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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       13 RGVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQIL 92
Cdd:cd07509   1 KAVLLDLSGTLYISGAAIPG----AAEALKRLRHAGLKVRFLTNTTKESRRTLAERLQRLGFDVSEEEIFTSLTAARQYL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       93 KERGLRPYLLIHDGVRSEFDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLmeLEKPVLISLGKGRYYAATSGLMLDVGP 172
Cdd:cd07509  77 EEKGLRPHLLVDDDALEDFIGIDTSDPNAVVIGDAGEHFNYQTLNRAFRLL--LDGAPLIALHKGRYYKRKDGLALDPGA 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A      173 YMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEHHPEVKAD 252
Cdd:cd07509 155 FVTGLEYATGIKATVVGKPSPEFFLSALRSLGVDPEEAVMIGDDLRDDVGGAQACGMRGILVRTGKYRPSDEKKPNVPPD 234

                       250
                ....*....|....
2X4D_A      253 GYVDNLAEAVDLLL 266
Cdd:cd07509 235 LTADSFADAVDHIL 248

HAD-hyrolase-like;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
2X4D_A        187 VVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEHHPEVKADGYVDNLAEA 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       13 RGVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQIL 92
Cdd:cd07509   1 KAVLLDLSGTLYISGAAIPG----AAEALKRLRHAGLKVRFLTNTTKESRRTLAERLQRLGFDVSEEEIFTSLTAARQYL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       93 KERGLRPYLLIHDGVRSEFDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLmeLEKPVLISLGKGRYYAATSGLMLDVGP 172
Cdd:cd07509  77 EEKGLRPHLLVDDDALEDFIGIDTSDPNAVVIGDAGEHFNYQTLNRAFRLL--LDGAPLIALHKGRYYKRKDGLALDPGA 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A      173 YMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEHHPEVKAD 252
Cdd:cd07509 155 FVTGLEYATGIKATVVGKPSPEFFLSALRSLGVDPEEAVMIGDDLRDDVGGAQACGMRGILVRTGKYRPSDEKKPNVPPD 234

                       250
                ....*....|....
2X4D_A      253 GYVDNLAEAVDLLL 266
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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A         15 VLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRL-GFDISEQEVTAPAPAACQILK 93
Cdd:TIGR01460   1 FLFDIDGVLWLGHKPIPG----AAEALNRLRAKGKPVVFLTNNSSRSEEDYAEKLSSLlGVDVSPDQIITSGSVTKDLLR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A         94 ER--GLRPYLLIHDGVRSE----------FDQIDTSNPN---CVVIADAGESFSYQNMNNAFQVLMELEKPVLIS----- 153
Cdd:TIGR01460  77 QRfeGEKVYVIGVGELRESleglgfrndfFDDIDHLAIEkipAAVIVGEPSDFSYDELAKAAYLLAEGDVPFIAAnrddl 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A        154 --LGKGRYYAATsglmldvGPYMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQ-AVMIGDDIVGDVGGAQRCGMR 230
Cdd:TIGR01460 157 vrLGDGRFRPGA-------GAIAAGIKELSGREPTVVGKPSPAIYRAALNLLQARPERrDVMVGDNLRTDILGAKNAGFD 229

                  ....*..
2X4D_A        231 ALQVRTG 237
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       14 GVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQILK 93
Cdd:cd07508   1 LVISDCDGVLWHDERAIPG----AAEFLEALKEAGKKIVFVSNNSSRSRQDYAEKFRKFGVDVPEDQIVTSAKATARFLR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       94 ER--GLRPYLLIHDGVRSEF----------------------DQIDTSNPNCVVIADAGESFSYQNMNNAFQVLMELEKp 149
Cdd:cd07508  77 SRkfGKKVYVLGEEGLKEELraagfriaggpskgietyaelvEHLEDDENVDAVIVGSDFKLNFAKLRKACRYLRNPGC- 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A      150 VLISLGKGRYY-AATSGLMLDVGPYMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCG 228
Cdd:cd07508 156 LFIATAPDRIHpLKDGGPIPGTGAFAAAVEAATGRQPLVLGKPSPWLGELALEKFGIDPERVLFVGDRLATDVLFGKACG 235

                       250       260       270
                ....*....|....*....|....*....|....*
2X4D_A      229 MRALQVRTGKFRPSD---EHHPEVKADGYVDNLAE 260
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       14 GVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQILK 93
Cdd:cd07531   2 GYIIDLDGTIGKGVTLIPG----AVEGVKTLRRLGKKIIFLSNNSTRSRRILLERLRSFGIEVGEDEILVSSYVTARFLA 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       94 E--RGLRPYLLIHDGVRSE-----FDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLMELEKpvLISLGKGRYYAATSGL 166
Cdd:cd07531  78 RekPNAKVFVTGEEGLIEElrlagLEIVDKYDEAEYVVVGSNRKITYELLTKAFRACLRGAR--YIATNPDRIFPAEDGP 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A      167 MLDVGPYMKALEYACGIKAE-VVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEH 245
Cdd:cd07531 156 IPDTAAIIGAIEWCTGREPEvVVGKPSEVMAREALDILGLDAKDCAIVGDQIDVDIAMGKAIGMETALVLTGVTTRENLD 235

                       250
                ....*....|....*..
2X4D_A      246 HPEVKADGYVDNLAEAV 262
Cdd:cd07531 236 RHGYKPDYVLNSIKDLV 252

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A         12 VRGVLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQI 91
Cdd:TIGR01452   2 AQGFIFDCDGVLWLGERVVPG----APELLDRLARAGKQILFVTNNSTKSRAEYALKFARLGFNGLAEQLFSSALCAARL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A         92 LKERGLRP---YLLIHDGVRSEFD----------------------QIDTSNPNC-VVIADAGESFSYQNMNNAFQVLME 145
Cdd:TIGR01452  78 LRQPPDAGkavYVIGEEGLRAELDaagirlagdpgekkqdeadgfmYDIKLDERVgAVVVGYDEHFSYVKLMEACAHLRE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A        146 lEKPVLISLGKGRYYAATSGLML-DVGPYMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGA 224
Cdd:TIGR01452 158 -PGCLFVATNRDPWHPLSDGSRTpGTGSLVAAIETASGRQPLVVGKPSPYMFNCITEKFSIDPARTLMVGDRLETDILFG 236

                         250
                  ....*....|...
2X4D_A        225 QRCGMRALQVRTG 237
Cdd:TIGR01452 237 HRCGMTTVLVLSG 249

uncharacterized subfamily of the UmpH/NagD phosphatase family, belongs to the haloacid dehalogenase-like superfamily; This uncharacterized 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       37 SVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQILKERGLRP--YLLIHDGVRSEFDQ- 113
Cdd:cd16422  20 TLEFLERLHEKKRRYIFLTNNSSKNLADYVEKLNRLGIDAGLDRVFTSGEATIDHLKKEFIKPkiFLLGTKSLREEFEKa 99

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A      114 ---IDTSNPNCVVIA-DAgeSFSYQNMNNAfqvlmelekpvLISLGKGRYYAATS---------GLMLDVGPYMKALEYA 180
Cdd:cd16422 100 gftLDGDDIDVVVLGfDT--ELTYEKLRTA-----------CLLLRRGIPYIATHpdincpseeGPIPDAGSIIALIETS 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A      181 CGIKAEVV-GKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTGKFRPSDEHHPEVKADGYVDNLA 259
Cdd:cd16422 167 TGRRPDLViGKPNPIILDPVLEKFDYSKEETVMVGDRLYTDIVLGINAGVDSILVLSGETTREDLEDLERKPTYVFDNVG 246

                .
2X4D_A      260 E 260
Cdd:cd16422 247 E 247

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A         15 VLLDISGVLYDSGAGGGTaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQILKE 94
Cdd:pfam13344   1 FLFDIDGVLWRGGEPIPG----AAEALRALRAAGKPVVFVTNNSSRSREEYAEKLRKLGFDIDEDEIITSGTAAADYLKE 76

                          90       100
                  ....*....|....*....|
2X4D_A         95 R--GLRPYLLIHDGVRSEFD 112
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
                ....*....|....*....|....*....|....*....|....*....|....*....
2X4D_A      190 KPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALqvrtgKFRPSDEHHPE 248
Cdd:cd16415  62 KPDPRIFQKALERLGVSPEEALHVGDDLKNDYLGARAVGWHAL-----LVDREGALHEL 115

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
                ....*....|....*....|....*....|....*....|....
2X4D_A      188 VGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRA 231
Cdd:cd04305  62 VQKPNPEIFDYALNQLGVKPEETLMVGDSLESDILGAKNAGIKT 105

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
                ....*....|....*....|....*....|....*....|....*.
2X4D_A      189 GKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQV 234
Cdd:cd16416  63 GKPRPRAFRRALKEMDLPPEQVAMVGDQLFTDILGGNRAGLYTILV 108

HAD-IIA family hydrolase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A        12 VRGVLLDISGVL-YDSGAGGGtaiagSVEAVARLKRSRLKVRFCTNESAASRAELVGQLQRLGFDISEQEVTAPAPAACQ 90
Cdd:PRK10444   1 IKNVICDIDGVLmHDNVAVPG-----AAEFLHRILDKGLPLVLLTNYPSQTGQDLANRFATAGVDVPDSVFYTSAMATAD 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A        91 ILK-ERGLRPYL-----LIHDGVRSEFDQIDTsNPNCVVIADAgESFSYQNMNNAFQVLMElekpvlislgkGRYYAATS 164
Cdd:PRK10444  76 FLRrQEGKKAYVigegaLIHELYKAGFTITDI-NPDFVIVGET-RSYNWDMMHKAAYFVAN-----------GARFIATN 142

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A       165 ------GLMLDVGPYMKALEYACGIKAEVVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRTG- 237
Cdd:PRK10444 143 pdthgrGFYPACGALCAGIEKISGRKPFYVGKPSPWIIRAALNKMQAHSEETVIVGDNLRTDILAGFQAGLETILVLSGv 222

                        250
                 ....*....|....
2X4D_A       238 ---------KFRPS 242
Cdd:PRK10444 223 stlddidsmPFRPS 236

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A        111 FDQIDTSNPNCVVIADAGESFSYQNMNNAFQVLMELEKPVLI---SLGKGRYYAATSglmldVGPYMKALEYACGIKAEV 187
Cdd:TIGR01662   5 LDLDGTLTDDVPYVSDEDERILYPEVPDALAELKEAGYKVVIvtnQSGIGRGYFSRS-----FSGRVARRLEELGVPIDI 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
2X4D_A        188 VG------KPSPEFFKSAL-QAIGVEAHQAVMIGDDIVGDVGGAQRCGMRALQVRT 236
Cdd:TIGR01662  80 LYacpgcrKPKPGMFLEALkRFNEIDPEESVYVGDQDLTDLQAAKRVGLATILVAP 135

Beta-phosphoglucomutase, HAD superfamily [Carbohydrate transport and metabolism];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
2X4D_A      189 GKPSPEFFKSALQAIGVEAHQAVMIGDDIVGdVGGAQRCGMRALQVRTgkfrPSDEHHPEVKADGYVDNLAE 260
Cdd:COG0637 141 GKPDPDIYLLAAERLGVDPEECVVFEDSPAG-IRAAKAAGMRVVGVPD----GGTAEEELAGADLVVDDLAE 207

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
                ....*....|....*....|....*....|....*....|....*..
2X4D_A      188 VGKPSPEFFKSALQAIGVEAHQAVMIgDDIVGDVGGAQRCGMRALQV 234
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
                ....*....|....*....|....*....|....*....|....*...
2X4D_A      187 VVGKPSPEFFKSALQAIGVEAHQAVMIGDDiVGDVGGAQRCGMRALQV 234
Cdd:cd01427  60 GTPKPKPKPLLLLLLKLGVDPEEVLFVGDS-ENDIEAARAAGGRTVAV 106

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A         15 VLLDISGVLYDSGAGGGTAIAGS----------VEAVARLKRS--RLKVRFCTNESAASRAELVGQLQRlgFDISEQEVT 82
Cdd:TIGR01509   2 ILFDLDGVLVDTEFAIAKLINREelglvpdelgVSAVGRLELAlrRFKAQYGRTISPEDAQLLYKQLFY--EQIEEEAKL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2X4D_A         83 APAPAACQI---LKERGLRPYLLihdgvrsefdqidTSNPNcvviadagesfsyqnmnNAFQVLMELEkpvLISLGKGRY 159
Cdd:TIGR01509  80 KPLPGVRALleaLRARGKKLALL-------------TNSPR-----------------AHKLVLALLG---LRDLFDVVI 126

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
2X4D_A        160 YAATSGlmldvgpymkaleyacgikaevVGKPSPEFFKSALQAIGVEAHQAVMIGDDIVGdVGGAQRCGMRA 231
Cdd:TIGR01509 127 DSSDVG----------------------LGKPDPDIYLQALKALGLEPSECVFVDDSPAG-IEAAKAAGMHT 175

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
2X4D_A        190 KPSPEFFKSALQAIGVEAHQAVMIGDDIVgDVGGAQRCGMRALQV 234
Cdd:pfam13419 135 KPDPDPILKALEQLGLKPEEVIYVGDSPR-DIEAAKNAGIKVIAV 178

Escherichia coli Gph phosphoglycolate phosphatase and related proteins; belongs to the haloacid dehalogenase-like superfamily; Phosphoglycolate phosphatase (PGP; EC 3.1.3.18) catalyzes the conversion of 2-phosphoglycolate into glycolate and phosphate. 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 (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. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
2X4D_A      190 KPSPEFFKSALQAIGVEAHQAVMIGDDIVgDVGGAQRCGMRALQVRTGKFRPSDEHHpeVKADGYVDNLAEAV 262
Cdd:cd16417 143 KPDPAPLLHACEKLGIAPAQMLMVGDSRN-DILAARAAGCPSVGLTYGYNYGEDIAA--SGPDAVIDSLAELL 212

haloacid dehalogenase-like hydrolase family protein

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
2X4D_A        190 KPSPEFFKSALQAIGVEAHQAVMIGDDIVGdVGGAQRCGMRALQVRT 236
Cdd:PLN02919  218 KPAPDIFLAAAKILGVPTSECVVIEDALAG-VQAARAAGMRCIAVTT 263