2FUE,3F9R,2I55,2AMY,4BND


Conserved Protein Domain Family
HAD_PMM

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cd02585: HAD_PMM 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 319784
Aligned: 22 rows
Threshold Bit Score: 274.923
Created: 25-Jun-2004
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 24 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1         #####    #                          ###   #                                 
2FUE_A     15 LCLFDVDGTLTPARqkidpEVAAFLQKLRsr---vQIGVVGGSDYCKIAEQLGdgde--viekFDYVFAENGTVQYKH-- 87  human
4BND_B      5 ILSFDIDNTLNEPKmpifpEMAELLATLSqk---yIIAPISGQKYDQFLIQIInnlpesanldNFHLFVAQGTQYYAHka 81  Lactococcus lactis...
O43976      5 MLIFDMDGTLTDPVqvinnDVKDILRRCKrk--nfEIAVVSGSKYEKIKGQLNdgf----ideFDYVFSENGTQVYVK-- 76  Babesia bovis
EAK87737   16 LFLFDLDGTLTLPRk---pIMEDMVMTLKnakskvKIGVVSGSDYSKICEQLQnne----lacSHYIFSENGVVFHDE-- 86  Cryptosporidium pa...
NP_597365   8 IFLFDVDGTLSESRakmpeKMGKMLESLRrk---vRIGFVGGSDLAKQKEQVGdni----leiFDYGFPENGVSFYKN-- 78  Encephalitozoon cu...
Q9VTZ6     12 LLLFDVDGTLTMPRsvvtpEFEEFFYSRVkp--raTIGIVGGSDLEKMFEQLNgrki---lneFDFIFPENGLVQIEG-- 84  fruit fly
BAE57269   21 ICLFDVDGTLTPARrtispEMLQLLSQLRhk---cAIGTVGGSDLAKQQEQLGtsstk-vsslFDFCFAENGLTAIRL-- 94  Aspergillus oryzae...
AAT12298    8 IFLFDVDGTLTRSRqkiepKMKETLQRLKkv---vYTAFVGGSDLQKQEEQIGddc----ldlFDFGFPENGVSFYRG-- 78  Antonospora locustae
Q54X03      8 ICLFDVDGTLTKPRnvitpEMKDFLAGLRtk---vELGVVGGSDINKIKEQLGenc----ineFHYLFAENGLLSFKD-- 78  Dictyostelium disc...
NP_266726   4 ILSFDIDNTLNEPKmpifpEMAELLATLSqk---yIIAPISGQKYDQFLIQIInnlpesanldNFHLFVAQGTQYYAH-- 78  Lactococcus lactis...
Feature 1                                                      #    #     #      #            
2FUE_A     88 GRLLSKQtiqnhLGEELLQDLINFCLSYXALLRLPk-----KRGTFIEFRNGXLNISPIGRSCTLEER-IEFSELDKKEK 161 human
4BND_B     82 GEWKQVFny--aLTDEQANAIMGALEKAAKELGHWdesvllPGDEINENRESMIAYSAIGQKAGVEAKqAWDPDMTKRNE 159 Lactococcus lactis...
O43976     77 NVLVKSLditeaIPETKLRKMVEFCLRYIADLDIPt-----KRGTFIEHRKSLINICPPGRNCSMVDR-RRFVEYDSIHH 150 Babesia bovis
EAK87737   87 GVKVSSEsiskhLGEDNIKRFVNFCLRYIADLDIPi-----KRGTFIEYRTGMLNISPIGRNCSYDER-LEFFELDKKNG 160 Cryptosporidium pa...
NP_597365  79 GTLESQEkiidvLGEEFYKEFANFVLRYLSDIDLPi-----KRGNFIEYRNSMINISPIGRNCSREER-MKFFELDKKEK 152 Encephalitozoon cu...
Q9VTZ6     85 GKEVGKQniimhLGEETVKRFINFVLRYLSELDVPi-----KRGTFIEFRNGMMNVCPIGRQCTREER-NMFAEYDIEHK 158 fruit fly
BAE57269   95 GRFLASNsfiawIGEEKYQKLANFCLKYIADLQLPk-----KRGTFVEFRNGMINVSPVGRNASVDER-IEFEAYDKQHN 168 Aspergillus oryzae...
AAT12298   79 RELVSQEsiiefMGEELHRELVEFTMRYIADLDIPv-----KRGTFLELRRSMINISPIGRNCSQDER-MMFFSLDKERG 152 Antonospora locustae
Q54X03     79 GSLLATQdikkfLGEENIKKFINFVLHYIADLDIPi-----KRGTFVEFRNGMINISPIGRNCSQQER-EEFEKYDLEHK 152 Dictyostelium disc...
NP_266726  79 KDGEWKQvfnyaLTDEQANAIMGALEKAAKELGHWdesvlaPGDEINENRESMIAYSAIGQKAGVEAKqAWDPDMTKRNE 158 Lactococcus lactis...
Feature 1                              #### #       #                        ##      ##       
2FUE_A    162 IReKFVEALktef--agkgLRFSRGGXISFDVFPeGWDKRYCLDSLDqds------fdtIHFFGNEtspGGNDFEIFADp 233 human
4BND_B    160 IA-KLASQYap-------eFEFEVAGTTTINGFVpGQNKEFGMNHLMeelnv---tkeeILYFGDMtqpGGNDYPVVQM- 227 Lactococcus lactis...
O43976    151 VRqKLIQVLksqfdsddcpLSFVAGGQISIDVYPkAWSKSIALSHIGkc--------dvIHFFGDNtreGGNDFEIYNHp 222 Babesia bovis
EAK87737  161 IReKFIQDLskef--sdldLQYSIGGQISIDVFPqGWDKRYCLRHVEnkf-------deIHFFGDKtypGGNDHEIYNDk 231 Cryptosporidium pa...
NP_597365 153 FReKMVTAMrdrf--kdscLVFSIGGQISIDCFPkGWDKTYCLRHIKkeg------venVYFFGDMtmeGGNDYEIYNHk 224 Encephalitozoon cu...
Q9VTZ6    159 VReKMIKDLkqef--advdLTYSIGGQISFDVFPhGWDKTYCLRHIEahyk-----fkeIHFFGDKtepGGNDYEIYSDp 231 fruit fly
BAE57269  169 IRkSFVEALktef--pdynLSYSIGGQISFDVFPaGWDKTYCLRHIEaekdisgikyktIHFFGDKsfpGGNDYEIYTDs 246 Aspergillus oryzae...
AAT12298  153 IRkEMVRELerrf--gergMHFCIGGQISIDCFPkGWDKTYCLRHLRdf--------ntIVFFGDKtekGGNDYEILTDe 222 Antonospora locustae
Q54X03    153 IRpTMVSILkekf--qslgLQYSIGGQISFDVFPiGWDKTYCLRHLPedk------yktIYFFGDKtfvGGNDYEIANDp 224 Dictyostelium disc...
NP_266726 159 IA-KLASQYap-------eFEFEVAGTTTINGFVpGQNKEFGMNHLMeelnv---tkeeILYFGDMtqpGGNDYPVVQMg 227 Lactococcus lactis...
Feature 1                          
2FUE_A    234 -RTVGHSVvsPQDTVQRCREI 253 human
4BND_B    228 -GIETITVrdWKETAAILKAI 247 Lactococcus lactis subsp. cremoris MG1363
O43976    223 -DVIGHTVtgYKDLVNQLEEL 242 Babesia bovis
EAK87737  232 -RVIGHNVinPNDTIQQLSRL 251 Cryptosporidium parvum Iowa II
NP_597365 225 -DVHGISVgnPDDTYRKVDQA 244 Encephalitozoon cuniculi GB-M1
Q9VTZ6    232 -RTISHRVytPKDTQRILTEI 251 fruit fly
BAE57269  247 -RTIGHAVkdPDDTMKQLKEI 266 Aspergillus oryzae RIB40
AAT12298  223 -RTVSVSVscPEDTIQKIDEM 242 Antonospora locustae
Q54X03    225 rITKSFTVtsPTDTKNFLSEL 245 Dictyostelium discoideum
NP_266726 228 iETITVRD--WKETAAILKAI 246 Lactococcus lactis subsp. lactis Il1403

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