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Conserved domains on  [gi|4557335|ref|NP_000040|]
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aspartoacylase [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

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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 ...
 10-300 8.13e-130

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: 371.13  E-value: 8.13e-130
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    10 HIQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLgkKMSEDLPYE 89
Cdd:PRK02259   1 KINRVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLL--QNPDLSGYE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    90 VRRAQEINHLFGPKDSEDsYDIIFDLHNTTSNMGCTLILEDsRNNFLIQMFHYIKTSLaPLPcyVYLIEHPSLKYATTRS 169
Cdd:PRK02259  79 QLRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYG-RRPFDLALAAYLQSRL-PLP--IYLHEKDEDQTGFLVE 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   170 IAKYPVGIEVGPQPQGVLRADILDQMRKMIKHALDFIHHFNEGK-EFPPCAIEVYKIIEKVDYPRDENGEIAAIIHPNLQ 248
Cdd:PRK02259 154 LWPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKlPLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQ 233

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 4557335   249 DQDWKPLHPGDPMFLTLDGKTIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 300
Cdd:PRK02259 234 GRDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 10-300 8.13e-130

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 371.13  E-value: 8.13e-130
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    10 HIQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLgkKMSEDLPYE 89
Cdd:PRK02259   1 KINRVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLL--QNPDLSGYE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    90 VRRAQEINHLFGPKDSEDsYDIIFDLHNTTSNMGCTLILEDsRNNFLIQMFHYIKTSLaPLPcyVYLIEHPSLKYATTRS 169
Cdd:PRK02259  79 QLRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYG-RRPFDLALAAYLQSRL-PLP--IYLHEKDEDQTGFLVE 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   170 IAKYPVGIEVGPQPQGVLRADILDQMRKMIKHALDFIHHFNEGK-EFPPCAIEVYKIIEKVDYPRDENGEIAAIIHPNLQ 248
Cdd:PRK02259 154 LWPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKlPLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQ 233

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 4557335   249 DQDWKPLHPGDPMFLTLDGKTIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 300
Cdd:PRK02259 234 GRDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 12-206 7.38e-107

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: 309.14  E-value: 7.38e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   12 QKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLgKKMSEDLPYEVR 91
Cdd:cd06909   1 KRVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENL-SSAPSSLPYEVR 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   92 RAQEINHLFGPKDsEDSYDIIFDLHNTTSNMGCTLILEDSRnNFLIQMFHYIKTSLapLPCYVYLIEHPSLKYATTRSIA 171
Cdd:cd06909  80 RAREINQILGPKG-NPACDFIIDLHNTTSNMGITLILSSSD-DFTLKLAAYLQQRL--PPVRVLLHESPSKESPFLRSVA 155

                       170       180       190
                ....*....|....*....|....*....|....*
gi 4557335  172 KYPVGIEVGPQPQGVLRADILDQMRKMIKHALDFI 206
Cdd:cd06909 156 KHGFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 11-300 6.40e-96

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: 285.01  E-value: 6.40e-96
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335     11 IQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLGKkmSEDLPYEV 90
Cdd:pfam04952   2 GPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYRA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335     91 RRAQEINHLFGPKDSEdSYDIIFDLHNTTSNMGCTLILEDSRNNFLIQMFHYIKTSLAPLPCYVYLIEHPSLKYATTRSI 170
Cdd:pfam04952  80 TRAERLADLFFPALLP-RADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEEL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    171 AKYPVGIEVGpqPQGVLRADILDQMRKMIKHALDFIHHFNEGKEFPPCAiEVYKIIEKVDYPRDENGEIAAIIHPNL--- 247
Cdd:pfam04952 159 GAPGFTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFEPP-KLYRVLREIDRPRDIRAELAGLVEFALnlg 235

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 4557335    248 QDQDWKPLHPGDPMFLTLDGKTIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 300
Cdd:pfam04952 236 DDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAK 288
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
11-291 1.03e-61

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 198.15  E-value: 1.03e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   11 IQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRT-GLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLgkkmSEDLPYE 89
Cdd:COG2988  24 IKAVVISGGIHGNETAPIELLDKLLQDLLLGERPlSFRLLLILGNPAAMRAGRRYLDEDLNRLFGGRHL----QNPESYE 99

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   90 VRRAQEINHLFGPK-DSEDSYDIIFDLHNTTSNMGCTLI--LEDSRNNFLIQMFHYIKTS--LAPlpcyVYLIEHPSLKY 164
Cdd:COG2988 100 AARAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFavYPFRGRPFDLALLAYLAAAgpEAV----VLHHAPGGTFS 175

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335  165 ATTRSIAKYP-VGIEVGPQ-PQGVLRADILDQMRKMIKHALDFIhhfnEGKEFPPCAIEVYKIIEKVdyprDENGeIAAI 242
Cdd:COG2988 176 HFSAELCGAQaFTLELGKVrPFGQNDLSRFAATEEALRALLSGA----ELPEHPAQDLDLYRVVQQI----IKHG-DDFM 246

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 4557335  243 IHPNLQDQDWKPLHPGDPMFLTlDGKTIPLGGDcTVYPVFVNEAAYYEK 291
Cdd:COG2988 247 LHPDLDTLNFTPLPPGTLLAED-GGKEYRVEGD-EERIVFPNEAVYYGQ 293
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 10-300 8.13e-130

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 371.13  E-value: 8.13e-130
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    10 HIQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLgkKMSEDLPYE 89
Cdd:PRK02259   1 KINRVAIVGGTHGNEITGIYLVKKWQQQPNLINRKGLEVQTVIGNPEAIEAGRRYIDRDLNRSFRLDLL--QNPDLSGYE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    90 VRRAQEINHLFGPKDSEDsYDIIFDLHNTTSNMGCTLILEDsRNNFLIQMFHYIKTSLaPLPcyVYLIEHPSLKYATTRS 169
Cdd:PRK02259  79 QLRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYG-RRPFDLALAAYLQSRL-PLP--IYLHEKDEDQTGFLVE 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   170 IAKYPVGIEVGPQPQGVLRADILDQMRKMIKHALDFIHHFNEGK-EFPPCAIEVYKIIEKVDYPRDENGEIAAIIHPNLQ 248
Cdd:PRK02259 154 LWPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKlPLPNEQLVVYRHLGSIDYPRDENGQIAAMIHPQLQ 233

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 4557335   249 DQDWKPLHPGDPMFLTLDGKTIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 300
Cdd:PRK02259 234 GRDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 12-206 7.38e-107

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: 309.14  E-value: 7.38e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   12 QKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLgKKMSEDLPYEVR 91
Cdd:cd06909   1 KRVAIVGGTHGNELTGVYLVKHWLKNPELIERKSFEVHPLLANPRAVEQCRRYIDTDLNRCFSLENL-SSAPSSLPYEVR 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   92 RAQEINHLFGPKDsEDSYDIIFDLHNTTSNMGCTLILEDSRnNFLIQMFHYIKTSLapLPCYVYLIEHPSLKYATTRSIA 171
Cdd:cd06909  80 RAREINQILGPKG-NPACDFIIDLHNTTSNMGITLILSSSD-DFTLKLAAYLQQRL--PPVRVLLHESPSKESPFLRSVA 155

                       170       180       190
                ....*....|....*....|....*....|....*
gi 4557335  172 KYPVGIEVGPQPQGVLRADILDQMRKMIKHALDFI 206
Cdd:cd06909 156 KHGFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 11-300 6.40e-96

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: 285.01  E-value: 6.40e-96
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335     11 IQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLGKkmSEDLPYEV 90
Cdd:pfam04952   2 GPTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAGERTLVPLANPPAFRAGSRYIPRDLNRSFPGRALGA--SSDEPYRA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335     91 RRAQEINHLFGPKDSEdSYDIIFDLHNTTSNMGCTLILEDSRNNFLIQMFHYIKTSLAPLPCYVYLIEHPSLKYATTRSI 170
Cdd:pfam04952  80 TRAERLADLFFPALLP-RADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGFSAFSAEEL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    171 AKYPVGIEVGpqPQGVLRADILDQMRKMIKHALDFIHHFNEGKEFPPCAiEVYKIIEKVDYPRDENGEIAAIIHPNL--- 247
Cdd:pfam04952 159 GAPGFTLELG--GAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFEPP-KLYRVLREIDRPRDIRAELAGLVEFALnlg 235

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 4557335    248 QDQDWKPLHPGDPMFLTLDGKTIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 300
Cdd:pfam04952 236 DDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAK 288
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
11-291 1.03e-61

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 198.15  E-value: 1.03e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   11 IQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRT-GLEVKPFITNPRAVKKCTRYIDCDLNRIFDLENLgkkmSEDLPYE 89
Cdd:COG2988  24 IKAVVISGGIHGNETAPIELLDKLLQDLLLGERPlSFRLLLILGNPAAMRAGRRYLDEDLNRLFGGRHL----QNPESYE 99

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   90 VRRAQEINHLFGPK-DSEDSYDIIFDLHNTTSNMGCTLI--LEDSRNNFLIQMFHYIKTS--LAPlpcyVYLIEHPSLKY 164
Cdd:COG2988 100 AARAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFavYPFRGRPFDLALLAYLAAAgpEAV----VLHHAPGGTFS 175

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335  165 ATTRSIAKYP-VGIEVGPQ-PQGVLRADILDQMRKMIKHALDFIhhfnEGKEFPPCAIEVYKIIEKVdyprDENGeIAAI 242
Cdd:COG2988 176 HFSAELCGAQaFTLELGKVrPFGQNDLSRFAATEEALRALLSGA----ELPEHPAQDLDLYRVVQQI----IKHG-DDFM 246

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 4557335  243 IHPNLQDQDWKPLHPGDPMFLTlDGKTIPLGGDcTVYPVFVNEAAYYEK 291
Cdd:COG2988 247 LHPDLDTLNFTPLPPGTLLAED-GGKEYRVEGD-EERIVFPNEAVYYGQ 293
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 14-201 9.56e-28

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: 106.24  E-value: 9.56e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   14 VAIFGGTHGNELTGVFLVKHWLENGAEIQRTG-LEVKPfITNPRAVKKCTRYID---CDLNRIFDLENLGkkmsedlPYE 89
Cdd:cd06230   1 LLILAGVHGDEYEGVEAIRRLLAELDPSELKGtVVLVP-VANPPAFEAGTRYTPldgLDLNRIFPGDPDG-------SPT 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   90 VRRAQEINHLFGPKdsedsYDIIFDLHNTTSNM-GCTLILEDSR--NNFLIQMFHYIKtslaplPCYVYLIEHP--SLKY 164
Cdd:cd06230  73 ERLAHELTELILKH-----ADALIDLHSGGTGRlVPYAILDYDSdaREKSRELARAFG------GTPVIWGGDPpgGTPV 141

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 4557335  165 ATTRSIAKYPVGIEVGpqPQGVLRADILDQMRKMIKH 201
Cdd:cd06230 142 AAARSAGIPAITVELG--GGGRLRAERLERYLRGIRN 176
M14_ASTE_ASPA_like cd18430
Succinylglutamate desuccinylase/aspartoacylase; uncharacterized; A functionally ...
 14-134 1.16e-11

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: 62.08  E-value: 1.16e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   14 VAIFGGTHGNELTGVFLVKHW---LENGAEIQRTgleVKPFITNPRAVKKCTRYIDCDLNRIFDlenlGKKMSEDlpYEV 90
Cdd:cd18430   1 LAVLGAVHGNETCGTRAVERLlaeLPSGALQKGP---VTLVPANERAYAEGVRFCEEDLNRVFP----GDPDPDT--YER 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 4557335   91 RRAQEINHLFgpkdseDSYDIIFDLHNTTSNmGCTLILEDSRNN 134
Cdd:cd18430  72 RLANRLCPEL------EGHDVVLDLHSTHSG-GQPFAILDYGDK 108
M14_ASTE_ASPA-like cd06910
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 14-119 1.19e-07

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: 51.20  E-value: 1.19e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   14 VAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKpfITNPRAVKK-------CTRYIDCDLNRIFDLENLGkkmSEDL 86
Cdd:cd06910  27 VMINALTHGNEICGAIALDWLLKNGVRPLRGRLTFC--FANVEAYERfdparptASRFVDEDLNRVWGPELLD---GPEQ 101

                        90       100       110
                ....*....|....*....|....*....|...
gi 4557335   87 PYEVRRAQEINHLFgpkdseDSYDIIFDLHNTT 119
Cdd:cd06910 102 SIELRRARELRPVV------DTVDYLLDIHSMQ 128
M14_ASTE_ASPA-like cd06256
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 21-140 2.38e-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: 349474  Cd Length: 204  Bit Score: 44.59  E-value: 2.38e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   21 HGNELTGVFLVKHWLENGAEIQ-RTgleVKPFITNPRAVKKCTRYID--CDLNRIFDlenlgkkmSEDLPYEVRRAQEIN 97
Cdd:cd06256  44 HGNEPTGLRAVQRLLKTGQAPLpRT---LLLFIGNVDAAKAGVRRLPgqPDYNRCWP--------GPFETPEGRLAAAVL 112

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 4557335   98 HLFGPKDSEDSYDIifdlHNTTSN---MGCtLILEDSRNNFLIQMF 140
Cdd:cd06256 113 ERLDTLRPFASIDI----HNNTGKnphYAC-VNRLDAAHLRLASLF 153
M14_ASTE cd03855
Peptidase M14 Succinylglutamate desuccinylase (ASTE) subfamily; Peptidase M14 ...
 19-116 3.94e-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: 44.12  E-value: 3.94e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   19 GTHGNELTGVFLVKHWLENgaeIQRTGLEVKP---FI-TNPRAVKKCTRYIDCDLNRIFDlenlGKKMSEDLPYEVRRAQ 94
Cdd:cd03855  51 GIHGNETAPIEILDQLIND---LIRGELALAHrllFIfGNPPAIRQGKRFIEENLNRLFS----GRHSKLPPSYETARAA 123

                        90       100
                ....*....|....*....|....*.
gi 4557335   95 EI----NHLFGpkDSEDSYDIIFDLH 116
Cdd:cd03855 124 ELeqavADFFA--KASGEVRWHLDLH 147
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 13-73 1.17e-04

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: 42.65  E-value: 1.17e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4557335   13 KVAIFGGTHGNELTGVFLVKHWLE---NGAEIQRTGLEVKPfITNPRAVKKCTRY----IdcDLNRIF 73
Cdd:cd06904  25 RILIIGGIHGDEPEGVSLVEHLLRwlkNHPASGDFHIVVVP-CLNPDGLAAGTRTnangV--DLNRNF 89
PRK05324 PRK05324
succinylglutamate desuccinylase; Provisional
 19-95 3.66e-04

succinylglutamate desuccinylase; Provisional


Pssm-ID: 235408  Cd Length: 329  Bit Score: 41.71  E-value: 3.66e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335    19 GTHGNELTGVFLVKHWLengAEIQRTGLEVKP---FI-TNPRAVKKCTRYIDCDLNRIFDlenlGKKMSEDLPYEVRRAQ 94
Cdd:PRK05324  55 GIHGNETAPIELLDQLV---RDLLAGELPLRArllVIlGNPPAMRAGKRYLDEDLNRLFG----GRHQQFPGSDEARRAA 127


                 .
gi 4557335    95 E 95
Cdd:PRK05324 128 E 128
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 13-119 4.72e-04

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: 40.75  E-value: 4.72e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   13 KVAIFGGTHGNELTGVFLVKHWLENGAEI--QRTGLEVKPFItNPRAVKKCTRYIDC--DLNRIFDLenlgkkmsEDLPY 88
Cdd:cd06231  44 RVLISAGIHGDEPAGVEALLRFLESLAEKylRRVNLLVLPCV-NPWGFERNTRENADgiDLNRSFLK--------DSPSP 114

                        90       100       110
                ....*....|....*....|....*....|.
gi 4557335   89 EVRRAQEinHLfgpkDSEDSYDIIFDLHNTT 119
Cdd:cd06231 115 EVRALME--FL----ASLGRFDLHLDLHEDW 139
M14_CP_Csd4-like cd06243
Peptidase M14 carboxypeptidase Csd4 and similar proteins; This family includes peptidase M14 ...
 13-74 1.01e-03

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: 39.65  E-value: 1.01e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557335   13 KVAIFGGTHGNE----LTGVFLVKHWLENGAeiqrtgLEVKPFItNPRAVKKCTRYIDCDLNRIFD 74
Cdd:cd06243  18 TLLIIGGIQGDEpggfLAADLLADLYLVKGN------VIVVPRL-NFPSILRNHRGLNGDMNRKFA 76
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 14-73 1.21e-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: 349471  Cd Length: 211  Bit Score: 39.51  E-value: 1.21e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   14 VAIFGGTHGNELTGVF----LVKhWL---ENGAEIQRTGLEVKPFItNPRAVKKCTRYI---DCDLNRIF 73
Cdd:cd06253  25 IAIVAGIHGDELNGLYvcsrLIR-FLkelEEGGYKLKGKVLVIPAV-NPLGINSGTRFWpfdNLDMNRMF 92
COG3608 COG3608
Predicted deacylase [General function prediction only];
13-122 2.59e-03

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 39.06  E-value: 2.59e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557335   13 KVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGlEVK--PFItNPRAVKKCTRY--IDC-DLNRIFdlenLGkkmSEDLP 87
Cdd:COG3608  28 TLLITAGIHGDELNGIEALRRLLRELDPGELRG-TVIlvPVA-NPPGFLQGSRYlpIDGrDLNRSF----PG---DADGS 98

                        90       100       110
                ....*....|....*....|....*....|....*
gi 4557335   88 YEVRRAQEINHLFGPKdsedsYDIIFDLHNTTSNM 122
Cdd:COG3608  99 LAERIAHALFEEILPD-----ADYVIDLHSGGIAR 128
 
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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