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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  88 GIEAVALLRTEGVRVGICSNLcEPYGAAVLQAF---PDLDGYAFSYQVGAMKPDVLIYQSICRALEVKPghlfgaksEQI 164
Cdd:cd16415    12 AVETLKDLKEKGLKLAVVSNF-DRRLRELLEALgldDYFDFVVFSYEVGYEKPDPRIFQKALERLGVSP--------EEA 82

                          90       100
                  ....*....|....*....|....*...
gi 2215570975 165 AMVGDSLKCDQDGPRAVGMLGFHLDRSG 192
Cdd:cd16415    83 LHVGDDLKNDYLGARAVGWHALLVDREG 110

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 2215570975   2 ISAVVFDAFGTLVD----------LRSKRHPFRQLLKEGIVGGRRASPEDLRVLVSNPWSLKDAADQLGIRVSLARLQAL 71
Cdd:pfam00702   1 IKAVVFDLDGTLTDgepvvteaiaELASEHPLAKAIVAAAEDLPIPVEDFTARLLLGKRDWLEELDILRGLVETLEAEGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  72 QDDLDREVASI------TPFEDGIEAVALLRTEGVRVGICSNLCEPYGAAVLQAF---PDLDGYAFSYQVGAMKPDVLIY 142
Cdd:pfam00702  81 TVVLVELLGVIaladelKLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLgldDYFDVVISGDDVGVGKPKPEIY 160

                         170       180
                  ....*....|....*....|....*....
gi 2215570975 143 QSICRALEVKPghlfgaksEQIAMVGDSL 171
Cdd:pfam00702 161 LAALERLGVKP--------EEVLMVGDGV 181

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  88 GIEAVALLRTEGVRVGICSNLcEPYGAAVLQAF---PDLDGYAFSYQVGAMKPDVLIYQSICRALEVKPghlfgaksEQI 164
Cdd:cd16415    12 AVETLKDLKEKGLKLAVVSNF-DRRLRELLEALgldDYFDFVVFSYEVGYEKPDPRIFQKALERLGVSP--------EEA 82

                          90       100
                  ....*....|....*....|....*...
gi 2215570975 165 AMVGDSLKCDQDGPRAVGMLGFHLDRSG 192
Cdd:cd16415    83 LHVGDDLKNDYLGARAVGWHALLVDREG 110

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975   2 ISAVVFDAFGTLVDLRSKRHPFRQL----LKEGIVGGRRASPEDLRVLV-SNPWSLKDAADQLGIRVSLARLQ-----AL 71
Cdd:TIGR01428   1 IKALVFDVYGTLFDVHSVAERAAELyggrGEALSQLWRQKQLEYSWLRTlMGPYKDFWDLTREALRYLLGRLGleddeSA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  72 QDDLDREVASITPFEDGIEAVALLRTEGVRVGICSNlcepygaAVLQAFPDLDGYA---------FSY-QVGAMKPDVLI 141
Cdd:TIGR01428  81 ADRLAEAYLRLPPHPDVPAGLRALKERGYRLAILSN-------GSPAMLKSLVKHAglddpfdavLSAdAVRAYKPAPQV 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2215570975 142 YQSICRALEVKPghlfgaksEQIAMVGDSLkCDQDGPRAVGMLGFHLDRSG 192
Cdd:TIGR01428 154 YQLALEALGVPP--------DEVLFVASNP-WDLGGAKKFGFKTAWINRPG 195

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 2215570975   4 AVVFDAFGTLVDL-RSKRHPFRQLLKEgiVGGRRASPEDLRVLVSNpwslkdAADQLGiRVSLARLQALQDDLDR--EVA 80
Cdd:TIGR01549   1 AILFDIDGTLVDIkFAIRRAFPQTFEE--FGLDPASFKALKQAGGL------AEEEWY-RIATSALEELQGRFWSeyDAE 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  81 SITpFEDGIEAVALLRTEGVRVGICSNLCEPYGAAVLQAF--PDLDGYAFSYQVGAMKPDVLIYQSICRALEVKPghlfg 158
Cdd:TIGR01549  72 EAY-IRGAADLLARLKSAGIKLGIISNGSLRAQKLLLRLFglGDYFELILVSDEPGSKPEPEIFLAALESLGVPP----- 145

                         170       180
                  ....*....|....*....|....
gi 2215570975 159 akseQIAMVGDSLKcDQDGPRAVG 182
Cdd:TIGR01549 146 ----EVLHVGDNLN-DIEGARNAG 164

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 2215570975   2 ISAVVFDAFGTLVDLrskrHPFRQLLKEGIVGGRRASPEDLRVLVSNPWSLKDAA------------DQLGIRVSLARLQ 69
Cdd:cd02603     1 IRAVLFDFGGVLIDP----DPAAAVARFEALTGEPSEFVLDTEGLAGAFLELERGriteeefweelrEELGRPLSAELFE 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  70 ALQDdldrevASITPFEDGIEAVALLRTEGVRVGICSNLCEPYGAAVLQAFPDLDGYA----FSYQVGAMKPDVLIYQSI 145
Cdd:cd02603    77 ELVL------AAVDPNPEMLDLLEALRAKGYKVYLLSNTWPDHFKFQLELLPRRGDLFdgvvESCRLGVRKPDPEIYQLA 150

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2215570975 146 CRALEVKPghlfgaksEQIAMVGDSLK-CdqDGPRAVGMLGFHLDRSGRgAVRDL 199
Cdd:cd02603   151 LERLGVKP--------EEVLFIDDREEnV--EAARALGIHAILVTDAED-ALREL 194

haloacid dehalogenase-like superfamily phosphoglycolate phosphatase, similar to Rhodobacter sphaeroides CbbZ; Phosphoglycolate phosphatase catalyzes the dephosphorylation of phosphoglycolate; its activity requires divalent cations, especially Mg++. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975   4 AVVFDAFGTLVD-----LRSKRHPFRQLlkegivGGRRASPEDLRVLVSN--PWSLKDAADQLGIRVSLARLQALQDD-L 75
Cdd:cd07512     1 AVIFDLDGTLIDsapdlHAALNAVLAAE------GLAPLSLAEVRSFVGHgaPALIRRAFAAAGEDLDGPLHDALLARfL 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  76 DREVASI----TPFEDGIEAVALLRTEGVRVGICSNlcEPYGAA--VLQAFpDLDGYaFSYQVGA-----MKPDvliyqs 144
Cdd:cd07512    75 DHYEADPpgltRPYPGVIEALERLRAAGWRLAICTN--KPEAPAraLLSAL-GLADL-FAAVVGGdtlpqRKPD------ 144

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 2215570975 145 icralevkPGHLF------GAKSEQIAMVGDSlKCDQDGPRAVGM 183
Cdd:cd07512   145 --------PAPLRaairrlGGDVSRALMVGDS-ETDAATARAAGV 180

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975   5 VVFDAFGTLVDlrSKR---HPFRQLLKE---GIVggrraSPEDLRVLVSNPwsLKDAADQLGIRVslaRLQALQDDLDRE 78
Cdd:pfam13419   1 IIFDFDGTLLD--TEEliiKSFNYLLEEfgyGEL-----SEEEILKFIGLP--LREIFRYLGVSE---DEEEKIEFYLRK 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  79 VAS------ITPFEDGIEAVALLRTEGVRVGICSNLCEPYGAAVLQAFpDLDGYaFSYQVGA-----MKPDVLIYQSICR 147
Cdd:pfam13419  69 YNEelhdklVKPYPGIKELLEELKEQGYKLGIVTSKSRENVEEFLKQL-GLEDY-FDVIVGGddvegKKPDPDPILKALE 146

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 2215570975 148 ALEVKPghlfgaksEQIAMVGDSLKcDQDGPRAVGM 183
Cdd:pfam13419 147 QLGLKP--------EEVIYVGDSPR-DIEAAKNAGI 173

pyrophosphatase similar to Bacillus subtilis PpaX; This family includes Bacillus subtilis PpaX which hydrolyzes pyrophosphate formed during serine-46-phosphorylated HPr (P-Ser-HPr) dephosphorylation by the bifunctional enzyme HPr kinase/phosphorylase. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975   2 ISAVVFDAFGTLVD-----LRSKRHPFRQLLKEGIvggrraSPED--------LRVLVS--NPWSLKDAADQLgirvsLA 66
Cdd:cd02616     1 ITTILFDLDGTLIDtneliIKSFNHTLKEYGLEGY------TREEvlpfigppLRETFEkiDPDKLEDMVEEF-----RK 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2215570975  67 RLQALQDDLdrevasITPFEDGIEAVALLRTEGVRVGICSNLCEPYGAAVLQAFpDLDGYaFSYQVGA-----MKPD--- 138
Cdd:cd02616    70 YYREHNDDL------TKEYPGVYETLARLKSQGIKLGVVTTKLRETALKGLKLL-GLDKY-FDVIVGGddvthHKPDpep 141

                         170       180       190
                  ....*....|....*....|....*....|..
gi 2215570975 139 VLiyqsicRALEvkpghLFGAKSEQIAMVGDS 170
Cdd:cd02616   142 VL------KALE-----LLGAEPEEALMVGDS 162

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2215570975 129 SYQVGAMKPDVLIYQSICRALEVKPghlfgaksEQIAMVGDSLKCDQDGPRAVGM 183
Cdd:cd04305    57 SEEVGVQKPNPEIFDYALNQLGVKP--------EETLMVGDSLESDILGAKNAGI 103

beta-phosphoglucomutase-like family of the haloacid dehalogenase-like (HAD) hydrolase superfamily; This family represents the beta-phosphoglucomutase-like family of the haloacid dehalogenase-like (HAD) hydrolase superfamily. Family members include Lactococcus lactis beta-PGM, a mutase which catalyzes the interconversion of beta-D-glucose 1-phosphate (G1P) and D-glucose 6-phosphate (G6P), 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. It 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 2215570975  50 WSLKDAADQLgirvsLARLQALQDDLDREVAsITPFEDGIEAVALLRTEGVRVGICSNLCEPYGAAVLQAFPDLDGY--- 126
Cdd:cd07505    14 EPLHRQAWQL-----LERKNALLLELIASEG-LKLKPGVVELLDALKAAGIPVAVATSSSRRNVELLLLELGLLRGYfdv 87

                          90       100       110
                  ....*....|....*....|....*....|
gi 2215570975 127 -AFSYQVGAMKPDVLIYQSICRALEVKPGH 155
Cdd:cd07505    88 iVSGDDVERGKPAPDIYLLAAERLGVDPER 117