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: 2-Oct-2020
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:
Feature 1                                 #                                                   
3PEP_A      4 EPLENYLDTEYFGTIGIGTPAQDFTVIFDTGSSNLWVPSVYCSSlACSDHNQFNPddSSTFEATSQELSITYGTGSMTGI 83  pig
1QRP_E      4 QPLENYLDMEYFGTIGIGTPAQDFTVVFDTGSSNLWVPSVYCSSlACTNHNRFNPedSSTYQSTSETVSITYGTGSMTGI 83  human
1PSO_E      4 QPLENYLDMEYFGTIGIGTPAQDFTVVFDTGSSNLWVPSVYCSSlACTNHNRFNPedSSTYQSTSETVSITYGTGSMTGI 83  human
1CZI_E      6 VPLTNYLDSQYFGKIYLGTPPQEFTVLFDTGSSDFWVPSIYCKSnACKNHQRFDPrkSSTFQNLGKPLSIHYGTGSMQGI 85  cattle
3CMS_A      6 VPLTNYLDSQYFGKIYLGTPPQEFTVLFDTGSSDFWVPSIYCKSnACKNHQRFDPrkSSTFQNLGKPLSIHYGTGSMQGI 85  cattle
1AM5_A      4 EQMKNEADTEYYGVISIGTPPESFKVIFDTGSSNLWVSSSHCSAqACSNHNKFKPrqSSTYVETGKTVDLTYGTGGMRGI 83  Atlantic cod
BAB20798   62 ETLQNYMDIEYYGTISIGTPPQEFTVIFDTGSANLWVPSVYCSSqACSNHNRFNPqqSSTFQATNTPVSIQYGTGSMSGF 141 African clawed frog
AAB35842   49 EPLTNYMDAEYFGTISIGTPAQDFTVVFDTGSSNLWVPSVTCSSaACTQHNRFNPsdSSTYRATSQNLSIQYGTGSMTGI 128 turtles
AAD56283   62 ESMTNDADLAYYGIISIGTPPQSFKVVFDTGSSNLWIPSIYCSSaACNNHDKYNPglSSTYKKNGGSLSIQYGTGSMTGI 141 winter flounder
P00793     49 EPMTNYMDASYYGTISIGTPQQDFSVIFDTGSSNLWVPSIYCKSsACSNHKRFDPskSSTYVSTNETVYIAYGTGSMSGI 128 chicken
AAB35843   43 EPMTNDADLSYYGVVSIGTPPQSFKVIFDTGSSNLWVPSVYCSSqACQNHKKFNPqqSSTFKWGDQPLSIQYGTGSMTGR 122 tuna
NP_990385  66 EPLLNTLDMEYYGTISIGTPPQDFTVVFDTGSSNLWVPSVSCTSpACQSHQMFNPsqSSTYKSTGQNLSIHYGTGDMEGT 145 chicken
Feature 1                                                                                     
3PEP_A     84 LGYDTVQVGGIsdtNQIFGLSETEPGSFLYYapFDGILGLAYPSISASgATPVFDNLWDQGLVsQDLFSVYLSSnddsGS 163 pig
1QRP_E     84 LGYDTVQVGGIsdtNQIFGLSETEPGSFLYYapFDGILGLAYPSISSSgATPVFDNIWNQGLVsQDLFSVYLSAddqsGS 163 human
1PSO_E     84 LGYDTVQVGGIsdtNQIFGLSETEPGSFLYYapFDGILGLAYPSISSSgATPVFDNIWNQGLVsQDLFSVYLSAddqsGS 163 human
1CZI_E     86 LGYDTVTVSNIvdiQQTVGLSTQEPGDVFTYaeFDGILGMAYPSLASEySIPVFDNMMNRHLVaQDLFSVYMDRng-qES 164 cattle
3CMS_A     86 LGYDTVTVSNIvdiQQTVGLSTQEPGDFFTYaeFDGILGMAYPSLASEySIPVFDNMMNRHLVaQDLFSVYMDRng-qES 164 cattle
1AM5_A     84 LGQDTVSVGGGsdpNQELGESQTEPGPFQAAapFDGILGLAYPSIAAAgAVPVFDNMGSQSLVeKDLFSFYLSGgganGS 163 Atlantic cod
BAB20798  142 LGYDTLQVGNIqisNQMFGLSESEPGSFLYYspFDGILGLAFPSIASSqATPVFDNMWSQGLIpQNLFSVYLSSdgqtGS 221 African clawed frog
AAB35842  129 LGYDNVQVGGLvdtNQIFGLSETEPGSTFYYapMDGILGLAYPSIASSgATPVFDNMMSEGLVsQDLFSVYLSSdeqsGS 208 turtles
AAD56283  142 LGYDTVTVGGLavkNQIFGLSQSEATFMQYMq-ADGILGLAYPSLSASgATPVFDNMMTEGLVdQDLFSVYLSPnaqqGS 220 winter flounder
P00793    129 LGYDTVAVSSIdvqNQIFGLSETEPGSFFYYcnFDGILGLAFPSISSSgATPVFDNMMSQHLVaQDLFSVYLSKdgetGS 208 chicken
AAB35843  123 LASDIVEVGGIsvnNQVFGISQSEAPFMAYMk-ADGILGLAFQSIASDnVVPVFDNMVSQGLVsQPLFSVYLSSnsqqGS 201 tuna
NP_990385 146 VGCDTVTVASLmdtNQLFGLSTSEPGQFFVYvkFDGILGLGYPSLAADgITPVFDNMVNESLLeQNLFSVYLSRep-mGS 224 chicken
Feature 1                                                        #                            
3PEP_A    164 VVLLGGIDSSYYtgSLNWVPVSvEGYWQITLDSItmdGETIACSGGCQAIVDTGTSLLTGPtsaianiqsdigasensdg 243 pig
1QRP_E    164 VVIFGGIDSSYYtgSLNWVPVTvEGYWQITVDSItmnGEAIACAEGCQAIVDTGTSLLTGPtspianiqsdigasensdg 243 human
1PSO_E    164 VVIFGGIDSSYYtgSLNWVPVTvEGYWQITVDSItmnGEAIACAEGCQAIVDTGTSLLTGPtspianiqsdigasensdg 243 human
1CZI_E    165 MLTLGAIDPSYYtgSLHWVPVTvQQYWQFTVDSVtisGVVVACEGGCQAILDTGTSKLVGPssdilniqqaigatqnqyg 244 cattle
3CMS_A    165 MLTLGAIDPSYYtgSLHWVPVTvQQYWQFTVDSVtisGVVVACEGGCQAILDTGTSKLVGPssdilniqqaigatqnqyg 244 cattle
1AM5_A    164 EVMLGGVDNSHYtgSIHWIPVTaEKYWQVALDGIt-vNGQTAACEGCQAIVDTGTSKIVAPvsalanimkdigase-nqg 241 Atlantic cod
BAB20798  222 YVLFGGVDNSYYsgSLNWVPLTaETYWQITLDSVsinGQVIACSQSCQAIVDTGTSLMTGPstpianiqnyigasqdsng 301 African clawed frog
AAB35842  209 FVMFGGNDTSYYsgSLNWIPLSaETYWEITMDSItmnGQTIACSGGCQAIIDTGTSLLAGPpsdvsninsyiga-----s 283 turtles
AAD56283  221 VVTFGGVDPNHYngAITWIPLSsELYWQITVDSVtvnGQVVACSGGCQAIVDTGTSLIVGPqssisninnyvgats-qng 299 winter flounder
P00793    209 FVLFGGIDPNYTtkGIYWVPLSaETYWQITMDRVtvgNKYVACFFTCQAIVDTGTSLLVMPqgaynriikdlgv----ss 284 chicken
AAB35843  202 EVVFGGIDSSHYtgQITWIPLTsATYWQIQMDSVtinGQTVACSGGCQAIIDTGTSLIVGPsrdiynmnawvgasttqng 281 tuna
NP_990385 225 MVVFGGIDESYFtgSINWIPVSyQGYWQISMDSIivnKQEIACSSGCQAIIDTGTSLVAGPasdindiqsavganqntyg 304 chicken
Feature 1                                                                                     
3PEP_A    244 emviscssidsLPDIVFTIDGVQYPLSPSAYIlqd-ddSCTSGFEGMdvptssgeLWILGDVFIRQYYTVFDRANNKVGL 322 pig
1QRP_E    244 dmvvscsaissLPDIVFTINGVQYPVPPSAYIlqs-egSCISGFQGMnlptesgeLWILGDVFIRQYFTVFDRANNQVGL 322 human
1PSO_E    244 dmvvscsaissLPDIVFTINGVQYPVPPSAYIlqs-egSCISGFQGMnlptesgeLWILGDVFIRQYFTVFDRANNQVGL 322 human
1CZI_E    245 efdidcdnlsyMPTVVFEINGKMYPLTPSAYTsqd-qgFCTSGFQSEnh----sqKWILGDVFIREYYSVFDRANNLVGL 319 cattle
3CMS_A    245 efdidcdnlsyMPTVVFEINGKMYPLTPSAYTsqd-qgFCTSGFQSEnh----sqKWILGDVFIREYYSVFDRANNLVGL 319 cattle
1AM5_A    242 emmgncasvqsLPDITFTINGVKQPLPPSAYIegd-qaFCTSGLGSSgvpsntseLWIFGDVFLRNYYTIYDRTNNKVGF 320 Atlantic cod
BAB20798  302 qyvincnnisnMPTIVFTINGVQYPLSPSAYVrqn-qqGCSSGFQAMnlptnsgdLWILGDVFIRQYFTVFDRANNYVAI 380 African clawed frog
AAB35842  284 ngevscssmssLPEIVFNINGIAFPVPASAYIind-ssSCSSSFESMdq-----gLWILGDVFIRLYYVVFDRANNQVGL 357 turtles
AAD56283  300 dyvvncnsisqMPDVIFHIHGQQFTIPASAYVrqsqyyGCSTGLGNGgd-----nLWILGDVFIRQYYSIFSRAQNMVGL 374 winter flounder
P00793    285 dgeiscddiskLPDVTFHINGHAFTLPASAYVlne-dgSCMLGFENMgtptelgeQWILGDVFIREYYVIFDRANNKVGL 363 chicken
AAB35843  282 datvncqniqsMPEVTFTLNGHAFTIPASAYVsqs-yyGCRTGFGGEgn----qqLWILGDVFIRQYYSIFDTQGQRIGL 356 tuna
NP_990385 305 eysvncshilaMPDVVFVIGGIQYPVPALAYTeqngqgTCMSSFQNSsa-----dLWILGDVFIRVYYSIFDRANNRVGL 379 chicken
Feature 1       
3PEP_A    323 AP 324 pig
1QRP_E    323 AP 324 human
1PSO_E    323 AP 324 human
1CZI_E    320 AK 321 cattle
3CMS_A    320 AK 321 cattle
1AM5_A    321 AP 322 Atlantic cod
BAB20798  381 AP 382 African clawed frog
AAB35842  358 AS 359 turtles
AAD56283  375 AQ 376 winter flounder
P00793    364 SP 365 chicken
AAB35843  357 AQ 358 tuna
NP_990385 380 AK 381 chicken

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