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 2254355600   4 RHVLWDADGVLqsLPGGWERAAAPWLGERDEASEALLREA--VAVEREALVGRSDFLADLAGVLERHGVDVPARDLHAAI 81
Cdd:cd02603     2 RAVLFDFGGVL--IDPDPAAAVARFEALTGEPSEFVLDTEglAGAFLELERGRITEEEFWEELREELGRPLSAELFEELV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2254355600  82 WLATEPDAASWAVVERVRAAGHGVHLGTNQ-EAHRAAHMRTVLGYDERFDVSVYSCDLGVAKPDPAYFERAVAMIGADPD 160
Cdd:cd02603    80 LAAVDPNPEMLDLLEALRAKGYKVYLLSNTwPDHFKFQLELLPRRGDLFDGVVESCRLGVRKPDPEIYQLALERLGVKPE 159

                         170       180
                  ....*....|....*....|....*....
gi 2254355600 161 DVVFVDDRADNVASACEVGLRGVHWTIAE 189
Cdd:cd02603   160 EVLFIDDREENVEAARALGIHAILVTDAE 188

haloacid dehalogenase superfamily, subfamily IA, variant 3 with third motif having DD or ED; This model represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The subfamilies are defined based on the location and the observed or predicted fold of a so-called "capping domain", or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions. The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that representing it with a single model is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an aparrent phylogenetic bifurcation. Subfamily IA is still too broad to model, but cannot be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms: (1) hhhhsDxxx(x)D, (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA. Individual models were made based on seeds exhibiting only one of the variants each. Variant 3 (this model) is found in the enzymes beta-phosphoglucomutase (TIGR01990) and deoxyglucose-6-phosphatase, while many other enzymes of subfamily IA exhibit this variant as well as variant 1 (TIGR01549). These three variant models were created with the knowledge that there will be overlap among them - this is by design and serves the purpose of eliminating the overlap with models of more distantly related HAD subfamilies caused by an overly broad single model. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2254355600   5 HVLWDADGVL-QSLPGGWERAAAPWLG--ERDEASEALLREAVAVER-EALVGRSDFLADLAGVLERhgvdVPARDLHAA 80
Cdd:TIGR01509   1 AILFDLDGVLvDTEFAIAKLINREELGlvPDELGVSAVGRLELALRRfKAQYGRTISPEDAQLLYKQ----LFYEQIEEE 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2254355600  81 IWLATEPDAAswAVVERVRAAGHGVHLGTNQEAHRAAHMRTvLGYDERFDVSVYSCDLGVAKPDPAYFERAVAMIG 156
Cdd:TIGR01509  77 AKLKPLPGVR--ALLEALRARGKKLALLTNSPRAHKLVLAL-LGLRDLFDVVIDSSDVGLGKPDPDIYLQALKALG 149

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 2254355600   4 RHVLWDADGVLqsLPGGWERAAAPWLGERDEASEALLREA--VAVEREALVGRSDFLADLAGVLERHGVDVPARDLHAAI 81
Cdd:cd02603     2 RAVLFDFGGVL--IDPDPAAAVARFEALTGEPSEFVLDTEglAGAFLELERGRITEEEFWEELREELGRPLSAELFEELV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2254355600  82 WLATEPDAASWAVVERVRAAGHGVHLGTNQ-EAHRAAHMRTVLGYDERFDVSVYSCDLGVAKPDPAYFERAVAMIGADPD 160
Cdd:cd02603    80 LAAVDPNPEMLDLLEALRAKGYKVYLLSNTwPDHFKFQLELLPRRGDLFDGVVESCRLGVRKPDPEIYQLALERLGVKPE 159

                         170       180
                  ....*....|....*....|....*....
gi 2254355600 161 DVVFVDDRADNVASACEVGLRGVHWTIAE 189
Cdd:cd02603   160 EVLFIDDREENVEAARALGIHAILVTDAE 188

haloacid dehalogenase superfamily, subfamily IA, variant 3 with third motif having DD or ED; This model represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The subfamilies are defined based on the location and the observed or predicted fold of a so-called "capping domain", or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions. The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that representing it with a single model is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an aparrent phylogenetic bifurcation. Subfamily IA is still too broad to model, but cannot be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms: (1) hhhhsDxxx(x)D, (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA. Individual models were made based on seeds exhibiting only one of the variants each. Variant 3 (this model) is found in the enzymes beta-phosphoglucomutase (TIGR01990) and deoxyglucose-6-phosphatase, while many other enzymes of subfamily IA exhibit this variant as well as variant 1 (TIGR01549). These three variant models were created with the knowledge that there will be overlap among them - this is by design and serves the purpose of eliminating the overlap with models of more distantly related HAD subfamilies caused by an overly broad single model. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2254355600   5 HVLWDADGVL-QSLPGGWERAAAPWLG--ERDEASEALLREAVAVER-EALVGRSDFLADLAGVLERhgvdVPARDLHAA 80
Cdd:TIGR01509   1 AILFDLDGVLvDTEFAIAKLINREELGlvPDELGVSAVGRLELALRRfKAQYGRTISPEDAQLLYKQ----LFYEQIEEE 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2254355600  81 IWLATEPDAAswAVVERVRAAGHGVHLGTNQEAHRAAHMRTvLGYDERFDVSVYSCDLGVAKPDPAYFERAVAMIG 156
Cdd:TIGR01509  77 AKLKPLPGVR--ALLEALRARGKKLALLTNSPRAHKLVLAL-LGLRDLFDVVIDSSDVGLGKPDPDIYLQALKALG 149

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2254355600   3 PRHVLWDADGVL-QSLPGgWERAAApwlgerdEASEALLREAVAVER-EALVGRS--DFLADLAGVLERHGVDvPARDLH 78
Cdd:COG0546     1 IKLVLFDLDGTLvDSAPD-IAAALN-------EALAELGLPPLDLEElRALIGLGlrELLRRLLGEDPDEELE-ELLARF 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2254355600  79 AAIWLATEPDAASW-----AVVERVRAAGHGVHLGTNQEAHRAAHMRTVLGYDERFDVSVYSCDLGVAKPDPAYFERAVA 153
Cdd:COG0546    72 RELYEEELLDETRLfpgvrELLEALKARGIKLAVVTNKPREFAERLLEALGLDDYFDAIVGGDDVPPAKPKPEPLLEALE 151

                  ....
gi 2254355600 154 MIGA 157
Cdd:COG0546   152 RLGL 155

uncharacterized family of the haloacid dehalogenase-like superfamily, similar to uncharacterized Drosophila melanogaster rhythmically expressed gene 2 protein and human haloacid dehalogenase-like hydrolase domain-containing protein 3; The haloacid dehalogenase-like (HAD) hydrolases are a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. Members are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 2254355600 123 LGYDERFDVSVYSCDLGVAKPDPAYFERAVAMIG 156
Cdd:cd16415    43 LGLDDYFDFVVFSYEVGYEKPDPRIFQKALERLG 76