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 489113680   12 TVLLDMDGTLLDLAFD-----NYFWQKLVPETYGAKQGISPQEAQDYIRQQYHAVQHTLNWYCLDYwseclDLDICAMTT 86
Cdd:TIGR01509   1 AILFDLDGVLVDTEFAiakliNREELGLVPDELGVSAVGRLELALRRFKAQYGRTISPEDAQLLYK-----QLFYEQIEE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680   87 EQGprAVLREDTVPFLDALKASGKRRILLTNAHPHnLAVKLEHTGLASHLDLLLSTHTFGYPKEDQRLWHAVAEETGMSA 166
Cdd:TIGR01509  76 EAK--LKPLPGVRALLEALRARGKKLALLTNSPRA-HKLVLALLGLRDLFDVVIDSSDVGLGKPDPDIYLQALKALGLEP 152

                         170       180
                  ....*....|....*....|....*
gi 489113680  167 EKTLFIDDSEPILDAAALYGIRYCL 191
Cdd:TIGR01509 153 SECVFVDDSPAGIEAAKAAGMHTVG 177

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 489113680   10 VDTVLLDMDGTLLDLAFDNY-FWQKLVPETYGAKqgiSPQEAQDYIRQQYHAVQHTLNWYCLDYWSECLDL-DICAMTTE 87
Cdd:pfam00702   1 IKAVVFDLDGTLTDGEPVVTeAIAELASEHPLAK---AIVAAAEDLPIPVEDFTARLLLGKRDWLEELDILrGLVETLEA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680   88 QGPRAV---------------LREDTVPFLDALKASGKRRILLTNAHPHNLAVKLEHTGLASHLDLLLSTHTFGYPKEDQ 152
Cdd:pfam00702  78 EGLTVVlvellgvialadelkLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFDVVISGDDVGVGKPKP 157

                         170       180       190
                  ....*....|....*....|....*....|.
gi 489113680  153 RLWHAVAEETGMSAEKTLFIDDSEPILDAAA 183
Cdd:pfam00702 158 EIYLAALERLGVKPEEVLMVGDGVNDIPAAK 188

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 489113680   12 TVLLDMDGTLLDLAFD-----NYFWQKLVPETYGAKQGISPQEAQDYIRQQYHAVQHTLNWYCLDYwseclDLDICAMTT 86
Cdd:TIGR01509   1 AILFDLDGVLVDTEFAiakliNREELGLVPDELGVSAVGRLELALRRFKAQYGRTISPEDAQLLYK-----QLFYEQIEE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680   87 EQGprAVLREDTVPFLDALKASGKRRILLTNAHPHnLAVKLEHTGLASHLDLLLSTHTFGYPKEDQRLWHAVAEETGMSA 166
Cdd:TIGR01509  76 EAK--LKPLPGVRALLEALRARGKKLALLTNSPRA-HKLVLALLGLRDLFDVVIDSSDVGLGKPDPDIYLQALKALGLEP 152

                         170       180
                  ....*....|....*....|....*
gi 489113680  167 EKTLFIDDSEPILDAAALYGIRYCL 191
Cdd:TIGR01509 153 SECVFVDDSPAGIEAAKAAGMHTVG 177

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 489113680   10 VDTVLLDMDGTLLDLAFDNY-FWQKLVPETYGAKqgiSPQEAQDYIRQQYHAVQHTLNWYCLDYWSECLDL-DICAMTTE 87
Cdd:pfam00702   1 IKAVVFDLDGTLTDGEPVVTeAIAELASEHPLAK---AIVAAAEDLPIPVEDFTARLLLGKRDWLEELDILrGLVETLEA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680   88 QGPRAV---------------LREDTVPFLDALKASGKRRILLTNAHPHNLAVKLEHTGLASHLDLLLSTHTFGYPKEDQ 152
Cdd:pfam00702  78 EGLTVVlvellgvialadelkLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFDVVISGDDVGVGKPKP 157

                         170       180       190
                  ....*....|....*....|....*....|.
gi 489113680  153 RLWHAVAEETGMSAEKTLFIDDSEPILDAAA 183
Cdd:pfam00702 158 EIYLAALERLGVKPEEVLMVGDGVNDIPAAK 188

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680  10 VDTVLLDMDGTLLD---LAFDnyFWQKLVpetygAKQGISPQEAQdyirqqYHAVQHTLNWYCLDYWSEC--LDLDICAM 84
Cdd:COG0637    2 IKAVIFDMDGTLVDsepLHAR--AWREAF-----AELGIDLTEEE------YRRLMGRSREDILRYLLEEygLDLPEEEL 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680  85 TTE---------QGPRAVLREDTVPFLDALKASGKRRILLTNAHPHNLAVKLEHTGLASHLDLLLSTHTFGYPKEDQRLW 155
Cdd:COG0637   69 AARkeelyrellAEEGLPLIPGVVELLEALKEAGIKIAVATSSPRENAEAVLEAAGLLDYFDVIVTGDDVARGKPDPDIY 148

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 489113680 156 HAVAEETGMSAEKTLFIDDSEPILDAAALYGIRyCLGVTNPDSGIAE 202
Cdd:COG0637  149 LLAAERLGVDPEECVVFEDSPAGIRAAKAAGMR-VVGVPDGGTAEEE 194

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 489113680  10 VDTVLLDMDGTLLDLAFDNYFwqklvpETYGAKQGISPQEAQDYIRqqYHAVQHTLN---WYCLDYWSECLD---LDICA 83
Cdd:cd02603    1 IRAVLFDFGGVLIDPDPAAAV------ARFEALTGEPSEFVLDTEG--LAGAFLELErgrITEEEFWEELREelgRPLSA 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680  84 MTTEQGPRA--VLREDTVPFLDALKASGKRRILLTNAHPHnlAVKLEHTGLA---SHLDLLLSTHTFGYPKEDQRLWHAV 158
Cdd:cd02603   73 ELFEELVLAavDPNPEMLDLLEALRAKGYKVYLLSNTWPD--HFKFQLELLPrrgDLFDGVVESCRLGVRKPDPEIYQLA 150

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 489113680 159 AEETGMSAEKTLFIDDSEPILDAAALYGIRYCLgVTNPDSGIAE 202
Cdd:cd02603  151 LERLGVKPEEVLFIDDREENVEAARALGIHAIL-VTDAEDALRE 193

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 489113680   12 TVLLDMDGTLLD----------LAFDNYFWQKLVPETYGAKQGISPQEAQDYIRQQYHAVQHtlnwyclDYWSECLDLDI 81
Cdd:TIGR01549   1 AILFDIDGTLVDikfairrafpQTFEEFGLDPASFKALKQAGGLAEEEWYRIATSALEELQG-------RFWSEYDAEEA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680   82 camtteqgpravLREDTVPFLDALKASGKRRILLTNAHPHNLAVKLEHTGLASHLDLLLSTHTFGYpKEDQRLWHAVAEE 161
Cdd:TIGR01549  74 ------------YIRGAADLLARLKSAGIKLGIISNGSLRAQKLLLRLFGLGDYFELILVSDEPGS-KPEPEIFLAALES 140

                         170
                  ....*....|....*
gi 489113680  162 TGMSaEKTLFIDDSE 176
Cdd:TIGR01549 141 LGVP-PEVLHVGDNL 154

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 489113680  97 DTVPFLDALKASGKRRILLTNAHPHNLAVKLEHTGLASHLDLLLSTHTFGYPKEDQRLWHAVAEETGMSAEKTLFI 172
Cdd:cd02588   95 DVVAGLRRLREAGYRLAILSNGSPDLIEDVVANAGLRDLFDAVLSAEDVRAYKPAPAVYELAAERLGVPPDEILHV 170

N-acetylmuramic acid 6-phosphate phosphatase MupP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680 102 LDALKASGKRRILLTNaHPHNLAVK-LEHTGLASHLDLLLSTHTFGYPKEDQR-LWHAvAEETGMSAEKTLFIDDSEPIL 179
Cdd:PRK13222 102 LAALKAAGYPLAVVTN-KPTPFVAPlLEALGIADYFSVVIGGDSLPNKKPDPApLLLA-CEKLGLDPEEMLFVGDSRNDI 179

                         90       100
                 ....*....|....*....|....*.
gi 489113680 180 DAAALYGIRyCLGVT---NPDSGIAE 202
Cdd:PRK13222 180 QAARAAGCP-SVGVTygyNYGEPIAL 204

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 489113680  10 VDTVLLDMDGTLLD------LAFDNYFwqklvpETYGAkQGISPQEAQDYIRQQYHAvqhTLNWYCLDYWSECLDLDICA 83
Cdd:cd02616    1 ITTILFDLDGTLIDtneliiKSFNHTL------KEYGL-EGYTREEVLPFIGPPLRE---TFEKIDPDKLEDMVEEFRKY 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489113680  84 MTTEQGPRAVLREDTVPFLDALKASGKRRILLTNAHPHNLAVKLEHTGLASHLDLLLSTHTFGYPKEDQRLWHAVAEETG 163
Cdd:cd02616   71 YREHNDDLTKEYPGVYETLARLKSQGIKLGVVTTKLRETALKGLKLLGLDKYFDVIVGGDDVTHHKPDPEPVLKALELLG 150

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 489113680 164 MSAEKTLFIDDSEPILDAAALYGIRYClGVTnpdSGIAEKQY 205
Cdd:cd02616  151 AEPEEALMVGDSPHDILAGKNAGVKTV-GVT---WGYKGREY 188

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 489113680 102 LDALKASGKRRILLTNaHPHNLAVK-LEHTGLASHLDLLLSTHTFGYPKEDQRLWHAVAEETGMSAEKTLFIDDSEPILD 180
Cdd:cd07512   95 LERLRAAGWRLAICTN-KPEAPARAlLSALGLADLFAAVVGGDTLPQRKPDPAPLRAAIRRLGGDVSRALMVGDSETDAA 173

                         90
                 ....*....|.
gi 489113680 181 AAALYGIRYCL 191
Cdd:cd07512  174 TARAAGVPFVL 184