Conserved Protein Domain Family
cPLA2_Grp-IVC

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cd07202: cPLA2_Grp-IVC 
Group IVC cytoplasmic phospholipase A2; catalytic domain; Ca-independent
Group IVC cPLA2, a small 61 kDa protein, is a single domain alpha/beta hydrolase. It lacks a C2 domain; therefore, it has no Ca-dependence. Group IVC cPLA2 is also referred to as cPLA2-gamma. The cPLA2-gamma enzyme is predominantly found in cardiac and skeletal muscles, and to a lesser extent in the brain. Human cPLA2-gamma is approximately 30% identical to cPLA2-alpha. 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). Includes PLA2G4C protein from human and Pla2g4c protein from mouse.
Statistics
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PSSM-Id: 132841
View PSSM: cd07202
Aligned: 6 rows
Threshold Bit Score: 703.853
Threshold Setting Gi: 55925353
Created: 10-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 47117337     4 SEVSIIPGLQKEEKAAVERRRLHVLKALKKLRI--EADEAPVVAVLGSGGGLRAHIACLGVLSEMKEQGLLDAVTYLAGV 81
gi 55925353     9 SEVRIAHSLNRNEEQFVVKRRKDVLQSLARLGIrcSQDKVPNIALLGSGGGQRAMVGLLGCLDQLDKAGLLDCVLYLSGV 88
gi 126330082   62 PKIIIHPGISDKEKKSVDNRQKRILGMLQKLDI--KTSKAPVVAVLGSGGGLRAAIACQGVLGELNHVGILDLTTYLAGV 139
gi 126330087  585 SDIHIRSGISEEEKAAVKKRKELVLTTLRNLGL--NANKAPVVSVLVSGGGLRAAIACQGILSELSNVGLLDLVTYLAGV 662
gi 189518723    9 SEVRIEPSLNKSEQEFVARRRISVLQSLQKLSTpcNQENVPNIALLGSGGGQRAMVGLLGCLDQLDKAGLLDCVLYLSGV 88
gi 120538517   15 SGVCPATRLQEAEKAAVHKRSPKVLEALRKLNI--QADQAPVIAVLGSGGGLRAHIACLGVLSELKELGLLDAVTYLAGV 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         #                                                                               
gi 47117337    82 SGSTWAISSLYTNDG---DMEALEADLKHR---FTRQEWDLAKSLQKTIQAAr-sENYSLTDFWAYMVISKQTRELPESH 154
gi 55925353    89 SGSTWCMASLYQEPDwstKLQTVKDRIFRRi-gGPAVSWSDAYAKMKEYYSEk--DYFTLTDVWAVLVVTTFVKEIDEST 165
gi 126330082  140 SGSTWCMSSLYVRKNwqdHLAEAEEELKVR---LQEGSWNPGTALKGIQEAArrsENFSLTDIWQYTLVYYMTKELLGSS 216
gi 126330087  663 SGSTWCMSSLYTKSDgwqNLQKAENELRRR---LQKDKWNFSHALTGLCMAAk-rDDYSLTDFWSYTLVYFLTKELLDAN 738
gi 189518723   89 SGSTWCMAALYQEPDwstKLQTVKDRIFSRisgPAVSLKDKFAKLKKYFKGK---DHFSLTDVWAVLAVTTFVKEIDEHT 165
gi 120538517   93 SGSTWALSSLYTKNG---NMEGIEEELKHR---YEKNEWDFHESLEKAIQASk-rENYSLTDFWAYLIVSRQIRELQDSN 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 47117337   155 LSNMKKPVeeGTLPYPIFAAIDNdlqpsWQEARAPETWFEFTPHHAGFPA-----LGAFVSITHFGSKFKKGRLVRTHPE 229
gi 55925353   166 PSDQREQH--KKDPFPIFTVIDKq----CKQSGDGDPWFEITPRETGYSL-----TGAFVSSPSFCSQFENGRKVKRQPE 234
gi 126330082  217 LSEVRTRSeeGEVPYPIFAAIDNsllseWNEKKSLETWFEFTPHVAGYPL-----PGAYVRTTHFGSKFNGGKLIKKEKE 291
gi 126330087  739 LSGSRSQSetGTVPYPIFATVDHyf-krKGKEKTLKSWFEFTPHEAGYPKldlstPGAYVSTTLYGSKFKAGKLIQQEAE 817
gi 189518723  166 LTDQHGHN--NKDPFPIYTVIDKt----CKQRNNGDPWFEITPYEAGYSL-----SGAFVNASTFGSQFHQGSRKSQQNE 234
gi 120538517  166 LSSLKKQVeeGVLPYPIFAAIDEdlladWRERKTQNSWFEFTPHHAGYPA-----LGAYVPITEFGSRFENGKLVKSEPE 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 47117337   230 RDLTFLRGLWGSALGNTEVIREYIfdqlrnltlkglwrravanaksighlifarllrlqessqgehpppedeg------- 302
gi 55925353   235 VDMLYLQALCGSALADGIEIAKFLwekikeffrhllrvmieemeredpmfgpiqkcsqvlleladmnicvlngqnptald 314
gi 126330082  292 KDFAYLRALWGSALADKETTQRTIqqfiwsflsqqdikkvsmsatyecsdehdaesymlslkdsadmqspvpilrlyvlq 371
gi 126330087  818 RDLSYLRGLFGSALADRNSILTSIrgdilktimeelvtlvyifttggdylpvleslhfkmagykdfsqsqrmi------- 890
gi 189518723  235 FDMLYLQALCGSALADELEIMKMLwqkikefcfhlfklpeinvfpfkdsnsasvdkcyqml------------------- 295
gi 120538517  241 RDLTFLRGLWGSAFADIKEIKNYIlnyfrnpfgklkfiegpvtyseaprmnvdamlldlvmayftdmndpsikdklcalq 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 47117337   303 ------------------------gepehtwltemlenwtrtslekqeqphedperkgslsnlmdfvkktgiCASKWEWG 358
gi 55925353   315 rsiri------klkelsggkrqfifqveklivpdkrdarlnmnqytldvctylqslqlewpvdismwmrinvCMALWIWG 388
gi 126330082  372 kfalpsvslklkcifrfetfptpssrkhfeidfvgseklssledehedrseqsfslremygsfsfgmlsvlqSLFTWTWG 451
gi 126330087  891 -----------------------tkmlqhsrqtssdqqrqsildlltevlkhdakeernirpfvqfiwktfkCLLFWTWG 947
gi 189518723  296 ------------------------------------mnlvdmnlavlngkdpsaldesiraklndawmyictCMDLWIWG 339
gi 120538517  321 qalgtetdefgiemaeiiqnwnetsaekkeqfldhlldrfkktqedtttyslmnwntglvwdrcvfvnetrkCVSKWQWG 400
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                      #                                                  
gi 47117337   359 TTHNFLYKHGGIRDKi---MSSRKHLHLVDAGLAINTPFPLVLPPTREVHLILSFDFSAGDPFeTIRATTDYCRRHKIPF 435
gi 55925353   389 RNYNFLHNMTDRAIPp--aQRTSDTRDYEDAGLLLNSPYLSVLRKERNTDLIISLDFSEGDPFmTVRGAAETCRKLNIPF 466
gi 126330082  452 STNNFLYQHEGLKDKpldgMESKEKLHLMDAGLAINSPYPLVLPPVRNTQLILSFDFSEGDPFeTIKTTAEYCSAHGIPF 531
gi 126330087  948 TTNNFLYKYGDIKDKd---LTDRENLYLMDAGLDINCAYPLVLPPVRDTDIILSFDFSEGDPFlTIKDTAKYCKACNIPF 1024
gi 189518723  340 RNYNFLHDITDEAVPs--tLPKGDTRDYIDAGLLLNSPYFSVLRKERNVDLIISLDFSEGDPFlTVKDAAEMCRKQNIPF 417
gi 120538517  401 TVYNFLYKHGKIADEt---MCSRELLHLVDAGFAINTPYPLVLPPVRETHLILSFDFSAGDPLeTIRATADYCQRHEIPF 477
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 47117337   436 PQVEEaeLDLWSKAPASCYILKGETGPVVMHFPLFNIDAcggdi-----------------------------eawsDTY 486
gi 55925353   467 PQVKI--PDQDIKKPKDFYVFKGKNTPTVIHIPLFNVVN--------------------------------------CGD 506
gi 126330082  532 PELDVakLNQEAEAPSDFYIFEGKEGPVVMHFPLFNKVN--------------------------------------CGK 573
gi 126330087 1025 PPVDEdkLDQDAEAPSDFYIFEREKGPVVMHFPLFNKVNcgspgpedlrvirgakqenalpreetpdfldnlfcraaCPL 1104
gi 189518723  418 PQVRI--PDQDIEKPKDFYVFKGQNTPTVIHIPLFNVVN--------------------------------------CGD 457
gi 120538517  478 PEVSEdqLKEWAKAPASCYVLRGETGPVVMHFTLFNKDN--------------------------------------CGD 519
                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|..
Feature 1                                                             
gi 47117337   487 DTFKLADT---------YTLDVVVLLLALAKKNVReNKKKILRELMNVAGLY 529
gi 55925353   507 QLEDWRNE---------YTTNQRAYSTQKITDLMTvAGKNISNNKGRLMQQI 549
gi 126330082  574 NISNMAKTyktf-qlgnYSQEDVHQLLELSKANVKnNKEKIMEKIRALAKEA 624
gi 126330087 1105 QVIKKRREtfatfrfddYSDDEVRQLLEDAKANAW-SAHNLRSDHRGTESQR 1155
gi 189518723  458 KLEDWRKKyrtf--qgaYSTEMITDLMNVAGINISnCKEKLMKEISAAIGQK 507
gi 120538517  520 DIETWRKKygtvklsdsYTPDLVRDLLRVSKENVKkNKINILSEMRKVAGNP 571

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