Haloacid Dehalogenase-like Hydrolases; The haloacid dehalogenase (HAD) superfamily includes carbon and phosphorus hydrolases such as 2-haloalkonoate dehalogenase, epoxide hydrolase, phosphoserine phosphatase, phosphomannomutase, phosphoglycolate phosphatase, P-type ATPase, among others. These proteins catalyze nucleophilic substitution reactions at phosphorus or carbon centers, using a conserved Asp carboxylate in covalent catalysis. All members possess a conserve alpha/beta core domain, and many also possess a small cap domain, with varying folds and functions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79328637    37 AELLEKEKLSINYANCRSWHLGVETSNIIDFDTVPANCKDYVEDYLiTSKQYQYDSKTVCKEAYFYAKGLALKNDTVNVW 116
Cdd:TIGR01675   1 LEILMKEKLSIDYGYCRSWRLGVETNNIRKWDTVPAECKDYVEDYM-TSKQYKRDSKRVVDEAYFYAKSLALSGDGMDAW 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79328637   117 IFDLDDTLLSSIPYYAKYGYGTEKTDPGAYWLWLGTGAStPGLPEALHLYQNIIELGIEPIILSDRWKLWKNVTLDNLEA 196
Cdd:TIGR01675  80 IFDVDDTLLSNIPYYKKHGYGTEKTDPTAFWDWLEKGEA-PALPETLKLYQKLLELGIKIFLLSGRWEELRSATVENLIN 158

                         170
                  ....*....|..
gi 79328637   197 AGVTYWKHLILK 208
Cdd:TIGR01675 159 AGFTGWKHLILR 170

plant acid phosphatase; This model represents a family of acid phosphatase from plants which are most closely related to the (so called) class B non-specific acid phosphatase OlpA (TIGR01533, which is believed to be a 5'-nucleotide phosphatase) and somewhat more distantly to another class B phosphatase, AphA (TIGR01672). Together these three clades define a subfamily (pfam03767) which corresponds to the IIIB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate nucleophile hydrolases. It has been reported that the best substrate for this enzyme that could be found was purine 5'-nucleoside phosphates. This is in concordance with the assignment of the H. influenzae hel protein (from TIGR01533) as a 5'-nucleotidase, however there is presently no other evidence to support this specific function for these plant phosphatases. Many genes from this family have been annotated as vegetative storage proteins due to their close homology with these earlier-characterized gene products, which are highly expressed in leaves. There are significant differences however, including expression levels and distribution. The most important difference is the lack in authentic VSPs of the nucleophilic aspartate residue, which is instead replaced by serine, glycine or asparagine. Thus these proteins can not be expected to be active phosphatases. This issue was confused by the publication in 1992 of an article claiming activity for the Glycine max VSP. In 1994 this assertion was refuted by the separation of the activity from the VSP. This model explicitly excludes the VSPs which lack the nucleophilc aspartate. The possibility exists, however, that some members of this family may, while containing all of the conserved HAD-superfamily catalytic residues, lack activity and have a function related to the function of the VSPs rather than the acid phosphatases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79328637    37 AELLEKEKLSINYANCRSWHLGVETSNIIDFDTVPANCKDYVEDYLiTSKQYQYDSKTVCKEAYFYAKGLALKNDTVNVW 116
Cdd:TIGR01675   1 LEILMKEKLSIDYGYCRSWRLGVETNNIRKWDTVPAECKDYVEDYM-TSKQYKRDSKRVVDEAYFYAKSLALSGDGMDAW 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79328637   117 IFDLDDTLLSSIPYYAKYGYGTEKTDPGAYWLWLGTGAStPGLPEALHLYQNIIELGIEPIILSDRWKLWKNVTLDNLEA 196
Cdd:TIGR01675  80 IFDVDDTLLSNIPYYKKHGYGTEKTDPTAFWDWLEKGEA-PALPETLKLYQKLLELGIKIFLLSGRWEELRSATVENLIN 158

                         170
                  ....*....|..
gi 79328637   197 AGVTYWKHLILK 208
Cdd:TIGR01675 159 AGFTGWKHLILR 170

vegetative storage proteins similar to soybean VSPalpha and VSPbeta proteins; belongs to the haloacid dehalogenase-like superfamily; Soybean [Glycine max (L.) Merr.] vegetative storage protein VSPalpha and VSPbeta levels were identified as storage proteins due to their abundance and pattern of expression in plant tissues, they accumulate to almost one-half the amount of soluble leaf protein when soybean plants are continually depodded. They possess acid phosphatase activity which appears to be low compared to several other plant acid phosphatases, it increases in the leaves of depodded soybean plants, but to no more than 0.1% of the total acid phosphatase activity in these leaves. This acid phosphatase activity has maximal activity at pH 5.0 - 5.5, and can liberate Pi from different substrates such as napthyl acid phosphate, carboxyphenyl phosphate, sugar-phosphates, glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, phosphoenolpyruvate, ATP, ADP, PPi, and short chain polyphosphates; they cleave phosphoenolpyruvate, ATP, ADP, PPI, and polyphosphates most efficiently. 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. Soybean VSPalpha and VSPbeta lack this active site aspartate, other members of this family have this aspartate and may be more active. 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 79328637  78 VEDYLITSKQYQYDS-KTVCKEAYFYAKGLalKNDTVNVWIFDLDDTLLSSIPYYAKYGYGTEKTDPGAYWLWLGTGaST 156
Cdd:cd07535   1 VEDYMKGGQYLRDSSvKTVNALAYAYSKVL--AGDGMDVWIFDIDDTLLSNIPYYKKHGYGGEKFDSTAFDEWVEKG-KA 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 79328637 157 PGLPEALHLYQNIIELGIEPIILSDRWKLWKNVTLDNLEAAGVTYWKHLILK 208
Cdd:cd07535  78 PALPESLKLYNKLLELGFKIFLLSGRDETLRNATVENLKKAGYHGWEHLILR 129

plant acid phosphatase; This model represents a family of acid phosphatase from plants which are most closely related to the (so called) class B non-specific acid phosphatase OlpA (TIGR01533, which is believed to be a 5'-nucleotide phosphatase) and somewhat more distantly to another class B phosphatase, AphA (TIGR01672). Together these three clades define a subfamily (pfam03767) which corresponds to the IIIB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate nucleophile hydrolases. It has been reported that the best substrate for this enzyme that could be found was purine 5'-nucleoside phosphates. This is in concordance with the assignment of the H. influenzae hel protein (from TIGR01533) as a 5'-nucleotidase, however there is presently no other evidence to support this specific function for these plant phosphatases. Many genes from this family have been annotated as vegetative storage proteins due to their close homology with these earlier-characterized gene products, which are highly expressed in leaves. There are significant differences however, including expression levels and distribution. The most important difference is the lack in authentic VSPs of the nucleophilic aspartate residue, which is instead replaced by serine, glycine or asparagine. Thus these proteins can not be expected to be active phosphatases. This issue was confused by the publication in 1992 of an article claiming activity for the Glycine max VSP. In 1994 this assertion was refuted by the separation of the activity from the VSP. This model explicitly excludes the VSPs which lack the nucleophilc aspartate. The possibility exists, however, that some members of this family may, while containing all of the conserved HAD-superfamily catalytic residues, lack activity and have a function related to the function of the VSPs rather than the acid phosphatases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79328637    37 AELLEKEKLSINYANCRSWHLGVETSNIIDFDTVPANCKDYVEDYLiTSKQYQYDSKTVCKEAYFYAKGLALKNDTVNVW 116
Cdd:TIGR01675   1 LEILMKEKLSIDYGYCRSWRLGVETNNIRKWDTVPAECKDYVEDYM-TSKQYKRDSKRVVDEAYFYAKSLALSGDGMDAW 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79328637   117 IFDLDDTLLSSIPYYAKYGYGTEKTDPGAYWLWLGTGAStPGLPEALHLYQNIIELGIEPIILSDRWKLWKNVTLDNLEA 196
Cdd:TIGR01675  80 IFDVDDTLLSNIPYYKKHGYGTEKTDPTAFWDWLEKGEA-PALPETLKLYQKLLELGIKIFLLSGRWEELRSATVENLIN 158

                         170
                  ....*....|..
gi 79328637   197 AGVTYWKHLILK 208
Cdd:TIGR01675 159 AGFTGWKHLILR 170

vegetative storage proteins similar to soybean VSPalpha and VSPbeta proteins; belongs to the haloacid dehalogenase-like superfamily; Soybean [Glycine max (L.) Merr.] vegetative storage protein VSPalpha and VSPbeta levels were identified as storage proteins due to their abundance and pattern of expression in plant tissues, they accumulate to almost one-half the amount of soluble leaf protein when soybean plants are continually depodded. They possess acid phosphatase activity which appears to be low compared to several other plant acid phosphatases, it increases in the leaves of depodded soybean plants, but to no more than 0.1% of the total acid phosphatase activity in these leaves. This acid phosphatase activity has maximal activity at pH 5.0 - 5.5, and can liberate Pi from different substrates such as napthyl acid phosphate, carboxyphenyl phosphate, sugar-phosphates, glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, phosphoenolpyruvate, ATP, ADP, PPi, and short chain polyphosphates; they cleave phosphoenolpyruvate, ATP, ADP, PPI, and polyphosphates most efficiently. 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. Soybean VSPalpha and VSPbeta lack this active site aspartate, other members of this family have this aspartate and may be more active. 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 79328637  78 VEDYLITSKQYQYDS-KTVCKEAYFYAKGLalKNDTVNVWIFDLDDTLLSSIPYYAKYGYGTEKTDPGAYWLWLGTGaST 156
Cdd:cd07535   1 VEDYMKGGQYLRDSSvKTVNALAYAYSKVL--AGDGMDVWIFDIDDTLLSNIPYYKKHGYGGEKFDSTAFDEWVEKG-KA 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 79328637 157 PGLPEALHLYQNIIELGIEPIILSDRWKLWKNVTLDNLEAAGVTYWKHLILK 208
Cdd:cd07535  78 PALPESLKLYNKLLELGFKIFLLSGRDETLRNATVENLKKAGYHGWEHLILR 129

vegetative storage proteins and related proteins, similar to soybean VSPalpha and VSPbeta proteins; belongs to the haloacid dehalogenase-like superfamily; Soybean [Glycine max (L.) Merr.] vegetative storage protein VSPalpha and VSPbeta levels were identified as storage proteins due to their abundance and pattern of expression in plant tissues, they accumulate to almost one-half the amount of soluble leaf protein when soybean plants are continually depodded. They possess acid phosphatase activity which appears to be low compared to several other plant acid phosphatases; it increases in the leaves of depodded soybean plants, but to no more than 0.1% of the total acid phosphatase activity in these leaves. This acid phosphatase activity has maximal activity at pH 5.0 - 5.5, and can liberate Pi from different substrates such as napthyl acid phosphate, carboxyphenyl phosphate, sugar-phosphates, glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, phosphoenolpyruvate, ATP, ADP, PPi, and short chain polyphosphates; they cleave phosphoenolpyruvate, ATP, ADP, PPI, and polyphosphates most efficiently. 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. Soybean VSPalpha and VSPbeta lack this active site aspartate, other members of this family have this aspartate and may be more active. 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 79328637  97 KEAYFYAKGLalknDTVNVWIFDLDDTLLSSIPYYAKYGyGTEKTDPGAYWLWLGTGAStPGLPEALHLYQNIIELGIEP 176
Cdd:cd01624   1 KEAIAYAAGL----DTVNAWVFDIDDTLLSSIDYLKKYG-GTEGTAPGIWNSWLERGDS-PPVPETLELAEYALEKGVEV 74

                        90       100       110
                ....*....|....*....|....*....|..
gi 79328637 177 IILSDRWKLWKNVTLDNLEAAGVTYWKHLILK 208
Cdd:cd01624  75 FFISDRWEKLREPTVENLKAAGYTVWSHLFLK 106

molecular class C acid phosphatases, similar to Haemophilus influenzae e (P4) acid phosphatase; belongs to the haloacid dehalogenase-like hydrolase superfamily; Molecular class C acid phosphatases (CAPs) are nonspecific acid phosphatases with generally broad substrate specificity and optimum activity at neutral to acidic pH. Members include Haemophilus influenzae lipoprotein e (P4), Elizabethkingia meningosepticum OlpA, Helicobacter pylori HppA, Enterobacter sp. 4 acid phosphatase PhoI, and Streptococcus pyogenes M1 GAS LppC. Lipoprotein e (P4) exhibits phosphomonoesterase activity with aryl phosphate substrates including nicotinamide mononucleotide (NMN), tyrosine phosphate, phenyl phosphate, p-nitrophenyl phosphate, and 4-methylumbelliferyl phosphate. The role of P4 in NAD+ uptake appears to be the dephosphorylation of NMN to nicotinamide riboside, which is then taken up by the organism. Elizabethkingia meningosepticum OlpA is a broad-spectrum nucleotidase with preference for 5'-nucleotides, it efficiently hydrolyzes nucleotide monophosphates, with a strong preference for 5'-nucleotides and for 3'-AMP; OlpA can also hydrolyze sugar phosphates and beta-glycerol phosphate, although with a lower efficiency. Helicobacter pylori HppA is also a 5' nucleotidase. 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 79328637 117 IFDLDDTLLSSIPYYAKYGYGTEKTDPGAYWLWLGTGASTPgLPEALHLYQNIIELGIEPIILSDRWKLWKNVTLDNLEA 196
Cdd:cd07534  35 VLDLDETVLDNSPYQARQVKNGKPFSPETWDKWVQEAQAKP-IPGAVDFLNYANAKGVTIFYVSNRDQKLKAATLKNLKR 113

                        90
                ....*....|....
gi 79328637 197 AGVTYW--KHLILK 208
Cdd:cd07534 114 LGFPQAsdDHLLLK 127