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Conserved domains on  [gi|166235886|ref|NP_031825|]
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cathepsin E preproprotein [Mus musculus]

Protein Classification

A1 family peptidase (domain architecture ID 10546414)

A1 family peptidase hydrolyzes the peptide bonds of substrates. similar to Felis catus chymosin that hydrolyzes casein to paracasein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
pepsin_retropepsin_like super family cl11403
Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular ...
79-394 0e+00

Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular and retroviral pepsin-like aspartate proteases. The cellular pepsin and pepsin-like enzymes are twice as long as their retroviral counterparts. The cellular pepsin-like aspartic proteases are found in mammals, plants, fungi and bacteria. These well known and extensively characterized enzymes include pepsins, chymosin, rennin, cathepsins, and fungal aspartic proteases. Several have long been known to be medically (rennin, cathepsin D and E, pepsin) or commercially (chymosin) important. The eukaryotic pepsin-like proteases contain two domains possessing similar topological features. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except in the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The eukaryotic pepsin-like proteases have two active site ASP residues with each N- and C-terminal lobe contributing one residue. While the fungal and mammalian pepsins are bilobal proteins, retropepsins function as dimers and the monomer resembles structure of the N- or C-terminal domains of eukaryotic enzyme. The active site motif (Asp-Thr/Ser-Gly-Ser) is conserved between the retroviral and eukaryotic proteases and between the N-and C-terminal of eukaryotic pepsin-like proteases. The retropepsin-like family includes pepsin-like aspartate proteases from retroviruses, retrotransposons and retroelements; as well as eukaryotic DNA-damage-inducible proteins (DDIs), and bacterial aspartate peptidases. Retropepsin is synthesized as part of the POL polyprotein that contains an aspartyl-protease, a reverse transcriptase, RNase H, and an integrase. The POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A) and A2 (retropepsin family).


The actual alignment was detected with superfamily member cd05486:

Pssm-ID: 416259 [Multi-domain]  Cd Length: 316  Bit Score: 546.02  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVSVEG 158
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYCTSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTVEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 159 LTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGGSGSELTFGGYD 238
Cdd:cd05486   81 ITVQNQQFAESVSEPGSTFQDSEFDGILGLAYPSLAVDGVTPVFDNMMAQNLVELPMFSVYMSRNPNSADGGELVFGGFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 239 PSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPIDGEYAVDCATL 318
Cdd:cd05486  161 TSRFSGQLNWVPVTVQGYWQIQLDNIQVGGTVIFCSDGCQAIVDTGTSLITGPSGDIKQLQNYIGATATDGEYGVDCSTL 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 166235886 319 DTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGNNQVGLAP 394
Cdd:cd05486  241 SLMPSVTFTINGIPYSLSPQAYTLEDQSDGGGYCSSGFQGLDIPPPAGPLWILGDVFIRQYYSVFDRGNNRVGFAP 316
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
22-50 9.04e-09

A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal and propeptides. The animal pepsin-like endopeptidase propeptides form a distinct family of propeptides, which contain a conserved motif approximately 30 residues long. In pepsinogen A, the first 11 residues of the mature pepsin sequence are displaced by residues of the propeptide. The propeptide contains two helices that block the active site cleft, in particular the conserved Asp11 residue, in pepsin, hydrogen bonds to a conserved Arg residues in the propeptide. This hydrogen bond stabilizes the propeptide conformation and is probably responsible for triggering the conversion of pepsinogen to pepsin under acidic conditions.


:

Pssm-ID: 400357  Cd Length: 29  Bit Score: 50.40  E-value: 9.04e-09
                          10        20
                  ....*....|....*....|....*....
gi 166235886   22 LHRVPLRRHQSLRKKLRAQGQLSEFWRSH 50
Cdd:pfam07966   1 LVRIPLKKGKSIRETLREKGLLEEFLKEH 29
 
Name Accession Description Interval E-value
Cathespin_E cd05486
Cathepsin E, non-lysosomal aspartic protease; Cathepsin E is an intracellular, non-lysosomal ...
79-394 0e+00

Cathepsin E, non-lysosomal aspartic protease; Cathepsin E is an intracellular, non-lysosomal aspartic protease expressed in a variety of cells and tissues. The protease has proposed physiological roles in antigen presentation by the MHC class II system, in the biogenesis of the vasoconstrictor peptide endothelin, and in neurodegeneration associated with brain ischemia and aging. Cathepsin E is the only A1 aspartic protease that exists as a homodimer with a disulfide bridge linking the two monomers. Like many other aspartic proteases, it is synthesized as a zymogen which is catalytically inactive towards its natural substrates at neutral pH and which auto-activates in an acidic environment. The overall structure follows the general fold of aspartic proteases of the A1 family, it is composed of two structurally similar beta barrel lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The catalytic Asp residues are contained in an Asp-Thr-Gly-Ser/thr motif in both N- and C-terminal lobes of the enzyme. The aspartic acid residues act together to allow a water molecule to attack the peptide bond. One aspartic acid residue (in its deprotonated form) activates the attacking water molecule, whereas the other aspartic acid residue (in its protonated form) polarizes the peptide carbonyl, increasing its susceptibility to attack. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133153 [Multi-domain]  Cd Length: 316  Bit Score: 546.02  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVSVEG 158
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYCTSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTVEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 159 LTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGGSGSELTFGGYD 238
Cdd:cd05486   81 ITVQNQQFAESVSEPGSTFQDSEFDGILGLAYPSLAVDGVTPVFDNMMAQNLVELPMFSVYMSRNPNSADGGELVFGGFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 239 PSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPIDGEYAVDCATL 318
Cdd:cd05486  161 TSRFSGQLNWVPVTVQGYWQIQLDNIQVGGTVIFCSDGCQAIVDTGTSLITGPSGDIKQLQNYIGATATDGEYGVDCSTL 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 166235886 319 DTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGNNQVGLAP 394
Cdd:cd05486  241 SLMPSVTFTINGIPYSLSPQAYTLEDQSDGGGYCSSGFQGLDIPPPAGPLWILGDVFIRQYYSVFDRGNNRVGFAP 316
Asp pfam00026
Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and ...
78-395 6.18e-163

Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and renins. Two-domain structure, probably arising from ancestral duplication. This family does not include the retroviral nor retrotransposon proteases (pfam00077), which are much smaller and appear to be homologous to a single domain of the eukaryotic asp proteases.


Pssm-ID: 394983 [Multi-domain]  Cd Length: 313  Bit Score: 459.43  E-value: 6.18e-163
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886   78 EYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCT-SPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVSV 156
Cdd:pfam00026   1 EYFGTISIGTPPQKFTVIFDTGSSDLWVPSSYCTkSSACKSHGTFDPSSSSTYKLNGTTFSISYGDGSASGFLGQDTVTV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  157 EGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDpqGGSGSELTFGG 236
Cdd:pfam00026  81 GGLTITNQEFGLATKEPGSFFEYAKFDGILGLGFPSISAVGATPVFDNLKSQGLIDSPAFSVYLNSP--DAAGGEIIFGG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  237 YDPSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPI-DGEYAVDC 315
Cdd:pfam00026 159 VDPSKYTGSLTYVPVTSQGYWQITLDSVTVGGSTSACSSGCQAILDTGTSLLYGPTSIVSKIAKAVGASSSeYGEYVVDC 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  316 ATLDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQfCGSGFQgldiPPPAGPLWILGDVFIRQFYSVFDRGNNQVGLAPA 395
Cdd:pfam00026 239 DSISTLPDITFVIGGAKITVPPSAYVLQNSQGGST-CLSGFQ----PPPGGPLWILGDVFLRSAYVVFDRDNNRIGFAPA 313
PTZ00165 PTZ00165
aspartyl protease; Provisional
23-395 4.74e-99

aspartyl protease; Provisional


Pssm-ID: 240300 [Multi-domain]  Cd Length: 482  Bit Score: 302.83  E-value: 4.74e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  23 HRVPLRRHQSL---RKKLRAQGQLSEfWRSHNLDMTRLSEscNVYSSVNEPLINYLDMEYFGTISIGTPPQNFTVIFDTG 99
Cdd:PTZ00165  65 HKVELHRFALLkkkRKKNSEKGYISR-VLTKHKYLETKDP--NGLQYLQQDLLNFHNSQYFGEIQVGTPPKSFVVVFDTG 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 100 SSNLWVPSVYCTSPACKAHPVFHPSQSDTYT------EVGNHFsIQYGTGSLTGIIGADQVSVEGLTVDGQQFGESVKEP 173
Cdd:PTZ00165 142 SSNLWIPSKECKSGGCAPHRKFDPKKSSTYTklklgdESAETY-IQYGTGECVLALGKDTVKIGGLKVKHQSIGLAIEES 220
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 174 GQTFVNAEFDGILGLGYPSLA---AGGVTPVFDNMMAQNLVALPMFSVYLSSDPQggSGSELTFGGYDPSH-FSG-SLNW 248
Cdd:PTZ00165 221 LHPFADLPFDGLVGLGFPDKDfkeSKKALPIVDNIKKQNLLKRNIFSFYMSKDLN--QPGSISFGSADPKYtLEGhKIWW 298
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 249 IPVTKQAYWQIALDGIQVGD-TVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPidgeyavDCATLDTMPNVTFL 327
Cdd:PTZ00165 299 FPVISTDYWEIEVVDILIDGkSLGFCDRKCKAAIDTGSSLITGPSSVINPLLEKIPLEE-------DCSNKDSLPRISFV 371
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 166235886 328 I-----NEVSYTLNPTDYILPDLVEGMQ--FCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGNNQVGLAPA 395
Cdd:PTZ00165 372 LedvngRKIKFDMDPEDYVIEEGDSEEQehQCVIGIIPMDVPAPRGPLFVLGNNFIRKYYSIFDRDHMMVGLVPA 446
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
22-50 9.04e-09

A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal and propeptides. The animal pepsin-like endopeptidase propeptides form a distinct family of propeptides, which contain a conserved motif approximately 30 residues long. In pepsinogen A, the first 11 residues of the mature pepsin sequence are displaced by residues of the propeptide. The propeptide contains two helices that block the active site cleft, in particular the conserved Asp11 residue, in pepsin, hydrogen bonds to a conserved Arg residues in the propeptide. This hydrogen bond stabilizes the propeptide conformation and is probably responsible for triggering the conversion of pepsinogen to pepsin under acidic conditions.


Pssm-ID: 400357  Cd Length: 29  Bit Score: 50.40  E-value: 9.04e-09
                          10        20
                  ....*....|....*....|....*....
gi 166235886   22 LHRVPLRRHQSLRKKLRAQGQLSEFWRSH 50
Cdd:pfam07966   1 LVRIPLKKGKSIRETLREKGLLEEFLKEH 29
 
Name Accession Description Interval E-value
Cathespin_E cd05486
Cathepsin E, non-lysosomal aspartic protease; Cathepsin E is an intracellular, non-lysosomal ...
79-394 0e+00

Cathepsin E, non-lysosomal aspartic protease; Cathepsin E is an intracellular, non-lysosomal aspartic protease expressed in a variety of cells and tissues. The protease has proposed physiological roles in antigen presentation by the MHC class II system, in the biogenesis of the vasoconstrictor peptide endothelin, and in neurodegeneration associated with brain ischemia and aging. Cathepsin E is the only A1 aspartic protease that exists as a homodimer with a disulfide bridge linking the two monomers. Like many other aspartic proteases, it is synthesized as a zymogen which is catalytically inactive towards its natural substrates at neutral pH and which auto-activates in an acidic environment. The overall structure follows the general fold of aspartic proteases of the A1 family, it is composed of two structurally similar beta barrel lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The catalytic Asp residues are contained in an Asp-Thr-Gly-Ser/thr motif in both N- and C-terminal lobes of the enzyme. The aspartic acid residues act together to allow a water molecule to attack the peptide bond. One aspartic acid residue (in its deprotonated form) activates the attacking water molecule, whereas the other aspartic acid residue (in its protonated form) polarizes the peptide carbonyl, increasing its susceptibility to attack. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133153 [Multi-domain]  Cd Length: 316  Bit Score: 546.02  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVSVEG 158
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYCTSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTVEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 159 LTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGGSGSELTFGGYD 238
Cdd:cd05486   81 ITVQNQQFAESVSEPGSTFQDSEFDGILGLAYPSLAVDGVTPVFDNMMAQNLVELPMFSVYMSRNPNSADGGELVFGGFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 239 PSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPIDGEYAVDCATL 318
Cdd:cd05486  161 TSRFSGQLNWVPVTVQGYWQIQLDNIQVGGTVIFCSDGCQAIVDTGTSLITGPSGDIKQLQNYIGATATDGEYGVDCSTL 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 166235886 319 DTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGNNQVGLAP 394
Cdd:cd05486  241 SLMPSVTFTINGIPYSLSPQAYTLEDQSDGGGYCSSGFQGLDIPPPAGPLWILGDVFIRQYYSVFDRGNNRVGFAP 316
pepsin_A cd05478
Pepsin A, aspartic protease produced in gastric mucosa of mammals; Pepsin, a well-known ...
69-394 2.88e-165

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).


Pssm-ID: 133145 [Multi-domain]  Cd Length: 317  Bit Score: 465.77  E-value: 2.88e-165
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  69 EPLINYLDMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGI 148
Cdd:cd05478    1 EPLTNYLDMEYYGTISIGTPPQDFTVIFDTGSSNLWVPSVYCSSQACSNHNRFNPRQSSTYQSTGQPLSIQYGTGSMTGI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 149 IGADQVSVEGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQggS 228
Cdd:cd05478   81 LGYDTVQVGGISDTNQIFGLSETEPGSFFYYAPFDGILGLAYPSIASSGATPVFDNMMSQGLVSQDLFSVYLSSNGQ--Q 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 229 GSELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPI- 307
Cdd:cd05478  159 GSVVTFGGIDPSYYTGSLNWVPVTAETYWQITVDSVTINGQVVACSGGCQAIVDTGTSLLVGPSSDIANIQSDIGASQNq 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 308 DGEYAVDCATLDTMPNVTFLINEVSYTLNPTDYILPDlvegMQFCGSGFQGLDipppAGPLWILGDVFIRQFYSVFDRGN 387
Cdd:cd05478  239 NGEMVVNCSSISSMPDVVFTINGVQYPLPPSAYILQD----QGSCTSGFQSMG----LGELWILGDVFIRQYYSVFDRAN 310

                 ....*..
gi 166235886 388 NQVGLAP 394
Cdd:cd05478  311 NKVGLAP 317
Asp pfam00026
Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and ...
78-395 6.18e-163

Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and renins. Two-domain structure, probably arising from ancestral duplication. This family does not include the retroviral nor retrotransposon proteases (pfam00077), which are much smaller and appear to be homologous to a single domain of the eukaryotic asp proteases.


Pssm-ID: 394983 [Multi-domain]  Cd Length: 313  Bit Score: 459.43  E-value: 6.18e-163
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886   78 EYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCT-SPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVSV 156
Cdd:pfam00026   1 EYFGTISIGTPPQKFTVIFDTGSSDLWVPSSYCTkSSACKSHGTFDPSSSSTYKLNGTTFSISYGDGSASGFLGQDTVTV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  157 EGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDpqGGSGSELTFGG 236
Cdd:pfam00026  81 GGLTITNQEFGLATKEPGSFFEYAKFDGILGLGFPSISAVGATPVFDNLKSQGLIDSPAFSVYLNSP--DAAGGEIIFGG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  237 YDPSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPI-DGEYAVDC 315
Cdd:pfam00026 159 VDPSKYTGSLTYVPVTSQGYWQITLDSVTVGGSTSACSSGCQAILDTGTSLLYGPTSIVSKIAKAVGASSSeYGEYVVDC 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  316 ATLDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQfCGSGFQgldiPPPAGPLWILGDVFIRQFYSVFDRGNNQVGLAPA 395
Cdd:pfam00026 239 DSISTLPDITFVIGGAKITVPPSAYVLQNSQGGST-CLSGFQ----PPPGGPLWILGDVFLRSAYVVFDRDNNRIGFAPA 313
Cathepsin_D2 cd05490
Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of ...
73-394 7.00e-157

Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of the lysosomal compartment where it functions in protein catabolism. It is a member of the pepsin family of proteinases. This enzyme is distinguished from other members of the pepsin family by two features that are characteristic of lysosomal hydrolases. First, mature Cathepsin D is found predominantly in a two-chain form due to a posttranslational cleavage event. Second, it contains phosphorylated, N-linked oligosaccharides that target the enzyme to lysosomes via mannose-6-phosphate receptors. Cathepsin D preferentially attacks peptide bonds flanked by bulky hydrophobic amino acids and its pH optimum is between pH 2.8 and 4.0. Two active site aspartic acid residues are essential for the catalytic activity of aspartic proteinases. Like other aspartic proteinases, Cathepsin D is a bilobed molecule; the two evolutionary related lobes are mostly made up of beta-sheets and flank a deep active site cleft. Each of the two related lobes contributes one active site aspartic acid residue and contains a single carbohydrate group. Cathepsin D is an essential enzyme. Mice deficient for proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia in the fourth week. The mice develop atrophy of ileal mucosa followed by other degradation of intestinal organs. In these knockout mice, lysosomal proteolysis was normal. These results suggest that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non-critical. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133157 [Multi-domain]  Cd Length: 325  Bit Score: 444.62  E-value: 7.00e-157
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  73 NYLDMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYC--TSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIG 150
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCslLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 151 ADQVSVEGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGGSGS 230
Cdd:cd05490   81 QDTVSIGGLQVEGQLFGEAVKQPGITFIAAKFDGILGMAYPRISVDGVTPVFDNIMAQKLVEQNVFSFYLNRDPDAQPGG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 231 ELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATP-IDG 309
Cdd:cd05490  161 ELMLGGTDPKYYTGDLHYVNVTRKAYWQIHMDQVDVGSGLTLCKGGCEAIVDTGTSLITGPVEEVRALQKAIGAVPlIQG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 310 EYAVDCATLDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGNNQ 389
Cdd:cd05490  241 EYMIDCEKIPTLPVISFSLGGKVYPLTGEDYILKVSQRGTTICLSGFMGLDIPPPAGPLWILGDVFIGRYYTVFDRDNDR 320

                 ....*
gi 166235886 390 VGLAP 394
Cdd:cd05490  321 VGFAK 325
Cathepsin_D_like cd05485
Cathepsin_D_like, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase ...
69-393 7.54e-141

Cathepsin_D_like, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of the lysosomal compartment where it functions in protein catabolism. It is a member of the pepsin family of proteinases. This enzyme is distinguished from other members of the pepsin family by two features that are characteristic of lysosomal hydrolases. First, mature Cathepsin D is found predominantly in a two-chain form due to a posttranslational cleavage event. Second, it contains phosphorylated, N-linked oligosaccharides that target the enzyme to lysosomes via mannose-6-phosphate receptors. Cathepsin D preferentially attacks peptide bonds flanked by bulky hydrophobic amino acids and its pH optimum is between pH 2.8 and 4.0. Two active site aspartic acid residues are essential for the catalytic activity of aspartic proteinases. Like other aspartic proteinases, Cathepsin D is a bilobed molecule; the two evolutionary related lobes are mostly made up of beta-sheets and flank a deep active site cleft. Each of the two related lobes contributes one active site aspartic acid residue and contains a single carbohydrate group. Cathepsin D is an essential enzyme. Mice deficient for proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia in the fourth week. The mice develop atrophy of ileal mucosa followed by other degradation of intestinal organs. In these knockout mice, lysosomal proteolysis was normal. These results suggest that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non-critical. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133152 [Multi-domain]  Cd Length: 329  Bit Score: 404.23  E-value: 7.54e-141
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  69 EPLINYLDMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYC--TSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLT 146
Cdd:cd05485    2 EPLSNYMDAQYYGVITIGTPPQSFKVVFDTGSSNLWVPSKKCswTNIACLLHNKYDSTKSSTYKKNGTEFAIQYGSGSLS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 147 GIIGADQVSVEGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQG 226
Cdd:cd05485   82 GFLSTDTVSVGGVSVKGQTFAEAINEPGLTFVAAKFDGILGMGYSSISVDGVVPVFYNMVNQKLVDAPVFSFYLNRDPSA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 227 GSGSELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDGIQVGDTvMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATP 306
Cdd:cd05485  162 KEGGELILGGSDPKHYTGNFTYLPVTRKGYWQFKMDSVSVGEG-EFCSGGCQAIADTGTSLIAGPVDEIEKLNNAIGAKP 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 307 I-DGEYAVDCATLDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDR 385
Cdd:cd05485  241 IiGGEYMVNCSAIPSLPDITFVLGGKSFSLTGKDYVLKVTQMGQTICLSGFMGIDIPPPAGPLWILGDVFIGKYYTEFDL 320

                 ....*...
gi 166235886 386 GNNQVGLA 393
Cdd:cd05485  321 GNNRVGFA 328
phytepsin cd06098
Phytepsin, a plant homolog of mammalian lysosomal pepsins; Phytepsin, a plant homolog of ...
70-393 1.22e-132

Phytepsin, a plant homolog of mammalian lysosomal pepsins; Phytepsin, a plant homolog of mammalian lysosomal pepsins, resides in grains, roots, stems, leaves and flowers. Phytepsin may participate in metabolic turnover and in protein processing events. In addition, it highly expressed in several plant tissues undergoing apoptosis. Phytepsin contains an internal region consisting of about 100 residues not present in animal or microbial pepsins. This region is thus called a plant specific insert. The insert is highly similar to saponins, which are lysosomal sphingolipid-activating proteins in mammalian cells. The saponin-like domain may have a role in the vacuolar targeting of phytepsin. Phytepsin, as its animal counterparts, possesses a topology typical of all aspartic proteases. They 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 has probably evolved from the other through a gene duplication event in the distant past. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133162 [Multi-domain]  Cd Length: 317  Bit Score: 382.88  E-value: 1.22e-132
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  70 PLINYLDMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYC-TSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGI 148
Cdd:cd06098    2 ALKNYLDAQYFGEIGIGTPPQKFTVIFDTGSSNLWVPSSKCyFSIACYFHSKYKSSKSSTYKKNGTSASIQYGTGSISGF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 149 IGADQVSVEGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGGS 228
Cdd:cd06098   82 FSQDSVTVGDLVVKNQVFIEATKEPGLTFLLAKFDGILGLGFQEISVGKAVPVWYNMVEQGLVKEPVFSFWLNRNPDEEE 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 229 GSELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDGIQVGD-TVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEaigatpi 307
Cdd:cd06098  162 GGELVFGGVDPKHFKGEHTYVPVTRKGYWQFEMGDVLIGGkSTGFCAGGCAAIADSGTSLLAGPTTIVTQINS------- 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 308 dgeyAVDCATLDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGN 387
Cdd:cd06098  235 ----AVDCNSLSSMPNVSFTIGGKTFELTPEQYILKVGEGAAAQCISGFTALDVPPPRGPLWILGDVFMGAYHTVFDYGN 310

                 ....*.
gi 166235886 388 NQVGLA 393
Cdd:cd06098  311 LRVGFA 316
renin_like cd05487
Renin stimulates production of angiotensin and thus affects blood pressure; Renin, also known ...
71-395 4.85e-128

Renin stimulates production of angiotensin and thus affects blood pressure; Renin, also known as angiotensinogenase, is a circulating enzyme that participates in the renin-angiotensin system that mediates extracellular volume, arterial vasoconstriction, and consequently mean arterial blood pressure. The enzyme is secreted by the kidneys from specialized juxtaglomerular cells in response to decreases in glomerular filtration rate (a consequence of low blood volume), diminished filtered sodium chloride and sympathetic nervous system innervation. The enzyme circulates in the blood stream and hydrolyzes angiotensinogen secreted from the liver into the peptide angiotensin I. Angiotensin I is further cleaved in the lungs by endothelial bound angiotensin converting enzyme (ACE) into angiotensin II, the final active peptide. Renin is a member of the aspartic protease family. 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. 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).


Pssm-ID: 133154 [Multi-domain]  Cd Length: 326  Bit Score: 371.42  E-value: 4.85e-128
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  71 LINYLDMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCtSP---ACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTG 147
Cdd:cd05487    1 LTNYLDTQYYGEIGIGTPPQTFKVVFDTGSSNLWVPSSKC-SPlytACVTHNLYDASDSSTYKENGTEFTIHYASGTVKG 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 148 IIGADQVSVEGLTVDgQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGG 227
Cdd:cd05487   80 FLSQDIVTVGGIPVT-QMFGEVTALPAIPFMLAKFDGVLGMGYPKQAIGGVTPVFDNIMSQGVLKEDVFSVYYSRDSSHS 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 228 SGSELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPI 307
Cdd:cd05487  159 LGGEIVLGGSDPQHYQGDFHYINTSKTGFWQIQMKGVSVGSSTLLCEDGCTAVVDTGASFISGPTSSISKLMEALGAKER 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 308 DGEYAVDCATLDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGN 387
Cdd:cd05487  239 LGDYVVKCNEVPTLPDISFHLGGKEYTLSSSDYVLQDSDFSDKLCTVAFHAMDIPPPTGPLWVLGATFIRKFYTEFDRQN 318

                 ....*...
gi 166235886 388 NQVGLAPA 395
Cdd:cd05487  319 NRIGFALA 326
gastricsin cd05477
Gastricsins, asparate proteases produced in gastric mucosa; Gastricsin is also called ...
76-395 9.91e-126

Gastricsins, asparate proteases produced in gastric mucosa; Gastricsin is also called pepsinogen C. Gastricsins are produced in gastric mucosa of mammals. It is synthesized by the chief cells in the stomach as an inactive zymogen. It is self-converted to a mature enzyme under acidic conditions. Human gastricsin is distributed throughout all parts of the stomach. Gastricsin is synthesized as an inactive progastricsin that has an approximately 40 residue prosequence. It is self-converting to a mature enzyme being triggered by a drop in pH from neutrality to acidic conditions. Like other aspartic proteases, gastricsin are characterized by two catalytic aspartic residues at the active site, and display optimal activity at acidic pH. Mature enzyme has a pseudo-2-fold symmetry that passes through the active site between the catalytic aspartate residues. 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. One lobe may be evolved from the other through ancient gene-duplication event. Although the three-dimensional structures of the two lobes are very similar, the amino acid sequences are more divergent, except for the conserved catalytic site motif. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133144 [Multi-domain]  Cd Length: 318  Bit Score: 365.36  E-value: 9.91e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  76 DMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVS 155
Cdd:cd05477    1 DMSYYGEISIGTPPQNFLVLFDTGSSNLWVPSVLCQSQACTNHTKFNPSQSSTYSTNGETFSLQYGSGSLTGIFGYDTVT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 156 VEGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDpQGGSGSELTFG 235
Cdd:cd05477   81 VQGIIITNQEFGLSETEPGTNFVYAQFDGILGLAYPSISAGGATTVMQGMMQQNLLQAPIFSFYLSGQ-QGQQGGELVFG 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 236 GYDPSHFSGSLNWIPVTKQAYWQIALDGIQV-GDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPID-GEYAV 313
Cdd:cd05477  160 GVDNNLYTGQIYWTPVTSETYWQIGIQGFQInGQATGWCSQGCQAIVDTGTSLLTAPQQVMSTLMQSIGAQQDQyGQYVV 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 314 DCATLDTMPNVTFLINEVSYTLNPTDYILpdlvEGMQFCGSGFQGLDIPPPAG-PLWILGDVFIRQFYSVFDRGNNQVGL 392
Cdd:cd05477  240 NCNNIQNLPTLTFTINGVSFPLPPSAYIL----QNNGYCTVGIEPTYLPSQNGqPLWILGDVFLRQYYSVYDLGNNQVGF 315

                 ...
gi 166235886 393 APA 395
Cdd:cd05477  316 ATA 318
Proteinase_A_fungi cd05488
Fungal Proteinase A , aspartic proteinase superfamily; Fungal Proteinase A, a proteolytic ...
70-394 6.07e-124

Fungal Proteinase A , aspartic proteinase superfamily; Fungal Proteinase A, a proteolytic enzyme distributed among a variety of organisms, is a member of the aspartic proteinase superfamily. In Saccharomyces cerevisiae, targeted to the vacuole as a zymogen, activation of proteinases A at acidic pH can occur by two different pathways: a one-step process to release mature proteinase A, involving the intervention of proteinase B, or a step-wise pathway via the auto-activation product known as pseudo-proteinase A. Once active, S. cerevisiae proteinase A is essential to the activities of other yeast vacuolar hydrolases, including proteinase B and carboxypeptidase Y. The mature enzyme is bilobal, with each lobe providing one of the two catalytically essential aspartic acid residues in the active site. The crystal structure of free proteinase A shows that flap loop is atypically pointing directly into the S(1) pocket of the enzyme. Proteinase A preferentially hydrolyzes hydrophobic residues such as Phe, Leu or Glu at the P1 position and Phe, Ile, Leu or Ala at P1'. Moreover, the enzyme is inhibited by IA3, a natural and highly specific inhibitor produced by S. cerevisiae. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133155 [Multi-domain]  Cd Length: 320  Bit Score: 360.98  E-value: 6.07e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  70 PLINYLDMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGII 149
Cdd:cd05488    2 PLTNYLNAQYFTDITLGTPPQKFKVILDTGSSNLWVPSVKCGSIACFLHSKYDSSASSTYKANGTEFKIQYGSGSLEGFV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 150 GADQVSVEGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGgsG 229
Cdd:cd05488   82 SQDTLSIGDLTIKKQDFAEATSEPGLAFAFGKFDGILGLAYDTISVNKIVPPFYNMINQGLLDEPVFSFYLGSSEED--G 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 230 SELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDGIQVGDTVMFCsEGCQAIVDTGTSLITGPPDKIKQLQEAIGATP-ID 308
Cdd:cd05488  160 GEATFGGIDESRFTGKITWLPVRRKAYWEVELEKIGLGDEELEL-ENTGAAIDTGTSLIALPSDLAEMLNAEIGAKKsWN 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 309 GEYAVDCATLDTMPNVTFLINEVSYTLNPTDYILPdlVEGMqfCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGNN 388
Cdd:cd05488  239 GQYTVDCSKVDSLPDLTFNFDGYNFTLGPFDYTLE--VSGS--CISAFTGMDFPEPVGPLAIVGDAFLRKYYSVYDLGNN 314

                 ....*.
gi 166235886 389 QVGLAP 394
Cdd:cd05488  315 AVGLAK 320
pepsin_like cd05471
Pepsin-like aspartic proteases, bilobal enzymes that cleave bonds in peptides at acidic pH; ...
79-394 2.94e-111

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).


Pssm-ID: 133138 [Multi-domain]  Cd Length: 283  Bit Score: 327.07  E-value: 2.94e-111
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFH--PSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVSV 156
Cdd:cd05471    1 YYGEITIGTPPQKFSVIFDTGSSLLWVPSSNCTSCSCQKHPRFKydSSKSSTYKDTGCTFSITYGDGSVTGGLGTDTVTI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 157 EGLTVDGQQFGESVKEPGqTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSSDPQGGSGSELTFGG 236
Cdd:cd05471   81 GGLTIPNQTFGCATSESG-DFSSSGFDGILGLGFPSLSVDGVPSFFDQLKSQGLISSPVFSFYLGRDGDGGNGGELTFGG 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 237 YDPSHFSGSLNWIPVTK--QAYWQIALDGIQVGDT-VMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGAT--PIDGEY 311
Cdd:cd05471  160 IDPSKYTGDLTYTPVVSngPGYWQVPLDGISVGGKsVISSSGGGGAIVDSGTSLIYLPSSVYDAILKALGAAvsSSDGGY 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 312 AVDCATLDTMPNVTFLInevsytlnptdyilpdlvegmqfcgsgfqgldipppagpLWILGDVFIRQFYSVFDRGNNQVG 391
Cdd:cd05471  240 GVDCSPCDTLPDITFTF---------------------------------------LWILGDVFLRNYYTVFDLDNNRIG 280

                 ...
gi 166235886 392 LAP 394
Cdd:cd05471  281 FAP 283
PTZ00165 PTZ00165
aspartyl protease; Provisional
23-395 4.74e-99

aspartyl protease; Provisional


Pssm-ID: 240300 [Multi-domain]  Cd Length: 482  Bit Score: 302.83  E-value: 4.74e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  23 HRVPLRRHQSL---RKKLRAQGQLSEfWRSHNLDMTRLSEscNVYSSVNEPLINYLDMEYFGTISIGTPPQNFTVIFDTG 99
Cdd:PTZ00165  65 HKVELHRFALLkkkRKKNSEKGYISR-VLTKHKYLETKDP--NGLQYLQQDLLNFHNSQYFGEIQVGTPPKSFVVVFDTG 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 100 SSNLWVPSVYCTSPACKAHPVFHPSQSDTYT------EVGNHFsIQYGTGSLTGIIGADQVSVEGLTVDGQQFGESVKEP 173
Cdd:PTZ00165 142 SSNLWIPSKECKSGGCAPHRKFDPKKSSTYTklklgdESAETY-IQYGTGECVLALGKDTVKIGGLKVKHQSIGLAIEES 220
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 174 GQTFVNAEFDGILGLGYPSLA---AGGVTPVFDNMMAQNLVALPMFSVYLSSDPQggSGSELTFGGYDPSH-FSG-SLNW 248
Cdd:PTZ00165 221 LHPFADLPFDGLVGLGFPDKDfkeSKKALPIVDNIKKQNLLKRNIFSFYMSKDLN--QPGSISFGSADPKYtLEGhKIWW 298
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 249 IPVTKQAYWQIALDGIQVGD-TVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPidgeyavDCATLDTMPNVTFL 327
Cdd:PTZ00165 299 FPVISTDYWEIEVVDILIDGkSLGFCDRKCKAAIDTGSSLITGPSSVINPLLEKIPLEE-------DCSNKDSLPRISFV 371
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 166235886 328 I-----NEVSYTLNPTDYILPDLVEGMQ--FCGSGFQGLDIPPPAGPLWILGDVFIRQFYSVFDRGNNQVGLAPA 395
Cdd:PTZ00165 372 LedvngRKIKFDMDPEDYVIEEGDSEEQehQCVIGIIPMDVPAPRGPLFVLGNNFIRKYYSIFDRDHMMVGLVPA 446
SAP_like cd05474
SAPs, pepsin-like proteinases secreted from pathogens to degrade host proteins; SAPs (Secreted ...
79-395 1.33e-53

SAPs, pepsin-like proteinases secreted from pathogens to degrade host proteins; SAPs (Secreted aspartic proteinases) are secreted from a group of pathogenic fungi, predominantly Candida species. They are secreted from the pathogen to degrade host proteins. SAP is one of the most significant extracellular hydrolytic enzymes produced by C. albicans. SAP proteins, encoded by a family of 10 SAP genes. All 10 SAP genes of C. albicans encode preproenzymes, approximately 60 amino acid longer than the mature enzyme, which are processed when transported via the secretory pathway. The mature enzymes contain sequence motifs typical for all aspartyl proteinases, including the two conserved aspartate residues other active site and conserved cysteine residues implicated in the maintenance of the three-dimensional structure. Most Sap proteins contain putative N-glycosylation sites, but it remains to be determined which Sap proteins are glycosylated. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA). The overall structure of Sap protein conforms to the classical aspartic proteinase fold typified by pepsin. SAP is a bilobal enzyme, 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. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133141 [Multi-domain]  Cd Length: 295  Bit Score: 179.68  E-value: 1.33e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPsvyctspackahpvfhpsqsdtytevgnHFSIQYGTGS-LTGIIGADQVSVE 157
Cdd:cd05474    3 YSAELSVGTPPQKVTVLLDTGSSDLWVP----------------------------DFSISYGDGTsASGTWGTDTVSIG 54
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 158 GLTVDGQQFGESVKEPGQTfvnaefdGILGLGYPSL-AAGGVTPVFDN----MMAQNLVALPMFSVYLSsDPQGGSGSeL 232
Cdd:cd05474   55 GATVKNLQFAVANSTSSDV-------GVLGIGLPGNeATYGTGYTYPNfpiaLKKQGLIKKNAYSLYLN-DLDASTGS-I 125
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 233 TFGGYDPSHFSGSLNWIPVTKQAYW------QIALDGIQVGD---TVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIG 303
Cdd:cd05474  126 LFGGVDTAKYSGDLVTLPIVNDNGGsepselSVTLSSISVNGssgNTTLLSKNLPALLDSGTTLTYLPSDIVDAIAKQLG 205
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 304 ATPIDGE--YAVDCATLDTMpNVTFLINEVSYTLNPTDYILPDLVEGMqfcGSGFQGLDIPPPAGPLWILGDVFIRQFYS 381
Cdd:cd05474  206 ATYDSDEglYVVDCDAKDDG-SLTFNFGGATISVPLSDLVLPASTDDG---GDGACYLGIQPSTSDYNILGDTFLRSAYV 281
                        330
                 ....*....|....
gi 166235886 382 VFDRGNNQVGLAPA 395
Cdd:cd05474  282 VYDLDNNEISLAQA 295
Aspergillopepsin_like cd06097
Aspergillopepsin_like, aspartic proteases of fungal origin; The members of this family are ...
79-394 2.37e-52

Aspergillopepsin_like, aspartic proteases of fungal origin; The members of this family are aspartic proteases of fungal origin, including aspergillopepsin, rhizopuspepsin, endothiapepsin, and rodosporapepsin. The various fungal species in this family may be the most economically important genus of fungi. They may serve as virulence factors or as industrial aids. For example, Aspergillopepsin from A. fumigatus is involved in invasive aspergillosis owing to its elastolytic activity and Aspergillopepsins from the mold A. saitoi are used in fermentation industry. Aspartic proteinases are a group of proteolytic enzymes in which the scissile peptide bond is attacked by a nucleophilic water molecule activated by two aspartic residues in a DT(S)G motif at the active site. They have a similar fold composed of two beta-barrel domains. Between the N-terminal and C-terminal domains, each of which contributes one catalytic aspartic residue, there is an extended active-site cleft capable of interacting with multiple residues of a substrate. Although members of the aspartic protease family of enzymes have very similar three-dimensional structures and catalytic mechanisms, each has unique substrate specificity. The members of this family has an optimal acidic pH (5.5) and cleaves protein substrates with similar specificity to that of porcine pepsin A, preferring hydrophobic residues at P1 and P1' in the cleave site. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133161 [Multi-domain]  Cd Length: 278  Bit Score: 175.95  E-value: 2.37e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNH-FSIQYGTGS-LTGIIGADQVSV 156
Cdd:cd06097    1 YLTPVKIGTPPQTLNLDLDTGSSDLWVFSSETPAAQQGGHKLYDPSKSSTAKLLPGAtWSISYGDGSsASGIVYTDTVSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 157 EGLTVDGQQFGESVKEPGQTFVNAEFDGILGLGYPSL---AAGGVTPVFDNMMAQnlVALPMFSVYLSSDpqggSGSELT 233
Cdd:cd06097   81 GGVEVPNQAIELATAVSASFFSDTASDGLLGLAFSSIntvQPPKQKTFFENALSS--LDAPLFTADLRKA----APGFYT 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 234 FGGYDPSHFSGSLNWIPVTK-QAYWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLITGPPDKIKQLQEAIGATPIDGEYA 312
Cdd:cd06097  155 FGYIDESKYKGEISWTPVDNsSGFWQFTSTSYTVGGDAPWSRSGFSAIADTGTTLILLPDAIVEAYYSQVPGAYYDSEYG 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 313 vdcatldtmpnvtflinevSYTLnPTDYILPDLVegmqfcgsgFQGLDipppagplwILGDVFIRQFYSVFDRGNNQVGL 392
Cdd:cd06097  235 -------------------GWVF-PCDTTLPDLS---------FAVFS---------ILGDVFLKAQYVVFDVGGPKLGF 276

                 ..
gi 166235886 393 AP 394
Cdd:cd06097  277 AP 278
PTZ00147 PTZ00147
plasmepsin-1; Provisional
68-395 7.12e-52

plasmepsin-1; Provisional


Pssm-ID: 140176 [Multi-domain]  Cd Length: 453  Bit Score: 179.68  E-value: 7.12e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  68 NEPLINYLDMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTG 147
Cdd:PTZ00147 129 NVELKDLANVMSYGEAKLGDNGQKFNFIFDTGSANLWVPSIKCTTEGCETKNLYDSSKSKTYEKDGTKVEMNYVSGTVSG 208
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 148 IIGADQVSVEGLTVDgQQFGESVKEPG--QTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLSsdPQ 225
Cdd:PTZ00147 209 FFSKDLVTIGNLSVP-YKFIEVTDTNGfePFYTESDFDGIFGLGWKDLSIGSVDPYVVELKNQNKIEQAVFTFYLP--PE 285
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 226 GGSGSELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDgIQVGDTVmfcSEGCQAIVDTGTSLITGPPDKIKQLQEAIGA- 304
Cdd:PTZ00147 286 DKHKGYLTIGGIEERFYEGPLTYEKLNHDLYWQVDLD-VHFGNVS---SEKANVIVDSGTSVITVPTEFLNKFVESLDVf 361
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 305 -TPIDGEYAVDCATlDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAgplWILGDVFIRQFYSVF 383
Cdd:PTZ00147 362 kVPFLPLYVTTCNN-TKLPTLEFRSPNKVYTLEPEYYLQPIEDIGSALCMLNIIPIDLEKNT---FILGDPFMRKYFTVF 437
                        330
                 ....*....|..
gi 166235886 384 DRGNNQVGLAPA 395
Cdd:PTZ00147 438 DYDNHTVGFALA 449
PTZ00013 PTZ00013
plasmepsin 4 (PM4); Provisional
76-395 1.23e-48

plasmepsin 4 (PM4); Provisional


Pssm-ID: 140051 [Multi-domain]  Cd Length: 450  Bit Score: 170.94  E-value: 1.23e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  76 DMEYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVS 155
Cdd:PTZ00013 136 NIMFYGEGEVGDNHQKFMLIFDTGSANLWVPSKKCDSIGCSIKNLYDSSKSKSYEKDGTKVDITYGSGTVKGFFSKDLVT 215
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 156 VEGLTVDgQQFGESVK----EPgqTFVNAEFDGILGLGYPSLAAGGVTPVFDNMMAQNLVALPMFSVYLS-SDPQGGSgs 230
Cdd:PTZ00013 216 LGHLSMP-YKFIEVTDtddlEP--IYSSSEFDGILGLGWKDLSIGSIDPIVVELKNQNKIDNALFTFYLPvHDVHAGY-- 290
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 231 eLTFGGYDPSHFSGSLNWIPVTKQAYWQIALDgIQVGDTVMfcsEGCQAIVDTGTSLITGPPDKIKQLQEAIGA--TPID 308
Cdd:PTZ00013 291 -LTIGGIEEKFYEGNITYEKLNHDLYWQIDLD-VHFGKQTM---QKANVIVDSGTTTITAPSEFLNKFFANLNVikVPFL 365
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 309 GEYAVDCATlDTMPNVTFLINEVSYTLNPTDYILPDLVEGMQFCGSGFQGLDIPPPAgplWILGDVFIRQFYSVFDRGNN 388
Cdd:PTZ00013 366 PFYVTTCDN-KEMPTLEFKSANNTYTLEPEYYMNPLLDVDDTLCMITMLPVDIDDNT---FILGDPFMRKYFTVFDYDKE 441

                 ....*..
gi 166235886 389 QVGLAPA 395
Cdd:PTZ00013 442 SVGFAIA 448
pepsin_retropepsin_like cd05470
Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular ...
81-188 5.05e-39

Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular and retroviral pepsin-like aspartate proteases. The cellular pepsin and pepsin-like enzymes are twice as long as their retroviral counterparts. The cellular pepsin-like aspartic proteases are found in mammals, plants, fungi and bacteria. These well known and extensively characterized enzymes include pepsins, chymosin, rennin, cathepsins, and fungal aspartic proteases. Several have long been known to be medically (rennin, cathepsin D and E, pepsin) or commercially (chymosin) important. The eukaryotic pepsin-like proteases contain two domains possessing similar topological features. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except in the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The eukaryotic pepsin-like proteases have two active site ASP residues with each N- and C-terminal lobe contributing one residue. While the fungal and mammalian pepsins are bilobal proteins, retropepsins function as dimers and the monomer resembles structure of the N- or C-terminal domains of eukaryotic enzyme. The active site motif (Asp-Thr/Ser-Gly-Ser) is conserved between the retroviral and eukaryotic proteases and between the N-and C-terminal of eukaryotic pepsin-like proteases. The retropepsin-like family includes pepsin-like aspartate proteases from retroviruses, retrotransposons and retroelements; as well as eukaryotic DNA-damage-inducible proteins (DDIs), and bacterial aspartate peptidases. Retropepsin is synthesized as part of the POL polyprotein that contains an aspartyl-protease, a reverse transcriptase, RNase H, and an integrase. The POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A) and A2 (retropepsin family).


Pssm-ID: 133137 [Multi-domain]  Cd Length: 109  Bit Score: 135.20  E-value: 5.05e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  81 GTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFH-PSQSDTYTEVGNHFSIQYGTGSLTGIIGADQVSVEGL 159
Cdd:cd05470    1 IEIGIGTPPQTFNVLLDTGSSNLWVPSVDCQSLAIYSHSSYDdPSASSTYSDNGCTFSITYGTGSLSGGLSTDTVSIGDI 80
                         90       100
                 ....*....|....*....|....*....
gi 166235886 160 TVDGQQFGESVKEPGQTFVNAEFDGILGL 188
Cdd:cd05470   81 EVVGQAFGCATDEPGATFLPALFDGILGL 109
beta_secretase_like cd05473
Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease; ...
79-393 1.17e-32

Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease; Beta-secretase also called BACE (beta-site of APP cleaving enzyme) or memapsin-2. Beta-secretase is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells. It cleaves amyloid precursor protein (APP) to reveal the N-terminus of the beta-amyloid peptides. The beta-amyloid peptides are the major components of the amyloid plaques formed in the brain of patients with Alzheimer's disease (AD). Since BACE mediates one of the cleavages responsible for generation of AD, it is regarded as a potential target for pharmacological intervention in AD. Beta-secretase is a member of pepsin family of aspartic proteases. Same as other aspartic proteases, beta-secretase is a bilobal enzyme, each lobe contributing a catalytic Asp 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. The enzymes 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. 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).


Pssm-ID: 133140 [Multi-domain]  Cd Length: 364  Bit Score: 126.00  E-value: 1.17e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVpsvyctspACKAHP----VFHPSQSDTYTEVGNHFSIQYGTGSLTGIIGADQV 154
Cdd:cd05473    4 YYIEMLIGTPPQKLNILVDTGSSNFAV--------AAAPHPfihtYFHRELSSTYRDLGKGVTVPYTQGSWEGELGTDLV 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 155 SV-EGLTVDGQQFGESVKEPGQTFVN-AEFDGILGLGYPSLA--AGGVTPVFDNMMAQ----NLVALPMFSVYLS--SDP 224
Cdd:cd05473   76 SIpKGPNVTFRANIAAITESENFFLNgSNWEGILGLAYAELArpDSSVEPFFDSLVKQtgipDVFSLQMCGAGLPvnGSA 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 225 QGGSGSELTFGGYDPSHFSGSLNWIPVTKQAYWQIALDGIQVG--DTVMFCSE--GCQAIVDTGTSLITGPPDKIKQLQE 300
Cdd:cd05473  156 SGTVGGSMVIGGIDPSLYKGDIWYTPIREEWYYEVIILKLEVGgqSLNLDCKEynYDKAIVDSGTTNLRLPVKVFNAAVD 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 301 AIGATPIDGEYAVD--------CATLDTMPNVTF------LINEVS-----YTLNPTDYILPDL-VEGMQFCgsgFQgLD 360
Cdd:cd05473  236 AIKAASLIEDFPDGfwlgsqlaCWQKGTTPWEIFpkisiyLRDENSsqsfrITILPQLYLRPVEdHGTQLDC---YK-FA 311
                        330       340       350
                 ....*....|....*....|....*....|...
gi 166235886 361 IPPPAGPLwILGDVFIRQFYSVFDRGNNQVGLA 393
Cdd:cd05473  312 ISQSTNGT-VIGAVIMEGFYVVFDRANKRVGFA 343
Plasmepsin_5 cd06096
Plasmepsins are a class of aspartic proteinases produced by the plasmodium parasite; The ...
79-391 1.76e-20

Plasmepsins are a class of aspartic proteinases produced by the plasmodium parasite; The family contains a group of aspartic proteinases homologous to plasmepsin 5. Plasmepsins are a class of at least 10 enzymes produced by the plasmodium parasite. Through their haemoglobin-degrading activity, they are an important cause of symptoms in malaria sufferers. This family of enzymes is a potential target for anti-malarial drugs. Plasmepsins are aspartic acid proteases, which means their active site contains two aspartic acid residues. These two aspartic acid residue act respectively as proton donor and proton acceptor, catalyzing the hydrolysis of peptide bond in proteins. Aspartic proteinases are composed of two structurally similar beta barrel lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The catalytic Asp residues are contained in an Asp-Thr-Gly-Ser/thr motif in both N- and C-terminal lobes of the enzyme. There are four types of plasmepsins, closely related but varying in the specificity of cleavage site. The name plasmepsin may come from plasmodium (the organism) and pepsin (a common aspartic acid protease with similar molecular structure). This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133160 [Multi-domain]  Cd Length: 326  Bit Score: 91.29  E-value: 1.76e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCtsPACKAH--PVFHPSQSDTYTEVGNH----------------FSIQY 140
Cdd:cd06096    4 YFIDIFIGNPPQKQSLILDTGSSSLSFPCSQC--KNCGIHmePPYNLNNSITSSILYCDcnkccyclsclnnkceYSISY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 141 GTGS-LTGIIGADQVSVE-GLTVDGQQFGESVKEPGQTFVNAEF-----DGILGLGYPSlaAGGVTPVFDNMMAQNLVAL 213
Cdd:cd06096   82 SEGSsISGFYFSDFVSFEsYLNSNSEKESFKKIFGCHTHETNLFltqqaTGILGLSLTK--NNGLPTPIILLFTKRPKLK 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 214 --PMFSVYLSSDpqggsGSELTFGGYDPSHFSGSLN----------WIPVTKQAYWQIALDGIQVGDTVMFCSE--GCQA 279
Cdd:cd06096  160 kdKIFSICLSED-----GGELTIGGYDKDYTVRNSSignnkvskivWTPITRKYYYYVKLEGLSVYGTTSNSGNtkGLGM 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 280 IVDTGTSLITGPPDKIKQLQEAIgatpidgeyavdcatldtmPNVTFLI-NEVSYTLNPTDYILPDlvEGMQFCGSGFQG 358
Cdd:cd06096  235 LVDSGSTLSHFPEDLYNKINNFF-------------------PTITIIFeNNLKIDWKPSSYLYKK--ESFWCKGGEKSV 293
                        330       340       350
                 ....*....|....*....|....*....|...
gi 166235886 359 LDIPppagplwILGDVFIRQFYSVFDRGNNQVG 391
Cdd:cd06096  294 SNKP-------ILGASFFKNKQIIFDLDNNRIG 319
pepsin_A_like_plant cd05476
Chroloplast Nucleoids DNA-binding Protease and Nucellin, pepsin-like aspartic proteases from ...
78-395 3.16e-19

Chroloplast Nucleoids DNA-binding Protease and Nucellin, pepsin-like aspartic proteases from plants; This family contains pepsin like aspartic proteases from plants including Chloroplast Nucleoids DNA-binding Protease and Nucellin. Chloroplast Nucleoids DNA-binding Protease catalyzes the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in senescent leaves of tobacco and Nucellins are important regulators of nucellar cell's progressive degradation after ovule fertilization. Structurally, aspartic proteases are bilobal enzymes, each lobe contributing a catalytic Asp 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. The enzymes 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. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH.


Pssm-ID: 133143 [Multi-domain]  Cd Length: 265  Bit Score: 86.55  E-value: 3.16e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  78 EYFGTISIGTPPQNFTVIFDTGSSNLWVPsvyCtspaCkahpvfhpsqsdtytevgnHFSIQYGTGSLT-GIIGADQVSV 156
Cdd:cd05476    1 EYLVTLSIGTPPQPFSLIVDTGSDLTWTQ---C----C-------------------SYEYSYGDGSSTsGVLATETFTF 54
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 157 EGLTVDGQQ--FGESVKEPGQTFVNAefDGILGLGYPSLAaggvtpvfdnMMAQNLVALPMFSVYLSSDPQGGSGSELTF 234
Cdd:cd05476   55 GDSSVSVPNvaFGCGTDNEGGSFGGA--DGILGLGRGPLS----------LVSQLGSTGNKFSYCLVPHDDTGGSSPLIL 122
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 235 GGYDpSHFSGSLNWIPVTKQA----YWQIALDGIQVGDTVMFCSEGCQAIVDTGTSLItgppdkikqlqeaigatpidge 310
Cdd:cd05476  123 GDAA-DLGGSGVVYTPLVKNPanptYYYVNLEGISVGGKRLPIPPSVFAIDSDGSGGT---------------------- 179
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 311 yAVDCATLDTM------PNVTF-LINEVSYTLNPTDYiLPDLVEGMqFCgSGFQgldiPPPAGPLWILGDVFIRQFYSVF 383
Cdd:cd05476  180 -IIDSGTTLTYlpdpayPDLTLhFDGGADLELPPENY-FVDVGEGV-VC-LAIL----SSSSGGVSILGNIQQQNFLVEY 251
                        330
                 ....*....|..
gi 166235886 384 DRGNNQVGLAPA 395
Cdd:cd05476  252 DLENSRLGFAPA 263
TAXi_N pfam14543
Xylanase inhibitor N-terminal; The N- and C-termini of the members of this family are jointly ...
79-236 3.75e-18

Xylanase inhibitor N-terminal; The N- and C-termini of the members of this family are jointly necessary for creating the catalytic pocket necessary for cleaving xylanase. Phytopathogens produce xylanase that destroys plant cells, so its destruction through proteolysis is vital for plant-survival.


Pssm-ID: 405265  Cd Length: 172  Bit Score: 81.17  E-value: 3.75e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886   79 YFGTISIGTPPQNFTVIFDTGSSNLWVP----------------------SVYCTSPACKAHPVFHPSQSDTYTEVGnHF 136
Cdd:pfam14543   1 YLVSISIGTPPVPFFLVVDTGSDLTWVQcdpccysqpdplfdpyksstyrPVPCSSPLCSLAIALSSPGPGCSSNTC-DY 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  137 SIQYGTGSLT-GIIGADQVSVE----GLTVDGQQFGESVKEPGQTFVNAefDGILGLGY-----PS-LAAGGVTPVfdnm 205
Cdd:pfam14543  80 EVSYGDGSSTsGVLATDTLTLNstggSVSVPNFVFGCGYGLLGGLPGGA--DGILGLGRgklslPSqLASQGFGNK---- 153
                         170       180       190
                  ....*....|....*....|....*....|.
gi 166235886  206 maqnlvalpmFSVYLSSDPqgGSGSELTFGG 236
Cdd:pfam14543 154 ----------FSYCLSSSS--SGSGVLFFGD 172
cnd41_like cd05472
Chloroplast Nucleoids DNA-binding Protease, catalyzes the degradation of ribulose-1, ...
78-395 7.24e-14

Chloroplast Nucleoids DNA-binding Protease, catalyzes the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase; Chloroplast Nucleoids DNA-binding Protease catalyzes the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in senescent leaves of tobacco. Antisense tobacco with reduced amount of CND41 maintained green leaves and constant protein levels, especially Rubisco. CND41 has DNA-binding as well as aspartic protease activities. The pepsin-like aspartic protease domain is located at the C-terminus of the protein. The enzyme is characterized by having two aspartic protease catalytic site motifs, the Asp-Thr-Gly-Ser in the N-terminal and Asp-Ser-Gly-Ser in the C-terminal region. Aspartic proteases 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. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).


Pssm-ID: 133139 [Multi-domain]  Cd Length: 299  Bit Score: 71.53  E-value: 7.24e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  78 EYFGTISIGTPPQNFTVIFDTGSSNLWVPsvyCtSPACKahpvfhpsqsdtytevgnhFSIQYGTGSLT-GIIGADQVSV 156
Cdd:cd05472    1 EYVVTVGLGTPARDQTVIVDTGSDLTWVQ---C-QPCCL-------------------YQVSYGDGSYTtGDLATDTLTL 57
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 157 EG-LTVDGQQFGESVKEPGqTFVNAefDGILGLG-----YPSLAA---GGVtpvfdnmmaqnlvalpmFSVYLSSDPQGG 227
Cdd:cd05472   58 GSsDVVPGFAFGCGHDNEG-LFGGA--AGLLGLGrgklsLPSQTAssyGGV-----------------FSYCLPDRSSSS 117
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 228 SGSeLTFGgyDPSHFSGSLNWIPVTKQA----YWQIALDGIQVGDTVM------FCSEGcqAIVDTGTSLITGPPDKIKQ 297
Cdd:cd05472  118 SGY-LSFG--AAASVPAGASFTPMLSNPrvptFYYVGLTGISVGGRRLpippasFGAGG--VIIDSGTVITRLPPSAYAA 192
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 298 LQEAIGATPIDGEYAVDCATLDT-----------MPNVTFLINE-VSYTLNPTDYILPDLVEGmQFCgSGFQGLDIPPPA 365
Cdd:cd05472  193 LRDAFRAAMAAYPRAPGFSILDTcydlsgfrsvsVPTVSLHFQGgADVELDASGVLYPVDDSS-QVC-LAFAGTSDDGGL 270
                        330       340       350
                 ....*....|....*....|....*....|
gi 166235886 366 GplwILGDVFIRQFYSVFDRGNNQVGLAPA 395
Cdd:cd05472  271 S---IIGNVQQQTFRVVYDVAGGRIGFAPG 297
PLN03146 PLN03146
aspartyl protease family protein; Provisional
78-307 3.71e-10

aspartyl protease family protein; Provisional


Pssm-ID: 178691 [Multi-domain]  Cd Length: 431  Bit Score: 61.19  E-value: 3.71e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  78 EYFGTISIGTPPQNFTVIFDTGSSNLWVPSVYCTSPACKAHPVFHPSQSDTYTEV----------GNH----------FS 137
Cdd:PLN03146  84 EYLMNISIGTPPVPILAIADTGSDLIWTQCKPCDDCYKQVSPLFDPKKSSTYKDVscdssqcqalGNQascsdentctYS 163
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 138 IQYGTGSLTGiigaDQVSVEGLTVDGQQfGESVKEPGQTF-----VNAEFD----GILGLGypslaaGGVTPVFDNMMAQ 208
Cdd:PLN03146 164 YSYGDGSFTK----GNLAVETLTIGSTS-GRPVSFPGIVFgcghnNGGTFDekgsGIVGLG------GGPLSLISQLGSS 232
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886 209 nlvALPMFS---VYLSSDPqgGSGSELTFGgyDPSHFSG----SLNWIPVTKQAYWQIALDGIQVGDTVM--------FC 273
Cdd:PLN03146 233 ---IGGKFSyclVPLSSDS--NGTSKINFG--TNAIVSGsgvvSTPLVSKDPDTFYYLTLEAISVGSKKLpytgssknGV 305
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 166235886 274 SEGcQAIVDTGTSLITGPPDKIKQL----QEAIGATPI 307
Cdd:PLN03146 306 EEG-NIIIDSGTTLTLLPSDFYSELesavEEAIGGERV 342
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
22-50 9.04e-09

A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal and propeptides. The animal pepsin-like endopeptidase propeptides form a distinct family of propeptides, which contain a conserved motif approximately 30 residues long. In pepsinogen A, the first 11 residues of the mature pepsin sequence are displaced by residues of the propeptide. The propeptide contains two helices that block the active site cleft, in particular the conserved Asp11 residue, in pepsin, hydrogen bonds to a conserved Arg residues in the propeptide. This hydrogen bond stabilizes the propeptide conformation and is probably responsible for triggering the conversion of pepsinogen to pepsin under acidic conditions.


Pssm-ID: 400357  Cd Length: 29  Bit Score: 50.40  E-value: 9.04e-09
                          10        20
                  ....*....|....*....|....*....
gi 166235886   22 LHRVPLRRHQSLRKKLRAQGQLSEFWRSH 50
Cdd:pfam07966   1 LVRIPLKKGKSIRETLREKGLLEEFLKEH 29
nucellin_like cd05475
Nucellins, plant aspartic proteases specifically expressed in nucellar cells during ...
79-190 5.04e-03

Nucellins, plant aspartic proteases specifically expressed in nucellar cells during degradation; Nucellins are important regulators of nucellar cell's progressive degradation after ovule fertilization. This degradation is a characteristic of programmed cell death. Nucellins are plant aspartic proteases specifically expressed in nucellar cells during degradation. The enzyme is characterized by having two aspartic protease catalytic site motifs, the Asp-Thr-Gly-Ser in the N-terminal and Asp-Ser-Gly-Ser in the C-terminal region, and two other regions nearly identical to two regions of plant aspartic proteases. Aspartic proteases 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. Although the three-dimensional structures of the two lobes are very similar, the amino acid sequences are more divergent, except for the conserved catalytic site motif.


Pssm-ID: 133142 [Multi-domain]  Cd Length: 273  Bit Score: 38.51  E-value: 5.04e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166235886  79 YFGTISIGTPPQNFTVIFDTGSSNLWVPSVY-CTSPACkahpvfhpsqsdtytevgnHFSIQY-GTGSLTGIIGADQVSV 156
Cdd:cd05475    3 YYVTINIGNPPKPYFLDIDTGSDLTWLQCDApCTGCQC-------------------DYEIEYaDGGSSMGVLVTDIFSL 63
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 166235886 157 EGltVDGQQFGESV-------KEPGQTFVNAEFDGILGLGY 190
Cdd:cd05475   64 KL--TNGSRAKPRIafgcgydQQGPLLNPPPPTDGILGLGR 102
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.19
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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