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 490605060  22 LKLIVIDVDGVLTDGKLYYNEHGEFFKIFDVKDGLGIKLLCKE-LNVAILSGNPSKIIHIRAESLGIKHCMIGINDKKAS 100
Cdd:cd01630    1 IKLLVLDVDGVLTDGRIYYDSNGEELKSFNVRDGLGIKLLQKSgIEVAIITGRQSEAVRRRAKELGIEDLFQGVKDKLEA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 490605060 101 LQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKSRGGNGAVREFAD 166
Cdd:cd01630   81 LEELLEKLGLSDEEVAYMGDDLPDLPVMKRVGLSVAPADAHPEVREAADYVTRARGGRGAVREVCE 146

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 490605060   22 LKLIVIDVDGVLTDGKLYYNEHGEFFKIFDVKDGLGIKLLCK-ELNVAILSGNPSKIIHIRAESLGIKHCMIGINDKKAS 100
Cdd:TIGR01670   1 IRLLILDVDGVLTDGKIYYTNNGEEIKAFNVRDGYGIRCALKsGIEVAIITGRKAKLVEDRCKTLGITHLYQGQSNKLIA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 490605060  101 LQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKSRGGNGAVREFADYVLSAKG 173
Cdd:TIGR01670  81 FSDILEKLALAPENVAYIGDDLIDWPVMEKVGLSVAVADAHPLLIPRADYVTRIAGGRGAVREVCELLLLAQG 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 490605060  22 LKLIVIDVDGVLTDGKLYYNEHGEFFKIFDVKDGLGIKLLCKE-LNVAILSGNPSKIIHIRAESLGIKHCMIGINDKKAS 100
Cdd:cd01630    1 IKLLVLDVDGVLTDGRIYYDSNGEELKSFNVRDGLGIKLLQKSgIEVAIITGRQSEAVRRRAKELGIEDLFQGVKDKLEA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 490605060 101 LQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKSRGGNGAVREFAD 166
Cdd:cd01630   81 LEELLEKLGLSDEEVAYMGDDLPDLPVMKRVGLSVAPADAHPEVREAADYVTRARGGRGAVREVCE 146

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 490605060   22 LKLIVIDVDGVLTDGKLYYNEHGEFFKIFDVKDGLGIKLLCK-ELNVAILSGNPSKIIHIRAESLGIKHCMIGINDKKAS 100
Cdd:TIGR01670   1 IRLLILDVDGVLTDGKIYYTNNGEEIKAFNVRDGYGIRCALKsGIEVAIITGRKAKLVEDRCKTLGITHLYQGQSNKLIA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 490605060  101 LQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKSRGGNGAVREFADYVLSAKG 173
Cdd:TIGR01670  81 FSDILEKLALAPENVAYIGDDLIDWPVMEKVGLSVAVADAHPLLIPRADYVTRIAGGRGAVREVCELLLLAQG 153

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 490605060   23 KLIVIDVDGVLTDGKLYYNEHGEFFKIFDVKDGLgIKLLCKELNVAILSGN-----------PSKIIHIRAESLGIKHCM 91
Cdd:TIGR01662   1 KAVVLDLDGTLTDDVPYVSDEDERILYPEVPDAL-AELKEAGYKVVIVTNQsgigrgyfsrsFSGRVARRLEELGVPIDI 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 490605060   92 IGI--NDKKAS---LQSLMDQL-GISSQEVAYIGDDVN 123
Cdd:TIGR01662  80 LYAcpGCRKPKpgmFLEALKRFnEIDPEESVYVGDQDL 117

phosphoglycolate phosphatase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 490605060  96 DKKASLQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKSRGGNGAV 161
Cdd:PRK01158 157 NKGTGLKKLAELMGIDPEEVAAIGDSENDLEMFEVAGFGVAVANADEELKEAADYVTEKSYGEGVA 222

sugar phosphate phosphatase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 490605060  96 DKKASLQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKSRGGNGAVREFADYVL 169
Cdd:PRK10513 196 NKGTGVKSLAEHLGIKPEEVMAIGDQENDIAMIEYAGVGVAMGNAIPSVKEVAQFVTKSNLEDGVAFAIEKYVL 269

Cof subfamily of IIB subfamily of haloacid dehalogenase superfamily; This subfamily of sequences falls within the Class-IIB subfamily (TIGR01484) of the Haloacid Dehalogenase superfamily of aspartate-nucleophile hydrolases. The use of the name "Cof" as an identifier here is arbitrary and refers to the E. coli Cof protein. This subfamily is notable for the large number of recent paralogs in many species. Listeria, for instance, has 12, Clostridium, Lactococcus and Streptococcus pneumoniae have 8 each, Enterococcus and Salmonella have 7 each, and Bacillus subtilus, Mycoplasma, Staphylococcus and E. coli have 6 each. This high degree of gene duplication is limited to the gamma proteobacteria and low-GC gram positive lineages. The profusion of genes in this subfamily is not coupled with a high degree of divergence, so it is impossible to determine an accurate phylogeny at the equivalog level. Considering the relationship of this subfamily to the other known members of the HAD-IIB subfamily (TIGR01484), sucrose and trehalose phosphatases and phosphomannomutase, it seems a reasonable hypothesis that these enzymes act on phosphorylated sugars. Possibly the diversification of genes in this subfamily represents the diverse sugars and polysaccharides that various bacteria find in their biological niches. The members of this subfamily are restricted almost exclusively to bacteria (one sequences from S. pombe scores above trusted, while another is between trusted and noise). It is notable that no archaea are found in this group, the closest relations to the archaea found here being two Deinococcus sequences. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490605060    4 LFKTFFRFLIKSNFVLKKLKLiviDVDGVLTDgKLYYNEHGEFFKIFDVKDGLGIKLlckELNVAILSGNPSKIIHIRAe 83
Cdd:TIGR00099 116 YFTIFKKFLGEPKLEVVDIQY---LPDDILKI-LLLFLDPEDLDLLIEALNKLELEE---NVSVVSSGPYSIEITAKGV- 187

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 490605060   84 slgikhcmiginDKKASLQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKS 154
Cdd:TIGR00099 188 ------------SKGSALQSLAEALGISLEDVIAFGDGMNDIEMLEAAGYGVAMGNADEELKALADYVTDS 246

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 490605060  93 GINdKKASLQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKS 154
Cdd:cd07516  181 GVS-KGNALKKLAEYLGISLEEVIAFGDNENDLSMLEYAGLGVAMGNAIDEVKEAADYVTLT 241

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 490605060  24 LIVIDVDGVLTdgklyynehgeffkifdVKDGLGiKLLCKELNVAILSGNPSKIIHIRAESLGIKHCMIGI--------- 94
Cdd:cd01427    1 AVLFDLDGTLL-----------------AVELLK-RLRAAGIKLAIVTNRSREALRALLEKLGLGDLFDGIigsdgggtp 62

                         90       100       110
                 ....*....|....*....|....*....|...
gi 490605060  95 -NDKKAsLQSLMDQLGISSQEVAYIGDDVNDLP 126
Cdd:cd01427   63 kPKPKP-LLLLLLKLGVDPEEVLFVGDSENDIE 94

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490605060  37 KLYYNEHGEFFKIFD-VKDGLGiKLLCKELNVAILSGNPSKIIHIRAESLGIKHC---MIGIND------KKASLQSLMD 106
Cdd:COG0546   73 ELYEEELLDETRLFPgVRELLE-ALKARGIKLAVVTNKPREFAERLLEALGLDDYfdaIVGGDDvppakpKPEPLLEALE 151

                         90
                 ....*....|....*....
gi 490605060 107 QLGISSQEVAYIGDDVNDL 125
Cdd:COG0546  152 RLGLDPEEVLMVGDSPHDI 170

hydrolase family protein

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 490605060  97 KKASLQSLMDQLGISSQEVAYIGDDVNDLPVRSITKLFVCPSDAHPSVKKVADLILKSRGGNG---AVREFA 165
Cdd:PLN02887 508 KGNGVKMLLNHLGVSPDEIMAIGDGENDIEMLQLASLGVALSNGAEKTKAVADVIGVSNDEDGvadAIYRYA 579