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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1250756190  29 TILTDLDNTLLAWDQLDATDEVINWFTILKEEGIKVMIFSNNNEERVARVAKAIDVPYLARAKKPLGANFRWALKEMDAT 108
Cdd:cd16416     1 GVITDLDNTLLAWDNPDLTPEVKAWLADLKEAGIKVVLVSNNNERRVAKVIEKLDLPFVARAGKPRPRAFRRALKEMDLP 80

                          90       100
                  ....*....|....*....|....*...
gi 1250756190 109 PEETVMIGDQIMTDIFGGNRQKLTTIFV 136
Cdd:cd16416    81 PEQVAMVGDQLFTDILGGNRAGLYTILV 108

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 1250756190  26 GKTTILTDLDNTLLAWDQLDATDEVINWFTILKEEGIKVMIFSNNNEERVARVAKAIDVPYLA---------RAKKPLGA 96
Cdd:pfam00702  79 GLTVVLVELLGVIALADELKLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFdvvisgddvGVGKPKPE 158

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1250756190  97 NFRWALKEMDATPEETVMIGDQImTDIFGGNR 128
Cdd:pfam00702 159 IYLAALERLGVKPEEVLMVGDGV-NDIPAAKA 189

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1250756190  29 TILTDLDNTLLAWDQLDATDEVINWFTILKEEGIKVMIFSNNNEERVARVAKAIDVPYLARAKKPLGANFRWALKEMDAT 108
Cdd:cd16416     1 GVITDLDNTLLAWDNPDLTPEVKAWLADLKEAGIKVVLVSNNNERRVAKVIEKLDLPFVARAGKPRPRAFRRALKEMDLP 80

                          90       100
                  ....*....|....*....|....*...
gi 1250756190 109 PEETVMIGDQIMTDIFGGNRQKLTTIFV 136
Cdd:cd16416    81 PEQVAMVGDQLFTDILGGNRAGLYTILV 108

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 1250756190  28 TTILTDLDNTLL-------AWDQLDATDEVINWFTILKEEGIKVMIFSNNN-----------EERVARVAKAIDVP---- 85
Cdd:TIGR01662   1 KAVVLDLDGTLTddvpyvsDEDERILYPEVPDALAELKEAGYKVVIVTNQSgigrgyfsrsfSGRVARRLEELGVPidil 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1250756190  86 -YLARAKKPLGANFRWALKEM-DATPEETVMIGDQIMTDIFGGNRQKLTTIFVRP 138
Cdd:TIGR01662  81 yACPGCRKPKPGMFLEALKRFnEIDPEESVYVGDQDLTDLQAAKRVGLATILVAP 135

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 1250756190  26 GKTTILTDLDNTLLAWDQLDATDEVINWFTILKEEGIKVMIFSNNNEERVARVAKAIDVPYLA---------RAKKPLGA 96
Cdd:pfam00702  79 GLTVVLVELLGVIALADELKLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFdvvisgddvGVGKPKPE 158

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1250756190  97 NFRWALKEMDATPEETVMIGDQImTDIFGGNR 128
Cdd:pfam00702 159 IYLAALERLGVKPEEVLMVGDGV-NDIPAAKA 189

human N-acetylneuraminate-9-phosphate phosphatase, Escherichia coli house-cleaning phosphatase YjjG, and related phosphatases; N-acetylneuraminate-9- phosphatase (Neu5Ac-9-Pase; E.C. 3.1.3.29) catalyzes the dephosphorylation of N-acylneuraminate 9-phosphate during the synthesis of N-acetylneuraminate; Escherichia coli nucleotide phosphatase YjjG has a broad pyrimidine nucleotide activity spectrum and functions as an in vivo house-cleaning phosphatase for noncanonical pyrimidine nucleotides. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1250756190  29 TILTDLDNTLLawdqlDATDEVINWFTilkeEGIKVMIFSNNN----EERVARVA-----KAIDVPYLARAKKPLGANFR 99
Cdd:cd04305     1 AIIFDLDDTLL-----PGAKELLEELK----KGYKLGIITNGPtevqWEKLEQLGihkyfDHIVISEEVGVQKPNPEIFD 71

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1250756190 100 WALKEMDATPEETVMIGDQIMTDIFGGNRQKLTTIFVR 137
Cdd:cd04305    72 YALNQLGVKPEETLMVGDSLESDILGAKNAGIKTVWFN 109

Ribonucleotide monophosphatase NagD, HAD superfamily [Nucleotide transport and metabolism];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1250756190  92 KPLGANFRWALKEMDATPEETVMIGDQIMTDIFGGNRQKLTTIFVR 137
Cdd:COG0647   186 KPSPPIYELALERLGVDPERVLMVGDRLDTDILGANAAGLDTLLVL 231

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1250756190  57 LKEEGIKVMIFSNNNEERVARVAKAIDV-PYLAR--------AKKPLGANFRWALKEMDATPEETVMIGDQImTDIFGGN 127
Cdd:COG0546    96 LKARGIKLAVVTNKPREFAERLLEALGLdDYFDAivggddvpPAKPKPEPLLEALERLGLDPEEVLMVGDSP-HDIEAAR 174

                          90
                  ....*....|
gi 1250756190 128 RQKLTTIFVR 137
Cdd:COG0546   175 AAGVPFIGVT 184

P-type heavy metal-transporting ATPase; Heavy metal-transporting ATPases (Type IB ATPases) transport heavy metal ions (Cu(+), Cu(2+), Zn(2+), Cd(2+), Co(2+), etc.) across biological membranes. These ATPases include mammalian copper-transporting ATPases, ATP7A and ATP7B, Bacillus subtilis CadA which transports cadmium, zinc and cobalt out of the cell, Bacillus subtilis ZosA/PfeT which transports copper, and perhaps also zinc and ferrous iron, Archaeoglobus fulgidus CopA and CopB, Staphylococcus aureus plasmid pI258 CadA, a cadmium-efflux ATPase, and Escherichia coli ZntA which is selective for Pb(2+), Zn(2+), and Cd(2+). The characteristic N-terminal heavy metal associated (HMA) domain of this group is essential for the binding of metal ions. This family belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1250756190   6 SPDKMLNTPFGITAAQLRKMGKTT-ILTDLDNTLLAW----DQL-DATDEVINWftiLKEEGIKVMIFSNNNEERVARVA 79
Cdd:cd02079   406 SLSFAEEEGLVEAADALSDAGKTSaVYVGRDGKLVGLfaleDQLrPEAKEVIAE---LKSGGIKVVMLTGDNEAAAQAVA 482

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1250756190  80 KA--IDVPY--LARAKKplgANFrwaLKEMDATPEETVMIGDQI 119
Cdd:cd02079   483 KElgIDEVHagLLPEDK---LAI---VKALQAEGGPVAMVGDGI 520

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1250756190  92 KPLGANFRWALKEMDATPEET-VMIGDQIMTDIFGGNRQKLTTIFVR 137
Cdd:TIGR01460 188 KPSPAIYRAALNLLQARPERRdVMVGDNLRTDILGAKNAGFDTLLVL 234

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1250756190  30 ILTDLDNTLLAWDQLDAtdevinwftiLKEEGIKVMIFSNNNEE--------RVARVAKAIDVPYLARAKKPLGANFRWA 101
Cdd:cd16415     2 ITFDVTGTLLAVETLKD----------LKEKGLKLAVVSNFDRRlrellealGLDDYFDFVVFSYEVGYEKPDPRIFQKA 71

                          90       100
                  ....*....|....*....|....
gi 1250756190 102 LKEMDATPEETVMIGDQIMTDIFG 125
Cdd:cd16415    72 LERLGVSPEEALHVGDDLKNDYLG 95

HAD-superfamily class IIA hydrolase, TIGR01459; 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 gram negative and primarily alpha proteobacteria. Only one sequence hase been annotated as other than "hypothetical." That one, from Brucella, is annotated as related to NagD, but only by sequence similarity and should be treated with some skepticism. (See comments for Class IIA subfamily model)

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1250756190  89 RAKKPLGANFRWALKEMDATPEETV-MIGDQIMTDIFGGNRQKLTTIFV 136
Cdd:TIGR01459 192 YSGKPYPAIFHKALKECSNIPKNRMlMVGDSFYTDILGANRLGIDTALV 240

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
                  ....*....|....*....|....*....|....*
gi 1250756190 102 LKEMDATPEETVMIGDQIMTDIFGGNRQKLTTIFV 136
Cdd:cd16422   187 LEKFDYSKEETVMVGDRLYTDIVLGINAGVDSILV 221

HAD-superfamily hydrolase, subfamily IIB; This subfamily falls within the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The Class II subfamilies are characterized by a domain that is located between the second and third conserved catalytic motifs of the superfamily domain. The IIB subfamily is distinguished from the IIA subfamily (TIGR01460) by homology and the predicted secondary structure of this domain by PSI-PRED. The IIB subfamily's Class II domain has the following predicted structure: Helix-Sheet-Sheet-(Helix or Sheet)-Helix-Sheet-(variable)-Helix-Sheet-Sheet. The IIB subfamily consists of Trehalose-6-phosphatase (TIGR00685), plant and cyanobacterial Sucrose-phosphatase and a closely related group of bacterial and archaeal sequences, eukaryotic phosphomannomutase (pfam03332), a large subfamily ("Cof-like hydrolases", TIGR00099) containing many closely related bacterial sequences, a hypothetical equivalog containing the E. coli YedP protein, as well as two small clusters containing OMNI|TC0379 and OMNI|SA2196 whose relationship to the other groups is unclear. [Unknown function, Enzymes of unknown specificity]

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1250756190  30 ILTDLDNTLLAWDQLDATDEVINWFTILKEEGIKVMIFS 68
Cdd:TIGR01484   2 LFFDLDGTLLDPNAHELSPETIEALERLREAGVKVVIVT 40

Mitochondrial PGP phosphatase; This is a family of proteins that acts as a mitochondrial phosphatase in cardiolipin biosynthesis. Cardiolipin is a unique dimeric phosphoglycerolipid predominantly present in mitochondrial membranes. The inverted phosphatase motif includes the highly conserved DKD triad.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1250756190  61 GIKVMIFSNN-------NEERVARVAKAIDVPYLA-RAKKPLGAN--FRWALKEMDAT-PEETVMIGDQIMTDIFGGNR 128
Cdd:pfam09419  77 GKRLLIVSNSagsnddkDGEQAKALEKSTGIPVLRhPVKKPGCGEevLEYFKERGVVTrPSEIAVVGDRLFTDILMANM 155

?-D-glucose-1-phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1250756190  49 EVINWFTILKEEGIKVMIFSNNNE-------ERVARVAKAIDVPYLAR---AKKPLGANFRWALKEMDATPEETVMIgDQ 118
Cdd:PRK09456   88 EVIAIMHKLREQGHRVVVLSNTNRlhttfwpEEYPEVRAAADHIYLSQdlgMRKPEARIYQHVLQAEGFSAADAVFF-DD 166

                          90
                  ....*....|....*...
gi 1250756190 119 IMTDIFGGNRQKLTTIFV 136
Cdd:PRK09456  167 NADNIEAANALGITSILV 184