D,D-heptose 1,7-bisphosphate phosphatase; This family of proteins formerly designated yaeD resembles the histidinol phosphatase domain of the bifunctional protein HisB. The member from E. coli has been characterized as D,D-heptose 1,7-bisphosphate phosphatase, GmhB, involved in inner core LPS assembly (). [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360    5 VPAIFLDRDGTINVDHGYVHEIDNFEFIDGVIDAMRELKEMGYALVLVTNQSGIARGKFTEAQFETLTEWMDWSLADRGV 84
Cdd:TIGR00213   1 NKAIFLDRDGTINIDHGYVHEIDNFEFIDGVIDALRELKKMGYALVLVTNQSGIARGYFTEAQFEQLTEWMDWSLAERDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360   85 DLDGIYYCPHHPQGaVEEYRQTCDCRKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAADVGTKVLVRTGKPLTEE 164
Cdd:TIGR00213  81 DLDGIYYCPHHPEG-VEEFRQVCDCRKPKPGMLLQARKELHIDMAQSYMVGDKLEDMQAGVAAKVKTNVLVRTGKPITPE 159

                         170
                  ....*....|....*.
gi 636340360  165 AEKAADWVLNSLAELP 180
Cdd:TIGR00213 160 AENIADWVLNSLADLP 175

histidinol phosphate phosphatase and related phosphatases; This family includes the N-terminal domain of the Escherichia coli bifunctional enzyme histidinol-phosphate phosphatase/imidazole-glycerol-phosphate dehydratase, HisB. The N-terminal histidinol-phosphate phosphatase domain catalyzes the dephosphorylation of histidinol phosphate, the eight step of L-histidine biosynthesis. This family also includes Escherichia coli GmhB phosphatase which is highly specific for D-glycero-D-manno-heptose-1,7-bisphosphate, it removes the C(7)phosphate and not the C(1)phosphate, and this is the third essential step of lipopolysaccharide heptose biosynthesis. 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 636340360   6 PAIFLDRDGTINVDHGYVHEIDNFEFIDGVIDAMRELKEMGYALVLVTNQSGIARGKFTEAQFETLTEWMDWSLADRGVD 85
Cdd:cd07503    1 KALFLDRDGVINVDVPYVHKPEDLEFLPGVIEALKKLKDAGYLVVVVTNQSGIARGYFSEADFEALHDKMRELLASQGVE 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 636340360  86 LDGIYYCPHHPQgaveeyrQTCDCRKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAADVGT 151
Cdd:cd07503   81 IDDIYYCPHHPD-------DGCPCRKPKPGMLLDAAKELGIDLARSFVIGDRLSDIQAARNAGCKG 139

D,D-heptose 1,7-bisphosphate phosphatase; This family of proteins formerly designated yaeD resembles the histidinol phosphatase domain of the bifunctional protein HisB. The member from E. coli has been characterized as D,D-heptose 1,7-bisphosphate phosphatase, GmhB, involved in inner core LPS assembly (). [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360    5 VPAIFLDRDGTINVDHGYVHEIDNFEFIDGVIDAMRELKEMGYALVLVTNQSGIARGKFTEAQFETLTEWMDWSLADRGV 84
Cdd:TIGR00213   1 NKAIFLDRDGTINIDHGYVHEIDNFEFIDGVIDALRELKKMGYALVLVTNQSGIARGYFTEAQFEQLTEWMDWSLAERDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360   85 DLDGIYYCPHHPQGaVEEYRQTCDCRKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAADVGTKVLVRTGKPLTEE 164
Cdd:TIGR00213  81 DLDGIYYCPHHPEG-VEEFRQVCDCRKPKPGMLLQARKELHIDMAQSYMVGDKLEDMQAGVAAKVKTNVLVRTGKPITPE 159

                         170
                  ....*....|....*.
gi 636340360  165 AEKAADWVLNSLAELP 180
Cdd:TIGR00213 160 AENIADWVLNSLADLP 175

histidinol phosphate phosphatase and related phosphatases; This family includes the N-terminal domain of the Escherichia coli bifunctional enzyme histidinol-phosphate phosphatase/imidazole-glycerol-phosphate dehydratase, HisB. The N-terminal histidinol-phosphate phosphatase domain catalyzes the dephosphorylation of histidinol phosphate, the eight step of L-histidine biosynthesis. This family also includes Escherichia coli GmhB phosphatase which is highly specific for D-glycero-D-manno-heptose-1,7-bisphosphate, it removes the C(7)phosphate and not the C(1)phosphate, and this is the third essential step of lipopolysaccharide heptose biosynthesis. 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 636340360   6 PAIFLDRDGTINVDHGYVHEIDNFEFIDGVIDAMRELKEMGYALVLVTNQSGIARGKFTEAQFETLTEWMDWSLADRGVD 85
Cdd:cd07503    1 KALFLDRDGVINVDVPYVHKPEDLEFLPGVIEALKKLKDAGYLVVVVTNQSGIARGYFSEADFEALHDKMRELLASQGVE 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 636340360  86 LDGIYYCPHHPQgaveeyrQTCDCRKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAADVGT 151
Cdd:cd07503   81 IDDIYYCPHHPD-------DGCPCRKPKPGMLLDAAKELGIDLARSFVIGDRLSDIQAARNAGCKG 139

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 636340360    6 PAIFLDRDGTINVDHGYVHEIDNFEFIDGVIDAMRELKEMGYALVLVTNQSGIARGKFTEAqfetLTEWMDWSLADRGVD 85
Cdd:TIGR01662   1 KAVVLDLDGTLTDDVPYVSDEDERILYPEVPDALAELKEAGYKVVIVTNQSGIGRGYFSRS----FSGRVARRLEELGVP 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 636340360   86 LDGIYYCPHhpqgaveeyrqtcdCRKPHPGMLISA-RDYLHIDMAASYMVGDK-LEDMQAAAAA 147
Cdd:TIGR01662  77 IDILYACPG--------------CRKPKPGMFLEAlKRFNEIDPEESVYVGDQdLTDLQAAKRV 126

bifunctional histidinol-phosphatase/imidazoleglycerol-phosphate dehydratase HisB;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360   6 PAIFLDRDGTInvdhgyVHE------IDNFE---FIDGVIDAMRELKEMGYALVLVTNQSGIARGKFTEAQFETLTEWMD 76
Cdd:PRK05446   3 KILFIDRDGTL------IEEpptdfqVDSLDklaFEPGVIPALLKLQKAGYKLVMVTNQDGLGTDSFPQEDFDPPHNLMM 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 636340360  77 WSLADRGVDLDGIYYCPHHPQgaveeyrQTCDCRKPHPGMLisaRDYLH---IDMAASYMVGDKLEDMQAA 144
Cdd:PRK05446  77 QIFESQGIKFDEVLICPHFPE-------DNCSCRKPKTGLV---EEYLAegaIDLANSYVIGDRETDVQLA 137

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360  24 HEIDNFEFIDGVIDAMRELKEMGYALVLVTNqsgiARGKFTEAQFETLtewmdwsladrgvdldGIYYCPHHPQGAVEEY 103
Cdd:COG0546   78 ELLDETRLFPGVRELLEALKARGIKLAVVTN----KPREFAERLLEAL----------------GLDDYFDAIVGGDDVP 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360 104 RqtcdcRKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAADVGTkVLVRTGKPLTEEAEKA-ADWVLNSLAELPAA 182
Cdd:COG0546  138 P-----AKPKPEPLLEALERLGLDPEEVLMVGDSPHDIEAARAAGVPF-IGVTWGYGSAEELEAAgADYVIDSLAELLAL 211

                 ...
gi 636340360 183 IKK 185
Cdd:COG0546  212 LAE 214

FMN and 5-amino-6-(5-phospho-D-ribitylamino)uracil phosphatase YigB, HAD superfamily (riboflavin biosynthesis) [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360  27 DNFEFIDGVIDAMRELKEMGYALVLVTNqsgiargkfteAQFETLTEWMDWS-LADRgvdLDGIYYcphhpqgaVEEYRq 105
Cdd:COG1011   90 ELVEPYPDALELLEALKARGYRLALLTN-----------GSAELQEAKLRRLgLDDL---FDAVVS--------SEEVG- 146

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 636340360 106 tcdCRKPHPGMLISARDYLHIDMAASYMVGDKLE-DMQAAAAAdvGTKVLVRTGKPLTEEAEKAADWVLNSLAELPAAI 183
Cdd:COG1011  147 ---VRKPDPEIFELALERLGVPPEEALFVGDSPEtDVAGARAA--GMRTVWVNRSGEPAPAEPRPDYVISDLAELLELL 220

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 636340360 111 KPHPGMLISARDYLHIDMAASYMVGDKLE-DMQAAAAADVGTkVLVRTGKPLTEEAEKAA---DWVLNSLAEL 179
Cdd:COG0647  186 KPSPPIYELALERLGVDPERVLMVGDRLDtDILGANAAGLDT-LLVLTGVTTAEDLEAAPirpDYVLDSLAEL 257

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 636340360   21 GYVHEIDNFEFIDGVIDAMRELKEMGYALVLVTNQsgiargkfteaqfetltewmDWSLADRGVDLDGIYYCPHHPQGAV 100
Cdd:pfam00702  89 GVIALADELKLYPGAAEALKALKERGIKVAILTGD--------------------NPEAAEALLRLLGLDDYFDVVISGD 148

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 636340360  101 EEYRqtcdcRKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAAD 148
Cdd:pfam00702 149 DVGV-----GKPKPEIYLAALERLGVKPEEVLMVGDGVNDIPAAKAAG 191

Polynucleotide kinase 3 phosphatase; Polynucleotide kinase 3 phosphatases play a role in the repair of single breaks in DNA induced by DNA-damaging agents such as gamma radiation and camptothecin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360    7 AIFlDRDGT-INVDHGYVHEI--DNFEFI-DGVIDAMRELKEMGYALVLVTNQSGIARGkfTEAQFETLTEWMDWSLADR 82
Cdd:pfam08645   3 AAF-DLDGTlIKTKSGKVFPRnpDDWKWLyPSVPEKLKKLHEDGYKIVIFTNQGGIGRK--GKKSLEKFKNKIEAILKKL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 636340360   83 GVDLDgIYYCPHHpqgavEEYrqtcdcRKPHPGMLIS-ARDYLH---IDMAASYMVGD 136
Cdd:pfam08645  80 GVPLQ-VYAATKK-----DIY------RKPNTGMWDEmKKDYNDgveIDLEKSFYVGD 125

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 636340360   7 AIFLDRDGTInvdhgYVHEidnfefidgvidAMRELKEMGYALVLVTNQSGiargKFTEAQFETLtewmdwslaDRGVDL 86
Cdd:cd01427    1 AVLFDLDGTL-----LAVE------------LLKRLRAAGIKLAIVTNRSR----EALRALLEKL---------GLGDLF 50

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 636340360  87 DGIYYCPHHPQgaveeyrqtcdcRKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAADvGTKVLV 155
Cdd:cd01427   51 DGIIGSDGGGT------------PKPKPKPLLLLLLKLGVDPEEVLFVGDSENDIEAARAAG-GRTVAV 106

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 636340360    8 IFLDRDGTINVDHgyvheidnfEFIDGVIDAMRELKEMGYALVLVTNQSGIARGKFTEaQFETL 71
Cdd:pfam13344   1 FLFDIDGVLWRGG---------EPIPGAAEALRALRAAGKPVVFVTNNSSRSREEYAE-KLRKL 54

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360  33 DGVIDAMRELKEMGYALVLVTNQSGiargKFTE---AQFEtLTEWMDWSLAdrGVDLdgiyycphhPQgaveeyrqtcdc 109
Cdd:cd16417   90 PGVKEGLAALKAQGYPLACVTNKPE----RFVApllEALG-ISDYFSLVLG--GDSL---------PE------------ 141

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 636340360 110 RKPHPGMLISARDYLHIDMAASYMVGDKLEDMQAAAAAdvGTKVLVRT-----GKPLTEEaekAADWVLNSLAELP 180
Cdd:cd16417  142 KKPDPAPLLHACEKLGIAPAQMLMVGDSRNDILAARAA--GCPSVGLTygynyGEDIAAS---GPDAVIDSLAELL 212

UmpH/NagD family phosphatase, similar to Escherichia coli UmpH UMP phosphatase/NagD nucleotide phosphatase and Mycobacterium tuberculosis Rv1692 glycerol 3-phosphate phosphatase; Escherichia coli UmpH/NagD is a ribonucleoside tri-, di-, and monophosphatase with a preference for purines, it shows peak activity with UMP and functions in UMP-degradation. It is also an effective phosphatase with AMP, GMP and CMP. Mycobacterium tuberculosis phosphatase, Rv1692 is a glycerol 3-phosphate phosphatase. Rv1692 is the final enzyme involved in glycerophospholipid recycling/catabolism. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 636340360 111 KPHPGMLISARDYLHIDMAASYMVGDKLE-DMQAAAAADVGTkVLVRTGKPLTEEAEKAA---DWVLNSLAE 178
Cdd:cd07530  177 KPEPIMMRAALEKLGLKSEETLMVGDRLDtDIAAGIAAGIDT-LLVLTGVTTREDLAKPPyrpTYIVPSLRE 247

polynucleotide 3'-phosphatase domain similar to the phosphatase domain of the bifunctional enzyme polynucleotide 5'-kinase/3'-phosphatase; Polynucleotide 3'-phosphatase (PNP) domain. This domain dephosphorylates single-stranded as well as double-stranded 3'-phospho termini. It is found in bifunctional enzyme polynucleotide kinase/phosphatase (PNKP) which contain both kinase and phosphatase domains. PNKP plays a key role in both base excision repair and non-homologous end-joining DNA repair pathway. DNA strand breaks can result from DNA damage by ionizing radiation and chemical agents, such as alkylating agents or anticancer agents. Such DNA damage often results in DNA strands with 5'-hydroxyl and 3'-phosphate termini. However, the repair of DNA damage by DNA polymerases and ligases requires 5'-phosphate and 3'-hydroxyl termini. PNKP acts as a 5'-kinase/3'-phosphatase to create 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for ligation during repair. 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 636340360  33 DGVIDAMRELKEMGYALVLVTNQSGIARGKFTEAQFETLTEWMDWSLADRGVdldgIYYCPHhpqgaVEEYrqtcdcRKP 112
Cdd:cd01625   32 PSVPEKLKALHKDGYKIVIFTNQGGIVRGKLTPEVFKGKIEAILEKLGVPIQ----VYAATK-----KGKY------RKP 96

                         90       100
                 ....*....|....*....|....*...
gi 636340360 113 HPGM----LISARDYLHIDMAASYMVGD 136
Cdd:cd01625   97 VTGMwdhlKEDLNSGIPINLKDSFYVGD 124

polynucleotide 5'-kinase 3'-phosphatase; This model represents the metazoan 5'-polynucleotide-kinase-3'-phosphatase, PNKP, which is believed to be involved in repair of oxidative DNA damage. Removal of 3' phosphates is essential for the further processing of the break by DNA polymerases. The central phosphatase domain is a member of the IIIA subfamily (TIGR01662) of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. As is common in this superfamily, the enzyme is magnesium dependent. A difference between this enzyme and other HAD-superfamily phosphatases is in the third conserved catalytic motif which usually contains two conserved aspartate residues believed to be involved in binding the magnesium ion. Here, the second aspartate is replaced by a conserved arginine residue which may indicate an interaction with the phosphate backbone of the substrate. Very close relatives of this domain are also found separate from the N- and C-terminal domains seen here, as in the 3'-phosphatase found in plants. The larger family of these domains is described by TIGR01664. Outside of the phosphatase domain is a P-loop ATP-binding motif associated with the kinase activity. The entry for the mouse homolog appears to be missing a large piece of sequence corresponding to the first conserved catalytic motif of the phosphatase domain as well as the conserved threonine of the second motif. Either this is a sequencing artifact or this may represent a pseudo- or non-functional gene. Note that the EC number for the kinase function is: 2.7.1.78

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 636340360   39 MRELKEMGYALVLVTNQSGIARGKFTEAQFETLTEWMdwsLADRGVDL-------DGIYycphhpqgaveeyrqtcdcRK 111
Cdd:TIGR01663 206 LKELEADGFKICIFTNQGGIARGKINADDFKAKIEAI---VAKLGVPFqvfiaigAGFY-------------------RK 263

                          90       100
                  ....*....|....*....|....*....
gi 636340360  112 PHPGML----ISARDYLHIDMAASYMVGD 136
Cdd:TIGR01663 264 PLTGMWdhlkEEANDGTEIQEDDCFFVGD 292

copper-(or silver)-translocating P-type ATPase; This model describes the P-type ATPase primarily responsible for translocating copper ions accross biological membranes. These transporters are found in prokaryotes and eukaryotes. This model encompasses those species which pump copper ions out of cells or organelles (efflux pumps such as CopA of Escherichia coli) as well as those which pump the ion into cells or organelles either for the purpose of supporting life in extremely low-copper environments (for example CopA of Enterococcus hirae) or for the specific delivery of copper to a biological complex for which it is a necessary component (for example FixI of Bradyrhizobium japonicum, or CtaA and PacS of Synechocystis). The substrate specificity of these transporters may, to a varying degree, include silver ions (for example, CopA from Archaeoglobus fulgidus). Copper transporters from this family are well known as the genes which are mutated in two human disorders of copper metabolism, Wilson's and Menkes' diseases. The sequences contributing to the seed of this model are all experimentally characterized. The copper P-type ATPases have been characterized as Type IB based on a phylogenetic analysis which combines the copper-translocating ATPases with the cadmium-translocating species. This model and that describing the cadmium-ATPases (TIGR01512) are well separated, and thus we further type the copper-ATPases as IB1 (and the cadmium-ATPases as IB2). Several sequences which have not been characterized experimentally fall just below the cutoffs for both of these models (SP|Q9CCL1 from Mycobacterium leprae, GP|13816263 from Sulfolobus solfataricus, OMNI|NTL01CJ01098 from Campylobacter jejuni, OMNI|NTL01HS01687 from Halobacterium sp., GP|6899169 from Ureaplasma urealyticum and OMNI|HP1503 from Helicobacter pylori). Accession PIR|A29576 from Enterococcus faecalis scores very high against this model, but yet is annotated as an "H+/K+ exchanging ATPase". BLAST of this sequence does not hit anything else annotated in this way. This error may come from the characterization paper published in 1987. Accession GP|7415611 from Saccharomyces cerevisiae appears to be mis-annotated as a cadmium resistance protein. Accession OMNI|NTL01HS00542 from Halobacterium which scores above trusted for this model is annotated as "molybdenum-binding protein" although no evidence can be found for this classification. [Cellular processes, Detoxification, Transport and binding proteins, Cations and iron carrying compounds]

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gi 636340360  133 MVGDKLEDMQAAAAADVGtkVLVRTGkplTEEAEKAADWVL--NSLAELPAAIKKQQK 188
Cdd:TIGR01511 471 MVGDGINDAPALAQADVG--IAIGAG---TDVAIEAADVVLlrNDLNDVATAIDLSRK 523