Haloacid Dehalogenase-like Hydrolases; The haloacid dehalogenase (HAD) superfamily includes carbon and phosphorus hydrolases such as 2-haloalkonoate dehalogenase, epoxide hydrolase, phosphoserine phosphatase, phosphomannomutase, phosphoglycolate phosphatase, P-type ATPase, among others. These proteins catalyze nucleophilic substitution reactions at phosphorus or carbon centers, using a conserved Asp carboxylate in covalent catalysis. All members possess a conserve alpha/beta core domain, and many also possess a small cap domain, with varying folds and functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   4 HLLIDLDGTLTDPKVGITTSARYGLAKIGHPLPESENIDWIIGPPLKASLAKILQvePNDVLAEQALMGYRERFAVTGLY 83
Cdd:cd04302    1 TILFDLDGTLTDSAEGITASVQYALEELGIPVPDESELRRFIGPPLEDSFRELLP--FDEEEAQRAVDAYREYYKEKGLF 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  84 ENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKDELIAYILEQEQLQASQCL 163
Cdd:cd04302   79 ENEVYPGIPELLEKLKAAGYRLYVATSKPEVFARRILEHFGLDEYFDGIAGASLDGSRVHKADVIRYALDTLGIAPEQAV 158

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 491321902 164 MVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKA 202
Cdd:cd04302  159 MIGDRKHDIIGARANGIDSIGVLYGYGSEDELEEAGATY 197

haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to the Pseudomonas aeruginosa PA0065; 5'-nucleotidases dephosphorylate nucleoside 5'-monophosphates to nucleosides and inorganic phosphate. Purified Pseudomonas aeruginosa PA0065 displayed high activity toward 5'-UMP and 5'-IMP, significant activity against 5'-XMP and 5'-TMP, and low activity against 5'-CMP. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   4 HLLIDLDGTLTDPKVGITTSARYGLAKIGHPLPESENIDWIIGPPLKASLAKILQvePNDVLAEQALMGYRERFAVTGLY 83
Cdd:cd04302    1 TILFDLDGTLTDSAEGITASVQYALEELGIPVPDESELRRFIGPPLEDSFRELLP--FDEEEAQRAVDAYREYYKEKGLF 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  84 ENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKDELIAYILEQEQLQASQCL 163
Cdd:cd04302   79 ENEVYPGIPELLEKLKAAGYRLYVATSKPEVFARRILEHFGLDEYFDGIAGASLDGSRVHKADVIRYALDTLGIAPEQAV 158

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 491321902 164 MVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKA 202
Cdd:cd04302  159 MIGDRKHDIIGARANGIDSIGVLYGYGSEDELEEAGATY 197

N-acetylmuramic acid 6-phosphate phosphatase MupP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   1 MIKHLLIDLDGTLTDPKVGITTSARYGLAKIGHP-LPESENIDWI-------IGPPLKASLAkilqvEPNDVLAEQALMG 72
Cdd:PRK13222   5 DIRAVAFDLDGTLVDSAPDLAAAVNAALAALGLPpAGEERVRTWVgngadvlVERALTWAGR-----EPDEELLEKLREL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  73 YRERFAVTGLYENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGselnGD-----RTHKDEL 147
Cdd:PRK13222  80 FDRHYAENVAGGSRLYPGVKETLAALKAAGYPLAVVTNKPTPFVAPLLEALGIADYFSVVIG----GDslpnkKPDPAPL 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 491321902 148 IaYILEQEQLQASQCLMVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKARIQQFSQLPNVVA 215
Cdd:PRK13222 156 L-LACEKLGLDPEEMLFVGDSRNDIQAARAAGCPSVGVTYGYNYGEPIALSEPDVVIDHFAELLPLLG 222

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 491321902    5 LLIDLDGTLTDPKVGITTSARYGLAKIGHP-LPESENIDWI-IGPPLKASLAKILQVEPNDVLAEQALMG-YRERFAVTG 81
Cdd:TIGR01449   1 VLFDLDGTLVDSAPDIAAAVNMALAALGLPpATLARVIGFIgNGVPVLMERVLAWAGQEPDAQRVAELRKlFDRHYEEVA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   82 LYENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSE-LNGDRTHKDELIAyILEQEQLQAS 160
Cdd:TIGR01449  81 GELTSVFPGVEATLGALRAKGLRLGLVTNKPTPLARPLLELLGLAKYFSVLIGGDsLAQRKPHPDPLLL-AAERLGVAPQ 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 491321902  161 QCLMVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKARIQQFSQLP 211
Cdd:TIGR01449 160 QMVYVGDSRVDIQAARAAGCPSVLLTYGYRYGEAIDLLPPDVLYDSLNELP 210

haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to the Pseudomonas aeruginosa PA0065; 5'-nucleotidases dephosphorylate nucleoside 5'-monophosphates to nucleosides and inorganic phosphate. Purified Pseudomonas aeruginosa PA0065 displayed high activity toward 5'-UMP and 5'-IMP, significant activity against 5'-XMP and 5'-TMP, and low activity against 5'-CMP. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   4 HLLIDLDGTLTDPKVGITTSARYGLAKIGHPLPESENIDWIIGPPLKASLAKILQvePNDVLAEQALMGYRERFAVTGLY 83
Cdd:cd04302    1 TILFDLDGTLTDSAEGITASVQYALEELGIPVPDESELRRFIGPPLEDSFRELLP--FDEEEAQRAVDAYREYYKEKGLF 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  84 ENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKDELIAYILEQEQLQASQCL 163
Cdd:cd04302   79 ENEVYPGIPELLEKLKAAGYRLYVATSKPEVFARRILEHFGLDEYFDGIAGASLDGSRVHKADVIRYALDTLGIAPEQAV 158

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 491321902 164 MVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKA 202
Cdd:cd04302  159 MIGDRKHDIIGARANGIDSIGVLYGYGSEDELEEAGATY 197

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 491321902   5 LLIDLDGTLTDPKVGITTSARYGLAKIGHP-LPESENIDWI---IGPPLKASLAKILQVEPNDVLAEQALMGYRERFAVT 80
Cdd:cd16417    2 VAFDLDGTLVDSAPDLAEAANAMLAALGLPpLPEETVRTWIgngADVLVERALTGAREAEPDEELFKEARALFDRHYAET 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  81 GLYENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGselnGD-----RTHKDELIaYILEQE 155
Cdd:cd16417   82 LSVHSHLYPGVKEGLAALKAQGYPLACVTNKPERFVAPLLEALGISDYFSLVLG----GDslpekKPDPAPLL-HACEKL 156

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 491321902 156 QLQASQCLMVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKARIQQFSQLP 211
Cdd:cd16417  157 GIAPAQMLMVGDSRNDILAARAAGCPSVGLTYGYNYGEDIAASGPDAVIDSLAELL 212

N-acetylmuramic acid 6-phosphate phosphatase MupP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   1 MIKHLLIDLDGTLTDPKVGITTSARYGLAKIGHP-LPESENIDWI-------IGPPLKASLAkilqvEPNDVLAEQALMG 72
Cdd:PRK13222   5 DIRAVAFDLDGTLVDSAPDLAAAVNAALAALGLPpAGEERVRTWVgngadvlVERALTWAGR-----EPDEELLEKLREL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  73 YRERFAVTGLYENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGselnGD-----RTHKDEL 147
Cdd:PRK13222  80 FDRHYAENVAGGSRLYPGVKETLAALKAAGYPLAVVTNKPTPFVAPLLEALGIADYFSVVIG----GDslpnkKPDPAPL 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 491321902 148 IaYILEQEQLQASQCLMVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKARIQQFSQLPNVVA 215
Cdd:PRK13222 156 L-LACEKLGLDPEEMLFVGDSRNDIQAARAAGCPSVGVTYGYNYGEPIALSEPDVVIDHFAELLPLLG 222

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 491321902   5 LLIDLDGTLTDPKVGITTSARYGLAKIGHPLPESENIDWIIGPPLKASLAKIL-QVEPNDV-LAEQALMGYRERFAVTGL 82
Cdd:cd07533    2 VIFDWDGTLADSQHNIVAAMTAAFADLGLPVPSAAEVRSIIGLSLDEAIARLLpMATPALVaVAERYKEAFDILRLLPEH 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  83 YEnKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKdELIAYILEQEQLQASQC 162
Cdd:cd07533   82 AE-PLFPGVREALDALAAQGVLLAVATGKSRRGLDRVLEQHGLGGYFDATRTADDTPSKPHP-EMLREILAELGVDPSRA 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 491321902 163 LMVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKARIQQFSQL 210
Cdd:cd07533  160 VMVGDTAYDMQMAANAGAHAVGVAWGYHSLEDLRSAGADAVVDHFSEL 207

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  90 TVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKDELIAYILEQEQLQASQCLMVGDRE 169
Cdd:cd01427   11 LAVELLKRLRAAGIKLAIVTNRSREALRALLEKLGLGDLFDGIIGSDGGGTPKPKPKPLLLLLLKLGVDPEEVLFVGDSE 90

                         90
                 ....*....|....*.
gi 491321902 170 YDVLGARHNGIEAVAV 185
Cdd:cd01427   91 NDIEAARAAGGRTVAV 106

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 491321902    5 LLIDLDGTLTDPKVGITTSARYGLAKIGHP-LPESENIDWI-IGPPLKASLAKILQVEPNDVLAEQALMG-YRERFAVTG 81
Cdd:TIGR01449   1 VLFDLDGTLVDSAPDIAAAVNMALAALGLPpATLARVIGFIgNGVPVLMERVLAWAGQEPDAQRVAELRKlFDRHYEEVA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   82 LYENKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSE-LNGDRTHKDELIAyILEQEQLQAS 160
Cdd:TIGR01449  81 GELTSVFPGVEATLGALRAKGLRLGLVTNKPTPLARPLLELLGLAKYFSVLIGGDsLAQRKPHPDPLLL-AAERLGVAPQ 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 491321902  161 QCLMVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKARIQQFSQLP 211
Cdd:TIGR01449 160 QMVYVGDSRVDIQAARAAGCPSVLLTYGYRYGEAIDLLPPDVLYDSLNELP 210

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 491321902    2 IKHLLIDLDGTLTDPKVGITTSARY-----------GLAKIGHPLPESENI-DWIIGPPLKASLAKILQVEPNDVLAEQA 69
Cdd:pfam00702   1 IKAVVFDLDGTLTDGEPVVTEAIAElasehplakaiVAAAEDLPIPVEDFTaRLLLGKRDWLEELDILRGLVETLEAEGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   70 LMGYRERFAVTGLYEN-KVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKDELI 148
Cdd:pfam00702  81 TVVLVELLGVIALADElKLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFDVVISGDDVGVGKPKPEIY 160

                         170       180       190
                  ....*....|....*....|....*....|.
gi 491321902  149 AYILEQEQLQASQCLMVGDREYDVLGARHNG 179
Cdd:pfam00702 161 LAALERLGVKPEEVLMVGDGVNDIPAAKAAG 191

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 491321902    4 HLLIDLDGTLTDPKVGITTSARYGLAKIGHPLPESENIDwiIGPPLKASLAKILQVEPNDVLAEQALMGYRERFAVtgly 83
Cdd:TIGR01549   1 AILFDIDGTLVDIKFAIRRAFPQTFEEFGLDPASFKALK--QAGGLAEEEWYRIATSALEELQGRFWSEYDAEEAY---- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   84 enkvYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKdELIAYILEQEQLqASQCL 163
Cdd:TIGR01549  75 ----IRGAADLLARLKSAGIKLGIISNGSLRAQKLLLRLFGLGDYFELILVSDEPGSKPEP-EIFLAALESLGV-PPEVL 148

                         170
                  ....*....|...
gi 491321902  164 MVGDREYDVLGAR 176
Cdd:TIGR01549 149 HVGDNLNDIEGAR 161

phosphoglycolate phosphatase, similar to Synechococcus elongates phosphoglycolate phosphatase PGP/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 491321902  88 YPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGdrthKDELIAYILEQEQLQASQCLMVGD 167
Cdd:cd04303   81 FPGVEDMLRALHARGVRLAVVSSNSEENIRRVLGPEELISLFAVIEGSSLFG----KAKKIRRVLRRTKITAAQVIYVGD 156

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 491321902 168 REYDVLGARHNGIEAVAVEYGYGTLQELDHAAPKARIQQFSQL 210
Cdd:cd04303  157 ETRDIEAARKVGLAFAAVSWGYAKPEVLKALAPDHMLEDPEDL 199

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  85 NKVYPTVAETLQTLKlQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGdrTHKD--ELIAYILEQEQLQASQC 162
Cdd:cd04305    8 DTLLPGAKELLEELK-KGYKLGIITNGPTEVQWEKLEQLGIHKYFDHIVISEEVG--VQKPnpEIFDYALNQLGVKPEET 84

                         90       100
                 ....*....|....*....|..
gi 491321902 163 LMVGDR-EYDVLGARHNGIEAV 183
Cdd:cd04305   85 LMVGDSlESDILGAKNAGIKTV 106

bifunctional 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase/phosphatase; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   1 MIKHLLIDLDGTL--TDPKVGITTSARYGLAK---IGHPLPESENIDWIIGPPLKASLAKILqvePNDVLA--EQALMGY 73
Cdd:PRK06698 240 MLQALIFDMDGTLfqTDKILELSLDDTFDHLRslqLWDTVTPIDKYREIMGVPLPKVWEALL---PDHSLEirEQTDAYF 316

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  74 RERfavtgLYEN------KVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSElNGDRTHKDEL 147
Cdd:PRK06698 317 LER-----LIENiksgkgALYPNVKEIFTYIKENNCSIYIASNGLTEYLRAIVSYYDLDQWVTETFSIE-QINSLNKSDL 390

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 491321902 148 IAYILEQEQLQasQCLMVGDREYDVLGARHNGIEAVAVEYGYGTLQELDHA 198
Cdd:PRK06698 391 VKSILNKYDIK--EAAVVGDRLSDINAAKDNGLIAIGCNFDFAQEDELAQA 439

phosphoglycolate phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   5 LLIDLDGTLTDPKVGITTSARYGLAKIGHPLPESENIDWIIGPPLKASLAKI---LQVEPNDVLAEQALMGYRerfAVTG 81
Cdd:PRK13226  15 VLFDLDGTLLDSAPDMLATVNAMLAARGRAPITLAQLRPVVSKGARAMLAVAfpeLDAAARDALIPEFLQRYE---ALIG 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  82 LYeNKVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNGDRTHKDELIAYILEQEQLQASQ 161
Cdd:PRK13226  92 TQ-SQLFDGVEGMLQRLECAGCVWGIVTNKPEYLARLILPQLGWEQRCAVLIGGDTLAERKPHPLPLLVAAERIGVAPTD 170

                        170       180
                 ....*....|....*....|....*...
gi 491321902 162 CLMVGDREYDVLGARHNGIEAVAVEYGY 189
Cdd:PRK13226 171 CVYVGDDERDILAARAAGMPSVAALWGY 198

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 491321902  86 KVYPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYFTGIYGSELNgdRTHK--DELIAYILEQEQLQASQCL 163
Cdd:cd02588   91 PPFPDVVAGLRRLREAGYRLAILSNGSPDLIEDVVANAGLRDLFDAVLSAEDV--RAYKpaPAVYELAAERLGVPPDEIL 168

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 491321902 164 MVGDREYDVLGARHNGIEAVAV----EYGYGTLQELDHAAP 200
Cdd:cd02588  169 HVASHAWDLAGARALGLRTAWInrpgEVPDPLGPAPDFVVP 209

Haloacid Dehalogenase superfamily, subfamily IB, phosphoserine phosphatase-like; This model represents a subfamily of the Haloacid Dehalogenase superfamily of aspartate-nucleophile hydrolases. Subfamily IA, B, C and D are distinguished from the rest of the superfamily by the presence of a variable domain between the first and second conserved catalytic motifs. In subfamilies IA and IB, this domain consists of an alpha-helical bundle. It was necessary to model these two subfamilies separately, breaking them at a an apparent phylogenetic bifurcation, so that the resulting model(s) are not so broadly defined that members of subfamily III (which lack the variable domain) are included. Subfamily IA includes the enzyme phosphoserine phosphatase (TIGR00338) as well as three hypothetical equivalogs. Many members of these hypothetical equivalogs have been annotated as PSPase-like or PSPase-family proteins. In particular, the hypothetical equivalog which appears to be most closely related to PSPase contains only Archaea (while TIGR00338 contains only eukaryotes and bacteria) of which some are annotated as PSPases. Although this is a reasonable conjecture, none of these sequences has sufficient evidence for this assignment. If such should be found, this model should be retired while the PSPase model should be broadened to include these sequences. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902    6 LIDLDGTLTDpkvgiTTSARYGLAKIGHPLPESENIdwiigpplkasLAKILQVEPNDVLAEQALMGYRERFAVTGLYEN 85
Cdd:TIGR01488   3 IFDFDGTLTR-----QDSLIDLLAKLLGTNDEVIEL-----------TRLAPSGRISFEDALGRRLALLHRSRSEEVAKE 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   86 KVYPTVA------ETLQTLKLQGYQLFLATAKPTIYARQILEHFELEQYF------------TGIYGSELNGDRTHKDEL 147
Cdd:TIGR01488  67 FLARQVAlrpgarELISWLKERGIDTVIVSGGFDFFVEPVAEKLGIDDVFanrlefddngllTGPIEGQVNPEGECKGKV 146

                         170       180
                  ....*....|....*....|....*
gi 491321902  148 IAYILEQEQLQASQCLMVGDREYDV 172
Cdd:TIGR01488 147 LKELLEESKITLKKIIAVGDSVNDL 171

HAD-hyrolase-like;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 491321902  146 ELIAYILEQEQLQASQCLMVGDREY-DVLGARHNGIEAVAVEYGYGTLQELDHAAPKA 202
Cdd:pfam13242   8 GMLERALARLGLDPERTVMIGDRLDtDILGAREAGARTILVLTGVTRPADLEKAPIRP 65

beta-phosphoglucomutase, similar to Lactococcus lactis beta-phosphoglucomutase (beta-PGM); Lactococcus lactis beta-PGM catalyzes the interconversion of beta-D-glucose 1-phosphate (G1P) and D-glucose 6-phosphate (G6P), forming beta-D-glucose 1,6-(bis)phosphate as an intermediate. In the forward G6P-forming direction, this reaction links polysaccharide phosphorolysis to glycolysis, in the reverse direction, the reaction provides G1P for the biosynthesis of exo-polysaccharides. This subfamily belongs to the beta-phosphoglucomutase-like family whose other members include 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 491321902   5 LLIDLDGTLTDpkvgittSARYGLAKIghplpesenidwiigpplkASLAKILQvepndvLAEQALMGYRErfAVTGLYE 84
Cdd:cd02598    2 VIFDLDGVITD-------TAEYHYRAW-------------------KKLADKEE------LAARKNRIYVE--LIEELTP 47

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902  85 NKVYPTVAETLQTLKLQGYQLFLATAkpTIYARQILEHFELEQYFTGIY-GSELNGDRTHKDeliAYILEQEQLQA--SQ 161
Cdd:cd02598   48 VDVLPGIASLLVDLKAKGIKIALASA--SKNAPKILEKLGLAEYFDAIVdGAVLAKGKPDPD---IFLAAAEGLGLnpKD 122

                        170       180
                 ....*....|....*....|....*..
gi 491321902 162 CLMVGDREYDVLGARHNGIEAVAVEYG 188
Cdd:cd02598  123 CIGVEDAQAGIRAIKAAGFLVVGVGRE 149

HAD-superfamily hydrolase, subfamily IIIA; This subfamily falls within the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The Class III subfamilies are characterized by the lack of any domains located between either between the first and second conserved catalytic motifs (as in the Class I subfamilies, TIGR01493, TIGR01509, TIGR01488 and TIGR01494) or between the second and third conserved catalytic motifs (as in the Class II subfamilies, TIGR01460 and TIGR01484) of the superfamily domain. The IIIA subfamily contains five major clades: histidinol-phosphatase (TIGR01261) and histidinol-phosphatase-related protein (TIGR00213) which together form a subfamily (TIGR01656), DNA 3'-phosphatase (TIGR01663, TIGR01664), YqeG (TIGR01668) and YrbI (TIGR01670). In the case of histidinol phosphatase and PNK-3'-phosphatase, this model represents a domain of a bifunctional system. In the histidinol phosphatase HisB, a C-terminal domain is an imidazoleglycerol-phosphate dehydratase which catalyzes a related step in histidine biosynthesis. In PNK-3'-phosphatase, N- and C-terminal domains constitute the polynucleotide kinase and DNA-binding components of the enzyme. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491321902   88 YPTVAETLQTLKLQGYQLFLATAKPTIYARQILEHF---------ELEQYFTGIYGSELNgdRTHKDELIAYILEQ-EQL 157
Cdd:TIGR01662  27 YPEVPDALAELKEAGYKVVIVTNQSGIGRGYFSRSFsgrvarrleELGVPIDILYACPGC--RKPKPGMFLEALKRfNEI 104