1YM4,1T6G,1HRN,1TZS,1QDM,1ZAP,1HTR,1G0V,1PPL,3PEP,1WKR,1MPP,2RMP,1LS5,1LS5,2ANL,1SME,2BJU,1YG9


Conserved Protein Domain Family
pepsin_like

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cd05471: pepsin_like 
Click on image for an interactive view with Cn3D
Pepsin-like aspartic proteases, bilobal enzymes that cleave bonds in peptides at acidic pH.
Pepsin-like aspartic proteases are found in mammals, plants, fungi and bacteria. These well known and extensively characterized enzymes include pepsins, chymosin, renin, cathepsins, and fungal aspartic proteases. Several have long been known to be medically (renin, cathepsin D and E, pepsin) or commercially (chymosin) important. Structurally, aspartic proteases are bilobal enzymes, each lobe contributing a catalytic Aspartate residue, with an extended active site cleft localized between the two lobes of the molecule. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. Most members of the pepsin family specifically cleave bonds in peptides that are 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.The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. 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: 133138
View PSSM: cd05471
Aligned: 366 rows
Threshold Bit Score: 68.9912
Threshold Setting Gi: 55669878
Created: 17-Aug-2006
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:
  • Structure:1ym4_a; catalytic aspartic acid residues of human Beta Secretase
    View structure with Cn3D
  • 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                          #                                                             
1YM4_A        30 YYVEMTVGsppqtLNILVDTGSSNFAVGaaphpflhryyq--------------------------------rqlsstyr 77  human
AAM64443      60 YNVTINIGqpprpYYLDLDTGSDLTWLQcdapcvrcleaphplyqpssdlip---------cndplckalhlnsnqrcet 130 thale cress
EDQ61569      37 YYTKIYLGtppvgYYVQVDTGSDVTWLNcapctscvtetqlpsiklttydpsrsstdgalscrdsncgaalgsnevscts 116 Physcomitrella ...
NP_563808     84 YYTKVKLGtppreFNVQIDTGSDVLWVSctscngcpktselqiqlsffdpgvsss--aslvscsdrrcysnfqtesgcsp 161 thale cress
Q9S9K4        74 YFTKIKLGsppkeYHVQVDTGSDILWINckpcpkcptktnlnfrlslfdmnasst---skkvgcdddfcsfisqsdscqp 150 thale cress
XP_001690254  13 FYTTLKLGtpertFSVIIDTGSTITYIPckdcshcgkhtaewfdpdksttak---------klacgdplcncgtpsctcn 83  Chlamydomonas r...
AAV59271      93 YTTRLWIGtppqmFALIVDSGSTVTYVPcsdceqcgkhqdpkfqpemss---------------tyqpvkcnmdcncddd 157 thale cress
XP_001422234  39 LVAEYALAdg-qtYDLIVDTGSARTYVPckgcarcgehahgyydydrsmeferl-----dcgeasdatlceetmkgtcqs 112 Ostreococcus lu...
CAL58575      35 LVASFELAga-qtFELIVDTGSSRTYLPckgcascgaheagryydydasad-----------fsrvecsacagiggkcgt 102 Ostreococcus tauri
EAZ40507      91 YTTRLYIGtpsqeFALIVDSGSTVTYVPcatceqcgnhqsespniieahdprfq-----pdlsstyspvkcnvdctcdne 165 Japanese rice
Feature 1                                                                                        
1YM4_A        78 dlrkGVYVPYTqGKWEGELg-tDLVSIphgpn------vtvrANIAAitesdkf-fingsnWEGILGLAYaeiarpddsl 149 human
AAM64443     131 peqcDYEVEYAdGGSSLGVlvrDVFSMnytqgl----rltprLALGCgydqipg-asshhpLDGVLGLGRgk-------- 197 thale cress
EDQ61569     117 agycAYSTTYGdGSSTQGYfiqDVMTFqeihnnt-qvngtasVYFGCgttqsgnllmssraLDGLIGFGQaa-------- 187 Physcomitrella ...
NP_563808    162 nnlcSYSFKYGdGSGTSGYyisDFMSFdtvitstlainssapFVFGCsnlqsgdlqrprraVDGIFGLGQgs-------- 233 thale cress
Q9S9K4       151 algcSYHIVYAdESTSDGKfirDMLTLeqvtgdlktgplgqeVVFGCgsdqsgqlgngdsaVDGVMGFGQsn-------- 222 thale cress
XP_001690254  84 ndrcYYSRTYAeRSSSEGWmieDTFGFpdsd-------spvrLVFGCengetg--eiyrqmADGIMGMGNnh-------- 146 Chlamydomonas r...
AAV59271     158 reqcVYEREYAeHSSSKGVlgeDLISFgnesq-----ltpqrAVFGCetvetg--dlysqrADGIIGLGQgd-------- 222 thale cress
XP_001422234 113 dgrcSYVVSYAeGSSSRGYvvrDRVRLgegt-------lsamLAFGCeeaetn--aiyeqkADGLFGFGRgt-------- 175 Ostreococcus lu...
CAL58575     103 sgvcRYDVHYLeGSGSEGYlvrDVVSLggsv-------gnatVVFGCeerelg--sikqqsADGLFGFGRqa-------- 165 Ostreococcus tauri
EAZ40507     166 rsqcTYERQYAeMSSSSGVlgeDIMSFgkese-----lkpqrAVFGCentetg--dlfsqhADGIMGLGRgq-------- 230 Japanese rice
Feature 1                                                                                        
1YM4_A       150 epFFDSLVkqthvpnLFSLQLcgagfplnqsevlasvGGSMIIGGIdhslytgSLWYTPIrr----ewYYEVIIvrvein 225 human
AAM64443     198 vsILSQLHsqgyvknVIGHCLss------------lgGGILFFGDDlyd--ssRVSWTPMsre--yskHYSPAMggellf 261 thale cress
EDQ61569     188 vsIPSQLAsmgkvgnRFAHCLqgd----------nqgGGTIVIGSVse----pNISYTPIvs----rnHYAVGMqniavn 249 Physcomitrella ...
NP_563808    234 lsVISQLAvqglaprVFSHCLkgd----------ksgGGIMVLGQIkr----pDTVYTPLvps---qpHYNVNLqsiavn 296 thale cress
Q9S9K4       223 tsVLSQLAatgdakrVFSHCLdnv-----------kgGGIFAVGVVds----pKVKTTPMvpn---qmHYNVMLmgmdvd 284 thale cress
XP_001690254 147 naFQSQLVqrkviedVFSLCFgy------------pkDGILLLGDVtlp-egaNTVYTPLlthl-hlhYYNVKMdgitvn 212 Chlamydomonas r...
AAV59271     223 lsLVDQLVdkglisnSFGLCYggm----------dvgGGSMILGGFdy---psDMVFTDSdpd--rspYYNIDLtgirva 287 thale cress
XP_001422234 176 atVHAQLAsaglienVFSFCVegf----------ganGGVLTLGRFdfgadapALARTPLvadpanpaFHNVRTsswklg 245 Ostreococcus lu...
CAL58575     166 yaLRAQLAsasviddLFSMCVegyekl-----sgehvGGLLTLGNFdfgadapALVYTPMvss---amYYQVTTtswtlg 237 Ostreococcus tauri
EAZ40507     231 lsIMDQLVekgvisdSFSLCYggm----------dvgGGTMVLGGMpa---ppDMVFSHSnpv--rspYYNIELkeihva 295 Japanese rice
Feature 1                              #                                                         
1YM4_A       226 gqdl----kmdckeynydKSIVDSGTTNLRLPkkvfeaavksikaasstekfpdg------------------------- 276 human
AAM64443     262 gg--------rttglknlLTVFDSGSSYTYFNskayqavtyllkrelsgkplkeardd---------------------- 311 thale cress
EDQ61569     250 grnvttpasfdttstsagGVIMDSGTTLAYLVdpaytqfvnavstfessmfs---------------------------- 301 Physcomitrella ...
NP_563808    297 gqilpi-dpsvftiatgdGTIIDTGTTLAYLPdeayspfiqavanavsqygrp--------------------------- 348 thale cress
Q9S9K4       285 gtsl----dlprsivrngGTIVDSGTTLAYFPkvlydslietilarqpvklhi--------------------------- 333 thale cress
XP_001690254 213 gqtla---fdasvfdrgyGTVLDSGTTFTYLPtdafkamakavgdyvekkglqstpga---------------------- 267 Chlamydomonas r...
AAV59271     288 gkqls---lhsrvfdgehGAVLDSGTTYAYLPdaafaafeeavmrevstlkqidgpd----------------------- 341 thale cress
XP_001422234 246 ds--------liehlnsyTTTLDSGTTFTFVPrsvwvsfktrldtqatqagleivagpdpq------------------- 298 Ostreococcus lu...
CAL58575     238 ns--------vvegsrgvLTIIDSGTSYTYVPgnmharflqlaedaaresglekvapp---------------------- 287 Ostreococcus tauri
EAZ40507     296 gkalr---ldpkifnskhGTVLDSGTTYAYLPeqafvafkdailfilflfssslsflkmeifkmdtpgkvtnkvnslkki 372 Japanese rice
Feature 1                                                                                        
1YM4_A       277 ------fwlgeqlvcwqagttpwnifpvISLYLmgevtnqsfritilpqqylrpvedvatsqddcykfaisqsstGTVMG 350 human
AAM64443     312 ---htlplcwqgrrpfmsieevkkyfkpLALSFktgwrsktlfeippeaylii--smkgnvclgilngteiglqnLNLIG 386 thale cress
EDQ61569     302 ---------shsqclqlawcslqadfptVKLFFdagavmnltprnylysqplqn-gqaaycmgwqksttkagylsYSILG 371 Physcomitrella ...
NP_563808    349 -------ityesyqcfeitagdvdvfpqVSLSFaggasmvlgpraylqifs------ssgssiwcigfqrmshrrITILG 415 thale cress
Q9S9K4       334 --------veetfqcfsfstnvdeafppVSFEFedsvkltvyphdylftlee----elycfgwqagglttderseVILLG 401 thale cress
XP_001690254 268 ---dpqyndicwkgapdqfkdldkyfppAEFVFgggakltlpplrylfl----------skpaeyclgifdngnsGALVG 334 Chlamydomonas r...
AAV59271     342 ---pnfkdtcfqvaasnyvselskifpsVEMVFksgqswllspenymfrhs-------kvhgayclgvfpngkdhTTLLG 411 thale cress
XP_001422234 299 yddvcygvsaaamnmtlsqstvsewfppLTIAYeggvsltlgpenylfah--------etnsaafcvgifanpnnQILLG 370 Ostreococcus lu...
CAL58575     288 ---edypdlcfgnsgglgwstvseyfpaLKIEYhgsarltlspetylywh--------qknasafcvgilehddnRILLG 356 Ostreococcus tauri
EAZ40507     373 rgpdpnykdicfagagrnvsqlsevfpdVDMVFgngqklslspenylfrhs-------kvegayclgvfqngkdpTTLLG 445 Japanese rice
Feature 1                              
1YM4_A       351 AvIMEGFYVVFDRarkRIGFAV 372 human
AAM64443     387 DiSMQDQMIIYDNekqSIGWMP 408 thale cress
EDQ61569     372 DiVLKDHLVVYDNdnrVVGWKS 393 Physcomitrella patens subsp. patens
NP_563808    416 DlVLKDKVVVYDLvrqRIGWAE 437 thale cress
Q9S9K4       402 DlVLSNKLVVYDLdneVIGWAD 423 thale cress
XP_001690254 335 GvSVRDVVVTYDRrnsKVGFTT 356 Chlamydomonas reinhardtii
AAV59271     412 GiVVRNTLVVYDRensKVGFWR 433 thale cress
XP_001422234 371 QiTMRDTLMEFDVansRVGMAP 392 Ostreococcus lucimarinus CCE9901
CAL58575     357 QiTMRNTFTEFDVarsQVGMAS 378 Ostreococcus tauri
EAZ40507     446 GiVVRNTLVTYDRhneKIGFWK 467 Japanese rice

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