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FUNCTION Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). 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 (PubMed:12724404). 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). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity (PubMed:19343227). May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (By similarity). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A (PubMed:21965678). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:35044827).CATALYTIC ACTIVITY N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + acetateCATALYTIC ACTIVITY N(6)-acetyl-L-lysyl-[protein] + H2O = L-lysyl-[protein] + acetateCATALYTIC ACTIVITY N(6)-(2E)-butenoyl-L-lysyl-[protein] + H2O = (2E)-2-butenoate + L-lysyl-[protein]CATALYTIC ACTIVITY N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] + H2O = 2-hydroxy-2-methylpropanoate + L-lysyl-[protein]CATALYTIC ACTIVITY N(6)-[(S)-lactoyl]-L-lysyl-[protein] + H2O = (S)-lactate + L-lysyl-[protein]COFACTOR Binds 2 Ca(2+) ions per subunit.ACTIVITY REGULATION Inositol tetraphosphate (1D-myo-inositol 1,4,5,6-tetrakisphosphate) may act as an intermolecular glue between HDAC2 and N-Cor repressor complex components.SUBUNIT Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7, the core complex associates with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex (PubMed:10904264). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:16428440, PubMed:25593309, PubMed:28977666, PubMed:33283408). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:16428440, PubMed:28977666, PubMed:33283408). Component of a RCOR/GFI/KDM1A/HDAC complex (By similarity). Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A (PubMed:12493763). The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I (PubMed:12493763). Part of a complex containing the core histones H2A, H2B, H3 and H4, DEK and unphosphorylated DAXX (PubMed:12140263). Part of a complex containing ATR and CHD4 (PubMed:10545197). Forms a heterologous complex at least with YY1 (PubMed:8917507). Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1 (PubMed:10888872). Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2 (PubMed:12724404). Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 (PubMed:10904264). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2 (PubMed:19061646). Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2 (PubMed:21573134). Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC1 (PubMed:19433865). Interacts directly with GFI1. Interacts directly with GFI1B (By similarity). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (PubMed:14633989). Interacts with ATR (PubMed:10545197). Interacts with BCL6 (non-acetylated form) (PubMed:12402037, PubMed:18212045). Interacts with BEND3 (PubMed:21914818). Interacts with CBFA2T3 (PubMed:11533236). Interacts with CDK2AP1 (PubMed:20523938). Interacts with CHD4 (PubMed:25593309). Interacts with CHD5 (By similarity). Interacts with CHFR (PubMed:19182791). Interacts with CRY1 (By similarity). Interacts with DNMT1 (PubMed:10888872). Interacts with GATAD2A (PubMed:33283408). Interacts with HCFC1 (PubMed:12670868). Interacts with HDAC7 (By similarity). Interacts with HDAC10 (PubMed:11739383). Interacts with INSM1 (By similarity). Interacts with KDM4A (PubMed:15927959). Interacts with MACROH2A1 (via the non-histone region) (By similarity). Interacts with MBD3L2 (PubMed:15701600). Interacts with MTA1, with a preference for sumoylated MTA1 (PubMed:21965678, PubMed:24970816). Interacts with NACC2 (PubMed:22926524). Interacts with NRIP1 (PubMed:15060175). Interacts with PELP1 (PubMed:15456770). Interacts with PIMREG (PubMed:18757745). Interacts with PRDM6 (By similarity). Interacts with PWWP2B (By similarity). Interacts with SAP30 (By similarity). Interacts with SAP30L (PubMed:16820529). Interacts with SETDB1 (By similarity). Interacts with SIX3 (By similarity). Interacts with SMARCAD1 (PubMed:21549307). Interacts with SNW1 (PubMed:10644367). Interacts with SPHK2 (PubMed:19729656). Interacts with SPEN/MINT (PubMed:11331609). Interacts (CK2 phosphorylated form) with SP3 (PubMed:12176973). Interacts with SUV39H1 (By similarity). Interacts with TSHZ3 (via its N-terminus) (PubMed:19343227). Interacts with ZMYND8 (PubMed:25593309). Interacts with ZNF431 (By similarity). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (PubMed:32051553). Identified in a complex with HDAC1, KCTD19, DNTTIP1 and ZNF541 (By similarity). Component of the SIN3B complex, which includes SIN3B, HDAC2, PHF12 and MORF4L1; interacts directly with all subunits (PubMed:37137925).INTERACTION Widely expressed; lower levels in brain and lung.PTM S-nitrosylated by GAPDH. In neurons, S-nitrosylation at Cys-262 and Cys-274 does not affect enzyme activity, but induces HDAC2 release from chromatin. This in turn increases acetylation of histones surrounding neurotrophin-dependent gene promoters and promotes their transcription. In embryonic cortical neurons, S-Nitrosylation regulates dendritic growth and branching.SIMILARITY Belongs to the histone deacetylase family. HD type 1 subfamily.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.
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