NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|18087825|ref|NP_542389|]
View 

N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming) [Homo sapiens]

Protein Classification

M14 family metallopeptidase( domain architecture ID 27772)

M14 family metallopeptidase is a zinc-binding carboxypeptidase (CP) which hydrolyzes single, C-terminal amino acids from polypeptide chains, and has a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity.

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
Peptidase_M14_like super family cl11393
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 11-300 3.03e-124

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.


The actual alignment was detected with superfamily member PRK02259:

Pssm-ID: 472171  Cd Length: 288  Bit Score: 357.26  E-value: 3.03e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   11 LRRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSRPTPDdpYEV 90
Cdd:PRK02259   2 INRVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLLQNPDLSG--YEQ 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   91 TRARELNQLLGPKASGQaFDFVLDLHNTTANMGTCLIAKSSHEvFAMHLCRHLQLQYPELscqVFLYQRSGEESYNLDSV 170
Cdd:PRK02259  80 LRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYGRRP-FDLALAAYLQSRLPLP---IYLHEKDEDQTGFLVEL 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  171 AKNGLGLELGPQPQGVLRADIFSRMRTLVATVLDFIELFNQGTA-FPAFEMEAYRPVGVVDFPRTEAGHLAGTVHPQLQD 249
Cdd:PRK02259 155 WPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKLpLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQG 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 18087825  250 RDFQPLQPGAPIFQMFSGEDLLYEGESTVYPVFINEAAYYEKGVAFVQTEK 300
Cdd:PRK02259 235 RDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 11-300 3.03e-124

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 357.26  E-value: 3.03e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   11 LRRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSRPTPDdpYEV 90
Cdd:PRK02259   2 INRVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLLQNPDLSG--YEQ 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   91 TRARELNQLLGPKASGQaFDFVLDLHNTTANMGTCLIAKSSHEvFAMHLCRHLQLQYPELscqVFLYQRSGEESYNLDSV 170
Cdd:PRK02259  80 LRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYGRRP-FDLALAAYLQSRLPLP---IYLHEKDEDQTGFLVEL 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  171 AKNGLGLELGPQPQGVLRADIFSRMRTLVATVLDFIELFNQGTA-FPAFEMEAYRPVGVVDFPRTEAGHLAGTVHPQLQD 249
Cdd:PRK02259 155 WPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKLpLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQG 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 18087825  250 RDFQPLQPGAPIFQMFSGEDLLYEGESTVYPVFINEAAYYEKGVAFVQTEK 300
Cdd:PRK02259 235 RDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 10-301 1.86e-103

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.).


Pssm-ID: 428216 [Multi-domain]  Cd Length: 289  Bit Score: 304.66  E-value: 1.86e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825    10 PLRRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSrpTPDDPYE 89
Cdd:pfam04952   1 PGPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825    90 VTRARELNQLLGPKASgQAFDFVLDLHNTTANMGTCLIAKSSHEVFAMHLCRHLQLQYPELSCQVFLYQRSGEESYNLDS 169
Cdd:pfam04952  79 ATRAERLADLFFPALL-PRADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   170 VAKNGLGLELGpqPQGVLRADIFSRMRTLVATVLDFIELFNQGTAFPAfEMEAYRPVGVVDFPRTEAGHLAGTVHPQL-- 247
Cdd:pfam04952 158 LGAPGFTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFE-PPKLYRVLREIDRPRDIRAELAGLVEFALnl 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 18087825   248 -QDRDFQPLQPGAPIFQMFSGEDLLYEGESTVYPVFINEAAYYEKGVAFVQTEKF 301
Cdd:pfam04952 235 gDDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAKF 289
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 12-206 1.13e-94

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.


Pssm-ID: 349480  Cd Length: 190  Bit Score: 278.32  E-value: 1.13e-94
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  12 RRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLnSRPTPDDPYEVT 91
Cdd:cd06909   1 KRVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENL-SSAPSSLPYEVR 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  92 RARELNQLLGPKASgQAFDFVLDLHNTTANMGTCLIAKSSHEvFAMHLCRHLQLQYPElsCQVFLYQRSGEESYNLDSVA 171
Cdd:cd06909  80 RAREINQILGPKGN-PACDFIIDLHNTTSNMGITLILSSSDD-FTLKLAAYLQQRLPP--VRVLLHESPSKESPFLRSVA 155

                       170       180       190
                ....*....|....*....|....*....|....*
gi 18087825 172 KNGLGLELGPQPQGVLRADIFSRMRTLVATVLDFI 206
Cdd:cd06909 156 KHGFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
12-300 1.39e-64

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 205.85  E-value: 1.39e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  12 RRVAVTGGTHGNEMSGVYLARHWLHAPAELQRA-SFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSRPTpddpYEV 90
Cdd:COG2988  25 KAVVISGGIHGNETAPIELLDKLLQDLLLGERPlSFRLLLILGNPAAMRAGRRYLDEDLNRLFGGRHLQNPES----YEA 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  91 TRARELNQLLGPK-ASGQAFDFVLDLHNTTANMGTCLIAKS--SHEVFAMHLCRHLQLQYPELScqVFLYQRSGEESYNL 167
Cdd:COG2988 101 ARAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFAVYpfRGRPFDLALLAYLAAAGPEAV--VLHHAPGGTFSHFS 178

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825 168 DSVAK-NGLGLELGPQ-PQGVLRADIFSRMRTLVATVLDFIELfnqgTAFPAFEMEAYRPVGVVDfpRTeagHLAGTVHP 245
Cdd:COG2988 179 AELCGaQAFTLELGKVrPFGQNDLSRFAATEEALRALLSGAEL----PEHPAQDLDLYRVVQQII--KH---GDDFMLHP 249

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18087825 246 QLQDRDFQPLQPGAPIFQMfSGEDLLYEGEsTVYPVFINEAAYYEKGVAFVQTEK 300
Cdd:COG2988 250 DLDTLNFTPLPPGTLLAED-GGKEYRVEGD-EERIVFPNEAVYYGQRAALLLTPK 302
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 11-300 3.03e-124

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 357.26  E-value: 3.03e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   11 LRRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSRPTPDdpYEV 90
Cdd:PRK02259   2 INRVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLLQNPDLSG--YEQ 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   91 TRARELNQLLGPKASGQaFDFVLDLHNTTANMGTCLIAKSSHEvFAMHLCRHLQLQYPELscqVFLYQRSGEESYNLDSV 170
Cdd:PRK02259  80 LRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYGRRP-FDLALAAYLQSRLPLP---IYLHEKDEDQTGFLVEL 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  171 AKNGLGLELGPQPQGVLRADIFSRMRTLVATVLDFIELFNQGTA-FPAFEMEAYRPVGVVDFPRTEAGHLAGTVHPQLQD 249
Cdd:PRK02259 155 WPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKLpLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQG 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 18087825  250 RDFQPLQPGAPIFQMFSGEDLLYEGESTVYPVFINEAAYYEKGVAFVQTEK 300
Cdd:PRK02259 235 RDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 10-301 1.86e-103

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.).


Pssm-ID: 428216 [Multi-domain]  Cd Length: 289  Bit Score: 304.66  E-value: 1.86e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825    10 PLRRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSrpTPDDPYE 89
Cdd:pfam04952   1 PGPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825    90 VTRARELNQLLGPKASgQAFDFVLDLHNTTANMGTCLIAKSSHEVFAMHLCRHLQLQYPELSCQVFLYQRSGEESYNLDS 169
Cdd:pfam04952  79 ATRAERLADLFFPALL-PRADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   170 VAKNGLGLELGpqPQGVLRADIFSRMRTLVATVLDFIELFNQGTAFPAfEMEAYRPVGVVDFPRTEAGHLAGTVHPQL-- 247
Cdd:pfam04952 158 LGAPGFTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFE-PPKLYRVLREIDRPRDIRAELAGLVEFALnl 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 18087825   248 -QDRDFQPLQPGAPIFQMFSGEDLLYEGESTVYPVFINEAAYYEKGVAFVQTEKF 301
Cdd:pfam04952 235 gDDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAKF 289
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 12-206 1.13e-94

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.


Pssm-ID: 349480  Cd Length: 190  Bit Score: 278.32  E-value: 1.13e-94
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  12 RRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLnSRPTPDDPYEVT 91
Cdd:cd06909   1 KRVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENL-SSAPSSLPYEVR 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  92 RARELNQLLGPKASgQAFDFVLDLHNTTANMGTCLIAKSSHEvFAMHLCRHLQLQYPElsCQVFLYQRSGEESYNLDSVA 171
Cdd:cd06909  80 RAREINQILGPKGN-PACDFIIDLHNTTSNMGITLILSSSDD-FTLKLAAYLQQRLPP--VRVLLHESPSKESPFLRSVA 155

                       170       180       190
                ....*....|....*....|....*....|....*
gi 18087825 172 KNGLGLELGPQPQGVLRADIFSRMRTLVATVLDFI 206
Cdd:cd06909 156 KHGFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
12-300 1.39e-64

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 205.85  E-value: 1.39e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  12 RRVAVTGGTHGNEMSGVYLARHWLHAPAELQRA-SFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSRPTpddpYEV 90
Cdd:COG2988  25 KAVVISGGIHGNETAPIELLDKLLQDLLLGERPlSFRLLLILGNPAAMRAGRRYLDEDLNRLFGGRHLQNPES----YEA 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  91 TRARELNQLLGPK-ASGQAFDFVLDLHNTTANMGTCLIAKS--SHEVFAMHLCRHLQLQYPELScqVFLYQRSGEESYNL 167
Cdd:COG2988 101 ARAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFAVYpfRGRPFDLALLAYLAAAGPEAV--VLHHAPGGTFSHFS 178

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825 168 DSVAK-NGLGLELGPQ-PQGVLRADIFSRMRTLVATVLDFIELfnqgTAFPAFEMEAYRPVGVVDfpRTeagHLAGTVHP 245
Cdd:COG2988 179 AELCGaQAFTLELGKVrPFGQNDLSRFAATEEALRALLSGAEL----PEHPAQDLDLYRVVQQII--KH---GDDFMLHP 249

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18087825 246 QLQDRDFQPLQPGAPIFQMfSGEDLLYEGEsTVYPVFINEAAYYEKGVAFVQTEK 300
Cdd:COG2988 250 DLDTLNFTPLPPGTLLAED-GGKEYRVEGD-EERIVFPNEAVYYGQRAALLLTPK 302
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 14-194 1.99e-15

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.


Pssm-ID: 349449 [Multi-domain]  Cd Length: 177  Bit Score: 73.11  E-value: 1.99e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  14 VAVTGGTHGNEMSGVYLARHWLH--APAELqRASFSAVPVlANPAATSGCRRYVD---HDLNRTFTssflnsrPTPDDPY 88
Cdd:cd06230   1 LLILAGVHGDEYEGVEAIRRLLAelDPSEL-KGTVVLVPV-ANPPAFEAGTRYTPldgLDLNRIFP-------GDPDGSP 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  89 EVTRARELNQLLGPKAsgqafDFVLDLHNTTANMGTCliaksshevfamHLCRHLQLQYPELSCQVFLY----------- 157
Cdd:cd06230  72 TERLAHELTELILKHA-----DALIDLHSGGTGRLVP------------YAILDYDSDAREKSRELARAfggtpviwggd 134

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 18087825 158 QRSGEESYNLDSVAKNGLGLELGpqPQGVLRADIFSR 194
Cdd:cd06230 135 PPGGTPVAAARSAGIPAITVELG--GGGRLRAERLER 169
COG3608 COG3608
Predicted deacylase [General function prediction only];
12-122 3.93e-10

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 59.86  E-value: 3.93e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  12 RRVAVTGGTHGNEMSGVYLARHWLHA--PAELqRASFSAVPVlANPAATSGCRRY---VDHDLNRTFtssflnsrptPDD 86
Cdd:COG3608  27 PTLLITAGIHGDELNGIEALRRLLREldPGEL-RGTVILVPV-ANPPGFLQGSRYlpiDGRDLNRSF----------PGD 94

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 18087825  87 P---YEVTRARELNQLLGPKAsgqafDFVLDLHNTTANM 122
Cdd:COG3608  95 AdgsLAERIAHALFEEILPDA-----DYVIDLHSGGIAR 128
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 7-119 6.23e-10

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.


Pssm-ID: 349450 [Multi-domain]  Cd Length: 239  Bit Score: 58.47  E-value: 6.23e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   7 PREPLRRVAVTGGTHGNEMSGVYLARHWL--HAPAELQRASFSAVPVLaNPAATSGCRRYvDH---DLNRTFTSsflnsr 81
Cdd:cd06231  38 PRGDKPRVLISAGIHGDEPAGVEALLRFLesLAEKYLRRVNLLVLPCV-NPWGFERNTRE-NAdgiDLNRSFLK------ 109

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 18087825  82 ptpDDPYEVTRAreLNQLLgpkASGQAFDFVLDLHNTT 119
Cdd:cd06231 110 ---DSPSPEVRA--LMEFL---ASLGRFDLHLDLHEDW 139
M14_ASTE_ASPA-like cd06910
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 13-120 1.12e-08

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.


Pssm-ID: 349481  Cd Length: 208  Bit Score: 54.28  E-value: 1.12e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  13 RVAVTGGTHGNEMSGVYLARHWLHApaELQ----RASFSAVPVLA-------NPAATsgcrRYVDHDLNRTFTSSFLNsr 81
Cdd:cd06910  26 HVMINALTHGNEICGAIALDWLLKN--GVRplrgRLTFCFANVEAyerfdpaRPTAS----RFVDEDLNRVWGPELLD-- 97

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 18087825  82 pTPDDPYEVTRARELNQLLgpkasgQAFDFVLDLHNTTA 120
Cdd:cd06910  98 -GPEQSIELRRARELRPVV------DTVDYLLDIHSMQE 129
M14_ASTE_ASPA_like cd18430
Succinylglutamate desuccinylase/aspartoacylase; uncharacterized; A functionally ...
 14-118 1.12e-08

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.


Pssm-ID: 349486 [Multi-domain]  Cd Length: 168  Bit Score: 53.60  E-value: 1.12e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  14 VAVTGGTHGNEMSGVYLARHwLHAPAE---LQRASFSAVPvlANPAATSGCRRYVDHDLNRTFTSSflnsrPTPDDpYEV 90
Cdd:cd18430   1 LAVLGAVHGNETCGTRAVER-LLAELPsgaLQKGPVTLVP--ANERAYAEGVRFCEEDLNRVFPGD-----PDPDT-YER 71

                        90       100
                ....*....|....*....|....*...
gi 18087825  91 TRARELNQLLgpkasgQAFDFVLDLHNT 118
Cdd:cd18430  72 RLANRLCPEL------EGHDVVLDLHST 93
M14_ASTE cd03855
Peptidase M14 Succinylglutamate desuccinylase (ASTE) subfamily; Peptidase M14 ...
 12-138 1.48e-08

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.


Pssm-ID: 349428  Cd Length: 239  Bit Score: 54.52  E-value: 1.48e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  12 RRVAVTGGTHGNEMSGVYLARHWLHApaeLQRASFS-AVPVL---ANPAATSGCRRYVDHDLNRTFtssflNSRPTPDDP 87
Cdd:cd03855  44 KSVVLSAGIHGNETAPIEILDQLIND---LIRGELAlAHRLLfifGNPPAIRQGKRFIEENLNRLF-----SGRHSKLPP 115

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18087825  88 -YEVTRARELNQLLG---PKASGQAFdFVLDLHntTAnmgtclIAKSSHEVFAMH 138
Cdd:cd03855 116 sYETARAAELEQAVAdffAKASGEVR-WHLDLH--TA------IRGSKHEQFAVY 161
PRK05324 PRK05324
succinylglutamate desuccinylase; Provisional
 7-136 1.08e-06

succinylglutamate desuccinylase; Provisional


Pssm-ID: 235408  Cd Length: 329  Bit Score: 49.41  E-value: 1.08e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825    7 PREPLRRVAVTGGTHGNEMSGVYLARHWLHAPAE-----LQRASFsavpVLANPAATSGCRRYVDHDLNRTFTSSFLNsr 81
Cdd:PRK05324  43 AAPSTKALVLSAGIHGNETAPIELLDQLVRDLLAgelplRARLLV----ILGNPPAMRAGKRYLDEDLNRLFGGRHQQ-- 116

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 18087825   82 ptPDDPYEVTRARELNQLLGP--KASGQAFDFVLDLHntTAnmgtclIAKSSHEVFA 136
Cdd:PRK05324 117 --FPGSDEARRAAELEQAVEDffAAGAERVRWHYDLH--TA------IRGSKHEQFA 163
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 4-92 1.28e-06

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.


Pssm-ID: 349475 [Multi-domain]  Cd Length: 214  Bit Score: 48.43  E-value: 1.28e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   4 LPVPREPLRRVAVTGGTHGNEMSGVYLARHWLHapaELQRASFSA------VPvLANP----AATSGCRRYVdhDLNRTF 73
Cdd:cd06904  16 YKFGPGSRARILIIGGIHGDEPEGVSLVEHLLR---WLKNHPASGdfhivvVP-CLNPdglaAGTRTNANGV--DLNRNF 89

                        90
                ....*....|....*....
gi 18087825  74 TSSflNSRPTPDDPYEVTR 92
Cdd:cd06904  90 PTK--NWEPDARKPKDPRY 106
M14_ASTE_ASPA-like cd06251
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 8-127 4.79e-06

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.


Pssm-ID: 349469 [Multi-domain]  Cd Length: 195  Bit Score: 46.38  E-value: 4.79e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   8 REPLRRVAVTGGTHGNEMSGVYLARHWLH--APAELqRASFSAVPVLaNPAATSGCRRYV---DHDLNRTFtssflnsrp 82
Cdd:cd06251   9 AKPGPTLLLTAAIHGDELNGIEVIQRLLEdlDPSKL-RGTLIAIPVV-NPLGFENNSRYLpddGRDLNRSF--------- 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 18087825  83 tPDDPYEVTRARELNQL---LGPKAsgqafDFVLDLHntTANMGTCLI 127
Cdd:cd06251  78 -PGSEKGSLASRLAHLLwneIVKKA-----DYVIDLH--TASTGRTNL 117
M14_ASTE_ASPA-like cd06256
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 21-121 9.64e-06

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.


Pssm-ID: 349474  Cd Length: 204  Bit Score: 45.75  E-value: 9.64e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  21 HGNEMSGVYLARHWLHAPAElqRASFSAVPVLANPAATSGCRRYVD--HDLNRTFtssflnsRPTPDDPYEVTRARELNQ 98
Cdd:cd06256  44 HGNEPTGLRAVQRLLKTGQA--PLPRTLLLFIGNVDAAKAGVRRLPgqPDYNRCW-------PGPFETPEGRLAAAVLER 114

                        90       100
                ....*....|....*....|....*
gi 18087825  99 L--LGPKASgqafdfvLDLHNTTAN 121
Cdd:cd06256 115 LdtLRPFAS-------IDIHNNTGK 132
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 7-117 7.37e-05

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.


Pssm-ID: 349471  Cd Length: 211  Bit Score: 42.97  E-value: 7.37e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   7 PREPLRRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFS------AVPVlANPAATSGCRRYV---DHDLNRTFtssf 77
Cdd:cd06253  18 GGNAEPRIAIVAGIHGDELNGLYVCSRLIRFLKELEEGGYKlkgkvlVIPA-VNPLGINSGTRFWpfdNLDMNRMF---- 92

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 18087825  78 lnsrptPDDPYEVTRARELNQLLgpkASGQAFDFVLDLHN 117
Cdd:cd06253  93 ------PGYNKGETTERIAAALF---EDLKGADYGIDLHS 123
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 14-116 1.64e-04

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.


Pssm-ID: 349427 [Multi-domain]  Cd Length: 216  Bit Score: 42.06  E-value: 1.64e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  14 VAVTGGTHGNEMSGV--------YLARHWLHAPAE--LQRASFSAVPVLaNPaatSGCRRYVDH---------DLNRTFT 74
Cdd:cd00596   1 ILITGGIHGNEVIGVelalalieYLLENYGNDPLKrlLDNVELWIVPLV-NP---DGFARVIDSggrknangvDLNRNFP 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 18087825  75 SSFlNSRPTPDDPYEVTRAREL-----NQLLGPKASGQAFDFVLDLH 116
Cdd:cd00596  77 YNW-GKDGTSGPSSPTYRGPAPfsepeTQALRDLAKSHRFDLAVSYH 122
M14_CP_Csd4-like cd06243
Peptidase M14 carboxypeptidase Csd4 and similar proteins; This family includes peptidase M14 ...
 8-116 1.66e-04

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.


Pssm-ID: 349462  Cd Length: 227  Bit Score: 42.35  E-value: 1.66e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825   8 REPLRRVAVTGGTHGNEMSGvYLARHWLhAPAELQRASFSAVPVLaNPAATSGCRRYVDHDLNRTFTSSFLNSrptPDDP 87
Cdd:cd06243  13 REPGPTLLIIGGIQGDEPGG-FLAADLL-ADLYLVKGNVIVVPRL-NFPSILRNHRGLNGDMNRKFAALDKKD---PEYK 86

                        90       100
                ....*....|....*....|....*....
gi 18087825  88 YeVTRARELnqLLGPKAsgqafDFVLDLH 116
Cdd:cd06243  87 T-IQEIKSL--IADFRP-----DVVLHLH 107
M14_ASTE_ASPA-like cd06252
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 14-116 3.09e-04

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.


Pssm-ID: 349470  Cd Length: 224  Bit Score: 41.40  E-value: 3.09e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087825  14 VAVTGGTHGNEMSGVYLARHWLHA-PAELQRASFSAVPVLANPAATSGCR-RYVDH-DLNRTFTssflnsrPTPDDPYEV 90
Cdd:cd06252  37 VLLTGGNHGDEYEGPIALRRLARDlDPEDVRGRLIIVPALNLPAVRAGTRtSPLDGgNLNRAFP-------GDADGTPTE 109

                        90       100
                ....*....|....*....|....*.
gi 18087825  91 TRARELNQLLGPKAsgqafDFVLDLH 116
Cdd:cd06252 110 RIAHFLETVLLPRA-----DAVIDLH 130
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH