3PEP,1QRP,1PSO,1CZI,3CMS,1AM5


Conserved Protein Domain Family
pepsin_A

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cd05478: pepsin_A 
Click on image for an interactive view with Cn3D
Pepsin A, aspartic protease produced in gastric mucosa of mammals.
Pepsin, a well-known aspartic protease, is produced by the human gastric mucosa in seven different zymogen isoforms, subdivided into two types: pepsinogen A and pepsinogen C. The prosequence of the zymogens are self cleaved under acidic pH. The mature enzymes are called pepsin A and pepsin C, correspondingly. The well researched porcine pepsin is also in this pepsin A family. Pepsins play an integral role in the digestion process of vertebrates. Pepsins are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localized between the two lobes of the molecule. One lobe may be evolved from the other through ancient gene-duplication event. More recently evolved enzymes have similar three-dimensional structures, however their amino acid sequences are more divergent except for the conserved catalytic site motif. Pepsins specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbor hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).
Statistics
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PSSM-Id: 133145
View PSSM: cd05478
Aligned: 12 rows
Threshold Bit Score: 561.682
Threshold Setting Gi: 157829957
Created: 8-Feb-2008
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 2 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic residue [active site]
Evidence:
  • Citation:PMID 2217165
  • Comment:The two ASPs at the active site plays key catalytic roles in the pepsin family and conserved for all family members.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                   #                                                   
3PEP_A        4 EPLENYLDTEYFGTIGIGTPAQDFTVIFDTGSSNLWVPSVYCSSlACSDHNQFNPddSSTFEATSQELSITYGTGSMTGI 83
1QRP_E        4 QPLENYLDMEYFGTIGIGTPAQDFTVVFDTGSSNLWVPSVYCSSlACTNHNRFNPedSSTYQSTSETVSITYGTGSMTGI 83
1PSO_E        4 QPLENYLDMEYFGTIGIGTPAQDFTVVFDTGSSNLWVPSVYCSSlACTNHNRFNPedSSTYQSTSETVSITYGTGSMTGI 83
1CZI_E        6 VPLTNYLDSQYFGKIYLGTPPQEFTVLFDTGSSDFWVPSIYCKSnACKNHQRFDPrkSSTFQNLGKPLSIHYGTGSMQGI 85
3CMS_A        6 VPLTNYLDSQYFGKIYLGTPPQEFTVLFDTGSSDFWVPSIYCKSnACKNHQRFDPrkSSTFQNLGKPLSIHYGTGSMQGI 85
1AM5_A        4 EQMKNEADTEYYGVISIGTPPESFKVIFDTGSSNLWVSSSHCSAqACSNHNKFKPrqSSTYVETGKTVDLTYGTGGMRGI 83
gi 12082176  62 ETLQNYMDIEYYGTISIGTPPQEFTVIFDTGSANLWVPSVYCSSqACSNHNRFNPqqSSTFQATNTPVSIQYGTGSMSGF 141
gi 1246038   49 EPLTNYMDAEYFGTISIGTPAQDFTVVFDTGSSNLWVPSVTCSSaACTQHNRFNPsdSSTYRATSQNLSIQYGTGSMTGI 128
gi 5921649   62 ESMTNDADLAYYGIISIGTPPQSFKVVFDTGSSNLWIPSIYCSSaACNNHDKYNPglSSTYKKNGGSLSIQYGTGSMTGI 141
gi 129791    49 EPMTNYMDASYYGTISIGTPQQDFSVIFDTGSSNLWVPSIYCKSsACSNHKRFDPskSSTYVSTNETVYIAYGTGSMSGI 128
gi 1246039   43 EPMTNDADLSYYGVVSIGTPPQSFKVIFDTGSSNLWVPSVYCSSqACQNHKKFNPqqSSTFKWGDQPLSIQYGTGSMTGR 122
gi 45384244  66 EPLLNTLDMEYYGTISIGTPPQDFTVVFDTGSSNLWVPSVSCTSpACQSHQMFNPsqSSTYKSTGQNLSIHYGTGDMEGT 145
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
3PEP_A       84 LGYDTVQVGGIsdtNQIFGLSETEPGSFLYYapFDGILGLAYPSISASgATPVFDNLWDQGLVsQDLFSVYLSSnddsGS 163
1QRP_E       84 LGYDTVQVGGIsdtNQIFGLSETEPGSFLYYapFDGILGLAYPSISSSgATPVFDNIWNQGLVsQDLFSVYLSAddqsGS 163
1PSO_E       84 LGYDTVQVGGIsdtNQIFGLSETEPGSFLYYapFDGILGLAYPSISSSgATPVFDNIWNQGLVsQDLFSVYLSAddqsGS 163
1CZI_E       86 LGYDTVTVSNIvdiQQTVGLSTQEPGDVFTYaeFDGILGMAYPSLASEySIPVFDNMMNRHLVaQDLFSVYMDRng-qES 164
3CMS_A       86 LGYDTVTVSNIvdiQQTVGLSTQEPGDFFTYaeFDGILGMAYPSLASEySIPVFDNMMNRHLVaQDLFSVYMDRng-qES 164
1AM5_A       84 LGQDTVSVGGGsdpNQELGESQTEPGPFQAAapFDGILGLAYPSIAAAgAVPVFDNMGSQSLVeKDLFSFYLSGgganGS 163
gi 12082176 142 LGYDTLQVGNIqisNQMFGLSESEPGSFLYYspFDGILGLAFPSIASSqATPVFDNMWSQGLIpQNLFSVYLSSdgqtGS 221
gi 1246038  129 LGYDNVQVGGLvdtNQIFGLSETEPGSTFYYapMDGILGLAYPSIASSgATPVFDNMMSEGLVsQDLFSVYLSSdeqsGS 208
gi 5921649  142 LGYDTVTVGGLavkNQIFGLSQSEATFMQYMq-ADGILGLAYPSLSASgATPVFDNMMTEGLVdQDLFSVYLSPnaqqGS 220
gi 129791   129 LGYDTVAVSSIdvqNQIFGLSETEPGSFFYYcnFDGILGLAFPSISSSgATPVFDNMMSQHLVaQDLFSVYLSKdgetGS 208
gi 1246039  123 LASDIVEVGGIsvnNQVFGISQSEAPFMAYMk-ADGILGLAFQSIASDnVVPVFDNMVSQGLVsQPLFSVYLSSnsqqGS 201
gi 45384244 146 VGCDTVTVASLmdtNQLFGLSTSEPGQFFVYvkFDGILGLGYPSLAADgITPVFDNMVNESLLeQNLFSVYLSRep-mGS 224
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                          #                            
3PEP_A      164 VVLLGGIDSSYYtgSLNWVPVSvEGYWQITLDSItmdGETIACSGGCQAIVDTGTSLLTGPtsaianiqsdigasensdg 243
1QRP_E      164 VVIFGGIDSSYYtgSLNWVPVTvEGYWQITVDSItmnGEAIACAEGCQAIVDTGTSLLTGPtspianiqsdigasensdg 243
1PSO_E      164 VVIFGGIDSSYYtgSLNWVPVTvEGYWQITVDSItmnGEAIACAEGCQAIVDTGTSLLTGPtspianiqsdigasensdg 243
1CZI_E      165 MLTLGAIDPSYYtgSLHWVPVTvQQYWQFTVDSVtisGVVVACEGGCQAILDTGTSKLVGPssdilniqqaigatqnqyg 244
3CMS_A      165 MLTLGAIDPSYYtgSLHWVPVTvQQYWQFTVDSVtisGVVVACEGGCQAILDTGTSKLVGPssdilniqqaigatqnqyg 244
1AM5_A      164 EVMLGGVDNSHYtgSIHWIPVTaEKYWQVALDGIt-vNGQTAACEGCQAIVDTGTSKIVAPvsalanimkdigase-nqg 241
gi 12082176 222 YVLFGGVDNSYYsgSLNWVPLTaETYWQITLDSVsinGQVIACSQSCQAIVDTGTSLMTGPstpianiqnyigasqdsng 301
gi 1246038  209 FVMFGGNDTSYYsgSLNWIPLSaETYWEITMDSItmnGQTIACSGGCQAIIDTGTSLLAGPpsdvsninsyiga-----s 283
gi 5921649  221 VVTFGGVDPNHYngAITWIPLSsELYWQITVDSVtvnGQVVACSGGCQAIVDTGTSLIVGPqssisninnyvgats-qng 299
gi 129791   209 FVLFGGIDPNYTtkGIYWVPLSaETYWQITMDRVtvgNKYVACFFTCQAIVDTGTSLLVMPqgaynriikdlgv----ss 284
gi 1246039  202 EVVFGGIDSSHYtgQITWIPLTsATYWQIQMDSVtinGQTVACSGGCQAIIDTGTSLIVGPsrdiynmnawvgasttqng 281
gi 45384244 225 MVVFGGIDESYFtgSINWIPVSyQGYWQISMDSIivnKQEIACSSGCQAIIDTGTSLVAGPasdindiqsavganqntyg 304
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
3PEP_A      244 emviscssidsLPDIVFTIDGVQYPLSPSAYIlqd-ddSCTSGFEGMdvptssgeLWILGDVFIRQYYTVFDRANNKVGL 322
1QRP_E      244 dmvvscsaissLPDIVFTINGVQYPVPPSAYIlqs-egSCISGFQGMnlptesgeLWILGDVFIRQYFTVFDRANNQVGL 322
1PSO_E      244 dmvvscsaissLPDIVFTINGVQYPVPPSAYIlqs-egSCISGFQGMnlptesgeLWILGDVFIRQYFTVFDRANNQVGL 322
1CZI_E      245 efdidcdnlsyMPTVVFEINGKMYPLTPSAYTsqd-qgFCTSGFQSEnh----sqKWILGDVFIREYYSVFDRANNLVGL 319
3CMS_A      245 efdidcdnlsyMPTVVFEINGKMYPLTPSAYTsqd-qgFCTSGFQSEnh----sqKWILGDVFIREYYSVFDRANNLVGL 319
1AM5_A      242 emmgncasvqsLPDITFTINGVKQPLPPSAYIegd-qaFCTSGLGSSgvpsntseLWIFGDVFLRNYYTIYDRTNNKVGF 320
gi 12082176 302 qyvincnnisnMPTIVFTINGVQYPLSPSAYVrqn-qqGCSSGFQAMnlptnsgdLWILGDVFIRQYFTVFDRANNYVAI 380
gi 1246038  284 ngevscssmssLPEIVFNINGIAFPVPASAYIind-ssSCSSSFESMdq-----gLWILGDVFIRLYYVVFDRANNQVGL 357
gi 5921649  300 dyvvncnsisqMPDVIFHIHGQQFTIPASAYVrqsqyyGCSTGLGNGgd-----nLWILGDVFIRQYYSIFSRAQNMVGL 374
gi 129791   285 dgeiscddiskLPDVTFHINGHAFTLPASAYVlne-dgSCMLGFENMgtptelgeQWILGDVFIREYYVIFDRANNKVGL 363
gi 1246039  282 datvncqniqsMPEVTFTLNGHAFTIPASAYVsqs-yyGCRTGFGGEgn----qqLWILGDVFIRQYYSIFDTQGQRIGL 356
gi 45384244 305 eysvncshilaMPDVVFVIGGIQYPVPALAYTeqngqgTCMSSFQNSsa-----dLWILGDVFIRVYYSIFDRANNRVGL 379

                ..
Feature 1         
3PEP_A      323 AP 324
1QRP_E      323 AP 324
1PSO_E      323 AP 324
1CZI_E      320 AK 321
3CMS_A      320 AK 321
1AM5_A      321 AP 322
gi 12082176 381 AP 382
gi 1246038  358 AS 359
gi 5921649  375 AQ 376
gi 129791   364 SP 365
gi 1246039  357 AQ 358
gi 45384244 380 AK 381

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