haloacid dehalogenase-like (HAD) hydrolase, similar to Escherichia coli 3-deoxy-D-manno-octulosonate 8-phosphate (KDO 8-P) phosphatase KdsC, and rainbow trout N-acylneuraminate cytidylyltransferase; KDO 8-P phosphatase catalyzes the hydrolysis of KDO 8-P to KDO (3-deoxy-D-manno-octulosonate) and inorganic phosphate and is the last enzyme in the KDO biosynthetic pathway. KDO is an 8-carbon sugar that links the lipid A and polysaccharide moieties of the lipopolysaccharide region in Gram-negative bacteria. An interruption in KDO biosynthesis leads to the accumulation of lipid A precursors and subsequent arrest in cell growth. The KDO biosynthesis pathway involves five sequential enzymatic reactions. This family also includes rainbow trout CMP-sialic acid synthetase which effectively converts both deaminoneuraminic acid (KDN, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) and N-acetylneuraminic acid (Neu5Ac) to CMP-KDN and CMP-Neu5Ac, respectively. 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 517284145  21 LLITDVDGVLTDGGVIYDDNYLEYKKYNVKDGLIVKVLQRHGILVGAITGRNSPVVQKRCEELHFDFHHHGIKDKGAKLL 100
Cdd:cd01630    3 LLVLDVDGVLTDGRIYYDSNGEELKSFNVRDGLGIKLLQKSGIEVAIITGRQSEAVRRRAKELGIEDLFQGVKDKLEALE 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 517284145 101 EVLDQYNLDLNEIAYIGDDLIDLPILVQVGLAVAPKDALPYIKEEVDFVSSLNGGKGVFRE 161
Cdd:cd01630   83 ELLEKLGLSDEEVAYMGDDLPDLPVMKRVGLSVAPADAHPEVREAADYVTRARGGRGAVRE 143

3-deoxy-D-manno-octulosonate 8-phosphate phosphatase, YrbI family; This family of proteins is a member of the IIIA subfamily of the haloacid dehalogenase (HAD) superfamily of hydrolases. All characterized members of this subfamily (TIGR01662) and most characterized members of the HAD superfamily are phosphatases. HAD superfamily phosphatases contain active site residues in several conserved catalytic motifs, all of which are found conserved here. One member of this family, the YrbI protein from H. influenzae has been cloned, expressed, purified and found to be an active 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase. Furthermore, its crystal structure has been determined. This family consists of sequences from beta, gamma and epsilon proteobacteria, Aquifex, Fusobacterium, Porphyromonas and Methanosarcina. The Methanosarcina sequence is distinctive in that it is linked to an N-terminal cytidylyltransferase domain (pfam02348) and is annotated as acylneuraminate cytidylyltransferase. This may give some clue as the function of these phosphatases. Several eukaryotic sequences scoring between trusted and noise are also closely related to this function such as the CMP-N-acetylneuraminic acid synthetase from mouse, but in these cases the phosphatase domain is clearly inactive as many of the active site residues are not conserved. [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 517284145   21 LLITDVDGVLTDGGVIYDDNYLEYKKYNVKDGLIVKVLQRHGILVGAITGRNSPVVQKRCEELHFDFHHHGIKDKGAKLL 100
Cdd:TIGR01670   3 LLILDVDGVLTDGKIYYTNNGEEIKAFNVRDGYGIRCALKSGIEVAIITGRKAKLVEDRCKTLGITHLYQGQSNKLIAFS 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 517284145  101 EVLDQYNLDLNEIAYIGDDLIDLPILVQVGLAVAPKDALPYIKEEVDFVSSLNGGKGVFRETGDLILSAQG 171
Cdd:TIGR01670  83 DILEKLALAPENVAYIGDDLIDWPVMEKVGLSVAVADAHPLLIPRADYVTRIAGGRGAVREVCELLLLAQG 153

haloacid dehalogenase-like (HAD) hydrolase, similar to Escherichia coli 3-deoxy-D-manno-octulosonate 8-phosphate (KDO 8-P) phosphatase KdsC, and rainbow trout N-acylneuraminate cytidylyltransferase; KDO 8-P phosphatase catalyzes the hydrolysis of KDO 8-P to KDO (3-deoxy-D-manno-octulosonate) and inorganic phosphate and is the last enzyme in the KDO biosynthetic pathway. KDO is an 8-carbon sugar that links the lipid A and polysaccharide moieties of the lipopolysaccharide region in Gram-negative bacteria. An interruption in KDO biosynthesis leads to the accumulation of lipid A precursors and subsequent arrest in cell growth. The KDO biosynthesis pathway involves five sequential enzymatic reactions. This family also includes rainbow trout CMP-sialic acid synthetase which effectively converts both deaminoneuraminic acid (KDN, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) and N-acetylneuraminic acid (Neu5Ac) to CMP-KDN and CMP-Neu5Ac, respectively. 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 517284145  21 LLITDVDGVLTDGGVIYDDNYLEYKKYNVKDGLIVKVLQRHGILVGAITGRNSPVVQKRCEELHFDFHHHGIKDKGAKLL 100
Cdd:cd01630    3 LLVLDVDGVLTDGRIYYDSNGEELKSFNVRDGLGIKLLQKSGIEVAIITGRQSEAVRRRAKELGIEDLFQGVKDKLEALE 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 517284145 101 EVLDQYNLDLNEIAYIGDDLIDLPILVQVGLAVAPKDALPYIKEEVDFVSSLNGGKGVFRE 161
Cdd:cd01630   83 ELLEKLGLSDEEVAYMGDDLPDLPVMKRVGLSVAPADAHPEVREAADYVTRARGGRGAVRE 143

3-deoxy-D-manno-octulosonate 8-phosphate phosphatase, YrbI family; This family of proteins is a member of the IIIA subfamily of the haloacid dehalogenase (HAD) superfamily of hydrolases. All characterized members of this subfamily (TIGR01662) and most characterized members of the HAD superfamily are phosphatases. HAD superfamily phosphatases contain active site residues in several conserved catalytic motifs, all of which are found conserved here. One member of this family, the YrbI protein from H. influenzae has been cloned, expressed, purified and found to be an active 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase. Furthermore, its crystal structure has been determined. This family consists of sequences from beta, gamma and epsilon proteobacteria, Aquifex, Fusobacterium, Porphyromonas and Methanosarcina. The Methanosarcina sequence is distinctive in that it is linked to an N-terminal cytidylyltransferase domain (pfam02348) and is annotated as acylneuraminate cytidylyltransferase. This may give some clue as the function of these phosphatases. Several eukaryotic sequences scoring between trusted and noise are also closely related to this function such as the CMP-N-acetylneuraminic acid synthetase from mouse, but in these cases the phosphatase domain is clearly inactive as many of the active site residues are not conserved. [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 517284145   21 LLITDVDGVLTDGGVIYDDNYLEYKKYNVKDGLIVKVLQRHGILVGAITGRNSPVVQKRCEELHFDFHHHGIKDKGAKLL 100
Cdd:TIGR01670   3 LLILDVDGVLTDGKIYYTNNGEEIKAFNVRDGYGIRCALKSGIEVAIITGRKAKLVEDRCKTLGITHLYQGQSNKLIAFS 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 517284145  101 EVLDQYNLDLNEIAYIGDDLIDLPILVQVGLAVAPKDALPYIKEEVDFVSSLNGGKGVFRETGDLILSAQG 171
Cdd:TIGR01670  83 DILEKLALAPENVAYIGDDLIDWPVMEKVGLSVAVADAHPLLIPRADYVTRIAGGRGAVREVCELLLLAQG 153

Hydroxymethylpyrimidine pyrophosphatase and other HAD family phosphatases [Coenzyme transport and metabolism, General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 517284145  54 IVKVLQRHGILVGAITgrnspvvqkRCEELHFDFHHHGIkDKGAKLLEVLDQYNLDLNEIAYIGDDLIDLPILVQVGLAV 133
Cdd:COG0561   91 ILELLREHGLHLQVVV---------RSGPGFLEILPKGV-SKGSALKKLAERLGIPPEEVIAFGDSGNDLEMLEAAGLGV 160

                         90       100
                 ....*....|....*....|....*
gi 517284145 134 APKDALPYIKEEVDFVSSLNGGKGV 158
Cdd:COG0561  161 AMGNAPPEVKAAADYVTGSNDEDGV 185

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 517284145   21 LLITDVDGVLTDGGVIYDDNYLEYKKYNVKDGLivKVLQRHGILVGAITG-----------RNSPVVQKRCEEL--HFDF 87
Cdd:TIGR01662   2 AVVLDLDGTLTDDVPYVSDEDERILYPEVPDAL--AELKEAGYKVVIVTNqsgigrgyfsrSFSGRVARRLEELgvPIDI 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 517284145   88 ---HHHGIKDKGAKLLEVLDQYN-LDLNEIAYIGD-DLIDLPILVQVGLAVA 134
Cdd:TIGR01662  80 lyaCPGCRKPKPGMFLEALKRFNeIDPEESVYVGDqDLTDLQAAKRVGLATI 131

Phosphoserine phosphatase [Amino acid transport and metabolism]; Phosphoserine phosphatase is part of the Pathway/BioSystem: Serine biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 517284145  55 VKVLQRHGILVGAITGRNSPVVQKRCEELHFDfHHHG----IKD----------------KGAKLLEVLDQYNLDLNEIA 114
Cdd:COG0560   97 IAEHRAAGHKVAIVSGGFTFFVEPIAERLGID-HVIAneleVEDgrltgevvgpivdgegKAEALRELAAELGIDLEQSY 175

                         90       100
                 ....*....|....*....|....*..
gi 517284145 115 YIGDDLIDLPILVQVGLAVA--PKDAL 139
Cdd:COG0560  176 AYGDSANDLPMLEAAGLPVAvnPDPAL 202

phosphatase, similar to Escherichia coli Cof and Thermotoga maritima TM0651; belongs to the haloacid dehalogenase-like superfamily; Escherichia coli Cof is involved in the hydrolysis of HMP-PP (4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate, an intermediate in thiamin biosynthesis), Cof also has phosphatase activity against the coenzymes pyridoxal phosphate (PLP) and FMN. Thermotoga maritima TM0651 acts as a phosphatase with a phosphorylated carbohydrate molecule as a possible substrate. Escherichia coli YbhA is also a member of this family and catalyzes the dephosphorylation of PLP, YbhA can also hydrolyze erythrose-4-phosphate and fructose-1,6-bis-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, 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 517284145  94 DKGAKLLEVLDQYNLDLNEIAYIGDDLIDLPILVQVGLAVAPKDALPYIKEEVDFV 149
Cdd:cd07516  183 SKGNALKKLAEYLGISLEEVIAFGDNENDLSMLEYAGLGVAMGNAIDEVKEAADYV 238

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 517284145   22 LITDVDGVLTDGGVIYDDNYLEYK----KYNVKDGLI--VKVLQRHGILVGAITGRNSPVVQKRCEEL----HFDFHHHG 91
Cdd:pfam00702  68 LRGLVETLEAEGLTVVLVELLGVIaladELKLYPGAAeaLKALKERGIKVAILTGDNPEAAEALLRLLglddYFDVVISG 147

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 517284145   92 IKDKGAK-----LLEVLDQYNLDLNEIAYIGDDLIDLPILVQVG 130
Cdd:pfam00702 148 DDVGVGKpkpeiYLAALERLGVKPEEVLMVGDGVNDIPAAKAAG 191

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 517284145  21 LLITDVDGVLTdggviyddnyleykkynVKDGLivKVLQRHGILVGAITGRNSPVVQKRCEEL----HFDF-----HHHG 91
Cdd:cd01427    1 AVLFDLDGTLL-----------------AVELL--KRLRAAGIKLAIVTNRSREALRALLEKLglgdLFDGiigsdGGGT 61

                         90       100       110
                 ....*....|....*....|....*....|...
gi 517284145  92 IKDKGAKLLEVLDQYNLDLNEIAYIGDDLIDLP 124
Cdd:cd01427   62 PKPKPKPLLLLLLKLGVDPEEVLFVGDSENDIE 94

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 517284145  22 LITDVDGVLtdggviyddnyLEYKKYNVKDGLI--VKVLQRHGILVGAITGRNSPVVQKRCEELHFDFHHHGIKDKGAKL 99
Cdd:cd16416    2 VITDLDNTL-----------LAWDNPDLTPEVKawLADLKEAGIKVVLVSNNNERRVAKVIEKLDLPFVARAGKPRPRAF 70

                         90       100
                 ....*....|....*....|..
gi 517284145 100 LEVLDQYNLDLNEIAYIGDDLI 121
Cdd:cd16416   71 RRALKEMDLPPEQVAMVGDQLF 92

P-type heavy metal-transporting ATPase, similar to Archaeoglobus fulgidus CopB, a Cu(2+)-ATPase; Archaeoglobus fulgidus CopB transports Cu(2+) from the cytoplasm to the exterior of the cell using ATP as energy source, it transports preferentially Cu(2+) over Cu(+), it is activated by Cu(2+) with high affinity and partially by Cu(+) and Ag(+). This subclass of P-type ATPase is also referred to as CPx-type ATPases because their amino acid sequences contain a characteristic CPC or CPH motif associated with a stretch of hydrophobic amino acids and N-terminal ion-binding sequences. This subfamily 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 517284145  55 VKVLQRHGILVGAITGRNSPVVQKRCEELHFDFHHHGIK--DKGAKLLEVLDQYnldlNEIAYIGDDLIDLPILVQ--VG 130
Cdd:cd07552  464 IRALKAQGITPVMLTGDNEEVAQAVAEELGIDEYFAEVLpeDKAKKVKELQAEG----KKVAMVGDGVNDAPALAQadVG 539

                 ...
gi 517284145 131 LAV 133
Cdd:cd07552  540 IAI 542