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 1958644479  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACRRYIDRDLNRTFTLTFLGStATPDDPYEVKR 92
Cdd:cd06909     2 RVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVRR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  93 AQELNQLLGPKGTcQAFDFILDLHNTTANTGACLISEvSQNPFNLHLCHYLQLQNPglPCRLFQFEPPGTESY------- 165
Cdd:cd06909    81 AREINQILGPKGN-PACDFIIDLHNTTSNMGITLILS-SSDDFTLKLAAYLQQRLP--PVRVLLHESPSKESPflrsvak 156

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1958644479 166 ---TLELGPQPQGVLRAELFSQMRAMVASILDFI 196
Cdd:cd06909   157 hgfTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190

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 1958644479  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACRRYIDRDLNRTFTLTFLGStATPDDPYEVKR 92
Cdd:cd06909     2 RVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVRR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  93 AQELNQLLGPKGTcQAFDFILDLHNTTANTGACLISEvSQNPFNLHLCHYLQLQNPglPCRLFQFEPPGTESY------- 165
Cdd:cd06909    81 AREINQILGPKGN-PACDFIIDLHNTTSNMGITLILS-SSDDFTLKLAAYLQQRLP--PVRVLLHESPSKESPflrsvak 156

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1958644479 166 ---TLELGPQPQGVLRAELFSQMRAMVASILDFI 196
Cdd:cd06909   157 hgfTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190

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 1958644479  10 PLLRVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACRRYIDRDLNRTFTLTFLGStaTPDDPYE 89
Cdd:pfam04952   1 PGPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  90 VKRAQELNQLLGPKGTcQAFDFILDLHNTTANTGACLISEVSQNPFNLHLCHYLQLQNPGLPCRLFQFEPPGTESY---- 165
Cdd:pfam04952  79 ATRAERLADLFFPALL-PRADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFsaee 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479 166 ------TLELGpqPQGVLRAELFSQMRAMVASILDFIELFNQGMEFPAfEMEVYKNLGSVDFPRTTDGHLTGTVHSRLQM 239
Cdd:pfam04952 158 lgapgfTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFE-PPKLYRVLREIDRPRDIRAELAGLVEFALNL 234

                  .
gi 1958644479 240 G 240
Cdd:pfam04952 235 G 235

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 1958644479  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACRRYIDRDLNRTFTLTFLGStATPDDPYEVKR 92
Cdd:cd06909     2 RVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVRR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  93 AQELNQLLGPKGTcQAFDFILDLHNTTANTGACLISEvSQNPFNLHLCHYLQLQNPglPCRLFQFEPPGTESY------- 165
Cdd:cd06909    81 AREINQILGPKGN-PACDFIIDLHNTTSNMGITLILS-SSDDFTLKLAAYLQQRLP--PVRVLLHESPSKESPflrsvak 156

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1958644479 166 ---TLELGPQPQGVLRAELFSQMRAMVASILDFI 196
Cdd:cd06909   157 hgfTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190

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 1958644479  10 PLLRVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACRRYIDRDLNRTFTLTFLGStaTPDDPYE 89
Cdd:pfam04952   1 PGPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  90 VKRAQELNQLLGPKGTcQAFDFILDLHNTTANTGACLISEVSQNPFNLHLCHYLQLQNPGLPCRLFQFEPPGTESY---- 165
Cdd:pfam04952  79 ATRAERLADLFFPALL-PRADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFsaee 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479 166 ------TLELGpqPQGVLRAELFSQMRAMVASILDFIELFNQGMEFPAfEMEVYKNLGSVDFPRTTDGHLTGTVHSRLQM 239
Cdd:pfam04952 158 lgapgfTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFE-PPKLYRVLREIDRPRDIRAELAGLVEFALNL 234

                  .
gi 1958644479 240 G 240
Cdd:pfam04952 235 G 235

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 1958644479  14 VAVTGGTHGNEMCGVYLARYWLQ--NPGELQRpSFSAMPVlANPAATAACRRYIDR---DLNRTFtltflgsTATPDDPY 88
Cdd:cd06230     1 LLILAGVHGDEYEGVEAIRRLLAelDPSELKG-TVVLVPV-ANPPAFEAGTRYTPLdglDLNRIF-------PGDPDGSP 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  89 EVKRAQELNQLLGPKGtcqafDFILDLHNTTAN-TGACLISEVS--QNPFNLHLCHYLQlqnpGLPCRLFQFEPPGTE-- 163
Cdd:cd06230    72 TERLAHELTELILKHA-----DALIDLHSGGTGrLVPYAILDYDsdAREKSRELARAFG----GTPVIWGGDPPGGTPva 142

                         170       180
                  ....*....|....*....|....*
gi 1958644479 164 --------SYTLELGpqPQGVLRAE 180
Cdd:cd06230   143 aarsagipAITVELG--GGGRLRAE 165

Predicted deacylase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  13 RVAVTGGTHGNEMCGVYLARYWLQ--NPGELqRPSFSAMPVlANPAATAACRRYI---DRDLNRTFtltflgstatPDDP 87
Cdd:COG3608    28 TLLITAGIHGDELNGIEALRRLLRelDPGEL-RGTVILVPV-ANPPGFLQGSRYLpidGRDLNRSF----------PGDA 95

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1958644479  88 ---YEVKRAQELNQLLgpkgtCQAFDFILDLH 116
Cdd:COG3608    96 dgsLAERIAHALFEEI-----LPDADYVIDLH 122

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 1958644479  14 VAVTGGTHGNE-----MCGVYLaRYWLQNPGELQRPsfsAMPVLANPAATAACRRYIDRDLNRTFTltflGSTATPDDPY 88
Cdd:cd03855    46 VVLSAGIHGNEtapieILDQLI-NDLIRGELALAHR---LLFIFGNPPAIRQGKRFIEENLNRLFS----GRHSKLPPSY 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  89 EVKRAQELNQLlgpkgtCQAF-------DFI-LDLHntTANTGacliSEVSQ---NPFNLHLCH---YLQ-LQNPGLPCR 153
Cdd:cd03855   118 ETARAAELEQA------VADFfakasgeVRWhLDLH--TAIRG----SKHEQfavYPFLEGRPHdreQLDfLGAAGIEAV 185

                         170       180
                  ....*....|....*....|....*...
gi 1958644479 154 LFQFEPPGTESY-----------TLELG 170
Cdd:cd03855   186 LLSNSPGGTFSYyssehfgaaafTVELG 213

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 1958644479   5 PGSRKPLLRVAVTGGTHGNEMCGVYLARYWLQN--PGELQRPSFSAMPVLaNPAATAACRRY-ID-RDLNRTFTLTflgs 80
Cdd:cd06231    36 PNPRGDKPRVLISAGIHGDEPAGVEALLRFLESlaEKYLRRVNLLVLPCV-NPWGFERNTREnADgIDLNRSFLKD---- 110

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958644479  81 TATPddpyEVKRAQELNQLLGPkgtcqaFDFILDLHNTT 119
Cdd:cd06231   111 SPSP----EVRALMEFLASLGR------FDLHLDLHEDW 139

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 1958644479   4 LPGSRKPLLrvAVTGGTHGNEMCGVYLARYWLQNpGELQRPsFSAMPVLANPAATAACRRYID--RDLNRTFTltflgst 81
Cdd:cd06256    29 LPGRRPRPL--FVSTLLHGNEPTGLRAVQRLLKT-GQAPLP-RTLLLFIGNVDAAKAGVRRLPgqPDYNRCWP------- 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958644479  82 aTPDDPYEVKRAQELNQLLGpkgTCQAFDFIlDLHNTTANTG--ACLISEvsqNPFNLHLCHYLQLqnpglpcRLFQFEP 159
Cdd:cd06256    98 -GPFETPEGRLAAAVLERLD---TLRPFASI-DIHNNTGKNPhyACVNRL---DAAHLRLASLFSR-------TLVYFTR 162

                  .
gi 1958644479 160 P 160
Cdd:cd06256   163 P 163

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958644479  13 RVAVTGGTHGNEMCGVYLARYWLQ---NPGELQRPSFSAMPvLANPAATAACRRYIDR--DLNRTF 73
Cdd:cd06904    25 RILIIGGIHGDEPEGVSLVEHLLRwlkNHPASGDFHIVVVP-CLNPDGLAAGTRTNANgvDLNRNF 89