Conserved Protein Domain Family
M14_CPE

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cd03865: M14_CPE (this model, PSSM-Id:199847 is obsolete and has been replaced by 349437)
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup
Peptidase M14 Carboxypeptidase (CP) E (CPE, also known as carboxypeptidase H, and enkephalin convertase; EC 3.4.17.10) belongs to the N/E subfamily of the M14 family of metallocarboxypeptidases (MCPs).The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPE is an important enzyme responsible for the proteolytic processing of prohormone intermediates (such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin-releasing hormone) by specifically removing C-terminal basic residues. In addition, it has been proposed that the regulated secretory pathway (RSP) of the nervous and endocrine systems utilizes membrane-bound CPE as a sorting receptor. A naturally occurring point mutation in CPE reduces the stability of the enzyme and causes its degradation, leading to an accumulation of numerous neuroendocrine peptides that result in obesity and hyperglycemia. Reduced CPE enzyme and receptor activity could underlie abnormal placental phenotypes from the observation that CPE is down-regulated in enlarged placentas of interspecific hybrid (interspecies hybrid placental dysplasia, IHPD) and cloned mice.
Statistics
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PSSM-Id: 199847
View PSSM: cd03865
Aligned: 4 rows
Threshold Bit Score: 752.229
Threshold Setting Gi: 115892
Created: 19-Oct-2005
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
Zn binding siteputative active
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:Metallocarboxypeptidases share the zinc binding motif HXXE...H, where the zinc ion is penta-coordinated to ND1 atoms of the histidines, OE1 and OE2 atoms of the glutamic acid, and to a water molecule in a slightly distorted tetrahedral manner.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                      #  #           
XP_420392 133 ISFEYHRYAELREALVAVWLQCPaISRIYTVGRSsEGRELLVIEVSDRPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLA 212 chicken
AAH70026   27 ISFEYHRYEEMRKSLVSVWLQCPsITRIYTVGESfEGRELLVLEMSDNPGIHEPGEPEFKYIGNMHGNEAVGRELLIYLA 106 zebrafish
AAI24929   37 ISFEYHRYPELRDALVSVWLQCPsISRIYTVGRSfEGRELLVIEISDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIYLA 116 African clawed frog
P16870     49 ISFEYHRYPELREALVSVWLQCTaISRIYTVGRSfEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLA 128 human
Feature 1                                                                                     
XP_420392 213 QYLCNEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGeLKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPN 292 chicken
AAH70026  107 QYLCNEYQEGNDTIIDLIHSTRIHIMPSMNPDGFEKAASQPGeMKDWFVGRSNAQGIDLNRNFPDLDRIVYMNEREGGAN 186 zebrafish
AAI24929  117 QYLCNEYQRENETIVNLIHNTRIHIMPSLNPDGFEKAAQQPGeIKDWFVGRSNAQSIDLNRNFPDLDRIVYLNEREGGTN 196 African clawed frog
P16870    129 QYLCNEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGeLKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPN 208 human
Feature 1                                            #                                        
XP_420392 293 NHLlknMKKAVDQNpKLAPETKGVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSaHEYSSCPDDAIFQSLARSYSSL 372 chicken
AAH70026  187 NHLlknMKKAVDENtKLAPETKAVIHWIMDIPFVLSANLHGGDVVANYPYDETRSGStHEYSASPDDLVFKSLAKAYSIY 266 zebrafish
AAI24929  197 NHLmqnLKKSVDENtKLAPETVAVIHWIMDIPFVLSANLHGGDIVANYPYDKTRSGSaHEYSACPDDSIFKSLARAYSSL 276 African clawed frog
P16870    209 NHLlknMKKIVDQNtKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSaHEYSSSPDDAIFQSLARAYSSF 288 human
Feature 1                                                                                     
XP_420392 373 NPAMSDPNRpPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINY 452 chicken
AAH70026  267 NPVMSDTNRpPCRKNDDDSSFKEGITNGGAWYSVPGGMQDFNYLSSNCFEITLELSCDKFPPEDSLKQYWDQNRNSLVNY 346 zebrafish
AAI24929  277 NPTMSDPDRkPCRKSDDDTSFIDGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELGCDKFPQEEKLKSYWEENKDSLVNY 356 African clawed frog
P16870    289 NPAMSDPNRpPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKTYWEDNKNSLISY 368 human
Feature 1        
XP_420392 453 IEQ 455 chicken
AAH70026  347 IEQ 349 zebrafish
AAI24929  357 LTQ 359 African clawed frog
P16870    369 LEQ 371 human

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