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Conserved domains on  [gi|849565237|ref|NP_571785|]
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cathepsin D precursor [Danio rerio]

Protein Classification

pepsin-like aspartic protease( domain architecture ID 10546413)

pepsin-like (A1 family) peptidase is an aspartic endoprotease that hydrolyzes the peptide bonds of substrates

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Cathepsin_D2 cd05490
Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of ...
70-394 0e+00

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: 685.75  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  70 NYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLS 149
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCSLLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 150 QDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQPGG 229
Cdd:cd05490   81 QDTVSIGGLQVEGQLFGEAVKQPGITFIAAKFDGILGMAYPRISVDGVTPVFDNIMAQKLVEQNVFSFYLNRDPDAQPGG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 230 ELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIPLMQG 309
Cdd:cd05490  161 ELMLGGTDPKYYTGDLHYVNVTRKAYWQIHMDQVDVGSGLTLCKGGCEAIVDTGTSLITGPVEEVRALQKAIGAVPLIQG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 310 EYMVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFDRENNR 389
Cdd:cd05490  241 EYMIDCEKIPTLPVISFSLGGKVYPLTGEDYILKVSQRGTTICLSGFMGLDIPPPAGPLWILGDVFIGRYYTVFDRDNDR 320

                 ....*
gi 849565237 390 VGFAK 394
Cdd:cd05490  321 VGFAK 325
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
21-44 3.39e-04

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: 462326  Cd Length: 27  Bit Score: 37.70  E-value: 3.39e-04
                          10        20
                  ....*....|....*....|....
gi 849565237   21 RIPLKKFRTLRRTLSDSGrSLEEL 44
Cdd:pfam07966   1 RIPLKKGKSIRETLREKG-LLEEF 23
 
Name Accession Description Interval E-value
Cathepsin_D2 cd05490
Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of ...
70-394 0e+00

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: 685.75  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  70 NYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLS 149
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCSLLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 150 QDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQPGG 229
Cdd:cd05490   81 QDTVSIGGLQVEGQLFGEAVKQPGITFIAAKFDGILGMAYPRISVDGVTPVFDNIMAQKLVEQNVFSFYLNRDPDAQPGG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 230 ELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIPLMQG 309
Cdd:cd05490  161 ELMLGGTDPKYYTGDLHYVNVTRKAYWQIHMDQVDVGSGLTLCKGGCEAIVDTGTSLITGPVEEVRALQKAIGAVPLIQG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 310 EYMVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFDRENNR 389
Cdd:cd05490  241 EYMIDCEKIPTLPVISFSLGGKVYPLTGEDYILKVSQRGTTICLSGFMGLDIPPPAGPLWILGDVFIGRYYTVFDRDNDR 320

                 ....*
gi 849565237 390 VGFAK 394
Cdd:cd05490  321 VGFAK 325
Asp pfam00026
Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and ...
75-395 1.96e-157

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: 445.57  E-value: 1.96e-157
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237   75 QYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTdIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLSQDTCT 154
Cdd:pfam00026   1 EYFGTISIGTPPQKFTVIFDTGSSDLWVPSSYCTKS-SACKSHGTFDPSSSSTYKLNGTTFSISYGDGSASGFLGQDTVT 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  155 IGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRnpDTQPGGELLLG 234
Cdd:pfam00026  80 VGGLTITNQEFGLATKEPGSFFEYAKFDGILGLGFPSISAVGATPVFDNLKSQGLIDSPAFSVYLNS--PDAAGGEIIFG 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  235 GTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIPLMQGEYMVD 314
Cdd:pfam00026 158 GVDPSKYTGSLTYVPVTSQGYWQITLDSVTVGGSTSACSSGCQAILDTGTSLLYGPTSIVSKIAKAVGASSSEYGEYVVD 237
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  315 CKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGhDICLSGFMgldiPPPAGPLWILGDVFIGQYYTVFDRENNRVGFAK 394
Cdd:pfam00026 238 CDSISTLPDITFVIGGAKITVPPSAYVLQNSQGG-STCLSGFQ----PPPGGPLWILGDVFLRSAYVVFDRDNNRIGFAP 312

                  .
gi 849565237  395 A 395
Cdd:pfam00026 313 A 313
PTZ00165 PTZ00165
aspartyl protease; Provisional
66-396 3.63e-81

aspartyl protease; Provisional


Pssm-ID: 240300 [Multi-domain]  Cd Length: 482  Bit Score: 256.99  E-value: 3.63e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  66 ETLKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTdiACLLHHKYNGGKSSTYVKN--GTQFA---IQYG 140
Cdd:PTZ00165 111 QDLLNFHNSQYFGEIQVGTPPKSFVVVFDTGSSNLWIPSKECKSG--GCAPHRKFDPKKSSTYTKLklGDESAetyIQYG 188
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 141 SGSLSGYLSQDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYP---RIAVDGVPPVFDMMMSQKKVEKNVFSF 217
Cdd:PTZ00165 189 TGECVLALGKDTVKIGGLKVKHQSIGLAIEESLHPFADLPFDGLVGLGFPdkdFKESKKALPIVDNIKKQNLLKRNIFSF 268
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 218 YLNRnpDTQPGGELLLGGTDPKY-YTGD----FNYVDISrqaYWQIHMDGMSI-GSGLSLCKGGCEAIVDTGTSLITGPA 291
Cdd:PTZ00165 269 YMSK--DLNQPGSISFGSADPKYtLEGHkiwwFPVISTD---YWEIEVVDILIdGKSLGFCDRKCKAAIDTGSSLITGPS 343
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 292 AEVKALQKAIGaiplMQGeymvDCKKVPTLPTISFSL----GGKV-YSLTGEQYILKE--SQGGHDICLSGFMGLDIPPP 364
Cdd:PTZ00165 344 SVINPLLEKIP----LEE----DCSNKDSLPRISFVLedvnGRKIkFDMDPEDYVIEEgdSEEQEHQCVIGIIPMDVPAP 415
                        330       340       350
                 ....*....|....*....|....*....|..
gi 849565237 365 AGPLWILGDVFIGQYYTVFDRENNRVGFAKAK 396
Cdd:PTZ00165 416 RGPLFVLGNNFIRKYYSIFDRDHMMVGLVPAK 447
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
21-44 3.39e-04

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: 462326  Cd Length: 27  Bit Score: 37.70  E-value: 3.39e-04
                          10        20
                  ....*....|....*....|....
gi 849565237   21 RIPLKKFRTLRRTLSDSGrSLEEL 44
Cdd:pfam07966   1 RIPLKKGKSIRETLREKG-LLEEF 23
 
Name Accession Description Interval E-value
Cathepsin_D2 cd05490
Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of ...
70-394 0e+00

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: 685.75  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  70 NYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLS 149
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCSLLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 150 QDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQPGG 229
Cdd:cd05490   81 QDTVSIGGLQVEGQLFGEAVKQPGITFIAAKFDGILGMAYPRISVDGVTPVFDNIMAQKLVEQNVFSFYLNRDPDAQPGG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 230 ELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIPLMQG 309
Cdd:cd05490  161 ELMLGGTDPKYYTGDLHYVNVTRKAYWQIHMDQVDVGSGLTLCKGGCEAIVDTGTSLITGPVEEVRALQKAIGAVPLIQG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 310 EYMVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFDRENNR 389
Cdd:cd05490  241 EYMIDCEKIPTLPVISFSLGGKVYPLTGEDYILKVSQRGTTICLSGFMGLDIPPPAGPLWILGDVFIGRYYTVFDRDNDR 320

                 ....*
gi 849565237 390 VGFAK 394
Cdd:cd05490  321 VGFAK 325
Cathepsin_D_like cd05485
Cathepsin_D_like, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase ...
65-393 0e+00

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: 515.17  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  65 PETLKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSL 144
Cdd:cd05485    1 PEPLSNYMDAQYYGVITIGTPPQSFKVVFDTGSSNLWVPSKKCSWTNIACLLHNKYDSTKSSTYKKNGTEFAIQYGSGSL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 145 SGYLSQDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPD 224
Cdd:cd05485   81 SGFLSTDTVSVGGVSVKGQTFAEAINEPGLTFVAAKFDGILGMGYSSISVDGVVPVFYNMVNQKLVDAPVFSFYLNRDPS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 225 TQPGGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGlSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAI 304
Cdd:cd05485  161 AKEGGELILGGSDPKHYTGNFTYLPVTRKGYWQFKMDSVSVGEG-EFCSGGCQAIADTGTSLIAGPVDEIEKLNNAIGAK 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 305 PLMQGEYMVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFD 384
Cdd:cd05485  240 PIIGGEYMVNCSAIPSLPDITFVLGGKSFSLTGKDYVLKVTQMGQTICLSGFMGIDIPPPAGPLWILGDVFIGKYYTEFD 319

                 ....*....
gi 849565237 385 RENNRVGFA 393
Cdd:cd05485  320 LGNNRVGFA 328
renin_like cd05487
Renin stimulates production of angiotensin and thus affects blood pressure; Renin, also known ...
68-395 1.92e-164

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: 463.87  E-value: 1.92e-164
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  68 LKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGY 147
Cdd:cd05487    1 LTNYLDTQYYGEIGIGTPPQTFKVVFDTGSSNLWVPSSKCSPLYTACVTHNLYDASDSSTYKENGTEFTIHYASGTVKGF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 148 LSQDTCTIGDIAVeKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQP 227
Cdd:cd05487   81 LSQDIVTVGGIPV-TQMFGEVTALPAIPFMLAKFDGVLGMGYPKQAIGGVTPVFDNIMSQGVLKEDVFSVYYSRDSSHSL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 228 GGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIpLM 307
Cdd:cd05487  160 GGEIVLGGSDPQHYQGDFHYINTSKTGFWQIQMKGVSVGSSTLLCEDGCTAVVDTGASFISGPTSSISKLMEALGAK-ER 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 308 QGEYMVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFDREN 387
Cdd:cd05487  239 LGDYVVKCNEVPTLPDISFHLGGKEYTLSSSDYVLQDSDFSDKLCTVAFHAMDIPPPTGPLWVLGATFIRKFYTEFDRQN 318

                 ....*...
gi 849565237 388 NRVGFAKA 395
Cdd:cd05487  319 NRIGFALA 326
phytepsin cd06098
Phytepsin, a plant homolog of mammalian lysosomal pepsins; Phytepsin, a plant homolog of ...
68-394 1.56e-161

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: 456.06  E-value: 1.56e-161
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  68 LKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTdIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGY 147
Cdd:cd06098    3 LKNYLDAQYFGEIGIGTPPQKFTVIFDTGSSNLWVPSSKCYFS-IACYFHSKYKSSKSSTYKKNGTSASIQYGTGSISGF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 148 LSQDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQP 227
Cdd:cd06098   82 FSQDSVTVGDLVVKNQVFIEATKEPGLTFLLAKFDGILGLGFQEISVGKAVPVWYNMVEQGLVKEPVFSFWLNRNPDEEE 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 228 GGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSI-GSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAigaipl 306
Cdd:cd06098  162 GGELVFGGVDPKHFKGEHTYVPVTRKGYWQFEMGDVLIgGKSTGFCAGGCAAIADSGTSLLAGPTTIVTQINSA------ 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 307 mqgeymVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFDRE 386
Cdd:cd06098  236 ------VDCNSLSSMPNVSFTIGGKTFELTPEQYILKVGEGAAAQCISGFTALDVPPPRGPLWILGDVFMGAYHTVFDYG 309

                 ....*...
gi 849565237 387 NNRVGFAK 394
Cdd:cd06098  310 NLRVGFAE 317
Asp pfam00026
Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and ...
75-395 1.96e-157

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: 445.57  E-value: 1.96e-157
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237   75 QYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTdIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLSQDTCT 154
Cdd:pfam00026   1 EYFGTISIGTPPQKFTVIFDTGSSDLWVPSSYCTKS-SACKSHGTFDPSSSSTYKLNGTTFSISYGDGSASGFLGQDTVT 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  155 IGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRnpDTQPGGELLLG 234
Cdd:pfam00026  80 VGGLTITNQEFGLATKEPGSFFEYAKFDGILGLGFPSISAVGATPVFDNLKSQGLIDSPAFSVYLNS--PDAAGGEIIFG 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  235 GTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIPLMQGEYMVD 314
Cdd:pfam00026 158 GVDPSKYTGSLTYVPVTSQGYWQITLDSVTVGGSTSACSSGCQAILDTGTSLLYGPTSIVSKIAKAVGASSSEYGEYVVD 237
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  315 CKKVPTLPTISFSLGGKVYSLTGEQYILKESQGGhDICLSGFMgldiPPPAGPLWILGDVFIGQYYTVFDRENNRVGFAK 394
Cdd:pfam00026 238 CDSISTLPDITFVIGGAKITVPPSAYVLQNSQGG-STCLSGFQ----PPPGGPLWILGDVFLRSAYVVFDRDNNRIGFAP 312

                  .
gi 849565237  395 A 395
Cdd:pfam00026 313 A 313
pepsin_A cd05478
Pepsin A, aspartic protease produced in gastric mucosa of mammals; Pepsin, a well-known ...
66-394 3.12e-140

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: 402.21  E-value: 3.12e-140
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  66 ETLKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSltDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLS 145
Cdd:cd05478    1 EPLTNYLDMEYYGTISIGTPPQDFTVIFDTGSSNLWVPSVYCS--SQACSNHNRFNPRQSSTYQSTGQPLSIQYGTGSMT 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 146 GYLSQDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDT 225
Cdd:cd05478   79 GILGYDTVQVGGISDTNQIFGLSETEPGSFFYYAPFDGILGLAYPSIASSGATPVFDNMMSQGLVSQDLFSVYLSSNGQQ 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 226 qpGGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIP 305
Cdd:cd05478  159 --GSVVTFGGIDPSYYTGSLNWVPVTAETYWQITVDSVTINGQVVACSGGCQAIVDTGTSLLVGPSSDIANIQSDIGASQ 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 306 LMQGEYMVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQGghdiCLSGFMGLDipppAGPLWILGDVFIGQYYTVFDR 385
Cdd:cd05478  237 NQNGEMVVNCSSISSMPDVVFTINGVQYPLPPSAYILQDQGS----CTSGFQSMG----LGELWILGDVFIRQYYSVFDR 308

                 ....*....
gi 849565237 386 ENNRVGFAK 394
Cdd:cd05478  309 ANNKVGLAP 317
Cathespin_E cd05486
Cathepsin E, non-lysosomal aspartic protease; Cathepsin E is an intracellular, non-lysosomal ...
76-393 1.17e-139

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: 400.80  E-value: 1.17e-139
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  76 YYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCslTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLSQDTCTI 155
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYC--TSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTV 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 156 GDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQPGGELLLGG 235
Cdd:cd05486   79 EGITVQNQQFAESVSEPGSTFQDSEFDGILGLAYPSLAVDGVTPVFDNMMAQNLVELPMFSVYMSRNPNSADGGELVFGG 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 236 TDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIPlMQGEYMVDC 315
Cdd:cd05486  159 FDTSRFSGQLNWVPVTVQGYWQIQLDNIQVGGTVIFCSDGCQAIVDTGTSLITGPSGDIKQLQNYIGATA-TDGEYGVDC 237
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 849565237 316 KKVPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFDRENNRVGFA 393
Cdd:cd05486  238 STLSLMPSVTFTINGIPYSLSPQAYTLEDQSDGGGYCSSGFQGLDIPPPAGPLWILGDVFIRQYYSVFDRGNNRVGFA 315
Proteinase_A_fungi cd05488
Fungal Proteinase A , aspartic proteinase superfamily; Fungal Proteinase A, a proteolytic ...
68-394 1.14e-132

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: 382.94  E-value: 1.14e-132
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  68 LKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCslTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGY 147
Cdd:cd05488    3 LTNYLNAQYFTDITLGTPPQKFKVILDTGSSNLWVPSVKC--GSIACFLHSKYDSSASSTYKANGTEFKIQYGSGSLEGF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 148 LSQDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTqp 227
Cdd:cd05488   81 VSQDTLSIGDLTIKKQDFAEATSEPGLAFAFGKFDGILGLAYDTISVNKIVPPFYNMINQGLLDEPVFSFYLGSSEED-- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 228 GGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIG-SGLSLCKGGceAIVDTGTSLITGPAAEVKALQKAIGAIPL 306
Cdd:cd05488  159 GGEATFGGIDESRFTGKITWLPVRRKAYWEVELEKIGLGdEELELENTG--AAIDTGTSLIALPSDLAEMLNAEIGAKKS 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 307 MQGEYMVDCKKVPTLPTISFSLGGKVYSLTGEQYILkESQGGhdiCLSGFMGLDIPPPAGPLWILGDVFIGQYYTVFDRE 386
Cdd:cd05488  237 WNGQYTVDCSKVDSLPDLTFNFDGYNFTLGPFDYTL-EVSGS---CISAFTGMDFPEPVGPLAIVGDAFLRKYYSVYDLG 312

                 ....*...
gi 849565237 387 NNRVGFAK 394
Cdd:cd05488  313 NNAVGLAK 320
pepsin_like cd05471
Pepsin-like aspartic proteases, bilobal enzymes that cleave bonds in peptides at acidic pH; ...
76-394 2.85e-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: 327.46  E-value: 2.85e-111
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  76 YYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLSQDTCTI 155
Cdd:cd05471    1 YYGEITIGTPPQKFSVIFDTGSSLLWVPSSNCTSCSCQKHPRFKYDSSKSSTYKDTGCTFSITYGDGSVTGGLGTDTVTI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 156 GDIAVEKQIFGEAIKQPGVaFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQPGGELLLGG 235
Cdd:cd05471   81 GGLTIPNQTFGCATSESGD-FSSSGFDGILGLGFPSLSVDGVPSFFDQLKSQGLISSPVFSFYLGRDGDGGNGGELTFGG 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 236 TDPKYYTGDFNYVDI--SRQAYWQIHMDGMSIGS-GLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAIGA-IPLMQGEY 311
Cdd:cd05471  160 IDPSKYTGDLTYTPVvsNGPGYWQVPLDGISVGGkSVISSSGGGGAIVDSGTSLIYLPSSVYDAILKALGAaVSSSDGGY 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 312 MVDCKKVPTLPTISFSLggkvysltgeqyilkesqgghdiclsgfmgldipppagpLWILGDVFIGQYYTVFDRENNRVG 391
Cdd:cd05471  240 GVDCSPCDTLPDITFTF---------------------------------------LWILGDVFLRNYYTVFDLDNNRIG 280

                 ...
gi 849565237 392 FAK 394
Cdd:cd05471  281 FAP 283
gastricsin cd05477
Gastricsins, asparate proteases produced in gastric mucosa; Gastricsin is also called ...
73-395 9.87e-106

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: 314.52  E-value: 9.87e-106
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  73 DAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTdiACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLSQDT 152
Cdd:cd05477    1 DMSYYGEISIGTPPQNFLVLFDTGSSNLWVPSVLCQSQ--ACTNHTKFNPSQSSTYSTNGETFSLQYGSGSLTGIFGYDT 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 153 CTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNPDTQpGGELL 232
Cdd:cd05477   79 VTVQGIIITNQEFGLSETEPGTNFVYAQFDGILGLAYPSISAGGATTVMQGMMQQNLLQAPIFSFYLSGQQGQQ-GGELV 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 233 LGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGSGLS-LCKGGCEAIVDTGTSLITGPAAEVKALQKAIGAIPLMQGEY 311
Cdd:cd05477  158 FGGVDNNLYTGQIYWTPVTSETYWQIGIQGFQINGQATgWCSQGCQAIVDTGTSLLTAPQQVMSTLMQSIGAQQDQYGQY 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 312 MVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESQgghdICLSGFMGLDIPPPAG-PLWILGDVFIGQYYTVFDRENNRV 390
Cdd:cd05477  238 VVNCNNIQNLPTLTFTINGVSFPLPPSAYILQNNG----YCTVGIEPTYLPSQNGqPLWILGDVFLRQYYSVYDLGNNQV 313

                 ....*
gi 849565237 391 GFAKA 395
Cdd:cd05477  314 GFATA 318
PTZ00165 PTZ00165
aspartyl protease; Provisional
66-396 3.63e-81

aspartyl protease; Provisional


Pssm-ID: 240300 [Multi-domain]  Cd Length: 482  Bit Score: 256.99  E-value: 3.63e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  66 ETLKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTdiACLLHHKYNGGKSSTYVKN--GTQFA---IQYG 140
Cdd:PTZ00165 111 QDLLNFHNSQYFGEIQVGTPPKSFVVVFDTGSSNLWIPSKECKSG--GCAPHRKFDPKKSSTYTKLklGDESAetyIQYG 188
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 141 SGSLSGYLSQDTCTIGDIAVEKQIFGEAIKQPGVAFIAAKFDGILGMAYP---RIAVDGVPPVFDMMMSQKKVEKNVFSF 217
Cdd:PTZ00165 189 TGECVLALGKDTVKIGGLKVKHQSIGLAIEESLHPFADLPFDGLVGLGFPdkdFKESKKALPIVDNIKKQNLLKRNIFSF 268
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 218 YLNRnpDTQPGGELLLGGTDPKY-YTGD----FNYVDISrqaYWQIHMDGMSI-GSGLSLCKGGCEAIVDTGTSLITGPA 291
Cdd:PTZ00165 269 YMSK--DLNQPGSISFGSADPKYtLEGHkiwwFPVISTD---YWEIEVVDILIdGKSLGFCDRKCKAAIDTGSSLITGPS 343
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 292 AEVKALQKAIGaiplMQGeymvDCKKVPTLPTISFSL----GGKV-YSLTGEQYILKE--SQGGHDICLSGFMGLDIPPP 364
Cdd:PTZ00165 344 SVINPLLEKIP----LEE----DCSNKDSLPRISFVLedvnGRKIkFDMDPEDYVIEEgdSEEQEHQCVIGIIPMDVPAP 415
                        330       340       350
                 ....*....|....*....|....*....|..
gi 849565237 365 AGPLWILGDVFIGQYYTVFDRENNRVGFAKAK 396
Cdd:PTZ00165 416 RGPLFVLGNNFIRKYYSIFDRDHMMVGLVPAK 447
PTZ00147 PTZ00147
plasmepsin-1; Provisional
67-396 1.21e-64

plasmepsin-1; Provisional


Pssm-ID: 140176 [Multi-domain]  Cd Length: 453  Bit Score: 213.19  E-value: 1.21e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  67 TLKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCslTDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSG 146
Cdd:PTZ00147 131 ELKDLANVMSYGEAKLGDNGQKFNFIFDTGSANLWVPSIKC--TTEGCETKNLYDSSKSKTYEKDGTKVEMNYVSGTVSG 208
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 147 YLSQDTCTIGDIAVEKQiFGEAIKQPGV--AFIAAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLnrNPD 224
Cdd:PTZ00147 209 FFSKDLVTIGNLSVPYK-FIEVTDTNGFepFYTESDFDGIFGLGWKDLSIGSVDPYVVELKNQNKIEQAVFTFYL--PPE 285
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 225 TQPGGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDgMSIGSgLSLCKGGCeaIVDTGTSLITGPAAEV-KALQKA-IG 302
Cdd:PTZ00147 286 DKHKGYLTIGGIEERFYEGPLTYEKLNHDLYWQVDLD-VHFGN-VSSEKANV--IVDSGTSVITVPTEFLnKFVESLdVF 361
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 303 AIPLMQgEYMVDCKKvPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAgplWILGDVFIGQYYTV 382
Cdd:PTZ00147 362 KVPFLP-LYVTTCNN-TKLPTLEFRSPNKVYTLEPEYYLQPIEDIGSALCMLNIIPIDLEKNT---FILGDPFMRKYFTV 436
                        330
                 ....*....|....
gi 849565237 383 FDRENNRVGFAKAK 396
Cdd:PTZ00147 437 FDYDNHTVGFALAK 450
PTZ00013 PTZ00013
plasmepsin 4 (PM4); Provisional
68-397 3.95e-56

plasmepsin 4 (PM4); Provisional


Pssm-ID: 140051 [Multi-domain]  Cd Length: 450  Bit Score: 190.97  E-value: 3.95e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  68 LKNYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSltDIACLLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGY 147
Cdd:PTZ00013 131 LDDVANIMFYGEGEVGDNHQKFMLIFDTGSANLWVPSKKCD--SIGCSIKNLYDSSKSKSYEKDGTKVDITYGSGTVKGF 208
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 148 LSQDTCTIGDIAVEKQiFGEAIKQPGVAFI--AAKFDGILGMAYPRIAVDGVPPVFDMMMSQKKVEKNVFSFYLNRNpdT 225
Cdd:PTZ00013 209 FSKDLVTLGHLSMPYK-FIEVTDTDDLEPIysSSEFDGILGLGWKDLSIGSIDPIVVELKNQNKIDNALFTFYLPVH--D 285
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 226 QPGGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDgmsIGSGLSLCKGGcEAIVDTGTSLITGPAAEVKALQKAIGAI- 304
Cdd:PTZ00013 286 VHAGYLTIGGIEEKFYEGNITYEKLNHDLYWQIDLD---VHFGKQTMQKA-NVIVDSGTTTITAPSEFLNKFFANLNVIk 361
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 305 -PLMQgEYMVDCKKvPTLPTISFSLGGKVYSLTGEQYILKESQGGHDICLSGFMGLDIPPPAgplWILGDVFIGQYYTVF 383
Cdd:PTZ00013 362 vPFLP-FYVTTCDN-KEMPTLEFKSANNTYTLEPEYYMNPLLDVDDTLCMITMLPVDIDDNT---FILGDPFMRKYFTVF 436
                        330
                 ....*....|....
gi 849565237 384 DRENNRVGFAKAKS 397
Cdd:PTZ00013 437 DYDKESVGFAIAKN 450
Aspergillopepsin_like cd06097
Aspergillopepsin_like, aspartic proteases of fungal origin; The members of this family are ...
76-394 1.87e-45

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: 157.85  E-value: 1.87e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  76 YYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIAclLHHKYNGGKSSTY-VKNGTQFAIQYGSGS-LSGYLSQDTC 153
Cdd:cd06097    1 YLTPVKIGTPPQTLNLDLDTGSSDLWVFSSETPAAQQG--GHKLYDPSKSSTAkLLPGATWSISYGDGSsASGIVYTDTV 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 154 TIGDIAVEKQIFgEAIKQPGVAFIAAKF-DGILGMAYPRI---AVDGVPPVFDMMMSQKkvEKNVFSFYLNRNPDtqpgG 229
Cdd:cd06097   79 SIGGVEVPNQAI-ELATAVSASFFSDTAsDGLLGLAFSSIntvQPPKQKTFFENALSSL--DAPLFTADLRKAAP----G 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 230 ELLLGGTDPKYYTGDFNYVDISR-QAYWQIHMDGMSIGSGLSLCKGGCEAIVDTGTSLITGPAAEVKALQKAI-GAI--P 305
Cdd:cd06097  152 FYTFGYIDESKYKGEISWTPVDNsSGFWQFTSTSYTVGGDAPWSRSGFSAIADTGTTLILLPDAIVEAYYSQVpGAYydS 231
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 306 LMQGeYMVDCKKvpTLPTISFslggKVYSltgeqyilkesqgghdiclsgfmgldipppagplwILGDVFIGQYYTVFDR 385
Cdd:cd06097  232 EYGG-WVFPCDT--TLPDLSF----AVFS-----------------------------------ILGDVFLKAQYVVFDV 269

                 ....*....
gi 849565237 386 ENNRVGFAK 394
Cdd:cd06097  270 GGPKLGFAP 278
SAP_like cd05474
SAPs, pepsin-like proteinases secreted from pathogens to degrade host proteins; SAPs (Secreted ...
76-395 6.03e-40

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: 143.86  E-value: 6.03e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  76 YYGEIGLGTPVQTFTVVFDTGSSNLWVPSvhcsltdiacllhhkynggksstyvkngtqFAIQYGSGS-LSGYLSQDTCT 154
Cdd:cd05474    3 YSAELSVGTPPQKVTVLLDTGSSDLWVPD------------------------------FSISYGDGTsASGTWGTDTVS 52
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 155 IGDIAVEKQIFGeaikqpgVAFIAAKFDGILGMAYPRI-AVDGVPPVFD----MMMSQKKVEKNVFSFYLNRNPDTQpgG 229
Cdd:cd05474   53 IGGATVKNLQFA-------VANSTSSDVGVLGIGLPGNeATYGTGYTYPnfpiALKKQGLIKKNAYSLYLNDLDAST--G 123
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 230 ELLLGGTDPKYYTGDFNYVDISRQAYW------QIHMDGMSIGSGLS---LCKGGCEAIVDTGTSLITGPAAEVKALQKA 300
Cdd:cd05474  124 SILFGGVDTAKYSGDLVTLPIVNDNGGsepselSVTLSSISVNGSSGnttLLSKNLPALLDSGTTLTYLPSDIVDAIAKQ 203
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 301 IGA--IPLmQGEYMVDCKKVPTLpTISFSLGGKVYSLTGEQYILK--ESQGGHDICLSGFMgldipPPAGPLWILGDVFI 376
Cdd:cd05474  204 LGAtyDSD-EGLYVVDCDAKDDG-SLTFNFGGATISVPLSDLVLPasTDDGGDGACYLGIQ-----PSTSDYNILGDTFL 276
                        330
                 ....*....|....*....
gi 849565237 377 GQYYTVFDRENNRVGFAKA 395
Cdd:cd05474  277 RSAYVVYDLDNNEISLAQA 295
pepsin_retropepsin_like cd05470
Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular ...
78-187 1.63e-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: 136.74  E-value: 1.63e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  78 GEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACLlHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLSQDTCTIGD 157
Cdd:cd05470    1 IEIGIGTPPQTFNVLLDTGSSNLWVPSVDCQSLAIYSH-SSYDDPSASSTYSDNGCTFSITYGTGSLSGGLSTDTVSIGD 79
                         90       100       110
                 ....*....|....*....|....*....|
gi 849565237 158 IAVEKQIFGEAIKQPGVAFIAAKFDGILGM 187
Cdd:cd05470   80 IEVVGQAFGCATDEPGATFLPALFDGILGL 109
beta_secretase_like cd05473
Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease; ...
76-393 1.25e-37

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: 139.48  E-value: 1.25e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  76 YYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLtdiaclLHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLSQDTCTI 155
Cdd:cd05473    4 YYIEMLIGTPPQKLNILVDTGSSNFAVAAAPHPF------IHTYFHRELSSTYRDLGKGVTVPYTQGSWEGELGTDLVSI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 156 GD-IAVEKQIFGEAIKQPGVAFI-AAKFDGILGMAYPRIAV--DGVPPVFDMMMSQKKVeKNVFS-------FYLNRNPD 224
Cdd:cd05473   78 PKgPNVTFRANIAAITESENFFLnGSNWEGILGLAYAELARpdSSVEPFFDSLVKQTGI-PDVFSlqmcgagLPVNGSAS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 225 TQPGGELLLGGTDPKYYTGDFNYVDISRQAYWQIHMDGMSIGsGLSL---CK--GGCEAIVDTGTSLITGPAAEVKALQK 299
Cdd:cd05473  157 GTVGGSMVIGGIDPSLYKGDIWYTPIREEWYYEVIILKLEVG-GQSLnldCKeyNYDKAIVDSGTTNLRLPVKVFNAAVD 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 300 AIGAIPLMQ--------GEYMVDCKKVPT----LPTISFSL----GGKVYSLT--GEQYILK-ESQGGHDICLSgfmgLD 360
Cdd:cd05473  236 AIKAASLIEdfpdgfwlGSQLACWQKGTTpweiFPKISIYLrdenSSQSFRITilPQLYLRPvEDHGTQLDCYK----FA 311
                        330       340       350
                 ....*....|....*....|....*....|...
gi 849565237 361 IPPPAGPLwILGDVFIGQYYTVFDRENNRVGFA 393
Cdd:cd05473  312 ISQSTNGT-VIGAVIMEGFYVVFDRANKRVGFA 343
pepsin_A_like_plant cd05476
Chroloplast Nucleoids DNA-binding Protease and Nucellin, pepsin-like aspartic proteases from ...
75-396 8.41e-20

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: 88.09  E-value: 8.41e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  75 QYYGEIGLGTPVQTFTVVFDTGSSNLWVPsvhCsltdiaCllhhkynggksstyvkngtQFAIQYGSGSLS-GYLSQDTC 153
Cdd:cd05476    1 EYLVTLSIGTPPQPFSLIVDTGSDLTWTQ---C------C-------------------SYEYSYGDGSSTsGVLATETF 52
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 154 TIGDIAVEKQ--IFGEAIKQPGVAFiaAKFDGILGMAYPRIAVdgvppvfdmmMSQKKVEKNVFSFYLNRNPDTQPGGEL 231
Cdd:cd05476   53 TFGDSSVSVPnvAFGCGTDNEGGSF--GGADGILGLGRGPLSL----------VSQLGSTGNKFSYCLVPHDDTGGSSPL 120
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 232 LLGGtDPKYYTGDFNYV----DISRQAYWQIHMDGMSIGSGL-----------SLCKGGceAIVDTGTSLiTgpaaevka 296
Cdd:cd05476  121 ILGD-AADLGGSGVVYTplvkNPANPTYYYVNLEGISVGGKRlpippsvfaidSDGSGG--TIIDSGTTL-T-------- 188
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 297 lqkaigaiplmqgeYMVDckkvPTLPTISFSLGGKVY-SLTGEQYILKESQGGhdICLsGFMgldiPPPAGPLWILGDVF 375
Cdd:cd05476  189 --------------YLPD----PAYPDLTLHFDGGADlELPPENYFVDVGEGV--VCL-AIL----SSSSGGVSILGNIQ 243
                        330       340
                 ....*....|....*....|.
gi 849565237 376 IGQYYTVFDRENNRVGFAKAK 396
Cdd:cd05476  244 QQNFLVEYDLENSRLGFAPAD 264
Plasmepsin_5 cd06096
Plasmepsins are a class of aspartic proteinases produced by the plasmodium parasite; The ...
74-396 4.22e-19

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: 87.43  E-value: 4.22e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  74 AQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCsltdIACLLHHK--YNGGKSSTY----------------VKNGTQF 135
Cdd:cd06096    2 AYYFIDIFIGNPPQKQSLILDTGSSSLSFPCSQC----KNCGIHMEppYNLNNSITSsilycdcnkccyclscLNNKCEY 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 136 AIQYGSGS-LSGYLSQDTCTIGD--------IAVEKqIFGEAIKQPGVaFIAAKFDGILGMAYprIAVDGVPPVFDMMMS 206
Cdd:cd06096   78 SISYSEGSsISGFYFSDFVSFESylnsnsekESFKK-IFGCHTHETNL-FLTQQATGILGLSL--TKNNGLPTPIILLFT 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 207 QKKVEKN--VFSFYLNRNpdtqpGGELLLGGTDPKY-----YTGDFNYVDISRQA-----YWQIHMDGMSIGSGLSLC-- 272
Cdd:cd06096  154 KRPKLKKdkIFSICLSED-----GGELTIGGYDKDYtvrnsSIGNNKVSKIVWTPitrkyYYYVKLEGLSVYGTTSNSgn 228
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 273 KGGCEAIVDTGTSLITGPAAEVKALQKAIgaiplmqgeymvdckkvPTLpTISFSLGGKVYsLTGEQY-ILKESQGGHDI 351
Cdd:cd06096  229 TKGLGMLVDSGSTLSHFPEDLYNKINNFF-----------------PTI-TIIFENNLKID-WKPSSYlYKKESFWCKGG 289
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*..
gi 849565237 352 CLSG--FMgldipppagplwILGDVFIGQYYTVFDRENNRVGFAKAK 396
Cdd:cd06096  290 EKSVsnKP------------ILGASFFKNKQIIFDLDNNRIGFVESN 324
TAXi_N pfam14543
Xylanase inhibitor N-terminal; The N- and C-termini of the members of this family are jointly ...
76-235 4.09e-13

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: 464203 [Multi-domain]  Cd Length: 172  Bit Score: 66.91  E-value: 4.09e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237   76 YYGEIGLGTPVQTFTVVFDTGSSNLWVPsvhCSLTDIACLLhHKYNGGKSSTY---------------------VKNGT- 133
Cdd:pfam14543   1 YLVTISIGTPPVPFFLVVDTGSDLTWVQ---CDPCCYSQPD-PLFDPYKSSTYkpvpcssplcslialsspgpcCSNNTc 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  134 QFAIQYGSGSLS-GYLSQDTCTIGD----IAVEKQIFGEAIKQPGvaFIAAKFDGILGMAYPRIAvdgvppvFDMMMSQK 208
Cdd:pfam14543  77 DYEVSYGDGSSTsGVLATDTLTLNStggsVSVPNFVFGCGYNLLG--GLPAGADGILGLGRGKLS-------LPSQLASQ 147
                         170       180
                  ....*....|....*....|....*..
gi 849565237  209 KVEKNVFSFYLnrNPDTQPGGELLLGG 235
Cdd:pfam14543 148 GIFGNKFSYCL--SSSSSGSGVLFFGD 172
cnd41_like cd05472
Chloroplast Nucleoids DNA-binding Protease, catalyzes the degradation of ribulose-1, ...
75-393 9.44e-11

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: 62.29  E-value: 9.44e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  75 QYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCsltdiaCLlhhkynggksstyvkngtqFAIQYGSGSLS-GYLSQDTC 153
Cdd:cd05472    1 EYVVTVGLGTPARDQTVIVDTGSDLTWVQCQPC------CL-------------------YQVSYGDGSYTtGDLATDTL 55
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 154 TIGD-IAVEKQIFGEAIKQPGvAFIAAkfDGILGMAYPRIAvdgvppvfdmMMSQKKVE-KNVFSFYLnrnPDTQPG--G 229
Cdd:cd05472   56 TLGSsDVVPGFAFGCGHDNEG-LFGGA--AGLLGLGRGKLS----------LPSQTASSyGGVFSYCL---PDRSSSssG 119
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 230 ELLLGGTDPKyyTGDFNY---VDISRQA-YWQIHMDGMSIG------SGLSLCKGGceAIVDTGTSLITGPAAEVKALQ- 298
Cdd:cd05472  120 YLSFGAAASV--PAGASFtpmLSNPRVPtFYYVGLTGISVGgrrlpiPPASFGAGG--VIIDSGTVITRLPPSAYAALRd 195
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 299 ---KAIGAIPLMQGEYMVD-C-----KKVPTLPTISFSL-GGKVYSLTGEQYILKESQGGhDICLsGFMGLDIPPPAGpl 368
Cdd:cd05472  196 afrAAMAAYPRAPGFSILDtCydlsgFRSVSVPTVSLHFqGGADVELDASGVLYPVDDSS-QVCL-AFAGTSDDGGLS-- 271
                        330       340
                 ....*....|....*....|....*
gi 849565237 369 wILGDVFIGQYYTVFDRENNRVGFA 393
Cdd:cd05472  272 -IIGNVQQQTFRVVYDVAGGRIGFA 295
A1_Propeptide pfam07966
A1 Propeptide; Most eukaryotic endopeptidases (Merops Family A1) are synthesized with signal ...
21-44 3.39e-04

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: 462326  Cd Length: 27  Bit Score: 37.70  E-value: 3.39e-04
                          10        20
                  ....*....|....*....|....
gi 849565237   21 RIPLKKFRTLRRTLSDSGrSLEEL 44
Cdd:pfam07966   1 RIPLKKGKSIRETLREKG-LLEEF 23
nucellin_like cd05475
Nucellins, plant aspartic proteases specifically expressed in nucellar cells during ...
75-395 2.03e-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: 39.66  E-value: 2.03e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237  75 QYYGEIGLGTPVQTFTVVFDTGSSNLWvpsVHCSLTDIACLLHHKynggksstyvkngtqfaIQYGSGSLS-GYLSQDTC 153
Cdd:cd05475    2 YYYVTINIGNPPKPYFLDIDTGSDLTW---LQCDAPCTGCQCDYE-----------------IEYADGGSSmGVLVTDIF 61
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 154 TI----GDIAVEKQIFGEAIKQPGVAFIA-AKFDGILGMAYPRIAvdgvppvfdmMMSQ---KKVEKNVFSFYLNRNpdt 225
Cdd:cd05475   62 SLkltnGSRAKPRIAFGCGYDQQGPLLNPpPPTDGILGLGRGKIS----------LPSQlasQGIIKNVIGHCLSSN--- 128
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 226 qPGGELLLGgtDPKYYTGDFNYVDISRQAYWQIHMDGMS---IGSGLSLCKGGcEAIVDTGTSLITGPAaevKALQKAIg 302
Cdd:cd05475  129 -GGGFLFFG--DDLVPSSGVTWTPMRRESQKKHYSPGPAsllFNGQPTGGKGL-EVVFDSGSSYTYFNA---QAYFKPL- 200
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 849565237 303 aiplmqgeymvdckkvptlpTISFSLGGKVYSLT--GEQYILKESQGghDICLSGFMGLDIppPAGPLWILGDVFIGQYY 380
Cdd:cd05475  201 --------------------TLKFGKGWRTRLLEipPENYLIISEKG--NVCLGILNGSEI--GLGNTNIIGDISMQGLM 256
                        330
                 ....*....|....*
gi 849565237 381 TVFDRENNRVGFAKA 395
Cdd:cd05475  257 VIYDNEKQQIGWVRS 271
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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