1H8L,1UWY,2NSM,3MN8,1QMU


Conserved Protein Domain Family
M14_CP_N-E_like

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cd03858: M14_CP_N-E_like 
Click on image for an interactive view with Cn3D
Peptidase M14 carboxypeptidase subfamily N/E-like
Carboxypeptidase (CP) N/E-like 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.
Statistics
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PSSM-Id: 349431
View PSSM: cd03858
Aligned: 24 rows
Threshold Bit Score: 397.022
Threshold Setting Gi: 115502368
Created: 18-Oct-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Zn binding siteactive site
Conserved site includes 3 residues -Click on image for an interactive view with Cn3D
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.
  • Structure:1QMU_A: duck carboxypeptidase D; contacts at 3.5A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                   #  #               
1H8L_A      10 HHHFsDMEIFLRRYANEYPsITRLYSVGKSvELRELYVMEISDNPGIHEaGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 89   crested duck
1UWY_A       5 YHRQeGMEAFLKTVAQNYSsVTHLHSIGKSvKGRNLWVLVVGRFPKEHRiGIPEFKYVANMHGDETVGRELLLHLIDYLV 84   human
3MN8_A      40 YASQeQLEDLFAGLEKAYPnQAKVHFLGRSlEGRNLLALQISRNTRSRNlLTPPVKYIANMHGDETVGRQLLVYMAQYLL 119  fruit fly
O75976     933 YHSYkDLSEFLRGLVMNYPhITNLTNLGQStEYRHIWSLEISNKPNVSEpEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012 human
NP_974126   65 YMTNdDLEKAMKDFTKRCSkISRLYSIGKSvNGFPLWVIEISDRPGEIE-AEPAFKYIGNVHGDEPVGRELLLRLANWIC 143  thale cress
XP_420392   46 YHRYaELREALVAVWLQCPaISRIYTVGRSsEGRELLVIEVSDRPGEHEpGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 125  chicken
1QMU_A      10 HHHFsDMEIFLRRYANEYPsITRLYSVGKSvELRELYVMEISDNPGIHEaGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 89   crested duck
NP_510625   58 HMNYsTLTDHIHNLHRKFPnLTHIYSAGQSvQGRELWVLVVSRYPIEHRkLIPEFKYVANMHGNEVTGRVFLVSLAHTLL 137  nematode
EEN52249    32 HHRYtELEQILRETAAAHPdITRLYSVGKSyEKRNLWALEISDNPGKHElGEPEFKYIGNMHGNEVVGRELLLNLVKYLT 111  Florida lancelet
CCD60934    59 YNHYdSLFEKMQEVSRRCPmITTLYTIGKSvAGRELWVLSFGKVSNYHVpGVPEVKFVGNMHGNEAIGRELILRLAYLLC 138  Schistosoma mansoni
Feature 1                                                                                      
1H8L_A      90 KNFg-tDPEVTDLVQsTRIHIMPSMNPDGYEksqegd----rggtvGRNNsNNYDLNRNFPDqffqv------------- 151  crested duck
1UWY_A      85 TSDg-kDPEITNLINsTRIHIMPSMNPDGFEavkkpd----cyysiGRENyNQYDLNRNFPDafeyn------------- 146  human
3MN8_A     120 GNHe-rISDLGQLVNsTDIYLVPTMNPDGYAlsqegnc-eslpnyvGRGNaANIDLNRDFPDrleqshvh---------- 187  fruit fly
O75976    1013 LNYk-kNPAVTQLVDrTRIVIVPSLNPDGREraqekd----ctskiGQTNaRGKDLDTDFTNna---------------- 1071 human
NP_974126  144 DNYk-kDPLAQMIVEnVHLHIMPSLNPDGFSi-------------rKRNNaNNVDLNRDFPDqffpfn------------ 197  thale cress
XP_420392  126 NEYqkgNETIINLIHsTRIHIMPSLNPDGFEkaasqpg-elkdwfvGRSNaQGIDLNRNFPDldrivyvnekeggpnn-- 202  chicken
1QMU_A      90 KNFg-tDPEVTDLVQsTRIHIMPSMNPDGYEksqegd----rggtvGRNNsNNYDLNRNFPDqffqv------------- 151  crested duck
NP_510625  138 ENYn-sNLWIRQLVDsTRIHLMPSMNPDGYEhasegd----qagvtGRQNaNGKDLNRNFPSrfpnyf------------ 200  nematode
EEN52249   112 TEYkkgNQRVRSLVDnTRIHIMPTMNPDGYEaaadmidsgkkdwltGRANaQGIDLNRNFPDldrivyrmetvggpnnhl 191  Florida lancelet
CCD60934   139 MNYg-sDEFVTLLVNyTQIHLMPSANPDGFEissegd----tsgliGRNNlHNVDLNRNFPDqfgkt------------- 200  Schistosoma mansoni
Feature 1                                              #                                       
1H8L_A     152 -------------tdppQPETLAVMSWLKTy-PFVLSANLHGGsLVVNYPFDddeqg---iaiySKSPDDAVFQQLALSY 214  crested duck
1UWY_A     147 -------------nvsrQPETVAVMKWLKTe-TFVLSANLHGGaLVASYPFDngvqatgalysrSLTPDDDVFQYLAHTY 212  human
3MN8_A     188 ----------qlraqsrQPETAALVNWIVSk-PFVLSANFHGGaVVASYPYDnslahn-ecceeSLTPDDRVFKQLAHTY 255  fruit fly
O75976    1072 ----------------sQPETKAIIENLIQkqDFSLSVALDGGsMLVTYPYDkp---------vQTVENKETLKHLASLY 1126 human
NP_974126  198 -----------ddlnlrQPETKAIMTWLRDi-RFTASATLHGGaLVANFPWDgtedk---rkyyYACPDDETFRFLARIY 262  thale cress
XP_420392  203 -hllknmkkavdqnpklAPETKGVIHWIMDi-PFVLSANLHGGdLVANYPYDetrsg--saheySSCPDDAIFQSLARSY 278  chicken
1QMU_A     152 -------------tdppQPETLAVMSWLKTy-PFVLSANLHGGsLVVNYPFDddeqg---iaiySKSPDDAVFQQLALSY 214  crested duck
NP_510625  201 ------------ptseiQPETIAIMNWTRQi-PFALSANLHGGtTLVNYPFDdfptrt-rqshyAPSPDNALFVRLAYTY 266  nematode
EEN52249   192 edgvsqqllksvnkkriAPETEAVIAWIEQy-PFALSANMHGGdLVANYPYDesrsg--rsqeyAECPDDAVFKRLARSY 268  Florida lancelet
CCD60934   201 -------------nenvEPETKLIMQWSQEh-SFVLSGNLHAGsLVASYPFDgsanm---ttyySASPDDATFKHLASVY 263  Schistosoma mansoni
Feature 1                                                                                      
1H8L_A     215 SKENKKMYQGspckd--lypteYFP----HGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCvKYPKAEELPKYWEQN 288  crested duck
1UWY_A     213 ASRNPNMKKGdeck-----nkmNFP----NGVTNGYSWYPLQGGMQDYNYIWAQCFEITLELSCcKYPREEKLPSFWNNN 283  human
3MN8_A     256 SDNHPIMRKGnnc-------ndSFS----GGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCcKYPAASTLPQEWQRN 324  fruit fly
O75976    1127 ANNHPSMHMGqpscp--nksdeNIP----GGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCcYFPSAARLPSLWADN 1200 human
NP_974126  263 SKSHRNMSLSk-----------EFE----EGITNGASWYPIYGGMQDWNYIYGGCFELTLEISDnKWPKASELSTIWDYN 327  thale cress
XP_420392  279 SSLNPAMSDPnrppcrkndddsSFV----DGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCeKFPPEETLKGYWEDN 354  chicken
1QMU_A     215 SKENKKMYQGspckd--lypteYFP----HGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCvKYPKAEELPKYWEQN 288  crested duck
NP_510625  267 ARGHERMWKKgprcl---dddlNISvdpqNGIINGADWYIVSGGMQDWNYLNTNCFEVTVEMNCeKFPQTKKLRYLWEEN 343  nematode
EEN52249   269 SLNQPEMSNPkrrgcd-mdngdKFA----DGITNGADWYSVDGGMQDFNYLISNSFEITLELGCdKFPPASELKKAWTDN 343  Florida lancelet
CCD60934   264 SRAHRSMYLGrpec-----dfmTFP----NGITNGNNWYPLQGGMQDWNYLVTGCMEITLELGCvKYPRGSEISTYWDDN 334  Schistosoma mansoni
Feature 1                
1H8L_A     289 RRSLLQFIKQ 298  crested duck
1UWY_A     284 KASLIEYIKQ 293  human
3MN8_A     325 KASLLQLLRQ 334  fruit fly
O75976    1201 KRSLLSMLVE 1210 human
NP_974126  328 RKSMLNLVAS 337  thale cress
XP_420392  355 KNSLINYIEQ 364  chicken
1QMU_A     289 RRSLLQFIKQ 298  crested duck
NP_510625  344 KYALLKFIDL 353  nematode
EEN52249   344 KESMLTFMEQ 353  Florida lancelet
CCD60934   335 KYSLIAFLSE 344  Schistosoma mansoni

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