Arginase-like and histone-like hydrolases; Arginase-like/histone-like hydrolase superfamily includes metal-dependent enzymes that belong to Arginase-like amidino hydrolase family and histone/histone-like deacetylase class I, II, IV family, respectively. These enzymes catalyze hydrolysis of amide bond. Arginases are known to be involved in control of cellular levels of arginine and ornithine, in histidine and arginine degradation and in clavulanic acid biosynthesis. Deacetylases play a role in signal transduction through histone and/or other protein modification and can repress/activate transcription of a number of different genes. They participate in different 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. Mammalian histone deacetyases 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.

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gi 30142019   1 TIVKPVAKEFDPDMVLVSAGFDALEGHTPPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNAL 80
Cdd:cd11681 262 TVVMPIAREFSPDIVLVSAGFDAAEGHPPPLGGYKVSPACFGYMTRQLMNLAGGKVVLALEGGYDLTAICDASEACVRAL 341

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gi 30142019  81 LGNE 84
Cdd:cd11681 342 LGDE 345

Histone deacetylases, class IIa; Class IIa histone deacetylases are Zn-dependent enzymes that catalyze hydrolysis of N(6)-acetyl-lysine residues of histones (EC 3.5.1.98) to yield deacetylated histones. This subclass includes animal HDAC4, HDAC5, HDAC7, and HDCA9. 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. HDAC7 is involved in regulation of myocyte migration and differentiation. HDAC5 is involved in integration of chronic drug (cocaine) addiction and depression with changes in chromatin structure and gene expression. HDAC4 participates in regulation of chondrocyte hypertrophy and skeletogenesis.

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gi 30142019   1 TIVKPVAKEFDPDMVLVSAGFDALEGHTPPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNAL 80
Cdd:cd11681 262 TVVMPIAREFSPDIVLVSAGFDAAEGHPPPLGGYKVSPACFGYMTRQLMNLAGGKVVLALEGGYDLTAICDASEACVRAL 341

                ....
gi 30142019  81 LGNE 84
Cdd:cd11681 342 LGDE 345

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

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gi 30142019   1 TIVKPVAKEFDPDMVLVSAGFDALEGHtpPLGGYKVTAKCFGHLTKQLMTLAD---GRVVLALEGGHDLTAICDASEACV 77
Cdd:COG0123 226 EALLPALEAFKPDLIVVSAGFDAHADD--PLGRLNLTTEGYAWRTRRVLELADhcgGPVVSVLEGGYNLDALARSVAAHL 303

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gi 30142019  78 NALLG 82
Cdd:COG0123 304 ETLLG 308

Histone deacetylases, class IIa; Class IIa histone deacetylases are Zn-dependent enzymes that catalyze hydrolysis of N(6)-acetyl-lysine residues of histones (EC 3.5.1.98) to yield deacetylated histones. This subclass includes animal HDAC4, HDAC5, HDAC7, and HDCA9. 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. HDAC7 is involved in regulation of myocyte migration and differentiation. HDAC5 is involved in integration of chronic drug (cocaine) addiction and depression with changes in chromatin structure and gene expression. HDAC4 participates in regulation of chondrocyte hypertrophy and skeletogenesis.

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gi 30142019   1 TIVKPVAKEFDPDMVLVSAGFDALEGHTPPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNAL 80
Cdd:cd11681 262 TVVMPIAREFSPDIVLVSAGFDAAEGHPPPLGGYKVSPACFGYMTRQLMNLAGGKVVLALEGGYDLTAICDASEACVRAL 341

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gi 30142019  81 LGNE 84
Cdd:cd11681 342 LGDE 345

Histone deacetylase 7; Histone deacetylase 7 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, having 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. HDAC7 is involved in regulation of myocyte migration and differentiation. Known interaction partners of class IIa HDAC7 are myocyte enhancer factors - MEF2A, -2C, and -2D, 14-3-3 proteins, SMRT and N-CoR co-repressors, HDAC3, ETA (endothelin receptor). This enzyme is also involved in the development of the immune system as well as brain and heart development. Multiple alternatively spliced transcript variants encoding several isoforms have been found for this gene.

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gi 30142019   1 TIVKPVAKEFDPDMVLVSAGFDALEGHTPPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNAL 80
Cdd:cd10008 263 IVVMPIAREFSPDLVLVSAGFDAAEGHPAPLGGYHVSAKCFGYMTQQLMNLAGGAVVLALEGGHDLTAICDASEACVAAL 342

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gi 30142019  81 LGNE 84
Cdd:cd10008 343 LGNE 346

Histone deacetylase 4; Histone deacetylase 4 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, having 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. HDAC4 participates in regulation of chondrocyte hypertrophy and skeletogenesis. However, biological substrates for HDAC4 have not been identified; only low lysine deacetylation activity has been demonstrated and active site mutant has enhanced activity toward acetylated lysines. HDAC4 does not bind DNA directly, but through transcription factors MEF2C (myocyte enhancer factor-2C) and MEF2D. Other known interaction partners of the protein are 14-3-3 proteins, SMRT and N-CoR co-repressors, BCL6, HP1, SUMO-1 ubiquitin-like protein, and ANKRA2. It appears to interact in a multiprotein complex with RbAp48 and HDAC3. Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation.

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gi 30142019   1 TIVKPVAKEFDPDMVLVSAGFDALEGHTPPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNAL 80
Cdd:cd10006 265 TVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSAKCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSAL 344

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gi 30142019  81 LGNE 84
Cdd:cd10006 345 LGNE 348

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.

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gi 30142019   2 IVKPVAKEFDPDMVLVSAGFDALEGHtpPLGGYKVTAKCFGHLTKQLMTLAD----GRVVLALEGGHDLTAICDASEACV 77
Cdd:cd09992 210 VLLPIAREFQPDLVLVSAGFDAHRGD--PLGGMNLTPEGYARLTRLLKELADehcgGRLVFVLEGGYNLEALAESVLAVL 287

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gi 30142019  78 NALL 81
Cdd:cd09992 288 EALL 291

Histone deacetylase 6, domain 1 and histone deacetylase 10; Histone deacetylases 6 and 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. HDAC6 is the only histone deacetylase with internal duplication of two catalytic domains which appear to function independently of each other, and also has a C-terminal ubiquitin-binding domain. It is located in the cytoplasm and associates with microtubule motor complex, functioning as the tubulin deacetylase and regulating microtubule-dependent cell motility. 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 HDAC6 are alpha tubulin (substrate) and ubiquitin-like modifier FAT10 (also known as Ubiquitin D or UBD) while interaction partners of HDAC10 are Pax3, KAP1, hsc70 and HDAC3 proteins.

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gi 30142019   2 IVKPVAKEFDPDMVLVSAGFDALEGHtpPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNALL 81
Cdd:cd10002 228 ILLPLALEFQPELVLVSAGFDASIGD--PEGEMAVTPAGYAHLTRLLMGLAGGKLLLVLEGGYLLESLAESVSMTLRGLL 305

                .
gi 30142019  82 G 82
Cdd:cd10002 306 G 306

Histone deacetylase 6, domain 1; Histone deacetylases 6 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. HDAC6 is the only histone deacetylase with internal duplication of two catalytic domains which appear to function independently of each other, and also has a C-terminal ubiquitin-binding domain. It is located in the cytoplasm and associates with microtubule motor complex, functioning as the tubulin deacetylase and regulating microtubule-dependent cell motility. Known interaction partners of HDAC6 are alpha tubulin (substrate) and ubiquitin-like modifier FAT10 (also known as Ubiquitin D or UBD).

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gi 30142019   2 IVKPVAKEFDPDMVLVSAGFDALEGHtpPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNALL 81
Cdd:cd11682 228 VLLPVALEFQPQLVLVAAGFDAVIGD--PKGEMAATPACFAHLTHLLMGLAGGKLILSLEGGYNLRSLAEGVCASLKALL 305

                ..
gi 30142019  82 GN 83
Cdd:cd11682 306 GD 307

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.

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gi 30142019   5 PVAKEFDPDMVLVSAGFDALEGHtpPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNALLGN 83
Cdd:cd11683 231 PLAFEFDPELVLVSAGFDSAIGD--PEGQMCATPECFAHLTHLLMVLAGGKLCAVLEGGYHLESLAESVCMTVQTLLGD 307

Histone deacetylases and histone-like deacetylases, classII; This subfamily includes bacterial as well as eukaryotic Class II histone deacetylase (HDAC) and related proteins. Deacetylases of class II 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. Included in this family is a bacterial HDAC-like amidohydrolase (Bordetella/Alcaligenes species FB18817, denoted as FB188 HDAH) shown to be most similar in sequence and function to class II HDAC6 domain 3 or b (HDAC6b). FB188 HDAH is able to remove the acetyl moiety from acetylated histones, and can be inhibited by common HDAC inhibitors such as SAHA (suberoylanilide hydroxamic acid) as well as class II-specific but not class I specific inhibitors.

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gi 30142019   2 IVKPVAKEFDPDMVLVSAGFDAleGHTPPLGGYKVTAKCFGHLTKQLMTLAD----GRVVLALEGGHDLT 67
Cdd:cd09996 243 IVLPALRAFRPELIIVASGFDA--SAFDPLGRMMLTSDGFRALTRKLRDLADelcgGRLVMVHEGGYSEA 310