1M63,4F0Z,1AUI,1MF8,1TCO,2JOG,2P6B,3LL8,4IL1


Conserved Protein Domain Family
MPP_PP2B

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cd07416: MPP_PP2B 
Click on image for an interactive view with Cn3D
PP2B, metallophosphatase domain
PP2B (calcineurin) is a unique serine/threonine protein phosphatase in its regulation by a second messenger (calcium and calmodulin). PP2B is involved in many biological processes including immune responses, the second messenger cAMP pathway, sodium/potassium ion transport in the nephron, cell cycle progression in lower eukaryotes, cardiac hypertrophy, and memory formation. PP2B is highly conserved from yeast to humans, but is absent from plants. PP2B is a heterodimer consisting of a catalytic subunit (CnA) and a regulatory subunit (CnB); CnB contains four Ca2+ binding motifs referred to as EF hands. The PPP (phosphoprotein phosphatase) family, to which PP2B belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP4, PP5, PP6, PP7, Bsu1, RdgC, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.
Statistics
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PSSM-Id: 277361
Aligned: 32 rows
Threshold Bit Score: 521.097
Created: 18-Oct-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:2P6B_A; Homo sapiens PP2B (calcineurin) subunit A binds a Zn2+ ion, an Fe3+ ion and a phosphate ion.
  • Citation:PMID 7543369
  • Structure:1M63_A; Homo sapiens PP2B (calcineurin) subunit A binds two divalent metal cations
  • Comment:Also inferred from the PP2A active site.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                      # #                           #
1M63_A     41 PRVDILKAHLMKEGRLEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFE--VGGSPAnTRYLFLGD 118 human
2P6B_A     44 PRVDILKAHLMKEGRLEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFE--VGGSPAnTRYLFLGD 121 human
P14747     95 PRHEFLRDHFKREGKLSAAQAARIVTLATELFSKEPNLISVPAPITVCGDIHGQYFDLLKLFE--VGGDPAtTSYLFLGD 172 Saccharomyces cere...
1279364    89 INLPKLQEHFFAEGRLNHDDVIEIVKMAAEILEKEPTLIQVEAPITVCGDTHGQFYDLIKIFEndIGGNPAnTNYLFLGD 168 Dictyostelium disc...
AAB80918   38 PDWKLLRDHLQKEGRVSKEDLYKLVGDCNKLLKNEGNVIYLQDPLTVVGDIHGQYYDLLKLLEpkVGGNPEtTKYLFLGD 117 Paramecium tetraur...
AAM97278   38 PNWQELKSHLQREGRLSKEDCLELIKNVTEITSNEPNLLRLNDPITVVGDIHGQFYDLLKLLD--VGGDPDtTQYLFLGD 115 Toxoplasma gondii
CAJ05636   31 ARPDVVREHLRKEGLLQEADALTIITQCALIWKDEPNVLRVDGPVAIAGDIHGQFFDLLNLIS--IGGDPSqQKYIFLGD 108 Leishmania major
CAI48024   45 PDTTVLQRHFKAGGVLQEADALWLIETASALFAQEPNVLRLEDPVTVCGDIHGQYYDLLTLLE--LGGDPGeTQYLFLGD 122 Trypanosoma cruzi
XP_803443  57 PLADNIKVHFGRGWRLHVEDALNIVHRCALIMKEEPNVVRLKGSAVVCGDLHGQFHDLLTLLE--VNGHPSvQQYVFLGD 134 Trypanosoma brucei...
Q7YSW8     89 INLPKLQEHFFAEGRLNHDDVIEIVKMAAEILEKEPTLIQVEAPITVCGDTHGQFYDLIKIFEndIGGNPAnTNYLFLGD 168 Dictyostelium disc...
Feature 1        #                           ##                                               
1M63_A    119 YVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNqqFLCV 198 human
2P6B_A    122 YVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNqqFLCV 201 human
P14747    173 YVDRGSFSFECLIYLYSLKLNFNDHFWLLRGNHECKHLTSYFTFKNEMLHKYNLDIYEKCCESFNNLPLAALMNgqYLCV 252 Saccharomyces cere...
1279364   169 YVDRGYFSMEVIIYLYACKINYPNTFFLLRGNHECRHLTEYFTFKEECLHKYSEEVYDFITESFNALPLAALMNgkFLCI 248 Dictyostelium disc...
AAB80918  118 FVDRGSYSIEVIILLYAIKLNYPNTVYFLRGNHECRQLTAFFNFKEECLYKYDQETYDMLMDSFDLFPLACIINskFIAI 197 Paramecium tetraur...
AAM97278  116 YVDRGSFSIEVLLLLYAIKLNHPTRVWLLRGNHECRQMTSFFNFRDECECKYDMTVYFAFMEAFDSLPLAAVINgkFLAL 195 Toxoplasma gondii
CAJ05636  109 YVDRGCFGMEVILLLMCYKICYPDTMIMLRGNHESRHLTTYFNFKREVLYKYSIAVYNAIMSAFDCLPLACILNnrFLCV 188 Leishmania major
CAI48024  123 YVDRGIFSCEVTLLLFAFKIRYPKSFWILRGNHECRHLSCCFTFRDECLRKYGEAVYDAFQLAFDRLPLAALVAaaFFCV 202 Trypanosoma cruzi
XP_803443 135 YVDRGDFSAEIVLLCMSFKLLYPRSFILLRGNHESRQLTSCFNFKQEIESKYSSMVYEEIMAAFDCFPLSCVVNdrFFCV 214 Trypanosoma brucei...
Q7YSW8    169 YVDRGYFSMEVIIYLYACKINYPNTFFLLRGNHECRHLTEYFTFKEECLHKYSEEVYDFITESFNALPLAALMNgkFLCI 248 Dictyostelium disc...
Feature 1     #                                #                                             #
1M63_A    199 HGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEdfgne------------------------ktqeHFTHNTVR 254 human
2P6B_A    202 HGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEdfgne------------------------ktqeHFTHNTVR 257 human
P14747    253 HGGISPELNSLQDINNLNRFREIPSHGLMCDLLWADPIEeydevldkdlteedivnsktmvphhgkmapsrdMFVPNSVR 332 Saccharomyces cere...
1279364   249 HGGLSPDIKTLDDIANIDRFKEPPSSGPMCDLLWSDPMEefsp-------------------------eireHFVPNDVR 303 Dictyostelium disc...
AAB80918  198 HGGISPDLKSLEDIKRLDRYHEPPRSGLLCDLLWSDPVDqdqg-------------------------nmdgQWKGNEVR 252 Paramecium tetraur...
AAM97278  196 HGGLSPELKVLSQIGGVNRFQEPPRGGLFCDLLWADPLDeskddv---------------------gqspedSFTPNDVR 254 Toxoplasma gondii
CAJ05636  189 HGGLSPELKRISDIGAIHRFREPPSSGPMCDLLWADPLDekeed-----------------------paaapLFVPNTTR 245 Leishmania major
CAI48024  203 HGGISPYIKTIREIDDIERVREPPMFGPMCDLLWSDPMEeeeeq-----------------------mcpdaLFLHNALR 259 Trypanosoma cruzi
XP_803443 215 HGGLSPLLTYLGEIDTVNRFRETPSTGPMCDLLWSDPMFgddtdc---------------------atpseeLFVFNTKR 273 Trypanosoma brucei...
Q7YSW8    249 HGGLSPDIKTLDDIANIDRFKEPPSSGPMCDLLWSDPMEefsp-------------------------eireHFVPNDVR 303 Dictyostelium disc...
Feature 1                               # #                                                   
1M63_A    255 GCSYFYSYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRksqtTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQF 334 human
2P6B_A    258 GCSYFYSYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRksqtTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQF 337 human
P14747    333 GCSYAFTYRAACHFLQETGLLSIIRAHEAQDAGYRMYKntktLGFPSLLTLFSAPNYLDTYNNKAAILKYENNVMNIRQF 412 Saccharomyces cere...
1279364   304 GCSYLYSYRAVCSFLQKNKLLSVIRAHEAQNAGYKMHLqndaTGFPSVITLFSAPNYLDAYNNKGAVLRYENNVMNIRQF 383 Dictyostelium disc...
AAB80918  253 GCSWFFGNEAASKFLQKNNLISIIRAHEAQLDGYKMHRwhggKDFPVVITIFSAPNYCDVYNNKGAVIKFENNTLNIQQF 332 Paramecium tetraur...
AAM97278  255 GCSFFFGYSAASKFLDRNGLLSVLRAHEAQLEGYKMHQtnqkTGFPTVITIFSAPNYCDVYNNKGAVLKFENNTLNIQQF 334 Toxoplasma gondii
CAJ05636  246 GCSYVYSNAAACNFLEENDLITIIRGHEAQDEGYHLYKkt-sKGFPAVICIFSAPNYCDTYDNRAAVVMLNRNIMSIRQF 324 Leishmania major
CAI48024  260 GCSFLYSSSAVEEFLTLNGLLSVIRAHEAQNEGFRFFRkvgsTGFPSVICIFSAPNYCDAYDNRASILKIERKTLRVIQF 339 Trypanosoma cruzi
XP_803443 274 GCSYNYSYEAVCRFLEANNLCTVIRGHETQPGGYKLYRht-pKGVPAVVCVFSASNYCGTYGNMAAVVAIDGDVMNIRQY 352 Trypanosoma brucei...
Q7YSW8    304 GCSYLYSYRAVCSFLQKNKLLSVIRAHEAQNAGYKMHLqndaTGFPSVITLFSAPNYLDAYNNKGAVLRYENNVMNIRQF 383 Dictyostelium disc...
Feature 1                
1M63_A    335 NCSPHPYWLPN 345 human
2P6B_A    338 NCSPHPYWLPN 348 human
P14747    413 NMTPHPYWLPD 423 Saccharomyces cerevisiae S288c
1279364   384 TCSPHPYWLPN 394 Dictyostelium discoideum
AAB80918  333 QYTPHPYLLPN 343 Paramecium tetraurelia
AAM97278  335 NFSPHPYHLPN 345 Toxoplasma gondii
CAJ05636  325 NSSPHPYYLPN 335 Leishmania major
CAI48024  340 MAAPHPYLLPN 350 Trypanosoma cruzi
XP_803443 353 MATSHDSCTPN 363 Trypanosoma brucei TREU927
Q7YSW8    384 TCSPHPYWLPN 394 Dictyostelium discoideum AX4

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