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 519052698   1 MQLVILDRDGVINHDSDdYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQSGLARGLFDLDDLEAMHAKLTELVEAAG 80
Cdd:COG0241    3 KKAVFLDRDGTINEDVG-YVKSPEEFEFLPGVLEALARLNEAGYRLVVVTNQSGIGRGLFTEEDLNAVHAKMLELLAAEG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698  81 GQLGAIFYCPHGPDDECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLVTTGKGETTLNKLrqad 160
Cdd:COG0241   82 GRIDAIYYCPHHPDDNCDCRKPKPGMLLQAAERLGIDLSNSYMIGDRLSDLQAAKAAGCKGILVLTGKGAEELAEA---- 157

                        170       180
                 ....*....|....*....|....*
gi 519052698 161 dvyyldeRDVEVFANLAQAVDTLTS 185
Cdd:COG0241  158 -------LPDTVADDLAEAVDYLLA 175

histidinol-phosphate phosphatase family domain; This domain is found in authentic histidinol-phosphate phosphatases which are sometimes found as stand-alone entities and sometimes as fusions with imidazoleglycerol-phosphate dehydratase (TIGR01261). Additionally, a family of proteins including YaeD from E. coli (TIGR00213) and various other proteins are closely related but may not have the same substrate specificity. This domain is a member of the haloacid-dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. This superfamily is distinguished by the presence of three motifs: an N-terminal motif containing the nucleophilic aspartate, a central motif containing an conserved serine or threonine, and a C-terminal motif containing a conserved lysine (or arginine) and conserved aspartates. More specifically, the domian modelled here is a member of subfamily III of the HAD-superfamily by virtue of lacking a "capping" domain in either of the two common positions, between motifs 1 and 2, or between motifs 2 and 3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698    2 QLVILDRDGVINHDSD-DYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQSGLARGLFDLDDLEAMHAKLTELVEAAG 80
Cdd:TIGR01656   1 PALFLDRDGVINEDTVsDYPRSLDDWQLRPGAVPALLTLRAAGYTVVVVTNQSGIGRGYFSAEAFRAPNGRLLELLRQLG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 519052698   81 GQLGAIFYCPHGPDDECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLVTTG 147
Cdd:TIGR01656  81 VAVDGVLFCPHHPADNCSCRKPKPGLILEALKRLGVDASRSLVVGDRLRDLQAARNAGAAAGLLVSG 147

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 519052698   1 MQLVILDRDGVINHDSDdYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQSGLARGLFDLDDLEAMHAKLTELVEAAG 80
Cdd:COG0241    3 KKAVFLDRDGTINEDVG-YVKSPEEFEFLPGVLEALARLNEAGYRLVVVTNQSGIGRGLFTEEDLNAVHAKMLELLAAEG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698  81 GQLGAIFYCPHGPDDECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLVTTGKGETTLNKLrqad 160
Cdd:COG0241   82 GRIDAIYYCPHHPDDNCDCRKPKPGMLLQAAERLGIDLSNSYMIGDRLSDLQAAKAAGCKGILVLTGKGAEELAEA---- 157

                        170       180
                 ....*....|....*....|....*
gi 519052698 161 dvyyldeRDVEVFANLAQAVDTLTS 185
Cdd:COG0241  158 -------LPDTVADDLAEAVDYLLA 175

histidinol-phosphate phosphatase family domain; This domain is found in authentic histidinol-phosphate phosphatases which are sometimes found as stand-alone entities and sometimes as fusions with imidazoleglycerol-phosphate dehydratase (TIGR01261). Additionally, a family of proteins including YaeD from E. coli (TIGR00213) and various other proteins are closely related but may not have the same substrate specificity. This domain is a member of the haloacid-dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. This superfamily is distinguished by the presence of three motifs: an N-terminal motif containing the nucleophilic aspartate, a central motif containing an conserved serine or threonine, and a C-terminal motif containing a conserved lysine (or arginine) and conserved aspartates. More specifically, the domian modelled here is a member of subfamily III of the HAD-superfamily by virtue of lacking a "capping" domain in either of the two common positions, between motifs 1 and 2, or between motifs 2 and 3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698    2 QLVILDRDGVINHDSD-DYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQSGLARGLFDLDDLEAMHAKLTELVEAAG 80
Cdd:TIGR01656   1 PALFLDRDGVINEDTVsDYPRSLDDWQLRPGAVPALLTLRAAGYTVVVVTNQSGIGRGYFSAEAFRAPNGRLLELLRQLG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 519052698   81 GQLGAIFYCPHGPDDECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLVTTG 147
Cdd:TIGR01656  81 VAVDGVLFCPHHPADNCSCRKPKPGLILEALKRLGVDASRSLVVGDRLRDLQAARNAGAAAGLLVSG 147

D,D-heptose 1,7-bisphosphate phosphatase; This family of proteins formerly designated yaeD resembles the histidinol phosphatase domain of the bifunctional protein HisB. The member from E. coli has been characterized as D,D-heptose 1,7-bisphosphate phosphatase, GmhB, involved in inner core LPS assembly (). [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698    4 VILDRDGVINHDSDdYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQSGLARGLFDLDDLEAMHAKLTELVEAAGGQL 83
Cdd:TIGR00213   4 IFLDRDGTINIDHG-YVHEIDNFEFIDGVIDALRELKKMGYALVLVTNQSGIARGYFTEAQFEQLTEWMDWSLAERDVDL 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 519052698   84 GAIFYCPHGPD------DECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAG-AAKGCRLMLVTTGKGET 151
Cdd:TIGR00213  83 DGIYYCPHHPEgveefrQVCDCRKPKPGMLLQARKELHIDMAQSYMVGDKLEDMQAGvAAKVKTNVLVRTGKPIT 157

HAD-IIIA family hydrolase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698   1 MQLVILDRDGVINhdSDDYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQSGLARGLFDLDDLEAmhakltelvEAAG 80
Cdd:PRK06769   4 IQAIFIDRDGTIG--GDTTIHYPGSFTLFPFTKASLQKLKANHIKIFSFTNQPGIADGIATIADFVQ---------ELKG 72

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 519052698  81 GQLGAIFYCPHGPDDECKCRKPLPG-LIDAIEaEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLVTTGKGETTLNKLR 157
Cdd:PRK06769  73 FGFDDIYLCPHKHGDGCECRKPSTGmLLQAAE-KHGLDLTQCAVIGDRWTDIVAAAKVNATTILVRTGAGYDALHTYR 149

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698  27 TPIEGSIEAIARLHKAGYTVVVATNqsglarglfdlddleAMHAKLTELVEAAGgqLGAIFYCPHGPDDECKcRKPLPGL 106
Cdd:COG0546   84 RLFPGVRELLEALKARGIKLAVVTN---------------KPREFAERLLEALG--LDDYFDAIVGGDDVPP-AKPKPEP 145

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698 107 IDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLVTTGKGetTLNKLRQADDVYYLD 166
Cdd:COG0546  146 LLEALERLGLDPEEVLMVGDSPHDIEAARAAGVPFIGVTWGYG--SAEELEAAGADYVID 203

polynucleotide 5'-kinase 3'-phosphatase; This model represents the metazoan 5'-polynucleotide-kinase-3'-phosphatase, PNKP, which is believed to be involved in repair of oxidative DNA damage. Removal of 3' phosphates is essential for the further processing of the break by DNA polymerases. The central phosphatase domain is a member of the IIIA subfamily (TIGR01662) of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. As is common in this superfamily, the enzyme is magnesium dependent. A difference between this enzyme and other HAD-superfamily phosphatases is in the third conserved catalytic motif which usually contains two conserved aspartate residues believed to be involved in binding the magnesium ion. Here, the second aspartate is replaced by a conserved arginine residue which may indicate an interaction with the phosphate backbone of the substrate. Very close relatives of this domain are also found separate from the N- and C-terminal domains seen here, as in the 3'-phosphatase found in plants. The larger family of these domains is described by TIGR01664. Outside of the phosphatase domain is a P-loop ATP-binding motif associated with the kinase activity. The entry for the mouse homolog appears to be missing a large piece of sequence corresponding to the first conserved catalytic motif of the phosphatase domain as well as the conserved threonine of the second motif. Either this is a sequencing artifact or this may represent a pseudo- or non-functional gene. Note that the EC number for the kinase function is: 2.7.1.78

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698   34 EAIARLHKAGYTVVVATNQSGLARGLFDLDDLEamhAKLTELVEAAGGQL------GAIFYcphgpddeckcRKPLPGLI 107
Cdd:TIGR01663 204 EKLKELEADGFKICIFTNQGGIARGKINADDFK---AKIEAIVAKLGVPFqvfiaiGAGFY-----------RKPLTGMW 269

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 519052698  108 DAIEAEFN----TSAQDVPFIGDSLRDLEAGAAKGCR 140
Cdd:TIGR01663 270 DHLKEEANdgteIQEDDCFFVGDAAGRPANGKAAGKK 306

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 519052698    7 DRDGVINHDSDDYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQSglarglfdlddleamhaklTELVEAAGGQLGAI 86
Cdd:pfam00702  78 EGLTVVLVELLGVIALADELKLYPGAAEALKALKERGIKVAILTGDN-------------------PEAAEALLRLLGLD 138

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 519052698   87 FYCPHGPD-DECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAA 136
Cdd:pfam00702 139 DYFDVVISgDDVGVGKPKPEIYLAALERLGVKPEEVLMVGDGVNDIPAAKA 189

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698   27 TPIEGSIEAIARLHKAGYTVVVATN--QSGLARGLFDLDDLEAMHAKLTElveaaggqlgaifycphgpdDECKCRKPLP 104
Cdd:pfam13419  79 KPYPGIKELLEELKEQGYKLGIVTSksRENVEEFLKQLGLEDYFDVIVGG--------------------DDVEGKKPDP 138

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 519052698  105 GLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCR 140
Cdd:pfam13419 139 DPILKALEQLGLKPEEVIYVGDSPRDIEAAKNAGIK 174

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519052698  17 DDYVRS-AEQWTPIEGSIEAIARLHKAGYTVVVATNqsglarglFDLDDLEAM--HAKLTELVEaaggqlgAIFYCphgp 93
Cdd:COG1011   82 EAFLAAlPELVEPYPDALELLEALKARGYRLALLTN--------GSAELQEAKlrRLGLDDLFD-------AVVSS---- 142

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 519052698  94 dDECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLR-DLEAGAA 136
Cdd:COG1011  143 -EEVGVRKPDPEIFELALERLGVPPEEALFVGDSPEtDVAGARA 185

polynucleotide 3'-phosphatase domain similar to the phosphatase domain of the bifunctional enzyme polynucleotide 5'-kinase/3'-phosphatase; Polynucleotide 3'-phosphatase (PNP) domain. This domain dephosphorylates single-stranded as well as double-stranded 3'-phospho termini. It is found in bifunctional enzyme polynucleotide kinase/phosphatase (PNKP) which contain both kinase and phosphatase domains. PNKP plays a key role in both base excision repair and non-homologous end-joining DNA repair pathway. DNA strand breaks can result from DNA damage by ionizing radiation and chemical agents, such as alkylating agents or anticancer agents. Such DNA damage often results in DNA strands with 5'-hydroxyl and 3'-phosphate termini. However, the repair of DNA damage by DNA polymerases and ligases requires 5'-phosphate and 3'-hydroxyl termini. PNKP acts as a 5'-kinase/3'-phosphatase to create 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for ligation during repair. 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 519052698  21 RSAEQWTPIEGSI-EAIARLHKAGYTVVVATNQSGLARGLFDLDDLEamhAKLTELVEAAGGQLgAIFYCPHGPddecKC 99
Cdd:cd01625   22 TNASDWQILYPSVpEKLKALHKDGYKIVIFTNQGGIVRGKLTPEVFK---GKIEAILEKLGVPI-QVYAATKKG----KY 93

                         90       100       110
                 ....*....|....*....|....*....|.
gi 519052698 100 RKPLPGLIDAIEAEFNTSA----QDVPFIGD 126
Cdd:cd01625   94 RKPVTGMWDHLKEDLNSGIpinlKDSFYVGD 124

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 519052698   9 DGVINHDSDDYVRSAEQwtPIEGSIEAIARLHKAGYTVVVATNQsGLARGLFDLDDLEAMHAKLTELVEAAggqlgaify 88
Cdd:cd02603   68 RPLSAELFEELVLAAVD--PNPEMLDLLEALRAKGYKVYLLSNT-WPDHFKFQLELLPRRGDLFDGVVESC--------- 135

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 519052698  89 cphgpddECKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLVT 145
Cdd:cd02603  136 -------RLGVRKPDPEIYQLALERLGVKPEEVLFIDDREENVEAARALGIHAILVT 185

UmpH/NagD family phosphatase, similar to Escherichia coli UmpH UMP phosphatase/NagD nucleotide phosphatase and Mycobacterium tuberculosis Rv1692 glycerol 3-phosphate phosphatase; Escherichia coli UmpH/NagD is a ribonucleoside tri-, di-, and monophosphatase with a preference for purines, it shows peak activity with UMP and functions in UMP-degradation. It is also an effective phosphatase with AMP, GMP and CMP. Mycobacterium tuberculosis phosphatase, Rv1692 is a glycerol 3-phosphate phosphatase. Rv1692 is the final enzyme involved in glycerophospholipid recycling/catabolism. This subfamily belongs to the UmpH/NagD phosphatase family, and to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 519052698   2 QLVILDRDGVINHDSddyvrsaeqwTPIEGSIEAIARLHKAGYTVVVATNQS 53
Cdd:cd07530    1 KGYLIDLDGTVYRGG----------TAIPGAVEFIERLREKGIPFLFLTNNS 42

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 519052698   14 HDSDDYVRSAEQWTPIEGSIEAIARLHKAGYTVVVATNQsglarglfdlddleamhAKLTELVEAAGGQLGAIFYCPHGP 93
Cdd:TIGR01509  67 QLFYEQIEEEAKLKPLPGVRALLEALRARGKKLALLTNS-----------------PRAHKLVLALLGLRDLFDVVIDSS 129

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 519052698   94 DdeCKCRKPLPGLIDAIEAEFNTSAQDVPFIGDSLRDLEAGAAKGCRLMLV 144
Cdd:TIGR01509 130 D--VGLGKPDPDIYLQALKALGLEPSECVFVDDSPAGIEAAKAAGMHTVGV 178

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 519052698   4 VILDRDGVINHDSddyvrsaeqwTPIEGSIEAIARLHKAGYTVVVATNQSGLAR 57
Cdd:cd07532    9 VIFDADGVLWTGD----------KPIPGAVEVFNALLDKGKKVFIVTNNSTKTR 52