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Conserved domains on  [gi|699045647|ref|NP_001289408|]
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N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming) isoform 1 [Mus musculus]

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

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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 ...
 13-300 8.69e-121

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: 348.40  E-value: 8.69e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGSTATPDdpYEVKR 92
Cdd:PRK02259   4 RVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLLQNPDLSG--YEQLR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  93 ARELNQLLGPKGTGQaFDFTLDLHNTTANTGVCLISESNISFNLHLCHYLQRQNPgMPcRLFLYEPAGTETFSVEsISKN 172
Cdd:PRK02259  82 AKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYGRRPFDLALAAYLQSRLP-LP-IYLHEKDEDQTGFLVE-LWPC 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647 173 GICLEMGPQPQGVLRADLFSRMRALVASILDFIELFNQG-MDLPAFEMDIYRNLGSVDFPRTADGDLAGTVHPQLQDHDF 251
Cdd:PRK02259 158 GLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGkLPLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQGRDW 237

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 699045647 252 EPLRPGEPIFKLFSGEDVLYEGDSIVYPVFINEAAYYEKHVAFLKSEKI 300
Cdd:PRK02259 238 QPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKKE 286
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 13-300 8.69e-121

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 348.40  E-value: 8.69e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGSTATPDdpYEVKR 92
Cdd:PRK02259   4 RVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLLQNPDLSG--YEQLR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  93 ARELNQLLGPKGTGQaFDFTLDLHNTTANTGVCLISESNISFNLHLCHYLQRQNPgMPcRLFLYEPAGTETFSVEsISKN 172
Cdd:PRK02259  82 AKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYGRRPFDLALAAYLQSRLP-LP-IYLHEKDEDQTGFLVE-LWPC 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647 173 GICLEMGPQPQGVLRADLFSRMRALVASILDFIELFNQG-MDLPAFEMDIYRNLGSVDFPRTADGDLAGTVHPQLQDHDF 251
Cdd:PRK02259 158 GLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGkLPLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQGRDW 237

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 699045647 252 EPLRPGEPIFKLFSGEDVLYEGDSIVYPVFINEAAYYEKHVAFLKSEKI 300
Cdd:PRK02259 238 QPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKKE 286
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 10-299 7.47e-102

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: 300.42  E-value: 7.47e-102
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647   10 PLLRVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGStaTPDDPYE 89
Cdd:pfam04952   1 PGPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647   90 VKRARELNQLLGPKGTgQAFDFTLDLHNTTANTGVCLISESNI-SFNLHLCHYLQRQNPGMPCRLFLYEPAGTETFSVES 168
Cdd:pfam04952  79 ATRAERLADLFFPALL-PRADIVLDLHTGTRGMGHLLFALAPIrDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  169 ISKNGICLEMGpqPQGVLRADLFSRMRALVASILDFIELFNQGMDLPAfEMDIYRNLGSVDFPRTADGDLAGTVHPQL-- 246
Cdd:pfam04952 158 LGAPGFTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFE-PPKLYRVLREIDRPRDIRAELAGLVEFALnl 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 699045647  247 -QDHDFEPLRPGEPIFKLFSGEDVLYEGDSIVYPVFINEAAYYEKHVAFLKSEK 299
Cdd:pfam04952 235 gDDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAK 288
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 13-205 9.94e-101

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: 293.73  E-value: 9.94e-101
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGStATPDDPYEVKR 92
Cdd:cd06909    2 RVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVRR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  93 ARELNQLLGPKGTgQAFDFTLDLHNTTANTGVCLISESNISFNLHLCHYLQRQNPgmPCRLFLYEPAGTETFSVESISKN 172
Cdd:cd06909   81 AREINQILGPKGN-PACDFIIDLHNTTSNMGITLILSSSDDFTLKLAAYLQQRLP--PVRVLLHESPSKESPFLRSVAKH 157

                        170       180       190
                 ....*....|....*....|....*....|...
gi 699045647 173 GICLEMGPQPQGVLRADLFSRMRALVASILDFI 205
Cdd:cd06909  158 GFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
13-295 1.49e-68

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 215.87  E-value: 1.49e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRP-SFSAMPVLANPAATAACCRYLDRDLNRSctltFLGSTATPDDPYEVK 91
Cdd:COG2988   26 AVVISGGIHGNETAPIELLDKLLQDLLLGERPlSFRLLLILGNPAAMRAGRRYLDEDLNRL----FGGRHLQNPESYEAA 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  92 RARELNQLLGPK-GTGQAFDFTLDLHNTTANTGVCLI---SESNISFNLHLCHYLQRQNPGmpCRLFLYEPAGTET-FSV 166
Cdd:COG2988  102 RAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFavyPFRGRPFDLALLAYLAAAGPE--AVVLHHAPGGTFShFSA 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647 167 ESISKNGICLEMGPQ-PQGVLRADLFSRMRALVASILDFIELFNQgmdlPAFEMDIYRNLGSVDfpRTADgdlAGTVHPQ 245
Cdd:COG2988  180 ELCGAQAFTLELGKVrPFGQNDLSRFAATEEALRALLSGAELPEH----PAQDLDLYRVVQQII--KHGD---DFMLHPD 250

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 699045647 246 LQDHDFEPLRPGEPIFKLfSGEDVLYEGDsIVYPVFINEAAYYEKHVAFL 295
Cdd:COG2988  251 LDTLNFTPLPPGTLLAED-GGKEYRVEGD-EERIVFPNEAVYYGQRAALL 298
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 13-300 8.69e-121

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 348.40  E-value: 8.69e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGSTATPDdpYEVKR 92
Cdd:PRK02259   4 RVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLLQNPDLSG--YEQLR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  93 ARELNQLLGPKGTGQaFDFTLDLHNTTANTGVCLISESNISFNLHLCHYLQRQNPgMPcRLFLYEPAGTETFSVEsISKN 172
Cdd:PRK02259  82 AKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYGRRPFDLALAAYLQSRLP-LP-IYLHEKDEDQTGFLVE-LWPC 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647 173 GICLEMGPQPQGVLRADLFSRMRALVASILDFIELFNQG-MDLPAFEMDIYRNLGSVDFPRTADGDLAGTVHPQLQDHDF 251
Cdd:PRK02259 158 GLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGkLPLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQGRDW 237

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 699045647 252 EPLRPGEPIFKLFSGEDVLYEGDSIVYPVFINEAAYYEKHVAFLKSEKI 300
Cdd:PRK02259 238 QPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKKE 286
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 10-299 7.47e-102

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: 300.42  E-value: 7.47e-102
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647   10 PLLRVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGStaTPDDPYE 89
Cdd:pfam04952   1 PGPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647   90 VKRARELNQLLGPKGTgQAFDFTLDLHNTTANTGVCLISESNI-SFNLHLCHYLQRQNPGMPCRLFLYEPAGTETFSVES 168
Cdd:pfam04952  79 ATRAERLADLFFPALL-PRADIVLDLHTGTRGMGHLLFALAPIrDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  169 ISKNGICLEMGpqPQGVLRADLFSRMRALVASILDFIELFNQGMDLPAfEMDIYRNLGSVDFPRTADGDLAGTVHPQL-- 246
Cdd:pfam04952 158 LGAPGFTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFE-PPKLYRVLREIDRPRDIRAELAGLVEFALnl 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 699045647  247 -QDHDFEPLRPGEPIFKLFSGEDVLYEGDSIVYPVFINEAAYYEKHVAFLKSEK 299
Cdd:pfam04952 235 gDDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAK 288
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 13-205 9.94e-101

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: 293.73  E-value: 9.94e-101
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRPSFSAMPVLANPAATAACCRYLDRDLNRSCTLTFLGStATPDDPYEVKR 92
Cdd:cd06909    2 RVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENLSS-APSSLPYEVRR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  93 ARELNQLLGPKGTgQAFDFTLDLHNTTANTGVCLISESNISFNLHLCHYLQRQNPgmPCRLFLYEPAGTETFSVESISKN 172
Cdd:cd06909   81 AREINQILGPKGN-PACDFIIDLHNTTSNMGITLILSSSDDFTLKLAAYLQQRLP--PVRVLLHESPSKESPFLRSVAKH 157

                        170       180       190
                 ....*....|....*....|....*....|...
gi 699045647 173 GICLEMGPQPQGVLRADLFSRMRALVASILDFI 205
Cdd:cd06909  158 GFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
13-295 1.49e-68

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 215.87  E-value: 1.49e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQNPGELQRP-SFSAMPVLANPAATAACCRYLDRDLNRSctltFLGSTATPDDPYEVK 91
Cdd:COG2988   26 AVVISGGIHGNETAPIELLDKLLQDLLLGERPlSFRLLLILGNPAAMRAGRRYLDEDLNRL----FGGRHLQNPESYEAA 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  92 RARELNQLLGPK-GTGQAFDFTLDLHNTTANTGVCLI---SESNISFNLHLCHYLQRQNPGmpCRLFLYEPAGTET-FSV 166
Cdd:COG2988  102 RAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFavyPFRGRPFDLALLAYLAAAGPE--AVVLHHAPGGTFShFSA 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647 167 ESISKNGICLEMGPQ-PQGVLRADLFSRMRALVASILDFIELFNQgmdlPAFEMDIYRNLGSVDfpRTADgdlAGTVHPQ 245
Cdd:COG2988  180 ELCGAQAFTLELGKVrPFGQNDLSRFAATEEALRALLSGAELPEH----PAQDLDLYRVVQQII--KHGD---DFMLHPD 250

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 699045647 246 LQDHDFEPLRPGEPIFKLfSGEDVLYEGDsIVYPVFINEAAYYEKHVAFL 295
Cdd:COG2988  251 LDTLNFTPLPPGTLLAED-GGKEYRVEGD-EERIVFPNEAVYYGQRAALL 298
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 14-189 9.42e-13

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: 65.41  E-value: 9.42e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  14 VAVTGGTHGNEMCGVYLARYWLQ--NPGELQRpSFSAMPVlANPAATAACCRYLDR---DLNRSctltFLGStatPDDPY 88
Cdd:cd06230    1 LLILAGVHGDEYEGVEAIRRLLAelDPSELKG-TVVLVPV-ANPPAFEAGTRYTPLdglDLNRI----FPGD---PDGSP 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  89 EVKRARELNQLLGPKGtgqafDFTLDLHNTTANTGVClisesniSFNLHLCHYLQRQNPGM-----PCRLFLYE--PAGT 161
Cdd:cd06230   72 TERLAHELTELILKHA-----DALIDLHSGGTGRLVP-------YAILDYDSDAREKSRELarafgGTPVIWGGdpPGGT 139

                        170       180
                 ....*....|....*....|....*...
gi 699045647 162 ETFSVESISKNGICLEMGpqPQGVLRAD 189
Cdd:cd06230  140 PVAAARSAGIPAITVELG--GGGRLRAE 165
M14_ASTE_ASPA_like cd18430
Succinylglutamate desuccinylase/aspartoacylase; uncharacterized; A functionally ...
 14-118 8.89e-10

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: 56.68  E-value: 8.89e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  14 VAVTGGTHGNEMCGVYLARYWLQ--NPGELQRPSFSAmpVLANPAATAACCRYLDRDLNRSctltfLGSTATPDDpYEVK 91
Cdd:cd18430    1 LAVLGAVHGNETCGTRAVERLLAelPSGALQKGPVTL--VPANERAYAEGVRFCEEDLNRV-----FPGDPDPDT-YERR 72

                         90       100
                 ....*....|....*....|....*..
gi 699045647  92 RARELNQLLgpkgtgQAFDFTLDLHNT 118
Cdd:cd18430   73 LANRLCPEL------EGHDVVLDLHST 93
COG3608 COG3608
Predicted deacylase [General function prediction only];
13-116 1.56e-09

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 57.93  E-value: 1.56e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLARYWLQ--NPGELqRPSFSAMPVlANPAATAACCRYL---DRDLNRSctltFLGStatPDDP 87
Cdd:COG3608   28 TLLITAGIHGDELNGIEALRRLLRelDPGEL-RGTVILVPV-ANPPGFLQGSRYLpidGRDLNRS----FPGD---ADGS 98

                         90       100
                 ....*....|....*....|....*....
gi 699045647  88 YEVKRARELNQLLGPKgtgqaFDFTLDLH 116
Cdd:COG3608   99 LAERIAHALFEEILPD-----ADYVIDLH 122
M14_ASTE_ASPA-like cd06910
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 2-120 5.42e-09

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: 55.43  E-value: 5.42e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647   2 SSLPGSRepllrVAVTGGTHGNEMCGVYLARYWLQNpgELQ----RPSFSampvLANPAATAA-------CCRYLDRDLN 70
Cdd:cd06910   20 SGQPGPH-----VMINALTHGNEICGAIALDWLLKN--GVRplrgRLTFC----FANVEAYERfdparptASRFVDEDLN 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 699045647  71 RSCTLTFLGstaTPDDPYEVKRARELNQLLgpkgtgQAFDFTLDLHNTTA 120
Cdd:cd06910   89 RVWGPELLD---GPEQSIELRRARELRPVV------DTVDYLLDIHSMQE 129
PRK05324 PRK05324
succinylglutamate desuccinylase; Provisional
 51-120 1.66e-05

succinylglutamate desuccinylase; Provisional


Pssm-ID: 235408  Cd Length: 329  Bit Score: 45.94  E-value: 1.66e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 699045647  51 VLANPAATAACCRYLDRDLNRsctlTFLGSTATPDDPYEVKRARELNQLLGP--KGTGQAFDFTLDLHntTA 120
Cdd:PRK05324  88 ILGNPPAMRAGKRYLDEDLNR----LFGGRHQQFPGSDEARRAAELEQAVEDffAAGAERVRWHYDLH--TA 153
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 5-124 2.02e-05

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: 44.99  E-value: 2.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647   5 PGSREPLLRVAVTGGTHGNEMCGVYLARYWLQN--PGELQRPSFSAMPVLaNPAATAACCRY--LDRDLNRSctltFLGS 80
Cdd:cd06231   36 PNPRGDKPRVLISAGIHGDEPAGVEALLRFLESlaEKYLRRVNLLVLPCV-NPWGFERNTREnaDGIDLNRS----FLKD 110

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 699045647  81 TATPddpyEVKRARELNQLLGPkgtgqaFDFTLDLHNTTANTGV 124
Cdd:cd06231  111 SPSP----EVRALMEFLASLGR------FDLHLDLHEDWDSDGF 144
M14_ASTE cd03855
Peptidase M14 Succinylglutamate desuccinylase (ASTE) subfamily; Peptidase M14 ...
 14-100 7.14e-05

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: 43.35  E-value: 7.14e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  14 VAVTGGTHGNE-----MCGVYLaRYWLQNPGELQRPsfsAMPVLANPAATAACCRYLDRDLNRsctlTFLGSTATPDDPY 88
Cdd:cd03855   46 VVLSAGIHGNEtapieILDQLI-NDLIRGELALAHR---LLFIFGNPPAIRQGKRFIEENLNR----LFSGRHSKLPPSY 117

                         90
                 ....*....|..
gi 699045647  89 EVKRARELNQLL 100
Cdd:cd03855  118 ETARAAELEQAV 129
M14_ASTE_ASPA-like cd06256
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 4-122 8.45e-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: 349474  Cd Length: 204  Bit Score: 39.97  E-value: 8.45e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647   4 LPGSREPLLrvAVTGGTHGNEMCGVYLARYWLQNpGELQRPsFSAMPVLANPAATAACCRYLD--RDLNRsctlTFLGst 81
Cdd:cd06256   29 LPGRRPRPL--FVSTLLHGNEPTGLRAVQRLLKT-GQAPLP-RTLLLFIGNVDAAKAGVRRLPgqPDYNR----CWPG-- 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 699045647  82 atPDDPYEVKRARELNQLLgpkgTGQAFDFTLDLHNTTANT 122
Cdd:cd06256   99 --PFETPEGRLAAAVLERL----DTLRPFASIDIHNNTGKN 133
M14_ASTE_ASPA-like cd06251
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 13-123 7.93e-03

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: 36.75  E-value: 7.93e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 699045647  13 RVAVTGGTHGNEMCGVYLAR---YWLqNPGELqRPSFSAMPVLaNPAATAACCRYL---DRDLNRSctltFLGStATPDD 86
Cdd:cd06251   14 TLLLTAAIHGDELNGIEVIQrllEDL-DPSKL-RGTLIAIPVV-NPLGFENNSRYLpddGRDLNRS----FPGS-EKGSL 85

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 699045647  87 PYEVkrAREL-NQLLgpkgtgQAFDFTLDLHntTANTG 123
Cdd:cd06251   86 ASRL--AHLLwNEIV------KKADYVIDLH--TASTG 113
 
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.
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