Conserved Protein Domain Family
Cathepsin_D_like

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cd05485: Cathepsin_D_like 
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).
Statistics
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PSSM-Id: 133152
View PSSM: cd05485
Aligned: 4 rows
Threshold Bit Score: 630.344
Threshold Setting Gi: 156406785
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_001008172  59 PEPLTNYMDVQYYGVISIGTPPQSFRVVFDTGSSNLWVPSKKCKWTDIACWlHRKYDSKKSSTYKANGTEFAIHYGTGSL 138 western clawed ...
XP_001641225  40 PEPLINYMDAQYYGEITIGTPPQKFTVVFDTGSSNLWVPSKKCSWTNIACLlHDKYDSTKSSTYKKNGTEFAIRYGSGSL 119 starlet sea ane...
BAD15111      62 PEPLSNYLDAQYYGVISIGTPAQNFKVVFDTGSSNLWVPSKKCKLSDIACLlHNKYDSTQSSTYKANGTDFHIQYGSGSL 141 Japanese flying...
Q03168        57 PEPLSNYLDAQYYGAITIGTPPQSFKVVFDTGSSNLWVPSKECSFTNIACLmHNKYNAKKSSTFEKNGTAFHIQYGSGSL 136 yellow fever mo...
Feature 1                                                                                        
NP_001008172 139 TGFLStDTVSVGslsvkSQTFAEAITQPGITFVAAKFDGILGMAYPSISVDgVVPVFNNMVNQKLvdqAIFSFYLSRDAs 218 western clawed ...
XP_001641225 120 SGFLSiDTVSVGgidvkGQTFAEALKEPGLTFVAAKFDGILGMGFSSISVDqVVPVFYDMVLQKLvpaPVFSFYLNREPg 199 starlet sea ane...
BAD15111     142 DGFLStDTVAIGsvaikAQTFAEATNQPGLVFVAAKFDGILGMAYDTISVDkVTPVFYQIISQKLvdqPVFSFYLNRDPs 221 Japanese flying...
Q03168       137 SGYLStDTVGLGgvsvtKQTFAEAINEPGLVFVAAKFDGILGLGYSSISVDgVVPVFYNMFNQGLidaPVFSFYLNRDPs 216 yellow fever mo...
Feature 1                                                                          #             
NP_001008172 219 akeGGEIILGGSDpdhyVGNFTYLDVTRkaYWQIKMDsvtvssesecmnammvgGEYCKGGCQAIADTGTSLIVGPSSDV 298 western clawed ...
XP_001641225 200 aspGGELLLGGSDpkyyKGNFSYVPVTQegYWQFKMDgis-----------vkeGSFCSDGCQAIADTGTSLIAGPTDEI 268 starlet sea ane...
BAD15111     222 gkeGGELILGGSDpkhyTGNFTYLPVTRkgYWQIKMDkvv-----------sgeNTFCSGGCQAIADTGTSLIAGPVDEI 290 Japanese flying...
Q03168       217 aaeGGEIIFGGSDsnkyTGDFTYLSVDRkaYWQFKMDsvk-----------vgdTEFCNNGCEAIADTGTSLIAGPVSEV 285 yellow fever mo...
Feature 1                                                                                        
NP_001008172 299 EKLNAEIGalpiisGEYWINCSKIasLPTINFVLGGKSFSLTGKDYVVvvtqmGQTICLSGFVAMDIPPPaGPLWILGDI 378 western clawed ...
XP_001641225 269 EKLNNLIGakiiigGEYTVNCSAIdsLPDITFTIGGKKYVLTGKQYILkvttlGQSVCISGFLGLDVPPPrGPLWILGDV 348 starlet sea ane...
BAD15111     291 KKLNEAIGgralpgGEYMVDCASIpkLPNVDFVLGGKTFSLKTSDYVLtikqaGQTICLSGFMGINIPPPaGPLWILGDV 370 Japanese flying...
Q03168       286 TAINKAIGgtpimnGEYMVDCSLIpkLPKISFVLGGKSFDLEGADYVLrvaqmGKTICLSGFMGIDIPPPnGPLWILGDV 365 yellow fever mo...
Feature 1                            
NP_001008172 379 FIGKYYTEFDLAnnRVGFAT 398 western clawed frog
XP_001641225 349 FIGPYYTEFDFGnkRVGFAE 368 starlet sea anemone
BAD15111     371 FIGKYYTVFDLGknQVGFAV 390 Japanese flying squid
Q03168       366 FIGKYYTEFDMGndRVGFAT 385 yellow fever mosquito

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