Conserved Protein Domain Family
Cathepsin_D2

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cd05490: Cathepsin_D2 
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).
Statistics
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PSSM-Id: 133157
View PSSM: cd05490
Aligned: 7 rows
Threshold Bit Score: 643.381
Threshold Setting Gi: 118344572
Created: 8-Feb-2008
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Feature 1:catalytic residue [active site]
Evidence:
  • Comment:The two ASPs at the active site plays key catalytic roles in the pepsin family and conserved for all family members.
  • Comment:Predicted based on homologous proteins woth structures.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                #                                                       
NP_001085403  75 NYLDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCSMFDIACwmHHKYDSSKSSTYVKNGTEFAIQYGTGSLSGYLS 154 African clawed ...
P80209        53 NYMDAQYYGEIGIGTPPQCFTVVFDTGSANLWVPSIHCKLLDIACwtHRKYNSDKSSTYVKNGTTFDIHYGSGSLSGYLS 132 cattle
Q05744        72 NYMDAQYYGEIGIGTPPQKFTVVFDTGSSNLWVPSVHCHLLDIACllHHKYDASKSSTYVENGTEFAIHYGTGSLSGFLS 151 chicken
AAH62824      70 NYLDAQYYGEIGLGTPVQTFTVVFDTGSSNLWVPSVHCSLTDIACllHHKYNGGKSSTYVKNGTQFAIQYGSGSLSGYLS 149 zebrafish
NP_956325     86 NFMDAQYYGMISIGTPPQDFSVLFDTGSSNLWVPSIHCAFLDIACwlHRRYNSKKSSTYVQNGTEFSIQYGRGSLSGFIS 165 zebrafish
NP_001072053  62 NIYDLQYFGKISIGTPPQEFTVLFDTGSSDLWVPSVYCSPLYLACglHRHYRSYRSSTYVQCDRGFFIEYQSGRLSGFVS 141 torafugu
P07339        73 NYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACwiHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLS 152 human
Feature 1                                                                                        
NP_001085403 155 kDTVTIGnlg-----------ikEQLFGEAIKQPGVTFIAaKFDGILGMAYPIISVDgvsPVFDNIMAQKLVESNVFSFY 223 African clawed ...
P80209       133 qDTVSVPcnpssss--pggvtvqRQTFGEAIKQPGVVFIAaKFDGILGMAYPRISVNnvlPVFDNLMQQKLVDKNVFSFF 210 cattle
Q05744       152 qDTVTLGnlk-----------ikNQIFGEAVKQPGITFIAaKFDGILGMAFPRISVDkvtPFFDNVMQQKLIEKNIFSFY 220 chicken
AAH62824     150 qDTCTIGdia-----------veKQIFGEAIKQPGVAFIAaKFDGILGMAYPRIAVDgvpPVFDMMMSQKKVEKNVFSFY 218 zebrafish
NP_956325    166 qDTVNLAgln-----------vtGQQFAEAVKQPGIVFAVaRFDGVLGMAYPAISVDrvtPVFDTAMAAKILPQNIFSFY 234 zebrafish
NP_001072053 142 kDTLSIGglq-----------vpGQLFGEAVRQPGETFIYtQFDGILGMAYPSISTIa--PVFDRIMAAKLLPQNVFSFY 208 torafugu
P07339       153 qDTVSVPcqsassasalggvkveRQVFGEATKQPGITFIAaKFDGILGMAYPRISVNnvlPVFDNLMQQKLVDQNIFSFY 232 human
Feature 1                                                                      #                 
NP_001085403 224 LNRNPdtqpGGELLLGGTDpkYYTGDFHYLNVTRKaYWQIHMdqlgvgdqLTLCKGGCEAIVDTGTSLITGPLEEVTALQ 303 African clawed ...
P80209       211 LNRDPkaqpGGELMLGGTDskYYRGSLMFHNVTRQaYWQIHMdqldvgssLTVCKGGCEAIVDTGTSLIVGPVEEVRELQ 290 cattle
Q05744       221 LNRDPtaqpGGELLLGGTDpkYYSGDFSWVNVTRKaYWQVHMdsvdvangLTLCKGGCEAIVDTGTSLITGPTKEVKELQ 300 chicken
AAH62824     219 LNRNPdtqpGGELLLGGTDpkYYTGDFNYVDISRQaYWQIHMdgmsigsgLSLCKGGCEAIVDTGTSLITGPAAEVKALQ 298 zebrafish
NP_956325    235 INRDPagdvGGELMLGGFDqqYFNGDLHYVNVTRKaYWQIKMdevqvgstLTLCKSGCQAIVDTGTSMITGPVQEVRALQ 314 zebrafish
NP_001072053 209 LNRDPeaaiGGQLILGGLNpeHYAGELHYVNVTRKaYWQIEVnrinvgdqLSLCKPSCQTIVDTGTSLITGPSEEIRALH 288 torafugu
P07339       233 LSRDPdaqpGGELMLGGTDskYYKGSLSYLNVTRKaYWQVHLdqvevasgLTLCKEGCEAIVDTGTSLMVGPVDEVRELQ 312 human
Feature 1                                                                                        
NP_001085403 304 KAIGAVPLIQGqymVQCDKIPTLPVISLTLGGQVYTLTGEQYIMKVSqrGSTICLSGFMGLNIPPPAGPLWILGDVFIGQ 383 African clawed ...
P80209       291 KAIGAVPLIQGeymIPCEKVSSLPEVTVKLGGKDYALSPEDYALKVSqaETTVCLSGFMGMDIPPPGGPLWILGDVFIGR 370 cattle
Q05744       301 TAIGAKPLIKGqyvISCDKISSLPVVTLMLGGKPYQLTGEQYVFKVSaqGETICLSGFSGLDVPPPGGPLWILGDVFIGP 380 chicken
AAH62824     299 KAIGAIPLMQGeymVDCKKVPTLPTISFSLGGKVYSLTGEQYILKESqgGHDICLSGFMGLDIPPPAGPLWILGDVFIGQ 378 zebrafish
NP_956325    315 KAIGAIPLLMGeywIDCKKIPTLPVVSFSLGGKMFNLTGQEYVMKMShmGMNVCLSGFMAMDIPPPAGPLWILGDVFIGR 394 zebrafish
NP_001072053 289 NAIPGMSRQKDeniIDCEQIPSMPVISFNIGGKLFPLNPEDYIWKEMdrGTAFCQSRFMALDMGPPAAPLWNLGDVFIMK 368 torafugu
P07339       313 KAIGAVPLIQGeymIPCEKVSTLPAITLKLGGKGYKLSPEDYTLKVSqaGKTLCLSGFMGMDIPPPSGPLWILGDVFIGR 392 human
Feature 1                        
NP_001085403 384 YYSVFDRAnDRVGFAK 399 African clawed frog
P80209       371 YYTVFDRDqNRVGLAE 386 cattle
Q05744       381 YYTVFDRDnDSVGFAK 396 chicken
AAH62824     379 YYTVFDREnNRVGFAK 394 zebrafish
NP_956325    395 YYTVFDRDqDRVGFAP 410 zebrafish
NP_001072053 369 YYTVFDRDaDRVGFAL 384 torafugu
P07339       393 YYTVFDRDnNRVGFAE 408 human

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