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 57528359  12 RGVLLDISGVLYDSGTGGGAaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRLGFDISEGEVTAPAPATCQIL 91
Cdd:cd07509   1 KAVLLDLSGTLYISGAAIPG----AAEALKRLRHAGLKVRFLTNTTKESRRTLAERLQRLGFDVSEEEIFTSLTAARQYL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359  92 KERGLRPHLLIHEGVRSEFDDIDMSNPNCVVIADAGEGFSYQNMNRAFQVLmeLENPVLISLGKGRYYKETSGLMLDVGG 171
Cdd:cd07509  77 EEKGLRPHLLVDDDALEDFIGIDTSDPNAVVIGDAGEHFNYQTLNRAFRLL--LDGAPLIALHKGRYYKRKDGLALDPGA 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359 172 YMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGAQQCGMRALQVRTGKFRPGDEHHPEVRAD 251
Cdd:cd07509 155 FVTGLEYATGIKATVVGKPSPEFFLSALRSLGVDPEEAVMIGDDLRDDVGGAQACGMRGILVRTGKYRPSDEKKPNVPPD 234

                       250
                ....*....|....
gi 57528359 252 GYVDNLAEAVDLLL 265
Cdd:cd07509 235 LTADSFADAVDHIL 248

HAD-hyrolase-like;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 57528359   186 VVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGAQQCGMRALQVRTGKFRPGDEHHPEVRADGYVDNLAEA 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 57528359  12 RGVLLDISGVLYDSGTGGGAaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRLGFDISEGEVTAPAPATCQIL 91
Cdd:cd07509   1 KAVLLDLSGTLYISGAAIPG----AAEALKRLRHAGLKVRFLTNTTKESRRTLAERLQRLGFDVSEEEIFTSLTAARQYL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359  92 KERGLRPHLLIHEGVRSEFDDIDMSNPNCVVIADAGEGFSYQNMNRAFQVLmeLENPVLISLGKGRYYKETSGLMLDVGG 171
Cdd:cd07509  77 EEKGLRPHLLVDDDALEDFIGIDTSDPNAVVIGDAGEHFNYQTLNRAFRLL--LDGAPLIALHKGRYYKRKDGLALDPGA 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359 172 YMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGAQQCGMRALQVRTGKFRPGDEHHPEVRAD 251
Cdd:cd07509 155 FVTGLEYATGIKATVVGKPSPEFFLSALRSLGVDPEEAVMIGDDLRDDVGGAQACGMRGILVRTGKYRPSDEKKPNVPPD 234

                       250
                ....*....|....
gi 57528359 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 57528359    14 VLLDISGVLYDSGTGGGAaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRL-GFDISEGEVTAPAPATCQILK 92
Cdd:TIGR01460   1 FLFDIDGVLWLGHKPIPG----AAEALNRLRAKGKPVVFLTNNSSRSEEDYAEKLSSLlGVDVSPDQIITSGSVTKDLLR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359    93 ER--GLRPHLLIHEGVRSE----------FDDIDMSNPN---CVVIADAGEGFSYQNMNRAFQVLMELENPVLIS----- 152
Cdd:TIGR01460  77 QRfeGEKVYVIGVGELRESleglgfrndfFDDIDHLAIEkipAAVIVGEPSDFSYDELAKAAYLLAEGDVPFIAAnrddl 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359   153 --LGKGRYYketsglmLDVGGYMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQ-AIMIGDDIVGDVGGAQQCGMR 229
Cdd:TIGR01460 157 vrLGDGRFR-------PGAGAIAAGIKELSGREPTVVGKPSPAIYRAALNLLQARPERrDVMVGDNLRTDILGAKNAGFD 229

                  ....*..
gi 57528359   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 57528359  13 GVLLDISGVLYDSGTGGGAaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRLGFDISEGEVTAPAPATCQILK 92
Cdd:cd07508   1 LVISDCDGVLWHDERAIPG----AAEFLEALKEAGKKIVFVSNNSSRSRQDYAEKFRKFGVDVPEDQIVTSAKATARFLR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359  93 ER---------------------GLR-------PHLLIHEGVRSEFDDidmSNPNCVVIaDAGEGFSYQNMNRAfqvLME 144
Cdd:cd07508  77 SRkfgkkvyvlgeeglkeelraaGFRiaggpskGIETYAELVEHLEDD---ENVDAVIV-GSDFKLNFAKLRKA---CRY 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359 145 LENP--VLISLGKGRYYK-ETSGLMLDVGGYMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVG 221
Cdd:cd07508 150 LRNPgcLFIATAPDRIHPlKDGGPIPGTGAFAAAVEAATGRQPLVLGKPSPWLGELALEKFGIDPERVLFVGDRLATDVL 229

                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 57528359 222 GAQQCGMRALQVRTGKFRPGD---EHHPEVRADGYVDNLAE 259
Cdd:cd07508 230 FGKACGFQTLLVLTGVTTLEDlqaYIDHELVPDYYADSLAD 270

HAD-hyrolase-like;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 57528359   186 VVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGAQQCGMRALQVRTGKFRPGDEHHPEVRADGYVDNLAEA 260
Cdd:pfam13242   1 VCGKPNPGMLERALARLGLDPERTVMIGDRLDTDILGAREAGARTILVLTGVTRPADLEKAPIRPDYVVDDLAEA 75

UmpH/NagD family phosphatase, similar to human PGP phosphoglycolate phosphatase and Schizosaccharomyces pombe PHO2 p-nitrophenylphosphatase; This subfamily includes the phosphoglycolate phosphatases (human PGP and Arabidopsis thaliana PGLP2) and p-nitrophenylphosphatases (Schizosaccharomyces pombe PHO2 and Saccharomyces PHO13p). It belongs to the UmpH/NagD phosphatase family, and to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359  11 VRGVLLDISGVLYDSGTGGGAaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRLGFD-ISEGEVTAPAPATCQ 89
Cdd:cd07510   1 VDTFLFDCDGVLWNGEKAIPG----APETLNLLRSLGKRLVFVTNNSTKSREAYAKKFARLGFTgLKEEEIFSSAYCAAR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359  90 ILKERGLRP-----HLLIHEGVRSEFD----------DIDMSNPNCVVIADAGEG-------------FSYQNMNRAFQV 141
Cdd:cd07510  77 YLRQRLPGPadgkvYVLGGEGLRAELEaagvahlggpDDGLRRAAPKDWLLAGLDpdvgavlvgldehVNYLKLAKATQY 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359 142 LMElENPVLISLGKGRYYKETSGLMLDVGGYM-KALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDV 220
Cdd:cd07510 157 LRD-PGCLFVATNRDPWHPLSDGSFIPGTGSLvAALETASGRQAIVVGKPSRFMFDCISSKFSIDPARTCMVGDRLDTDI 235

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 57528359 221 GGAQQCGMRALQVRTGKFRPGD---EHHPEVRADGYVDNLAEAVDLL 264
Cdd:cd07510 236 LFGQNCGLKTLLVLTGVSTLEEalaKLSNDLVPDYYVESLADLLELL 282

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359    11 VRGVLLDISGVLYDSGTGGGAaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRLGFDISEGEVTAPAPATCQI 90
Cdd:TIGR01452   2 AQGFIFDCDGVLWLGERVVPG----APELLDRLARAGKQILFVTNNSTKSRAEYALKFARLGFNGLAEQLFSSALCAARL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359    91 LKERGLRP---HLLIHEGVRSEFD-----------------------DIDMSNPNCVVIADAGEGFSYQNMNRAFQVLME 144
Cdd:TIGR01452  78 LRQPPDAGkavYVIGEEGLRAELDaagirlagdpgekkqdeadgfmyDIKLDERVGAVVVGYDEHFSYVKLMEACAHLRE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359   145 lENPVLISLGKGRYYKETSGLML-DVGGYMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGA 223
Cdd:TIGR01452 158 -PGCLFVATNRDPWHPLSDGSRTpGTGSLVAAIETASGRQPLVVGKPSPYMFNCITEKFSIDPARTLMVGDRLETDILFG 236

                         250
                  ....*....|...
gi 57528359   224 QQCGMRALQVRTG 236
Cdd:TIGR01452 237 HRCGMTTVLVLSG 249

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359    14 VLLDISGVLYDSGTGGGAaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRLGFDISEGEVTAPAPATCQILKE 93
Cdd:pfam13344   1 FLFDIDGVLWRGGEPIPG----AAEALRALRAAGKPVVFVTNNSSRSREEYAEKLRKLGFDIDEDEIITSGTAAADYLKE 76

                          90       100
                  ....*....|....*....|.
gi 57528359    94 R--GLRPHLLIHEGVRSEFDD 112
Cdd:pfam13344  77 RkfGKKVLVIGSEGLREELEE 97

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 57528359 189 KPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGAQQCGMRALQVRtgkfRPGDEH 244
Cdd:cd16415  62 KPDPRIFQKALERLGVSPEEALHVGDDLKNDYLGARAVGWHALLVD----REGALH 113

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 57528359    11 VRGVLLDISGVLYDSGTGGgaaiagsVEAVARLK-RSPLKVRFctnesqksrrelvgVLQRLGFDISEGEVTAPAPATCQ 89
Cdd:pfam00702   1 IKAVVFDLDGTLTDGEPVV-------TEAIAELAsEHPLAKAI--------------VAAAEDLPIPVEDFTARLLLGKR 59

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359    90 ILKERgLRPHLLIHEGVRSEFDDIDMSNPnCVVIADAGEGFSYQNMNRAFQVLMELENPVLISLGKgryYKETSGLMLDV 169
Cdd:pfam00702  60 DWLEE-LDILRGLVETLEAEGLTVVLVEL-LGVIALADELKLYPGAAEALKALKERGIKVAILTGD---NPEAAEALLRL 134

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 57528359   170 GGYMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVgDVGGAQQCG 227
Cdd:pfam00702 135 LGLDDYFDVVISGDDVGVGKPKPEIYLAALERLGVKPEEVLMVGDGVN-DIPAAKAAG 191

HAD-IIA family hydrolase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359   11 VRGVLLDISGVL-YDSGTGGGaaiagSVEAVARLKRSPLKVRFCTNESQKSRRELVGVLQRLGFDISEGEVTAPAPATCQ 89
Cdd:PRK10444   1 IKNVICDIDGVLmHDNVAVPG-----AAEFLHRILDKGLPLVLLTNYPSQTGQDLANRFATAGVDVPDSVFYTSAMATAD 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359   90 ILK-ERGLRPHL-----LIHEGVRSEFDDIDMsNPNCVVIADAgEGFSYQNMNRAFQVLME-----LENPvlislgkgry 158
Cdd:PRK10444  76 FLRrQEGKKAYVigegaLIHELYKAGFTITDI-NPDFVIVGET-RSYNWDMMHKAAYFVANgarfiATNP---------- 143

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359  159 ykETSGLMLD--VGGYMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGAQQCGMRALQVRTG 236
Cdd:PRK10444 144 --DTHGRGFYpaCGALCAGIEKISGRKPFYVGKPSPWIIRAALNKMQAHSEETVIVGDNLRTDILAGFQAGLETILVLSG 221

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 57528359 188 GKPSPEFFRSALQAIGVEAHQAIMIGDDIVGDVGGAQQCGMRALQVR 234
Cdd:COG2179  90 KKPLPRGFRKALKLMGLPPEETAVVGDQLFTDVLGGNRAGLYTILVK 136

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57528359   153 LGKGRYYKETSGLMLDVGGymKALEYacgieaEVVGKPSPEFFRSALQAIGVEA-------------HQAIMIGDDIVGD 219
Cdd:TIGR01456 205 FGQGAFRLLLERIYLELNG--KPLQY------YTLGKPTKLTYDFAEDVLIDWEkrlsgtkpstspfHALYMVGDNPASD 276

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 57528359   220 VGGAQQCGMRALQVRTGKFRPGDEHHpEVRADGYVDNLAEAVDLLL 265
Cdd:TIGR01456 277 IIGAQNYGWFSCLVKTGVYNGGDDLK-ECKPTLIVNDVFDAVTKIL 321

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 57528359 188 GKPSPEFFRSALQAIGVEAHQAIMIGDDIVGdVGGAQQCGMRALQVRTgkfrPGDEHHPEVRADGYVDNLAE 259
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
                ....*....|....*....|....*....|....*....|....*..
gi 57528359 187 VGKPSPEFFRSALQAIGVEAHQAIMIgDDIVGDVGGAQQCGMRALQV 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 57528359 149 VLISlgkGRYYKETSGLmLDVGGYMKALEYACGIEAEVVGKPSPEFFRSALQAIGVEAHQAIMIGDDiVGDVGGAQQCGM 228
Cdd:cd01427  27 AIVT---NRSREALRAL-LEKLGLGDLFDGIIGSDGGGTPKPKPKPLLLLLLKLGVDPEEVLFVGDS-ENDIEAARAAGG 101

                ....*
gi 57528359 229 RALQV 233
Cdd:cd01427 102 RTVAV 106

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 57528359 189 KPSPEFFRSALQAIGVEAHQAIMIGDDIVgDVGGAQQCGMRALQVRTGkfrPGDEHHPEVRADGYVDNLAEAVDLL 264
Cdd:cd07512 142 KPDPAPLRAAIRRLGGDVSRALMVGDSET-DAATARAAGVPFVLVTFG---YRHAPVAELPHDAVFSDFDALPDLL 213

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 57528359 184 AEVV--GKPSPEFFRSALQAIGVEAHQAIMIGDDIVGdVGGAQQCGMRALQVRT 235
Cdd:cd07505  91 GDDVerGKPAPDIYLLAAERLGVDPERCLVFEDSLAG-IEAAKAAGMTVVAVPD 143

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 57528359   189 KPSPEFFRSALQAIGVEAHQAIMIGDDIVgDVGGAQQCGMRALQV 233
Cdd:pfam13419 135 KPDPDPILKALEQLGLKPEEVIYVGDSPR-DIEAAKNAGIKVIAV 178

haloacid dehalogenase-like hydrolase family protein

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 57528359   189 KPSPEFFRSALQAIGVEAHQAIMIGDDIVGdVGGAQQCGMRALQVRT 235
Cdd:PLN02919  218 KPAPDIFLAAAKILGVPTSECVVIEDALAG-VQAARAAGMRCIAVTT 263

?-D-glucose-1-phosphatase; Provisional