uncharacterized family of the haloacid dehalogenase-like superfamily, similar to uncharacterized Drosophila melanogaster rhythmically expressed gene 2 protein and human haloacid dehalogenase-like hydrolase domain-containing protein 3; The haloacid dehalogenase-like (HAD) hydrolases are a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. Members are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382 103 ALEAIKLLKK--MPVALIafsSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRALEGM---PSSALAVGDS 177
Cdd:cd16415    12 AVETLKDLKEkgLKLAVV---SNFDRRLRELLEALGLDDYFDFVVFSYEVGYEKPDPRIFQKALERLgvsPEEALHVGDD 88

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1490960382 178 LFFDVYGAKNAGIPAVLVVREKFSSIDDFLkaKYIREKI 216
Cdd:cd16415    89 LKNDYLGARAVGWHALLVDREGALHELPSL--ANLLERL 125

REG-2-like, HAD superfamily (subfamily IA) hydrolase; This family of proteins includes uncharacterized sequences from eukaryotes, cyanobacteria and Leptospira as well as the DREG-2 protein from Drosophila melanogaster which has been identified as a rhythmically (diurnally) regulated gene. This family is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The subfamilies are defined based on the location and the observed or predicted fold of a so-called 'capping domain', or the absence of such a domain. This family is a member of subfamily 1A in which the cap domain consists of a predicted alpha helical bundle found in between the first and second catalytic motifs. A distinctive feature of this family is a conserved tandem pair of tryptophan residues in the cap domain. The most divergent sequences included within the scope of this model are from plants and have "FW" at this position instead. Most likely, these sequences, like the vast majority of HAD sequences, represent phosphatase enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  64 YQDIIEKVYRKLGLREEVPILS---ELLKDYLREDYLKIYIDALEAIKLLKKMPVALIAFSSGYSEYQvPLLDKIGLLKY 140
Cdd:TIGR02252  68 WQKLVRDTFGRAGVPDPESFEKifeELYSYFATPEPWQVYPDAIKLLKDLRERGLILGVISNFDSRLR-GLLEALGLLEY 146

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1490960382 141 FDKIATPDILGYGKPDRRAYMRALEGM---PSSALAVGDSLFFDVYGAKNAGIPAVL 194
Cdd:TIGR02252 147 FDFVVTSYEVGAEKPDPKIFQEALERAgisPEEALHIGDSLRNDYQGARAAGWRALL 203

Phosphoglycolate phosphatase, HAD superfamily [Energy production and conversion];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  65 QDIIEKVYrKLGLREEVPILSELLKDYLREDYL---KIYIDALEAIKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYF 141
Cdd:COG0546    49 RELLRRLL-GEDPDEELEELLARFRELYEEELLdetRLFPGVRELLEALKARGIKLAVVTNKPREFAERLLEALGLDDYF 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382 142 DKIATPDILGYGKPDRRAYMRALEGM---PSSALAVGDSLfFDVYGAKNAGIPAVLvVREKFSSIDDFLKAKyirekisl 218
Cdd:COG0546   128 DAIVGGDDVPPAKPKPEPLLEALERLgldPEEVLMVGDSP-HDIEAARAAGVPFIG-VTWGYGSAEELEAAG-------- 197

                         170       180
                  ....*....|....*....|....*
gi 1490960382 219 eidypfqrPDYIITSMLDLPCIVES 243
Cdd:COG0546   198 --------ADYVIDSLAELLALLAE 214

haloacid dehalogenase-like hydrolase; This family is structurally different from the alpha/beta hydrolase family (pfam00561). This family includes L-2-haloacid dehalogenase, epoxide hydrolases and phosphatases. The structure of the family consists of two domains. One is an inserted four helix bundle, which is the least well conserved region of the alignment, between residues 16 and 96 of Swiss:P24069. The rest of the fold is composed of the core alpha/beta domain. Those members with the characteriztic DxD triad at the N-terminus are probably phosphatidylglycerolphosphate (PGP) phosphatases involved in cardiolipin biosynthesis in the mitochondria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382   5 VLMDIDQVIVERNPLSY-VIRDLAELLFRRKGISREVFLNEIRRKRIARIKSGDYMGAYNYQDIIEKVYRKLGLREEVPI 83
Cdd:pfam00702   4 VVFDLDGTLTDGEPVVTeAIAELASEHPLAKAIVAAAEDLPIPVEDFTARLLLGKRDWLEELDILRGLVETLEAEGLTVV 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  84 LSELLKDYLREDYLKIYIDALEAIKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRA 163
Cdd:pfam00702  84 LVELLGVIALADELKLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFDVVISGDDVGVGKPKPEIYLAA 163

                         170       180
                  ....*....|....*....|....*....
gi 1490960382 164 LEGM---PSSALAVGDSLfFDVYGAKNAG 189
Cdd:pfam00702 164 LERLgvkPEEVLMVGDGV-NDIPAAKAAG 191

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382   5 VLMDIDQVIVERNPLSYVIrdlaellFRRkgISREVFLNEIRRKRIARiksgdYMGAyNYQDIIEKVYRKLGLREEVPIL 84
Cdd:pfam13419   1 IIFDFDGTLLDTEELIIKS-------FNY--LLEEFGYGELSEEEILK-----FIGL-PLREIFRYLGVSEDEEEKIEFY 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  85 SELLKDYLREDYLKIYIDALEAIKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRAL 164
Cdd:pfam13419  66 LRKYNEELHDKLVKPYPGIKELLEELKEQGYKLGIVTSKSRENVEEFLKQLGLEDYFDVIVGGDDVEGKKPDPDPILKAL 145

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1490960382 165 EGM---PSSALAVGDSLfFDVYGAKNAGIPAVLV 195
Cdd:pfam13419 146 EQLglkPEEVIYVGDSP-RDIEAAKNAGIKVIAV 178

Haloacid dehalogenase-like hydrolases; The haloacid dehalogenase-like (HAD) superfamily includes L-2-haloacid dehalogenase, epoxide hydrolase, phosphoserine phosphatase, phosphomannomutase, phosphoglycolate phosphatase, P-type ATPase, and many others. This superfamily includes a variety of enzymes that catalyze the cleavage of substrate C-Cl, P-C, and P-OP bonds via nucleophilic substitution pathways. All of which use a nucleophilic aspartate in their phosphoryl transfer reaction. They catalyze nucleophilic substitution reactions at phosphorus or carbon centers, using a conserved Asp carboxylate in covalent catalysis. All members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. Members of this superfamily are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382 103 ALEAIKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRALEGM---PSSALAVGDSLf 179
Cdd:cd01427    12 AVELLKRLRAAGIKLAIVTNRSREALRALLEKLGLGDLFDGIIGSDGGGTPKPKPKPLLLLLLKLgvdPEEVLFVGDSE- 90

                          90
                  ....*....|....*.
gi 1490960382 180 FDVYGAKNAGIPAVLV 195
Cdd:cd01427    91 NDIEAARAAGGRTVAV 106

human N-acetylneuraminate-9-phosphate phosphatase, Escherichia coli house-cleaning phosphatase YjjG, and related phosphatases; N-acetylneuraminate-9- phosphatase (Neu5Ac-9-Pase; E.C. 3.1.3.29) catalyzes the dephosphorylation of N-acylneuraminate 9-phosphate during the synthesis of N-acetylneuraminate; Escherichia coli nucleotide phosphatase YjjG has a broad pyrimidine nucleotide activity spectrum and functions as an in vivo house-cleaning phosphatase for noncanonical pyrimidine nucleotides. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382 105 EAIKLLKKM----PVALIafSSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRALEGM---PSSALAVGDS 177
Cdd:cd04305    13 GAKELLEELkkgyKLGII--TNGPTEVQWEKLEQLGIHKYFDHIVISEEVGVQKPNPEIFDYALNQLgvkPEETLMVGDS 90

                          90
                  ....*....|....*.
gi 1490960382 178 LFFDVYGAKNAGIPAV 193
Cdd:cd04305    91 LESDILGAKNAGIKTV 106

haloacid dehalogenase-like superfamily phosphoglycolate phosphatase, similar to Rhodobacter sphaeroides CbbZ; Phosphoglycolate phosphatase catalyzes the dephosphorylation of phosphoglycolate; its activity requires divalent cations, especially Mg++. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  68 IEKVYRKLGLREEVPILSELLKDYLR------EDYLKIYIDALEAIKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYF 141
Cdd:cd07512    50 IRRAFAAAGEDLDGPLHDALLARFLDhyeadpPGLTRPYPGVIEALERLRAAGWRLAICTNKPEAPARALLSALGLADLF 129

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1490960382 142 DKIATPDILGYGKPDR---RAYMRALEGMPSSALAVGDSLfFDVYGAKNAGIPAVLV 195
Cdd:cd07512   130 AAVVGGDTLPQRKPDPaplRAAIRRLGGDVSRALMVGDSE-TDAATARAAGVPFVLV 185

haloacid dehalogenase superfamily, subfamily IA, variant 1 with third motif having Dx(3-4)D or Dx(3-4)E; This model represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The subfamilies are defined based on the location and the observed or predicted fold of a so-called "capping domain", or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions.The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that representing it with a single model is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an aparrent phylogenetic bifurcation. Subfamily IA is still too broad to model, but cannot be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms: (1) hhhhsDxxx(x)(D/E), (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA. Individual models were made based on seeds exhibiting only one of the variants each. Variant 1 (this model) is found in the enzymes phosphoglycolate phosphatase (TIGR01449) and enolase-phosphatase. These three variant models (see also TIGR01493 and TIGR01509) were created withthe knowledge that there will be overlap among them - this is by design and serves the purpose of eliminating the overlap with models of more distantly relatedHAD subfamilies caused by an overly broad single model. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382   5 VLMDIDQVIVERNPlsyVIRDLAELLFRRKGISREVFlNEIRRKRIARIKsgdymgayNYQDIIEKVYRKLGLREEVPIL 84
Cdd:TIGR01549   2 ILFDIDGTLVDIKF---AIRRAFPQTFEEFGLDPASF-KALKQAGGLAEE--------EWYRIATSALEELQGRFWSEYD 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  85 SEllkdylrEDYLKIYIDALEAIKLlKKMPVALIafSSGYSEYQVPLLDKIGLLKYFDkIATPDILGYGKPDRRAYMRAL 164
Cdd:TIGR01549  70 AE-------EAYIRGAADLLARLKS-AGIKLGII--SNGSLRAQKLLLRLFGLGDYFE-LILVSDEPGSKPEPEIFLAAL 138

                         170       180
                  ....*....|....*....|....*..
gi 1490960382 165 E--GMPSSALAVGDSLfFDVYGAKNAG 189
Cdd:TIGR01549 139 EslGVPPEVLHVGDNL-NDIEGARNAG 164

L-2-haloacid dehalogenase; L-2-Haloacid dehalogenase catalyzes the hydrolytic dehalogenation of L-2-haloacids to produce the corresponding D-2-hydroxyacids with an inversion of the C2-configuration. 2-haloacid dehalogenases are of interest for their potential to degrade recalcitrant halogenated environmental pollutants and their use in the synthesis of industrial chemicals. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  20 SYVIRDLAELLFRRKGISREVFLNEIRRKRIARIksgdyMGAY-NYQDIIEKVYRKLGLREEVPiLSELLKDYLREDY-- 96
Cdd:cd02588    16 SGLAAAERAFPGRGEELSRLWRQKQLEYTWLVTL-----MGPYvDFDELTRDALRATAAELGLE-LDESDLDELGDAYlr 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  97 LKIYIDALEAIKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRALEGM---PSSALA 173
Cdd:cd02588    90 LPPFPDVVAGLRRLREAGYRLAILSNGSPDLIEDVVANAGLRDLFDAVLSAEDVRAYKPAPAVYELAAERLgvpPDEILH 169

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1490960382 174 VGDSlFFDVYGAKNAGIPAVLVVR--EKFssiddflkakyirekisleiDYPFQRPDYIITSMLDLP 238
Cdd:cd02588   170 VASH-AWDLAGARALGLRTAWINRpgEVP--------------------DPLGPAPDFVVPDLGELA 215

beta-phosphoglucomutase-like family of the haloacid dehalogenase-like (HAD) hydrolase superfamily; This family represents the beta-phosphoglucomutase-like family of the haloacid dehalogenase-like (HAD) hydrolase superfamily. Family members include Lactococcus lactis beta-PGM, a mutase which catalyzes the interconversion of beta-D-glucose 1-phosphate (G1P) and D-glucose 6-phosphate (G6P), Saccharomyces cerevisiae phosphatases GPP1 and GPP2 that dephosphorylate DL-glycerol-3-phosphate and DOG1 and DOG2 that dephosphorylate 2-deoxyglucose-6-phosphate, and Escherichia coli 6-phosphogluconate phosphatase YieH. It belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  86 ELLKDYLREDYLKIYIDALEAIKLLK--KMPVAlIAFSSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRA 163
Cdd:cd07505    29 ALLLELIASEGLKLKPGVVELLDALKaaGIPVA-VATSSSRRNVELLLLELGLLRGYFDVIVSGDDVERGKPAPDIYLLA 107

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1490960382 164 LEGM---PSSALAVGDSLfFDVYGAKNAGIPAVLV 195
Cdd:cd07505   108 AERLgvdPERCLVFEDSL-AGIEAAKAAGMTVVAV 141

Ribonucleotide monophosphatase NagD, HAD superfamily [Nucleotide transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382 153 GKPDRRAYMRALEGM---PSSALAVGDSLFFDVYGAKNAGIPAVLvVREKFSSIDDFLKAKYirekisleidypfqRPDY 229
Cdd:COG0647   185 GKPSPPIYELALERLgvdPERVLMVGDRLDTDILGANAAGLDTLL-VLTGVTTAEDLEAAPI--------------RPDY 249

                  ....*...
gi 1490960382 230 IITSMLDL 237
Cdd:COG0647   250 VLDSLAEL 257

HAD-hyrolase-like;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382 152 YGKPDRRAYMRALEGM---PSSALAVGDSLFFDVYGAKNAGIPAVLVVREKFSSiDDFLKAKYirekisleidypfqRPD 228
Cdd:pfam13242   2 CGKPNPGMLERALARLgldPERTVMIGDRLDTDILGAREAGARTILVLTGVTRP-ADLEKAPI--------------RPD 66

                  ....*....
gi 1490960382 229 YIITSMLDL 237
Cdd:pfam13242  67 YVVDDLAEA 75

Uncharacterized family of the the haloacid dehalogenase-like superfamily, similar to the uncharacterized protein Bacillus subtilis YqeG; The haloacid dehalogenase-like (HAD) hydrolases are a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. Members are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382 139 KYFDKIATPDILGYGKPDRRAYMRALEGM---PSSALAVGDSLFFDVYGAKNAGIPAVLV 195
Cdd:cd16416    49 KVIEKLDLPFVARAGKPRPRAFRRALKEMdlpPEQVAMVGDQLFTDILGGNRAGLYTILV 108

haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to Saccharomyces cerevisiae Phm8p and Sdt1p; This family includes Saccharomyces cerevisiae Phm8p (phosphate metabolism protein 8) and Sdt1p (Suppressor of disruption of TFIIS). Phm8p participates in the ribose salvage pathway, it catalyzes the dephosphorylation of nucleotide monophosphates to nucleosides, its preferred substrates are nucleotide monophosphates AMP, GMP, CMP, and UMP. Phm8p is also a lysophosphatidic acid phosphatase, dephosphorylating lysophosphatidic acids (LPAs) to monoacylglycerol in response to phosphate starvation. Sdt1p is a pyrimidine and pyridine-specific 5'-nucleotidase; it is an NMN/NaMN 5'-nucleotidases involved in the production of nicotinamide riboside and nicotinic acid riboside, and is a pyrimidine 5'-nucleotidase with high specificity for UMP and CMP. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  89 KDYLREDYLKIYIDALEA----IKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYFDKIATPDILGY-GKPDRRAYMRA 163
Cdd:cd02604    67 DEFLDRVVHLILYDHLKPdpklRNLLLALPGRKIIFTNASKNHAIRVLKRLGLADLFDGIFDIEYAGPdPKPHPAAFEKA 146

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1490960382 164 LEgmpSSALAVGDSLFFD-----VYGAKNAGIPAVLVVR 197
Cdd:cd02604   147 IR---EAGLDPKRAAFFDdsirnLLAAKALGMKTVLVGP 182

phosphoglycolate phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  99 IYIDALEAIKLLKKMPVALIAFSSGYSEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAY---MRALEGMPSSALAVG 175
Cdd:PRK13223  102 VYPGVRDTLKWLKKQGVEMALITNKPERFVAPLLDQMKIGRYFRWIIGGDTLPQKKPDPAALlfvMKMAGVPPSQSLFVG 181

                          90
                  ....*....|....*...
gi 1490960382 176 DSLfFDVYGAKNAGIPAV 193
Cdd:PRK13223  182 DSR-SDVLAAKAAGVQCV 198

N-terminal lipase phosphatase domain of human soluble epoxide hydrolase, Escherichia coli YihX/HAD4 alpha-D-glucose 1-phosphate phosphatase, and related domains, may be inactive; This family includes the N-terminal phosphatase domain of human soluble epoxide hydrolase (sEH). sEH is a bifunctional enzyme with two distinct enzyme activities, the C-terminal domain has epoxide hydrolysis activity and the N-terminal domain (Ntermphos), which belongs to this family, has lipid phosphatase activity. The latter prefers mono-phosphate esters, and lysophosphatidic acids (LPAs) are the best natural substrates found to date. In addition this family includes Gallus gallus sEH and Xenopus sEH which appears to lack phosphatase activity, and Escherichia coli YihX/HAD4 which selectively hydrolyzes alpha-Glucose-1-P, phosphatase, has significant phosphatase activity against pyridoxal phosphate, and has low beta phosphoglucomutase activity. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  76 GLREEVPILSELLK-DYLREDYLKIYIDALEAIKLL--KKMPVALIA-FSSGYSEYQVPLLDKIGllKYFDKIATPDILG 151
Cdd:cd02603    61 ELREELGRPLSAELfEELVLAAVDPNPEMLDLLEALraKGYKVYLLSnTWPDHFKFQLELLPRRG--DLFDGVVESCRLG 138

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1490960382 152 YGKPDRRAYMRALEgmpSSALAVGDSLFFD-----VYGAKNAGIPAVLVVREK 199
Cdd:cd02603   139 VRKPDPEIYQLALE---RLGVKPEEVLFIDdreenVEAARALGIHAILVTDAE 188

Escherichia coli Gph phosphoglycolate phosphatase and related proteins; belongs to the haloacid dehalogenase-like superfamily; Phosphoglycolate phosphatase (PGP; EC 3.1.3.18) catalyzes the conversion of 2-phosphoglycolate into glycolate and phosphate. Members of this family belong to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1490960382  99 IYIDALEAIKLLKKM--PVALIAFSSgySEYQVPLLDKIGLLKYFDKIATPDILGYGKPDRRAYMRALEGM---PSSALA 173
Cdd:cd16417    88 LYPGVKEGLAALKAQgyPLACVTNKP--ERFVAPLLEALGISDYFSLVLGGDSLPEKKPDPAPLLHACEKLgiaPAQMLM 165

                          90       100
                  ....*....|....*....|..
gi 1490960382 174 VGDSLfFDVYGAKNAGIPAVLV 195
Cdd:cd16417   166 VGDSR-NDILAARAAGCPSVGL 186

uncharacterized family of the haloacid dehalogenase-like (HAD) hydrolase superfamily; The haloacid dehalogenase-like (HAD) hydrolases are a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. Members are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1490960382 152 YGKPDRRAYMRALEGMPSSA----LAVGDSLFFDVYGAKNAGIPAVLVVREKFSSIDDFLKAKY 211
Cdd:cd07525   181 FGKPHPPIYDLALARLGRPAkariLAVGDGLHTDILGANAAGLDSLFVTGGIHRRLAAEAGIKS 244

Haloacid Dehalogenase Superfamily Class (subfamily) IIA; This model represents one structural subclass of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The classes are defined based on the location and the observed or predicted fold of a so-called "capping domain", or the absence of such a domain. Class I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Class II consists of sequences in which the capping domain is found between the second and third motifs. Class III sequences have no capping domain in iether of these positions. The Class IIA capping domain is predicted by PSI-PRED to consist of a mixed alpha-beta fold with the basic pattern: Helix-Helix-Helix-Sheet-Helix-Loop-Sheet-Helix-Sheet-Helix. Presently, this subfamily encompasses a single equivalog model (TIGR01452) for the eukaryotic phosphoglycolate phosphatase, as well as four hypothetical equivalogs covering closely related sequences (TIGR01456 and TIGR01458 in eukaryotes, TIGR01457 in gram positive bacteria and TIGR01459 in gram negative bacteria). The Escherishia coli NagD gene and the Bacillus subtilus AraL gene are members of this subfamily but are not members of the any of the presently defined equivalogs within it. NagD is part of the NAG operon responsible for N-acetylglucosamine metabolism. The function of this gene is unknown. Genes from several organisms have been annotated as NagD, or NagD-like. However, without data on the presence of other members of this pathway, (such as in the case of Yersinia pestis) these assignments should not be given great weight. The AraL gene is similar: it is part of the L-arabinose operon, but the function is unknown. A gene from Halobacterium has been annotated as AraL, but no other Ara operon genes have been annotated. Many of the genes in this subfamily have been annotated as "pNPPase" "4-nitrophenyl phosphatase" or "NPPase". These all refer to the same activity versus a common lab test compound used to determine phosphatase activity. There is no evidence that this activity is physiologically relevant. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1490960382 152 YGKPDRRAYMRALEGM----PSSALAVGDSLFFDVYGAKNAGIPAVLV 195
Cdd:TIGR01460 186 VGKPSPAIYRAALNLLqarpERRDVMVGDNLRTDILGAKNAGFDTLLV 233