HAD-superfamily subfamily IIA hydrolase, TIGR01458; This hypothetical equivalog is a member of the IIA subfamily (TIGR01460) of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases. One sequence (GP|10716807) has been annotated as a "phospholysine phosphohistidine inorganic pyrophosphatase," probably in reference to studies on similarly described (but unsequenced) enzymes from bovine and rat tissues. However, the supporting information for this annotation has never been published. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761    1 MERLKKLEFDISEDEIFTSLTAARNLVEQKQVRPMLLVDDRALPDFKGIQTSDPNAVVIGLAPEHFHYQILNQAFRLLLD 80
Cdd:TIGR01458  55 LERLQRLGFDISEDEVFTPAPAARQLLEEKQLRPMLLVDDRVLPDFDGIDTSDPNCVVMGLAPEHFSYQILNQAFRLLLD 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   81 GAP--LIAIHKARYYKRKDGLALGPGPFVTALEFATDTKATVVGKPAQTFFLEALRGTGCEPEEAVMIGDDCRDDVGGAQ 158
Cdd:TIGR01458 135 GAKpvLIAIGKGRYYKRKDGLALDVGPFVTALEYATDTKATVVGKPSKTFFLEALRATGCEPEEAVMIGDDCRDDVGGAQ 214

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 744594761  159 NVGMRGILVKTGKYRAADEEKINPAPYLTCESFPHAVDHILQH 201
Cdd:TIGR01458 215 DCGMRGIQVRTGKYRPSDEEKINVPPDLTCDSLPHAVDLILQH 257

HAD-hyrolase-like;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 744594761  120 VVGKPAQTFFLEALRGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGILVKTGKYRAADEEKINPAPYLTCESFPHA 194
Cdd:pfam13242   1 VCGKPNPGMLERALARLGLDPERTVMIGDRLDTDILGAREAGARTILVLTGVTRPADLEKAPIRPDYVVDDLAEA 75

HAD-superfamily subfamily IIA hydrolase, TIGR01458; This hypothetical equivalog is a member of the IIA subfamily (TIGR01460) of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases. One sequence (GP|10716807) has been annotated as a "phospholysine phosphohistidine inorganic pyrophosphatase," probably in reference to studies on similarly described (but unsequenced) enzymes from bovine and rat tissues. However, the supporting information for this annotation has never been published. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761    1 MERLKKLEFDISEDEIFTSLTAARNLVEQKQVRPMLLVDDRALPDFKGIQTSDPNAVVIGLAPEHFHYQILNQAFRLLLD 80
Cdd:TIGR01458  55 LERLQRLGFDISEDEVFTPAPAARQLLEEKQLRPMLLVDDRVLPDFDGIDTSDPNCVVMGLAPEHFSYQILNQAFRLLLD 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   81 GAP--LIAIHKARYYKRKDGLALGPGPFVTALEFATDTKATVVGKPAQTFFLEALRGTGCEPEEAVMIGDDCRDDVGGAQ 158
Cdd:TIGR01458 135 GAKpvLIAIGKGRYYKRKDGLALDVGPFVTALEYATDTKATVVGKPSKTFFLEALRATGCEPEEAVMIGDDCRDDVGGAQ 214

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 744594761  159 NVGMRGILVKTGKYRAADEEKINPAPYLTCESFPHAVDHILQH 201
Cdd:TIGR01458 215 DCGMRGIQVRTGKYRPSDEEKINVPPDLTCDSLPHAVDLILQH 257

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   2 ERLKKLEFDISEDEIFTS-LTAARNLVEQKQVRPMLLVDDRALPD------FKGIQTsDPNAVVIGLAPeHFHYQILNQA 74
Cdd:cd07530   51 AKLAEMGIDVPEEDVYTSaLATAQYLAEQLPGAKVYVIGEEGLRTalheagLTLTDE-NPDYVVVGLDR-DLTYEKLAEA 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761  75 FRLLLDGAPLIAIHKARYYKRKDGLALGPGPFVTALEFATDTKATVVGKPAQTFFLEALRGTGCEPEEAVMIGDDCRDDV 154
Cdd:cd07530  129 TLAIRNGAKFIATNPDLTLPTERGLLPGNGSVVAALEAATGVKPLFIGKPEPIMMRAALEKLGLKSEETLMVGDRLDTDI 208

                        170       180
                 ....*....|....*....|..
gi 744594761 155 GGAQNVGMRGILVKTGKYRAAD 176
Cdd:cd07530  209 AAGIAAGIDTLLVLTGVTTRED 230

UmpH/NagD family phosphatase, similar to Bacillus AraL phosphatase, a putative sugar phosphatase; Bacillus subtilis AraL is a phosphatase displaying activity towards different sugar phosphate substrates; it is encoded by the arabinose metabolic operon araABDLMNPQ-abfA and may play a role in the dephosphorylation of substrates related to l-arabinose metabolism. 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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   2 ERLKKLEFDISEDEIFTSLTA-ARNLVEQKQVRPMLLVDDRALPD---FKGIQTSDP---NAVVIGLAPEHFHYQILNQA 74
Cdd:cd07531   51 ERLRSFGIEVGEDEILVSSYVtARFLAREKPNAKVFVTGEEGLIEelrLAGLEIVDKydeAEYVVVGSNRKITYELLTKA 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761  75 FRLLLDGAPLIAIHKARYYKRKDGLALGPGPFVTALEFATDTKA-TVVGKPAQTFFLEALRGTGCEPEEAVMIGDDCRDD 153
Cdd:cd07531  131 FRACLRGARYIATNPDRIFPAEDGPIPDTAAIIGAIEWCTGREPeVVVGKPSEVMAREALDILGLDAKDCAIVGDQIDVD 210

                        170       180
                 ....*....|....*....|....*.
gi 744594761 154 VGGAQNVGMRGILVKTGKYRAADEEK 179
Cdd:cd07531  211 IAMGKAIGMETALVLTGVTTRENLDR 236

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   1 MERLKKLEFDISEDEIFTS-LTAARNLVEQK----------------------QVRPMLLVDDRALPDFKGIQTSDPN-- 55
Cdd:cd07508   49 AEKFRKFGVDVPEDQIVTSaKATARFLRSRKfgkkvyvlgeeglkeelraagfRIAGGPSKGIETYAELVEHLEDDENvd 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761  56 AVVIGLApEHFHYQILNQAFRLLLD-GAPLIAIHKARYYK-RKDGLALGPGPFVTALEFATDTKATVVGKPAQTFFLEAL 133
Cdd:cd07508  129 AVIVGSD-FKLNFAKLRKACRYLRNpGCLFIATAPDRIHPlKDGGPIPGTGAFAAAVEAATGRQPLVLGKPSPWLGELAL 207

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 744594761 134 RGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGILVKTG 170
Cdd:cd07508  208 EKFGIDPERVLFVGDRLATDVLFGKACGFQTLLVLTG 244

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 744594761  56 AVVIGLAPeHFHYQILNQAFRLLLD-GAPLIAIHKARYYKRKDGLAL-GPGPFVTALEFATDTKATVVGKPAQTFFLEAL 133
Cdd:cd07510  136 AVLVGLDE-HVNYLKLAKATQYLRDpGCLFVATNRDPWHPLSDGSFIpGTGSLVAALETASGRQAIVVGKPSRFMFDCIS 214

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 744594761 134 RGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGILVKTG 170
Cdd:cd07510  215 SKFSIDPARTCMVGDRLDTDILFGQNCGLKTLLVLTG 251

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   1 MERLKKLEFDISEDEIFTSLTA-ARNLVEQKQVRPMLLVDDRALP---DFKGIQT-----------------------SD 53
Cdd:cd07532   56 AKKAKKLGFNVKENNILSSAAViADYLKEKGFKKKVYVIGEEGIRkelEEAGIVScggdgedekddsmgdfahnleldPD 135

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761  54 PNAVVIGLaPEHFHYQILNQAFRLLLDgaPLI--------AIHKARYYKRkdglALGPGPFVTALEFATDTKATVVGKPA 125
Cdd:cd07532  136 VGAVVVGR-DEHFSYPKLMKACNYLRN--PDVlflatnmdATFPGPVGRV----IPGAGAMVAAIEAVSGRKPLVLGKPN 208

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 744594761 126 QTFFLEALRGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGILVKTGKYRAADEEKI 180
Cdd:cd07532  209 PQILNFLMKSGVIKPERTLMIGDRLKTDILFANNCGFQSLLVGTGVNSLEDAEKI 263

phosphoglycolate/pyridoxal phosphate phosphatase family; 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 mammals, PGP is found in many tissues, notably in red blood cells where P-glycolate is and important activator of the hydrolysis of 2,3-bisphosphoglycerate, a major modifier of the oxygen affinity of hemoglobin. Pyridoxal phosphate (PLP, Vitamin B6) phosphatase is involved in the degradation of PLP in mammals and is widely distributed in human tissues including erythrocyes. The enzymes described here are members of the Haloacid dehalogenase superfamily of hydrolase enzymes (pfam00702). Unlike the bacterial PGP equivalog (TIGR01449), which is a member of class (subfamily) I, these enzymes are members of class (subfamily) II. These two families have almost certainly arisen from convergent evolution (although these two ancestors may themselves have diverged from a more distant HAD superfamily progenitor). The primary seed sequence for this model comes from Chlamydomonas reinhardtii, a photosynthetic alga. The enzyme has been purified and characterized and these data are fully consistent with the assignment of function as a PGPase involved in photorespiration. The second seed, from Homo sapiens chromosome 22 has been characterized as a pyridoxal phosphatase. Biochemical characterization of partially purified PGP's from various tissues including red blood cells have been performed while one gene for PGP has been localized to chromosome 16p13.3. The sequence used here maps to chromosome 22. There is indeed a related gene on chromosome 16 (and it is expressed, since EST's are found) which shows 46% identity. The chromosome 16 gene is not in evidence in nraa but translated from the genomic sequence. The third seed, from C. elegans, is only supported by sequence similarity. This model is limited to eukaryotic species including S. pombe and S. cerevisiae, although several archaea score between the trusted and noise cutoffs. This model is closely related to a family of bacterial sequences including the E. coli NagD and B. subtilus AraL genes which are characterized by the ability to hydrolyze para-nitrophenylphosphate (pNPPases or NPPases). The chlamydomonas PGPase d

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761    1 MERLKKLEFDISEDEIFTSLTAARNLVEQ-----KQVRPMLLVDDRALPDFKGIQ--------------------TSDPN 55
Cdd:TIGR01452  52 ALKFARLGFNGLAEQLFSSALCAARLLRQppdagKAVYVIGEEGLRAELDAAGIRlagdpgekkqdeadgfmydiKLDER 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   56 --AVVIGLaPEHFHYQILNQAFRLLLD-GAPLIAIHKARYYKRKDGLAL-GPGPFVTALEFATDTKATVVGKPAQTFFLE 131
Cdd:TIGR01452 132 vgAVVVGY-DEHFSYVKLMEACAHLREpGCLFVATNRDPWHPLSDGSRTpGTGSLVAAIETASGRQPLVVGKPSPYMFNC 210

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 744594761  132 ALRGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGILVKTG--------KYRAADEEKINP---APYL 186
Cdd:TIGR01452 211 ITEKFSIDPARTLMVGDRLETDILFGHRCGMTTVLVLSGvsqleeaqEYLMAGQDDLVPdyvVESL 276

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
                 ....*....|....*....|....*....|....*....|....*
gi 744594761 121 VGKPAQTFFLEALRGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGI 165
Cdd:cd04305   62 VQKPNPEIFDYALNQLGVKPEETLMVGDSLESDILGAKNAGIKTV 106

HAD-IIA family hydrolase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   3 RLKKLEFDISEDEIFTSLTAARNLVEQKQVRPMLLVDDRALPD--FKG---IQTSDPNAVVIGlAPEHFHYQILNQAFRL 77
Cdd:PRK10444  53 RFATAGVDVPDSVFYTSAMATADFLRRQEGKKAYVIGEGALIHelYKAgftITDINPDFVIVG-ETRSYNWDMMHKAAYF 131

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761  78 LLDGAPLIAIHKARYykrkdGLALGP--GPFVTALEFATDTKATVVGKPAQTFFLEALRGTGCEPEEAVMIGDDCRDDVG 155
Cdd:PRK10444 132 VANGARFIATNPDTH-----GRGFYPacGALCAGIEKISGRKPFYVGKPSPWIIRAALNKMQAHSEETVIVGDNLRTDIL 206

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 744594761 156 GAQNVGMRGILVKTGKYRAADeekINPAPYLTCESFPHAVD 196
Cdd:PRK10444 207 AGFQAGLETILVLSGVSTLDD---IDSMPFRPSWIYPSVAD 244

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 744594761   61 LAPEHFHY-QILNQAFRLLLDGA-PLIAIHKARYYK--------RKDGLALGPGPFVTALEFATDTKATVVGKPAQTFFL 130
Cdd:TIGR01509  63 LLYKQLFYeQIEEEAKLKPLPGVrALLEALRARGKKlalltnspRAHKLVLALLGLRDLFDVVIDSSDVGLGKPDPDIYL 142

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 744594761  131 EALRGTGCEPEEAVMIgDDCRDDVGGAQNVGMRGILV 167
Cdd:TIGR01509 143 QALKALGLEPSECVFV-DDSPAGIEAAKAAGMHTVGV 178

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 744594761 122 GKPAQTFFLEALRGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGILVK 168
Cdd:COG2179   90 KKPLPRGFRKALKLMGLPPEETAVVGDQLFTDVLGGNRAGLYTILVK 136

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
                 ....*....|....*....|....*....|....*....|....*...
gi 744594761 121 VGKPAQTFFLEALRGTGCEPEEAVMIgDDCRDDVGGAQNVGMRGILVK 168
Cdd:cd02603  139 VRKPDPEIYQLALERLGVKPEEVLFI-DDREENVEAARALGIHAILVT 185

HAD-superfamily class IIA hydrolase, TIGR01456, CECR5; This hypothetical equivalog is a member of the Class IIA subfamily of the haloacid dehalogenase superfamily of aspartate-nucleophile hydrolases. The sequences modelled by this equivalog are all eukaryotes. One sequence (GP|13344995) is called "Cat Eye Syndrome critical region protein 5" (CECR5). This gene has been cloned from a pericentromere region of human chromosome 22 believed to be the location of the gene or genes responsible for Cat Eye Syndrome. This is one of a number of candidate genes. The Schizosaccharomyces pombe sequence (EGAD|138276) is annotated as "phosphatidyl synthase," however this is due entirely to a C-terminal region of the protein (outside the region of similarity of this model) which is highly homologous to a family of CDP-alcohol phosphatidyltransferases. (Thus, the annotation of GP|4226073 from C. elegans as similar to phosphatidyl synthase, is a mistake as this gene does not contain the C-terminal portion). The physical connection of the phosphatidyl synthase and the HAD-superfamily hydrolase domain in S. pombe may, however, be an important clue to the substrate for the hydrolases in this equivalog.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761   74 AFRLLLD-------GAPLiaihkaRYYkrkdglALG-PGPFVtaLEFATDTKATVVGKPAQTfflealRGTGCEPEEAVM 145
Cdd:TIGR01456 209 AFRLLLEriylelnGKPL------QYY------TLGkPTKLT--YDFAEDVLIDWEKRLSGT------KPSTSPFHALYM 268

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 744594761  146 IGDDCRDDVGGAQNVGMRGILVKTGKYRAADEEKINPaPYLTCESFPHAVDHIL 199
Cdd:TIGR01456 269 VGDNPASDIIGAQNYGWFSCLVKTGVYNGGDDLKECK-PTLIVNDVFDAVTKIL 321

D-glycero-beta-D-manno-heptose 1,7-bisphosphate 7-phosphatase;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 744594761 123 KPAQTFFLEALRGTGCEPEEAVMIGDDcRDDVGGAQNVGMRGILVKTGKYRAADEEKiNPAPYLTCESFPHAVDHILQH 201
Cdd:PRK08942 103 KPKPGMLLSIAERLNIDLAGSPMVGDS-LRDLQAAAAAGVTPVLVRTGKGVTTLAEG-AAPGTWVLDSLADLPQALKKQ 179

Haloacid dehalogenase-like hydrolase; This family is part of the HAD superfamily.

                          10        20        30
                  ....*....|....*....|....*....|
gi 744594761    1 MERLKKLEFDISEDEIFTSLTAARNLVEQK 30
Cdd:pfam13344  48 AEKLRKLGFDIDEDEIITSGTAAADYLKER 77

pyrophosphatase PpaX; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 744594761 123 KPAQTFFLEALRGTGCEPEEAVMIGDDCRDDVGGaQNVGmrgilVKTG--KYRAADEEKI 180
Cdd:PRK13288 138 KPDPEPVLKALELLGAKPEEALMVGDNHHDILAG-KNAG-----TKTAgvAWTIKGREYL 191

2-haloalkanoic acid dehalogenase, type II; Catalyzes the hydrolytic dehalogenation of small L-2-haloalkanoic acids to yield the corresponding D-2-hydroxyalkanoic acids. Belongs to the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases (pfam00702), class (subfamily) I. Note that the Type I HAD enzymes have not yet been fully characterized, but clearly utilize a substantially different catalytic mechanism and are thus unlikely to be related.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 744594761  123 KPAQTFFLEALRGTGCEPEEAVMIGDDcRDDVGGAQNVGMRGILV 167
Cdd:TIGR01428 148 KPAPQVYQLALEALGVPPDEVLFVASN-PWDLGGAKKFGFKTAWI 191

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
                  ....*....|....*....|....*....|....*....|....*.
gi 744594761  123 KPAQTFFLEAL-RGTGCEPEEAVMIGDDCRDDVGGAQNVGMRGILV 167
Cdd:TIGR01662  88 KPKPGMFLEALkRFNEIDPEESVYVGDQDLTDLQAAKRVGLATILV 133