Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family includes Francisella tularensis protein rapid encystment phenotype 34 (REP34) which is a zinc-containing monomeric protein demonstrating carboxypeptidase B-like activity. REP34 possesses a novel topology with its substrate binding pocket deviating from the canonical M14 peptidases with a possible catalytic role for a conserved tyrosine and distinct S1' recognition site. Thus, REP34, identified as an active carboxypeptidase and a potential key F. tularensis effector protein, may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells. 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 491527390  33 SYQDEVVSKIDAlrERFDVEQYGALSYNeaRFPLFCIKTRNWDSTKPAVLVTGGVHGYETSGVHGALKFVETEAERYAEH 112
Cdd:cd06231    1 SYLRDVAERLGA--RRFKVRELGEVGYQ--GYPLFALKSPNPRGDKPRVLISAGIHGDEPAGVEALLRFLESLAEKYLRR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 113 FNIVVAPCVSPWGYEVINRWNPNAIDPNRSFYKDSPAEESANLMKLVATLGDVLMHIDLHETTDSDET---EFRPAL-AA 188
Cdd:cd06231   77 VNLLVLPCVNPWGFERNTRENADGIDLNRSFLKDSPSPEVRALMEFLASLGRFDLHLDLHEDWDSDGFylyELGPALkAG 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 189 RDGIEY-------------IEGMI-PDGFYTVGDS--ENPQPDFQKAVIES--VAKVTHIAPADE--NGEIIGSPVVQFG 248
Cdd:cd06231  157 RDGLQAvdavippdpisltIDGSPaPDGVILRPDDpaERPGWPFAIYLVANgaVRTYTTETPSDFplERRVAAHLAAIRT 236

                 ..
gi 491527390 249 VI 250
Cdd:cd06231  237 AL 238

Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family includes Francisella tularensis protein rapid encystment phenotype 34 (REP34) which is a zinc-containing monomeric protein demonstrating carboxypeptidase B-like activity. REP34 possesses a novel topology with its substrate binding pocket deviating from the canonical M14 peptidases with a possible catalytic role for a conserved tyrosine and distinct S1' recognition site. Thus, REP34, identified as an active carboxypeptidase and a potential key F. tularensis effector protein, may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells. 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 491527390  33 SYQDEVVSKIDAlrERFDVEQYGALSYNeaRFPLFCIKTRNWDSTKPAVLVTGGVHGYETSGVHGALKFVETEAERYAEH 112
Cdd:cd06231    1 SYLRDVAERLGA--RRFKVRELGEVGYQ--GYPLFALKSPNPRGDKPRVLISAGIHGDEPAGVEALLRFLESLAEKYLRR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 113 FNIVVAPCVSPWGYEVINRWNPNAIDPNRSFYKDSPAEESANLMKLVATLGDVLMHIDLHETTDSDET---EFRPAL-AA 188
Cdd:cd06231   77 VNLLVLPCVNPWGFERNTRENADGIDLNRSFLKDSPSPEVRALMEFLASLGRFDLHLDLHEDWDSDGFylyELGPALkAG 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 189 RDGIEY-------------IEGMI-PDGFYTVGDS--ENPQPDFQKAVIES--VAKVTHIAPADE--NGEIIGSPVVQFG 248
Cdd:cd06231  157 RDGLQAvdavippdpisltIDGSPaPDGVILRPDDpaERPGWPFAIYLVANgaVRTYTTETPSDFplERRVAAHLAAIRT 236

                 ..
gi 491527390 249 VI 250
Cdd:cd06231  237 AL 238

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390   76 STKPAVLVTGGVHGYETSGVHGALKFVE---------TEAERYAEHFNIVVAPCVSPWGYEV---------INRWNPNA- 136
Cdd:pfam00246  44 PGKPAVFIDGGIHAREWIGPATALYLIHqlltnygrdPEITELLDDTDIYILPVVNPDGYEYthttdrlwrKNRSNANGs 123

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390  137 ----IDPNRSF-----------------YKDSPAE---ESANLMKLVATLGDVLMHIDLH 172
Cdd:pfam00246 124 scigVDLNRNFpdhwnevgassnpcsetYRGPAPFsepETRAVADFIRSKKPFVLYISLH 183

Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family includes Francisella tularensis protein rapid encystment phenotype 34 (REP34) which is a zinc-containing monomeric protein demonstrating carboxypeptidase B-like activity. REP34 possesses a novel topology with its substrate binding pocket deviating from the canonical M14 peptidases with a possible catalytic role for a conserved tyrosine and distinct S1' recognition site. Thus, REP34, identified as an active carboxypeptidase and a potential key F. tularensis effector protein, may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells. 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 491527390  33 SYQDEVVSKIDAlrERFDVEQYGALSYNeaRFPLFCIKTRNWDSTKPAVLVTGGVHGYETSGVHGALKFVETEAERYAEH 112
Cdd:cd06231    1 SYLRDVAERLGA--RRFKVRELGEVGYQ--GYPLFALKSPNPRGDKPRVLISAGIHGDEPAGVEALLRFLESLAEKYLRR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 113 FNIVVAPCVSPWGYEVINRWNPNAIDPNRSFYKDSPAEESANLMKLVATLGDVLMHIDLHETTDSDET---EFRPAL-AA 188
Cdd:cd06231   77 VNLLVLPCVNPWGFERNTRENADGIDLNRSFLKDSPSPEVRALMEFLASLGRFDLHLDLHEDWDSDGFylyELGPALkAG 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 189 RDGIEY-------------IEGMI-PDGFYTVGDS--ENPQPDFQKAVIES--VAKVTHIAPADE--NGEIIGSPVVQFG 248
Cdd:cd06231  157 RDGLQAvdavippdpisltIDGSPaPDGVILRPDDpaERPGWPFAIYLVANgaVRTYTTETPSDFplERRVAAHLAAIRT 236

                 ..
gi 491527390 249 VI 250
Cdd:cd06231  237 AL 238

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 491527390  81 VLVTGGVHGYETSGVHGALKFVETEAERYAEH--------FNIVVAPCVSPWGYEVIN----RWNPNAIDPNRSFYKDSP 148
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALIEYLLENYGNDplkrlldnVELWIVPLVNPDGFARVIdsggRKNANGVDLNRNFPYNWG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 491527390 149 AE-------------------ESANLMKLVATLGDVLmHIDLH 172
Cdd:cd00596   81 KDgtsgpssptyrgpapfsepETQALRDLAKSHRFDL-AVSYH 122

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390   76 STKPAVLVTGGVHGYETSGVHGALKFVE---------TEAERYAEHFNIVVAPCVSPWGYEV---------INRWNPNA- 136
Cdd:pfam00246  44 PGKPAVFIDGGIHAREWIGPATALYLIHqlltnygrdPEITELLDDTDIYILPVVNPDGYEYthttdrlwrKNRSNANGs 123

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390  137 ----IDPNRSF-----------------YKDSPAE---ESANLMKLVATLGDVLMHIDLH 172
Cdd:pfam00246 124 scigVDLNRNFpdhwnevgassnpcsetYRGPAPFsepETRAVADFIRSKKPFVLYISLH 183

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; uncharacterized bacterial subgroup; A bacterial subgroup of the Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP),-like proteins. The Peptidase M14 family of metallocarboxypeptidases 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. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins (such as alpha-tubulin in eukaryotes) to remove a C-terminal tyrosine. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390  65 PLFCIKTRNWDStKPAVLVTGGVHGYETSGVHGALKFVET------EAERYAEHFNIVVAPCVSPWGyeVIN---RWNPN 135
Cdd:cd06237   29 PIEALTIGNPDS-KELVVLLGRQHPPEVTGALAMQAFVETlladteLAKAFRARFRVLVVPLLNPDG--VDLghwRHNAG 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 136 AIDPNRSFYKDSPAEESA---NLMKLVATLG-DVLMHIDLHET-------TDSDETEFRPALaARDGIEYIEGMIPDgfY 204
Cdd:cd06237  106 GVDLNRDWGPFTQPETRAvrdFLLELVEEPGgKVVFGLDFHSTwedvfytQPDDEKTNPPGF-TPDWLAAIEERLPG--Y 182

                        170
                 ....*....|.
gi 491527390 205 TVGDSENPQPD 215
Cdd:cd06237  183 EVNIKPSHNPG 193

Predicted deacylase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390  79 PAVLVTGGVHGYETSGVHGALKFVEtEAERYAEHFNIVVAPCVSPWGYEVINRWNPN-AIDPNRSF--YKD-SPAEESAN 154
Cdd:COG3608   27 PTLLITAGIHGDELNGIEALRRLLR-ELDPGELRGTVILVPVANPPGFLQGSRYLPIdGRDLNRSFpgDADgSLAERIAH 105

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 491527390 155 -LMKLVATLGDVLmhIDLHetTDSDETEFRPALAARDGIEYIEGM 198
Cdd:COG3608  106 aLFEEILPDADYV--IDLH--SGGIARDNLPHVRAGPGDEELRAL 146

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390  75 DSTKPAVLVTGGVHGYETSGVHGALKFVETEAERYAEHFNI---------VVAPCVSPWGYEvinRWNPNAIDPNRSFYK 145
Cdd:cd06905   54 ADEKPALWVDGNIHGNEVTGSEVALYLAEYLLTNYGKDPEItrlldtrtfYILPRLNPDGAE---AYKLKTERSGRSSPR 130

                 ...
gi 491527390 146 DSP 148
Cdd:cd06905  131 DDD 133

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 491527390  32 RSYqDEVVSKIDALRERF----DVEQYGaLSYnEARfPLFCIK--TRNWDSTKPAVLVTGGVHGYETSGVHGALKFV--- 102
Cdd:cd03860    2 HPL-DDIVQWLDDLAAAFpdnvEIFTIG-KSY-EGR-DITGIHiwGSGGKGGKPAIVIHGGQHAREWISTSTVEYLAhql 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 103 ------ETEAERYAEHFNIVVAPCVSPWGYEV---INR-W------NPNA----IDPNRSF-----------------YK 145
Cdd:cd03860   78 lsgygsDATITALLDKFDFYIIPVVNPDGYVYtwtTDRlWrknrqpTGGSscvgIDLNRNWgykwggpgastnpcsetYR 157

                        170       180       190
                 ....*....|....*....|....*....|...
gi 491527390 146 -DSPAE--ESANLMKLVATLG---DVLMHIDLH 172
Cdd:cd03860  158 gPSAFSapETKALADFINALAagqGIKGFIDLH 190

Peptidase M14-like domain; uncharacterized subfamily; 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 491527390  78 KPAVLVTGGVHGYETSGVHGALKFVE---TEAERYAEHFNIVVAPCVSPWGYEV---INRWNP---------NAID---P 139
Cdd:cd06232   34 KPTILISARHHANEVSSTNAALRLAEllaTDPPEILKKVNLVIIPLENPDGYALheeLQKDNPehklhaaryNALGdeyA 113

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390 140 NRSFYKDSPAEESANLMKLVATLG-DVlmHIDLH-----ETTdsdetefRPaLAARDGIEYIEGMIPDGFYTVG-----D 208
Cdd:cd06232  114 YEYFNDDPRFPEAEVRPRAWERWLpDI--HVDLHgypshEWV-------QP-FSGYAPRGFRSYWLPRGLFYGYfpyldD 183

                        170       180       190
                 ....*....|....*....|....*....|...
gi 491527390 209 SENPQPDFQKAVIESVAK--VTHIAPADENGEI 239
Cdd:cd06232  184 EAYPGGELAEELAEAITKalNQDPALAAFNRRW 216

Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the Succinylglutamate desuccinylase/aspartoacylase subfamily of the M14 family of metallocarboxypeptidases. ASPA (also known as aminoacylase 2; EC:3.5.1.15) cleaves N-acetyl L-aspartic acid (NAA) into aspartate and acetate. NAA is abundant in the brain, and hydrolysis of NAA by ASPA may help maintain white matter. ASPA is an NAA scavenger in other tissues. Mutations in the gene encoding ASPA cause Canavan disease (CD), a fatal progressive neurodegenerative disorder involving dysmyelination and spongiform degeneration of white matter in children. This enzyme binds zinc which is necessary for activity. Measurement of elevated NAA levels in urine is used in the diagnosis of CD.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390  81 VLVTGGVHGYETSGVHGALKFVETEAERYAEHFNIVvaPCVSpwgyevinrwNPNAI---------DPNRSFYKD--SPA 149
Cdd:cd06909    3 VAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVH--PLLA----------NPRAVeqcrryidtDLNRCFSLEnlSSA 70

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 491527390 150 EESANL-----MKLVATLG-------DVLmhIDLHETT 175
Cdd:cd06909   71 PSSLPYevrraREINQILGpkgnpacDFI--IDLHNTT 106

Succinylglutamate desuccinylase / Aspartoacylase family; This family includes Succinylglutamate desuccinylase EC:3.1.-.- that catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway. The family also include aspartoacylase EC:3.5.1.15 which cleaves acylaspartate into a fatty acid and aspartate. Mutations in Swiss:P45381 lead to Canavan disease. This family is probably structurally related to pfam00246 (Bateman A pers. obs.).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491527390   79 PAVLVTGGVHGYETSGVHGALKFVETEAERYAEHFNIVVaPCVSPWGYEVINRWNPNaiDPNRSF------------YKD 146
Cdd:pfam04952   3 PTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLV-PLANPPAFRAGSRYIPR--DLNRSFpgralgassdepYRA 79

                          90       100
                  ....*....|....*....|....*....
gi 491527390  147 SPAEESANLMKLVAtLGDVLMHIDLHETT 175
Cdd:pfam04952  80 TRAERLADLFFPAL-LPRADIVLDLHTGT 107

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 491527390  79 PAVLVTGG-VHGYETSGVHGALKFVE-------TEAERYAEHFNIVVAPCVSPWGYEVINRWN 133
Cdd:cd06238    1 PAILWMGYsIHGNELSGSEAAMQVAYhlaagqdEATRALLENTVIVIDPNQNPDGRERFVNWF 63