PubMed:34180153, CC ECO:0000269|PubMed:35341968, ECO:0000269|PubMed:9702189}. CC -!- INTERACTION: CC P70288; Q6ZQ88: Kdm1a; NbExp=4; IntAct=EBI-302251, EBI-1216284; CC P70288; Q9R190: Mta2; NbExp=7; IntAct=EBI-302251, EBI-904134; CC P70288; P11103: Parp1; NbExp=3; IntAct=EBI-302251, EBI-642213; CC P70288; Q8C796: Rcor2; NbExp=2; IntAct=EBI-302251, EBI-3043949; CC P70288; Q60520: Sin3a; NbExp=7; IntAct=EBI-302251, EBI-349034; CC P70288; Q62233: Six3; NbExp=2; IntAct=EBI-302251, EBI-2297327; CC P70288; Q3TKT4: Smarca4; NbExp=4; IntAct=EBI-302251, EBI-1210244; CC P70288; E9QAG8: Znf431; NbExp=3; IntAct=EBI-302251, EBI-9549639; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q92769}. Cytoplasm CC {ECO:0000250|UniProtKB:Q92769}. CC -!- PTM: S-nitrosylated by GAPDH. In neurons, S-nitrosylation at Cys-262 CC and Cys-274 does not affect enzyme activity, but induces HDAC2 release CC from chromatin. This in turn increases acetylation of histones CC surrounding neurotrophin-dependent gene promoters and promotes their CC transcription. In embryonic cortical neurons, S-Nitrosylation regulates CC dendritic growth and branching. {ECO:0000269|PubMed:18754010, CC ECO:0000269|PubMed:20519513, ECO:0000269|PubMed:20972425}. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1 CC subfamily. {ECO:0000305}. CC -!- CAUTION: Was originally thought to be S-nitrosylated and to interact CC with MTA1 (PubMed:20519513). However, this work was later retracted CC (PubMed:28314777). Nevertheless, other publications demonstrate that it CC is S-nitrosylated and there are several publications in the human CC ortholog demonstrating its interaction with MTA1 (PubMed:18754010, CC PubMed:20972425). {ECO:0000269|PubMed:18754010, CC ECO:0000269|PubMed:20519513, ECO:0000269|PubMed:20972425, CC ECO:0000305|PubMed:28314777}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U31758; AAC52889.1; -; mRNA. DR EMBL; CH466540; EDL04897.1; -; Genomic_DNA. DR EMBL; BC138517; AAI38518.1; -; mRNA. DR CCDS; CCDS23783.1; -. DR RefSeq; NP_032255.2; NM_008229.2. DR AlphaFoldDB; P70288; -. DR SMR; P70288; -. DR BioGRID; 200260; 68. DR ComplexPortal; CPX-3441; SIN3A histone deacetylase complex, ES cell-specific variant. DR ComplexPortal; CPX-3443; SIN3A histone deacetylase complex. DR ComplexPortal; CPX-3444; SIN3B histone deacetylase complex. DR ComplexPortal; CPX-953; MBD2/NuRD nucleosome remodeling and deacetylase complex. DR ComplexPortal; CPX-954; MBD3/NuRD nucleosome remodeling and deacetylase complex. DR CORUM; P70288; -. DR DIP; DIP-32854N; -. DR IntAct; P70288; 41. DR MINT; P70288; -. DR STRING; 10090.ENSMUSP00000019911; -. DR BindingDB; P70288; -. DR ChEMBL; CHEMBL3832944; -. DR ChEMBL; CHEMBL3883302; -. DR ChEMBL; CHEMBL4523989; -. DR GlyGen; P70288; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P70288; -. DR PhosphoSitePlus; P70288; -. DR EPD; P70288; -. DR jPOST; P70288; -. DR MaxQB; P70288; -. DR PaxDb; 10090-ENSMUSP00000019911; -. DR PeptideAtlas; P70288; -. DR ProteomicsDB; 269728; -. DR Pumba; P70288; -. DR DNASU; 15182; -. DR GeneID; 15182; -. DR KEGG; mmu:15182; -. DR UCSC; uc007evf.1; mouse. DR AGR; MGI:1097691; -. DR CTD; 3066; -. DR MGI; MGI:1097691; Hdac2. DR eggNOG; KOG1342; Eukaryota. DR InParanoid; P70288; -. DR OrthoDB; 1327607at2759; -. DR PhylomeDB; P70288; -. DR TreeFam; TF106171; -. DR BRENDA; 3.5.1.98; 3474. DR Reactome; R-MMU-3214815; HDACs deacetylate histones. DR Reactome; R-MMU-350054; Notch-HLH transcription pathway. DR Reactome; R-MMU-4551638; SUMOylation of chromatin organization proteins. DR Reactome; R-MMU-6804758; Regulation of TP53 Activity through Acetylation. DR Reactome; R-MMU-73762; RNA Polymerase I Transcription Initiation. DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription. DR Reactome; R-MMU-9022692; Regulation of MECP2 expression and activity. DR Reactome; R-MMU-9701898; STAT3 nuclear events downstream of ALK signaling. DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production. DR BioGRID-ORCS; 15182; 5 hits in 85 CRISPR screens. DR ChiTaRS; Hdac2; mouse. DR PRO; PR:P70288; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P70288; Protein. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0035098; C:ESC/E(Z) complex; ISS:UniProtKB. DR GO; GO:0000792; C:heterochromatin; IDA:MGI. DR GO; GO:0000118; C:histone deacetylase complex; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016581; C:NuRD complex; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0005657; C:replication fork; IDA:MGI. DR GO; GO:0090571; C:RNA polymerase II transcription repressor complex; IDA:BHF-UCL. DR GO; GO:0070822; C:Sin3-type complex; ISO:MGI. DR GO; GO:0005667; C:transcription regulator complex; IPI:MGI. DR GO; GO:0017053; C:transcription repressor complex; IPI:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI. DR GO; GO:0019213; F:deacetylase activity; ISO:MGI. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI. DR GO; GO:0042393; F:histone binding; ISO:MGI. DR GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0160009; F:histone decrotonylase activity; IDA:UniProtKB. DR GO; GO:0034739; F:histone H4K16 deacetylase activity; IMP:CACAO. DR GO; GO:0035851; F:Krueppel-associated box domain binding; IPI:UniProtKB. DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI. DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI. DR GO; GO:0160010; F:protein de-2-hydroxyisobutyrylase activity; ISS:UniProtKB. DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:BHF-UCL. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0001222; F:transcription corepressor binding; IPI:BHF-UCL. DR GO; GO:0055013; P:cardiac muscle cell development; IMP:MGI. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:MGI. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI. DR GO; GO:0035984; P:cellular response to trichostatin A; IDA:MGI. DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; ISO:MGI. DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:UniProtKB. DR GO; GO:0016358; P:dendrite development; IMP:UniProtKB. DR GO; GO:0042733; P:embryonic digit morphogenesis; IGI:BHF-UCL. DR GO; GO:0009913; P:epidermal cell differentiation; IGI:BHF-UCL. DR GO; GO:0061029; P:eyelid development in camera-type eye; IGI:BHF-UCL. DR GO; GO:0061198; P:fungiform papilla formation; IGI:BHF-UCL. DR GO; GO:0060789; P:hair follicle placode formation; IGI:BHF-UCL. DR GO; GO:0031507; P:heterochromatin formation; ISO:MGI. DR GO; GO:0021766; P:hippocampus development; IGI:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; IGI:BHF-UCL. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI. DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IMP:MGI. DR GO; GO:0030336; P:negative regulation of cell migration; NAS:ComplexPortal. DR GO; GO:0061000; P:negative regulation of dendritic spine development; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IGI:MGI. DR GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:BHF-UCL. DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:BHF-UCL. DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; ISO:MGI. DR GO; GO:1902455; P:negative regulation of stem cell population maintenance; NAS:ComplexPortal. DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:BHF-UCL. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; NAS:ComplexPortal. DR GO; GO:0030182; P:neuron differentiation; IGI:MGI. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IGI:BHF-UCL. DR GO; GO:0048709; P:oligodendrocyte differentiation; IGI:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; NAS:ComplexPortal. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:MGI. DR GO; GO:0032732; P:positive regulation of interleukin-1 production; ISO:MGI. DR GO; GO:1902437; P:positive regulation of male mating behavior; ISO:MGI. DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IGI:MGI. DR GO; GO:0045862; P:positive regulation of proteolysis; ISO:MGI. DR GO; GO:1902459; P:positive regulation of stem cell population maintenance; NAS:ComplexPortal. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI. DR GO; GO:0006476; P:protein deacetylation; IDA:BHF-UCL. DR GO; GO:0036211; P:protein modification process; ISO:MGI. DR GO; GO:0042659; P:regulation of cell fate specification; NAS:ComplexPortal. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI. DR GO; GO:0090311; P:regulation of protein deacetylation; IGI:MGI. DR GO; GO:0060297; P:regulation of sarcomere organization; IMP:MGI. DR GO; GO:2000736; P:regulation of stem cell differentiation; NAS:ComplexPortal. DR CDD; cd10011; HDAC2; 1. DR Gene3D; 3.40.800.20; Histone deacetylase domain; 1. DR InterPro; IPR000286; His_deacetylse. DR InterPro; IPR003084; His_deacetylse_1. DR InterPro; IPR023801; His_deacetylse_dom. DR InterPro; IPR037138; His_deacetylse_dom_sf. DR InterPro; IPR023696; Ureohydrolase_dom_sf. DR PANTHER; PTHR10625:SF2; HISTONE DEACETYLASE 2; 1. DR PANTHER; PTHR10625; HISTONE DEACETYLASE HDAC1-RELATED; 1. DR Pfam; PF00850; Hist_deacetyl; 1. DR PIRSF; PIRSF037913; His_deacetylse_1; 1. DR PRINTS; PR01270; HDASUPER. DR PRINTS; PR01271; HISDACETLASE. DR SUPFAM; SSF52768; Arginase/deacetylase; 1. PE 1: Evidence at protein level; KW Acetylation; Biological rhythms; Calcium; Chromatin regulator; Cytoplasm; KW Hydrolase; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repressor; S-nitrosylation; Transcription; KW Transcription regulation; Ubl conjugation; Zinc. FT CHAIN 1..488 FT /note="Histone deacetylase 2" FT /id="PRO_0000114694" FT REGION 9..322 FT /note="Histone deacetylase" FT REGION 389..488 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 398..480 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 142 FT /evidence="ECO:0000250|UniProtKB:Q13547" FT BINDING 175 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 177 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 177 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 179 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 188 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 191 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 194 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 198 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 223 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT BINDING 265 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT MOD_RES 75 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q13547" FT MOD_RES 221 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q13547" FT MOD_RES 262 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:18754010" FT MOD_RES 274 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:18754010" FT MOD_RES 394 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:19144319, FT ECO:0007744|PubMed:21183079" FT MOD_RES 407 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT MOD_RES 422 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079" FT MOD_RES 424 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19131326" FT CROSSLNK 75 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT CROSSLNK 439 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q13547" FT CROSSLNK 452 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT CROSSLNK 458 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT CROSSLNK 462 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT CROSSLNK 478 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q92769" FT CROSSLNK 481 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q13547" FT MUTAGEN 152 FT /note="C->A: Does not affect S-nitrosylation." FT /evidence="ECO:0000269|PubMed:18754010" FT MUTAGEN 262 FT /note="C->A: Impairs S-nitrosylation. Abolishes FT S-nitrosylation; when associated with A-274." FT /evidence="ECO:0000269|PubMed:18754010" FT MUTAGEN 274 FT /note="C->A: Impairs S-nitrosylation. Abolishes FT S-nitrosylation; when associated with A-262." FT /evidence="ECO:0000269|PubMed:18754010" FT CONFLICT 289 FT /note="A -> V (in Ref. 2; EDL04897)" FT /evidence="ECO:0000305" SQ SEQUENCE 488 AA; 55302 MW; B9843D24A775157C CRC64; MAYSQGGGKK KVCYYYDGDI GNYYYGQGHP MKPHRIRMTH NLLLNYGLYR KMEIYRPHKA TAEEMTKYHS DEYIKFLRSI RPDNMSEYSK QMQRFNVGED CPVFDGLFEF CQLSTGGSVA GAVKLNRQQT DMAVNWAGGL HHAKKSEASG FCYVNDIVLA ILELLKYHQR VLYIDIDIHH GDGVEEAFYT TDRVMTVSFH KYGEYFPGTG DLRDIGAGKG KYYAVNFPMR DGIDDESYGQ IFKPIISKVM EMYQPSAVVL QCGADSLSGD RLGCFNLTVK GHAKCVEVAK TFNLPLLMLG GGGYTIRNVA RCWTYETAVA LDCEIPNELP YNDYFEYFGP DFKLHISPSN MTNQNTPEYM EKIKQRLFEN LRMLPHAPGV QMQAIPEDAV HEDSGDEDGE DPDKRISIRA SDKRIACDEE FSDSEDEGEG GRRNVADHKK GAKKARIEED KKETEDKKTD VKEEDKSKDN SGEKTDPKGA KSEQLSNP //