1YM4,2HIZ,2EWY


Conserved Protein Domain Family
beta_secretase_like

?
cd05473: beta_secretase_like 
Click on image for an interactive view with Cn3D
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).
Statistics
?
PSSM-Id: 133140
View PSSM: cd05473
Aligned: 11 rows
Threshold Bit Score: 647.944
Threshold Setting Gi: 156379353
Created: 8-Sep-2006
Updated: 2-Oct-2020
Structure
?
Program:
Drawing:
Aligned Rows:
 
Conserved site includes 2 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic residue [active site]
Evidence:
  • Structure:1ym4_a; catalytic aspartic acid residues of human Beta Secretase
    View structure with Cn3D
  • Comment:The two ASPs at the active site plays key catalytic roles in the pepsin family and conserved for all family members.

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                             #                                                          
1YM4_A        27 GQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHG 106 human
AAI21913      73 GQGYYVEMRVGTPPQTLNILVDTGSSNFAVGAAPHPFLKRYYHRQHSRTYRDVRRGVYVPYTQGKWEGELGTDLVTIPHG 152 western clawed ...
AAH65973      77 GQGYYIEMAVGSPAQRLNILVDTGSSNFAVGAAAHPFLHRYYHRSLSSSYRDLGRGVYVPYTQGRWEGELGTDVVSVPCG 156 zebrafish
Q9Y5Z0        89 GRGYYLEMLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKG 168 human
AAH55989      73 GRGYYLELLIGSPPQKVNILVDTGSSNFAVAGSPNPDVNTFFDSKLSTSYQSLNTEVTVRYTQGSWTGLLGKDVVSIPKG 152 African clawed ...
CAF90923      24 GRGYYIEMSIGTPGQKMNILVDTGSSNFAVAAAPHPFITHFFNTALSTSYRSAGRPVAVRYTQGNWEGELGVDLVSMPTG 103 Tetraodon nigro...
XP_416735     71 GRGYFLEMLIGTPPQALNILVDTGSSNFAVAGVPDPDVTSYFNTELSSTYQSQGIEVTVKYSQGSWTGVLGTDVVTIPKG 150 chicken
2HIZ_A        74 GQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHG 153 human
2EWY_A        12 GRGYYLEMLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKG 91  human
XP_001187192  78 GLGYYIEVDIGTPPQKLNVLIDTGSSNFAVAASSHNAISTYYRRNESSTYEDQGTYVKVPYTQGEWSGDLGQDLVQIASL 157 purple urchin
XP_001631422   9 GQGYYIASNLGSPPQRINVLVDTGSSNFAVAASAHPYIPYYFHIDKSTSYKDLNKPVSVPYTQGSWEGELGSDLIKFVDG 88  starlet sea ane...
Feature 1                                                                                        
1YM4_A       107 pnvTVRANIAAITESDKFFIngSNWEGILGLAYAEIARPDdslepFFDSLVKQth-vPNLFSLQLCGAGfplnqs----- 180 human
AAI21913     153 pnvTVTANIAAITDSDKFFIngSNWEGILGLAYAEIARPDdtlepFFDSLVKQtr-vPNIFSLQLCGTGfhfnes----- 226 western clawed ...
AAH65973     157 pnvSLRANIAAITQSDRFFIngSNWEGILGLAYAEIARPDetlepFFDSLLRQst-vADVFSLQLCGAGynhnyst---- 231 zebrafish
Q9Y5Z0       169 fntSFLVNIATIFESENFFLpgIKWNGILGLAYATLAKPSssletFFDSLVTQan-iPNVFSMQMCGAGlpvag------ 241 human
AAH55989     153 vngTFLINIASIFQSESFFLpnINWQGILGLAYSTLAKPSssvepFFDSLVQQen-iPDVFSMQMCGAGqsspg------ 225 African clawed ...
CAF90923     104 pngTVPINIAAILSSDGFFLpdIHWQGILGLAYPLLARPDssvtpFFDSLVRQlg-iPDVFSLQMCGAGlsagaa----- 177 Tetraodon nigro...
XP_416735    151 idgRYTINIATILESENFFLpgVKWHGILGLAYDTLAKPSssvetFFDSLVKQak-iPNIFSLQMCGAGlpvsg------ 223 chicken
2HIZ_A       154 pnvTVRANIAAITESDKFFIngSNWEGILGLAYAEIARPDdslepFFDSLVKQth-vPNLFSLQLCGAGfplnqs----- 227 human
2EWY_A        92 fntSFLVNIATIFESENFFLpgIKWNGILGLAYATLAKPSssletFFDSLVTQan-iPNVFSMQMCGAGlpvag------ 164 human
XP_001187192 158 gnqSFQANIAAITESKMFFLndSRWQGILGLGYAEIARPDssvepFFDSLTSQts-iQDIFALQMCGALastndtnlgss 236 purple urchin
XP_001631422  89 pnvTLRVDVASILQSENFFIngSMWEGILGLGYARLAKPDssvtpVFDQFVLDhgveKDSFSMQLCGSSeidps------ 162 starlet sea ane...
Feature 1                                                                         #              
1YM4_A       181 --evlasvGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFE 258 human
AAI21913     227 --dtsasvGGSMVIGGIDPSLYIGSIWYTPIRKEWYYEVIIVKIEINGQDLHMDCKEYNYDKSIVDSGTTNLRLPKRVFD 304 western clawed ...
AAH65973     232 --gssstvGGSMIIGGVDPSLYVGELWYTPIRREWYYEVIIVRIEVNGQDLNMDCKEYNYDKSIVDSGTTNLRLPRKVFQ 309 zebrafish
Q9Y5Z0       242 ----sgtnGGSLVLGGIEPSLYKGDIWYTPIKEEWYYQIEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFD 317 human
AAH55989     226 ----nginAGSLVLGGVEPSLYKGNIWYTPITEEWYYQVEVLKFEVGGQRLNLDCTVYNSDKAIVDSGTTLLRLPDKVFN 301 African clawed ...
CAF90923     178 ---aaaalGGSLIMGGTEPTLHRGPVWYTPIVEEWYYQVEVLKLEVGDQNLDLDCREYNTDKAIVDSGTTLLRLPVPVFN 254 Tetraodon nigro...
XP_416735    224 ----sgtnGGSLVLGGIEPSLYKGNIWYTPIKEEWYYQVEILKLEVGGQNLELDCREYNADKAIVDSGTTLLRLPQKVFS 299 chicken
2HIZ_A       228 --evlasvGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFE 305 human
2EWY_A       165 ----sgtnGGSLVLGGIEPSLYKGDIWYTPIKEEWYYQIEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFD 240 human
XP_001187192 237 adgpveevIGSMNIGGLDASLYHGTMQYAPLRDEWFYEVIMTDIRVGNDSLGLDCKEYNFDKTIVDSGTTNLRLPVRVFE 316 purple urchin
XP_001631422 163 ---aeptvAGTMVFGEIDEELYKGDLLYTPIVKKWYYEVVITDVAVDGDSLALDCKKYNYDKTIVDSGTTNLRVSEEVFN 239 starlet sea ane...
Feature 1                                                                                        
1YM4_A       259 AAVKSIKAASst--------------------ekFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLmgev---tnqSFRIT 315 human
AAI21913     305 AAVKSIKAASst--------------------ekFPDGFWLGEQLVCWQEGTTPWHIFPVISLYLmgev---anqSFKIT 361 western clawed ...
AAH65973     310 AAVKAIEAASst--------------------eqFPSGFWLGEQLVCWQAGTTPWHIFPVISLYLmsen---rnqSFRIS 366 zebrafish
Q9Y5Z0       318 AVVEAVARASli--------------------peFSDGFWTGSQLACWTNSETPWSYFPKISIYLrden---ssrSFRIT 374 human
AAH55989     302 AMVDAIVQTSli--------------------qnFNAEFWAGLQLACWDKTQQPWNYFPDISIYLrdtn---tsrSFRLT 358 African clawed ...
CAF90923     255 ALVDAITRSSlvrrrsragltagvdlplicqiqdFSAGFWDGSKLACWMKGETPWRFFPKLSIYLratn---tseSFRIT 331 Tetraodon nigro...
XP_416735    300 AVVQAIARTSli--------------------qeFSSGFWSGSQLACWDKTERPWSLFPKLSIYMrden---ssrSFRIS 356 chicken
2HIZ_A       306 AAVKSIKAASst--------------------ekFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLmgev---tnqSFRIT 362 human
2EWY_A       241 AVVEAVARASli--------------------peFSDGFWTGSQLACWTNSETPWSYFPKISIYLrden---ssrSFRIT 297 human
XP_001187192 317 AITNAIKAHTtkh------------------mpdVPSEFWTGMNLMCPTDSTSPYEPYHWFPTLTldlqstnqgqAFSLV 378 purple urchin
XP_001631422 240 AILDRLRKFDkv--------------------nlIPDDFWYGRQMMCWNYDRTPWEEFPDMSISLlssl--ssskEFRLK 297 starlet sea ane...
Feature 1                                                                                       
1YM4_A       316 ILPQQYLRPVEDvats-qddCYKFAISQSStGTVMGAVIMEGFYVVFDRARKRIGFAVsachvhd-efrtaaVEGPFVT 392 human
AAI21913     362 ILPQQYLRPVEDiata-qedCYKFAVSQSTtGTVMGAVIMEGFYVVFDRANKRIGFAVstchvhd-yfrtasVEGPFFA 438 western clawed frog
AAH65973     367 ILPQQYLRPVEDvasa-qedCYKFAVSQSStGTVMGAVIMEGFYVVFERQHKRIGFAVstchvhd-efrtaaVEGPFHG 443 zebrafish
Q9Y5Z0       375 ILPQLYIQPMMGagl--nyeCYRFGISPSTnALVIGATVMEGFYVIFDRAQKRVGFAAspcaeia-gaavseISGPFST 450 human
AAH55989     359 LKPQLYIQSVLTfqe--slnCFRFGISQSAsTLVIGATVMEGFYVIFDRAEKRVGFAVsscaevs-gitvseIAGPFGT 434 African clawed frog
CAF90923     332 ILPQLYIQQITDldg--tldCFRFGVSSSVnGLVIGATVMEGFYVVFDRAQRRLGFALstcaasg-glplseIAGPFSA 407 Tetraodon nigrov...
XP_416735    357 ILPQLYIQPILGige--nlqCYRFGISSSTnALVIGATVMEGFYVIFDRAQRRVGFAVspcaevd-gspvseIEGPFTT 432 chicken
2HIZ_A       363 ILPQQYLRPVEDvats-qddCYKFAISQSStGTVMGAVIMEGFYVVFDRARKRIGFAVsachvhd-efrtaaVEGPFVT 439 human
2EWY_A       298 ILPQLYIQPMMGagl--nyeCYRFGISPSTnALVIGATVMEGFYVIFDRAQKRVGFAAspcaeia-gaavseISGPFST 373 human
XP_001187192 379 VSPQQYLRRDYDhed--kknCFKFAIAPSTnHAVIGAVIMEGFYVVFDRENKRVGFARstcpgacektgtcvGNSPLIT 455 purple urchin
XP_001631422 298 IPPQLYLRETIEhgpimgqhCYKFAITRAErGTVIGAVIMEGFYVVFDRENVQVGFAAttcggk--epmrylLSSKFYL 374 starlet sea anemone

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap