Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  49 FRILLTFGQHGRELITSELAFRILSILSEEQFLPNKN--GGILKNTLDKLVIKMVPIENPNGRKRVESGDLCERRNGRGV 126
Cdd:cd06227    2 PRVLLVFGEHARELISVESALRLLRQLCGGLQEPAASalRELAREILDNVELKIIPNANPDGRRLVESGDYCWRGNENGV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 127 DLNRNWGVDWGKKEKDYdPSEENPGTAPFSEPETQIMRKLAISFDPHIWINVHSGMEALFMPYDHKNITPEGLPSQKMRT 206
Cdd:cd06227   82 DLNRNWGVDWGKGEKGA-PSEEYPGPKPFSEPETRALRDLALSFKPHAFVSVHSGMLAIYTPYAYSASVPRPNRAADMDD 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186528528 207 LLEKLNKfHCHDRCMIGSGGGSVGYLAHGTATDYIYDVVKAPMAFTFEIYGDNQTA-SRDCFKMF 270
Cdd:cd06227  161 LLDVVAK-ASCGDCTVGSAGKLVGYLADGTAMDYMYGKLKVPYSFTFEIYGDSGKArCFDCFNPF 224

Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  49 FRILLTFGQHGRELITSELAFRILSILSEEQFLPNKN--GGILKNTLDKLVIKMVPIENPNGRKRVESGDLCERRNGRGV 126
Cdd:cd06227    2 PRVLLVFGEHARELISVESALRLLRQLCGGLQEPAASalRELAREILDNVELKIIPNANPDGRRLVESGDYCWRGNENGV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 127 DLNRNWGVDWGKKEKDYdPSEENPGTAPFSEPETQIMRKLAISFDPHIWINVHSGMEALFMPYDHKNITPEGLPSQKMRT 206
Cdd:cd06227   82 DLNRNWGVDWGKGEKGA-PSEEYPGPKPFSEPETRALRDLALSFKPHAFVSVHSGMLAIYTPYAYSASVPRPNRAADMDD 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186528528 207 LLEKLNKfHCHDRCMIGSGGGSVGYLAHGTATDYIYDVVKAPMAFTFEIYGDNQTA-SRDCFKMF 270
Cdd:cd06227  161 LLDVVAK-ASCGDCTVGSAGKLVGYLADGTAMDYMYGKLKVPYSFTFEIYGDSGKArCFDCFNPF 224

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528   51 ILLTFGQHGRELITSELAFRILsilseEQFLPNKNGG-ILKNTLDKLVIKMVPIENPNGRKRVESGDLCERRN------- 122
Cdd:pfam00246  49 VFIDGGIHAREWIGPATALYLI-----HQLLTNYGRDpEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNrsnangs 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  123 -GRGVDLNRNWGVDWGKKEKDYDP-SEENPGTAPFSEPETQIMRKL---AISFDPhiWINVHSGMEALFMPYDHKNITP- 196
Cdd:pfam00246 124 sCIGVDLNRNFPDHWNEVGASSNPcSETYRGPAPFSEPETRAVADFirsKKPFVL--YISLHSYSQVLLYPYGYTRDEPp 201

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 186528528  197 ---EGLPS---------QKMRTLLEKlnkfhchdrcmigSGGGSVG---YLAHGTATDYIYDVVKAPMAFTFE 254
Cdd:pfam00246 202 pddEELKSlaraaakalQKMVRGTSY-------------TYGITNGatiYPASGGSDDWAYGRLGIKYSYTIE 261

murein tripeptide amidase MpaA;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 186528528 105 NPNGRKrvesgdLCERRNGRGVDLNRNW-GVDWGKKEKDYDPSEENP--------GTAPFSEPETQ 161
Cdd:PRK10602  80 NPDGCQ------LGLRANANGVDLNRNFpAANWKEGETVYRWNSAAEerdvvlltGDKPGSEPETQ 139

Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  49 FRILLTFGQHGRELITSELAFRILSILSEEQFLPNKN--GGILKNTLDKLVIKMVPIENPNGRKRVESGDLCERRNGRGV 126
Cdd:cd06227    2 PRVLLVFGEHARELISVESALRLLRQLCGGLQEPAASalRELAREILDNVELKIIPNANPDGRRLVESGDYCWRGNENGV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 127 DLNRNWGVDWGKKEKDYdPSEENPGTAPFSEPETQIMRKLAISFDPHIWINVHSGMEALFMPYDHKNITPEGLPSQKMRT 206
Cdd:cd06227   82 DLNRNWGVDWGKGEKGA-PSEEYPGPKPFSEPETRALRDLALSFKPHAFVSVHSGMLAIYTPYAYSASVPRPNRAADMDD 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186528528 207 LLEKLNKfHCHDRCMIGSGGGSVGYLAHGTATDYIYDVVKAPMAFTFEIYGDNQTA-SRDCFKMF 270
Cdd:cd06227  161 LLDVVAK-ASCGDCTVGSAGKLVGYLADGTAMDYMYGKLKVPYSFTFEIYGDSGKArCFDCFNPF 224

M14 family of metallocarboxypeptidases and related proteins; The M14 family of metallocarboxypeptidases (MCPs), also known as funnelins, are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  51 ILLTFGQHGRELITSELAFRILsilseEQFLPNKNGGILKNTLDKLVIKMVPIENPNGRKRVEsgDLCERRNGRGVDLNR 130
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALI-----EYLLENYGNDPLKRLLDNVELWIVPLVNPDGFARVI--DSGGRKNANGVDLNR 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 131 NWGVDWGKKEKDYDPSEENPGTAPFSEPETQIMRKLAISFDPHIWINVHSGMEALFMPYDHKNiTPEGLPSQkMRTLLEK 210
Cdd:cd00596   74 NFPYNWGKDGTSGPSSPTYRGPAPFSEPETQALRDLAKSHRFDLAVSYHSSSEAILYPYGYTN-EPPPDFSE-FQELAAG 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 186528528 211 LNKFHCHDRCmiGSGGGSVGYLAHGTATDYIYDVVKAPmAFTFEIYG 257
Cdd:cd00596  152 LARALGAGEY--GYGYSYTWYSTTGTADDWLYGELGIL-AFTVELGT 195

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528   51 ILLTFGQHGRELITSELAFRILsilseEQFLPNKNGG-ILKNTLDKLVIKMVPIENPNGRKRVESGDLCERRN------- 122
Cdd:pfam00246  49 VFIDGGIHAREWIGPATALYLI-----HQLLTNYGRDpEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNrsnangs 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  123 -GRGVDLNRNWGVDWGKKEKDYDP-SEENPGTAPFSEPETQIMRKL---AISFDPhiWINVHSGMEALFMPYDHKNITP- 196
Cdd:pfam00246 124 sCIGVDLNRNFPDHWNEVGASSNPcSETYRGPAPFSEPETRAVADFirsKKPFVL--YISLHSYSQVLLYPYGYTRDEPp 201

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 186528528  197 ---EGLPS---------QKMRTLLEKlnkfhchdrcmigSGGGSVG---YLAHGTATDYIYDVVKAPMAFTFE 254
Cdd:pfam00246 202 pddEELKSlaraaakalQKMVRGTSY-------------TYGITNGatiYPASGGSDDWAYGRLGIKYSYTIE 261

Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528   2 EQIHS----LVHRHPDKLSIELIksgnkGYNAEVNVVTYCRGGKESDDRSNFRILLTFGQHGRELI-TSELAFRILSILS 76
Cdd:cd03860    5 DDIVQwlddLAAAFPDNVEIFTI-----GKSYEGRDITGIHIWGSGGKGGKPAIVIHGGQHAREWIsTSTVEYLAHQLLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  77 EEqflpnKNGGILKNTLDKLVIKMVPIENPNG-----------RK--RVESGDLCerrngRGVDLNRNWGVDWGKKEKDY 143
Cdd:cd03860   80 GY-----GSDATITALLDKFDFYIIPVVNPDGyvytwttdrlwRKnrQPTGGSSC-----VGIDLNRNWGYKWGGPGAST 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 144 DP-SEENPGTAPFSEPETQIM----RKLAISFDPHIWINVHS-GMEALFmPYDHK-NITPEGLP-----SQKMRTLLEKL 211
Cdd:cd03860  150 NPcSETYRGPSAFSAPETKALadfiNALAAGQGIKGFIDLHSySQLILY-PYGYScDAVPPDLEnlmelALGAAKAIRAV 228

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 186528528 212 N--KFhchdrcMIGSgGGSVGYLAHGTATDYIYDVVKAPMAFTFE 254
Cdd:cd03860  229 HgtTY------TVGP-ACSTLYPASGSSLDWAYDVAKIKYSYTIE 266

Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like domain of Gamma-D-glutamyl-L-diamino acid endopeptidase 1 (also known as Gamma-D-glutamyl-meso-diaminopimelate peptidase I, and Endopeptidase I (ENP1); EC 3.4.19.11). ENP1 is a member of the M14 family of metallocarboxypeptidases (MCPs), and is classified as belonging to subfamily C. However it has an exceptional type of activity of hydrolyzing the gamma-D-Glu-(L)meso-diaminopimelic acid (gamma-D-Glu-Dap) bond of L-Ala-gamma-D-Glu-(L)meso-diaminopimelic acid and L-Ala-gamma-D-Glu-(L)meso-diaminopimelic acid(L)-D-Ala peptides. ENP1 has a different substrate specificity and cellular role than MpaA (MpaA does not belong to this group). ENP1 hydrolyzes the gamma-D-Glu-Dap bond of MurNAc-tripeptide and MurNAc-tetrapeptide, as well as the amide bond of free tripeptide and tetrapeptide. ENP1 is active on spore cortex peptidoglycan, and is produced at stage IV of sporulation in forespore and spore integuments.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  51 ILLTFGQHGRELITSELAFRILsilseEQFLPNKNGGIL------KNTLDKLVIKMVPIENP-------NGRKRVESGDL 117
Cdd:cd06229    1 VLYNASFHAREYITTLLLMKFI-----EDYAKAYVNKSYirgkdvGELLNKVTLHIVPMVNPdgveisqNGSNAINPYYL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 118 CERR-------------NGRGVDLNRNWGVDWGKkEKDYDPSE----ENPGTAPFSEPETQIMRKLAISFDPHIWINVHS 180
Cdd:cd06229   76 RLVAwnkkgtdftgwkaNIRGVDLNRNFPAGWEK-EKRLGPKApgprDYPGKEPLSEPETKAMAALTRQNDFDLVLAYHS 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 181 GMEALFmpYDHKNITPEGLpsqkmRTLLEKLNKfhchdrcMIG-SGGGSVGYLAHGTATDYIYDVVKAPmAFTFEI-YGD 258
Cdd:cd06229  155 QGEEIY--WGYNGLEPEES-----KAMAEKFAS-------VSGyEPVEAEAIDSYGGFKDWFIYEFKKP-SFTIETgKGN 219

                        250
                 ....*....|....
gi 186528528 259 NQTASRDCFKMFNP 272
Cdd:cd06229  220 NPLPISQFDEIYEK 233

Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 carboxypeptidases found specifically in insects, including B-type carboxypeptidase of H. zea (CPBHz, insect gut carboxypeptidase-3) that is insensitive to potato carboxypeptidase inhibitor (PCI) in corn earworm, and midgut procarboxypeptidase A (PCPAHa, insect gut carboxypeptidase-1) from Helicoverpa armigera larva, a devastating pest of crops. PCPAHa preferentially cleaves aliphatic and aromatic residues. The peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  32 NVVTYCRGGKESDDRS---------NFR------ILLTFGQHGRELITSELAFRILSILSEEQFLPNKnggilknTLDKL 96
Cdd:cd06248   20 DVVTVVEGGYTFEGRPikyvrirstNSEdtskptIMIEGGINPREWISPPAALYAIHKLVEDVETQSD-------LLNNF 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  97 VIKMVPIENPNGRKRVESGDLCERRNGR-----------GVDLNRNWGVDWGKKEKDYDPSEEN-PGTAPFSEPETQIMR 164
Cdd:cd06248   93 DWIILPVANPDGYVFTHTNDREWTKNRStnsnplgqicfGVNINRNFDYQWNPVLSSESPCSELyAGPSAFSEAESRAIR 172

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 165 KLAISFDP--HIWINVHSGMEALFMPYDHKNITPeglpsQKMRTL----LEKLNKFHCHD-RCMIGSGGGSVGYLAHGTA 237
Cdd:cd06248  173 DILHEHGNriHLYISFHSGGSFILYPWGYDGSTS-----SNARQLhlagVAAAAAISSNNgRPYVVGQSSVLLYRAAGTS 247

                        250
                 ....*....|....*...
gi 186528528 238 TDYIYDVvkAPMAFTFEI 255
Cdd:cd06248  248 SDYAMGI--AGIDYTYEL 263

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 Carboxypeptidase (CP) A (CPA) belongs to the A/B 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. CPA enzymes generally favor hydrophobic residues. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. This subfamily includes CPA1, CPA2 and CPA4 forms. Within these A forms, there are slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528   7 LVHRHPDKLSieLIKSGNKGYNAEVNVVTYCRGGKESDDrsnfrILLTFGQHGRELITSELAFRILSILSEEQflpnKNG 86
Cdd:cd03870   19 LVAEHPNLVS--KLQIGSSFENRPMYVLKFSTGGEERPA-----IWIDAGIHSREWVTQASAIWTAEKIVSDY----GKD 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  87 GILKNTLDKLVIKMVPIENPNG-----------RK--RVESGDLCErrngrGVDLNRNWGVDWGKKEKDYDP-SEENPGT 152
Cdd:cd03870   88 PSITSILDTMDIFLEIVTNPDGyvfthssnrlwRKtrSVNPGSLCI-----GVDPNRNWDAGFGGPGASSNPcSETYHGP 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 153 APFSEPETqimrKLAISF-DPH----IWINVHSGMEALFMPYDHkniTPEGLPSQK-----MRTLLEKLNKFHcHDRCMI 222
Cdd:cd03870  163 HANSEVEV----KSIVDFiQSHgnfkAFISIHSYSQLLMYPYGY---TVEKAPDQEeldevAKKAVKALASLH-GTEYKV 234

                        250       260       270
                 ....*....|....*....|....*....|....
gi 186528528 223 GSGGGSVgYLAHGTATDYIYDV-VKapMAFTFEI 255
Cdd:cd03870  235 GSISTTI-YQASGSSIDWAYDNgIK--YAFTFEL 265

bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial carboxypeptidase (CP) members of the M14 family of metallocarboxypeptidases (MCPs), mostly of which have yet to be characterized. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  50 RILLTFGQHGRELITSELAFR-ILSILSEEqflpNKNGGIlKNTLDKLVIKMVPIENPNG--RKRVESGDLCERRNGRGV 126
Cdd:cd18173   56 EFKYTSTMHGDETTGYELMLRlIDYLLTNY----GTDPRI-TNLVDNTEIWINPLANPDGtyAGGNNTVSGATRYNANGV 130

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186528528 127 DLNRNWGvdwgkkekdyDPSEENPGTAPFSEPETQIMRKLAISFDPHIWINVHSGMEALFMPYDH 191
Cdd:cd18173  131 DLNRNFP----------DPVDGDHPDGNGWQPETQAMMNFADEHNFVLSANFHGGAEVVNYPWDT 185

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 carboxypeptidase (CP) O (CPO, also known as metallocarboxypeptidase C; EC 3.4.17.) belongs to the carboxypeptidase A/B 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. CPO has not been well characterized as yet, and little is known about it. Based on modeling studies, CPO has been suggested to have specificity for acidic residues rather than aliphatic/aromatic residues as in A-like enzymes or basic residues as in B-like enzymes. It remains to be demonstrated that CPO is functional as an MCP.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528   1 MEQIHSLVHRHPDKLSiELIKSGNKGYNAEVNVVTYCRGGKESDDRSNFrILLTFGQHGRELITseLAF---RILSILSE 77
Cdd:cd06247    7 MDEIYQWMDQMQEKNS-EVVSQHYLGQTYEKRPMYYLKIGWPSDKPKKI-IWMDCGIHAREWIA--PAFcqwFVKEILQN 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  78 eqflpNKNGGILKNTLDKLVIKMVPIENPNG--------RKRVESGDLCERRNGRGVDLNRNWGVDWGKKEKDYDPSEEN 149
Cdd:cd06247   83 -----YKTDSRLNKLLKNLDFYVLPVLNIDGyiyswttdRLWRKSRSPHNNGTCYGTDLNRNFNSQWCSIGASRNCCSII 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 150 -PGTAPFSEPETQIMRKLAISFDPHI--WINVHSGMEALFMPYDHKNITPEGLP-----SQK-MRTLLEKLNKFHchdrc 220
Cdd:cd06247  158 fCGTGPESEPETKAVADLIEKKKSDIlcYLTIHSYGQLILLPYGYTKEPSPNHEemmevGEKaAAALKEKHGTSY----- 232

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 186528528 221 MIGSgGGSVGYLAHGTATDYIYDvVKAPMAFTFEI 255
Cdd:cd06247  233 RVGS-SADILYSNSGSSRDWARD-IGIPFSYTFEL 265

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; The third carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain III. CPD differs from all other metallocarboxypeptidases in that it contains multiple CP-like domains. CPD belongs to the 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. CPD is a single-chain protein containing a signal peptide, three tandem repeats of CP-like domains separated by short bridge regions, followed by a transmembrane domain, and a C-terminal cytosolic tail. The first two CP-like domains of CPD contain all of the essential active site and substrate-binding residues, the third CP-like domain lacks critical residues necessary for enzymatic activity and is inactive towards standard CP substrates. Domain I is optimally active at pH 6.3-7.5 and prefers substrates with C-terminal Arg, whereas domain II is active at pH 5.0-6.5 and prefers substrates with C-terminal Lys. CPD functions in the processing of proteins that transit the secretory pathway, and is present in all vertebrates as well as Drosophila. It is broadly distributed in all tissue types. Within cells, CPD is present in the trans-Golgi network and immature secretory vesicles, but is excluded from mature vesicles. It is thought to play a role in the processing of proteins that are initially processed by furin or related endopeptidases present in the trans-Golgi network, such as growth factors and receptors. CPD is implicated in the pathogenesis of lupus erythematosus (LE), it is regulated by TGF-beta in various cell types of murine and human origin and is significantly down-regulated in CD14 positive cells isolated from patients with LE. As down -regulation of CPD leads to down-modulation of TGF-beta, CPD may have a role in a positive feedback loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  39 GGKESD-DRSNFRILLTFGQHGRELITSELafrilsILSEEQFLPN--KNGGILKNTLDKLVIKMVPIENPNGRKRVESG 115
Cdd:cd06245   42 GNKPNEsEPSEPKILFVGGIHGNAPVGTEL------LLLLAHFLCHnyKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEK 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 116 DlCE----RRNGRGVDLnrnwgvdwgkkEKDYDPSEENPGTAPfsEPETQIMRKLAISFDPHIWINVHSGMEALFMPYDH 191
Cdd:cd06245  116 K-CTskigEKNANGVDL-----------DTDFESNANNRSGAA--QPETKAIMDWLKEKDFTLSVALDGGSLVVTYPYDK 181

                 ....*.
gi 186528528 192 KNITPE 197
Cdd:cd06245  182 PVQTVE 187

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  50 RILLTFGQHGRELITSELAFRILSILSEEQFLPNKnggilknTLDKLVIKMVPIENPNGrkrvesGDLCERRNGRGVDLN 129
Cdd:cd06239    1 KVLLWSQMHGNEPTGTEALLDLISYLRRERQEFEK-------ILERLTLVAIPMLNPDG------AELFTRHNAEGIDLN 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 186528528 130 RNwgvdwGKKekdydpseenpgtapFSEPETQIMRKLAISFDPHIWINVH 179
Cdd:cd06239   68 RD-----ARA---------------LQTPESRALKAVLDSFSPKFAFNLH 97

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  50 RILLTFGQHGRE-------LITS-ELAFrilsilseeqflpnknGGILKNTLDKLVIKMVPIENPNGRkrvesgDLCERR 121
Cdd:cd06242    3 TVLLVGQQHGNEpagreaaLALArDLAF----------------GDDARELLEKVNVLVVPRANPDGR------AANTRG 60

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 186528528 122 NGRGVDLNRNwgvdwgkkekdydpseenpgTAPFSEPETQIMRKLAISFDPHIWINVH 179
Cdd:cd06242   61 NANGVDLNRD--------------------HLLLSTPETRALARVLRDYRPEVVIDAH 98

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  87 GILKNTLDKLVIKMVPIENPNGRKR------------VESGDlceRRNGRGVDLNRnwgvDWGKKEKdydpseenpgtap 154
Cdd:cd06241   31 GGKKHLLDNLILLFVPIFNADGNDRrskgnrpnqngpLEVGW---RTNAQGLDLNR----DFMKLEA------------- 90

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 186528528 155 fsePETQIMRKLAISFDPHIWINVHSgMEALFMPYD 190
Cdd:cd06241   91 ---PETRALAKLFNQWDPDLFIDTHT-TDGSDHQYD 122

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528  53 LTFGQHGRELITSELAFRILSILSEEQflpnknGGILKNTLDKLVIKMVPIENPNGRKR-----------VESGDLCER- 120
Cdd:cd06238    6 MGYSIHGNELSGSEAAMQVAYHLAAGQ------DEATRALLENTVIVIDPNQNPDGRERfvnwfnqnrgaVGDPDPQSMe 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 121 RN-----GRG----VDLNRNWgvdwgkkekdydpseenpgtAPFSEPETQIMRKLAISFDPHIWINVHsGMEA----LFM 187
Cdd:cd06238   80 HNepwpgGRTnhylFDLNRDW--------------------LAQTQPESRARAAAIHRWRPQVVVDFH-EMGTdqtfFFP 138

                        170
                 ....*....|...
gi 186528528 188 PYD---HKNITPE 197
Cdd:cd06238  139 PPAepvNPLIPRQ 151

Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (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. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186528528 125 GVDLNRNWGVDWgkkekDYDPSEENPGTAPFSEPETQIMrklaisfdphiwinvhsgmeALFMpYDHKNI 194
Cdd:cd06905  207 GVDLNRNFPYNW-----QPFYVQPGAGPYPLSEPETRAV--------------------ADFL-LAHPNI 250