Conserved Protein Domain Family
cPLA2_Grp-IVB-IVD-IVE-IVF

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cd07201: cPLA2_Grp-IVB-IVD-IVE-IVF 
Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent
Group IVB, IVD, IVE, and IVF cPLA2 consists of two domains: the regulatory C2 domain and alpha/beta hydrolase PLA2 domain. Group IVB, IVD, IVE, and IVF cPLA2 are also referred to as cPLA2-beta, -delta, -epsilon, and -zeta respectively. cPLA2-beta is approximately 30% identical to cPLA2-alpha and it shows low enzymatic activity compared to cPLA2alpha. cPLA2-beta hydrolyzes palmitic acid from 1-[14C]palmitoyl-2-arachidonoyl-PC and arachidonic acid from 1-palmitoyl-2[14C]arachidonoyl-PC, but not from 1-O-alkyl-2[3H]arachidonoyl-PC. cPLA2-delta, -epsilon, and -zeta are approximately 45-50% identical to cPLA2-beta and 31-37% identical to cPLA2-alpha. It's possible that cPLA2-beta, -delta, -epsilon, and -zeta may have arisen by gene duplication from an ancestral gene. The catalytic domain of cytosolic phospholipase A2 (PLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms. Movement of the cPLA2 lid possibly exposes a greater hydrophobic surface and the active site. cPLA2 belongs to the alpha-beta hydrolase family which is identified by a characteristic nucleophile elbow with a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). Calcium is required for cPLA2 to bind with membranes or phospholipids. The calcium-dependent phospholipid binding domain resides in the N-terminal region of cPLA2; it is homologous to the C2 domain superfamily which is not included in this hierarchy. It includes PLA2G4B, PLA2G4D, PLA2G4E, and PLA2G4F from humans.
Statistics
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PSSM-Id: 132840
View PSSM: cd07201
Aligned: 11 rows
Threshold Bit Score: 916.726
Threshold Setting Gi: 189530897
Created: 9-Feb-2009
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
Feature 1:active site [active site]
Evidence:
  • Comment:Based on Human Cytosolic Phospholipase A2 structure (1CJY)
  • Comment:catalytic mechanism proceeds through a serine-acyl intermediate using Ser-228 as the nucleophilic residue.
  • Comment:catalytic dyad is formed by Ser and Asp
  • Comment:an oxyanion hole is formed by two Gly residues that polarizes the sn-2 ester
  • Comment:Arg may play a role in substrate stabilization in the cleft

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                     ## #               
gi 74750540  269 LKAEGCPEELAVHLGFNLCAEEQAFLSRRKQVVAKALKQALQLDRDLQEDEVPVVGIMATGGGARAMTSLYGHLLALQKL 348
gi 205829268 243 LKKEAGLRELAVRLGFGPCAEEQAFLSRRKQVVAAALRQALQLDGDLQEDEIPVVAIMATGGGIRAMTSLYGQLAGLKEL 322
gi 118091654 301 LKAEESTWDLDVRLGFDLCKGEREFVDKRKKRVSEALKKILNLKQLPQRDEVPVVAVLGSGGGMRALTSFYGSLAGLQQL 380
gi 118091648 265 AKANEWPRNLDARLGFGLCMDEQNFLQNRRKVVAAALKDVLHLEEDLQDHEVPIVAVTTAGCGIRALTGMYGSMLGLQKL 344
gi 110815894 290 GESLGSPETLDVRLGFSLCPAELEFLQKRKVVVAKALKQVLQLEEDLQEDEVPLIAIMATGGGTRSMTSMYGHLLGLQKL 369
gi 118091640 261 LKTKQCQEDLDVRLGFDLCEQEKDFICKRKKVVAAALKDILQLEEDLEDDEVPVVAIMTTGGGTRALTAMYAHLLSVQEL 340
gi 118091650 294 LTSRKCSGDLDVRLGYSLCREEQDFLRKRKKYVAAALKKILNLEEDLKEHEVPVVAITTTGGGTRSLTAMYGSLLGLQKL 373
gi 110815895 303 MKVEMSSGDLDLRLGFDLSDGEQEFLDRRKQVVSKALQQVLGLSEALDSGQVPVVAVLGSGGGTRAMSSLYGSLAGLQEL 382
gi 118091652 313 VKEEDGSKNLDLRLGFDLCAEEKDFICKRKKVVAAALKNVLQLDEDLQEDEVPVVAVMTTAGGVRSMTSMFGSLLALQEL 392
gi 118091646 280 VKSVDWSRNLDVRLEFDLCMEEKNFLQKRRKLVASALKKALNLEQDLQDHEVPVVAVMTTGGGTRALTSLLGNLLGLQKL 359
gi 189530897 238 KTDDRSDEEMDVRLDFDIPEEEKRFLAKRRKVVSQALQKALNLSSAPDPSKVPLVAVVCSGGGSRALTSTYGSLKGLQNI 317
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    #                                                                   
gi 74750540  349 GLLDCVTYFSGISGSTWTMAHLYGDPEWSQRDLEGPIRYAREHLAKSKLe-VFSPERLASYRRELELRAEQGHPTTFVDL 427
gi 205829268 323 GLLDCVSYITGASGSTWALANLYEDPEWSQKDLAGPTELLKTQVTKNKLg-VLAPSQLQRYRQELAERARLGYPSCFTNL 401
gi 118091654 381 GLLDAAMYLSGISGSTWCLSTLYQDPNWSQKDLRDAINRAQRAVSSSKGg-AFSPERLKYYFQELSAMESSGRKVSFTDL 459
gi 118091648 345 RVLDCVSYISGSSGTTWTMTKLYEDAEWSHKDIGEIIIEARKQAAKCKMg-AFCLRSLRNYYKELSQRTQAGHKTSFIDL 423
gi 110815894 370 NLLDCASYITGLSGATWTMATLYRDPDWSSKNLEPAIFEARRHVVKDKLp-SLFPDQLRKFQEELRQRSQEGYRVTFTDF 448
gi 118091640 341 NVLDCVSYVTGLSGTTWTMANLYEDPDWSQKNLKKALDDIRRHVLKNKFvaCFAPDRLKYYLKELCQRKQEGHQISFTDL 420
gi 118091650 374 NLLDCISYIGGLSGTTWTMANLYEDAGWSEKYLEEAIKEARKQVTKNKIc-CFSLDCLKYYYNDLMERVKEGRNTSFIDL 452
gi 110815895 383 GLLDTVTYLSGVSGSTWCISTLYRDPAWSQVALQGPIERAQVHVCSSKMg-ALSTERLQYYTQELGVRERSGHSVSLIDL 461
gi 118091652 393 GVLDCISYISGLSATTWTMAKLYEDANWSQKDLRGPIDDIRKYVIKSKLh-CFSTDHLKYYEKELCERKLEGHKLSFTDL 471
gi 118091646 360 GLLDAISYITGSSGSTWTLAHLYQSPDWSHKDISGQIREVRRHMTKSKLs-CFSLESLKYYDRELKLRKQEGYQISSIDF 438
gi 189530897 318 QILDTVSYITGVSGATWALASIYEEPNWSKGDIDKTMESVKKELSKTIFs-LFSSEQLQRYKEKIDEREKQGHIVSLIDM 396
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 74750540  428 WALVLESMLHGQVMDQKLSGQRAALerGQNPLPLYLSLNVKenNLETLDFKEWVEFSPYEVGFLKYGAFVPPELFGSEFF 507
gi 205829268 402 WALINEALLHDEPHDHKLSDQREALshGQNPLPIYCALNTKgqSLTTFEFGEWCEFSPYEVGFPKYGAFIPSELFGSEFF 481
gi 118091654 460 WGLIVEYFLQQKVDPSKLSDQQEAVkwAQNPYPIYAAVNVRp-NISSGDFAEWCEFTPYEVGFRKYGAFVRTEDFDSEFF 538
gi 118091648 424 WGLMIESMLNDGKCYHRLSDQRRAVnhGQNPLPIYLALNVKd-KVTTKDFREWVEFTPYEVGFLKYGAFIRAEDFGSEFF 502
gi 110815894 449 WGLLIETCLGDERNECKLSDQRAALscGQNPLPIYLTINVKd-DVSNQDFREWFEFSPYEVGLQKYGAFIPSELFGSEFF 527
gi 118091640 421 WGLIIESMFRDKEDSQKLTDQQQALnrGQNPLPIYLSLNVKd-KISDQDFREWVEFTPYEVGFLKYSAYISAEDFGSEFF 499
gi 118091650 453 WGLVIESMLHDKKDEHRLSDQRQAVdnGQNPLPIYVAINLKs-NYSAQAFREWLEFTPYEVSLLKYGASIRVEHFGSEFF 531
gi 110815895 462 WGLLVEYLLYQEENPAKLSDQQEAVrqGQNPYPIYTSVNVRt-NLSGEDFAEWCEFTPYEVGFPKYGAYVPTELFGSELF 540
gi 118091652 472 WGLFIDSMLHNEENTHKLSDQQLAVnqGQNPLPIYLSLNVRd-KFSTLDFKEWVEFTPYEVGALKYGAFVRSEDFGSEFF 550
gi 118091646 439 WGLLLERALSDGKNNHKLSDERWALtqGQNPLPIYMILNIKd-DYSLSEFKEWVEFTPYEVGFLKYGAFIRAEDFGSKFF 517
gi 189530897 397 WGLALEYLFRGKKHMGTLSELQRTVseGQNPLPIFTSVNIKngRTESIEDAEWCEFTPYEVGFPKYGAFIPAQNFGSEYY 476
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 74750540  508 MGRLMRRIPEPRICFLEAIWSNIFSLNLLDAWydltssgeswkqHIKDKTRSLEKEPlttsgtssrleas---wlqpgta 584
gi 205829268 482 MGQLMKRLPESRICFLEGIWSNLYAANLQDSLywasepsqfwdrWVRNQANLDKEQVpllkieepps---------tagr 552
gi 118091654 539 MGRLIQKRPEPRICFLQGMWGSAFAASLDDIClkvvgvglsfldPFKDVIKVIDDCRrfhfrdptrlktr---livpggp 615
gi 118091648 503 MGRLMKKLPESRICFMQGMWSSIFSKNLLDAWhaadnsedfwhrWTQDKVTEIEEQPdlpekpyematcm----ftptsg 578
gi 110815894 528 MGRLVKRIPESRICYMLGLWSSIFSLNLLDAWnlshtseeffhrWTREKVQDIEDEPilpeipkcdanilettvvipgsw 607
gi 118091640 500 MGRLMKKIPESRICFLEGIWSSVFSLNLLDAWyisvhsedfwhkWTRDKITDIDDETlfpkrpneletrv----vcptds 575
gi 118091650 532 MGRLVKKLPETRICYMQGMWSSIFSIDVMYVWnlaadsedfwfrWTRDRVKDIEEEPflsmnpyevdtcl----ltpsst 607
gi 110815895 541 MGRLLQLQPEPRICYLQGMWGSAFATSLDEIFlktagsglsfleWYRGSVNITDDCQkpqlhnpsrlrtr---lltpqgp 617
gi 118091652 551 MGHLMKKIPESRICFLEGTWSNIFSQSFMDVVylsghsedfwhrWTRGTEHDIEEHPalptrpheqttcl----slpkgy 626
gi 118091646 518 MGRLMKKLPESRICFMKGLWSNVFSYNLLDAWhssdpsdrcslrCTQPTAVDVEGDEpsppvrnnelety---ivtpecg 594
gi 189530897 477 LGHMIKKLPETALSILVGMWSSIFSVNLTNIWsiatg---aapsWTPQVEGGKSNTEtskptaltthli------npvtd 547
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                       #                
gi 74750540  585 laqafkGFLTGRPLHQRSPNFLQGLQLHQDYCShkdfstwa-dyqldsmPSQLTPKEPRLCLVDAAYFINT-SSPSMfRP 662
gi 205829268 553 iaefftDLLTWRPLAQATHNFLRGLHFHKDYFQhphfstwk-attldglPNQLTPSEPHLCLLDVGYLINTsCLPLL-QP 630
gi 118091654 616 llqifqDFFKSRVTCGETFNFMHGLYLHKDYVKikefvvwr-gthldafPNQLSPMEENLYLVDGGFSINS-PFPLVlQP 693
gi 118091648 579 lsttlrDILTDRPAVSKYHNFLRGFQMHNEYIQheqfakwk-dtlldtsPNDLRGHSEHLELVDAAFFFETsCPPLM-RP 656
gi 110815894 608 lsnsfrEILTHRSFVSEFHNFLSGLQLHTNYLQngqfsrwk-dtvldgfPNQLTESANHLCLLDTAFFVNSsYPPLL-RP 685
gi 118091640 576 fsdifrDVVTLRPAASEIRNFLKGLQMNNNYLEsefskwk--dceldsqPNHLTGAADYLILIDTAFVFATsYPPLM-RP 652
gi 118091650 608 fssvlrDVLTGRPTIAQYPNFIRGLQMHSKYLEsdgfstwkdtvidcfpNKLMETANDELSLVDTGFFINTsYPPLL-RS 686
gi 110815895 618 fsqavlDIFTSRFTSAQSFNFTRGLCLHKDYVAgrefvawk-dthpdafPNQLTPMRDCLYLVDGGFAINS-PFPLAlLP 695
gi 118091652 627 lsnalrEMMTGRPVVSYYHNFIKGLQLHNKYLEnesfcmwk-dtvldssPNQLNAMGDYLKLVDTAFFINTsCPPFL-RP 704
gi 118091646 595 imgivrEVLTERVMVSKFFNFLKGFQMHNEYLQsksfciwk-dtvlenfPNQLTETAEFLCLADTAGYIDIsYPPLM-RP 672
gi 189530897 548 fakmlcGFMTSRPIVSQMFNFLRGFNLHRNYQEntgfiawk-ekhpdafPNTMTPSDPVLSLVDAGFALNAgFPPIV-RS 625
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 74750540  663 GRRLDLILSFDYSl-SAPFEALQQTELYCRARGLPFPRVEPSpQDQHQPRECHLFSDPacPEAPILLHFPLVNASFKDHS 741
gi 205829268 631 TRDVDLILSLDYNl-HGAFQQLQLLGRFCQEQGIPFPPISPSpEEQLQPRECHTFSDPtcPGAPAVLHFPLVSDSFREYS 709
gi 118091654 694 ERDVDVILSFNFSw-EAPFEVLELTQQYCEEREIPFPKIEVSeEDEKKPKECYVFLDDdnPKAPIVLHFPLVNDTFQKYK 772
gi 118091648 657 ERKVDVIIHLNYTg-GSQTLPLKQACSYFSEQGIPFPKFGLK-DDEKNLKECYMFNGAdnPGAPLLLYFPLVNDTFQRYV 734
gi 110815894 686 ERKADLIIHLNYCa-GSQTKPLKQTCEYCTVQNIPFPKYELP-DENENLKECYLMENPqePDAPIVTFFPLINDTFRKYK 763
gi 118091640 653 ERKVDVILHFNYSs-GSQTRPLKEASNYFAKQGIPFPKEVPDdQETPQLKECYIVGEKesPETPIVIFFPLVNDTFREYK 731
gi 118091650 687 KREVDVILHLNYSg-GSQTLPLDQIAKYISGQGIPFPKIEISdEDRENLKECYVFEDAdsPQVPTVLFFPLVNDTFKNYK 765
gi 110815895 696 QRAVDLILSFDYSl-EAPFEVLKMTEKYCLDRGIPFPSIEVGpEDVEEARECYLFAKAedPRSPIVLHFPLVNRTFRTHL 774
gi 118091652 705 ERKVDVILHLNYSg-GSQTLPLDLFSEYCLEQGIPFPCTELScEDREHLKECYVFEDN--LEAPILVYFPLVCDTFQRYK 781
gi 118091646 673 ERKVDVVLHLNYSs-GSQTSPLEEASKYFSKQGIPFPKIRLSeEEKKNLKECYIFEDAetPEAPTVVFFPLVNDTFRKYK 751
gi 189530897 626 HRNVDVILSINYSweLDQFKVVKQAQEYCTDRKIPFPKIDFKkLESEPLREVYVFEDKnnPDAPIVLHFPLVNVSFKQFK 705
                        490       500       510       520       530       540       550
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
Feature 1                                                                                 
gi 74750540  742 APGVQRSPAELQGgqvdl---tgatCPYTLSNMTYKEEDFERLLRLSDYNVQTSQGAILQALRTALKHRTLEA 811
gi 205829268 710 APGVRRTPEEAAAgevnl---sssdSPYHYTKVTYSQEDVDKLLHLTHYNVCNNQEQLLEALRQAVQRRRQRR 779
gi 118091654 773 GPGVKRESEDEKSfgdfv--ietkdSPYRTLNFTFEPYDFSRLVEVNRYNVLNSSDTLLKTLNLALQRRKLKN 843
gi 118091648 735 APGMSRSAAEMEQgkvdl---ssfsSPYSTREVSLKAEDFNKLQKLTTYNIMNNENVILQALRMAVARKKQAL 804
gi 110815894 764 APGVERSPEELEQgqvdi---ygpkTPYATKELTYTEATFDKLVKLSEYNILNNKDTLLQALRLAVEKKKRLK 833
gi 118091640 732 APGVRRSPSEMAEgdvdv---anscGPYYINNLSYSEEDFDKLVNLSYYNVQNNKDLILQALRAAVERKKQQK 801
gi 118091650 766 APGVERSPEELAEgkvdv---csilSPFTTREVCFSEENFDKLVKLTDYNVLNNEKLIIQALRMAVARRKQRN 835
gi 110815895 775 APGVERQTAEEKAfgdfv--inrpdTPYGMMNFTYEPQDFYRLVALSRYNVLNNVETLKCALQLALDRHQARE 845
gi 118091652 782 APNVERSPAEMEKgrvdv---sncfAPYGTGQLTYTEGNFNKLLNLCNYNILNNKRLILQALKTAVERKKRFK 851
gi 118091646 752 EPGVERSSAEMAQgnvdv---sglfSPYCINSFTYTEEQFDNLVKLTSYNIQNNKHLILQALNSAIEQKRQHK 821
gi 189530897 706 APGVKREGEKELKegavdvdfnsntSPYATHKLTYTPEDFQRLINLTSYNIQNNKDVILNALNKALNRNRDKR 778

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