Conserved Protein Domain Family
M14_CPE

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cd03865: M14_CPE 
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: 349437
View PSSM: cd03865
Aligned: 5 rows
Threshold Bit Score: 683.634
Threshold Setting Gi: 1215457371
Created: 19-Oct-2005
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Zn binding siteactive site
Feature 1: Zn binding site [ion binding site], 3 residue positions
Conserved feature residue pattern:[H] [ED] [H]Click to see conserved feature residue pattern help
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  46 YHRYAELREALVAVWLQCPaISRIYTVGRSsEGRELLVIEVSDRPGEHE------------------------------- 94  chicken
AAH70026   31 YHRYEEMRKSLVSVWLQCPsITRIYTVGESfEGRELLVLEMSDNPGIHE------------------------------- 79  zebrafish
AAI24929   41 YHRYPELRDALVSVWLQCPsISRIYTVGRSfEGRELLVIEISDNPGEHE------------------------------- 89  African clawed frog
P16870     53 YHRYPELREALVSVWLQCTaISRIYTVGRSfEGRELLVIELSDNPGVHE------------------------------- 101 human
OXB58586   47 YHRYAELREALVAVWLQCPaVSRIYTVGRSsEGRELLVIEVSDRPGEHEpgelkrdeewlcvtskstvdpsycmeevsll 126 scaled quail
Feature 1                                            #  #                                     
XP_420392  95 ---------------------------PGEPEFKYVGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIINLIHSTRIHIM 147 chicken
AAH70026   80 ---------------------------PGEPEFKYIGNMHGNEAVGRELLIYLAQYLCNEYQEGNDTIIDLIHSTRIHIM 132 zebrafish
AAI24929   90 ---------------------------PGEPEFKYVGNMHGNEAVGRELLIYLAQYLCNEYQRENETIVNLIHNTRIHIM 142 African clawed frog
P16870    102 ---------------------------PGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIVNLIHSTRIHIM 154 human
OXB58586  127 fcgtiantpradmnnhtgvvvnalklkPGEPEFKYVGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIINLIHSTQYTNL 206 scaled quail
Feature 1                                                                                     
XP_420392 148 P-SLNPDGFEKAASQPGe----------------------------------LKDWFVGRSNAQGIDLNRNFPDLDRIVY 192 chicken
AAH70026  133 P-SMNPDGFEKAASQPGe----------------------------------MKDWFVGRSNAQGIDLNRNFPDLDRIVY 177 zebrafish
AAI24929  143 P-SLNPDGFEKAAQQPGe----------------------------------IKDWFVGRSNAQSIDLNRNFPDLDRIVY 187 African clawed frog
P16870    155 P-SLNPDGFEKAASQPGe----------------------------------LKDWFVGRSNAQGIDLNRNFPDLDRIVY 199 human
OXB58586  207 SaFMVKETVKLFIQQPDrraaknlralylmskrmspssgnnkvgfviklpgeLKDWFVGRSNAQGIDLNRNFPDLDRIVY 286 scaled quail
Feature 1                                                     #                               
XP_420392 193 VNEKEGGPNNHLlknMKKAVDQNpKLAPETKGVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSaHEYSSCPDDAIFQ 272 chicken
AAH70026  178 MNEREGGANNHLlknMKKAVDENtKLAPETKAVIHWIMDIPFVLSANLHGGDVVANYPYDETRSGStHEYSASPDDLVFK 257 zebrafish
AAI24929  188 LNEREGGTNNHLmqnLKKSVDENtKLAPETVAVIHWIMDIPFVLSANLHGGDIVANYPYDKTRSGSaHEYSACPDDSIFK 267 African clawed frog
P16870    200 VNEKEGGPNNHLlknMKKIVDQNtKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSaHEYSSSPDDAIFQ 279 human
OXB58586  287 VNEKEGGPNNHLlknMKKAVDQNpKLAPETKGVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSaHEYSSCPDDAIFQ 366 scaled quail
Feature 1                                                                                     
XP_420392 273 SLARSYSSLNPAMSDPNRpPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWE 352 chicken
AAH70026  258 SLAKAYSIYNPVMSDTNRpPCRKNDDDSSFKEGITNGGAWYSVPGGMQDFNYLSSNCFEITLELSCDKFPPEDSLKQYWD 337 zebrafish
AAI24929  268 SLARAYSSLNPTMSDPDRkPCRKSDDDTSFIDGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELGCDKFPQEEKLKSYWE 347 African clawed frog
P16870    280 SLARAYSSFNPAMSDPNRpPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKTYWE 359 human
OXB58586  367 SLARSYSSLNPAMSDPNRpPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWE 446 scaled quail
Feature 1                 
XP_420392 353 DNKNSLINYIEQ 364 chicken
AAH70026  338 QNRNSLVNYIEQ 349 zebrafish
AAI24929  348 ENKDSLVNYLTQ 359 African clawed frog
P16870    360 DNKNSLISYLEQ 371 human
OXB58586  447 DNKNSLINYIEQ 458 scaled quail

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