haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to human cytosolic IIIA and IIIB; 5'-nucleotidases dephosphorylate nucleoside 5prime-monophosphates. This family includes human 5'-nucleotidase, cytosolic IIIA (cN-IIIA, previously called cN-III; NT5C3A) the main pyrimidine 5'-nucleotidase in erythrocytes which dephosphorylates the pyrimidine nucleotides CMP, UMP, TMP, and the purine 7-methylguanosine monophosphate (m7GM), and possesses phosphotransferase activity. It also includes human 5'-nucleotidase, cytosolic IIIB (cN-IIIB; NT5C3B) which has a strong preference for m7GMP, dephosphorylates CMP and UMP and, with significantly lower efficiency, GMP and AMP, and can also act as a phosphotransferase. 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 25148796  71 DPTAVAAKLRKMVVGGAGKTVVISDFDYTLSRFANEQGERLsTTHGVFDDNVMrLKPELGQKFVDLKNKYYPIEFSPNLT 150
Cdd:cd07504   1 DPTRVEEKICGLVKGGADKLQIISDFDMTLSRFRYNGGRCP-TCHNIFDNCKL-LTEECRAKLVQLKEKYYPIEIDPHLT 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796 151 MEEKIPHMEKWWGTSHSLIVNEKFSKNTIEDFVRQSRIVFKDGAEDFIEALDAHNIPLVIFSAGIGNIIEYFLQQKLGAi 230
Cdd:cd07504  79 IEEKVPYMEEWWTKSHELLIEQGFQKDAIDQIVAESDIALRDGYEEFFEKLQQHGIPVLIFSAGLGDIIEEVLRQAGVY- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796 231 PRNTHFISNMILFDEDDNACAFSEPLIHTFCKNSSVIqKETSFFHDIAGRVNVILLGDSMGDIHMDVGVERDGPTLKVGY 310
Cdd:cd07504 158 HPNVKVVSNFMDFDDNGVLTGFKGPLIHVFNKNESAL-KNTDYFKQLKGRTNIILLGDSIGDLRMADGVPNVEHILKIGF 236

                       250       260       270
                ....*....|....*....|....*....|....*....
gi 25148796 311 YNGSLDdtAALQHYEEVYDIVLIHDPTLNVAQKIVDIIN 349
Cdd:cd07504 237 LNDKVE--ELLEKYMDSYDIVLVNDETLDVPNSILQKIL 273

Beta-phosphoglucomutase, HAD superfamily [Carbohydrate transport and metabolism];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796 149 LTMEEKIPHMEKWWGTSHSL--IVNEKfsKNTIEDFVRQSRIVFKDGAEDFIEALDAHNIPLVIFSAGIGNIIEYFLqQK 226
Cdd:COG0637  46 RSREDILRYLLEEYGLDLPEeeLAARK--EELYRELLAEEGLPLIPGVVELLEALKEAGIKIAVATSSPRENAEAVL-EA 122

                ....*.
gi 25148796 227 LGAIPR 232
Cdd:COG0637 123 AGLLDY 128

haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to human cytosolic IIIA and IIIB; 5'-nucleotidases dephosphorylate nucleoside 5prime-monophosphates. This family includes human 5'-nucleotidase, cytosolic IIIA (cN-IIIA, previously called cN-III; NT5C3A) the main pyrimidine 5'-nucleotidase in erythrocytes which dephosphorylates the pyrimidine nucleotides CMP, UMP, TMP, and the purine 7-methylguanosine monophosphate (m7GM), and possesses phosphotransferase activity. It also includes human 5'-nucleotidase, cytosolic IIIB (cN-IIIB; NT5C3B) which has a strong preference for m7GMP, dephosphorylates CMP and UMP and, with significantly lower efficiency, GMP and AMP, and can also act as a phosphotransferase. 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 25148796  71 DPTAVAAKLRKMVVGGAGKTVVISDFDYTLSRFANEQGERLsTTHGVFDDNVMrLKPELGQKFVDLKNKYYPIEFSPNLT 150
Cdd:cd07504   1 DPTRVEEKICGLVKGGADKLQIISDFDMTLSRFRYNGGRCP-TCHNIFDNCKL-LTEECRAKLVQLKEKYYPIEIDPHLT 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796 151 MEEKIPHMEKWWGTSHSLIVNEKFSKNTIEDFVRQSRIVFKDGAEDFIEALDAHNIPLVIFSAGIGNIIEYFLQQKLGAi 230
Cdd:cd07504  79 IEEKVPYMEEWWTKSHELLIEQGFQKDAIDQIVAESDIALRDGYEEFFEKLQQHGIPVLIFSAGLGDIIEEVLRQAGVY- 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796 231 PRNTHFISNMILFDEDDNACAFSEPLIHTFCKNSSVIqKETSFFHDIAGRVNVILLGDSMGDIHMDVGVERDGPTLKVGY 310
Cdd:cd07504 158 HPNVKVVSNFMDFDDNGVLTGFKGPLIHVFNKNESAL-KNTDYFKQLKGRTNIILLGDSIGDLRMADGVPNVEHILKIGF 236

                       250       260       270
                ....*....|....*....|....*....|....*....
gi 25148796 311 YNGSLDdtAALQHYEEVYDIVLIHDPTLNVAQKIVDIIN 349
Cdd:cd07504 237 LNDKVE--ELLEKYMDSYDIVLVNDETLDVPNSILQKIL 273

phosphoserine phosphatase eukaryotic-like, similar to human phosphoserine phosphatase; Human PSP, EC 3.1.3.3, catalyzes the third and final of the L-serine biosynthesis pathway, the Mg2+-dependent hydrolysis of phospho-L-serine to L-serine and inorganic phosphate, L-serine is a precursor for the biosynthesis of glycine. HPSP regulates the levels of glycine and D-serine (converted from L-serine), the putative co-agonists for the glycine site of the NMDA receptor in the brain. Plant 3-PSP catalyzes the conversion of 3-phosphoserine to serine in the last step of the plastidic pathway of serine 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 25148796 173 KFSKNTIEDFVRQSRIVFKDGAEDFIEALDAHNIPLVIFSAGIGNIIEYFLQQkLGaIPRnTHFISNMILFDEDDNACAF 252
Cdd:cd04309  56 NPTKEQVDEFLEEHPPRLTPGVEELVSRLKARGVEVYLISGGFRELIEPVASQ-LG-IPL-ENVFANRLLFDFNGEYAGF 132

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 25148796 253 --SEPLIHTFCKnSSVIQKETSFFHDiagrVNVILLGDSMGDI 293
Cdd:cd04309 133 deTQPTSRSGGK-AKVIEQLKEKHHY----KRVIMIGDGATDL 170

Haloacid Dehalogenase superfamily, subfamily IB, phosphoserine phosphatase-like; This model represents a subfamily of the Haloacid Dehalogenase superfamily of aspartate-nucleophile hydrolases. Subfamily IA, B, C and D are distinguished from the rest of the superfamily by the presence of a variable domain between the first and second conserved catalytic motifs. In subfamilies IA and IB, this domain consists of an alpha-helical bundle. It was necessary to model these two subfamilies separately, breaking them at a an apparent phylogenetic bifurcation, so that the resulting model(s) are not so broadly defined that members of subfamily III (which lack the variable domain) are included. Subfamily IA includes the enzyme phosphoserine phosphatase (TIGR00338) as well as three hypothetical equivalogs. Many members of these hypothetical equivalogs have been annotated as PSPase-like or PSPase-family proteins. In particular, the hypothetical equivalog which appears to be most closely related to PSPase contains only Archaea (while TIGR00338 contains only eukaryotes and bacteria) of which some are annotated as PSPases. Although this is a reasonable conjecture, none of these sequences has sufficient evidence for this assignment. If such should be found, this model should be retired while the PSPase model should be broadened to include these sequences. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796    91 VVISDFDYTLSRFanEQGERLSTTHGVFDDNVMRLKPELGQKFvdlknkyypIEFSPNLTMEEKIPHMekwwgtshsliv 170
Cdd:TIGR01488   1 LAIFDFDGTLTRQ--DSLIDLLAKLLGTNDEVIELTRLAPSGR---------ISFEDALGRRLALLHR------------ 57

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796   171 neKFSKNTIEDFVRQSRIVfKDGAEDFIEALDAHNIPLVIFSAGIGNIIEYFLqQKLGaIPRNthfISNMILFDEDDN-A 249
Cdd:TIGR01488  58 --SRSEEVAKEFLARQVAL-RPGARELISWLKERGIDTVIVSGGFDFFVEPVA-EKLG-IDDV---FANRLEFDDNGLlT 129

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 25148796   250 CAFSEPLIHTFCKNSSVIQK---ETSFfhdiaGRVNVILLGDSMGDIHM 295
Cdd:TIGR01488 130 GPIEGQVNPEGECKGKVLKElleESKI-----TLKKIIAVGDSVNDLPM 173

haloacid dehalogenase superfamily, subfamily IA, variant 3 with third motif having DD or ED; This model represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The subfamilies 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. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions. The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that representing it with a single model is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an aparrent phylogenetic bifurcation. Subfamily IA is still too broad to model, but cannot be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms: (1) hhhhsDxxx(x)D, (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA. Individual models were made based on seeds exhibiting only one of the variants each. Variant 3 (this model) is found in the enzymes beta-phosphoglucomutase (TIGR01990) and deoxyglucose-6-phosphatase, while many other enzymes of subfamily IA exhibit this variant as well as variant 1 (TIGR01549). These three variant models were created with the knowledge that there will be overlap among them - this is by design and serves the purpose of eliminating the overlap with models of more distantly related HAD subfamilies caused by an overly broad single model. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25148796    91 VVISDFDYTLsrfaneqgerLSTTHGVFDDNVMRLKPELGQkfvDLKNKYYpiefspnLTMEEKIP-HMEKWWGTSHSLI 169
Cdd:TIGR01509   1 AILFDLDGVL----------VDTEFAIAKLINREELGLVPD---ELGVSAV-------GRLELALRrFKAQYGRTISPED 60

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 25148796   170 VNEKFSKNTIEDFVRQSRIVFKDGAEDFIEALDAHNIPLVIFSAG 214
Cdd:TIGR01509  61 AQLLYKQLFYEQIEEEAKLKPLPGVRALLEALRARGKKLALLTNS 105

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 25148796 188 IVF-KDG---AEDFIEALDAHNIPLVIFSAGIGNIIEYFLQQkLGAIPRNTHFISNmilfDEDDNACAFSEPLIHtfckn 263
Cdd:cd01427   2 VLFdLDGtllAVELLKRLRAAGIKLAIVTNRSREALRALLEK-LGLGDLFDGIIGS----DGGGTPKPKPKPLLL----- 71

                        90       100       110
                ....*....|....*....|....*....|..
gi 25148796 264 ssviqketSFFHDIAGRVNVILLGDSMGDIHM 295
Cdd:cd01427  72 --------LLLKLGVDPEEVLFVGDSENDIEA 95