Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; uncharacterized subgroup; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-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 1012713358  42 VPIHVINGRRPGPVLMVSAAIHGDELNGVEIIRRLLRHSALKSLNGTLLAVPVVNVFGFIHKTRYLPD-RRDLNRCFPGS 120
Cdd:cd06251     1 VPVLVARGAKPGPTLLLTAAIHGDELNGIEVIQRLLEDLDPSKLRGTLIAIPVVNPLGFENNSRYLPDdGRDLNRSFPGS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358 121 ETGSLGARMAWQFKSQVLDRATHAVDLHTGAIHRANLPQIRADLSNEDTAAMANAFGVPVVINSVLGEGTLREVAEAQGI 200
Cdd:cd06251    81 EKGSLASRLAHLLWNEIVKKADYVIDLHTASTGRTNLPYVRADLRDPESRRMAEAFGAPVIVDDPGEDGSLRGAAVELGI 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1012713358 201 PVITYEAGEALRFEESCIRAGVKGVLNIMQHLGMT 235
Cdd:cd06251   161 PAITVELGEALRFDEDIIRRGVEGVLNVLRHLGML 195

succinylglutamate desuccinylase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358  56 LMVSAAIHGDELNGVEIIRRLLRhsALksLNGTL-LAVPVVNVFG---FIHK-TRYLPDrrDLNRCFPGSE---TGSLGA 127
Cdd:PRK05324   50 LVLSAGIHGNETAPIELLDQLVR--DL--LAGELpLRARLLVILGnppAMRAgKRYLDE--DLNRLFGGRHqqfPGSDEA 123

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1012713358 128 RMAWQFKSQVLD----RATHA---VDLHTgAIhRA 155
Cdd:PRK05324  124 RRAAELEQAVEDffaaGAERVrwhYDLHT-AI-RG 156

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; uncharacterized subgroup; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-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 1012713358  42 VPIHVINGRRPGPVLMVSAAIHGDELNGVEIIRRLLRHSALKSLNGTLLAVPVVNVFGFIHKTRYLPD-RRDLNRCFPGS 120
Cdd:cd06251     1 VPVLVARGAKPGPTLLLTAAIHGDELNGIEVIQRLLEDLDPSKLRGTLIAIPVVNPLGFENNSRYLPDdGRDLNRSFPGS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358 121 ETGSLGARMAWQFKSQVLDRATHAVDLHTGAIHRANLPQIRADLSNEDTAAMANAFGVPVVINSVLGEGTLREVAEAQGI 200
Cdd:cd06251    81 EKGSLASRLAHLLWNEIVKKADYVIDLHTASTGRTNLPYVRADLRDPESRRMAEAFGAPVIVDDPGEDGSLRGAAVELGI 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1012713358 201 PVITYEAGEALRFEESCIRAGVKGVLNIMQHLGMT 235
Cdd:cd06251   161 PAITVELGEALRFDEDIIRRGVEGVLNVLRHLGML 195

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily belongs to the M14 family of metallocarboxypeptidases (MCPs), and includes ASTE, which catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-2; EC:3.5.1.15) which 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 1012713358  56 LMVSAAIHGDELNGVEIIRRLLRHSALKSLNGTLLAVPVVNVFGFIHKTRYLP-DRRDLNRCFPGSETGSLGARMAWQFK 134
Cdd:cd06230     1 LLILAGVHGDEYEGVEAIRRLLAELDPSELKGTVVLVPVANPPAFEAGTRYTPlDGLDLNRIFPGDPDGSPTERLAHELT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358 135 SQVLDRATHAVDLHTGAIHRANLPQI--RADLSNEDTAAMANAFGVPVVINSVLGE-GTLREVAEAQGIPVITYEAGEAL 211
Cdd:cd06230    81 ELILKHADALIDLHSGGTGRLVPYAIldYDSDAREKSRELARAFGGTPVIWGGDPPgGTPVAAARSAGIPAITVELGGGG 160

                         170
                  ....*....|....*..
gi 1012713358 212 RFEESCIRAGVKGVLNI 228
Cdd:cd06230   161 RLRAERLERYLRGIRNV 177

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; uncharacterized subgroup; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-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 1012713358  43 PIHVINGRRPGPVLMVSAAIHGDELNGVEIIRRLLRHSALKSLNGTLLAVPVVNVFGFIHKTRYL-P-DRRDLNRCFPGS 120
Cdd:cd06254     1 PVTLINGAKPGPTLLITAGIHGGEYPGILAAIRLARELDPADVKGTLIIVHIANVSGFEARTPFVvPeDGKNLNRVFPGD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358 121 ETGSLGARMAWQFKSQVLDRATHAVDLHTGAIHRANLP----QIRADLSNEDTA-AMANAFGVPVVINSVLGEGT-LREV 194
Cdd:cd06254    81 PDGTLTERIAYFLTREIISRADFLIDLHGGDANEALTPfvyyPGGASEEVNDISrAAAQALGLPYIVISSSEKGTgYYSY 160

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1012713358 195 AEAQGIPVITYEAGEALRFEESCIRAGVKGVLNIMQHL 232
Cdd:cd06254   161 AALRGIPSILVERGGLGTCDEEDVQAHKDGIKNLLRHL 198

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; uncharacterized subgroup; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-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 1012713358  27 VELPLAQlytqtPLNVPIHVINGRRPGPVLMVSAAIHGDELNGVEI----IRRLLRHSALK-SLNGTLLAVPVVNVFGFI 101
Cdd:cd06253     1 LESPFRE-----PLEVKGFRFGGGNAEPRIAIVAGIHGDELNGLYVcsrlIRFLKELEEGGyKLKGKVLVIPAVNPLGIN 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358 102 HKTRYLP-DRRDLNRCFPGSETGSLGARMA-WQFKSqvLDRATHAVDLHTGAIHRANLPQIRADLSN-EDTAAMANAFGV 178
Cdd:cd06253    76 SGTRFWPfDNLDMNRMFPGYNKGETTERIAaALFED--LKGADYGIDLHSSNDFLREIPQVRVIESGaQDLLPLAKFLGL 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1012713358 179 PVVI---NSVLGEGTLREVAEAQGIPVITYEAGEALRF-EESCIRAgVKGVLNIMQHLG 233
Cdd:cd06253   154 DVVWvhpASTVDTGTLAYNWNEWGTKALVLEMGVGMRIdKEYCEQL-FEGILRFLLKMG 211

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 1012713358  46 VINGRRPGPVLMVSAAIHGDELNGVEIIRRLLRHSALKSLNG-TLLAVPVVNVFGFIHKTRYLPDRRDLNRCFpGSETGS 124
Cdd:cd06231    35 SPNPRGDKPRVLISAGIHGDEPAGVEALLRFLESLAEKYLRRvNLLVLPCVNPWGFERNTRENADGIDLNRSF-LKDSPS 113

                          90       100
                  ....*....|....*....|....
gi 1012713358 125 LGARMAWQFKSQVLDRATHaVDLH 148
Cdd:cd06231   114 PEVRALMEFLASLGRFDLH-LDLH 136

Succinylglutamate desuccinylase [Amino acid transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358  56 LMVSAAIHGDELNGVEIIRRLLRHSALKSLngtLLAVPVVNVFG-----FIHKtRYLPdrRDLNRCFPGSE---TGSLGA 127
Cdd:COG2988    27 VVISGGIHGNETAPIELLDKLLQDLLLGER---PLSFRLLLILGnpaamRAGR-RYLD--EDLNRLFGGRHlqnPESYEA 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358 128 RMAWQFKSQVLDRATHA------VDLHTgAIHR------ANLPQIRADLSNEDTAAMANAfGVPVVINSVLGEGT----L 191
Cdd:COG2988   101 ARAKELEQAVGPFFAAGgrvrlhIDLHT-AIRNsgherfAVYPFRGRPFDLALLAYLAAA-GPEAVVLHHAPGGTfshfS 178

                         170       180
                  ....*....|....*....|..
gi 1012713358 192 REVAEAQGipvITYEAGEALRF 213
Cdd:COG2988   179 AELCGAQA---FTLELGKVRPF 197

Peptidase M14 Succinylglutamate desuccinylase (ASTE) subfamily; Peptidase M14 Succinylglutamate desuccinylase (ASTE, also known as N-succinyl-L-glutamate amidohydrolase, N2-succinylglutamate desuccinylase, and SGDS; EC 3.5.1.96) belongs to the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily of the M14 family of metallocarboxypeptidases. This group includes succinylglutamate desuccinylase that catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway. It hydrolyzes N-succinyl-L-glutamate to succinate and L-glutamate.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358  56 LMVSAAIHGDELNGVEIIRRLLRhsalKSLNGTL-LAVPVVNVFG---FIHK-TRYLPDrrDLNRCFPG---SETGSLGA 127
Cdd:cd03855    46 VVLSAGIHGNETAPIEILDQLIN----DLIRGELaLAHRLLFIFGnppAIRQgKRFIEE--NLNRLFSGrhsKLPPSYET 119

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1012713358 128 RMAWQFKSQV---LDRATHAV----DLHTgAIHRANLPQ 159
Cdd:cd03855   120 ARAAELEQAVadfFAKASGEVrwhlDLHT-AIRGSKHEQ 157

Succinylglutamate desuccinylase/aspartoacylase; uncharacterized; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-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 1012713358  56 LMVSAAIHGDELNGVEIIRRLLRH-SALKSLNGTLLAVPvVNVFGFIHKTRYLpdRRDLNRCFPGSETGS-----LGARM 129
Cdd:cd18430     1 LAVLGAVHGNETCGTRAVERLLAElPSGALQKGPVTLVP-ANERAYAEGVRFC--EEDLNRVFPGDPDPDtyerrLANRL 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1012713358 130 AwqfksQVLDRATHAVDLHTgaIHRANLPQIRADLSNEDTAAMANAFGVPVVINSVLGE 188
Cdd:cd18430    78 C-----PELEGHDVVLDLHS--THSGGQPFAILDYGDKASRRLARSVGIPKGWRVVYGR 129

Peptidase M14 carboxypeptidase Csd4 and similar proteins; This family includes peptidase M14 carboxypeptidase Csd4 from H. pylori which has been shown to be DL-carboxypeptidase with a modified zinc binding site containing a glutamine residue in place of a conserved histidine. It is an archetype of a new carboxypeptidase subfamily with a domain arrangement that differs from this family of peptide-cleaving enzymes. Csd4 plays a role in trimming uncrosslinked peptidoglycan peptide chains by cleaving the amide bond between meso-diaminopimelate and iso-D-glutamic acid in truncated peptidoglycan side chains. It acts as a cell shape determinant, similar to Campylobacter jejuni Pgp1. 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 1012713358  38 TPLNVPIHVINGRRPGPVLMVSAAIHGDELNGVEIIRRLLRHsalKSLNGTLLAVPVVNVFGFIHKTRYLpdRRDLNRCF 117
Cdd:cd06243     1 EDIEKPFTRLEGREPGPTLLIIGGIQGDEPGGFLAADLLADL---YLVKGNVIVVPRLNFPSILRNHRGL--NGDMNRKF 75

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1012713358  56 LMVSAAIHGDELNGVEI----IRRLLRHSALKS----LNGT-LLAVPVVNVFGF----IHKTRYLPDRRDLNRCFP 118
Cdd:cd00596     1 ILITGGIHGNEVIGVELalalIEYLLENYGNDPlkrlLDNVeLWIVPLVNPDGFarviDSGGRKNANGVDLNRNFP 76

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like subfamily; subgroup includes Pseudomonas aeruginosa AotO; An uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the the M14 family of metallocarboxypeptidases. This subgroup includes Pseudomonas aeruginosa AotO and related proteins. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-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. The gene encoding P. aeruginosa AotO was characterized as part of an operon encoding an arginine and ornithine transport system, however it is not essential for arginine and ornithine uptake.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012713358  28 ELPLAQLYTQTPLNVPIHVINGRRPGPVLMVSAAIHGDELNGV----EIIRRLLRHSALKSLNGTLLAVPVVN------- 96
Cdd:cd06250     2 RIPLDSPAPGTERSLTVFRFGGAGAGPKVYIQAALHADELPGNlvihHLLERLKALEAAGRIKGEIVLVPQANpiglsqk 81

                          90       100
                  ....*....|....*....|...
gi 1012713358  97 VFGFiHKTRY-LPDRRDLNRCFP 118
Cdd:cd06250    82 IGGY-HQGRFdLATGDNFNRNFP 103

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1012713358  53 GPVLMVSAAIHGDELNGVE----IIRRLLRHSALKSLNG--TLLAVPVVNVFGFIHKTRYLPDRRDLNR 115
Cdd:cd06242     1 KPTVLLVGQQHGNEPAGREaalaLARDLAFGDDARELLEkvNVLVVPRANPDGRAANTRGNANGVDLNR 69

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 1012713358  54 PVLMVSAAIHGDELNGVEII--------RRL----LRHSALKSLNgtLLAVPVVNVFGFIHKTRYLPDRRDLNRCFP--G 119
Cdd:cd03862     1 PVVGLVGGVHGLERIGTQVIlaflrsllARLkwdkLLQELLEEVR--LVVIPIVNPGGMALKTRSNPNGVDLMRNAPveA 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1012713358 120 SETGS-------LGARMAW-------QFKSQVLDR----------ATHAVDLHTG 150
Cdd:cd03862    79 VEKVPflvggqrISPHLPWyrgrnglETESQALIRyvnehlleskMSISLDCHSG 133