Histone deacetylase domain; Histones can be reversibly acetylated on several lysine residues. Regulation of transcription is caused in part by this mechanism. Histone deacetylases catalyze the removal of the acetyl group. Histone deacetylases are related to other proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965   51 HKQMRDEASGFCYLNDAVLGILRLRRK--FERILYVDLDLHHGDGT--------------------------GDVSDVGL 102
Cdd:pfam00850 112 HHAERDRASGFCIFNNVAIAAKYLREKygLKRVAIVDFDVHHGNGTqeifyddpsvltlsihqypggfypgtGFADETGE 191

                          90       100       110
                  ....*....|....*....|....*....|..
gi 262072965  103 GKGRYYSVNVPIQDGIQDEKYYQICERYEPPA 134
Cdd:pfam00850 192 GKGKGYTLNVPLPPGTGDAEYLAAFEEILLPA 223

Acetoin utilization deacetylase AcuC or a related deacetylase [Secondary metabolites biosynthesis, transport and catabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  54 MRDEASGFCYLNDAVLGILRLRRK-FERILYVDLDLHHGDGT------------------------GDVSDVGLGKGRYY 108
Cdd:COG0123  126 ERDRAMGFCLFNNAAIAARYLLAKgLERVAIVDFDVHHGNGTqdifyddpdvltisihqdplypgtGAADETGEGAGEGS 205

                         90       100
                 ....*....|....*....|....*.
gi 262072965 109 SVNVPIQDGIQDEKYYQICERYEPPA 134
Cdd:COG0123  206 NLNVPLPPGTGDAEYLAALEEALLPA 231

Class I histone deacetylases; Class I histone deacetylases (HDACs) are Zn-dependent enzymes that catalyze hydrolysis of N(6)-acetyl-lysine residues in histone amino termini to yield a deacetylated histone (EC 3.5.1.98). Enzymes belonging to this group participate in regulation of a number of processes through protein (mostly different histones) modification (deacetylation). Class I histone deacetylases in general act via the formation of large multiprotein complexes. This group includes animal HDAC1, HDAC2, HDAC3, HDAC8, fungal RPD3, HOS1 and HOS2, plant HDA9, protist, archaeal and bacterial (AcuC) deacetylases. Members of this class are involved in cell cycle regulation, DNA damage response, embryonic development, cytokine signaling important for immune response and in posttranslational control of the acetyl coenzyme A synthetase. In mammals, they are known to be involved in progression of various tumors. Specific inhibitors of mammalian histone deacetylases are an emerging class of promising novel anticancer drugs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  50 LHKQMRDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGDG-------------------------TGDVSDVGLGK 104
Cdd:cd09991  126 LHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHGDGveeafyttdrvmtvsfhkfgeyffpGTGLRDIGAGK 205

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 262072965 105 GRYYSVNVPIQDGIQDEKYYQIC--------ERYEPPA 134
Cdd:cd09991  206 GKYYAVNVPLKDGIDDESYLQIFepvlskvmEVFQPSA 243

Class I histone deacetylases including ScHos2 and SpPhd1; This subfamily includes Class I histone deacetylase (HDAC) Hos2 from Saccharomyces cerevisiae as well as a histone deacetylase Phd1 from Schizosaccharomyces pombe. Hos2 binds to the coding regions of genes during gene activation, specifically it deacetylates the lysines in H3 and H4 histone tails. It is preferentially associated with genes of high activity genome-wide and is shown to be necessary for efficient transcription. Thus, Hos2 is directly required for gene activation in contrast to other class I histone deacetylases. Protein encoded by phd1 is inhibited by trichostatin A (TSA), a specific inhibitor of histone deacetylase, and is involved in the meiotic cell cycle in S. pombe. Class 1 HDACs are Zn-dependent enzymes that catalyze hydrolysis of N(6)-acetyl-lysine residues in histone amino termini to yield a deacetylated histone (EC 3.5.1.98).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  50 LHKQMRDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGDG--------------------------TGDVSDVGLG 103
Cdd:cd11598  130 LHHAKKSEASGFCYVNDIVLAILNLLRYFPRVLYIDIDVHHGDGveeafyrtdrvmtlsfhkyngeffpgTGDLDDNGGT 209

                         90       100
                 ....*....|....*....|
gi 262072965 104 KGRYYSVNVPIQDGIQDEKY 123
Cdd:cd11598  210 PGKHFALNVPLEDGIDDEQY 229

Histone deacetylase 3 (HDAC3); HDAC3 is a Zn-dependent class I histone deacetylase that catalyzes hydrolysis of N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone (EC 3.5.1.98). Histone acetylation/deacetylation process is important for mediation of transcriptional regulation of many genes. In order to target specific chromatin regions, HDAC3 can interact with DNA-binding proteins (transcriptional factors) either directly or after forming complexes with a number of other proteins, as observed for the SMPT/N-CoR complex which recruits human HDAC3 to specific chromatin loci and activates deacetylation. Human HDAC3 is also involved in deacetylation of non-histone substrates such as RelA, SPY and p53 factors. This protein can also down-regulate p53 function and subsequently modulate cell growth and apoptosis. This gene is therefore regarded as a potential tumor suppressor gene. HDAC3 plays a role in various physiological processes, including subcellular protein localization, cell cycle progression, cell differentiation, apoptosis and survival. HDAC3 has been found to be overexpressed in some tumors including leukemia, lung carcinoma, colon cancer and maxillary carcinoma. Thus, inhibitors precisely targeting HDAC3 (in some cases together with retinoic acid or hyperthermia) could be a therapeutic drug option.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  50 LHKQMRDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGD--------------------------GTGDVSDVGLG 103
Cdd:cd10005  131 LHHAKKFEASGFCYVNDIVIAILELLKYHPRVLYIDIDIHHGDgvqeafyltdrvmtvsfhkygnyffpGTGDMYEVGAE 210

                         90       100
                 ....*....|....*....|...
gi 262072965 104 KGRYYSVNVPIQDGIQDEKYYQI 126
Cdd:cd10005  211 SGRYYSVNVPLKDGIDDQSYLQL 233

Histone deacetylase 2 (HDAC2); Histone deacetylase 2 (HDAC2) is a Zn-dependent class I enzyme that catalyzes hydrolysis of N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone (EC 3.5.1.98). Histone acetylation/deacetylation process is important for mediation of transcriptional regulation of many genes. HDAC2 is involved in regulation through association with DNA binding proteins to target specific chromatin regions. It forms transcriptional repressor complexes by associating with several proteins, including the mammalian zinc-finger transcription factor YY1, thus playing an important role in transcriptional regulation, cell cycle progression and developmental events. Additionally, a few non-histone HDAC2 substrates have been found. HDAC2 plays a role in embryonic development and cytokine signaling important for immune response, and is over-expressed in several solid tumors including oral, prostate, ovarian, endometrial and gastric cancer. It participates in DNA-damage response, along with HDAC1; together, they can promote DNA non-homologous end-joining. HDAC2 is considered an important cancer prognostic marker. Inhibitors specifically targeting HDAC2 could be a therapeutic drug option.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  47 AYALHKQMRDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGD-------------------------GTGDVSDVG 101
Cdd:cd10011  129 AGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHGDgveeafyttdrvmtvsfhkygeyfpGTGDLRDIG 208

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 262072965 102 LGKGRYYSVNVPIQDGIQDEKYYQI--------CERYEPPA 134
Cdd:cd10011  209 AGKGKYYAVNFPMRDGIDDESYGQIfkpiiskvMEMYQPSA 249

Histone deacetylase 1 (HDAC1); Histone deacetylase 1 (HDAC1) is a Zn-dependent class I enzyme that catalyzes hydrolysis of N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone (EC 3.5.1.98). Histone acetylation/deacetylation process is important for mediation of transcriptional regulation of many genes. HDAC1 is involved in regulation through association with DNA binding proteins to target specific chromatin regions. In particular, HDAC1 appears to play a major role in pre-implantation embryogenesis in establishing a repressive chromatin state. Its interaction with retinoblastoma tumor-suppressor protein is essential in the control of cell proliferation and differentiation. Together with metastasis-associated protein-2 (MTA2), it deacetylates p53, thereby modulating its effect on cell growth and apoptosis. It participates in DNA-damage response, along with HDAC2; together, they promote DNA non-homologous end-joining. HDAC1 is also involved in tumorogenesis; its overexpression modulates cancer progression. Specific inhibitors of HDAC1 are currently used in cancer therapy.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  49 ALHKQMRDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGD-------------------------GTGDVSDVGLG 103
Cdd:cd10010  135 GLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHGDgveeafyttdrvmtvsfhkygeyfpGTGDLRDIGAG 214

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 262072965 104 KGRYYSVNVPIQDGIQDEKY--------YQICERYEPPA 134
Cdd:cd10010  215 KGKYYAVNYPLRDGIDDESYeaifkpvmSKVMEMFQPSA 253

Histone deacetylase (HDAC) classes I, II, IV and related proteins; The HDAC/HDAC-like family includes Zn-dependent histone deacetylase classes I, II and IV (class III HDACs, also called sirtuins, are NAD-dependent and structurally unrelated, and therefore not part of this family). Histone deacetylases catalyze hydrolysis of N(6)-acetyl-lysine residues in histone amino termini to yield a deacetylated histone (EC 3.5.1.98), as opposed to the acetylation reaction by some histone acetyltransferases (EC 2.3.1.48). Deacetylases of this family are involved in signal transduction through histone and other protein modification, and can repress/activate transcription of a number of different genes. They usually act via the formation of large multiprotein complexes. They are involved in various cellular processes, including cell cycle regulation, DNA damage response, embryonic development, cytokine signaling important for immune response and post-translational control of the acetyl coenzyme A synthetase. In mammals, they are known to be involved in progression of different tumors. Specific inhibitors of mammalian histone deacetylases are an emerging class of promising novel anticancer drugs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  49 ALHKQMRDEASGFCYLNDAVLGILRLRRK-FERILYVDLDLHHGDGT-----------------GDVSDVGLGKGRYYSV 110
Cdd:cd09301  103 GGHHAGKSRAWGFCYFNDVVLAIKFLRERgISRILIIDTDAHHGDGTreafydddrvlhmsfhnYDIYPFGRGKGKGYKI 182

                         90
                 ....*....|....*....
gi 262072965 111 NVPIQDGIQDEKYYQICER 129
Cdd:cd09301  183 NVPLEDGLGDEEYLDAVER 201

Class I histone deacetylases Hos1 and related proteins; Saccharomyces cerevisiae Hos1 is responsible for Smc3 deacetylation. Smc3 is an important player during the establishment of sister chromatid cohesion. Hos1 belongs to the class I histone deacetylases (HDACs). HDACs are Zn-dependent enzymes that catalyze hydrolysis of N(6)-acetyl-lysine residues in histone amino termini to yield a deacetylated histone (EC 3.5.1.98). Enzymes belonging to this group participate in regulation of a number of processes through protein (mostly different histones) modification (deacetylation). Class I histone deacetylases in general act via the formation of large multiprotein complexes. Other class I HDACs are animal HDAC1, HDAC2, HDAC3, HDAC8, fungal RPD3 and HOS2, plant HDA9, protist, archaeal and bacterial (AcuC) deacetylases. Members of this class are involved in cell cycle regulation, DNA damage response, embryonic development, cytokine signaling important for immune response and in posttranslational control of the acetyl coenzyme A synthetase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  51 HKQMRDEASGFCYLNDAVLGILRLRRK-FERILYVDLDLHHGDGT----------GDVS----DVGL--GKG------RY 107
Cdd:cd11680  115 HHAQKSRASGFCYVNDIVLAILRLRRArFRRVFYLDLDLHHGDGVesafffsknvLTCSihryDPGFfpGTGslknssDK 194

                         90       100       110
                 ....*....|....*....|....*....|...
gi 262072965 108 YSVNVPIQDGIQDEKYYQIC--------ERYEP 132
Cdd:cd11680  195 GMLNIPLKRGLSDKTLLRIIdsivrpliEKFEP 227

Histone deacetylases and histone-like deacetylases, classII; Class II histone deacetylases are Zn-dependent enzymes that catalyze hydrolysis of N(6)-acetyl-lysine residues of histones (EC 3.5.1.98) and possibly other proteins to yield deacetylated histones/other proteins. This group includes animal HDAC4,5,6,7,8,9,10, fungal HOS3 and HDA1, plant HDA5 and HDA15 as well as other eukaryotes, archaeal and bacterial histone-like deacetylases. Eukaryotic deacetylases mostly use histones (H2, H3, H4) as substrates for deacetylation; however, non-histone substrates are known (for example, tubulin). Substrates for prokaryotic histone-like deacetylases are not known. Histone acetylation/deacetylation process is important for mediation of transcriptional regulation of many genes. Histone deacetylases usually act via association with DNA binding proteins to target specific chromatin regions. Interaction partners of class II deacetylases include 14-3-3 proteins, MEF2 family of transcriptional factors, CtBP, calmodulin (CaM), SMRT, N-CoR, BCL6, HP1alpha and SUMO. Histone deacetylases play a role in the regulation of cell cycle, cell differentiation and survival. Class II mammalian HDACs are differentially inhibited by structurally diverse compounds with known antitumor activities, thus presenting them as potential drug targets for human diseases resulting from aberrant acetylation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  47 AYAL-----HKQMRDEASGFCYLNDAVLGI--LRLRRKFERILYVDLDLHHGDGT------------------------G 95
Cdd:cd09992   96 AFALvrppgHHAEPDRAMGFCLFNNVAIAAryAQKRYGLKRVLIVDWDVHHGNGTqdifyddpsvlyfsihqypfypgtG 175

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 262072965  96 DVSDVGLGKGRYYSVNVPIQDGIQDEKYYQ--------ICERYEP 132
Cdd:cd09992  176 AAEETGGGAGEGFTINVPLPPGSGDAEYLAafeevllpIAREFQP 220

Class II Histone deacetylase Clr3 and similar proteins; Clr3 is a class II Histone deacetylase Zn-dependent enzyme that catalyzes hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone (EC 3.5.1.98). Clr3 is the homolog of the class-II HDAC HdaI in S. cerevisiae, and is essential for silencing in heterochromatin regions, such as centromeric regions, ribosomal DNA, the mating-type region and telomeric loci. Clr3 has also been implicated in the regulation of stress-related genes; the histone acetyltransferase, Gcn5, in S. cerevisiae, preferentially acetylates global histone H3K14 while Clr3 preferentially deacetylates H3K14ac, and therefore, interplay between Gcn5 and Clr3 is crucial for the regulation of many stress-response genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  56 DEASGFCYLNDAVLG--ILRLRR--KFERILYVDLDLHHGDGT-----------------------------GDVSDVGL 102
Cdd:cd11600  120 DESMGFCFFNNVAVAakWLQTEYpdKIKKILILDWDIHHGNGTqrafyddpnvlyislhrfenggfypgtpyGDYESVGE 199

                         90       100
                 ....*....|....*....|..
gi 262072965 103 GKGRYYSVNVP-IQDGIQDEKY 123
Cdd:cd11600  200 GAGLGFNVNIPwPQGGMGDADY 221

Histone deacetylase 10; Histone deacetylases 10 are class IIb Zn-dependent enzymes that catalyze hydrolysis of N(6)-acetyl-lysine of a histone to yield a deacetylated histone (EC 3.5.1.98). Histone acetylation/deacetylation process is important for mediation of transcriptional regulation of many genes. HDACs usually act via association with DNA binding proteins to target specific chromatin regions. HDAC10 has an N-terminal deacetylase domain and a C-terminal pseudo-repeat that shares significant similarity with its catalytic domain. It is located in the nucleus and cytoplasm, and is involved in regulation of melanogenesis. It transcriptionally down-regulates thioredoxin-interacting protein (TXNIP), leading to altered reactive oxygen species (ROS) signaling in human gastric cancer cells. Known interaction partners of HDAC10 are Pax3, KAP1, hsc70 and HDAC3 proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262072965  51 HKQMRDEASGFCYLNDAVLGILRLRRKF--ERILYVDLDLHHGDGT-----------------------------GDVSD 99
Cdd:cd11683  117 HHSQRNAANGFCVFNNVAIAAEYAKKKYglHRILIVDWDVHHGQGIqyifeedpsvlyfswhryehqrfwpflreSDYDA 196

                         90
                 ....*....|....
gi 262072965 100 VGLGKGRYYSVNVP 113
Cdd:cd11683  197 VGRGKGLGFNINLP 210

Histone deacetylase 9; Histone deacetylase 9 is a class IIa Zn-dependent enzyme that catalyzes hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone (EC 3.5.1.98). Histone acetylation/deacetylation process is important for mediation of transcriptional regulation of many genes. Histone deacetylases usually act via association with DNA binding proteins to target specific chromatin regions. Class IIa histone deacetylases are signal-dependent co-repressors, they have N-terminal regulatory domain with two or three conserved serine residues, phosphorylation of these residues is important for ability to shuttle between the nucleus and cytoplasm and act as transcriptional co-repressors. HDAC9 is involved in regulation of gene expression and dendritic growth in developing cortical neurons. It also plays a role in hematopoiesis. Its deregulated expression may be associated with some human cancers. HDAC5 and HDAC9 have been found to be significantly up-regulated in high-risk medulloblastoma compared with low-risk and may potentially be novel drug targets.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 262072965  51 HKQMRDEASGFCYLNDAVLGILRLRRKFE--RILYVDLDLHHGDGT 94
Cdd:cd10009  152 HHAEESTAMGFCFFNSVAITAKYLRDQLNisKILIVDLDVHHGNGT 197