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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  36 IPIHIFNSKKPGPILFVCAGIHGDEISGVEIVRHLLKLNVIKNLsKGTLIAAPIVNIYGFIYQSRYLPD-RRDLNRNFPG 114
Cdd:cd06251    1 VPVLVARGAKPGPTLLLTAAIHGDELNGIEVIQRLLEDLDPSKL-RGTLIAIPVVNPLGFENNSRYLPDdGRDLNRSFPG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310 115 LRKGSLASRLAKLFIDEIVSHCTHGIDLHSAAVHRRNLPQIRVNLTQPGTEKLARAFGAPVILDSNLRDGSLRQAANEMN 194
Cdd:cd06251   80 SEKGSLASRLAHLLWNEIVKKADYVIDLHTASTGRTNLPYVRADLRDPESRRMAEAFGAPVIVDDPGEDGSLRGAAVELG 159

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 492183310 195 IPVLIYEAGEALRFDEAPIRLGVRGILRVMRELGML 230
Cdd:cd06251  160 IPAITVELGEALRFDEDIIRRGVEGVLNVLRHLGML 195

Zn_pept domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310    38 IHIFNSKKPG-PILFVCAGIHGDEISGVEIVRHLLKL---------NVIKNLSKGTLIAAPIVNIYGFIY---QSRYLPD 104
Cdd:smart00631  39 LKISNGGSHDkPAIFIDAGIHAREWIGPATALYLINQllenygrdpRVTNLLDKTDIYIVPVLNPDGYEYthtGDRLWRK 118

                           90
                   ....*....|....*...
gi 492183310   105 RR---------DLNRNFP 113
Cdd:smart00631 119 NRspnsncrgvDLNRNFP 136

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  36 IPIHIFNSKKPGPILFVCAGIHGDEISGVEIVRHLLKLNVIKNLsKGTLIAAPIVNIYGFIYQSRYLPD-RRDLNRNFPG 114
Cdd:cd06251    1 VPVLVARGAKPGPTLLLTAAIHGDELNGIEVIQRLLEDLDPSKL-RGTLIAIPVVNPLGFENNSRYLPDdGRDLNRSFPG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310 115 LRKGSLASRLAKLFIDEIVSHCTHGIDLHSAAVHRRNLPQIRVNLTQPGTEKLARAFGAPVILDSNLRDGSLRQAANEMN 194
Cdd:cd06251   80 SEKGSLASRLAHLLWNEIVKKADYVIDLHTASTGRTNLPYVRADLRDPESRRMAEAFGAPVIVDDPGEDGSLRGAAVELG 159

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 492183310 195 IPVLIYEAGEALRFDEAPIRLGVRGILRVMRELGML 230
Cdd:cd06251  160 IPAITVELGEALRFDEDIIRRGVEGVLNVLRHLGML 195

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  50 LFVCAGIHGDEISGVEIVRHLLK-LNVIKnlSKGTLIAAPIVNIYGFIYQSRYLP-DRRDLNRNFPGLRKGSLASRLAKL 127
Cdd:cd06230    1 LLILAGVHGDEYEGVEAIRRLLAeLDPSE--LKGTVVLVPVANPPAFEAGTRYTPlDGLDLNRIFPGDPDGSPTERLAHE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310 128 FIDEIVSHCTHGIDLHSAAVHrRNLPQIRVNLTQPGTEK---LARAFG-APVILDSNLRDGSLRQAANEMNIPVLIYEAG 203
Cdd:cd06230   79 LTELILKHADALIDLHSGGTG-RLVPYAILDYDSDAREKsreLARAFGgTPVIWGGDPPGGTPVAAARSAGIPAITVELG 157

                        170       180
                 ....*....|....*....|
gi 492183310 204 EALRFDEAPIRLGVRGILRV 223
Cdd:cd06230  158 GGGRLRAERLERYLRGIRNV 177

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  37 PIHIFNSKKPGPILFVCAGIHGDEISGVEIVRHLlklnvIKNLS----KGTLIAAPIVNIYGFIYQSRYL-P-DRRDLNR 110
Cdd:cd06254    1 PVTLINGAKPGPTLLITAGIHGGEYPGILAAIRL-----ARELDpadvKGTLIIVHIANVSGFEARTPFVvPeDGKNLNR 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310 111 NFPGLRKGSLASRLAKLFIDEIVSHCTHGIDLHS----------AAVHRRNLPQIRvnltqPGTEKLARAFGAPVIL--D 178
Cdd:cd06254   76 VFPGDPDGTLTERIAYFLTREIISRADFLIDLHGgdanealtpfVYYPGGASEEVN-----DISRAAAQALGLPYIVisS 150

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 492183310 179 SNLRDGSLRQAANeMNIPVLIYEAGEALRFDEAPIRLGVRGILRVMREL 227
Cdd:cd06254  151 SEKGTGYYSYAAL-RGIPSILVERGGLGTCDEEDVQAHKDGIKNLLRHL 198

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  50 LFVCAGIHGDEISGVEIVRHLLKLNVIKNLSkGTLIAAPIVNIYGFIYQSRYL-P-DRRDLNRNFPGLRKGSLASRLAKL 127
Cdd:cd18174    1 LLVTAGVHGYEYASIEALQRLIKELDPAKLS-GTVIVVPIANIPAFEGRSIYVnPlDGKNLNRSFPGDPDGTPTERLAHW 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310 128 FIDEIVSHCTHGIDLHSAAVHRRNLPQIRVNLTQPG-----TEKLARAFGAPVIL-------DSNLRDGSLRQAANeMNI 195
Cdd:cd18174   80 LTTNVIARADYYIDLHGGDLNEDLRPFVYYYETGNAaldaaSREMAEAFGLDHIVfykarlkASRGSLYTQAAALL-RGI 158

                        170       180
                 ....*....|....*....|....*....
gi 492183310 196 PVLIYEAGEALRFDEAPIRLGVRGILRVM 224
Cdd:cd18174  159 PAILVEAGGLGSRDEEDVARHVEGVLNVL 187

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  37 PIHI--FNSKKPGPILFVcAGIHGDEISGVEIVRHLLKLNVIKNLSKGTLIA-APIVNIYGFIYQSRYLPDRRDLNRNFP 113
Cdd:cd06904   12 PILAykFGPGSRARILII-GGIHGDEPEGVSLVEHLLRWLKNHPASGDFHIVvVPCLNPDGLAAGTRTNANGVDLNRNFP 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310 114 --GLRKGSLASRLAKLF-----------------IDE-----IVShcthgidLHSAAVhrrnlpqirVNLTQPG----TE 165
Cdd:cd06904   91 tkNWEPDARKPKDPRYYpgpkpasepetralvelIERfkpdrIIS-------LHAPYL---------VNYDGPAksllAE 154

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 492183310 166 KLARAFGAPVILDSNLRDGSLRQ-AANEMNIPVLIYEAGEALRFDEAPIRLG 216
Cdd:cd06904  155 KLAQATGYPVVGDVGYTPGSLGTyAGIERNIPVITLELPEAVSIDELWQDLK 206

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  32 TPVDIPIHIFNSKKPGPILFVCAGIHGDEISGVEIVRHLLKLNVIknlsKGTLIAAPIVNIYGFIYQSRYLpdRRDLNRN 111
Cdd:cd06243    1 EDIEKPFTRLEGREPGPTLLIIGGIQGDEPGGFLAADLLADLYLV----KGNVIVVPRLNFPSILRNHRGL--NGDMNRK 74

                 .
gi 492183310 112 F 112
Cdd:cd06243   75 F 75

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 492183310  50 LFVCAGIHGDEISGVEIVRHLLK-------LNVIKNLSKGT-LIAAPIVNIYGFIY----QSRYLPDRRDLNRNFP 113
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALIEyllenygNDPLKRLLDNVeLWIVPLVNPDGFARvidsGGRKNANGVDLNRNFP 76

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  49 ILFVCaGIHGDEISGVE----IVRHL----LKLNViknLSKGTLIAAPIVNIYGFIYQSRYLPDRRDLNRNFPGLRkgSL 120
Cdd:cd06242    4 VLLVG-QQHGNEPAGREaalaLARDLafgdDAREL---LEKVNVLVVPRANPDGRAANTRGNANGVDLNRDHLLLS--TP 77

                         90       100
                 ....*....|....*....|....*..
gi 492183310 121 ASR-LAKLFID---EIVshcthgIDLH 143
Cdd:cd06242   78 ETRaLARVLRDyrpEVV------IDAH 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  15 PGEHLSIRLPTPKLftytpvdipIHIfNSKKPGPiLFVCAGIHGDEISGVEIVRHLLKLNviknlsKGTLIAAP---IVN 91
Cdd:cd06256   13 PAAELLENLPGPTL---------IHL-PGRRPRP-LFVSTLLHGNEPTGLRAVQRLLKTG------QAPLPRTLllfIGN 75

                         90       100
                 ....*....|....*....|...
gi 492183310  92 IYGFIYQSRYLPDRRDLNRNFPG 114
Cdd:cd06256   76 VDAAKAGVRRLPGQPDYNRCWPG 98

Succinylglutamate desuccinylase [Amino acid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  50 LFVCAGIHGDEISGVEIVRHLLklnviKNLSKGTLI-AAPIVNIYG----FIYQSRYLPdrRDLNRNFPG---------- 114
Cdd:COG2988   27 VVISGGIHGNETAPIELLDKLL-----QDLLLGERPlSFRLLLILGnpaaMRAGRRYLD--EDLNRLFGGrhlqnpesye 99

                         90       100       110
                 ....*....|....*....|....*....|..
gi 492183310 115 -LRKGSLASRLAKlFIDEIVSHCTHgIDLHSA 145
Cdd:COG2988  100 aARAKELEQAVGP-FFAAGGRVRLH-IDLHTA 129

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  52 VCAGIHGDEISGVEIVRHLLK---LNVIKNLSKGTLIAAPIvniyGFIYQSRYLpDrRDLNRNF----------PGLRKG 118
Cdd:cd06909    5 IVGGTHGNELTGVYLVKHWLKnpeLIERKSFEVHPLLANPR----AVEQCRRYI-D-TDLNRCFslenlssapsSLPYEV 78

                         90       100
                 ....*....|....*....|....*.
gi 492183310 119 SLASRLAKLFIDEIVSHCTHGIDLHS 144
Cdd:cd06909   79 RRAREINQILGPKGNPACDFIIDLHN 104

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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  48 PILFVCAGIHGDEISGVE----IVRHLLKLNVIKNLSKGTLIAAPIVNIYGFIYQSRYLPDRR---------------DL 108
Cdd:cd06241    2 PVVLIQAGIHPGEVEGKEaslmLLRDIAQGGKKHLLDNLILLFVPIFNADGNDRRSKGNRPNQngplevgwrtnaqglDL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 492183310 109 NRNFPGLRK---GSLASRLAK----LFIDeivSHCTHGID 141
Cdd:cd06241   82 NRDFMKLEApetRALAKLFNQwdpdLFID---THTTDGSD 118

aspartoacylase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492183310  49 ILFVcAGIHGDEISGVEIVRHLLK-LNVI--KNLSKGTLIAAPIVniygfIYQS-RYLpdRRDLNRNFpglRKGSLAS-- 122
Cdd:PRK02259   5 VAIV-GGTHGNEITGIYLVKKWQQqPNLInrKGLEVQTVIGNPEA-----IEAGrRYI--DRDLNRSF---RLDLLQNpd 73

                         90       100       110
                 ....*....|....*....|....*....|..
gi 492183310 123 ------RLAKLFIDEIVSH----CTHGIDLHS 144
Cdd:PRK02259  74 lsgyeqLRAKELVQQLGPKgnspCDFIIDLHS 105