NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|657704537|ref|WP_029503340|]
View 

M14 family metallopeptidase [Lachnoclostridium phytofermentans]

Protein Classification

M14 family metallopeptidase( domain architecture ID 10154712)

M14 family metallopeptidase is a zinc-binding carboxypeptidase which hydrolyzes a single, C-terminal amino acid from a polypeptide chain, and has a recognition site for the free C-terminal carboxyl group

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 10-218 8.34e-105

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: 304.52  E-value: 8.34e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  10 LPVLETMHIKKNHLEPENkkgNEKRICIVTGVHGDELEGQYICYELIRRIR---EENEFLTGIVDVYPCVNPLGMESITR 86
Cdd:cd06253    3 SPFREPLEVKGFRFGGGN---AEPRIAIVAGIHGDELNGLYVCSRLIRFLKeleEGGYKLKGKVLVIPAVNPLGINSGTR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  87 RIPTFDLDMNRSFPGDMDGDMSEYVAAKLVEDLEGADFCVDLHASNIFLREIPQVRLDKQHEESLLEYAKLLNTDFIWVH 166
Cdd:cd06253   80 FWPFDNLDMNRMFPGYNKGETTERIAAALFEDLKGADYGIDLHSSNDFLREIPQVRVIESGAQDLLPLAKFLGLDVVWVH 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 657704537 167 SSPTVEPASLYHSLNQNGVPTLSIEMGVGMRITKEFGDQILEGIFCLMHKLG 218
Cdd:cd06253  160 PASTVDTGTLAYNWNEWGTKALVLEMGVGMRIDKEYCEQLFEGILRFLLKMG 211
 
Name Accession Description Interval E-value
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 10-218 8.34e-105

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: 304.52  E-value: 8.34e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  10 LPVLETMHIKKNHLEPENkkgNEKRICIVTGVHGDELEGQYICYELIRRIR---EENEFLTGIVDVYPCVNPLGMESITR 86
Cdd:cd06253    3 SPFREPLEVKGFRFGGGN---AEPRIAIVAGIHGDELNGLYVCSRLIRFLKeleEGGYKLKGKVLVIPAVNPLGINSGTR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  87 RIPTFDLDMNRSFPGDMDGDMSEYVAAKLVEDLEGADFCVDLHASNIFLREIPQVRLDKQHEESLLEYAKLLNTDFIWVH 166
Cdd:cd06253   80 FWPFDNLDMNRMFPGYNKGETTERIAAALFEDLKGADYGIDLHSSNDFLREIPQVRVIESGAQDLLPLAKFLGLDVVWVH 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 657704537 167 SSPTVEPASLYHSLNQNGVPTLSIEMGVGMRITKEFGDQILEGIFCLMHKLG 218
Cdd:cd06253  160 PASTVDTGTLAYNWNEWGTKALVLEMGVGMRIDKEYCEQLFEGILRFLLKMG 211
COG3608 COG3608
Predicted deacylase [General function prediction only];
33-307 8.55e-78

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 238.98  E-value: 8.55e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  33 KRICIVTGVHGDELEGQYICYELIRRIREENefLTGIVDVYPCVNPLGMESITRRIPTFDLDMNRSFPGDMDGDMSEYVA 112
Cdd:COG3608   27 PTLLITAGIHGDELNGIEALRRLLRELDPGE--LRGTVILVPVANPPGFLQGSRYLPIDGRDLNRSFPGDADGSLAERIA 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 113 AKLVED-LEGADFCVDLHASNIFLREIPQVRLDKQHEESlLEYAKLLNTDFIWVhsSPTVEPASLYHSLNQNGVPTLSIE 191
Cdd:COG3608  105 HALFEEiLPDADYVIDLHSGGIARDNLPHVRAGPGDEEL-RALARAFGAPVILD--SPEGGDGSLREAAAEAGIPALTLE 181

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 192 MGVGMRITKEFGDQILEGIFCLMHKLGIWNGSVITP--KTSVISSDRDKVtliHAEASGIFLPCVEHLMDIKAGDVVGNI 269
Cdd:COG3608  182 LGGGGRFDEESIEAGVRGILNVLRHLGMLDGEAPPPplAPPVLARGSEWV---RAPAGGLFEPLVELGDRVKKGDVLGRI 258

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 657704537 270 VDsLNGTVVQHIIAPCDGVVFTLREYPVVYDGSLIARI 307
Cdd:COG3608  259 TD-PFGEEVEEVRAPVDGIVIGRRTNPLVNPGDALFHI 295
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 33-307 3.00e-30

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: 115.52  E-value: 3.00e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537   33 KRICIVTGVHGDELEGQYICYELIRRIREENefLTGIVDVYPCVNPLGMESITRRIPTfdlDMNRSFPGDMDGDMS---- 108
Cdd:pfam04952   3 PTLLLSAGIHGNETNGVELLRRLLRQLDPGD--IAGERTLVPLANPPAFRAGSRYIPR---DLNRSFPGRALGASSdepy 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  109 ------EYVAAKLVEDLEGADFCVDLHASNIFLREIPQVRLDKQ-HEESLLEYAKLLNTDFI-WVHSSPTVepASLYHSL 180
Cdd:pfam04952  78 ratraeRLADLFFPALLPRADIVLDLHTGTRGMGHLLFALAPIRdDPLHLLALLRAFGAPAVlKLHSKPSA--GFSAFSA 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  181 NQNGVPTLSIEMGVGMRITKEFGDQILEGIFCLMHKLGIWNG-------SVITPKTSVISSDRDkvtlIHAEASGIFLPC 253
Cdd:pfam04952 156 EELGAPGFTLELGGAGPFGANLISRTAAGVLNVLRLIGVLNGgpdafepPKLYRVLREIDRPRD----IRAELAGLVEFA 231

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 657704537  254 VEHLMDIKAGDVVGN--IVDSLNGTVVQhIIAPCDGVVFTLREYPVVYDGSLIARI 307
Cdd:pfam04952 232 LNLGDDVDAGPLLPGgpLFAPFGGEETE-YRAPEDGYPVFPNEAAYVGKGAALALV 286
PRK02259 PRK02259
aspartoacylase; Provisional
 33-129 6.79e-04

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 40.63  E-value: 6.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  33 KRICIVTGVHGDELEGQYicyeLIRRIREENEFLT--GIVDVYPCVNPLGMESITRRIptfDLDMNRSFPGDMDGDMS-- 108
Cdd:PRK02259   3 NRVAIVGGTHGNEITGIY----LVKKWQQQPNLINrkGLEVQTVIGNPEAIEAGRRYI---DRDLNRSFRLDLLQNPDls 75

                         90       100
                 ....*....|....*....|....*....
gi 657704537 109 --EYVAAK-LVEDL-----EGADFCVDLH 129
Cdd:PRK02259  76 gyEQLRAKeLVQQLgpkgnSPCDFIIDLH 104
 
Name Accession Description Interval E-value
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 10-218 8.34e-105

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: 304.52  E-value: 8.34e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  10 LPVLETMHIKKNHLEPENkkgNEKRICIVTGVHGDELEGQYICYELIRRIR---EENEFLTGIVDVYPCVNPLGMESITR 86
Cdd:cd06253    3 SPFREPLEVKGFRFGGGN---AEPRIAIVAGIHGDELNGLYVCSRLIRFLKeleEGGYKLKGKVLVIPAVNPLGINSGTR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  87 RIPTFDLDMNRSFPGDMDGDMSEYVAAKLVEDLEGADFCVDLHASNIFLREIPQVRLDKQHEESLLEYAKLLNTDFIWVH 166
Cdd:cd06253   80 FWPFDNLDMNRMFPGYNKGETTERIAAALFEDLKGADYGIDLHSSNDFLREIPQVRVIESGAQDLLPLAKFLGLDVVWVH 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 657704537 167 SSPTVEPASLYHSLNQNGVPTLSIEMGVGMRITKEFGDQILEGIFCLMHKLG 218
Cdd:cd06253  160 PASTVDTGTLAYNWNEWGTKALVLEMGVGMRIDKEYCEQLFEGILRFLLKMG 211
COG3608 COG3608
Predicted deacylase [General function prediction only];
33-307 8.55e-78

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 238.98  E-value: 8.55e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  33 KRICIVTGVHGDELEGQYICYELIRRIREENefLTGIVDVYPCVNPLGMESITRRIPTFDLDMNRSFPGDMDGDMSEYVA 112
Cdd:COG3608   27 PTLLITAGIHGDELNGIEALRRLLRELDPGE--LRGTVILVPVANPPGFLQGSRYLPIDGRDLNRSFPGDADGSLAERIA 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 113 AKLVED-LEGADFCVDLHASNIFLREIPQVRLDKQHEESlLEYAKLLNTDFIWVhsSPTVEPASLYHSLNQNGVPTLSIE 191
Cdd:COG3608  105 HALFEEiLPDADYVIDLHSGGIARDNLPHVRAGPGDEEL-RALARAFGAPVILD--SPEGGDGSLREAAAEAGIPALTLE 181

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 192 MGVGMRITKEFGDQILEGIFCLMHKLGIWNGSVITP--KTSVISSDRDKVtliHAEASGIFLPCVEHLMDIKAGDVVGNI 269
Cdd:COG3608  182 LGGGGRFDEESIEAGVRGILNVLRHLGMLDGEAPPPplAPPVLARGSEWV---RAPAGGLFEPLVELGDRVKKGDVLGRI 258

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 657704537 270 VDsLNGTVVQHIIAPCDGVVFTLREYPVVYDGSLIARI 307
Cdd:COG3608  259 TD-PFGEEVEEVRAPVDGIVIGRRTNPLVNPGDALFHI 295
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 35-211 6.62e-48

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: 158.24  E-value: 6.62e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  35 ICIVTGVHGDELEGQYICYELIRRIREEneFLTGIVDVYPCVNPLGMESITRRIPTFDLDMNRSFPGDMDGDMSEYVAAK 114
Cdd:cd06230    1 LLILAGVHGDEYEGVEAIRRLLAELDPS--ELKGTVVLVPVANPPAFEAGTRYTPLDGLDLNRIFPGDPDGSPTERLAHE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 115 LVED-LEGADFCVDLHASNIFlREIPQVRLDKQHE--ESLLEYAKLLN-TDFIWVHSSPTVEPASLYHSLnqnGVPTLSI 190
Cdd:cd06230   79 LTELiLKHADALIDLHSGGTG-RLVPYAILDYDSDarEKSRELARAFGgTPVIWGGDPPGGTPVAAARSA---GIPAITV 154

                        170       180
                 ....*....|....*....|.
gi 657704537 191 EMGVGMRITKEFGDQILEGIF 211
Cdd:cd06230  155 ELGGGGRLRAERLERYLRGIR 175
M14_ASTE_ASPA-like cd06251
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 33-219 1.77e-31

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: 116.49  E-value: 1.77e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  33 KRICIVTGVHGDELEGQYICYELIRRIreENEFLTGIVDVYPCVNPLGMESITRRIPTFDLDMNRSFPGDMDGDMSEYVA 112
Cdd:cd06251   13 PTLLLTAAIHGDELNGIEVIQRLLEDL--DPSKLRGTLIAIPVVNPLGFENNSRYLPDDGRDLNRSFPGSEKGSLASRLA 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 113 AKLVEDL-EGADFCVDLHASNIFLREIPQVRLDKQHEESlLEYAKLLNTDFIwVHSSPtvEPASLYHSLNQNGVPTLSIE 191
Cdd:cd06251   91 HLLWNEIvKKADYVIDLHTASTGRTNLPYVRADLRDPES-RRMAEAFGAPVI-VDDPG--EDGSLRGAAVELGIPAITVE 166

                        170       180
                 ....*....|....*....|....*...
gi 657704537 192 MGVGMRITKEFGDQILEGIFCLMHKLGI 219
Cdd:cd06251  167 LGEALRFDEDIIRRGVEGVLNVLRHLGM 194
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 33-307 3.00e-30

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: 115.52  E-value: 3.00e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537   33 KRICIVTGVHGDELEGQYICYELIRRIREENefLTGIVDVYPCVNPLGMESITRRIPTfdlDMNRSFPGDMDGDMS---- 108
Cdd:pfam04952   3 PTLLLSAGIHGNETNGVELLRRLLRQLDPGD--IAGERTLVPLANPPAFRAGSRYIPR---DLNRSFPGRALGASSdepy 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  109 ------EYVAAKLVEDLEGADFCVDLHASNIFLREIPQVRLDKQ-HEESLLEYAKLLNTDFI-WVHSSPTVepASLYHSL 180
Cdd:pfam04952  78 ratraeRLADLFFPALLPRADIVLDLHTGTRGMGHLLFALAPIRdDPLHLLALLRAFGAPAVlKLHSKPSA--GFSAFSA 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  181 NQNGVPTLSIEMGVGMRITKEFGDQILEGIFCLMHKLGIWNG-------SVITPKTSVISSDRDkvtlIHAEASGIFLPC 253
Cdd:pfam04952 156 EELGAPGFTLELGGAGPFGANLISRTAAGVLNVLRLIGVLNGgpdafepPKLYRVLREIDRPRD----IRAELAGLVEFA 231

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 657704537  254 VEHLMDIKAGDVVGN--IVDSLNGTVVQhIIAPCDGVVFTLREYPVVYDGSLIARI 307
Cdd:pfam04952 232 LNLGDDVDAGPLLPGgpLFAPFGGEETE-YRAPEDGYPVFPNEAAYVGKGAALALV 286
M14_ASTE_ASPA-like cd06255
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 41-220 1.38e-21

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: 349473  Cd Length: 223  Bit Score: 90.85  E-value: 1.38e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  41 VHGDELEGQYICYELIRRIREENefLTGIVDVYPCVNPLGMESITRRIPTFDLDMNRSFPGDMDGDMSEYVAAKLVEDLE 120
Cdd:cd06255   32 VHGDELNGPLAALELFRELDPAQ--LSGTLVATPIANPLAFQGRQKFSPQDGEDLDQSFPGDPDGLITERMAHALFSEVK 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 121 G-ADFCVDLHASNIFLREIPQVR------LDKQHEESLLEYAKLLN-TDFIWVHSSPTVEPASLYHSL------NQNGVP 186
Cdd:cd06255  110 EvADYLIDFHTGGTPFDANPYTVyklfpeSGPVEEKRLLRLARAFGvHANCRVDVSGAGGELPGNTAGaldyqcMAQGIP 189

                        170       180       190
                 ....*....|....*....|....*....|....
gi 657704537 187 TLSIEMGVGMRITKEFGDQILEGIFCLMHKLGIW 220
Cdd:cd06255  190 AFMVELGGGGRAEEEAVRFAARGLRNLLRYLGML 223
M14_ASTE_ASPA-like cd06252
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 40-201 1.75e-20

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; uncharacterized subgroup; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-2; EC:3.5.1.15) cleaves N-acetyl L-aspartic acid (NAA) into aspartate and acetate. NAA is abundant in the brain, and hydrolysis of NAA by ASPA may help maintain white matter. ASPA is an NAA scavenger in other tissues. Mutations in the gene encoding ASPA cause Canavan disease (CD), a fatal progressive neurodegenerative disorder involving dysmyelination and spongiform degeneration of white matter in children. This enzyme binds zinc which is necessary for activity. Measurement of elevated NAA levels in urine is used in the diagnosis of CD.


Pssm-ID: 349470  Cd Length: 224  Bit Score: 88.01  E-value: 1.75e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  40 GVHGDELEGQYICYELIRRIREENefLTGIVDVYPCVNPLGMESITRRIPTFDLDMNRSFPGDMDGDMSEYVAAKLVEDL 119
Cdd:cd06252   42 GNHGDEYEGPIALRRLARDLDPED--VRGRLIIVPALNLPAVRAGTRTSPLDGGNLNRAFPGDADGTPTERIAHFLETVL 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 120 -EGADFCVDLHASNIFLREIP--QVRL--DKQHEESLLEYAKLLNTDFIWVHSSPTvEPASLYHSLNQNGVPTLSIEMGV 194
Cdd:cd06252  120 lPRADAVIDLHSGGSSLDFVPcaAVHLlpDPAQRARSLALAEAFGAPLSVVVDNVD-APGTLDSAAERAGKIFVSTELGG 198


                 ....*..
gi 657704537 195 GMRITKE 201
Cdd:cd06252  199 GGTVTPA 205
M14_ASTE_ASPA-like cd06254
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 29-217 6.11e-19

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: 349472  Cd Length: 198  Bit Score: 83.01  E-value: 6.11e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  29 KGNE--KRICIVTGVHGDELEGQYICYELIRRIREENefLTGIVDVYPCVNPLGMEsiTRRIPTFDLD---MNRSFPGDM 103
Cdd:cd06254    6 NGAKpgPTLLITAGIHGGEYPGILAAIRLARELDPAD--VKGTLIIVHIANVSGFE--ARTPFVVPEDgknLNRVFPGDP 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537 104 DGDMSEYVAAKLVEDLEG-ADFCVDLHASNIFLREIPQVRLDKQHEESLLE--YAKLLNTDFIWVHSSPTVEPASLYHSL 180
Cdd:cd06254   82 DGTLTERIAYFLTREIISrADFLIDLHGGDANEALTPFVYYPGGASEEVNDisRAAAQALGLPYIVISSSEKGTGYYSYA 161

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 657704537 181 NQNGVPTLSIEMGVGMRITKEFGDQILEGIFCLMHKL 217
Cdd:cd06254  162 ALRGIPSILVERGGLGTCDEEDVQAHKDGIKNLLRHL 198
M14_ASTE_ASPA_like cd18174
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 35-130 3.39e-12

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: 349484  Cd Length: 187  Bit Score: 64.18  E-value: 3.39e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  35 ICIVTGVHGDELEGQYICYELIRRIreENEFLTGIVDVYPCVNPLGMESitRRIPTFDLD---MNRSFPGDMDGDMSEYV 111
Cdd:cd18174    1 LLVTAGVHGYEYASIEALQRLIKEL--DPAKLSGTVIVVPIANIPAFEG--RSIYVNPLDgknLNRSFPGDPDGTPTERL 76

                         90       100
                 ....*....|....*....|
gi 657704537 112 AAKLVEDL-EGADFCVDLHA 130
Cdd:cd18174   77 AHWLTTNViARADYYIDLHG 96
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 25-129 5.66e-11

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: 61.55  E-value: 5.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  25 PENKKGNEKRICIVTGVHGDELEGqyiCYELIRRIRE-ENEFLTGI-VDVYPCVNPLGMESITRRIPTfDLDMNRSFpgd 102
Cdd:cd06231   35 SPNPRGDKPRVLISAGIHGDEPAG---VEALLRFLESlAEKYLRRVnLLVLPCVNPWGFERNTRENAD-GIDLNRSF--- 107

                         90       100
                 ....*....|....*....|....*....
gi 657704537 103 MDGDMSEYVAA--KLVEDLEGADFCVDLH 129
Cdd:cd06231  108 LKDSPSPEVRAlmEFLASLGRFDLHLDLH 136
M14_ASTE_ASPA_like cd18430
Succinylglutamate desuccinylase/aspartoacylase; uncharacterized; A functionally ...
 35-131 2.18e-09

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: 55.53  E-value: 2.18e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  35 ICIVTGVHGDELEGQYICyeliRRIREENE---FLTGIVDVYPCvNPLGMESITRRIptfDLDMNRSFPGDMDGDMSE-Y 110
Cdd:cd18430    1 LAVLGAVHGNETCGTRAV----ERLLAELPsgaLQKGPVTLVPA-NERAYAEGVRFC---EEDLNRVFPGDPDPDTYErR 72

                         90       100
                 ....*....|....*....|.
gi 657704537 111 VAAKLVEDLEGADFCVDLHAS 131
Cdd:cd18430   73 LANRLCPELEGHDVVLDLHST 93
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 23-100 2.36e-09

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: 56.51  E-value: 2.36e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  23 LEPENKKGNekRICIVTGVHGDELEGQYICYELIRRIREENEFLTGIVDVYPCVNPLGMESITR---RiptfDLDMNRSF 99
Cdd:cd06904   16 YKFGPGSRA--RILIIGGIHGDEPEGVSLVEHLLRWLKNHPASGDFHIVVVPCLNPDGLAAGTRtnaN----GVDLNRNF 89


                 .
gi 657704537 100 P 100
Cdd:cd06904   90 P 90
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
23-133 1.44e-06

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 49.07  E-value: 1.44e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  23 LEPENKkgNEKRICIVTGVHGDELEGQYICYELIRRIREEN-------EFLTGivdvypcvNPLGMESITRRIPTfdlDM 95
Cdd:COG2988   17 LTPHAP--GIKAVVISGGIHGNETAPIELLDKLLQDLLLGErplsfrlLLILG--------NPAAMRAGRRYLDE---DL 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 657704537  96 NRSFPG-DMDGDMS----------EYVAAKLVEDlEGADFCVDLHaSNI 133
Cdd:COG2988   84 NRLFGGrHLQNPESyeaarakeleQAVGPFFAAG-GRVRLHIDLH-TAI 130
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 33-129 4.87e-05

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: 43.35  E-value: 4.87e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  33 KRICIVTGVHGDELEGQYicyeLIRRIREENEFLTGI-VDVYPCV-NPLGMESITRRIptfDLDMNRSFPGDM-----DG 105
Cdd:cd06909    1 KRVAIVGGTHGNELTGVY----LVKHWLKNPELIERKsFEVHPLLaNPRAVEQCRRYI---DTDLNRCFSLENlssapSS 73

                         90       100       110
                 ....*....|....*....|....*....|
gi 657704537 106 DMSEYVAAK-LVEDL--EGA---DFCVDLH 129
Cdd:cd06909   74 LPYEVRRAReINQILgpKGNpacDFIIDLH 103
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 37-102 1.80e-04

M14 family of metallocarboxypeptidases and related proteins; The M14 family of metallocarboxypeptidases (MCPs), also known as funnelins, are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.


Pssm-ID: 349427 [Multi-domain]  Cd Length: 216  Bit Score: 42.06  E-value: 1.80e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 657704537  37 IVTGVHGDELEGQYICYELIRRIREE--NEFLTGIVD-----VYPCVNPLGME---SITRRIPTFDLDMNRSFPGD 102
Cdd:cd00596    3 ITGGIHGNEVIGVELALALIEYLLENygNDPLKRLLDnvelwIVPLVNPDGFArviDSGGRKNANGVDLNRNFPYN 78
PRK02259 PRK02259
aspartoacylase; Provisional
 33-129 6.79e-04

aspartoacylase; Provisional


Pssm-ID: 235019  Cd Length: 288  Bit Score: 40.63  E-value: 6.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  33 KRICIVTGVHGDELEGQYicyeLIRRIREENEFLT--GIVDVYPCVNPLGMESITRRIptfDLDMNRSFPGDMDGDMS-- 108
Cdd:PRK02259   3 NRVAIVGGTHGNEITGIY----LVKKWQQQPNLINrkGLEVQTVIGNPEAIEAGRRYI---DRDLNRSFRLDLLQNPDls 75

                         90       100
                 ....*....|....*....|....*....
gi 657704537 109 --EYVAAK-LVEDL-----EGADFCVDLH 129
Cdd:PRK02259  76 gyEQLRAKeLVQQLgpkgnSPCDFIIDLH 104
M14_PaAOTO_like cd06250
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like subfamily; ...
 30-119 9.15e-04

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like subfamily; subgroup includes Pseudomonas aeruginosa AotO; An uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the the M14 family of metallocarboxypeptidases. This subgroup includes Pseudomonas aeruginosa AotO and related proteins. 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. The gene encoding P. aeruginosa AotO was characterized as part of an operon encoding an arginine and ornithine transport system, however it is not essential for arginine and ornithine uptake.


Pssm-ID: 349468  Cd Length: 267  Bit Score: 40.30  E-value: 9.15e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657704537  30 GNEKRICIVTGVHGDELEGQYICYELIRRIR--EENEFLTGIVDVYPCVNPLGM------ESITRriptFDLD----MNR 97
Cdd:cd06250   25 GAGPKVYIQAALHADELPGNLVIHHLLERLKalEAAGRIKGEIVLVPQANPIGLsqkiggYHQGR----FDLAtgdnFNR 100

                         90       100
                 ....*....|....*....|..
gi 657704537  98 SFPgdmdgDMSEYVAAKLVEDL 119
Cdd:cd06250  101 NFP-----DLAKAVAARVEERL 117
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 33-97 5.72e-03

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of 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: 349461 [Multi-domain]  Cd Length: 220  Bit Score: 37.28  E-value: 5.72e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 657704537  33 KRICIVTGVHGDELEGQYICYELIRRI---REENEFLTGI-VDVYPCVNPLGMESITRRIPTfDLDMNR 97
Cdd:cd06242    2 PTVLLVGQQHGNEPAGREAALALARDLafgDDARELLEKVnVLVVPRANPDGRAANTRGNAN-GVDLNR 69
M14_CP_Csd4-like cd06243
Peptidase M14 carboxypeptidase Csd4 and similar proteins; This family includes peptidase M14 ...
 22-99 7.16e-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: 37.34  E-value: 7.16e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 657704537  22 HLEPENKKGNEKRICIVTGVHGDELeGQYICYELIRRIREENefltGIVDVYPCVNPlgmESITRRIPTFDLDMNRSF 99
Cdd:cd06243    6 PFTRLEGREPGPTLLIIGGIQGDEP-GGFLAADLLADLYLVK----GNVIVVPRLNF---PSILRNHRGLNGDMNRKF 75
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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