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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   5 PRAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQDAALAASYRSRFVAHADRVMV 84
Cdd:COG0546    1 IKLVLFDLDGTLVDSAPDIAAALNEALAELGLPPLDLEELRALIGLGLRELLRRLLGEDPDEELEELLARFRELYEEELL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  85 GMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEA 164
Cdd:COG0546   81 DETRLFPGVRELLEALKARGIKLAVVTNKPREFAERLLEALGLDDYFDAIVGGDDVPPAKPKPEPLLEALERLGLDPEEV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 738081520 165 IYVGDHTADQQAAAAAGTRFVGAVTGKISSAQWRERGCRAIERELGEVL 213
Cdd:COG0546  161 LMVGDSPHDIEAARAAGVPFIGVTWGYGSAEELEAAGADYVIDSLAELL 209

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   5 PRAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQDAALAASYRSRFVAHADRVMV 84
Cdd:COG0546    1 IKLVLFDLDGTLVDSAPDIAAALNEALAELGLPPLDLEELRALIGLGLRELLRRLLGEDPDEELEELLARFRELYEEELL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  85 GMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEA 164
Cdd:COG0546   81 DETRLFPGVRELLEALKARGIKLAVVTNKPREFAERLLEALGLDDYFDAIVGGDDVPPAKPKPEPLLEALERLGLDPEEV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 738081520 165 IYVGDHTADQQAAAAAGTRFVGAVTGKISSAQWRERGCRAIERELGEVL 213
Cdd:COG0546  161 LMVGDSPHDIEAARAAGVPFIGVTWGYGSAEELEAAGADYVIDSLAELL 209

pyrophosphatase similar to Bacillus subtilis PpaX; This family includes Bacillus subtilis PpaX which hydrolyzes pyrophosphate formed during serine-46-phosphorylated HPr (P-Ser-HPr) dephosphorylation by the bifunctional enzyme HPr kinase/phosphorylase. 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 738081520   6 RAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQDAALAASYRSRFVAHADRvmvg 85
Cdd:cd02616    2 TTILFDLDGTLIDTNELIIKSFNHTLKEYGLEGYTREEVLPFIGPPLRETFEKIDPDKLEDMVEEFRKYYREHNDD---- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  86 MTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAI 165
Cdd:cd02616   78 LTKEYPGVYETLARLKSQGIKLGVVTTKLRETALKGLKLLGLDKYFDVIVGGDDVTHHKPDPEPVLKALELLGAEPEEAL 157

                        170       180
                 ....*....|....*....|..
gi 738081520 166 YVGDHTADQQAAAAAGTRFVGA 187
Cdd:cd02616  158 MVGDSPHDILAGKNAGVKTVGV 179

2-phosphoglycolate phosphatase, prokaryotic; 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 Ralstonia (Alcaligenes) eutropha and Rhodobacter sphaeroides, the PGP gene (CbbZ) is located on an operon along with other Calvin cycle enzymes including RubisCO. The only other pertinent experimental evidence concerns the gene from E. coli. The in vitro activity of the Ralstonia and Escherichia enzymes was determined with crude cell extracts of strains containing PGP on expression plasmids and compared to controls. In E. coli, however, there does not appear to be a functional Calvin cycle (RubisCO is absent), although the E. coli PGP gene (gph) is on the same operon (dam) with ribulose-5-phosphate-3-epimerase (rpe), a gene in the pentose-phosphate pathway (along with other, unrelated genes). The E. coli enzyme is not expressed under normal laboratory conditions; the pathway to which it belongs has not been determined. In fact, the possibility exists, although unlikely, that the E. coli enzyme and others within this equivalog have as their physiological substrate another, closely related molecule. The other seed chosen for this model, from Xylella fastidiosa has no experimental evidence, but is a plant pathogen and thus may obtain phosphoglycolate from its host. This model has been restricted to encompass only proteobacteria as no related PGP has been verified outside of this clade. Sequences from Aquifex aeolicus and Treponema pallidum fall between the trusted and noise cutoffs. Just below the noise cutoff is a gene which is part of the operon for the biosynthesis of the blue pigment, indigoidine, from Erwinia (Pectobacterium) chrysanthemi, a plant pathogen. It does not seem likely, considering the proposed biosynthetic mechanism, that the dephosphorylation of phosphoglycolate or a closely related compound is required. Possibly, this gene is fortuitously located in this operon, or has an indirect relationship to the necessity for the biosynthesis of this compound. Sequences from 11 species have been annotated as PGP or putative PGP but fall below the noise cutoff. None of these have experimental validation. This enzyme is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolase enzymes (pfam00702). [Energy metabolism, Sugars]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520    9 LFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIG----LTLEQTFAFLTGNQDAALAASYRSRFVAHADRVMV 84
Cdd:TIGR01449   2 LFDLDGTLVDSAPDIAAAVNMALAALGLPPATLARVIGFIGngvpVLMERVLAWAGQEPDAQRVAELRKLFDRHYEEVAG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   85 GMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEA 164
Cdd:TIGR01449  82 ELTSVFPGVEATLGALRAKGLRLGLVTNKPTPLARPLLELLGLAKYFSVLIGGDSLAQRKPHPDPLLLAAERLGVAPQQM 161

                         170       180
                  ....*....|....*....|....*.
gi 738081520  165 IYVGDHTADQQAAAAAGTRFVGAVTG 190
Cdd:TIGR01449 162 VYVGDSRVDIQAARAAGCPSVLLTYG 187

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   5 PRAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQDAALAASYRSRFVAHADRVMV 84
Cdd:COG0546    1 IKLVLFDLDGTLVDSAPDIAAALNEALAELGLPPLDLEELRALIGLGLRELLRRLLGEDPDEELEELLARFRELYEEELL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  85 GMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEA 164
Cdd:COG0546   81 DETRLFPGVRELLEALKARGIKLAVVTNKPREFAERLLEALGLDDYFDAIVGGDDVPPAKPKPEPLLEALERLGLDPEEV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 738081520 165 IYVGDHTADQQAAAAAGTRFVGAVTGKISSAQWRERGCRAIERELGEVL 213
Cdd:COG0546  161 LMVGDSPHDIEAARAAGVPFIGVTWGYGSAEELEAAGADYVIDSLAELL 209

pyrophosphatase similar to Bacillus subtilis PpaX; This family includes Bacillus subtilis PpaX which hydrolyzes pyrophosphate formed during serine-46-phosphorylated HPr (P-Ser-HPr) dephosphorylation by the bifunctional enzyme HPr kinase/phosphorylase. 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 738081520   6 RAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQDAALAASYRSRFVAHADRvmvg 85
Cdd:cd02616    2 TTILFDLDGTLIDTNELIIKSFNHTLKEYGLEGYTREEVLPFIGPPLRETFEKIDPDKLEDMVEEFRKYYREHNDD---- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  86 MTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAI 165
Cdd:cd02616   78 LTKEYPGVYETLARLKSQGIKLGVVTTKLRETALKGLKLLGLDKYFDVIVGGDDVTHHKPDPEPVLKALELLGAEPEEAL 157

                        170       180
                 ....*....|....*....|..
gi 738081520 166 YVGDHTADQQAAAAAGTRFVGA 187
Cdd:cd02616  158 MVGDSPHDILAGKNAGVKTVGV 179

Beta-phosphoglucomutase, HAD superfamily [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   5 PRAYLFDFDLTLADSSDAICFCAAAALGDMGqAVPPRERIEDSIGLTLEQTFAFLTGNQ-----DAALAASYRSRFVAha 79
Cdd:COG0637    2 IKAVIFDMDGTLVDSEPLHARAWREAFAELG-IDLTEEEYRRLMGRSREDILRYLLEEYgldlpEEELAARKEELYRE-- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  80 drvMVGMTGF--YPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLL 157
Cdd:COG0637   79 ---LLAEEGLplIPGVVELLEALKEAGIKIAVATSSPRENAEAVLEAAGLLDYFDVIVTGDDVARGKPDPDIYLLAAERL 155

                        170
                 ....*....|..
gi 738081520 158 GVKADEAIYVGD 169
Cdd:COG0637  156 GVDPEECVVFED 167

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 738081520   5 PRAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIE-------------DSIGLTLEQTFAFLTGNQDAALAASY 71
Cdd:COG1011    1 IKAVLFDLDGTLLDFDPVIAEALRALAERLGLLDEAEELAEayraieyalwrryERGEITFAELLRRLLEELGLDLAEEL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  72 RSRFVAHADRvmvgMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLL 151
Cdd:COG1011   81 AEAFLAALPE----LVEPYPDALELLEALKARGYRLALLTNGSAELQEAKLRRLGLDDLFDAVVSSEEVGVRKPDPEIFE 156

                        170
                 ....*....|....*....
gi 738081520 152 KALDLLGVKADEAIYVGDH 170
Cdd:COG1011  157 LALERLGVPPEEALFVGDS 175

2-phosphoglycolate phosphatase, prokaryotic; 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 Ralstonia (Alcaligenes) eutropha and Rhodobacter sphaeroides, the PGP gene (CbbZ) is located on an operon along with other Calvin cycle enzymes including RubisCO. The only other pertinent experimental evidence concerns the gene from E. coli. The in vitro activity of the Ralstonia and Escherichia enzymes was determined with crude cell extracts of strains containing PGP on expression plasmids and compared to controls. In E. coli, however, there does not appear to be a functional Calvin cycle (RubisCO is absent), although the E. coli PGP gene (gph) is on the same operon (dam) with ribulose-5-phosphate-3-epimerase (rpe), a gene in the pentose-phosphate pathway (along with other, unrelated genes). The E. coli enzyme is not expressed under normal laboratory conditions; the pathway to which it belongs has not been determined. In fact, the possibility exists, although unlikely, that the E. coli enzyme and others within this equivalog have as their physiological substrate another, closely related molecule. The other seed chosen for this model, from Xylella fastidiosa has no experimental evidence, but is a plant pathogen and thus may obtain phosphoglycolate from its host. This model has been restricted to encompass only proteobacteria as no related PGP has been verified outside of this clade. Sequences from Aquifex aeolicus and Treponema pallidum fall between the trusted and noise cutoffs. Just below the noise cutoff is a gene which is part of the operon for the biosynthesis of the blue pigment, indigoidine, from Erwinia (Pectobacterium) chrysanthemi, a plant pathogen. It does not seem likely, considering the proposed biosynthetic mechanism, that the dephosphorylation of phosphoglycolate or a closely related compound is required. Possibly, this gene is fortuitously located in this operon, or has an indirect relationship to the necessity for the biosynthesis of this compound. Sequences from 11 species have been annotated as PGP or putative PGP but fall below the noise cutoff. None of these have experimental validation. This enzyme is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolase enzymes (pfam00702). [Energy metabolism, Sugars]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520    9 LFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIG----LTLEQTFAFLTGNQDAALAASYRSRFVAHADRVMV 84
Cdd:TIGR01449   2 LFDLDGTLVDSAPDIAAAVNMALAALGLPPATLARVIGFIGngvpVLMERVLAWAGQEPDAQRVAELRKLFDRHYEEVAG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   85 GMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEA 164
Cdd:TIGR01449  82 ELTSVFPGVEATLGALRAKGLRLGLVTNKPTPLARPLLELLGLAKYFSVLIGGDSLAQRKPHPDPLLLAAERLGVAPQQM 161

                         170       180
                  ....*....|....*....|....*.
gi 738081520  165 IYVGDHTADQQAAAAAGTRFVGAVTG 190
Cdd:TIGR01449 162 VYVGDSRVDIQAARAAGCPSVLLTYG 187

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 738081520    6 RAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQD------------AALAASYRS 73
Cdd:pfam00702   2 KAVVFDLDGTLTDGEPVVTEAIAELASEHPLAKAIVAAAEDLPIPVEDFTARLLLGKRDwleeldilrglvETLEAEGLT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   74 RFVAHADRVMVGMTGF--YPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLL 151
Cdd:pfam00702  82 VVLVELLGVIALADELklYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFDVVISGDDVGVGKPKPEIYL 161

                         170
                  ....*....|....*...
gi 738081520  152 KALDLLGVKADEAIYVGD 169
Cdd:pfam00702 162 AALERLGVKPEEVLMVGD 179

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 738081520    9 LFDFDLTLADSSDAICFCAAAAlgdmGQAVPPRERIEDSIG---LTLEQTFAFLTGNQDAALAASYRSRFVAHAdRVMVG 85
Cdd:TIGR01509   3 LFDLDGVLVDTEFAIAKLINRE----ELGLVPDELGVSAVGrleLALRRFKAQYGRTISPEDAQLLYKQLFYEQ-IEEEA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   86 MTGFYPDAVALLAELHARRIPVAIVSTKYRYRiEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAI 165
Cdd:TIGR01509  78 KLKPLPGVRALLEALRARGKKLALLTNSPRAH-KLVLALLGLRDLFDVVIDSSDVGLGKPDPDIYLQALKALGLEPSECV 156

                  ....
gi 738081520  166 YVGD 169
Cdd:TIGR01509 157 FVDD 160

uncharacterized family of the haloacid dehalogenase-like (HAD) hydrolase superfamily, similar to Parvibaculum lavamentivorans HAD-superfamily hydrolase, subfamily IA, variant 1; 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 738081520   9 LFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGN---QDAALAASYRSRFVAHADRVMVG 85
Cdd:cd07533    3 IFDWDGTLADSQHNIVAAMTAAFADLGLPVPSAAEVRSIIGLSLDEAIARLLPMatpALVAVAERYKEAFDILRLLPEHA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  86 MTGFyPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVtVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAI 165
Cdd:cd07533   83 EPLF-PGVREALDALAAQGVLLAVATGKSRRGLDRVLEQHGLGGYF-DATRTADDTPSKPHPEMLREILAELGVDPSRAV 160

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 738081520 166 YVGDHTADQQAAAAAGTRFVGAVTGKISSAQWRERG 201
Cdd:cd07533  161 MVGDTAYDMQMAANAGAHAVGVAWGYHSLEDLRSAG 196

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 738081520    7 AYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQDAALAASYRSRFVAHAdrvmvgm 86
Cdd:TIGR01549   1 AILFDIDGTLVDIKFAIRRAFPQTFEEFGLDPASFKALKQAGGLAEEEWYRIATSALEELQGRFWSEYDAEEA------- 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   87 tgFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRhKPDPEGLLKALDLLGVkADEAIY 166
Cdd:TIGR01549  74 --YIRGAADLLARLKSAGIKLGIISNGSLRAQKLLLRLFGLGDYFELILVSDEPGS-KPEPEIFLAALESLGV-PPEVLH 149

                  ....*
gi 738081520  167 VGDHT 171
Cdd:TIGR01549 150 VGDNL 154

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 738081520   90 YPDAVALLAELHARRIPVAIVSTkYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAIYVGD 169
Cdd:TIGR02252 107 YPDAIKLLKDLRERGLILGVISN-FDSRLRGLLEALGLLEYFDFVVTSYEVGAEKPDPKIFQEALERAGISPEEALHIGD 185

                  .
gi 738081520  170 H 170
Cdd:TIGR02252 186 S 186

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 738081520  90 YPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAIYVGD 169
Cdd:cd02588   93 FPDVVAGLRRLREAGYRLAILSNGSPDLIEDVVANAGLRDLFDAVLSAEDVRAYKPAPAVYELAAERLGVPPDEILHVAS 172

                 .
gi 738081520 170 H 170
Cdd:cd02588  173 H 173

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 738081520   91 PDAVALLAELHARRIPVAIVSTkyRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAIYVGD 169
Cdd:TIGR02009  91 PGIRNLLKRLKAKGIAVGLGSS--SKNAPRILAKLGLRDYFDAIVDASEVKNGKPHPETFLLAAELLGVPPNECIVFED 167

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 738081520   6 RAYLFDFDLTLADSSDAICFcaAAALGDMGQAVPPRERIEDSIGLTLEQTFAFLTGNQ-DAALAASYRSRFVAHA-DRVM 83
Cdd:cd02603    2 RAVLFDFGGVLIDPDPAAAV--ARFEALTGEPSEFVLDTEGLAGAFLELERGRITEEEfWEELREELGRPLSAELfEELV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  84 VGMTGFYPDAVALLAELHARRIPVAIVS-TKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKAD 162
Cdd:cd02603   80 LAAVDPNPEMLDLLEALRAKGYKVYLLSnTWPDHFKFQLELLPRRGDLFDGVVESCRLGVRKPDPEIYQLALERLGVKPE 159

                 ....*..
gi 738081520 163 EAIYVGD 169
Cdd:cd02603  160 EVLFIDD 166

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 738081520  94 VALLAELHARRIPVAIVSTKYRYRIEQILRHLdLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAIYVGD 169
Cdd:cd16421   13 LELLKALRQKGIKLAVLSNKPNEAVQVLVEEL-FPGSFDFVLGEKEGIRRKPDPT*ALECAKVLGVPPDEVLYVGD 87

haloacid dehalogenase-like hydrolase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  28 AAALGDMGQAVPPRERIEDSIGLTLEQTFA-FLTGNQDAALAASYRSRFVAHADRVMVGMTGFYPDAVALLAELHARRIP 106
Cdd:PLN03243  48 RALAEEEGKRPPPAFLLKRAEGMKNEQAISeVLCWSRDFLQMKRLAIRKEDLYEYMQGGLYRLRPGSREFVQALKKHEIP 127

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 738081520 107 VAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAIYVGD 169
Cdd:PLN03243 128 IAVASTRPRRYLERAIEAVGMEGFFSVVLAAEDVYRGKPDPEMFMYAAERLGFIPERCIVFGN 190

fructose-1-phosphate/6-phosphogluconate phosphatase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 738081520 101 HARRiPVAiVSTKYRYRI-EQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLLGVKADEAI 165
Cdd:PRK10725 100 HGRR-PMA-VGTGSESAIaEALLAHLGLRRYFDAVVAADDVQHHKPAPDTFLRCAQLMGVQPTQCV 163

haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520    9 LFDFDLTLADSSDAICFCAAAALGDmgqAVPPRERIEDSIGLTLEQTFAFLTGNQDAALAAS----YRSRFVAHADRVMV 84
Cdd:pfam12710   2 LFDLDGTLLDGDSLFLLIRALLRRG---GPDLWRALLVLLLLALLRLLGRLSRAGARELLRAllagLPEEDAAELERFVA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   85 GMT--GFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLV--------------TVIVGHEDVGRHKPDPE 148
Cdd:pfam12710  79 EVAlpRLHPGALELLAAHRAAGDRVVVVTGGLRPLVEPVLAELGFDEVLatelevddgrftgeLRLIGPPCAGEGKVRRL 158

                         170       180
                  ....*....|....*....|..
gi 738081520  149 GLLKALDLLGVKADEAIYVGDH 170
Cdd:pfam12710 159 RAWLAARGLGLDLADSVAYGDS 180

phosphoglycolate phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520   5 PRAYLFDFDLTLADSSDAICFCAAAALGDMGQAVPPRERIEDSIG----LTLEQTFAFLTGNQ--DAALAASYRSRFV-A 77
Cdd:PRK13223  13 PRLVMFDLDGTLVDSVPDLAAAVDRMLLELGRPPAGLEAVRHWVGngapVLVRRALAGSIDHDgvDDELAEQALALFMeA 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520  78 HADRVmvGMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHLDLAQLVTVIVGHEDVGRHKPDPEGLLKALDLL 157
Cdd:PRK13223  93 YADSH--ELTVVYPGVRDTLKWLKKQGVEMALITNKPERFVAPLLDQMKIGRYFRWIIGGDTLPQKKPDPAALLFVMKMA 170

                        170       180       190
                 ....*....|....*....|....*....|...
gi 738081520 158 GVKADEAIYVGDHTADQQAAAAAGTRFVGAVTG 190
Cdd:PRK13223 171 GVPPSQSLFVGDSRSDVLAAKAAGVQCVALSYG 203

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 738081520  62 NQDAALAASYRSRFVAHADRVMVGMTGFYPDAVALLAELHARRIPVAIVSTKYRYRIEQILRHL---DLAQLVTVIVGHE 138
Cdd:cd07528   69 DLKELIADLHKAKTERYAELIAAGLLPLRPGVARLIDEAKAAGVRLAIATTTSPANVDALLSALlgpERRAIFDAIAAGD 148

                         90       100       110
                 ....*....|....*....|....*....|.
gi 738081520 139 DVGRHKPDPEGLLKALDLLGVKADEAIYVGD 169
Cdd:cd07528  149 DVAEKKPDPDIYLLALERLGVSPSDCLAIED 179

haloacid dehalogenase-like hydrolase family protein

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 738081520    6 RAYLFDFDLTLADSSDAICFCAAAALGDMGQAVppreRIEDSIGL--TLEQTF----AFLTGNQDAALAASYRSRFVAHA 79
Cdd:PLN02919   76 SAVLFDMDGVLCNSEEPSRRAAVDVFAEMGVEV----TVEDFVPFmgTGEANFlggvASVKGVKGFDPDAAKKRFFEIYL 151