HAD superfamily (subfamily IA) hydrolase, TIGR02253; This family of sequences from archaea and metazoans includes the human uncharacterized protein CTE7. Pyrococcus species appear to have three different forms of this enzyme, so it is unclear whether all members of this family have the same function. This family is a member of the haloacid dehalogenase (HAD) superfamily of hydrolases which are characterized by three conserved sequence motifs. By virtue of an alpha helical domain in-between the first and second conserved motif, this family is a member of subfamily IA (TIGR01549).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173   20 RLQVIKLLQSKYHY--KEEAEIICDKVQvklsKECFHPYSTCITDVRTSHWEEAiqetkggaDNRKLAEECYFLWKsTRL 97
Cdd:TIGR02253  24 RRNAIEVLIEAGLNvdFEEAYEELLKLI----KEYGSNYPTHFDYLIRRLWEEY--------NPKLVAAFVYAYHK-LKF 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173   98 QHMILADDVKAMLTELRK-EVRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDC 176
Cdd:TIGR02253  91 AYLRVYPGVRDTLMELREsGYRLGIITDGLPVKQWEKLERLGVRDFFDAVITSEEEGVEKPHPKIFYAALKRLGVKPEEA 170

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568918173  177 VMVGDTLETDIQGGLNAGLKaTVWINKSG--RVPLTSSPMPHYMVSSVLELP 226
Cdd:TIGR02253 171 VMVGDRLDKDIKGAKNAGMK-TVWINQGKssKMEDDVYPYPDYEISSLRELL 221

HAD superfamily (subfamily IA) hydrolase, TIGR02253; This family of sequences from archaea and metazoans includes the human uncharacterized protein CTE7. Pyrococcus species appear to have three different forms of this enzyme, so it is unclear whether all members of this family have the same function. This family is a member of the haloacid dehalogenase (HAD) superfamily of hydrolases which are characterized by three conserved sequence motifs. By virtue of an alpha helical domain in-between the first and second conserved motif, this family is a member of subfamily IA (TIGR01549).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173   20 RLQVIKLLQSKYHY--KEEAEIICDKVQvklsKECFHPYSTCITDVRTSHWEEAiqetkggaDNRKLAEECYFLWKsTRL 97
Cdd:TIGR02253  24 RRNAIEVLIEAGLNvdFEEAYEELLKLI----KEYGSNYPTHFDYLIRRLWEEY--------NPKLVAAFVYAYHK-LKF 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173   98 QHMILADDVKAMLTELRK-EVRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDC 176
Cdd:TIGR02253  91 AYLRVYPGVRDTLMELREsGYRLGIITDGLPVKQWEKLERLGVRDFFDAVITSEEEGVEKPHPKIFYAALKRLGVKPEEA 170

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568918173  177 VMVGDTLETDIQGGLNAGLKaTVWINKSG--RVPLTSSPMPHYMVSSVLELP 226
Cdd:TIGR02253 171 VMVGDRLDKDIKGAKNAGMK-TVWINQGKssKMEDDVYPYPDYEISSLRELL 221

FMN and 5-amino-6-(5-phospho-D-ribitylamino)uracil phosphatase YigB, HAD superfamily (riboflavin biosynthesis) [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173 104 DDVKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDT 182
Cdd:COG1011   96 PDALELLEALKARgYRLALLTNGSAELQEAKLRRLGLDDLFDAVVSSEEVGVRKPDPEIFELALERLGVPPEEALFVGDS 175

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568918173 183 LETDIQGGLNAGLKaTVWINKSGRvPLTSSPMPHYMVSSVLELPALL 229
Cdd:COG1011  176 PETDVAGARAAGMR-TVWVNRSGE-PAPAEPRPDYVISDLAELLELL 220

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173  104 DDVKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDT 182
Cdd:pfam13419  82 PGIKELLEELKEQgYKLGIVTSKSRENVEEFLKQLGLEDYFDVIVGGDDVEGKKPDPDPILKALEQLGLKPEEVIYVGDS 161

                          90
                  ....*....|....*....
gi 568918173  183 LeTDIQGGLNAGLKaTVWI 201
Cdd:pfam13419 162 P-RDIEAAKNAGIK-VIAV 178

HAD superfamily (subfamily IA) hydrolase, TIGR02253; This family of sequences from archaea and metazoans includes the human uncharacterized protein CTE7. Pyrococcus species appear to have three different forms of this enzyme, so it is unclear whether all members of this family have the same function. This family is a member of the haloacid dehalogenase (HAD) superfamily of hydrolases which are characterized by three conserved sequence motifs. By virtue of an alpha helical domain in-between the first and second conserved motif, this family is a member of subfamily IA (TIGR01549).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173   20 RLQVIKLLQSKYHY--KEEAEIICDKVQvklsKECFHPYSTCITDVRTSHWEEAiqetkggaDNRKLAEECYFLWKsTRL 97
Cdd:TIGR02253  24 RRNAIEVLIEAGLNvdFEEAYEELLKLI----KEYGSNYPTHFDYLIRRLWEEY--------NPKLVAAFVYAYHK-LKF 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173   98 QHMILADDVKAMLTELRK-EVRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDC 176
Cdd:TIGR02253  91 AYLRVYPGVRDTLMELREsGYRLGIITDGLPVKQWEKLERLGVRDFFDAVITSEEEGVEKPHPKIFYAALKRLGVKPEEA 170

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568918173  177 VMVGDTLETDIQGGLNAGLKaTVWINKSG--RVPLTSSPMPHYMVSSVLELP 226
Cdd:TIGR02253 171 VMVGDRLDKDIKGAKNAGMK-TVWINQGKssKMEDDVYPYPDYEISSLRELL 221

FMN and 5-amino-6-(5-phospho-D-ribitylamino)uracil phosphatase YigB, HAD superfamily (riboflavin biosynthesis) [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173 104 DDVKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDT 182
Cdd:COG1011   96 PDALELLEALKARgYRLALLTNGSAELQEAKLRRLGLDDLFDAVVSSEEVGVRKPDPEIFELALERLGVPPEEALFVGDS 175

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568918173 183 LETDIQGGLNAGLKaTVWINKSGRvPLTSSPMPHYMVSSVLELPALL 229
Cdd:COG1011  176 PETDVAGARAAGMR-TVWVNRSGE-PAPAEPRPDYVISDLAELLELL 220

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173  91 LWKSTRLQHMILADDVKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLL 169
Cdd:COG0546   74 LYEEELLDETRLFPGVRELLEALKARgIKLAVVTNKPREFAERLLEALGLDDYFDAIVGGDDVPPAKPKPEPLLEALERL 153

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568918173 170 GVQPGDCVMVGDTlETDIQGGLNAGLKaTVWIN--KSGRVPLTSSPmPHYMVSSVLELPALLQS 231
Cdd:COG0546  154 GLDPEEVLMVGDS-PHDIEAARAAGVP-FIGVTwgYGSAEELEAAG-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 568918173   64 RTSHWEEAIQETKGGADNRKLAEECYFLWKSTRLQHMilaDDVKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSY 142
Cdd:pfam00702  64 ELDILRGLVETLEAEGLTVVLVELLGVIALADELKLY---PGAAEALKALKERgIKVAILTGDNPEAAEALLRLLGLDDY 140

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568918173  143 FDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTLeTDIQGGLNAG 194
Cdd:pfam00702 141 FDVVISGDDVGVGKPKPEIYLAALERLGVKPEEVLMVGDGV-NDIPAAKAAG 191

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 568918173 105 DVKAMLTELR-KEVRLLLLTNGDRQTqrekIEACACQS----YFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMV 179
Cdd:cd02588   95 DVVAGLRRLReAGYRLAILSNGSPDL----IEDVVANAglrdLFDAVLSAEDVRAYKPAPAVYELAAERLGVPPDEILHV 170

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 568918173 180 GDTlETDIQGGLNAGLKaTVWINKSGRVPLTSSPMPHYMVSSVLELPA 227
Cdd:cd02588  171 ASH-AWDLAGARALGLR-TAWINRPGEVPDPLGPAPDFVVPDLGELAD 216

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 568918173 110 LTELRKE-VRLLLLTNGDRqTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTLETDIQ 188
Cdd:cd16415   16 LKDLKEKgLKLAVVSNFDR-RLRELLEALGLDDYFDFVVFSYEVGYEKPDPRIFQKALERLGVSPEEALHVGDDLKNDYL 94

                         90       100
                 ....*....|....*....|...
gi 568918173 189 GGLNAGLKATVWINKSGRVPLTS 211
Cdd:cd16415   95 GARAVGWHALLVDREGALHELPS 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173 144 DAIVIGgeqkeeKPAPSIFYHCCDLLGVQPGDCVMVGDTLETDIQGGLNAGLKaTVWIN--KSGRVPLTSSPM-PHYMVS 220
Cdd:COG0647  180 EPLVVG------KPSPPIYELALERLGVDPERVLMVGDRLDTDILGANAAGLD-TLLVLtgVTTAEDLEAAPIrPDYVLD 252

                 ....*
gi 568918173 221 SVLEL 225
Cdd:COG0647  253 SLAEL 257

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 568918173 102 LADDVKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSYFDaIVIGGEQ-KEEKPAPSIFYHCCDLLGVQPGDCVMV 179
Cdd:cd16417   88 LYPGVKEGLAALKAQgYPLACVTNKPERFVAPLLEALGISDYFS-LVLGGDSlPEKKPDPAPLLHACEKLGIAPAQMLMV 166

                         90
                 ....*....|....*
gi 568918173 180 GDTLeTDIQGGLNAG 194
Cdd:cd16417  167 GDSR-NDILAARAAG 180

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173  91 LWKSTRLQhmiLADDVKAMLTELRKEVRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEqKEEKPAPSIFyhccDLLG 170
Cdd:cd07515   10 LWHNEPIE---LLPGVREALAALKADYRLVLITKGDLLDQEQKLARSGLSDYFDAVEVVSE-KDPDTYRRVL----SRYG 81

                         90       100
                 ....*....|....*....|....
gi 568918173 171 VQPGDCVMVGDTLETDIQGGLNAG 194
Cdd:cd07515   82 IGPERFVMVGNSLRSDILPVLAAG 105

haloacid dehalogenase superfamily, subfamily IA, variant 3 with third motif having DD or ED; 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, (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 3 (this model) is found in the enzymes beta-phosphoglucomutase (TIGR01990) and deoxyglucose-6-phosphatase, while many other enzymes of subfamily IA exhibit this variant as well as variant 1 (TIGR01549). These three variant models were created with the 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 related HAD subfamilies caused by an overly broad single model. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173  104 DDVKAMLTELRKE-VRLLLLTNGDRQTQReKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDT 182
Cdd:TIGR01509  83 PGVRALLEALRARgKKLALLTNSPRAHKL-VLALLGLRDLFDVVIDSSDVGLGKPDPDIYLQALKALGLEPSECVFVDDS 161

                          90
                  ....*....|....*....
gi 568918173  183 LEtDIQGGLNAGLKaTVWI 201
Cdd:TIGR01509 162 PA-GIEAAKAAGMH-TVGV 178

beta-phosphoglucomutase family hydrolase; This subfamily model groups together three clades: the characterized beta-phosphoglucomutases (including those from E.coli, B.subtilus and L.lactis, TIGR01990), a clade of putative bPGM's from mycobacteria and a clade including the uncharacterized E.coli and H.influenzae yqaB genes which may prove to be beta-mutases of a related 1-phosphosugar. All of these are members of the larger Haloacid dehalogenase (HAD) subfamily IA and include the "variant 3" glu-asp version of the third conserved HAD domain (TIGR01509).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568918173  141 SYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTlETDIQGGLNAGLKATV 199
Cdd:TIGR02009 127 DYFDAIVDASEVKNGKPHPETFLLAAELLGVPPNECIVFEDA-LAGVQAARAAGMFAVA 184

pyrophosphatase PpaX; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173 104 DDVKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDT 182
Cdd:PRK13288  85 ETVYETLKTLKKQgYKLGIVTTKMRDTVEMGLKLTGLDEFFDVVITLDDVEHAKPDPEPVLKALELLGAKPEEALMVGDN 164

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568918173 183 LEtDIQGGLNAGLK--ATVWINKsGRVPLTSSPmPHYMVSSVLELPALL 229
Cdd:PRK13288 165 HH-DILAGKNAGTKtaGVAWTIK-GREYLEQYK-PDFMLDKMSDLLAIV 210

UmpH/NagD family phosphatase, similar to Escherichia coli UmpH UMP phosphatase/NagD nucleotide phosphatase and Mycobacterium tuberculosis Rv1692 glycerol 3-phosphate phosphatase; Escherichia coli UmpH/NagD is a ribonucleoside tri-, di-, and monophosphatase with a preference for purines, it shows peak activity with UMP and functions in UMP-degradation. It is also an effective phosphatase with AMP, GMP and CMP. Mycobacterium tuberculosis phosphatase, Rv1692 is a glycerol 3-phosphate phosphatase. Rv1692 is the final enzyme involved in glycerophospholipid recycling/catabolism. This subfamily belongs to the UmpH/NagD phosphatase family, and 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 568918173 144 DAIVIGgeqkeeKPAPSIFYHCCDLLGVQPGDCVMVGDTLETDIQGGLNAGLKA-TVWINKSGRVPLTSSPM-PHYMVSS 221
Cdd:cd07530  171 KPLFIG------KPEPIMMRAALEKLGLKSEETLMVGDRLDTDIAAGIAAGIDTlLVLTGVTTREDLAKPPYrPTYIVPS 244

                 ...
gi 568918173 222 VLE 224
Cdd:cd07530  245 LRE 247

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 568918173  82 RKLAEECYFLWKSTRLQHMILAD-----DVKAMLTELR-KEVRLLLLTN---GDRQTQREKIEACacQSYFDAIVIGGEQ 152
Cdd:cd02603   60 EELREELGRPLSAELFEELVLAAvdpnpEMLDLLEALRaKGYKVYLLSNtwpDHFKFQLELLPRR--GDLFDGVVESCRL 137

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568918173 153 KEEKPAPSIFYHCCDLLGVQPGDCVMVGDTLEtDIQGGLNAGLKATVWINK 203
Cdd:cd02603  138 GVRKPDPEIYQLALERLGVKPEEVLFIDDREE-NVEAARALGIHAILVTDA 187

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 568918173  93 KSTRLQHMILADDVKAM------LTELRKE-VRLLLLTNGDRQTQREKIEACACQ-SYFDAIVIGGEQKEEKPAPSIFYH 164
Cdd:cd07505   27 KNALLLELIASEGLKLKpgvvelLDALKAAgIPVAVATSSSRRNVELLLLELGLLrGYFDVIVSGDDVERGKPAPDIYLL 106

                         90       100       110
                 ....*....|....*....|....*....|..
gi 568918173 165 CCDLLGVQPGDCVMVGDTLeTDIQGGLNAGLK 196
Cdd:cd07505  107 AAERLGVDPERCLVFEDSL-AGIEAAKAAGMT 137

UmpH/NagD family phosphatase, similar to human PGP phosphoglycolate phosphatase and Schizosaccharomyces pombe PHO2 p-nitrophenylphosphatase; This subfamily includes the phosphoglycolate phosphatases (human PGP and Arabidopsis thaliana PGLP2) and p-nitrophenylphosphatases (Schizosaccharomyces pombe PHO2 and Saccharomyces PHO13p). It belongs to the UmpH/NagD phosphatase family, and 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 568918173 113 LRKEVRLLLLTNGDRQTQREK----------IEACACQSYFDAIVIGgeqkeeKPAPSIFYHCCDLLGVQPGDCVMVGDT 182
Cdd:cd07510  157 LRDPGCLFVATNRDPWHPLSDgsfipgtgslVAALETASGRQAIVVG------KPSRFMFDCISSKFSIDPARTCMVGDR 230

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568918173 183 LETDIQGGLNAGLKaTVW----INKSGRV--PLTSSPMPHYMVSSVLEL 225
Cdd:cd07510  231 LDTDILFGQNCGLK-TLLvltgVSTLEEAlaKLSNDLVPDYYVESLADL 278

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 568918173 106 VKAMLTELRKE-VRLLLLTNGDRQTQREKIEACACQSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTlE 184
Cdd:cd07512   91 VIEALERLRAAgWRLAICTNKPEAPARALLSALGLADLFAAVVGGDTLPQRKPDPAPLRAAIRRLGGDVSRALMVGDS-E 169

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568918173 185 TDIQGGLNAGLKATVWINKSGRVPLTSSPmPHYMVSSVLELPALL 229
Cdd:cd07512  170 TDAATARAAGVPFVLVTFGYRHAPVAELP-HDAVFSDFDALPDLL 213

subfamily of beta-phosphoglucomutase-like family, similar to Escherichia coli 6-phosphogluconate phosphatase YieH; This subfamily includes Escherichia coli YieH/HAD3 an 6-phosphogluconate phosphatase, which can hydrolyzed purines and pyrimidines as secondary substrates. It belongs to the beta-phosphoglucomutase-like family whose other 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. 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
                 ....*....|....*....|....*....|....*....|....*
gi 568918173 156 KPAPSIFYHCCDLLGVQPGDCVMVGDTLeTDIQGGLNAGlkATVW 200
Cdd:cd07526   96 KPAPDLFLHAAAQMGVAPERCLVIEDSP-TGVRAALAAG--MTVF 137

fructose-1-phosphate/6-phosphogluconate phosphatase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568918173 142 YFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTlETDIQGGLNAGLKA 197
Cdd:PRK10725 128 YFDAVVAADDVQHHKPAPDTFLRCAQLMGVQPTQCVVFEDA-DFGIQAARAAGMDA 182

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173 102 LADDVKAMLTELRKE-VRLLLLTNgdrQTQREKIEacacqsYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVG 180
Cdd:cd16416   18 LTPEVKAWLADLKEAgIKVVLVSN---NNERRVAK------VIEKLDLPFVARAGKPRPRAFRRALKEMDLPPEQVAMVG 88

                         90
                 ....*....|....*
gi 568918173 181 DTLETDIQGGLNAGL 195
Cdd:cd16416   89 DQLFTDILGGNRAGL 103

phosphoglycolate/pyridoxal phosphate phosphatase family; PGP is an essential enzyme in the glycolate salvage pathway in higher organisms (photorespiration in plants). Phosphoglycolate results from the oxidase activity of RubisCO in the Calvin cycle when concentrations of carbon dioxide are low relative to oxygen. In mammals, PGP is found in many tissues, notably in red blood cells where P-glycolate is and important activator of the hydrolysis of 2,3-bisphosphoglycerate, a major modifier of the oxygen affinity of hemoglobin. Pyridoxal phosphate (PLP, Vitamin B6) phosphatase is involved in the degradation of PLP in mammals and is widely distributed in human tissues including erythrocyes. The enzymes described here are members of the Haloacid dehalogenase superfamily of hydrolase enzymes (pfam00702). Unlike the bacterial PGP equivalog (TIGR01449), which is a member of class (subfamily) I, these enzymes are members of class (subfamily) II. These two families have almost certainly arisen from convergent evolution (although these two ancestors may themselves have diverged from a more distant HAD superfamily progenitor). The primary seed sequence for this model comes from Chlamydomonas reinhardtii, a photosynthetic alga. The enzyme has been purified and characterized and these data are fully consistent with the assignment of function as a PGPase involved in photorespiration. The second seed, from Homo sapiens chromosome 22 has been characterized as a pyridoxal phosphatase. Biochemical characterization of partially purified PGP's from various tissues including red blood cells have been performed while one gene for PGP has been localized to chromosome 16p13.3. The sequence used here maps to chromosome 22. There is indeed a related gene on chromosome 16 (and it is expressed, since EST's are found) which shows 46% identity. The chromosome 16 gene is not in evidence in nraa but translated from the genomic sequence. The third seed, from C. elegans, is only supported by sequence similarity. This model is limited to eukaryotic species including S. pombe and S. cerevisiae, although several archaea score between the trusted and noise cutoffs. This model is closely related to a family of bacterial sequences including the E. coli NagD and B. subtilus AraL genes which are characterized by the ability to hydrolyze para-nitrophenylphosphate (pNPPases or NPPases). The chlamydomonas PGPase d

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918173  136 ACACQSYFDAIVIGgeqkeeKPAPSIFYHCCDLLGVQPGDCVMVGDTLETDIQGGLNAGLKATVWInkSGRVPLTSSP-- 213
Cdd:TIGR01452 188 AIETASGRQPLVVG------KPSPYMFNCITEKFSIDPARTLMVGDRLETDILFGHRCGMTTVLVL--SGVSQLEEAQey 259

                          90       100
                  ....*....|....*....|
gi 568918173  214 --------MPHYMVSSVLEL 225
Cdd:TIGR01452 260 lmagqddlVPDYVVESLADL 279

subfamily of beta-phosphoglucomutase-like family, similar to Rhodobacter sphaeroides xylulose-1,5-bisphosphate phosphatase CbbY; This family includes Rhodobacter sphaeroides and Arabidopsis thaliana xylulose-1,5-bisphosphate phosphatase CbbY which convert xylulose-1,5-bisphosphate (a potent inhibitor of Ribulose-1,5-bisphosphate carboxylase/oxygenase, Rubisco), to the non-inhibitory compound xylulose-5-phosphate. It belongs to the beta-phosphoglucomutase-like family whose other 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. 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 568918173  64 RTSHWEEAIQ-ETKGGADNRKLAEECYfLWKSTRLQHMIladdvKAMLTELRKEV-RLL--LLTNGDRQ-----TQREKI 134
Cdd:cd07528   52 RIAAYFEKVGwPESAPKDLKELIADLH-KAKTERYAELI-----AAGLLPLRPGVaRLIdeAKAAGVRLaiattTSPANV 125

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568918173 135 EACaCQSY--------FDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTLeTDIQGGLNAGLKATV 199
Cdd:cd07528  126 DAL-LSALlgperraiFDAIAAGDDVAEKKPDPDIYLLALERLGVSPSDCLAIEDSA-IGLQAAKAAGLPCIV 196

haloacid dehalogenase-like hydrolase family protein

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568918173  140 QSYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTLeTDIQGGLNAGLK 196
Cdd:PLN02919  202 LSMFDAIVSADAFENLKPAPDIFLAAAKILGVPTSECVVIEDAL-AGVQAARAAGMR 257

uncharacterized subfamily of beta-phosphoglucomutase-like family, similar to uncharacterized Bacillus subtilis YhcW; This subfamily includes the uncharacterized Bacillus subtilis YhcW. It belongs to the beta-phosphoglucomutase-like family whose other 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. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568918173 141 SYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTLeTDIQGGLNAGLKATVWINK-SGRVPLTS 211
Cdd:cd16423   85 DYFEVIVTGDDVEKSKPDPDLYLEAAERLGVNPEECVVIEDSR-NGVLAAKAAGMKCVGVPNPvTGSQDFSK 155

phosphoglycolate phosphatase; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568918173 145 AIVIGGEQ-KEEKPAPSIFYHCCDLLGVQPGDCVMVGDTlETDIQGGLNAGLK--ATVW 200
Cdd:PRK13226 139 AVLIGGDTlAERKPHPLPLLVAAERIGVAPTDCVYVGDD-ERDILAARAAGMPsvAALW 196

Rhodobacter capsulatus Cbbz phosphoglycolate phosphatase and related proteins; ; belongs to the haloacid dehalogenase-like superfamily; Phosphoglycolate phosphatase (PGPase; 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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568918173 141 SYFDAIVIGGEQKEEKPAPSIFYHCCDLLGVQPGDCVMVGDTlETDIQGGLNAGL 195
Cdd:cd16421   47 GSFDFVLGEKEGIRRKPDPT*ALECAKVLGVPPDEVLYVGDS-GVDMQTARNAGM 100