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Conserved domains on  [gi|1155024105|ref|WP_078929316|]
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M14 family metallopeptidase [Succinivibrio dextrinosolvens]

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

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List of domain hits

 Name Accession Description Interval E-value
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 9-217 8.34e-102

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: 297.20  E-value: 8.34e-102
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105   9 ELPVGEQLLIKKNVIRNGNSSKRLCIVTGTHGDELEGQYVAFLLNSILSRDDALA-CLNGSVEIYPALNPLGIDSITRGV 87
Cdd:cd06253     2 ESPFREPLEVKGFRFGGGNAEPRIAIVAGIHGDELNGLYVCSRLIRFLKELEEGGyKLKGKVLVIPAVNPLGINSGTRFW 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  88 PNFDIDMNRIFPGSLGGSLVEAAAHYIVEDLRGADLVIDIHSSNIFLNEIPQVRICVNQQSELVPLANLLNVDFVWVHDA 167
Cdd:cd06253    82 PFDNLDMNRMFPGYNKGETTERIAAALFEDLKGADYGIDLHSSNDFLREIPQVRVIESGAQDLLPLAKFLGLDVVWVHPA 161

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1155024105 168 ATVLESTLAHSLNIVGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLG 217
Cdd:cd06253   162 STVDTGTLAYNWNEWGTKALVLEMGVGMRIDKEYCEQLFEGILRFLLKMG 211
 
Name Accession Description Interval E-value
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 9-217 8.34e-102

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: 297.20  E-value: 8.34e-102
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105   9 ELPVGEQLLIKKNVIRNGNSSKRLCIVTGTHGDELEGQYVAFLLNSILSRDDALA-CLNGSVEIYPALNPLGIDSITRGV 87
Cdd:cd06253     2 ESPFREPLEVKGFRFGGGNAEPRIAIVAGIHGDELNGLYVCSRLIRFLKELEEGGyKLKGKVLVIPAVNPLGINSGTRFW 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  88 PNFDIDMNRIFPGSLGGSLVEAAAHYIVEDLRGADLVIDIHSSNIFLNEIPQVRICVNQQSELVPLANLLNVDFVWVHDA 167
Cdd:cd06253    82 PFDNLDMNRMFPGYNKGETTERIAAALFEDLKGADYGIDLHSSNDFLREIPQVRVIESGAQDLLPLAKFLGLDVVWVHPA 161

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1155024105 168 ATVLESTLAHSLNIVGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLG 217
Cdd:cd06253   162 STVDTGTLAYNWNEWGTKALVLEMGVGMRIDKEYCEQLFEGILRFLLKMG 211
COG3608 COG3608
Predicted deacylase [General function prediction only];
8-306 1.51e-73

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 228.19  E-value: 1.51e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105   8 AELPVGEQLLIKKNVIRNGNSSKRLCIVTGTHGDELEGQYVAF-LLNSILSRDdalacLNGSVEIYPALNPLGIDSITRG 86
Cdd:COG3608     5 SRLASGTPVSLPVTVFRGAGPGPTLLITAGIHGDELNGIEALRrLLRELDPGE-----LRGTVILVPVANPPGFLQGSRY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  87 VPNFDIDMNRIFPGSLGGSLVEAAAHYIVED-LRGADLVIDIHSSNIFLNEIPQVRICVNQQsELVPLANLLNVDFVWVH 165
Cdd:COG3608    80 LPIDGRDLNRSFPGDADGSLAERIAHALFEEiLPDADYVIDLHSGGIARDNLPHVRAGPGDE-ELRALARAFGAPVILDS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 166 DAATvlESTLAHSLNIVGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLGMWSGSVSENIKTPILsVKDEVEFVNASS 245
Cdd:COG3608   159 PEGG--DGSLREAAAEAGIPALTLELGGGGRFDEESIEAGVRGILNVLRHLGMLDGEAPPPPLAPPV-LARGSEWVRAPA 235

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1155024105 246 SGVFVTRYSNNCMVKKGESIGRIISSLTGEIIEdVKAPTDGLMFTLRAYPVVYEGSLLARI 306
Cdd:COG3608   236 GGLFEPLVELGDRVKKGDVLGRITDPFGEEVEE-VRAPVDGIVIGRRTNPLVNPGDALFHI 295
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 30-306 3.57e-19

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: 85.48  E-value: 3.57e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  30 KRLCIVTGTHGDELEGQYVAF-LLNSILSRDDAlaclnGSVEIYPALNPLGIDSITRGVPNfdiDMNRIFPGS-LGGSLV 107
Cdd:pfam04952   3 PTLLLSAGIHGNETNGVELLRrLLRQLDPGDIA-----GERTLVPLANPPAFRAGSRYIPR---DLNRSFPGRaLGASSD 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 108 EAA--------AHYI-VEDLRGADLVIDIHSSNIFLNEIPQVRICVNQ-QSELVPLANLLNVDFV-WVH--DAATVLEST 174
Cdd:pfam04952  75 EPYratraerlADLFfPALLPRADIVLDLHTGTRGMGHLLFALAPIRDdPLHLLALLRAFGAPAVlKLHskPSAGFSAFS 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 175 LAHSlnivGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLGMWSGSVSENIK---TPILSVKDEVEFVNASSSGVFVT 251
Cdd:pfam04952 155 AEEL----GAPGFTLELGGAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFEPpklYRVLREIDRPRDIRAELAGLVEF 230

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1155024105 252 RYSNNCMVKKGESIGR--IISSLTGEIIEdVKAPTDGLMFTLRAYPVVYEGSLLARI 306
Cdd:pfam04952 231 ALNLGDDVDAGPLLPGgpLFAPFGGEETE-YRAPEDGYPVFPNEAAYVGKGAALALV 286
 
Name Accession Description Interval E-value
M14_ASTE_ASPA-like cd06253
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 9-217 8.34e-102

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: 297.20  E-value: 8.34e-102
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105   9 ELPVGEQLLIKKNVIRNGNSSKRLCIVTGTHGDELEGQYVAFLLNSILSRDDALA-CLNGSVEIYPALNPLGIDSITRGV 87
Cdd:cd06253     2 ESPFREPLEVKGFRFGGGNAEPRIAIVAGIHGDELNGLYVCSRLIRFLKELEEGGyKLKGKVLVIPAVNPLGINSGTRFW 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  88 PNFDIDMNRIFPGSLGGSLVEAAAHYIVEDLRGADLVIDIHSSNIFLNEIPQVRICVNQQSELVPLANLLNVDFVWVHDA 167
Cdd:cd06253    82 PFDNLDMNRMFPGYNKGETTERIAAALFEDLKGADYGIDLHSSNDFLREIPQVRVIESGAQDLLPLAKFLGLDVVWVHPA 161

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1155024105 168 ATVLESTLAHSLNIVGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLG 217
Cdd:cd06253   162 STVDTGTLAYNWNEWGTKALVLEMGVGMRIDKEYCEQLFEGILRFLLKMG 211
COG3608 COG3608
Predicted deacylase [General function prediction only];
8-306 1.51e-73

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 228.19  E-value: 1.51e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105   8 AELPVGEQLLIKKNVIRNGNSSKRLCIVTGTHGDELEGQYVAF-LLNSILSRDdalacLNGSVEIYPALNPLGIDSITRG 86
Cdd:COG3608     5 SRLASGTPVSLPVTVFRGAGPGPTLLITAGIHGDELNGIEALRrLLRELDPGE-----LRGTVILVPVANPPGFLQGSRY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  87 VPNFDIDMNRIFPGSLGGSLVEAAAHYIVED-LRGADLVIDIHSSNIFLNEIPQVRICVNQQsELVPLANLLNVDFVWVH 165
Cdd:COG3608    80 LPIDGRDLNRSFPGDADGSLAERIAHALFEEiLPDADYVIDLHSGGIARDNLPHVRAGPGDE-ELRALARAFGAPVILDS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 166 DAATvlESTLAHSLNIVGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLGMWSGSVSENIKTPILsVKDEVEFVNASS 245
Cdd:COG3608   159 PEGG--DGSLREAAAEAGIPALTLELGGGGRFDEESIEAGVRGILNVLRHLGMLDGEAPPPPLAPPV-LARGSEWVRAPA 235

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1155024105 246 SGVFVTRYSNNCMVKKGESIGRIISSLTGEIIEdVKAPTDGLMFTLRAYPVVYEGSLLARI 306
Cdd:COG3608   236 GGLFEPLVELGDRVKKGDVLGRITDPFGEEVEE-VRAPVDGIVIGRRTNPLVNPGDALFHI 295
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 32-212 1.62e-34

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: 123.96  E-value: 1.62e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  32 LCIVTGTHGDELEGQYVAF-LLNSIlsrddALACLNGSVEIYPALNPLGIDSITRGVPNFDIDMNRIFPGSLGGSLVEAA 110
Cdd:cd06230     1 LLILAGVHGDEYEGVEAIRrLLAEL-----DPSELKGTVVLVPVANPPAFEAGTRYTPLDGLDLNRIFPGDPDGSPTERL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 111 AHYIVED-LRGADLVIDIHSSNIFlNEIPQVRICVNQQS--ELVPLANLLNV-DFVWVHDAATVLESTLAHSLNIVgtrT 186
Cdd:cd06230    76 AHELTELiLKHADALIDLHSGGTG-RLVPYAILDYDSDAreKSRELARAFGGtPVIWGGDPPGGTPVAAARSAGIP---A 151

                         170       180
                  ....*....|....*....|....*.
gi 1155024105 187 LVVEMGVGMRITSEYGEALIDGIFNL 212
Cdd:cd06230   152 ITVELGGGGRLRAERLERYLRGIRNV 177
M14_ASTE_ASPA-like cd06251
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 22-218 3.77e-29

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: 110.32  E-value: 3.77e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  22 VIRNGNSSKRLCIVTGTHGDELEGQYVAF-LLNSILsrddaLACLNGSVEIYPALNPLGIDSITRGVPNFDIDMNRIFPG 100
Cdd:cd06251     5 VARGAKPGPTLLLTAAIHGDELNGIEVIQrLLEDLD-----PSKLRGTLIAIPVVNPLGFENNSRYLPDDGRDLNRSFPG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 101 SLGGSLVEAAAHYIVEDL-RGADLVIDIHSSNIFLNEIPQVRICVNQQsELVPLANLLNVDFVwVHDAatVLESTLAHSL 179
Cdd:cd06251    80 SEKGSLASRLAHLLWNEIvKKADYVIDLHTASTGRTNLPYVRADLRDP-ESRRMAEAFGAPVI-VDDP--GEDGSLRGAA 155

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1155024105 180 NIVGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLGM 218
Cdd:cd06251   156 VELGIPAITVELGEALRFDEDIIRRGVEGVLNVLRHLGM 194
M14_ASTE_ASPA-like cd06255
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 8-219 1.66e-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: 90.46  E-value: 1.66e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105   8 AELPVGEQLLIKKNVIRNGNSSKRLCIVTGTHGDELEGQYVAFLLnsilSRDDALACLNGSVEIYPALNPLGIDSITRGV 87
Cdd:cd06255     2 GELASGAPVTIPVIVVRGAKPGPCLWINGAVHGDELNGPLAALEL----FRELDPAQLSGTLVATPIANPLAFQGRQKFS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  88 PNFDIDMNRIFPGSLGGSLVEAAAHYIVEDLRG-ADLVIDIHSSNIFLNEIPQVRICV------NQQSELVPLANLLNVD 160
Cdd:cd06255    78 PQDGEDLDQSFPGDPDGLITERMAHALFSEVKEvADYLIDFHTGGTPFDANPYTVYKLfpesgpVEEKRLLRLARAFGVH 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1155024105 161 FVWVHDAATVLES---TLAHSLNIV----GTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLGMW 219
Cdd:cd06255   158 ANCRVDVSGAGGElpgNTAGALDYQcmaqGIPAFMVELGGGGRAEEEAVRFAARGLRNLLRYLGML 223
M14_ASTE_ASPA-like cd06252
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 22-218 5.50e-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: 349470  Cd Length: 224  Bit Score: 89.17  E-value: 5.50e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  22 VIRNGNSSKRLcIVTGTHGDELEGQYVAfllnSILSRDDALACLNGSVEIYPALNPLGIDSITRGVPNFDIDMNRIFPGS 101
Cdd:cd06252    28 VINNGSGPTVL-LTGGNHGDEYEGPIAL----RRLARDLDPEDVRGRLIIVPALNLPAVRAGTRTSPLDGGNLNRAFPGD 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 102 LGGSLVEAAAHYIVEDL-RGADLVIDIHSSNIFLNEIPQVRICVN----QQSELVPLANLLNVDFVWVHDA--ATVLEST 174
Cdd:cd06252   103 ADGTPTERIAHFLETVLlPRADAVIDLHSGGSSLDFVPCAAVHLLpdpaQRARSLALAEAFGAPLSVVVDNvdAPGTLDS 182

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1155024105 175 LAHSLNIVgtrTLVVEMGVGMRITSE---YGEaliDGIFNLMKHLGM 218
Cdd:cd06252   183 AAERAGKI---FVSTELGGGGTVTPAalrIAE---RGVLNVLIHLGV 223
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 30-306 3.57e-19

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: 85.48  E-value: 3.57e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  30 KRLCIVTGTHGDELEGQYVAF-LLNSILSRDDAlaclnGSVEIYPALNPLGIDSITRGVPNfdiDMNRIFPGS-LGGSLV 107
Cdd:pfam04952   3 PTLLLSAGIHGNETNGVELLRrLLRQLDPGDIA-----GERTLVPLANPPAFRAGSRYIPR---DLNRSFPGRaLGASSD 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 108 EAA--------AHYI-VEDLRGADLVIDIHSSNIFLNEIPQVRICVNQ-QSELVPLANLLNVDFV-WVH--DAATVLEST 174
Cdd:pfam04952  75 EPYratraerlADLFfPALLPRADIVLDLHTGTRGMGHLLFALAPIRDdPLHLLALLRAFGAPAVlKLHskPSAGFSAFS 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 175 LAHSlnivGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHLGMWSGSVSENIK---TPILSVKDEVEFVNASSSGVFVT 251
Cdd:pfam04952 155 AEEL----GAPGFTLELGGAGPFGANLISRTAAGVLNVLRLIGVLNGGPDAFEPpklYRVLREIDRPRDIRAELAGLVEF 230

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1155024105 252 RYSNNCMVKKGESIGR--IISSLTGEIIEdVKAPTDGLMFTLRAYPVVYEGSLLARI 306
Cdd:pfam04952 231 ALNLGDDVDAGPLLPGgpLFAPFGGEETE-YRAPEDGYPVFPNEAAYVGKGAALALV 286
M14_ASTE_ASPA-like cd06254
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 22-216 5.89e-15

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: 71.84  E-value: 5.89e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  22 VIRNGNSSKRLCIVTGTHGDElegqYVAFLLNSILSRDDALACLNGSVEIYPALNPLGIDSITRG-VPNFDIDMNRIFPG 100
Cdd:cd06254     4 LINGAKPGPTLLITAGIHGGE----YPGILAAIRLARELDPADVKGTLIIVHIANVSGFEARTPFvVPEDGKNLNRVFPG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 101 SLGGSLVEAAAHYIVEDL-RGADLVIDIHSSNIFLNEIPQVRICVNQQSELVP----LANLLNVDFVWVHDA--ATVLES 173
Cdd:cd06254    80 DPDGTLTERIAYFLTREIiSRADFLIDLHGGDANEALTPFVYYPGGASEEVNDisraAAQALGLPYIVISSSekGTGYYS 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1155024105 174 TLAHSlnivGTRTLVVEMGVGMRITSEYGEALIDGIFNLMKHL 216
Cdd:cd06254   160 YAALR----GIPSILVERGGLGTCDEEDVQAHKDGIKNLLRHL 198
M14_ASTE_ASPA_like cd18430
Succinylglutamate desuccinylase/aspartoacylase; uncharacterized; A functionally ...
 32-130 1.96e-08

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


Pssm-ID: 349486 [Multi-domain]  Cd Length: 168  Bit Score: 52.83  E-value: 1.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  32 LCIVTGTHGDELEGQYVaflLNSILSRDDALACLNGSVEIYPAlNPLgidSITRGVPNFDIDMNRIFPGSLGGSLVEAA- 110
Cdd:cd18430     1 LAVLGAVHGNETCGTRA---VERLLAELPSGALQKGPVTLVPA-NER---AYAEGVRFCEEDLNRVFPGDPDPDTYERRl 73

                          90       100
                  ....*....|....*....|
gi 1155024105 111 AHYIVEDLRGADLVIDIHSS 130
Cdd:cd18430    74 ANRLCPELEGHDVVLDLHST 93
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 28-99 8.57e-08

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: 51.89  E-value: 8.57e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1155024105  28 SSKRLCIVTGTHGDELEGQYVAFLLNSILSRDDALACLNgsVEIYPALNPLGIDSITRGVPNfDIDMNRIFP 99
Cdd:cd06904    22 SRARILIIGGIHGDEPEGVSLVEHLLRWLKNHPASGDFH--IVVVPCLNPDGLAAGTRTNAN-GVDLNRNFP 90
M14_ASTE_ASPA_like cd18174
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 32-213 1.80e-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: 349484  Cd Length: 187  Bit Score: 50.32  E-value: 1.80e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  32 LCIVTGTHGDElegqYVAFL-LNSILSRDDALAcLNGSVEIYPALNPLGIDSITRGV-PNFDIDMNRIFPGSLGGSLVEA 109
Cdd:cd18174     1 LLVTAGVHGYE----YASIEaLQRLIKELDPAK-LSGTVIVVPIANIPAFEGRSIYVnPLDGKNLNRSFPGDPDGTPTER 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 110 AAHYIVEDL-RGADLVIDIHSSNifLNE--IPQVrIC-------VNQQSELVPLAnlLNVDFVWVHDAATVLE------S 173
Cdd:cd18174    76 LAHWLTTNViARADYYIDLHGGD--LNEdlRPFV-YYyetgnaaLDAASREMAEA--FGLDHIVFYKARLKASrgslytQ 150

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1155024105 174 TLAHSLNIVgtrTLVVEMGVGMRITSEYGEALIDGIFNLM 213
Cdd:cd18174   151 AAALLRGIP---AILVEAGGLGSRDEEDVARHVEGVLNVL 187
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 22-128 3.48e-06

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: 47.30  E-value: 3.48e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  22 VIRNGNSSK-RLCIVTGTHGDELEGQY--VAFLlnsilsRDDALACLNG-SVEIYPALNPLGIDSITRGvpNFD-IDMNR 96
Cdd:cd06231    34 KSPNPRGDKpRVLISAGIHGDEPAGVEalLRFL------ESLAEKYLRRvNLLVLPCVNPWGFERNTRE--NADgIDLNR 105

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1155024105  97 IF---PGSLGGSLVEAAahyiVEDLRGADLVIDIH 128
Cdd:cd06231   106 SFlkdSPSPEVRALMEF----LASLGRFDLHLDLH 136
M14_CP_Csd4-like cd06243
Peptidase M14 carboxypeptidase Csd4 and similar proteins; This family includes peptidase M14 ...
 29-128 1.46e-04

Peptidase M14 carboxypeptidase Csd4 and similar proteins; This family includes peptidase M14 carboxypeptidase Csd4 from H. pylori which has been shown to be DL-carboxypeptidase with a modified zinc binding site containing a glutamine residue in place of a conserved histidine. It is an archetype of a new carboxypeptidase subfamily with a domain arrangement that differs from this family of peptide-cleaving enzymes. Csd4 plays a role in trimming uncrosslinked peptidoglycan peptide chains by cleaving the amide bond between meso-diaminopimelate and iso-D-glutamic acid in truncated peptidoglycan side chains. It acts as a cell shape determinant, similar to Campylobacter jejuni Pgp1. The M14 family of metallocarboxypeptidases (MCPs), also known as funnelins, are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.


Pssm-ID: 349462  Cd Length: 227  Bit Score: 42.35  E-value: 1.46e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  29 SKRLCIVTGTHGDELEGQYVAFLLNSILSRddalaclNGSVEIYPALNPLgidSITRGVPNFDIDMNRIFpgslgGSLVE 108
Cdd:cd06243    16 GPTLLIIGGIQGDEPGGFLAADLLADLYLV-------KGNVIVVPRLNFP---SILRNHRGLNGDMNRKF-----AALDK 80

                          90       100
                  ....*....|....*....|....*..
gi 1155024105 109 AAAHY-IVEDLRG------ADLVIDIH 128
Cdd:cd06243    81 KDPEYkTIQEIKSliadfrPDVVLHLH 107
M14_ASPA cd06909
Peptidase M14 Aspartoacylase (ASPA) subfamily; Aspartoacylase (ASPA) belongs to the ...
 30-131 3.98e-04

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: 40.65  E-value: 3.98e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  30 KRLCIVTGTHGDELEGQYvafLLNSILSRDDALAClnGSVEIYPAL-NPLGIDSITRGVpnfDIDMNRIF-----PGSLG 103
Cdd:cd06909     1 KRVAIVGGTHGNELTGVY---LVKHWLKNPELIER--KSFEVHPLLaNPRAVEQCRRYI---DTDLNRCFslenlSSAPS 72

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1155024105 104 GSLVEAA-AHYIVEDLRGA-----DLVIDIHS--SN 131
Cdd:cd06909    73 SLPYEVRrAREINQILGPKgnpacDFIIDLHNttSN 108
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 39-99 7.74e-04

Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes only plant members of the carboxypeptidase (CP) N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs). It includes Arabidopsis thaliana SOL1 carboxypeptidase D which is known to possess enzymatic activity to remove the C-terminal arginine residue of CLE19 proprotein in vitro, and SOL1-dependent cleavage of the C-terminal arginine residue is necessary for CLE19 activity in vivo. The M14 family are zinc-binding 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.


Pssm-ID: 349482 [Multi-domain]  Cd Length: 276  Bit Score: 40.47  E-value: 7.74e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1155024105  39 HGDELEGQYVAFLLNSIL----SRDDALACL---NGSVEIYPALNPLGIDSITRGVPNfDIDMNRIFP 99
Cdd:cd18172    61 HGDEPVGRELLLRLADWLcanyKAKDPLAAKiveNAHLHLVPTMNPDGFARRRRNNAN-NVDLNRDFP 127
AstE COG2988
Succinylglutamate desuccinylase [Amino acid transport and metabolism];
28-129 8.13e-04

Succinylglutamate desuccinylase [Amino acid transport and metabolism];


Pssm-ID: 442227  Cd Length: 305  Bit Score: 40.60  E-value: 8.13e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  28 SSKRLCIVTGTHGDELEGQYvafLLNSILsRDDALACLNGSVEIYPAL-NPLGIDSITRGVpnfDIDMNRIFPGSLGGS- 105
Cdd:COG2988    23 GIKAVVISGGIHGNETAPIE---LLDKLL-QDLLLGERPLSFRLLLILgNPAAMRAGRRYL---DEDLNRLFGGRHLQNp 95

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1155024105 106 ----------LVEAAAHYIVEDLRgADLVIDIHS 129
Cdd:COG2988    96 esyeaarakeLEQAVGPFFAAGGR-VRLHIDLHT 128
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 34-134 2.31e-03

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: 38.59  E-value: 2.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  34 IVTGTHGDELEGQYVAF-LLNSILSR--DDALACLNGSVEIY--PALNPLGIDSIT--------RGVpnfdiDMNRIFPG 100
Cdd:cd00596     3 ITGGIHGNEVIGVELALaLIEYLLENygNDPLKRLLDNVELWivPLVNPDGFARVIdsggrknaNGV-----DLNRNFPY 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1155024105 101 SLG-----------------GSLVEAAAHYIVEDLRGADLVIDIHSSNIFL 134
Cdd:cd00596    78 NWGkdgtsgpssptyrgpapFSEPETQALRDLAKSHRFDLAVSYHSSSEAI 128
M14_PaAOTO_like cd06250
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like subfamily; ...
 39-132 4.08e-03

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: 37.99  E-value: 4.08e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105  39 HGDELEGQYVAFLLNSILSRDDALACLNGSVEIYPALNPLGI------------DSITRGvpNFdidmNRIFP------- 99
Cdd:cd06250    37 HADELPGNLVIHHLLERLKALEAAGRIKGEIVLVPQANPIGLsqkiggyhqgrfDLATGD--NF----NRNFPdlakava 110

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1155024105 100 GSLGGSLVEAAAHYI-------------------VEDLR--------GADLVIDIHSSNI 132
Cdd:cd06250   111 ARVEERLGDDAAANValiraalkealdalpprteLQRLKltllrlalDADIVLDLHCDDE 170
 
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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