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 1992479035  14 KRVAIFGGTHGNEMSGIMLVNMWIKNAAEIERNRLVTKPFISNPRAVEKCTRYINTDLNRAFTPENLSSqDVQGLPYEVQ 93
Cdd:cd06909     1 KRVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992479035  94 RAKEINQMFGPKGsSDAYDVIFDLHNTTSNMGSTLILESSTDlFNLQMVHYIKKAMAPqtCSVLLNEHPQLKYSTTRSVA 173
Cdd:cd06909    80 RAREINQILGPKG-NPACDFIIDLHNTTSNMGITLILSSSDD-FTLKLAAYLQQRLPP--VRVLLHESPSKESPFLRSVA 155

                  ....*
gi 1992479035 174 KHPIG 178
Cdd:cd06909   156 KHGFT 160

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 1992479035  14 KRVAIFGGTHGNEMSGIMLVNMWIKNAAEIERNRLVTKPFISNPRAVEKCTRYINTDLNRAFTPENLSSqDVQGLPYEVQ 93
Cdd:cd06909     1 KRVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992479035  94 RAKEINQMFGPKGsSDAYDVIFDLHNTTSNMGSTLILESSTDlFNLQMVHYIKKAMAPqtCSVLLNEHPQLKYSTTRSVA 173
Cdd:cd06909    80 RAREINQILGPKG-NPACDFIIDLHNTTSNMGITLILSSSDD-FTLKLAAYLQQRLPP--VRVLLHESPSKESPFLRSVA 155

                  ....*
gi 1992479035 174 KHPIG 178
Cdd:cd06909   156 KHGFT 160

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 1992479035  14 KRVAIFGGTHGNEMSGIMLVNMWIKNAAEIERNRLVTKPFISNPRAVEKCTRYINTDLNRAFTPENLSSQDvqGLPYEVQ 93
Cdd:pfam04952   3 PTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGASS--DEPYRAT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992479035  94 RAKEINQMFGPKgSSDAYDVIFDLHNTTSNMGSTLILESSTDLFNLQMVHYIKKAMAPQTCSVLLNEHPQLKYSTTRSVA 173
Cdd:pfam04952  81 RAERLADLFFPA-LLPRADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEELG 159

                  .
gi 1992479035 174 K 174
Cdd:pfam04952 160 A 160

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 1992479035  14 KRVAIFGGTHGNEMSGIMLVNMWIKNAAEIERNRLVTKPFISNPRAVEKCTRYINTDLNRAFTPENLSSqDVQGLPYEVQ 93
Cdd:cd06909     1 KRVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992479035  94 RAKEINQMFGPKGsSDAYDVIFDLHNTTSNMGSTLILESSTDlFNLQMVHYIKKAMAPqtCSVLLNEHPQLKYSTTRSVA 173
Cdd:cd06909    80 RAREINQILGPKG-NPACDFIIDLHNTTSNMGITLILSSSDD-FTLKLAAYLQQRLPP--VRVLLHESPSKESPFLRSVA 155

                  ....*
gi 1992479035 174 KHPIG 178
Cdd:cd06909   156 KHGFT 160

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 1992479035  14 KRVAIFGGTHGNEMSGIMLVNMWIKNAAEIERNRLVTKPFISNPRAVEKCTRYINTDLNRAFTPENLSSQDvqGLPYEVQ 93
Cdd:pfam04952   3 PTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGASS--DEPYRAT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992479035  94 RAKEINQMFGPKgSSDAYDVIFDLHNTTSNMGSTLILESSTDLFNLQMVHYIKKAMAPQTCSVLLNEHPQLKYSTTRSVA 173
Cdd:pfam04952  81 RAERLADLFFPA-LLPRADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEELG 159

                  .
gi 1992479035 174 K 174
Cdd:pfam04952 160 A 160

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 1992479035  16 VAIFGGTHGNEMSGIMLVNMWIKNAAEIERNRLVTKPFISNPRAVEKCTRYI---NTDLNRAFTPENLSSqdvqglpYEV 92
Cdd:cd06230     1 LLILAGVHGDEYEGVEAIRRLLAELDPSELKGTVVLVPVANPPAFEAGTRYTpldGLDLNRIFPGDPDGS-------PTE 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992479035  93 QRAKEINQMFGPKgssdaYDVIFDLHNTTSNM-GSTLILESS--TDLFNLQMVHYIkkamapQTCSVLLNEHPQ--LKYS 167
Cdd:cd06230    74 RLAHELTELILKH-----ADALIDLHSGGTGRlVPYAILDYDsdAREKSRELARAF------GGTPVIWGGDPPggTPVA 142

                  ....*..
gi 1992479035 168 TTRSVAK 174
Cdd:cd06230   143 AARSAGI 149

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 1992479035  11 QEAKRVAIFGGTHGNEMSGIMLVNMWIKNaaeIERNRLVTKP---FI-SNPRAVEKCTRYINTDLNRAFTPENlsSQDVQ 86
Cdd:cd03855    41 SASKSVVLSAGIHGNETAPIEILDQLIND---LIRGELALAHrllFIfGNPPAIRQGKRFIEENLNRLFSGRH--SKLPP 115

                          90
                  ....*....|....
gi 1992479035  87 GlpYEVQRAKEINQ 100
Cdd:cd03855   116 S--YETARAAELEQ 127

Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A (MpaA) and related proteins. MpaA is a member of the M14 family of metallocarboxypeptidases (MCPs), however it has an exceptional type of activity, it hydrolyzes the gamma-D-glutamyl-meso-diaminopimelic acid (gamma-D-Glu-Dap) bond in murein peptides. MpaA is specific for cleavage of the gamma-D-Glu-Dap bond of free murein tripeptide; it may also cleave murein tetrapeptide. MpaA has a different substrate specificity and cellular role than endopeptidase I, ENP1 (ENP1 does not belong to this group). MpaA works on free murein peptide in the recycling pathway.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1992479035  14 KRVAIFGGTHGNEMSGIMLVNMW---IKNAAEIERNRLVTKPfISNPRAVEKCTRYiN---TDLNRAFTPEN 79
Cdd:cd06904    24 ARILIIGGIHGDEPEGVSLVEHLlrwLKNHPASGDFHIVVVP-CLNPDGLAAGTRT-NangVDLNRNFPTKN 93

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 1992479035  12 EAKRVAIFGGTHGNEMSGImlvnmwikNAAEIERNRLVTK------PFIsNPRAVEKCTRYINTDLNRAFtpENLSSQDV 85
Cdd:cd06243    15 PGPTLLIIGGIQGDEPGGF--------LAADLLADLYLVKgnvivvPRL-NFPSILRNHRGLNGDMNRKF--AALDKKDP 83

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1992479035  86 QglpYE-VQRAKEINQMFGPkgssdayDVIFDLH 118
Cdd:cd06243    84 E---YKtIQEIKSLIADFRP-------DVVLHLH 107

Predicted deacylase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992479035  11 QEAKRVAIFGGTHGNEMSGIM----LVNMWikNAAEIeRNRLVTKPFIsNPRAVEKCTRYI---NTDLNRAFtPENLSSq 83
Cdd:COG3608    24 GPGPTLLITAGIHGDELNGIEalrrLLREL--DPGEL-RGTVILVPVA-NPPGFLQGSRYLpidGRDLNRSF-PGDADG- 97

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1992479035  84 dvqglPYEVQRAKEINQMFGPKgssdaYDVIFDLHNTTSNM 124
Cdd:COG3608    98 -----SLAERIAHALFEEILPD-----ADYVIDLHSGGIAR 128

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1992479035  11 QEAKRVAIFGGTHGNEMSGIMLVNmwiKNAAEIERNRL----VTKPfISNPRAVEKCTRYIN---TDLNRAF 75
Cdd:cd06251    10 KPGPTLLLTAAIHGDELNGIEVIQ---RLLEDLDPSKLrgtlIAIP-VVNPLGFENNSRYLPddgRDLNRSF 77