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Conserved domains on  [gi|114572172|ref|XP_001163151|]
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cathepsin E isoform X1 [Pan troglodytes]

Protein Classification

A1_Propeptide and Cathespin_E domain-containing protein( domain architecture ID 10546411)

A1_Propeptide and Cathespin_E domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Cathespin_E cd05486
Cathepsin E, non-lysosomal aspartic protease; Cathepsin E is an intracellular, non-lysosomal ...
78-393 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: 608.81  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSVEG 157
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYCTSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTVEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 158 LTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGGAGSELIFGGYD 237
Cdd:cd05486   81 ITVQNQQFAESVSEPGSTFQDSEFDGILGLAYPSLAVDGVTPVFDNMMAQNLVELPMFSVYMSRNPNSADGGELVFGGFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 238 HSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPVDGEYAVECANL 317
Cdd:cd05486  161 TSRFSGQLNWVPVTVQGYWQIQLDNIQVGGTVIFCSDGCQAIVDTGTSLITGPSGDIKQLQNYIGATATDGEYGVDCSTL 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 114572172 318 NVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGNNRVGLAP 393
Cdd:cd05486  241 SLMPSVTFTINGIPYSLSPQAYTLEDQSDGGGYCSSGFQGLDIPPPAGPLWILGDVFIRQYYSVFDRGNNRVGFAP 316
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
21-49 1.31e-07

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: 429758  Cd Length: 29  Bit Score: 47.33  E-value: 1.31e-07
                          10        20
                  ....*....|....*....|....*....
gi 114572172   21 LHRVPLRRHPSLKKKLRARSQLSEFWKSH 49
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 ...
78-393 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: 608.81  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSVEG 157
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYCTSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTVEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 158 LTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGGAGSELIFGGYD 237
Cdd:cd05486   81 ITVQNQQFAESVSEPGSTFQDSEFDGILGLAYPSLAVDGVTPVFDNMMAQNLVELPMFSVYMSRNPNSADGGELVFGGFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 238 HSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPVDGEYAVECANL 317
Cdd:cd05486  161 TSRFSGQLNWVPVTVQGYWQIQLDNIQVGGTVIFCSDGCQAIVDTGTSLITGPSGDIKQLQNYIGATATDGEYGVDCSTL 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 114572172 318 NVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGNNRVGLAP 393
Cdd:cd05486  241 SLMPSVTFTINGIPYSLSPQAYTLEDQSDGGGYCSSGFQGLDIPPPAGPLWILGDVFIRQYYSVFDRGNNRVGFAP 316
Asp pfam00026
Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and ...
77-394 2.08e-164

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: 463.28  E-value: 2.08e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172   77 EYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCT-SPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSV 155
Cdd:pfam00026   1 EYFGTISIGTPPQKFTVIFDTGSSDLWVPSSYCTkSSACKSHGTFDPSSSSTYKLNGTTFSISYGDGSASGFLGQDTVTV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  156 EGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSnpEGGAGSELIFGG 235
Cdd:pfam00026  81 GGLTITNQEFGLATKEPGSFFEYAKFDGILGLGFPSISAVGATPVFDNLKSQGLIDSPAFSVYLNS--PDAAGGEIIFGG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  236 YDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPV-DGEYAVEC 314
Cdd:pfam00026 159 VDPSKYTGSLTYVPVTSQGYWQITLDSVTVGGSTSACSSGCQAILDTGTSLLYGPTSIVSKIAKAVGASSSeYGEYVVDC 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  315 ANLNVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQfCSSGFQGldihPPAGPLWILGDVFIRQFYSVFDRGNNRVGLAPA 394
Cdd:pfam00026 239 DSISTLPDITFVIGGAKITVPPSAYVLQNSQGGST-CLSGFQP----PPGGPLWILGDVFLRSAYVVFDRDNNRIGFAPA 313
PTZ00165 PTZ00165
aspartyl protease; Provisional
22-394 2.07e-93

aspartyl protease; Provisional


Pssm-ID: 240300 [Multi-domain]  Cd Length: 482  Bit Score: 288.58  E-value: 2.07e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  22 HRVPLRRHPSLKKKlRARSQLSEF---WKSHNLDMIQFTESCSmdQSAKEPLINYLDMEYFGTISIGSPPQNFTVIFDTG 98
Cdd:PTZ00165  65 HKVELHRFALLKKK-RKKNSEKGYisrVLTKHKYLETKDPNGL--QYLQQDLLNFHNSQYFGEIQVGTPPKSFVVVFDTG 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  99 SSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQ---PGQSFS--IQYGTGSLSGIIGADQVSVEGLTVVGQQFGESVTEPG 173
Cdd:PTZ00165 142 SSNLWIPSKECKSGGCAPHRKFDPKKSSTYTKlklGDESAEtyIQYGTGECVLALGKDTVKIGGLKVKHQSIGLAIEESL 221
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 174 QTFVDAEFDGILGLGYPSLAV---GGVTPVFDNMMAQNLVDLPMFSVYMS--SNPEGgagsELIFGGYDHSH-FSG-SLN 246
Cdd:PTZ00165 222 HPFADLPFDGLVGLGFPDKDFkesKKALPIVDNIKKQNLLKRNIFSFYMSkdLNQPG----SISFGSADPKYtLEGhKIW 297
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 247 WVPVTKQAYWQIALDNIQVGG-TVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPvdgeyavECANLNVMPDVTF 325
Cdd:PTZ00165 298 WFPVISTDYWEIEVVDILIDGkSLGFCDRKCKAAIDTGSSLITGPSSVINPLLEKIPLEE-------DCSNKDSLPRISF 370
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 114572172 326 T---ING--VPYTLSPTAYTLLDFVDGMQ--FCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGNNRVGLAPA 394
Cdd:PTZ00165 371 VledVNGrkIKFDMDPEDYVIEEGDSEEQehQCVIGIIPMDVPAPRGPLFVLGNNFIRKYYSIFDRDHMMVGLVPA 446
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
21-49 1.31e-07

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: 429758  Cd Length: 29  Bit Score: 47.33  E-value: 1.31e-07
                          10        20
                  ....*....|....*....|....*....
gi 114572172   21 LHRVPLRRHPSLKKKLRARSQLSEFWKSH 49
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 ...
78-393 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: 608.81  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSVEG 157
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYCTSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTVEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 158 LTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGGAGSELIFGGYD 237
Cdd:cd05486   81 ITVQNQQFAESVSEPGSTFQDSEFDGILGLAYPSLAVDGVTPVFDNMMAQNLVELPMFSVYMSRNPNSADGGELVFGGFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 238 HSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPVDGEYAVECANL 317
Cdd:cd05486  161 TSRFSGQLNWVPVTVQGYWQIQLDNIQVGGTVIFCSDGCQAIVDTGTSLITGPSGDIKQLQNYIGATATDGEYGVDCSTL 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 114572172 318 NVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGNNRVGLAP 393
Cdd:cd05486  241 SLMPSVTFTINGIPYSLSPQAYTLEDQSDGGGYCSSGFQGLDIPPPAGPLWILGDVFIRQYYSVFDRGNNRVGFAP 316
pepsin_A cd05478
Pepsin A, aspartic protease produced in gastric mucosa of mammals; Pepsin, a well-known ...
68-393 1.26e-169

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: 476.55  E-value: 1.26e-169
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  68 EPLINYLDMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGI 147
Cdd:cd05478    1 EPLTNYLDMEYYGTISIGTPPQDFTVIFDTGSSNLWVPSVYCSSQACSNHNRFNPRQSSTYQSTGQPLSIQYGTGSMTGI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 148 IGADQVSVEGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEggA 227
Cdd:cd05478   81 LGYDTVQVGGISDTNQIFGLSETEPGSFFYYAPFDGILGLAYPSIASSGATPVFDNMMSQGLVSQDLFSVYLSSNGQ--Q 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 228 GSELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPV- 306
Cdd:cd05478  159 GSVVTFGGIDPSYYTGSLNWVPVTAETYWQITVDSVTINGQVVACSGGCQAIVDTGTSLLVGPSSDIANIQSDIGASQNq 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 307 DGEYAVECANLNVMPDVTFTINGVPYTLSPTAYTLLDFvdgmQFCSSGFQGLDihppAGPLWILGDVFIRQFYSVFDRGN 386
Cdd:cd05478  239 NGEMVVNCSSISSMPDVVFTINGVQYPLPPSAYILQDQ----GSCTSGFQSMG----LGELWILGDVFIRQYYSVFDRAN 310

                 ....*..
gi 114572172 387 NRVGLAP 393
Cdd:cd05478  311 NKVGLAP 317
Asp pfam00026
Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and ...
77-394 2.08e-164

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: 463.28  E-value: 2.08e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172   77 EYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCT-SPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSV 155
Cdd:pfam00026   1 EYFGTISIGTPPQKFTVIFDTGSSDLWVPSSYCTkSSACKSHGTFDPSSSSTYKLNGTTFSISYGDGSASGFLGQDTVTV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  156 EGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSnpEGGAGSELIFGG 235
Cdd:pfam00026  81 GGLTITNQEFGLATKEPGSFFEYAKFDGILGLGFPSISAVGATPVFDNLKSQGLIDSPAFSVYLNS--PDAAGGEIIFGG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  236 YDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPV-DGEYAVEC 314
Cdd:pfam00026 159 VDPSKYTGSLTYVPVTSQGYWQITLDSVTVGGSTSACSSGCQAILDTGTSLLYGPTSIVSKIAKAVGASSSeYGEYVVDC 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  315 ANLNVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQfCSSGFQGldihPPAGPLWILGDVFIRQFYSVFDRGNNRVGLAPA 394
Cdd:pfam00026 239 DSISTLPDITFVIGGAKITVPPSAYVLQNSQGGST-CLSGFQP----PPGGPLWILGDVFLRSAYVVFDRDNNRIGFAPA 313
Cathepsin_D2 cd05490
Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of ...
72-393 1.34e-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: 446.54  E-value: 1.34e-157
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  72 NYLDMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYC--TSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIG 149
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCslLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 150 ADQVSVEGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGGAGS 229
Cdd:cd05490   81 QDTVSIGGLQVEGQLFGEAVKQPGITFIAAKFDGILGMAYPRISVDGVTPVFDNIMAQKLVEQNVFSFYLNRDPDAQPGG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 230 ELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAP-VDG 308
Cdd:cd05490  161 ELMLGGTDPKYYTGDLHYVNVTRKAYWQIHMDQVDVGSGLTLCKGGCEAIVDTGTSLITGPVEEVRALQKAIGAVPlIQG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 309 EYAVECANLNVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGNNR 388
Cdd:cd05490  241 EYMIDCEKIPTLPVISFSLGGKVYPLTGEDYILKVSQRGTTICLSGFMGLDIPPPAGPLWILGDVFIGRYYTVFDRDNDR 320

                 ....*
gi 114572172 389 VGLAP 393
Cdd:cd05490  321 VGFAK 325
Cathepsin_D_like cd05485
Cathepsin_D_like, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase ...
68-392 7.96e-138

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: 396.53  E-value: 7.96e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  68 EPLINYLDMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYC--TSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLS 145
Cdd:cd05485    2 EPLSNYMDAQYYGVITIGTPPQSFKVVFDTGSSNLWVPSKKCswTNIACLLHNKYDSTKSSTYKKNGTEFAIQYGSGSLS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 146 GIIGADQVSVEGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEG 225
Cdd:cd05485   82 GFLSTDTVSVGGVSVKGQTFAEAINEPGLTFVAAKFDGILGMGYSSISVDGVVPVFYNMVNQKLVDAPVFSFYLNRDPSA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 226 GAGSELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTvMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAP 305
Cdd:cd05485  162 KEGGELILGGSDPKHYTGNFTYLPVTRKGYWQFKMDSVSVGEG-EFCSGGCQAIADTGTSLIAGPVDEIEKLNNAIGAKP 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 306 V-DGEYAVECANLNVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDR 384
Cdd:cd05485  241 IiGGEYMVNCSAIPSLPDITFVLGGKSFSLTGKDYVLKVTQMGQTICLSGFMGIDIPPPAGPLWILGDVFIGKYYTEFDL 320

                 ....*...
gi 114572172 385 GNNRVGLA 392
Cdd:cd05485  321 GNNRVGFA 328
phytepsin cd06098
Phytepsin, a plant homolog of mammalian lysosomal pepsins; Phytepsin, a plant homolog of ...
69-392 1.25e-134

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: 387.88  E-value: 1.25e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  69 PLINYLDMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYC-TSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGI 147
Cdd:cd06098    2 ALKNYLDAQYFGEIGIGTPPQKFTVIFDTGSSNLWVPSSKCyFSIACYFHSKYKSSKSSTYKKNGTSASIQYGTGSISGF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 148 IGADQVSVEGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGGA 227
Cdd:cd06098   82 FSQDSVTVGDLVVKNQVFIEATKEPGLTFLLAKFDGILGLGFQEISVGKAVPVWYNMVEQGLVKEPVFSFWLNRNPDEEE 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 228 GSELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGG-TVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNaigaapv 306
Cdd:cd06098  162 GGELVFGGVDPKHFKGEHTYVPVTRKGYWQFEMGDVLIGGkSTGFCAGGCAAIADSGTSLLAGPTTIVTQINS------- 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 307 dgeyAVECANLNVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGN 386
Cdd:cd06098  235 ----AVDCNSLSSMPNVSFTIGGKTFELTPEQYILKVGEGAAAQCISGFTALDVPPPRGPLWILGDVFMGAYHTVFDYGN 310

                 ....*.
gi 114572172 387 NRVGLA 392
Cdd:cd06098  311 LRVGFA 316
renin_like cd05487
Renin stimulates production of angiotensin and thus affects blood pressure; Renin, also known ...
70-394 8.76e-130

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: 376.04  E-value: 8.76e-130
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  70 LINYLDMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCtSP---ACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSG 146
Cdd:cd05487    1 LTNYLDTQYYGEIGIGTPPQTFKVVFDTGSSNLWVPSSKC-SPlytACVTHNLYDASDSSTYKENGTEFTIHYASGTVKG 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 147 IIGADQVSVEGLTVVgQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGG 226
Cdd:cd05487   80 FLSQDIVTVGGIPVT-QMFGEVTALPAIPFMLAKFDGVLGMGYPKQAIGGVTPVFDNIMSQGVLKEDVFSVYYSRDSSHS 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 227 AGSELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPV 306
Cdd:cd05487  159 LGGEIVLGGSDPQHYQGDFHYINTSKTGFWQIQMKGVSVGSSTLLCEDGCTAVVDTGASFISGPTSSISKLMEALGAKER 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 307 DGEYAVECANLNVMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGN 386
Cdd:cd05487  239 LGDYVVKCNEVPTLPDISFHLGGKEYTLSSSDYVLQDSDFSDKLCTVAFHAMDIPPPTGPLWVLGATFIRKFYTEFDRQN 318

                 ....*...
gi 114572172 387 NRVGLAPA 394
Cdd:cd05487  319 NRIGFALA 326
gastricsin cd05477
Gastricsins, asparate proteases produced in gastric mucosa; Gastricsin is also called ...
75-394 1.49e-128

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: 372.30  E-value: 1.49e-128
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  75 DMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVS 154
Cdd:cd05477    1 DMSYYGEISIGTPPQNFLVLFDTGSSNLWVPSVLCQSQACTNHTKFNPSQSSTYSTNGETFSLQYGSGSLTGIFGYDTVT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 155 VEGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMsSNPEGGAGSELIFG 234
Cdd:cd05477   81 VQGIIITNQEFGLSETEPGTNFVYAQFDGILGLAYPSISAGGATTVMQGMMQQNLLQAPIFSFYL-SGQQGQQGGELVFG 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 235 GYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVM-FCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPVD-GEYAV 312
Cdd:cd05477  160 GVDNNLYTGQIYWTPVTSETYWQIGIQGFQINGQATgWCSQGCQAIVDTGTSLLTAPQQVMSTLMQSIGAQQDQyGQYVV 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 313 ECANLNVMPDVTFTINGVPYTLSPTAYTLldfvDGMQFCSSGFQGLDIHPPAG-PLWILGDVFIRQFYSVFDRGNNRVGL 391
Cdd:cd05477  240 NCNNIQNLPTLTFTINGVSFPLPPSAYIL----QNNGYCTVGIEPTYLPSQNGqPLWILGDVFLRQYYSVYDLGNNQVGF 315

                 ...
gi 114572172 392 APA 394
Cdd:cd05477  316 ATA 318
Proteinase_A_fungi cd05488
Fungal Proteinase A , aspartic proteinase superfamily; Fungal Proteinase A, a proteolytic ...
69-393 1.38e-125

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: 364.84  E-value: 1.38e-125
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  69 PLINYLDMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGII 148
Cdd:cd05488    2 PLTNYLNAQYFTDITLGTPPQKFKVILDTGSSNLWVPSVKCGSIACFLHSKYDSSASSTYKANGTEFKIQYGSGSLEGFV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 149 GADQVSVEGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGgaG 228
Cdd:cd05488   82 SQDTLSIGDLTIKKQDFAEATSEPGLAFAFGKFDGILGLAYDTISVNKIVPPFYNMINQGLLDEPVFSFYLGSSEED--G 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 229 SELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGTVMFCsEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPV-D 307
Cdd:cd05488  160 GEATFGGIDESRFTGKITWLPVRRKAYWEVELEKIGLGDEELEL-ENTGAAIDTGTSLIALPSDLAEMLNAEIGAKKSwN 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 308 GEYAVECANLNVMPDVTFTINGVPYTLSPTAYTLLdfVDGMqfCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGNN 387
Cdd:cd05488  239 GQYTVDCSKVDSLPDLTFNFDGYNFTLGPFDYTLE--VSGS--CISAFTGMDFPEPVGPLAIVGDAFLRKYYSVYDLGNN 314

                 ....*.
gi 114572172 388 RVGLAP 393
Cdd:cd05488  315 AVGLAK 320
pepsin_like cd05471
Pepsin-like aspartic proteases, bilobal enzymes that cleave bonds in peptides at acidic pH; ...
78-393 5.39e-113

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: 331.70  E-value: 5.39e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQ--PSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSV 155
Cdd:cd05471    1 YYGEITIGTPPQKFSVIFDTGSSLLWVPSSNCTSCSCQKHPRFKydSSKSSTYKDTGCTFSITYGDGSVTGGLGTDTVTI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 156 EGLTVVGQQFGESVTEPGqTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNPEGGAGSELIFGG 235
Cdd:cd05471   81 GGLTIPNQTFGCATSESG-DFSSSGFDGILGLGFPSLSVDGVPSFFDQLKSQGLISSPVFSFYLGRDGDGGNGGELTFGG 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 236 YDHSHFSGSLNWVPVTK--QAYWQIALDNIQVGGT-VMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPV--DGEY 310
Cdd:cd05471  160 IDPSKYTGDLTYTPVVSngPGYWQVPLDGISVGGKsVISSSGGGGAIVDSGTSLIYLPSSVYDAILKALGAAVSssDGGY 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 311 AVECANLNVMPDVTFTIngvpytlsptaytlldfvdgmqfcssgfqgldihppagpLWILGDVFIRQFYSVFDRGNNRVG 390
Cdd:cd05471  240 GVDCSPCDTLPDITFTF---------------------------------------LWILGDVFLRNYYTVFDLDNNRIG 280

                 ...
gi 114572172 391 LAP 393
Cdd:cd05471  281 FAP 283
PTZ00165 PTZ00165
aspartyl protease; Provisional
22-394 2.07e-93

aspartyl protease; Provisional


Pssm-ID: 240300 [Multi-domain]  Cd Length: 482  Bit Score: 288.58  E-value: 2.07e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  22 HRVPLRRHPSLKKKlRARSQLSEF---WKSHNLDMIQFTESCSmdQSAKEPLINYLDMEYFGTISIGSPPQNFTVIFDTG 98
Cdd:PTZ00165  65 HKVELHRFALLKKK-RKKNSEKGYisrVLTKHKYLETKDPNGL--QYLQQDLLNFHNSQYFGEIQVGTPPKSFVVVFDTG 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  99 SSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQ---PGQSFS--IQYGTGSLSGIIGADQVSVEGLTVVGQQFGESVTEPG 173
Cdd:PTZ00165 142 SSNLWIPSKECKSGGCAPHRKFDPKKSSTYTKlklGDESAEtyIQYGTGECVLALGKDTVKIGGLKVKHQSIGLAIEESL 221
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 174 QTFVDAEFDGILGLGYPSLAV---GGVTPVFDNMMAQNLVDLPMFSVYMS--SNPEGgagsELIFGGYDHSH-FSG-SLN 246
Cdd:PTZ00165 222 HPFADLPFDGLVGLGFPDKDFkesKKALPIVDNIKKQNLLKRNIFSFYMSkdLNQPG----SISFGSADPKYtLEGhKIW 297
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 247 WVPVTKQAYWQIALDNIQVGG-TVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPvdgeyavECANLNVMPDVTF 325
Cdd:PTZ00165 298 WFPVISTDYWEIEVVDILIDGkSLGFCDRKCKAAIDTGSSLITGPSSVINPLLEKIPLEE-------DCSNKDSLPRISF 370
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 114572172 326 T---ING--VPYTLSPTAYTLLDFVDGMQ--FCSSGFQGLDIHPPAGPLWILGDVFIRQFYSVFDRGNNRVGLAPA 394
Cdd:PTZ00165 371 VledVNGrkIKFDMDPEDYVIEEGDSEEQehQCVIGIIPMDVPAPRGPLFVLGNNFIRKYYSIFDRDHMMVGLVPA 446
PTZ00147 PTZ00147
plasmepsin-1; Provisional
70-394 1.82e-53

plasmepsin-1; Provisional


Pssm-ID: 140176 [Multi-domain]  Cd Length: 453  Bit Score: 183.91  E-value: 1.82e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  70 LINYLDMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIG 149
Cdd:PTZ00147 132 LKDLANVMSYGEAKLGDNGQKFNFIFDTGSANLWVPSIKCTTEGCETKNLYDSSKSKTYEKDGTKVEMNYVSGTVSGFFS 211
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 150 ADQVSVEGLTvVGQQFGESVTEPG--QTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSsnPEGGA 227
Cdd:PTZ00147 212 KDLVTIGNLS-VPYKFIEVTDTNGfePFYTESDFDGIFGLGWKDLSIGSVDPYVVELKNQNKIEQAVFTFYLP--PEDKH 288
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 228 GSELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDnIQVGGTVmfcSEGCQAIVDTGTSLITGPSDKIKQ-LQNA-IGAAP 305
Cdd:PTZ00147 289 KGYLTIGGIEERFYEGPLTYEKLNHDLYWQVDLD-VHFGNVS---SEKANVIVDSGTSVITVPTEFLNKfVESLdVFKVP 364
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 306 VDGEYAVECANLNvMPDVTFTINGVPYTLSPTAYTLLDFVDGMQFCSSGFQGLDIHPPAgplWILGDVFIRQFYSVFDRG 385
Cdd:PTZ00147 365 FLPLYVTTCNNTK-LPTLEFRSPNKVYTLEPEYYLQPIEDIGSALCMLNIIPIDLEKNT---FILGDPFMRKYFTVFDYD 440

                 ....*....
gi 114572172 386 NNRVGLAPA 394
Cdd:PTZ00147 441 NHTVGFALA 449
SAP_like cd05474
SAPs, pepsin-like proteinases secreted from pathogens to degrade host proteins; SAPs (Secreted ...
78-394 4.54e-52

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: 175.45  E-value: 4.54e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSvyctspackthsrfqpsqsstysqpgqsFSIQYGTGS-LSGIIGADQVSVE 156
Cdd:cd05474    3 YSAELSVGTPPQKVTVLLDTGSSDLWVPD----------------------------FSISYGDGTsASGTWGTDTVSIG 54
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 157 GLTVVGQQFGESVTEPGQTfvdaefdGILGLGYPSL-AVGGVTPVFDN----MMAQNLVDLPMFSVYMSSnPEGGAGSeL 231
Cdd:cd05474   55 GATVKNLQFAVANSTSSDV-------GVLGIGLPGNeATYGTGYTYPNfpiaLKKQGLIKKNAYSLYLND-LDASTGS-I 125
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 232 IFGGYDHSHFSGSLNWVPVTKQAYW------QIALDNIQVGG---TVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIG 302
Cdd:cd05474  126 LFGGVDTAKYSGDLVTLPIVNDNGGsepselSVTLSSISVNGssgNTTLLSKNLPALLDSGTTLTYLPSDIVDAIAKQLG 205
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 303 AA--PVDGEYAVECaNLNVMPDVTFTING----VPytLSPTAYTLLDFVDGMQFCssgfqGLDIHPPAGPLWILGDVFIR 376
Cdd:cd05474  206 ATydSDEGLYVVDC-DAKDDGSLTFNFGGatisVP--LSDLVLPASTDDGGDGAC-----YLGIQPSTSDYNILGDTFLR 277
                        330
                 ....*....|....*...
gi 114572172 377 QFYSVFDRGNNRVGLAPA 394
Cdd:cd05474  278 SAYVVYDLDNNEISLAQA 295
Aspergillopepsin_like cd06097
Aspergillopepsin_like, aspartic proteases of fungal origin; The members of this family are ...
78-393 2.45e-51

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: 173.26  E-value: 2.45e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTY-SQPGQSFSIQYGTGS-LSGIIGADQVSV 155
Cdd:cd06097    1 YLTPVKIGTPPQTLNLDLDTGSSDLWVFSSETPAAQQGGHKLYDPSKSSTAkLLPGATWSISYGDGSsASGIVYTDTVSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 156 EGLTVVGQQFGESVTEPGQTFVDAEFDGILGLGYPSL---AVGGVTPVFDNMMAQnlVDLPMFSVYMSSNPEGgagsELI 232
Cdd:cd06097   81 GGVEVPNQAIELATAVSASFFSDTASDGLLGLAFSSIntvQPPKQKTFFENALSS--LDAPLFTADLRKAAPG----FYT 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 233 FGGYDHSHFSGSLNWVPVTK-QAYWQIALDNIQVGGTVMFCSEGCQAIVDTGTSLITGPSDKIKQLQNAIGAAPVDGEYA 311
Cdd:cd06097  155 FGYIDESKYKGEISWTPVDNsSGFWQFTSTSYTVGGDAPWSRSGFSAIADTGTTLILLPDAIVEAYYSQVPGAYYDSEYG 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 312 ---VECaNLNvMPDVTFTINGvpytlsptaytlldfvdgmqfcssgfqgldihppagplwILGDVFIRQFYSVFDRGNNR 388
Cdd:cd06097  235 gwvFPC-DTT-LPDLSFAVFS---------------------------------------ILGDVFLKAQYVVFDVGGPK 273

                 ....*
gi 114572172 389 VGLAP 393
Cdd:cd06097  274 LGFAP 278
PTZ00013 PTZ00013
plasmepsin 4 (PM4); Provisional
75-394 7.47e-50

plasmepsin 4 (PM4); Provisional


Pssm-ID: 140051 [Multi-domain]  Cd Length: 450  Bit Score: 174.02  E-value: 7.47e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  75 DMEYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVS 154
Cdd:PTZ00013 136 NIMFYGEGEVGDNHQKFMLIFDTGSANLWVPSKKCDSIGCSIKNLYDSSKSKSYEKDGTKVDITYGSGTVKGFFSKDLVT 215
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 155 VEGLTvVGQQFGEsVT-----EPgqTFVDAEFDGILGLGYPSLAVGGVTPVFDNMMAQNLVDLPMFSVYMSSNpEGGAGS 229
Cdd:PTZ00013 216 LGHLS-MPYKFIE-VTdtddlEP--IYSSSEFDGILGLGWKDLSIGSIDPIVVELKNQNKIDNALFTFYLPVH-DVHAGY 290
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 230 eLIFGGYDHSHFSGSLNWVPVTKQAYWQIALDnIQVGGTVMfcsEGCQAIVDTGTSLITGPSDKIKQL---QNAIgAAPV 306
Cdd:PTZ00013 291 -LTIGGIEEKFYEGNITYEKLNHDLYWQIDLD-VHFGKQTM---QKANVIVDSGTTTITAPSEFLNKFfanLNVI-KVPF 364
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 307 DGEYAVECANlNVMPDVTFTINGVPYTLSPTAYT--LLDFVDGMqfCSSGFQGLDIHPPAgplWILGDVFIRQFYSVFDR 384
Cdd:PTZ00013 365 LPFYVTTCDN-KEMPTLEFKSANNTYTLEPEYYMnpLLDVDDTL--CMITMLPVDIDDNT---FILGDPFMRKYFTVFDY 438
                        330
                 ....*....|
gi 114572172 385 GNNRVGLAPA 394
Cdd:PTZ00013 439 DKESVGFAIA 448
pepsin_retropepsin_like cd05470
Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular ...
80-187 1.26e-43

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: 147.53  E-value: 1.26e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  80 GTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRF-QPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSVEGL 158
Cdd:cd05470    1 IEIGIGTPPQTFNVLLDTGSSNLWVPSVDCQSLAIYSHSSYdDPSASSTYSDNGCTFSITYGTGSLSGGLSTDTVSIGDI 80
                         90       100
                 ....*....|....*....|....*....
gi 114572172 159 TVVGQQFGESVTEPGQTFVDAEFDGILGL 187
Cdd:cd05470   81 EVVGQAFGCATDEPGATFLPALFDGILGL 109
beta_secretase_like cd05473
Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease; ...
78-392 2.53e-31

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: 122.15  E-value: 2.53e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSvyctSPACKTHSRFQPSQSSTYSQPGQSFSIQYGTGSLSGIIGADQVSV-E 156
Cdd:cd05473    4 YYIEMLIGTPPQKLNILVDTGSSNFAVAA----APHPFIHTYFHRELSSTYRDLGKGVTVPYTQGSWEGELGTDLVSIpK 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 157 GLTVVGQQFGESVTEPGQTFV-DAEFDGILGLGYPSLAV--GGVTPVFDNMMAQ-NLVDLpmFSVYM-------SSNPEG 225
Cdd:cd05473   80 GPNVTFRANIAAITESENFFLnGSNWEGILGLAYAELARpdSSVEPFFDSLVKQtGIPDV--FSLQMcgaglpvNGSASG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 226 GAGSELIFGGYDHSHFSGSLNWVPVTKQAYWQIALDNIQVGGT--VMFCSE--GCQAIVDTGTSLITGPSDKIKQLQNAI 301
Cdd:cd05473  158 TVGGSMVIGGIDPSLYKGDIWYTPIREEWYYEVIILKLEVGGQslNLDCKEynYDKAIVDSGTTNLRLPVKVFNAAVDAI 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 302 GAAPVDGEYAVE--------CAN-----LNVMPDVT-----------FTIngvpyTLSPTAY--TLLDFVDGMQfC---- 351
Cdd:cd05473  238 KAASLIEDFPDGfwlgsqlaCWQkgttpWEIFPKISiylrdenssqsFRI-----TILPQLYlrPVEDHGTQLD-Cykfa 311
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|..
gi 114572172 352 -SSGFQGLdihppagplwILGDVFIRQFYSVFDRGNNRVGLA 392
Cdd:cd05473  312 iSQSTNGT----------VIGAVIMEGFYVVFDRANKRVGFA 343
Plasmepsin_5 cd06096
Plasmepsins are a class of aspartic proteinases produced by the plasmodium parasite; The ...
78-390 1.44e-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: 1.44e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCtsPACKTHSR--FQPSQSSTYSQPGQS----------------FSIQY 139
Cdd:cd06096    4 YFIDIFIGNPPQKQSLILDTGSSSLSFPCSQC--KNCGIHMEppYNLNNSITSSILYCDcnkccyclsclnnkceYSISY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 140 GTGS-LSGIIGADQVSVE-GLTVVGQQFGESVTEPGQTFVDAEF-----DGILGLGYPSLAvgGVTPVFDNMMAQNLVDL 212
Cdd:cd06096   82 SEGSsISGFYFSDFVSFEsYLNSNSEKESFKKIFGCHTHETNLFltqqaTGILGLSLTKNN--GLPTPIILLFTKRPKLK 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 213 --PMFSVYMSSNpeggaGSELIFGGYDHSHFSGSLN----------WVPVTKQAYWQIALDNIQVGGTVMFCSE--GCQA 278
Cdd:cd06096  160 kdKIFSICLSED-----GGELTIGGYDKDYTVRNSSignnkvskivWTPITRKYYYYVKLEGLSVYGTTSNSGNtkGLGM 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 279 IVDTGTSLITGPSDKIKQLqnaigaapvdgeyavecanLNVMPDVTFTI-NGVPYTLSPTAYTLLDFVdgmQFCSSGFQG 357
Cdd:cd06096  235 LVDSGSTLSHFPEDLYNKI-------------------NNFFPTITIIFeNNLKIDWKPSSYLYKKES---FWCKGGEKS 292
                        330       340       350
                 ....*....|....*....|....*....|...
gi 114572172 358 LDIHPpagplwILGDVFIRQFYSVFDRGNNRVG 390
Cdd:cd06096  293 VSNKP------ILGASFFKNKQIIFDLDNNRIG 319
pepsin_A_like_plant cd05476
Chroloplast Nucleoids DNA-binding Protease and Nucellin, pepsin-like aspartic proteases from ...
77-394 5.12e-18

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: 83.08  E-value: 5.12e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  77 EYFGTISIGSPPQNFTVIFDTGSSNLWVPsvyCtspaCkthsrfqpsqsstysqpgqSFSIQYGTGSLS-GIIGADQVSV 155
Cdd:cd05476    1 EYLVTLSIGTPPQPFSLIVDTGSDLTWTQ---C----C-------------------SYEYSYGDGSSTsGVLATETFTF 54
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 156 EGLTVVGQQ--FGESVTEPGQTFvdAEFDGILGLGYPSLAVggvtpvfdnmMAQNLVDLPMFSVYMSSNPEGGAGSELIF 233
Cdd:cd05476   55 GDSSVSVPNvaFGCGTDNEGGSF--GGADGILGLGRGPLSL----------VSQLGSTGNKFSYCLVPHDDTGGSSPLIL 122
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 234 GGYDhSHFSGSLNWVPVTKQA----YWQIALDNIQVGGTVMFCSEGCQA---------IVDTGTSLITGPSdkikqlqna 300
Cdd:cd05476  123 GDAA-DLGGSGVVYTPLVKNPanptYYYVNLEGISVGGKRLPIPPSVFAidsdgsggtIIDSGTTLTYLPD--------- 192
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 301 igaapvdgeyavecanlNVMPDVTFT-INGVPYTLSPTAYtlldFVDGMQ--FCSSGFQGldihpPAGPLWILGDVFIRQ 377
Cdd:cd05476  193 -----------------PAYPDLTLHfDGGADLELPPENY----FVDVGEgvVCLAILSS-----SSGGVSILGNIQQQN 246
                        330
                 ....*....|....*..
gi 114572172 378 FYSVFDRGNNRVGLAPA 394
Cdd:cd05476  247 FLVEYDLENSRLGFAPA 263
TAXi_N pfam14543
Xylanase inhibitor N-terminal; The N- and C-termini of the members of this family are jointly ...
78-235 5.15e-15

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: 434031 [Multi-domain]  Cd Length: 174  Bit Score: 72.32  E-value: 5.15e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172   78 YFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKThsRFQPSQSSTYS------------------QPGQS----- 134
Cdd:pfam14543   1 YLVTISIGTPPVPFKLVVDTGSDLTWVQCDPCCYSQPDP--LFDPYKSSTYKpvpcssplcslaialsspGPCCSnntcd 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  135 FSIQYGTGSLS-GIIGADQVSVE-----GLTVVGQQFGESVTEPGQTFVDAefDGILGLGYPSLAVG---GVTPVFDNmm 205
Cdd:pfam14543  79 YEVSYGDGSSTsGVLATDTLTLNstdggSVSVPNFVFGCGYNLLGGLPAGA--DGILGLGRGKLSLPsqlASAGIFGN-- 154
                         170       180       190
                  ....*....|....*....|....*....|
gi 114572172  206 aqnlvdlpMFSVYMSSNPegGAGSELIFGG 235
Cdd:pfam14543 155 --------KFSYCLSSSS--SGSGVLFFGD 174
cnd41_like cd05472
Chloroplast Nucleoids DNA-binding Protease, catalyzes the degradation of ribulose-1, ...
77-394 3.73e-13

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: 69.22  E-value: 3.73e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  77 EYFGTISIGSPPQNFTVIFDTGSSNLWVPsvyCtSPACkthsrfqpsqsstysqpgqSFSIQYGTGSLS-GIIGADQVSV 155
Cdd:cd05472    1 EYVVTVGLGTPARDQTVIVDTGSDLTWVQ---C-QPCC-------------------LYQVSYGDGSYTtGDLATDTLTL 57
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 156 EGLTVV-GQQFGESVTEPGqTFVDAefDGILGLGYPSLA-VGGVTPVFDNMMAQNLVDLpmfsvymssnpEGGAGSELIF 233
Cdd:cd05472   58 GSSDVVpGFAFGCGHDNEG-LFGGA--AGLLGLGRGKLSlPSQTASSYGGVFSYCLPDR-----------SSSSSGYLSF 123
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 234 GGYdhSHFSGSLNWVPVTKQA----YWQIALDNIQVGGTVM------FCSEGcqAIVDTGTSLITGPSDKIKQLQNAIGA 303
Cdd:cd05472  124 GAA--ASVPAGASFTPMLSNPrvptFYYVGLTGISVGGRRLpippasFGAGG--VIIDSGTVITRLPPSAYAALRDAFRA 199
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 304 A----PVDGEYAV--ECANLNVMPDVTF-TI-----NGVPYTLSPTAYtLLDFVDGMQFCsSGFQGLDIHPPAGplwILG 371
Cdd:cd05472  200 AmaayPRAPGFSIldTCYDLSGFRSVSVpTVslhfqGGADVELDASGV-LYPVDDSSQVC-LAFAGTSDDGGLS---IIG 274
                        330       340
                 ....*....|....*....|...
gi 114572172 372 DVFIRQFYSVFDRGNNRVGLAPA 394
Cdd:cd05472  275 NVQQQTFRVVYDVAGGRIGFAPG 297
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
21-49 1.31e-07

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: 429758  Cd Length: 29  Bit Score: 47.33  E-value: 1.31e-07
                          10        20
                  ....*....|....*....|....*....
gi 114572172   21 LHRVPLRRHPSLKKKLRARSQLSEFWKSH 49
Cdd:pfam07966   1 LVRIPLKKGKSIRETLREKGLLEEFLKEH 29
PLN03146 PLN03146
aspartyl protease family protein; Provisional
77-306 1.77e-07

aspartyl protease family protein; Provisional


Pssm-ID: 178691 [Multi-domain]  Cd Length: 431  Bit Score: 52.71  E-value: 1.77e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172  77 EYFGTISIGSPPQNFTVIFDTGSSNLWVPSVYCTSPACKTHSRFQPSQSSTY------------------SQPGQ--SFS 136
Cdd:PLN03146  84 EYLMNISIGTPPVPILAIADTGSDLIWTQCKPCDDCYKQVSPLFDPKKSSTYkdvscdssqcqalgnqasCSDENtcTYS 163
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 137 IQYGTGSLSGiigaDQVSVEGLTvVGQQFGESVTEPGQTF-----VDAEFD----GILGLGYPSLA-VGGVTPVFDNMMA 206
Cdd:PLN03146 164 YSYGDGSFTK----GNLAVETLT-IGSTSGRPVSFPGIVFgcghnNGGTFDekgsGIVGLGGGPLSlISQLGSSIGGKFS 238
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114572172 207 QNLVDLpmfsvymSSNPegGAGSELIFGgyDHSHFSG----SLNWVPVTKQAYWQIALDNIQVG-------GTVMFCSEG 275
Cdd:PLN03146 239 YCLVPL-------SSDS--NGTSKINFG--TNAIVSGsgvvSTPLVSKDPDTFYYLTLEAISVGskklpytGSSKNGVEE 307
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 114572172 276 CQAIVDTGTSLITGPSDKIKQL----QNAIGAAPV 306
Cdd:PLN03146 308 GNIIIDSGTTLTLLPSDFYSELesavEEAIGGERV 342
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
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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