1CJY


Conserved Protein Domain Family
cPLA2_Grp-IVA

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cd07200: cPLA2_Grp-IVA 
Click on image for an interactive view with Cn3D
Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent
Group IVA cPLA2, an 85 kDa protein, consists of two domains: the regulatory C2 domain and the alpha/beta hydrolase PLA2 domain. Group IVA cPLA2 is also referred to as cPLA2-alpha. The catalytic domain of cytosolic phospholipase A2 (cPLA2; 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. A 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. Includes PLA2G4A from chicken, human, and frog.
Statistics
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PSSM-Id: 132839
View PSSM: cd07200
Aligned: 9 rows
Threshold Bit Score: 721.927
Threshold Setting Gi: 198435444
Created: 10-Feb-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 5 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • 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
  • Comment:the flexible lid (residues Arg413 to Gln457 in CJY_A) caps the catalytic pocket

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                               ## #                     
1CJY_A       144 LRFSMA-LCDQEKTFRQQRKEHIRESMKKLLGPKNSEgl-hSARDVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCA 221 human
P49147       144 LRFSMA-LCDEEKKFRQQRKDNIMQSMKSFLGEENSKnl-tTSRDVPVIAVLGSGGGFRAMVGFAGVMKALYESGVLDCA 221 chicken
1709550      138 LRFSMT-LCDQEKLFMQTRRDRVMLSIKKLLKMENPRflpsSPREVPTIAILGSGGGFRAMVGFSGVMKALYESGVFDCA 216 zebrafish
Q7T0T9       144 LRFSMA-LCDQEKLFRQKRKNKVINGLRKLLGPEKTQdlnsTSRDVPVIAVLGSGGGFRAMIGFSGVMKALYESGVLDCA 222 African clawed ...
XP_002127884 228 IRSSLA-LCKEEKEFRSARKRRAFSAMRNMMTAGGPR----SLRETPTIAILGSGGGFRAMTGMSGAVKALNDSGILNCA 302 Ciona intestinalis
XP_002129582 160 FRLGHE-LHNGERIFRKKRFPKVFKALNKILGEDGPK----NLLETPVVALASSGGGYRAAVGLCGAMEAFKDIGVLDTF 234 Ciona intestinalis
XP_002124513 139 SRLLSFgLHEKEKEFRRRRLMNVREALQKILQLEPDVv--tSPDDTPVISLVGSGGGYRAIIGMCGAMEAFRDAGISDAF 216 Ciona intestinalis
XP_002239734 118 LRYSLA-LCDEEKNFMVARKKRVGYAIRDLVGEERGPr---HYKEVPRVAVLGSGGGFRAMIGMAGAVKALSDSGVLDCA 193 Florida lancelet
CAB42689     144 LRFSMA-LCDQEKTFRQQRKEHIRESMKKLLGPKNSEgl-hSARDVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCA 221 human
Feature 1              #                                                                         
1CJY_A       222 TYVAGLSGSTWYMSTLYSHPDFpekGPEEINEELMKNVSHNPLl-LLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIG 300 human
P49147       222 TYIAGLSGSTWYMSTLYSHPDFpekGPKEINQELMNSVSHNPLl-LLTPQKVKRYIEALWNKKSSGQPVTFTDIFGMLIG 300 chicken
1709550      217 TYVAGLSGSTWYMSMLYSHPEFpakGPGDINKELMNRVSNNPLk-LLLPQNINRYVKALWKKKSAGQPVTFTDIFGMLIG 295 zebrafish
Q7T0T9       223 TYVAGLSGSTWYMSTLYSHPDFptkGPKEINKELMHNVSYNPLl-LLTPQKVKRYVEALWKKKSSGQPVTFTDIFAMLIG 301 African clawed ...
XP_002127884 303 TYICGLSGSSWYLSVLFAHGDFpsvGTSEVNAEIRRHIASSPFw-LLRPECLMRYSHRLHTKMKAGQPVTFTDFFGLLIG 381 Ciona intestinalis
XP_002129582 235 MYTAGVSGSAWYFTTAYQQHRMtpkEITQFVKSLKQNVIQKWVsvALQVVLREGYFNFVEEKQQYGQPTSFVDFFGYLIG 314 Ciona intestinalis
XP_002124513 217 TYVSGISGSAWYLYTAYALSGMhdsEIDRVHKSLRRSMKKSLYryFFNLPHLAKHTKLSLEKVKHGLPATFVDFFGFSVG 296 Ciona intestinalis
XP_002239734 194 TYLVGLSGSSWYISTLYSHKDWpkaPPGDLQEELKHHVDSSLFy-LLKPHLLYRYTDAIMRKRNLGQPVSFTDFFGHLVG 272 Florida lancelet
CAB42689     222 TYVAGLSGSTWYMSTLYSHPDFpekGPEEINEELMKNVSHNPLl-LLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIG 300 human
Feature 1                                                                                        
1CJY_A       301 ETLIH--NRMNTTLSSLKEKVNTAQCPLPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVV 378 human
P49147       301 ETLIH--NRMDTTLSDMKEKVSEAQCALPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYGTFMSPDLFGSKFFMGTVV 378 chicken
1709550      296 ETLIP--GRMNIKLSSLKGKINEGQSPLPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYGTFMSPGLFGSKFFMGSVV 373 zebrafish
Q7T0T9       302 ETLIK--DRMNRKLSHMQEKINDGQCPLPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYGTFMPPGLFGSKFFMGTVI 379 African clawed ...
XP_002127884 382 QTLLGpeRMETAKLTDFQEKVRDGKAPLPILTCLHVRPDISAMTFHDWVEFSPYEIGMAKYGTFMKSKYFGSKFYMGVLA 461 Ciona intestinalis
XP_002129582 315 TSLLGk-EDRWKKLSTIQSYLTSADVPFPLIEMLHVKNRALASTFHVYIECSPYEYNLPVFGYGIPVDQFGSVFNGGFLA 393 Ciona intestinalis
XP_002124513 297 QQLLK--EKVDSLVSELVPYVEDGKVPYPIFVSMHVKSDTPTSQYNAYMEITPHEVAFPEFGMGFSPDTCGSVWNGGFLA 374 Ciona intestinalis
XP_002239734 273 ETLIK--DRLDFKLSDMQQKIQDGQAPMPLLTCVHVRHDVAALVFHEWVEFTPYEVGMAKYGTFMRTELFGSKFYMGCLA 350 Florida lancelet
CAB42689     301 ETLIH--NRMNTTLSSLKEKVNTAQCPLPLFTCLHVKPDVSELMFADWVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVV 378 human
Feature 1                                                                                        
1CJY_A       379 KKYEENPLHFLMGVWGSAFSILFNRVLGvsgsqsrgstmeeelenittkhivsndssdsddesh---------------- 442 human
P49147       379 KKYSENPLHFLMGVWGSAFSILFNRVLGvsnsqnkgptmeeelenirlkhlvsndssdsedesq---------------- 442 chicken
1709550      374 KQYEENPLHFLMGVWGSAFSILFNRVLGvkettssstmeeeleqikpehivgddsadneeetq----------------- 436 zebrafish
Q7T0T9       380 KKYEENPLHFFMGVWGSAFSILINRVLGvsnnskgstmeeeienlkpkhilgndssdsddemqe---------------- 443 African clawed ...
XP_002127884 462 KEYEEYPLHFLMGVWGSAFSILFNRLVEksqglkrnspglnqeedmrtilgnkidqsfkretgsnkgdissdsddsdded 541 Ciona intestinalis
XP_002129582 394 RRCPELPLHFLQGTVGSAFSVIFNAFATgetslefnkyidhlrvkgksksktgttngtnknkekleiesdseids----- 468 Ciona intestinalis
XP_002124513 375 RKCPELPLHFHMGCTGNAFGIILKNYIDdggeesasfvdfienlksratnlvrrlskkifdaagser------------- 441 Ciona intestinalis
XP_002239734 351 KRFPEAPLHFLMGIWGSAFTILFNRLMMekksepedlqkelgafclskstyydktlhippeetl---------------- 414 Florida lancelet
CAB42689     379 KKYEENPLHFLMGVWGSAFSILFNRVLGvsgsqsrgstmeeelenittkhivsndssdsddesh---------------- 442 human
Feature 1                                                                                        
1CJY_A       443 ----------------------------epkgtenedagsdyqsdnqaswihrmimalvsdsalFNTREGRAGKVHNFML 494 human
P49147       443 ----------------------------hpkgtenseaneeyqnssqeswvqrmlmalvgdsalFNTREGRAGKVHNFML 494 chicken
1709550      437 -----------------------------rggtesadaederqrhaqaswvqrmltsimgdttlFTTREGRAGKVHNFML 487 zebrafish
Q7T0T9       444 -----------------------------pkgtenakaeeeylrnnqaswvqrmlmailgdsaiFNTREGRAGKVHNFML 494 African clawed ...
XP_002127884 542 kywdaaeeenmkkqeqktdkrpsiwgslfgggsapppsneeekekpkkggffntiiggmfgtnfMESREYRAGKILNYMR 621 Ciona intestinalis
XP_002129582 469 -----------------ddeeendrdpvtsqgngdqengensereksflstilaslkdtelfqsRVSFLGRTAKYFNFSR 531 Ciona intestinalis
XP_002124513 442 -------------------------rfeesvnerlindrgndqgkqgietilvnklrhksffydRTSFIGRVGKIFNFAY 496 Ciona intestinalis
XP_002239734 415 -----------------------------ardaqrekaekkklertnsfldddsesdddevrygRELVVNISGLVVNVFS 465 Florida lancelet
CAB42689     443 ----------------------------epkgtenedagsdyqsdnqaswihrmimalvsdsalFNTREGRAGKVHNFML 494 human
Feature 1                                                              #                         
1CJY_A       495 GLNlntsyplsplsdfatqdsfdddeldaavadpdefeRIYEPLDVKSKKIHVVDSGLTFN-LPYPLIl----RPQRGVD 569 human
P49147       495 GLNlnscyplspladlltqesveedeldaavadpdefeRIYEPLDVKSKKIHIVDSGLTFN-LPYPLIl----RPQRGVD 569 chicken
1709550      488 GLNlnstlpfspfsgithqt--sleeevdavtdpdefeRIYEPLDVKSKKIHVVDSGLTFN-LPYPLIl----RCQRGVD 560 zebrafish
Q7T0T9       495 GLNlntsypysplsglctqqsmeedeldaavadpdefeQIYEPLDVKSKKIHIVDSGLTFN-LPYPLIl----RPQRGVD 569 African clawed ...
XP_002127884 622 GIVisrtypispfspls-------avpevtiaeanefgKIHEPMEVKKKKVHLVDAGLTFN-SPYPCIl----RPQRAVD 689 Ciona intestinalis
XP_002129582 532 GFKdittyymnplgepay------qgpeqkqlaarlgiRERKKMSTKRDIISVVDAGVLNN-VPTDVIl----RPQRAVD 600 Ciona intestinalis
XP_002124513 497 NFNsikstmlnplaa------------pseeeettttaAGLDPISTSETTISLCDAGILKNvCTEPVI-----RPQRFSD 559 Ciona intestinalis
XP_002239734 466 SRSsrelellls------------------ekwaringVPFPPIDTSVFVHVYVYSRNCCC-LCLCLLqelllFMFMLLQ 526 Florida lancelet
CAB42689     495 GLNlntsyplsplsdfatqdsfdddeldaavadpdefeRIYEPLDVKSKKIHVVDSGLTFN-LPYPLIl----RPQRGVD 569 human
Feature 1                                                                                        
1CJY_A       570 LIISFDFSARPSDSSPPFKELLLAEKWAKMNKLPFPKIDpyVFDREGLKECYVFKPKnpdmEKDCPTIIHFVLANINFRK 649 human
P49147       570 LIISFDFSARPSDSSPPFKEILLAEKWAKMNKLPFPKIDpnVFDREGLKECYVFKPKdtssEKDCPTIIHFVLANINFRK 649 chicken
1709550      561 LIISFDFSARPSDSSPPFKELLLAEKWARMNKLPFPKIDskVFDREGLKECYVFKPAk--gDKNCPTIIHFVLANINFRN 638 zebrafish
Q7T0T9       570 LIISFDFSARPSDSSPPFKELLLAEKWARMNKLPFPKIDphVFDREGLKECYIFKPKntsvEKDCPTVIHFVLANLQFRN 649 African clawed ...
XP_002127884 690 LIISFDFSGRPSEVCEPFKEILLAEKWARMHHLPFPKIDrtVYDREGMKECYIFQDHs---DDRAPVIMHFVLCNIMFRK 766 Ciona intestinalis
XP_002129582 601 VLIVTDFTASPSDEKLDFTQILIAAVQAWQNGMKFPPISfdKIANLPPQEYIVLEDEn---DDECPIVVWITLCNKKFQN 677 Ciona intestinalis
XP_002124513 560 LVLVIDCSSNDSDSSFDYMSLLQSAEHAKAQGIKFPPIDfkKIANSPPKEFQVFESN----EDDCPTVLWFTLCNKGFRN 635 Ciona intestinalis
XP_002239734 527 ELLLFMFMFTPGAAVVYVYELLLAEKWARINGVPFPPIDtsVFDREGMKECYVFKHPt---DEKCPIVIHFVLVNIEFRK 603 Florida lancelet
CAB42689     570 LIISFDFSARPSDSSPPFKELLLAEKWAKMNKLPFPKIDpyVFDREGLKECYVFKPKnpdmEKDCPTIIHFVLANINFRK 649 human
Feature 1                                                                                        
1CJY_A       650 YKAPGVPREteeekei--adfdifdDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRRQNPSRCS 727 human
P49147       650 YKAPGLPREskeekdf--adfdifdDPNTPFSTFNFQYPNEAFKRLHDLMEFNTLNNLDVIKQAMMESIEYRKENPSRCS 727 chicken
1709550      639 FKAPGVPRDsdkdief--gdfdifdEPASPYSTFNFKYNNQAFKRLHDLMEFNTLNNIEVIKEAIKDSILLRRENPARCS 716 zebrafish
Q7T0T9       650 FKAPGVPREtteekes--adfdifdDPETPFSTFNFQYPNVAFKQLHDLMEFNTLNNINVIKQAMVESIEYRRQHPSRCS 727 African clawed ...
XP_002127884 767 YSKPGVKREagdtrg-----dfniyDPKSPYSTFNFQYPNEAFDRLHELMEFNTLLHIEDIKDQIRHCISLRRHSQSRCS 841 Ciona intestinalis
XP_002129582 678 LKNFKPRYStedvpegqkfndfnvfTKETAFSTFDFDYTGLEFDQLVELMYYNVTSCSDTIQAAIKRAIKKKRRKRANQS 757 Ciona intestinalis
XP_002124513 636 LKDYQPRSTatppddkp-fndfpvfDEGNSYKTHYFSYTDYHFDQLRELMYHNVMSNIEEVKVQLRNAIAKKKRRLNTHD 714 Ciona intestinalis
XP_002239734 604 FSKPGVKREteeelef--anfdlfdDPNTPFSTFNFCYPHKAFDRLAQLMEFNTLLSLDTIKDNITECVQRRRRGGPRPN 681 Florida lancelet
CAB42689     650 YRAPGVPREteeekei--adfdifdDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRRQNPSRCS 727 human
Feature 1           
1CJY_A       728 VSL 730 human
P49147       728 VSL 730 chicken
1709550      717 VSL 719 zebrafish
Q7T0T9       728 VSL 730 African clawed frog
XP_002127884 842 ITL 844 Ciona intestinalis
XP_002129582 758 DID 760 Ciona intestinalis
XP_002124513 715 KSY 717 Ciona intestinalis
XP_002239734 682 LDL 684 Florida lancelet
CAB42689     728 VSL 730 human

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