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: 17-Jan-2013
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:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                     #                                                  
gi 56118817   59 PEPLTNYMDVQYYGVISIGTPPQSFRVVFDTGSSNLWVPSKKCKWTDIACWlHRKYDSKKSSTYKANGTEFAIHYGTGSL 138
gi 156406785  40 PEPLINYMDAQYYGEITIGTPPQKFTVVFDTGSSNLWVPSKKCSWTNIACLlHDKYDSTKSSTYKKNGTEFAIRYGSGSL 119
gi 46309251   62 PEPLSNYLDAQYYGVISIGTPAQNFKVVFDTGSSNLWVPSKKCKLSDIACLlHNKYDSTQSSTYKANGTDFHIQYGSGSL 141
gi 205831550  57 PEPLSNYLDAQYYGAITIGTPPQSFKVVFDTGSSNLWVPSKECSFTNIACLmHNKYNAKKSSTFEKNGTAFHIQYGSGSL 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 56118817  139 TGFLStDTVSVGslsvkSQTFAEAITQPGITFVAAKFDGILGMAYPSISVDgVVPVFNNMVNQKLvdqAIFSFYLSRDAs 218
gi 156406785 120 SGFLSiDTVSVGgidvkGQTFAEALKEPGLTFVAAKFDGILGMGFSSISVDqVVPVFYDMVLQKLvpaPVFSFYLNREPg 199
gi 46309251  142 DGFLStDTVAIGsvaikAQTFAEATNQPGLVFVAAKFDGILGMAYDTISVDkVTPVFYQIISQKLvdqPVFSFYLNRDPs 221
gi 205831550 137 SGYLStDTVGLGgvsvtKQTFAEAINEPGLVFVAAKFDGILGLGYSSISVDgVVPVFYNMFNQGLidaPVFSFYLNRDPs 216
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                          #             
gi 56118817  219 akeGGEIILGGSDpdhyVGNFTYLDVTRkaYWQIKMDsvtvssesecmnammvgGEYCKGGCQAIADTGTSLIVGPSSDV 298
gi 156406785 200 aspGGELLLGGSDpkyyKGNFSYVPVTQegYWQFKMDgis-----------vkeGSFCSDGCQAIADTGTSLIAGPTDEI 268
gi 46309251  222 gkeGGELILGGSDpkhyTGNFTYLPVTRkgYWQIKMDkvv-----------sgeNTFCSGGCQAIADTGTSLIAGPVDEI 290
gi 205831550 217 aaeGGEIIFGGSDsnkyTGDFTYLSVDRkaYWQFKMDsvk-----------vgdTEFCNNGCEAIADTGTSLIAGPVSEV 285
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 56118817  299 EKLNAEIGalpiisGEYWINCSKIasLPTINFVLGGKSFSLTGKDYVVvvtqmGQTICLSGFVAMDIPPPaGPLWILGDI 378
gi 156406785 269 EKLNNLIGakiiigGEYTVNCSAIdsLPDITFTIGGKKYVLTGKQYILkvttlGQSVCISGFLGLDVPPPrGPLWILGDV 348
gi 46309251  291 KKLNEAIGgralpgGEYMVDCASIpkLPNVDFVLGGKTFSLKTSDYVLtikqaGQTICLSGFMGINIPPPaGPLWILGDV 370
gi 205831550 286 TAINKAIGgtpimnGEYMVDCSLIpkLPKISFVLGGKSFDLEGADYVLrvaqmGKTICLSGFMGIDIPPPnGPLWILGDV 365
                        330       340
                 ....*....|....*....|
Feature 1                            
gi 56118817  379 FIGKYYTEFDLAnnRVGFAT 398
gi 156406785 349 FIGPYYTEFDFGnkRVGFAE 368
gi 46309251  371 FIGKYYTVFDLGknQVGFAV 390
gi 205831550 366 FIGKYYTEFDMGndRVGFAT 385

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