phosphomannomutase, similar to human PMM1 and PMM2, Saccharomyces Sec53p, and Arabidopsis thaliana PMM; PMM catalyzes the interconversion of mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P); the conversion of M6P to M1P is an essential step in mannose activation and the biosynthesis of glycoconjugates in all eukaryotes. M1P is the substrate for the synthesis of GDP-mannose, which is an intermediate for protein glycosylation, protein sorting and secretion, and maintaining a functional endomembrane system in eukaryotic cells. Proteins in this family contains a conserved phosphorylated motif DxDx(T/V) shared with some other phosphotransferases. This family contains two human homologs, PMM1 and PMM2; PMM2 deficiency causes congenital disorder of glycosylation type I-a, also known as Jaeken syndrome. PMM1 can also act as glucose-1,6-bisphosphatase in the brain after stimulation with inosine monophosphate; PMM2 on the other hand, is insensitive to IMP and demonstrates low glucose-1,6-bisphosphatase activity. Arabidopsis thaliana PMM converted M1P into M6P and glucose-1-phosphate into glucose-6-phosphate, with the latter reaction being less efficient. Arabidopsis thaliana and Nicotiana benthamian PPMs are involved in ascorbic acid 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 4557839    8 LCLFDVDGTLTAPRQKITKEMDDFLQKLRQKIKIGVVGGSDFEKVQEQLGNDV-VEKYDYVFPENGLVAYKDGKLLCRQN 86
Cdd:cd02585   1 LLLFDVDGTLTPPRQPITPEMAEFLAELRQKVKIGVVGGSDYDKIKEQLGDNVpLLDFDYVFPENGLVAYRDGELLSRQS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839   87 IQSHLGEALIQDLINYCLSYIAKIKLPKKRGTFIEFRNGMLNVSPIGRSCSQEERIEFYELDKKENIRQKFVADLRKEFA 166
Cdd:cd02585  81 IIRALGEEKLQALINFCLRYIADLDLPKKRGTFIEFRNGMINISPIGRNCSQEERIEFEELDKKHKIREKFVSALKEEFA 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4557839  167 GKGLTFSIGGQISFDVFPDGWDKRYCLRHVENDGYKTIYFFGDKTMPGGNDHEIFTDPRTMGYSVTAPEDTRRICELL 244
Cdd:cd02585 161 DKGLTFSIGGQISFDVFPKGWDKTYCLRHLEEDLYEEIHFFGDKTQPGGNDYEIYQDPRTIGHSVTSPKDTVRILEEL 238

phosphomannomutase, similar to human PMM1 and PMM2, Saccharomyces Sec53p, and Arabidopsis thaliana PMM; PMM catalyzes the interconversion of mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P); the conversion of M6P to M1P is an essential step in mannose activation and the biosynthesis of glycoconjugates in all eukaryotes. M1P is the substrate for the synthesis of GDP-mannose, which is an intermediate for protein glycosylation, protein sorting and secretion, and maintaining a functional endomembrane system in eukaryotic cells. Proteins in this family contains a conserved phosphorylated motif DxDx(T/V) shared with some other phosphotransferases. This family contains two human homologs, PMM1 and PMM2; PMM2 deficiency causes congenital disorder of glycosylation type I-a, also known as Jaeken syndrome. PMM1 can also act as glucose-1,6-bisphosphatase in the brain after stimulation with inosine monophosphate; PMM2 on the other hand, is insensitive to IMP and demonstrates low glucose-1,6-bisphosphatase activity. Arabidopsis thaliana PMM converted M1P into M6P and glucose-1-phosphate into glucose-6-phosphate, with the latter reaction being less efficient. Arabidopsis thaliana and Nicotiana benthamian PPMs are involved in ascorbic acid 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 4557839    8 LCLFDVDGTLTAPRQKITKEMDDFLQKLRQKIKIGVVGGSDFEKVQEQLGNDV-VEKYDYVFPENGLVAYKDGKLLCRQN 86
Cdd:cd02585   1 LLLFDVDGTLTPPRQPITPEMAEFLAELRQKVKIGVVGGSDYDKIKEQLGDNVpLLDFDYVFPENGLVAYRDGELLSRQS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839   87 IQSHLGEALIQDLINYCLSYIAKIKLPKKRGTFIEFRNGMLNVSPIGRSCSQEERIEFYELDKKENIRQKFVADLRKEFA 166
Cdd:cd02585  81 IIRALGEEKLQALINFCLRYIADLDLPKKRGTFIEFRNGMINISPIGRNCSQEERIEFEELDKKHKIREKFVSALKEEFA 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4557839  167 GKGLTFSIGGQISFDVFPDGWDKRYCLRHVENDGYKTIYFFGDKTMPGGNDHEIFTDPRTMGYSVTAPEDTRRICELL 244
Cdd:cd02585 161 DKGLTFSIGGQISFDVFPKGWDKTYCLRHLEEDLYEEIHFFGDKTQPGGNDYEIYQDPRTIGHSVTSPKDTVRILEEL 238

phosphomannomutase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839     8 LCLFDVDGTLTAPRQKITKEMDDFLQKLRQK-IKIGVVGGSDFEKVQEQLGNDVVEKYDYVFPENGLVAYKDGKLLCRQN 86
Cdd:PTZ00174   7 ILLFDVDGTLTKPRNPITQEMKDTLAKLKSKgFKIGVVGGSDYPKIKEQLGEDVLEDFDYVFSENGLVAYKDGELFHSQS 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839    87 IQSHLGEALIQDLINYCLSYIAKIKLPKKRGTFIEFRNGMLNVSPIGRSCSQEERIEFYELDKKENIRQKFVADLRKEFA 166
Cdd:PTZ00174  87 ILKFLGEEKLKKFINFCLRYIADLDIPVKRGTFIEYRNGMINISPIGRNCSQEERDEFEKYDKEHHIREKFIQDLKKEFS 166

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4557839   167 GKGLTFSIGGQISFDVFPDGWDKRYCLRHVENDgYKTIYFFGDKTMPGGNDHEIFTDPRTMGYSVTAPEDTRRICELLF 245
Cdd:PTZ00174 167 DLGLKFSIGGQISFDVFPKGWDKTYCLRHLEND-FKEIHFFGDKTFEGGNDYEIYNDPRTIGHSVKNPEDTIKILKELF 244

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839   11 FDVDGTLTAPRQKITKEMDDFLQKLRQK-IKIGVVGG---SDFEKVQEQLGNDvvekyDYVFPENG-LVAYKDGKLLCRQ 85
Cdd:COG0561   7 LDLDGTLLNDDGEISPRTKEALRRLREKgIKVVIATGrplRSALPLLEELGLD-----DPLITSNGaLIYDPDGEVLYER 81

                        90
                ....*....|....
gi 4557839   86 NIQSHLGEALIQDL 99
Cdd:COG0561  82 PLDPEDVREILELL 95

phosphomannomutase, similar to human PMM1 and PMM2, Saccharomyces Sec53p, and Arabidopsis thaliana PMM; PMM catalyzes the interconversion of mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P); the conversion of M6P to M1P is an essential step in mannose activation and the biosynthesis of glycoconjugates in all eukaryotes. M1P is the substrate for the synthesis of GDP-mannose, which is an intermediate for protein glycosylation, protein sorting and secretion, and maintaining a functional endomembrane system in eukaryotic cells. Proteins in this family contains a conserved phosphorylated motif DxDx(T/V) shared with some other phosphotransferases. This family contains two human homologs, PMM1 and PMM2; PMM2 deficiency causes congenital disorder of glycosylation type I-a, also known as Jaeken syndrome. PMM1 can also act as glucose-1,6-bisphosphatase in the brain after stimulation with inosine monophosphate; PMM2 on the other hand, is insensitive to IMP and demonstrates low glucose-1,6-bisphosphatase activity. Arabidopsis thaliana PMM converted M1P into M6P and glucose-1-phosphate into glucose-6-phosphate, with the latter reaction being less efficient. Arabidopsis thaliana and Nicotiana benthamian PPMs are involved in ascorbic acid 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 4557839    8 LCLFDVDGTLTAPRQKITKEMDDFLQKLRQKIKIGVVGGSDFEKVQEQLGNDV-VEKYDYVFPENGLVAYKDGKLLCRQN 86
Cdd:cd02585   1 LLLFDVDGTLTPPRQPITPEMAEFLAELRQKVKIGVVGGSDYDKIKEQLGDNVpLLDFDYVFPENGLVAYRDGELLSRQS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839   87 IQSHLGEALIQDLINYCLSYIAKIKLPKKRGTFIEFRNGMLNVSPIGRSCSQEERIEFYELDKKENIRQKFVADLRKEFA 166
Cdd:cd02585  81 IIRALGEEKLQALINFCLRYIADLDLPKKRGTFIEFRNGMINISPIGRNCSQEERIEFEELDKKHKIREKFVSALKEEFA 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4557839  167 GKGLTFSIGGQISFDVFPDGWDKRYCLRHVENDGYKTIYFFGDKTMPGGNDHEIFTDPRTMGYSVTAPEDTRRICELL 244
Cdd:cd02585 161 DKGLTFSIGGQISFDVFPKGWDKTYCLRHLEEDLYEEIHFFGDKTQPGGNDYEIYQDPRTIGHSVTSPKDTVRILEEL 238

phosphomannomutase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839     8 LCLFDVDGTLTAPRQKITKEMDDFLQKLRQK-IKIGVVGGSDFEKVQEQLGNDVVEKYDYVFPENGLVAYKDGKLLCRQN 86
Cdd:PTZ00174   7 ILLFDVDGTLTKPRNPITQEMKDTLAKLKSKgFKIGVVGGSDYPKIKEQLGEDVLEDFDYVFSENGLVAYKDGELFHSQS 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839    87 IQSHLGEALIQDLINYCLSYIAKIKLPKKRGTFIEFRNGMLNVSPIGRSCSQEERIEFYELDKKENIRQKFVADLRKEFA 166
Cdd:PTZ00174  87 ILKFLGEEKLKKFINFCLRYIADLDIPVKRGTFIEYRNGMINISPIGRNCSQEERDEFEKYDKEHHIREKFIQDLKKEFS 166

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4557839   167 GKGLTFSIGGQISFDVFPDGWDKRYCLRHVENDgYKTIYFFGDKTMPGGNDHEIFTDPRTMGYSVTAPEDTRRICELLF 245
Cdd:PTZ00174 167 DLGLKFSIGGQISFDVFPKGWDKTYCLRHLEND-FKEIHFFGDKTFEGGNDYEIYNDPRTIGHSVKNPEDTIKILKELF 244

HAD-superfamily hydrolase, subfamily IIB; This subfamily falls within the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The Class II subfamilies are characterized by a domain that is located between the second and third conserved catalytic motifs of the superfamily domain. The IIB subfamily is distinguished from the IIA subfamily (TIGR01460) by homology and the predicted secondary structure of this domain by PSI-PRED. The IIB subfamily's Class II domain has the following predicted structure: Helix-Sheet-Sheet-(Helix or Sheet)-Helix-Sheet-(variable)-Helix-Sheet-Sheet. The IIB subfamily consists of Trehalose-6-phosphatase (TIGR00685), plant and cyanobacterial Sucrose-phosphatase and a closely related group of bacterial and archaeal sequences, eukaryotic phosphomannomutase (pfam03332), a large subfamily ("Cof-like hydrolases", TIGR00099) containing many closely related bacterial sequences, a hypothetical equivalog containing the E. coli YedP protein, as well as two small clusters containing OMNI|TC0379 and OMNI|SA2196 whose relationship to the other groups is unclear. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839     10 LFDVDGTLTAPRQ-KITKEMDDFLQKLRQK-IKIGVVGGSDFEKVQEQLGNDVVEKYdyVFPENG-LVAYKDGKLLcRQN 86
Cdd:TIGR01484   3 FFDLDGTLLDPNAhELSPETIEALERLREAgVKVVIVTGRSLAEIKELLKQLNLPLP--LIAENGaLIFYPGEILY-IEP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839     87 IQSHLG-EALIQDLINYCLSYIAKIKLpkkrGTFIEFRNGMLNVSPIGRSCSQEerIEFYELDKKENIRQKFvADLRKEF 165
Cdd:TIGR01484  80 SDVFEEiLGIKFEEIGAELKSLSEHYV----GTFIEDKAIAVAIHYVGAELGQE--LDSKMRERLEKIGRND-LELEAIY 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 4557839    166 AGKGLtfsiggqisFDVFPDGWDKRYCLRHVENDGY---KTIYFFGDktmpGGNDHEIF 221
Cdd:TIGR01484 153 SGKTD---------LEVLPAGVNKGSALQALLQELNgkkDEILAFGD----SGNDEEMF 198

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 4557839      8 LCLFDVDGTLTAPRQKITKEMDDFLQKLRQK-IKIGVVGGSDFEKVQEQLGNDVVEKYdYVFPENGLVAYKDGKLLCRQN 86
Cdd:TIGR00099   1 LIFIDLDGTLLNDDHTISPSTKEALAKLREKgIKVVLATGRPYKEVKNILKELGLDTP-FITANGAAVIDDQGEILYKKP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557839     87 IQSHLGEALIQDLINYCLSYIA----------------KIKLPKKRGTFIEFRNGMLNVSPIGRSCsqeeriefYELDKK 150
Cdd:TIGR00099  80 LDLDLVEEILNFLKKHGLDVILygddsiyaskndpeyfTIFKKFLGEPKLEVVDIQYLPDDILKIL--------LLFLDP 151

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4557839    151 ENIrQKFVADLRKEFAGKGLTFSIGGQISFDVFPDGWDKRYCLRH-VENDGY--KTIYFFGDktmpGGNDHEIF 221
Cdd:TIGR00099 152 EDL-DLLIEALNKLELEENVSVVSSGPYSIEITAKGVSKGSALQSlAEALGIslEDVIAFGD----GMNDIEML 220

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4557839    8 LCLFDVDGTLTAPrqkitkemdDFLQKLRQK-IKIGVVGGSDFEKVQEQLGNDVVEKY-DYVFPENGLVAYKD 78
Cdd:cd01427   1 AVLFDLDGTLLAV---------ELLKRLRAAgIKLAIVTNRSREALRALLEKLGLGDLfDGIIGSDGGGTPKP 64