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 145361638   35 GVVFDMDGTLT-VPVIDFAAMYRAVLGED----AYKRIKAESPSGIDILHHIESWSPDKQQKAYEIIADYEKQGIdklqi 109
Cdd:TIGR01549   1 AILFDIDGTLVdIKFAIRRAFPQTFEEFGldpaSFKALKQAGGLAEEEWYRIATSALEELQGRFWSEYDAEEAYI----- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  110 mPGTAELCGFLDSKKIKRGLITRNVQKAIDIFHQRFEV--IFSPALGREFRPYKPNPDPLLHICSTWDIQPnEVMMVGDS 187
Cdd:TIGR01549  76 -RGAADLLARLKSAGIKLGIISNGSLRAQKLLLRLFGLgdYFELILVSDEPGSKPEPEIFLAALESLGVPP-EVLHVGDN 153

                         170
                  ....*....|..
gi 145361638  188 LkDDIACGKRAG 199
Cdd:TIGR01549 154 L-NDIEGARNAG 164

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 145361638  35 GVVFDMDGTL--TVPVIDFAA------MYRAVLGEDaykRIKAESPSGIDIL-HHIESWS----PDKQ--QKAYEIIAD- 98
Cdd:cd16417    1 LVAFDLDGTLvdSAPDLAEAAnamlaaLGLPPLPEE---TVRTWIGNGADVLvERALTGAreaePDEElfKEARALFDRh 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  99 YEKQGIDKLQIMPGTAELCGFLDSKKIKRGLIT----RNVQ---KAIDIFHQrFEVIFSpalGREFRPYKPNPDPLLHIC 171
Cdd:cd16417   78 YAETLSVHSHLYPGVKEGLAALKAQGYPLACVTnkpeRFVApllEALGISDY-FSLVLG---GDSLPEKKPDPAPLLHAC 153

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145361638 172 STWDIQPNEVMMVGDSlKDDIACGKRAGAFTCLLdetgRYGPDD-FSVSGLQPDFKVDSLSKI 233
Cdd:cd16417  154 EKLGIAPAQMLMVGDS-RNDILAARAAGCPSVGL----TYGYNYgEDIAASGPDAVIDSLAEL 211

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 145361638   35 GVVFDMDGTLT-VPVIDFAAMYRAVLGED----AYKRIKAESPSGIDILHHIESWSPDKQQKAYEIIADYEKQGIdklqi 109
Cdd:TIGR01549   1 AILFDIDGTLVdIKFAIRRAFPQTFEEFGldpaSFKALKQAGGLAEEEWYRIATSALEELQGRFWSEYDAEEAYI----- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  110 mPGTAELCGFLDSKKIKRGLITRNVQKAIDIFHQRFEV--IFSPALGREFRPYKPNPDPLLHICSTWDIQPnEVMMVGDS 187
Cdd:TIGR01549  76 -RGAADLLARLKSAGIKLGIISNGSLRAQKLLLRLFGLgdYFELILVSDEPGSKPEPEIFLAALESLGVPP-EVLHVGDN 153

                         170
                  ....*....|..
gi 145361638  188 LkDDIACGKRAG 199
Cdd:TIGR01549 154 L-NDIEGARNAG 164

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 145361638  35 GVVFDMDGTL--TVPVIDFAA------MYRAVLGEDaykRIKAESPSGIDIL-HHIESWS----PDKQ--QKAYEIIAD- 98
Cdd:cd16417    1 LVAFDLDGTLvdSAPDLAEAAnamlaaLGLPPLPEE---TVRTWIGNGADVLvERALTGAreaePDEElfKEARALFDRh 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  99 YEKQGIDKLQIMPGTAELCGFLDSKKIKRGLIT----RNVQ---KAIDIFHQrFEVIFSpalGREFRPYKPNPDPLLHIC 171
Cdd:cd16417   78 YAETLSVHSHLYPGVKEGLAALKAQGYPLACVTnkpeRFVApllEALGISDY-FSLVLG---GDSLPEKKPDPAPLLHAC 153

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145361638 172 STWDIQPNEVMMVGDSlKDDIACGKRAGAFTCLLdetgRYGPDD-FSVSGLQPDFKVDSLSKI 233
Cdd:cd16417  154 EKLGIAPAQMLMVGDS-RNDILAARAAGCPSVGL----TYGYNYgEDIAASGPDAVIDSLAEL 211

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 145361638   33 LRGVVFDMDGTLT--VPVIDFAAMYRA-----------------VLGEDAYKRIKAESPSGIDILHHIESWSPDKQQKAY 93
Cdd:pfam00702   1 IKAVVFDLDGTLTdgEPVVTEAIAELAsehplakaivaaaedlpIPVEDFTARLLLGKRDWLEELDILRGLVETLEAEGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638   94 EII---ADYEKQGIDKLQIMPGTAELCGFLDSKKIKRGLIT----RNVQKAIDIFHQRFEVIFSpALGREFRPYKPNPDP 166
Cdd:pfam00702  81 TVVlveLLGVIALADELKLYPGAAEALKALKERGIKVAILTgdnpEAAEALLRLLGLDDYFDVV-ISGDDVGVGKPKPEI 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 145361638  167 LLHICSTWDIQPNEVMMVGDSLkDDIACGKRAG 199
Cdd:pfam00702 160 YLAALERLGVKPEEVLMVGDGV-NDIPAAKAAG 191

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638   36 VVFDMDGTL--TVPVIDFAAMYraVLGEDAYKRIKAE------SPSGIDILHH--IESWSPDKQQKAYEIIADYEKQgiD 105
Cdd:pfam13419   1 IIFDFDGTLldTEELIIKSFNY--LLEEFGYGELSEEeilkfiGLPLREIFRYlgVSEDEEEKIEFYLRKYNEELHD--K 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  106 KLQIMPGTAELCGFLDSKKIKRGLITRNVQKAIDIF------HQRFEVIFSpalGREFRPYKPNPDPLLHICSTWDIQPN 179
Cdd:pfam13419  77 LVKPYPGIKELLEELKEQGYKLGIVTSKSRENVEEFlkqlglEDYFDVIVG---GDDVEGKKPDPDPILKALEQLGLKPE 153

                         170       180
                  ....*....|....*....|....
gi 145361638  180 EVMMVGDSLKdDIACGKRAGAFTC 203
Cdd:pfam13419 154 EVIYVGDSPR-DIEAAKNAGIKVI 176

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 145361638   36 VVFDMDGTLTVPVID--------FAAMYRAVLGEDaykRIKAESPSGIDIL-HHIESWS---PDKQQKAY---EIIADYE 100
Cdd:TIGR01449   1 VLFDLDGTLVDSAPDiaaavnmaLAALGLPPATLA---RVIGFIGNGVPVLmERVLAWAgqePDAQRVAElrkLFDRHYE 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  101 KQGIDKLQIMPGTAELCGFLDSKKIKRGLIT-------RNVQKAIDIFhQRFEVIFSpalGREFRPYKPNPDPLLHICST 173
Cdd:TIGR01449  78 EVAGELTSVFPGVEATLGALRAKGLRLGLVTnkptplaRPLLELLGLA-KYFSVLIG---GDSLAQRKPHPDPLLLAAER 153

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145361638  174 WDIQPNEVMMVGDSlKDDIACGKRAGAFTCLLDETGRYGPddfSVSGLQPDFKVDSLSKIQNLL 237
Cdd:TIGR01449 154 LGVAPQQMVYVGDS-RVDIQAARAAGCPSVLLTYGYRYGE---AIDLLPPDVLYDSLNELPPLL 213

pyrophosphatase PpaX; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  32 RLRGVVFDMDGTLtvpvID----FAAMYRAVLGEDAYKRIKAEspsgiDILHHI-----ESWSPDKQQKAYEIIADYEKQ 102
Cdd:PRK13288   2 KINTVLFDLDGTL----INtnelIISSFLHTLKTYYPNQYKRE-----DVLPFIgpslhDTFSKIDESKVEEMITTYREF 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638 103 GIDK----LQIMPGTAELCGFLDSKKIKRGLIT----RNVQKAIDIF--HQRFEVIFSPalgREFRPYKPNPDPLLHICS 172
Cdd:PRK13288  73 NHEHhdelVTEYETVYETLKTLKKQGYKLGIVTtkmrDTVEMGLKLTglDEFFDVVITL---DDVEHAKPDPEPVLKALE 149

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145361638 173 TWDIQPNEVMMVGDSlKDDIACGKRAGAFTCLLDETGRyGPDdfSVSGLQPDFKVDSLSKIQNLLETNF 241
Cdd:PRK13288 150 LLGAKPEEALMVGDN-HHDILAGKNAGTKTAGVAWTIK-GRE--YLEQYKPDFMLDKMSDLLAIVGDMN 214

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638 152 ALGREfrPY---KPNPDPLLHICSTWDIQPNEVMMVGDSLKDDIACGKRAGAFTCLLDeTGRYGPDDFSVSGLQPDFKVD 228
Cdd:COG0647  176 ATGGE--PLvvgKPSPPIYELALERLGVDPERVLMVGDRLDTDILGANAAGLDTLLVL-TGVTTAEDLEAAPIRPDYVLD 252

                 ..
gi 145361638 229 SL 230
Cdd:COG0647  253 SL 254

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 145361638  35 GVVFDMDGTLtvpvIDFAAMYRAVLgedaykRIKAESPsgiDILHHIESWSPDKqqkayeiiadyekqgidklqIMPGTA 114
Cdd:cd07505    1 AVIFDMDGVL----IDTEPLHRQAW------QLLERKN---ALLLELIASEGLK--------------------LKPGVV 47

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638 115 ELCGFLDSKKIKRGLIT----RNVQKAIDIFH---QRFEVIFSpalGREFRPYKPNPDPLLHICSTWDIQPNEVMMVGDS 187
Cdd:cd07505   48 ELLDALKAAGIPVAVATsssrRNVELLLLELGllrGYFDVIVS---GDDVERGKPAPDIYLLAAERLGVDPERCLVFEDS 124

                        170
                 ....*....|....*
gi 145361638 188 LKdDIACGKRAGAFT 202
Cdd:cd07505  125 LA-GIEAAKAAGMTV 138

Histidinol phosphatase/D-glycero-mannoheptose bisphosphatephosphatase, HAD superfamily [Amino acid transport and metabolism]; Histidinol phosphatase/D-glycero-mannoheptose bisphosphatephosphatase, HAD superfamily is part of the Pathway/BioSystem: Histidine biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638 104 IDKLQIMPGTAELCGFLDSKKIK-----------RGLITrnvQKAIDIFHQRFEVIFSPALGR----EFRPY-------- 160
Cdd:COG0241   24 PEEFEFLPGVLEALARLNEAGYRlvvvtnqsgigRGLFT---EEDLNAVHAKMLELLAAEGGRidaiYYCPHhpddncdc 100

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 145361638 161 -KPNPDPLLHICSTWDIQPNEVMMVGDSLkDDIACGKRAGAFTCLLDeTGrYGPDDfsVSGLQPDFKVDSLSKIQNLL 237
Cdd:COG0241  101 rKPKPGMLLQAAERLGIDLSNSYMIGDRL-SDLQAAKAAGCKGILVL-TG-KGAEE--LAEALPDTVADDLAEAVDYL 173

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 145361638   36 VVFDMDGTLTVPVIDfAAMYRAVLGEDAYKRIKAESPSGIDIL----HHIESWSPD--------KQQKAYEIIADYEkqg 103
Cdd:TIGR01509   2 ILFDLDGVLVDTEFA-IAKLINREELGLVPDELGVSAVGRLELalrrFKAQYGRTIspedaqllYKQLFYEQIEEEA--- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638  104 idKLQIMPGTAELCGFLDSKKIKRGLIT---RNVQKAIDIFHQR--FE-VIFSPALGREfrpyKPNPDPLLHICSTWDIQ 177
Cdd:TIGR01509  78 --KLKPLPGVRALLEALRARGKKLALLTnspRAHKLVLALLGLRdlFDvVIDSSDVGLG----KPDPDIYLQALKALGLE 151

                         170       180
                  ....*....|....*....|....*...
gi 145361638  178 PNEVMMVGDSLkDDIACGKRAGAFTCLL 205
Cdd:TIGR01509 152 PSECVFVDDSP-AGIEAAKAAGMHTVGV 178

Predicted phosphohydrolase YqeG, HAD superfamily [General function prediction only];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 145361638 161 KPNPDPLLHICSTWDIQPNEVMMVGDSLKDDIACGKRAGAFTCL 204
Cdd:COG2179   91 KPLPRGFRKALKLMGLPPEETAVVGDQLFTDVLGGNRAGLYTIL 134

histidinol phosphate phosphatase and related phosphatases; This family includes the N-terminal domain of the Escherichia coli bifunctional enzyme histidinol-phosphate phosphatase/imidazole-glycerol-phosphate dehydratase, HisB. The N-terminal histidinol-phosphate phosphatase domain catalyzes the dephosphorylation of histidinol phosphate, the eight step of L-histidine biosynthesis. This family also includes Escherichia coli GmhB phosphatase which is highly specific for D-glycero-D-manno-heptose-1,7-bisphosphate, it removes the C(7)phosphate and not the C(1)phosphate, and this is the third essential step of lipopolysaccharide heptose biosynthesis. 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 145361638 104 IDKLQIMPGTAELCGFLDSKKIK-----------RGLITrnvQKAIDIFHQRFEVIFS---------------PALGREF 157
Cdd:cd07503   21 PEDLEFLPGVIEALKKLKDAGYLvvvvtnqsgiaRGYFS---EADFEALHDKMRELLAsqgveiddiyycphhPDDGCPC 97

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 145361638 158 RpyKPNPDPLLHICSTWDIQPNEVMMVGDSLKdDIACGKRAGAFTCLL 205
Cdd:cd07503   98 R--KPKPGMLLDAAKELGIDLARSFVIGDRLS-DIQAARNAGCKGILV 142

haloacid dehalogenase-like superfamily phosphatases, UmpH/NagD family; Phosphatases in this UmpH/NagD family include Escherichia coli UmpH UMP phosphatase/NagD nucleotide phosphatase , Mycobacterium tuberculosis Rv1692 glycerol 3-phosphate phosphatase, human PGP phosphoglycolate phosphatase, Schizosaccharomyces pombe PHO2 p-nitrophenylphosphatase, Bacillus AraL a putative sugar phosphatase, and Plasmodium falciparum para nitrophenyl phosphate phosphatase PNPase. 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 145361638 161 KPNPDPLLHICSTWDIQPNEVMMVGDSLKDDIACGKRAGaFTCLLDETGRYGPDDFS---VSGLQPDFKVDSL 230
Cdd:cd07508  197 KPSPWLGELALEKFGIDPERVLFVGDRLATDVLFGKACG-FQTLLVLTGVTTLEDLQayiDHELVPDYYADSL 268

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 145361638 161 KPNPDPLLHICSTWDIQPNEVMMVGDSLKDDIACGKRAGaFTCLLDETGRYGPDD---FSVSGLQPDFKVDSLSKIQNLL 237
Cdd:cd07510  204 KPSRFMFDCISSKFSIDPARTCMVGDRLDTDILFGQNCG-LKTLLVLTGVSTLEEalaKLSNDLVPDYYVESLADLLELL 282

uncharacterized family of the haloacid dehalogenase-like superfamily, similar to the uncharacterized Lactococcus lactis YsbA; The specific function of Lactococcus lactis YsbA is unknown. 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, 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 145361638  37 VFDMDGTL--TVPVidFAAMYRAVLGE-----DAYKRIKAESPSGIDILHHIESWSPDKQQKayeiIADYEKQGIDKLQI 109
Cdd:cd07523    3 IWDLDGTLldSYPA--MTKALSETLADfgipqDLETVYKIIKESSVQFAIQYYAEVPDLEEE----YKELEAEYLAKPIL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145361638 110 MPGTAELCGFLDSKKIKRGLITRNVQKAIDIFHQR-----FEVIFSPALGreFrPYKPNPDPLLHICSTWDIQPNEVMMV 184
Cdd:cd07523   77 FPGAKAVLRWIKEQGGKNFLMTHRDHSALTILKKDgiasyFTEIVTSDNG--F-PRKPNPEAINYLLNKYQLNPEETVMI 153

                        170       180
                 ....*....|....*....|.
gi 145361638 185 GD-SLkdDIACGKRAGAFTCL 204
Cdd:cd07523  154 GDrEL--DIEAGHNAGISTIL 172

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 145361638 115 ELCGFLDSKKIKRGLITRNVQKAIDIF-HQRFEVIFSPALG-REFRPYKPNPDPLLHICSTWDIQPNEVMMVGDS 187
Cdd:cd16421   14 ELLKALRQKGIKLAVLSNKPNEAVQVLvEELFPGSFDFVLGeKEGIRRKPDPT*ALECAKVLGVPPDEVLYVGDS 88

noncanonical pyrimidine nucleotidase, YjjG family; This HAD superfamily includes including YjjG from E. coli and YfnB from B. subtilis. YjjG has been shown to act as a house-cleaning enzyme, cleaving nucleotides with non-canonical nucleotide bases. 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 145361638  105 DKLQIMPGTAELCGFLdSKKIKRGLIT---RNVQKA------IDIFHQRfeVIFSPALGREfrpyKPNPDPLLHICS-TW 174
Cdd:TIGR02254  94 EGHQLLPGAFELMENL-QQKFRLYIVTngvRETQYKrlrksgLFPFFDD--IFVSEDAGIQ----KPDKEIFNYALErMP 166

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145361638  175 DIQPNEVMMVGDSLKDDIACGKRAGAFTCLLDETGRYGPDDFSvsglqPDFKVDSLSKIQNLL 237
Cdd:TIGR02254 167 KFSKEEVLMIGDSLTADIKGGQNAGLDTCWMNPDMHPNPDDII-----PTYEIRSLEELYEIL 224

UmpH/NagD family phosphatase para nitrophenyl phosphate phosphatase, similar to Plasmodium falciparum PNPase; Plasmodium falciparum para nitrophenyl phosphate phosphatase (PNPase) catalyzes the dephosphorylation of thiamine monophosphate to thiamine, other substrates on which its active are nucleotides, phosphorylated sugars, pyridoxal-5-phosphate, and paranitrophenyl phosphate. 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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 145361638 161 KPNPDPLLHICSTWDIQPNEVMMVGDSLKDDIACGKRAGaFTCLLDETGRYGPDD 215
Cdd:cd07532  206 KPNPQILNFLMKSGVIKPERTLMIGDRLKTDILFANNCG-FQSLLVGTGVNSLED 259

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
                 ....*....|....*....|....*....|....*....|....*...
gi 145361638 157 FRPYKPNPDPLLHICSTWDIQPNEVMMVGDSLKDDIACGKRAGAFTCL 204
Cdd:cd16416   60 ARAGKPRPRAFRRALKEMDLPPEQVAMVGDQLFTDILGGNRAGLYTIL 107

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 145361638 145 FEVIFSpalGREFRPYKPNPDPLLHICSTWDIQPNEVMMVGDSLKDDIACgKRAGAFTCLLDETGRYGPDdfsvSGLQPD 224
Cdd:cd02588  134 FDAVLS---AEDVRAYKPAPAVYELAAERLGVPPDEILHVASHAWDLAGA-RALGLRTAWINRPGEVPDP----LGPAPD 205

                 ....*..
gi 145361638 225 FKVDSLS 231
Cdd:cd02588  206 FVVPDLG 212