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Conserved domains on  [gi|1907079645|ref|XP_036012133|]
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aspartoacylase isoform X3 [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 ...
 12-231 1.89e-90

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: 268.28  E-value: 1.89e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  12 EMSEDLPYEVRRAQEINHLFGPKNSDDaYDLVFDLHNTTSNMGCTLILEDsRNDFLIQMFHYIKTCMaPLPcsVYLIEHP 91
Cdd:PRK02259   70 QNPDLSGYEQLRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYG-RRPFDLALAAYLQSRL-PLP--IYLHEKD 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  92 SLKYATTRSIAKYPVGIEVGPQPHGVLRADILDQMRKMIKHALDFIQHFNEGK-EFPPCSIDVYKIMEKVDYPRNESGDM 170
Cdd:PRK02259  145 EDQTGFLVELWPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKlPLPNEQLVVYRHLGSIDYPRDENGQI 224

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907079645 171 AAVIHPNLQDQDWKPLHPGDPVFVSLDGKVIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 231
Cdd:PRK02259  225 AAMIHPQLQGRDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 12-231 1.89e-90

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 268.28  E-value: 1.89e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  12 EMSEDLPYEVRRAQEINHLFGPKNSDDaYDLVFDLHNTTSNMGCTLILEDsRNDFLIQMFHYIKTCMaPLPcsVYLIEHP 91
Cdd:PRK02259   70 QNPDLSGYEQLRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYG-RRPFDLALAAYLQSRL-PLP--IYLHEKD 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  92 SLKYATTRSIAKYPVGIEVGPQPHGVLRADILDQMRKMIKHALDFIQHFNEGK-EFPPCSIDVYKIMEKVDYPRNESGDM 170
Cdd:PRK02259  145 EDQTGFLVELWPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKlPLPNEQLVVYRHLGSIDYPRDENGQI 224

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907079645 171 AAVIHPNLQDQDWKPLHPGDPVFVSLDGKVIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 231
Cdd:PRK02259  225 AAMIHPQLQGRDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 7-137 3.02e-61

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: 190.50  E-value: 3.02e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645   7 EKCIKEMSEDLPYEVRRAQEINHLFGPKNsDDAYDLVFDLHNTTSNMGCTLILEDSRnDFLIQMFHYIKTCMapLPCSVY 86
Cdd:cd06909    64 LENLSSAPSSLPYEVRRAREINQILGPKG-NPACDFIIDLHNTTSNMGITLILSSSD-DFTLKLAAYLQQRL--PPVRVL 139

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907079645  87 LIEHPSLKYATTRSIAKYPVGIEVGPQPHGVLRADILDQMRKMIKHALDFI 137
Cdd:cd06909   140 LHESPSKESPFLRSVAKHGFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 14-231 4.62e-60

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: 191.02  E-value: 4.62e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  14 SEDLPYEVRRAQEINHLFGPKNSDdAYDLVFDLHNTTSNMGCTLILEDSRNDFLIQMFHYIKTCMAPLPCSVYLIEHPSL 93
Cdd:pfam04952  72 SSDEPYRATRAERLADLFFPALLP-RADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGF 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  94 KYATTRSIAKYPVGIEVGPQphGVLRADILDQMRKMIKHALDFIQHFNEGKEFPPCSIdVYKIMEKVDYPRNESGDMAAV 173
Cdd:pfam04952 151 SAFSAEELGAPGFTLELGGA--GPFGANLISRTAAGVLNVLRLIGVLNGGPDAFEPPK-LYRVLREIDRPRDIRAELAGL 227

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907079645 174 IHPNL---QDQDWKPLHPGDPVFVSLDGKVIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 231
Cdd:pfam04952 228 VEFALnlgDDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAK 288
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
19-222 7.45e-37

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 131.51  E-value: 7.45e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  19 YEVRRAQEINHLFGPK-NSDDAYDLVFDLHNTTSNMGCTLI--LEDSRNDFLIQMFHYIKTCMAPLPcsVYLIEHPSLKY 95
Cdd:COG2988    98 YEAARAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFavYPFRGRPFDLALLAYLAAAGPEAV--VLHHAPGGTFS 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  96 ATTRSIAKYP-VGIEVGPQ-PHGVLRADILDQMRKMIKHALDFIqhfnEGKEFPPCSIDVYKIMEKVDyprnESGDmAAV 173
Cdd:COG2988   176 HFSAELCGAQaFTLELGKVrPFGQNDLSRFAATEEALRALLSGA----ELPEHPAQDLDLYRVVQQII----KHGD-DFM 246

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1907079645 174 IHPNLQDQDWKPLHPGDPVFvSLDGKVIPLGGDcTVYPVFVNEAAYYEK 222
Cdd:COG2988   247 LHPDLDTLNFTPLPPGTLLA-EDGGKEYRVEGD-EERIVFPNEAVYYGQ 293
 
Name Accession Description Interval E-value
PRK02259 PRK02259
aspartoacylase; Provisional
 12-231 1.89e-90

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 268.28  E-value: 1.89e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  12 EMSEDLPYEVRRAQEINHLFGPKNSDDaYDLVFDLHNTTSNMGCTLILEDsRNDFLIQMFHYIKTCMaPLPcsVYLIEHP 91
Cdd:PRK02259   70 QNPDLSGYEQLRAKELVQQLGPKGNSP-CDFIIDLHSTTANMGLSLILYG-RRPFDLALAAYLQSRL-PLP--IYLHEKD 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  92 SLKYATTRSIAKYPVGIEVGPQPHGVLRADILDQMRKMIKHALDFIQHFNEGK-EFPPCSIDVYKIMEKVDYPRNESGDM 170
Cdd:PRK02259  145 EDQTGFLVELWPCGLVIEVGPVPQGVLDAEIFEQTELLIESILDYLEKYNQGKlPLPNEQLVVYRHLGSIDYPRDENGQI 224

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907079645 171 AAVIHPNLQDQDWKPLHPGDPVFVSLDGKVIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 231
Cdd:PRK02259  225 AAMIHPQLQGRDWQPLKPGDPLFLTFDGKTIFYEGDSTVYPVFINEAAYYEKGIAMSLTKK 285
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 7-137 3.02e-61

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: 190.50  E-value: 3.02e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645   7 EKCIKEMSEDLPYEVRRAQEINHLFGPKNsDDAYDLVFDLHNTTSNMGCTLILEDSRnDFLIQMFHYIKTCMapLPCSVY 86
Cdd:cd06909    64 LENLSSAPSSLPYEVRRAREINQILGPKG-NPACDFIIDLHNTTSNMGITLILSSSD-DFTLKLAAYLQQRL--PPVRVL 139

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907079645  87 LIEHPSLKYATTRSIAKYPVGIEVGPQPHGVLRADILDQMRKMIKHALDFI 137
Cdd:cd06909   140 LHESPSKESPFLRSVAKHGFTIEVGPVPQGVLRADIFEQTRKLVKAILDFI 190
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 14-231 4.62e-60

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: 191.02  E-value: 4.62e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  14 SEDLPYEVRRAQEINHLFGPKNSDdAYDLVFDLHNTTSNMGCTLILEDSRNDFLIQMFHYIKTCMAPLPCSVYLIEHPSL 93
Cdd:pfam04952  72 SSDEPYRATRAERLADLFFPALLP-RADIVLDLHTGTRGMGHLLFALAPIRDDPLHLLALLRAFGAPAVLKLHSKPSAGF 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  94 KYATTRSIAKYPVGIEVGPQphGVLRADILDQMRKMIKHALDFIQHFNEGKEFPPCSIdVYKIMEKVDYPRNESGDMAAV 173
Cdd:pfam04952 151 SAFSAEELGAPGFTLELGGA--GPFGANLISRTAAGVLNVLRLIGVLNGGPDAFEPPK-LYRVLREIDRPRDIRAELAGL 227

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907079645 174 IHPNL---QDQDWKPLHPGDPVFVSLDGKVIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 231
Cdd:pfam04952 228 VEFALnlgDDVDAGPLLPGGPLFAPFGGEETEYRAPEDGYPVFPNEAAYVGKGAALALVAK 288
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
19-222 7.45e-37

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 131.51  E-value: 7.45e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  19 YEVRRAQEINHLFGPK-NSDDAYDLVFDLHNTTSNMGCTLI--LEDSRNDFLIQMFHYIKTCMAPLPcsVYLIEHPSLKY 95
Cdd:COG2988    98 YEAARAKELEQAVGPFfAAGGRVRLHIDLHTAIRNSGHERFavYPFRGRPFDLALLAYLAAAGPEAV--VLHHAPGGTFS 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  96 ATTRSIAKYP-VGIEVGPQ-PHGVLRADILDQMRKMIKHALDFIqhfnEGKEFPPCSIDVYKIMEKVDyprnESGDmAAV 173
Cdd:COG2988   176 HFSAELCGAQaFTLELGKVrPFGQNDLSRFAATEEALRALLSGA----ELPEHPAQDLDLYRVVQQII----KHGD-DFM 246

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1907079645 174 IHPNLQDQDWKPLHPGDPVFvSLDGKVIPLGGDcTVYPVFVNEAAYYEK 222
Cdd:COG2988   247 LHPDLDTLNFTPLPPGTLLA-EDGGKEYRVEGD-EERIVFPNEAVYYGQ 293
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 14-132 4.60e-09

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: 54.24  E-value: 4.60e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907079645  14 SEDLPYEVRRAQEINHLFGPKnsddaYDLVFDLHNTTSNM-GCTLILEDSR--NDFLIQMFHYIKtcmaplPCSVYLIEH 90
Cdd:cd06230    66 DPDGSPTERLAHELTELILKH-----ADALIDLHSGGTGRlVPYAILDYDSdaREKSRELARAFG------GTPVIWGGD 134

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907079645  91 P--SLKYATTRSIAKYPVGIEVGpqPHGVLRADILDQMRKMIKH 132
Cdd:cd06230   135 PpgGTPVAAARSAGIPAITVELG--GGGRLRAERLERYLRGIRN 176
 
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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