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 1958790685   1 MQATPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLMVPCQSALESIQSVRTAQTPHW 80
Cdd:cd11683   258 MCATPECFAHLTHLLMVLAGGKLCAVLEGGYHLESLAESVCMTVQTLLGDPLPRLSGEMTPCQSALESIQNVRAAQAPYW 337

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 1958790685   1 MQATPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLMVPCQSALESIQSVRTAQTPHW 80
Cdd:cd11683   258 MCATPECFAHLTHLLMVLAGGKLCAVLEGGYHLESLAESVCMTVQTLLGDPLPRLSGEMTPCQSALESIQNVRAAQAPYW 337

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

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958790685   1 MQATPECFAHLTQLLQVLA---GGRICAVLEGGYHLESLAQSVCMMVQTLLG 49
Cdd:COG0123   257 LNLTTEGYAWRTRRVLELAdhcGGPVVSVLEGGYNLDALARSVAAHLETLLG 308

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 1958790685   1 MQATPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLMVPCQSALESIQSVRTAQTPHW 80
Cdd:cd11683   258 MCATPECFAHLTHLLMVLAGGKLCAVLEGGYHLESLAESVCMTVQTLLGDPLPRLSGEMTPCQSALESIQNVRAAQAPYW 337

Histone deacetylase 6, domain 2; Histone deacetylase 6 is a class IIb Zn-dependent 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. 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 and ubiquitin-like modifier FAT10 (also known as Ubiquitin D or UBD).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790685   2 QATPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLMVPCQSALESIQSVRTAQTPHWT 81
Cdd:cd10003   268 KVTPEGYAHMTHMLMSLAGGRVIVILEGGYNLTSISESMSMCTKTLLGDPPPVLDLPRPPCSSALKSINNVLQVHQKYWK 347

                  ..
gi 1958790685  82 SL 83
Cdd:cd10003   348 SL 349

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 1958790685   2 QATPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLM---VPCQSALESIQSVRTAQTP 78
Cdd:cd11681   296 KVSPACFGYMTRQLMNLAGGKVVLALEGGYDLTAICDASEACVRALLGDELDPLSEEElerRPNPNAVTSLEKVIAIQSP 375

                  ..
gi 1958790685  79 HW 80
Cdd:cd11681   376 YW 377

Histone deacetylase 5; Histone deacetylase 5 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. HDAC5 is involved in integration of chronic drug (cocaine) addiction and depression with changes in chromatin structure and gene expression; cocaine regulates HDAC5 function to antagonize the rewarding impact of cocaine, possibly by blocking drug-stimulated gene expression that supports drug-induced behavioral change. It is also involved in regulation of angiogenesis and cell cycle as well as immune system development. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790685   4 TPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLMV---PCQSALESIQSVRTAQTPHW 80
Cdd:cd10007   301 TAKCFGHLTKQLMTLAGGRVVLALEGGHDLTAICDASEACVSALLGMELTPLDNTVLqqkPNDNAVATLERVIEIQSKHW 380

                          90
                  ....*....|
gi 1958790685  81 TSLQQNVAPV 90
Cdd:cd10007   381 SCLKRFAATL 390

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 1958790685   4 TPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLMV---PCQSALESIQSVRTAQTPHW 80
Cdd:cd10006   301 SAKCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLqqrPNANAVRSMEKVMEIHSKYW 380

                          90
                  ....*....|
gi 1958790685  81 TSLQQNVAPV 90
Cdd:cd10006   381 RCLQRTTSTA 390

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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1958790685   1 MQATPECFAHLTQLLQVLA---GGRICAVLEGGYHLESLAQSVCMMVQTL 47
Cdd:pfam00850 249 LNLTTEGFAEITRILLELAdplCIRVVSVLEGGYNLDALARSATAVLAAL 298

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958790685   2 QATPECFAHLTQLLQVLAGGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPPLPGLMV---PCQSALESIQSVRTAQTP 78
Cdd:cd10009   297 KVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTAICDASEACVNALLGNELEPLAEDILhqsPNMNAVISLQKIIEIQSK 376

                  ..
gi 1958790685  79 HW 80
Cdd:cd10009   377 YW 378

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958790685   1 MQATPECFAHLTQLLQVLA----GGRICAVLEGGYHLESLAQSVCMMVQTLLGDPTPP 54
Cdd:cd09996   273 MMLTSDGFRALTRKLRDLAdelcGGRLVMVHEGGYSEAYVPFCGLAVLEELSGVRTGI 330