2FJU,1GYM,1AOD,1DJX,2ZKM


Conserved Protein Domain Family
PI-PLCc

?
cd00137: PI-PLCc 
Click on image for an interactive view with Cn3D
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C
This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.
Statistics
?
PSSM-Id: 176497
View PSSM: cd00137
Aligned: 5 rows
Threshold Bit Score: 325.373
Threshold Setting Gi: 2392276
Created: 1-Nov-2000
Updated: 20-Aug-2013
Structure
?
Program:
Drawing:
Aligned Rows:
 
catalytic siteactive site
Conserved site includes 2 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic site [active site]
Evidence:
  • Comment:Both prokaryotic and eukaryotic phosphatidylinositol-specific phospholipase Cs utilize a similar catalytic mechanism, a general base and acid catalysis involving two well conserved histidines. It consists of two steps, a phosphotransfer and a phosphodiesterase reaction.
  • Comment:Due to replacement of critical catalytic residues, metazoan Phospholipase C Related but Catalytically Inactive Proteins (PRIP) do not have PLC enzymatic activity.
  • Structure:1GYM; Bacillus cereus phosphatidylinositol-specific phospholipase C catalytic residues are well conserved in all bacterial PI-PLCs.
    View structure with Cn3D
  • Structure:1DJX; Rat Phosphoinositide-specific phospholipase C-Delta1 catalytic residues
    View structure with Cn3D
  • Citation:PMID 8386017
  • Citation:PMID 7664726
  • Citation:PMID 9048554

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
                      10        20        30        40        50        60        70        80
              ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     #                                                     #         
2FJU_B    311 HHDMTQPLNHYFINSSHNTYLtagqfs-------glssaEMYRQVLLSgCRCVELDCWKgkppdeePIITHGFTmttdiF 383
1GYM_A     16 PIPDSIPLARISIPGTHDSGTfklqnpik--qvwgmtqeYDFRYQMDHgARIFDIRGRLtdd--ntIVLHHGPLyl-yvT 90
1AOD_A     23 ALPDTTNLAALSIPGTHDTMSyngditwtltkplaqtqtMSLYQQLEAgIRYIDIRAKDn------LNIYHGPIfl-naS 95
1DJX_B    163 YQDMDQPLSHYLVSSSHNTYLledqlt-------gpsstEAYIRALCKgCRCLELDCWDgpn--qePIIYHGYTftskiL 233
2ZKM_X    311 HHDMTQPLNHYFINSSHNTYLtagqfs-------glssaEMYRQVLLSgCRCVELDCWKgkppdeePIITHGFTmttdiF 383
                      90       100       110       120       130       140       150       160
              ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                     
2FJU_B    384 FKEAIEAIAESAFKTsPYPIILSFENHVds-----prQQAKMAEYCRtifgdmllteplekfplkpgvplPSPEDLRGKI 458
1GYM_A     91 LHEFINEAKQFLKDNpSETIIMSLKKEYedmkgaedsFSSTFEKKYFvdpifl------------ktegnIKLGDARGKI 158
1AOD_A     96 LSGVLETITQFLKKNpKETIIMRLKDEQnsn----dsFDYRIQPLINiykdyfytt-----prtdtsnkiPTLKDVRGKI 166
1DJX_B    234 FCDVLRAIRDYAFKAsPYPVILSLENHCsl------eQQRVMARHLRailgpilldq----pldgvttslPSPEQLKGKI 303
2ZKM_X    384 FKEAIEAIAESAFKTsPYPIILSFENHVds-----prQQAKMAEYCRtifgdmllteplekfplkpgvplPSPEDLRGKI 458
                     170       180       190       200       210       220       230       240
              ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                     
2FJU_B    459 LIKNKknqfsgptssskdtggeaegssppsapavwageegteleeeeveeeeeeesgnldeeeikkmqsdegtaglevta 538
1GYM_A    159 VLLKRysgsnepggynnfyw------------------------------------------------------------ 178
1AOD_A    167 LLLSEnhtkkplvins---------------------------------------------------------------- 182
1DJX_B    304 LLKGKklggllpaggengseatdvsdeveaaemedeavrsqvqh--------------------------kpkedklklv 357
2ZKM_X    459 LIKNKknqfsgptssskdtggeaegssppsapavwageegteleeeeveeeeeeesgnldeeeikkmqsdegtaglevta 538
                     250       260       270       280       290       300       310       320
              ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                     
2FJU_B    539 yeemsslvnyiqptkfvsfefsaqknrsyVISSFTElkayd-----llskaSVQFVDYNk---rQMSRIYPKGtr----- 605
1GYM_A    179 ---------------pdnetftttvnqnaNVTVQDKykvsyde-kvksikdTMDETMNNsedlnHLYINFTSLssggtaw 242
1AOD_A    183 -------------------rkfgmqfgapNQVIQDDyngpsvktkfkeivqTAYQASKAd---nKLFLNHISAtsltftp 240
1DJX_B    358 pelsdmiiycksvhfggfsspgtsgqafyEMASFSEsralr-----llqesGNGFVRHNv---sCLSRIYPAGwr----- 424
2ZKM_X    539 yeemsslvnyiqptkfvsfefsaqknrsyVISSFTElkayd-----llskaSVQFVDYNk---rQMSRIYPKGtr----- 605
                     330       340       350       360       370
              ....*....|....*....|....*....|....*....|....*....|...
Feature 1                                                          
2FJU_B    606 -------mdSSNYMPQMFWNa------gCQMVALNFQtmdlpmqQNMAVFEFN 645
1GYM_A    243 nspyyyasyINPEIANYIKQknp---arVGWVIQDYInekwsplLYQEVIRAN 292
1AOD_A    241 ---rqyaaaLNNKVEQFVLNltsekvrgLGILIMDFPek----qTIKNIIKNN 286
1DJX_B    425 -------tdSSNYSPVEMWNg------gCQIVALNFQtpgpemdVYLGCFQDN 464
2ZKM_X    606 -------mdSSNYMPQMFWNa------gCQMVALNFQtmdlpmqQNMAVFEFN 645

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap