inorganic pyrophosphatase similar to a human phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP); LHPP hydrolyzes nitrogen-phosphorus bonds in phospholysine, phosphohistidine and imidodiphosphate as well as oxygen-phosphorus bonds in inorganic pyrophosphate in vitro. This family also includes human haloacid dehalogenase like hydrolase domain containing 2 protine (HDHD2) a phosphatase which may be involved in polygenic hypertension. 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, 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 269847098  12 RGVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESQKSRAELVGQLQRLGFDISEQEVTAPAPAACQIL 91
Cdd:cd07509    1 KAVLLDLSGTLYISGAAIPG----AAEALKRLRHAGLKVRFLTNTTKESRRTLAERLQRLGFDVSEEEIFTSLTAARQYL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098  92 KEQGLRPYLLIHDGVRSEFDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLmeLEKPVLISLGKGRYYKETSGLMLDVGP 171
Cdd:cd07509   77 EEKGLRPHLLVDDDALEDFIGIDTSDPNAVVIGDAGEHFNYQTLNRAFRLL--LDGAPLIALHKGRYYKRKDGLALDPGA 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 172 YMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEHHPEVKAD 251
Cdd:cd07509  155 FVTGLEYATGIKATVVGKPSPEFFLSALRSLGVDPEEAVMIGDDLRDDVGGAQACGMRGILVRTGKYRPSDEKKPNVPPD 234

                        250
                 ....*....|....
gi 269847098 252 GYVDNLAEAVDLLL 265
Cdd:cd07509  235 LTADSFADAVDHIL 248

HAD-hyrolase-like;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 269847098  186 VVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEHHPEVKADGYVDNLAEA 260
Cdd:pfam13242   1 VCGKPNPGMLERALARLGLDPERTVMIGDRLDTDILGAREAGARTILVLTGVTRPADLEKAPIRPDYVVDDLAEA 75

inorganic pyrophosphatase similar to a human phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP); LHPP hydrolyzes nitrogen-phosphorus bonds in phospholysine, phosphohistidine and imidodiphosphate as well as oxygen-phosphorus bonds in inorganic pyrophosphate in vitro. This family also includes human haloacid dehalogenase like hydrolase domain containing 2 protine (HDHD2) a phosphatase which may be involved in polygenic hypertension. 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, 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 269847098  12 RGVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESQKSRAELVGQLQRLGFDISEQEVTAPAPAACQIL 91
Cdd:cd07509    1 KAVLLDLSGTLYISGAAIPG----AAEALKRLRHAGLKVRFLTNTTKESRRTLAERLQRLGFDVSEEEIFTSLTAARQYL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098  92 KEQGLRPYLLIHDGVRSEFDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLmeLEKPVLISLGKGRYYKETSGLMLDVGP 171
Cdd:cd07509   77 EEKGLRPHLLVDDDALEDFIGIDTSDPNAVVIGDAGEHFNYQTLNRAFRLL--LDGAPLIALHKGRYYKRKDGLALDPGA 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 172 YMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEHHPEVKAD 251
Cdd:cd07509  155 FVTGLEYATGIKATVVGKPSPEFFLSALRSLGVDPEEAVMIGDDLRDDVGGAQACGMRGILVRTGKYRPSDEKKPNVPPD 234

                        250
                 ....*....|....
gi 269847098 252 GYVDNLAEAVDLLL 265
Cdd:cd07509  235 LTADSFADAVDHIL 248

Haloacid Dehalogenase Superfamily Class (subfamily) IIA; This model represents one structural subclass of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The classes 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. Class I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Class II consists of sequences in which the capping domain is found between the second and third motifs. Class III sequences have no capping domain in iether of these positions. The Class IIA capping domain is predicted by PSI-PRED to consist of a mixed alpha-beta fold with the basic pattern: Helix-Helix-Helix-Sheet-Helix-Loop-Sheet-Helix-Sheet-Helix. Presently, this subfamily encompasses a single equivalog model (TIGR01452) for the eukaryotic phosphoglycolate phosphatase, as well as four hypothetical equivalogs covering closely related sequences (TIGR01456 and TIGR01458 in eukaryotes, TIGR01457 in gram positive bacteria and TIGR01459 in gram negative bacteria). The Escherishia coli NagD gene and the Bacillus subtilus AraL gene are members of this subfamily but are not members of the any of the presently defined equivalogs within it. NagD is part of the NAG operon responsible for N-acetylglucosamine metabolism. The function of this gene is unknown. Genes from several organisms have been annotated as NagD, or NagD-like. However, without data on the presence of other members of this pathway, (such as in the case of Yersinia pestis) these assignments should not be given great weight. The AraL gene is similar: it is part of the L-arabinose operon, but the function is unknown. A gene from Halobacterium has been annotated as AraL, but no other Ara operon genes have been annotated. Many of the genes in this subfamily have been annotated as "pNPPase" "4-nitrophenyl phosphatase" or "NPPase". These all refer to the same activity versus a common lab test compound used to determine phosphatase activity. There is no evidence that this activity is physiologically relevant. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098   14 VLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESQKSRAELVGQLQRL-GFDISEQEVTAPAPAACQILK 92
Cdd:TIGR01460   1 FLFDIDGVLWLGHKPIPG----AAEALNRLRAKGKPVVFLTNNSSRSEEDYAEKLSSLlGVDVSPDQIITSGSVTKDLLR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098   93 E--QGLRPYLLIHDGVRSE----------FDQIDTSNPN---CVVIADAGESFSYQNMNNAFQVLMELEKPVLIS----- 152
Cdd:TIGR01460  77 QrfEGEKVYVIGVGELRESleglgfrndfFDDIDHLAIEkipAAVIVGEPSDFSYDELAKAAYLLAEGDVPFIAAnrddl 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098  153 --LGKGRYYketsglmLDVGPYMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQ-AVMIGDDIVGDVGGAQRCGMR 229
Cdd:TIGR01460 157 vrLGDGRFR-------PGAGAIAAGIKELSGREPTVVGKPSPAIYRAALNLLQARPERrDVMVGDNLRTDILGAKNAGFD 229

                  ....*..
gi 269847098  230 ALQVRTG 236
Cdd:TIGR01460 230 TLLVLTG 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 269847098  13 GVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESQKSRAELVGQLQRLGFDISEQEVTAPAPAACQILK 92
Cdd:cd07508    1 LVISDCDGVLWHDERAIPG----AAEFLEALKEAGKKIVFVSNNSSRSRQDYAEKFRKFGVDVPEDQIVTSAKATARFLR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098  93 EQ--GLRPYLLIHDGVRSEF----------------------DQIDTSNPNCVVIADAGESFSYQNMNNAFQVLMELEKp 148
Cdd:cd07508   77 SRkfGKKVYVLGEEGLKEELraagfriaggpskgietyaelvEHLEDDENVDAVIVGSDFKLNFAKLRKACRYLRNPGC- 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 149 VLISLGKGRYYK-ETSGLMLDVGPYMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCG 227
Cdd:cd07508  156 LFIATAPDRIHPlKDGGPIPGTGAFAAAVEAATGRQPLVLGKPSPWLGELALEKFGIDPERVLFVGDRLATDVLFGKACG 235

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 269847098 228 MRALQVRTGKFRPSD---EHHPEVKADGYVDNLAE 259
Cdd:cd07508  236 FQTLLVLTGVTTLEDlqaYIDHELVPDYYADSLAD 270

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 269847098  13 GVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESQKSRAELVGQLQRLGFDISEQEVTAPAPAACQILK 92
Cdd:cd07531    2 GYIIDLDGTIGKGVTLIPG----AVEGVKTLRRLGKKIIFLSNNSTRSRRILLERLRSFGIEVGEDEILVSSYVTARFLA 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098  93 EQ--GLRPYLLIHDGVRSE-----FDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLMELEKpvLISLGKGRYYKETSGL 165
Cdd:cd07531   78 REkpNAKVFVTGEEGLIEElrlagLEIVDKYDEAEYVVVGSNRKITYELLTKAFRACLRGAR--YIATNPDRIFPAEDGP 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 166 MLDVGPYMKALEYACGIKAE-VVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEH 244
Cdd:cd07531  156 IPDTAAIIGAIEWCTGREPEvVVGKPSEVMAREALDILGLDAKDCAIVGDQIDVDIAMGKAIGMETALVLTGVTTRENLD 235

                        250
                 ....*....|....*..
gi 269847098 245 HPEVKADGYVDNLAEAV 261
Cdd:cd07531  236 RHGYKPDYVLNSIKDLV 252

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 269847098   8 LAGVRGVLLDISGVLYdsgaGGGTAIAGSVEAVARLKRSRLKVRFCTNESQKSRAELVGQLQRLGFDISEQEVTAPAPAA 87
Cdd:cd07532    3 LANIDTVIFDADGVLW----TGDKPIPGAVEVFNALLDKGKKVFIVTNNSTKTREELAKKAKKLGFNVKENNILSSAAVI 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098  88 CQILKEQGLRPYLLI--HDGVRSEFDQ-------------IDTS------------NPNCVVIA-DagESFSYQNMNNAF 139
Cdd:cd07532   79 ADYLKEKGFKKKVYVigEEGIRKELEEagivscggdgedeKDDSmgdfahnleldpDVGAVVVGrD--EHFSYPKLMKAC 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 140 QVLMElekPVLISLGKGR--YYKETSGLML-DVGPYMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDI 216
Cdd:cd07532  157 NYLRN---PDVLFLATNMdaTFPGPVGRVIpGAGAMVAAIEAVSGRKPLVLGKPNPQILNFLMKSGVIKPERTLMIGDRL 233

                        250       260
                 ....*....|....*....|
gi 269847098 217 VGDVGGAQRCGMRALQVRTG 236
Cdd:cd07532  234 KTDILFANNCGFQSLLVGTG 253

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 269847098 184 AEVVG--KPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRtgkfRPSDEHHPEVKADGYVDNLAEAV 261
Cdd:COG1011  142 SEEVGvrKPDPEIFELALERLGVPPEEALFVGDSPETDVAGARAAGMRTVWVN----RSGEPAPAEPRPDYVISDLAELL 217

                 ...
gi 269847098 262 DLL 264
Cdd:COG1011  218 ELL 220

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098   14 VLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESQKSRAELVGQLQRLGFDISEQEVTAPAPAACQILKE 93
Cdd:pfam13344   1 FLFDIDGVLWRGGEPIPG----AAEALRALRAAGKPVVFVTNNSSRSREEYAEKLRKLGFDIDEDEIITSGTAAADYLKE 76

                          90       100
                  ....*....|....*....|
gi 269847098   94 Q--GLRPYLLIHDGVRSEFD 111
Cdd:pfam13344  77 RkfGKKVLVIGSEGLREELE 96

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 269847098 189 KPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALqvrtgKFRPSDEHHPE 247
Cdd:cd16415   62 KPDPRIFQKALERLGVSPEEALHVGDDLKNDYLGARAVGWHAL-----LVDREGALHEL 115

phosphoglycolate phosphatase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098  38 EAVARLKRSRLKVRFCTNESQKSRAELVGQLQRLGFDISEQEVTAPAPAACQILKEQGLRP----YLLIHDGVRSEFDQI 113
Cdd:PLN02645  51 ETLDMLRSMGKKLVFVTNNSTKSRAQYGKKFESLGLNVTEEEIFSSSFAAAAYLKSINFPKdkkvYVIGEEGILEELELA 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 114 DTsnpNCVviadAGESFSYQNMNNAFQVLMELEKPV-LISLGKGR---YYK---------ETSGLM-----LD-VGPYMK 174
Cdd:PLN02645 131 GF---QYL----GGPEDGDKKIELKPGFLMEHDKDVgAVVVGFDRyinYYKiqyatlcirENPGCLfiatnRDaVTHLTD 203

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 175 ALEYA----------CGIKAE--VVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSD 242
Cdd:PLN02645 204 AQEWAgagsmvgaikGSTEREplVVGKPSTFMMDYLANKFGIEKSQICMVGDRLDTDILFGQNGGCKTLLVLSGVTSESM 283

                        250       260
                 ....*....|....*....|....
gi 269847098 243 EHHPE--VKADGYVDNLAEAVDLL 264
Cdd:PLN02645 284 LLSPEnkIQPDFYTSKISDFLTLK 307

Uncharacterized family of the the haloacid dehalogenase-like superfamily, similar to the uncharacterized protein Bacillus subtilis YqeG; 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
                 ....*....|....*....|....*....|....*....|....*.
gi 269847098 188 GKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQV 233
Cdd:cd16416   63 GKPRPRAFRRALKEMDLPPEQVAMVGDQLFTDILGGNRAGLYTILV 108

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 269847098 188 GKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVR 234
Cdd:COG2179   90 KKPLPRGFRKALKLMGLPPEETAVVGDQLFTDVLGGNRAGLYTILVK 136

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 269847098  110 FDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLMELEKPVLI---SLGKGRYYKETSglmldVGPYMKALEYACGIKAEV 186
Cdd:TIGR01662   5 LDLDGTLTDDVPYVSDEDERILYPEVPDALAELKEAGYKVVIvtnQSGIGRGYFSRS-----FSGRVARRLEELGVPIDI 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 269847098  187 VG------KPSPEFFKSAL-QAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRT 235
Cdd:TIGR01662  80 LYacpgcrKPKPGMFLEALkRFNEIDPEESVYVGDQDLTDLQAAKRVGLATILVAP 135

N-acetylmuramic acid 6-phosphate phosphatase MupP;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098 189 KPSPEFFKSALQAIGVEAHQAVMIGDDIVgDVGGAQRCGMRALQVRTGkFRpSDEHHPEVKADGYVDNLAEAVDLLLQHA 268
Cdd:PRK13222 149 KPDPAPLLLACEKLGLDPEEMLFVGDSRN-DIQAARAAGCPSVGVTYG-YN-YGEPIALSEPDVVIDHFAELLPLLGLAL 225

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 269847098 187 VGKPSPEFFKSALQAIGVEAHQAVMIgDDIVGDVGGAQRCGMRALQV 233
Cdd:cd02603  139 VRKPDPEIYQLALERLGVKPEEVLFI-DDREENVEAARALGIHAILV 184

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 269847098 147 KPVLISlgkGRYYKETSGLM--LDVGPYMKALEYACGIkaeVVGKPSPEFFKSALQAIGVEAHQAVMIGDDiVGDVGGAQ 224
Cdd:cd01427   25 KLAIVT---NRSREALRALLekLGLGDLFDGIIGSDGG---GTPKPKPKPLLLLLLKLGVDPEEVLFVGDS-ENDIEAAR 97

                 ....*....
gi 269847098 225 RCGMRALQV 233
Cdd:cd01427   98 AAGGRTVAV 106

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 269847098 189 KPSPEFFKSALQAIGVEAHQAVMIGDDIVgDVGGAQRCGMRALQVRTGkfRPSDEHHPEVKADGYVDNLAEAVDL 263
Cdd:cd02616  136 KPDPEPVLKALELLGAEPEEALMVGDSPH-DILAGKNAGVKTVGVTWG--YKGREYLKAFNPDFIIDKMSDLLTI 207

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 269847098   14 VLLDISGVLYDSGAGGGTAIAGS----------VEAVARLKRS--RLKVRFCTNESQKSRAELVGQLQRlgFDISEQEVT 81
Cdd:TIGR01509   2 ILFDLDGVLVDTEFAIAKLINREelglvpdelgVSAVGRLELAlrRFKAQYGRTISPEDAQLLYKQLFY--EQIEEEAKL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269847098   82 APAPAACQI---LKEQGLRPYLLihdgvrsefdqidTSNPN--CVVIADAGesfsyqnmnnafqvLMELEKPVLISLGKG 156
Cdd:TIGR01509  80 KPLPGVRALleaLRARGKKLALL-------------TNSPRahKLVLALLG--------------LRDLFDVVIDSSDVG 132

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 269847098  157 RyyketsglmldvgpymkaleyacgikaevvGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGdVGGAQRCGMRA 230
Cdd:TIGR01509 133 L------------------------------GKPDPDIYLQALKALGLEPSECVFVDDSPAG-IEAAKAAGMHT 175

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 269847098  189 KPSPEFFKSALQAIGVEAHQAVMIGDDIVgDVGGAQRCGMRALQV 233
Cdd:pfam13419 135 KPDPDPILKALEQLGLKPEEVIYVGDSPR-DIEAAKNAGIKVIAV 178

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 269847098 184 AEVV--GKPSPEFFKSALQAIGVEAHQAVMIGDDIVGdVGGAQRCGMRALQVRT 235
Cdd:cd07505   91 GDDVerGKPAPDIYLLAAERLGVDPERCLVFEDSLAG-IEAAKAAGMTVVAVPD 143