Cytosolic carboxypeptidase N-terminal domain; This entry corresponds to the N-terminal domain of cytosolic carboxypeptidases. The N-terminal domain folds into a nine-stranded antiparallel beta sandwich. This domain is specific to CCP proteins and is absent in other carboxypeptidases. It has been hypothesized that the N-terminal domain might contribute to folding, might have a regulatory function and/or might be involved in binding other proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051   10 FSSRFDSGNLahvEKVETVSSDgegvggvatapasgsaaspdyEFNVWTRPDcAETEYengnRSWFYFSVRGGTPGKLIk 89
Cdd:pfam18027   1 ISSNFDSGNI---EVVSASDPD---------------------AIRLRIRPD-NGSEH----FQWFYFRVSGARGRPLT- 50

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568934051   90 INIMNMNKQSklYSQGMAPFvRTLPS--RPRWERI 122
Cdd:pfam18027  51 FVIENAGEAS--YPDGWTGY-RVVASydRENWFRV 82

Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 188 FSYSDCQDLLSQLDQRfsenysthsspldSIYYHRELLCYSLDGLRVDLLTITSchglrddreprleqlfpdlgtprpfR 267
Cdd:COG2866   20 YTYEELLALLAKLAAA-------------SPLVELESIGKSVEGRPIYLLKIGD-------------------------P 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 268 FTGKRIFFLSSRVHPGETPSSFVFNGFLDFILRPDDPRAQTLRRLFVFKLIPMLNPDGVVRgHYRTDSRGVNLNRQYLKP 347
Cdd:COG2866   62 AEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAP 140

                 ..
gi 568934051 348 DA 349
Cdd:COG2866  141 WL 142

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051  260 LGTPRPFRFTGKRIFFLSSRVHPGETPSSFVFNGFLDFILRP--DDPRAQTLRRLFVFKLIPMLNPDGVVRGHY------ 331
Cdd:pfam00246  35 ISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygRDPEITELLDDTDIYILPVVNPDGYEYTHTtdrlwr 114

                          90       100
                  ....*....|....*....|
gi 568934051  332 --RTDSR-----GVNLNRQY 344
Cdd:pfam00246 115 knRSNANgssciGVDLNRNF 134

Peptidase M14-like domain of human Nna1/AGTPBP-1, AGBL2 -5, and related proteins; Subgroup of the Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP), and related proteins. The Peptidase M14 family of metallocarboxypeptidases 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. This eukaryotic subgroup includes the human Nna1/AGTPBP-1 and AGBL -2, -3, -4, and -5, and the mouse Nna1/CCP-1 and CCP -2 through -6. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Nna1 is widely expressed in the developing and adult nervous systems, including cerebellar Purkinje and granule neurons, miral cells of the olfactory bulb and retinal photoreceptors. Nna1 is also induced in axotomized motor neurons. Mutations in Nna1 cause Purkinje cell degeneration (pcd). The Nna1 CP domain is required to prevent the retinal photoreceptor loss and cerebellar ataxia phenotypes of pcd mice, and a functional zinc-binding domain is needed for Nna-1 to support neuron survival in these mice. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 218 IYYHRELLCYSLDGLRVDLLTITSCHGLRDdreprleqlfpdlgTPRPFRFTGKRIFFLSSRVHPGETPSSFVFNGFLDF 297
Cdd:cd06235    1 IYFEREVLCHSLDGRKLDLLTITSPNNKKL--------------GPYPREFAGKKVVFLSGRVHPGETPASFVMKGFLDF 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 298 ILRPDdPRAQTLRRLFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKPDAVLHPAIYGAKAVLLYHHVHsrlnakspt 377
Cdd:cd06235   67 LLSND-PRAQLLREHFVFKIVPMLNPDGVIRGNYRCSLNGFNLNRHYKNPDPELHPTIYGAKKVIDYLQKT--------- 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 378 nqqptlhlppeaplsdlekannlhneahlgqspdgenpatwpetepaeektdpvwlmpqpipeleepapdtippKESGVA 457
Cdd:cd06235  137 --------------------------------------------------------------------------YKRRVL 142

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 458 YYVDLHGHASKRGCFMYGNSFSDESTQVENMLYPKLISLNSAHFDFQGCNfseknmyarDRRDGQSKEGSGRVAIYKASG 537
Cdd:cd06235  143 MYCDFHGHSSKSNGFMYGNSFPDTVQFHWNMVFPKILSLNAPDFFSSSCC---------SFGVMKSKEGTGRVVFGRRLI 213

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 538 IIHSYTLECNYNTGRSVNSIpAACHdngraspppppafpsrYTVELFEQVGRAMAIAALD 597
Cdd:cd06235  214 HSHSYTLESTFFSNNRGNID-GACG----------------YTEENLEDLGYSVASTLLD 256

Peptidase M14-like domain of ATP/GTP binding protein AGBL-4 and related proteins; Peptidase M14-like domain of ATP/GTP binding protein_like (AGBL)-4, and related proteins. The Peptidase M14 family of metallocarboxypeptidases 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. This eukaryotic subgroup includes the human AGBL4 and the mouse cytosolic carboxypeptidase (CCP)-6. ATP/GTP binding protein (AGTPBP-1/Nna1)-like proteins are active metallopeptidases that are thought to act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Mutations in AGTPBP-1/Nna1 cause Purkinje cell degeneration (pcd). AGTPBP-1/Nna1 however does not belong to this subgroup. AGTPBP-1/Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 219 YYHRELLCYSLDGLRVDLLTITSchglrDDREPRLEQLFpdlgtprpfrftgKRIFFLSSRVHPGETPSSFVFNGFLDFI 298
Cdd:cd06908    2 FFTRELLGKSVQQRRLDLLTITD-----PVNKHLTVEKK-------------KKVVFITARVHPGETPSSFVCQGLIDFL 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 299 LRpDDPRAQTLRRLFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKPDAVLHPAIYGAKAVLLyhhvhsrlnaksptn 378
Cdd:cd06908   64 VS-NHPVAKVLRDHLVFKIVPMLNPDGVFLGNYRCSLMGFDLNRHWHEPSPWAHPTLYAVKNLLR--------------- 127

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 379 qqptlhlppeaplsdlekannlhneaHLGQSPDGEnpatwpetepaeektdpvwlmpqpipeleepapdtippkesgVAY 458
Cdd:cd06908  128 --------------------------ELDNDPTVQ------------------------------------------LDF 139

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 459 YVDLHGHASKRGCFMYGNSFSDESTQVENMLYPKLISLNSAHFDFQGCNFSeknmyaRDrrdgQSKEGSGRVAIykaSGI 538
Cdd:cd06908  140 YIDIHAHSTLMNGFMYGNIYDDVYRFERQAVFPKLLCQNAEDFSLSNTVFN------RD----PVKAGTGRRFL---GGL 206

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568934051 539 I----HSYTLECN---YNTGRSVNSIPaachdngraspppppafpsrYTVELFEQVGRAMAIAALD 597
Cdd:cd06908  207 LddtaNCYTLEVSfysYRLSDSSSATP--------------------YTEEGYMKLGRNMARALLD 252

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP), and related proteins. The Peptidase M14 family of metallocarboxypeptidases 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. This eukaryotic subgroup includes the mouse Nna1/CCP-1, and -4 proteins, and the human Nna1/AGTPBP-1 protein. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Nna1 is widely expressed in the developing and adult nervous systems, including cerebellar Purkinje and granule neurons, miral cells of the olfactory bulb and retinal photoreceptors. Nna1 is also induced in axotomized motor neurons. Mutations in Nna1 cause Purkinje cell degeneration (pcd). The Nna1 CP domain is required to prevent the retinal photoreceptor loss and cerebellar ataxia phenotypes of pcd mice, and a functional zinc-binding domain is needed for Nna-1 to support neuron survival in these mice. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 217 SIYYHRELLCYSLDGLRVDLLTITScHGLRDDREPRLEqlFPDlgtpRPFrftgkriFFLSSRVHPGETPSSFVFNGFLD 296
Cdd:cd06906    2 QIYYRQQTLCETLGGNSCPVLTITA-MPESNNEEHICQ--FRN----RPY-------IFLSARVHPGESNASWVMKGTLD 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 297 FILRpDDPRAQTLRRLFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKPDAVLHPAIYGAKAVLLYhhvhsrLNAksp 376
Cdd:cd06906   68 FLLS-SSPAAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQY------LRS--- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 377 tnqqptlhlppeaplsdlekannlhneahLGQSPdgenpatwpetepaeektdpvwlmpqpipeleepapdtippkesgv 456
Cdd:cd06906  138 -----------------------------IGRLP---------------------------------------------- 142

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 457 AYYVDLHGHASKRGCFMYGNSFSDESTQ----------VENMLY---PKLISLNSAHFDFQGCNFS-EKnmyardrrdgq 522
Cdd:cd06906  143 LVYCDYHGHSRKKNVFMYGCSPKESWSHgdtnnpsgdiVEDLGYrtlPKLLSHFAPAFSLSSCSFVvEK----------- 211

                        330       340
                 ....*....|....*....|....*.
gi 568934051 523 SKEGSGRVAIYKASGIIHSYTLECNY 548
Cdd:cd06906  212 SKESTARVVVWREIGVLRSYTMESTY 237

Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 188 FSYSDCQDLLSQLDQRfsenysthsspldSIYYHRELLCYSLDGLRVDLLTITSchglrddreprleqlfpdlgtprpfR 267
Cdd:COG2866   20 YTYEELLALLAKLAAA-------------SPLVELESIGKSVEGRPIYLLKIGD-------------------------P 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 268 FTGKRIFFLSSRVHPGETPSSFVFNGFLDFILRPDDPRAQTLRRLFVFKLIPMLNPDGVVRgHYRTDSRGVNLNRQYLKP 347
Cdd:COG2866   62 AEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAP 140

                 ..
gi 568934051 348 DA 349
Cdd:COG2866  141 WL 142

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; uncharacterized bacterial subgroup; A bacterial subgroup of the Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP),-like proteins. The Peptidase M14 family of metallocarboxypeptidases 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. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins (such as alpha-tubulin in eukaryotes) to remove a C-terminal tyrosine. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 275 FLSSRVHPGETPSSFVFNGFLDFILRPDDPRAQTLRRlFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKP-DAVLHP 353
Cdd:cd18429   44 FLRARAHPWEAGGNWVVEGLVERLLQNDEEAKRFLKR-YCVYILPMANKDGVARGRTRFNANGKDLNREWDKPaDPVLAP 122

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051  260 LGTPRPFRFTGKRIFFLSSRVHPGETPSSFVFNGFLDFILRP--DDPRAQTLRRLFVFKLIPMLNPDGVVRGHY------ 331
Cdd:pfam00246  35 ISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygRDPEITELLDDTDIYILPVVNPDGYEYTHTtdrlwr 114

                          90       100
                  ....*....|....*....|
gi 568934051  332 --RTDSR-----GVNLNRQY 344
Cdd:pfam00246 115 knRSNANgssciGVDLNRNF 134

Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; 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
                 ....*....|....*....|....*....|....*....|....*
gi 568934051 305 RAQTLRRLFVFKLIPMLNPDG---VVRGHY--RTDSRGVNLNRQY 344
Cdd:cd06227   43 LAREILDNVELKIIPNANPDGrrlVESGDYcwRGNENGVDLNRNW 87

bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial carboxypeptidase (CP) members of the M14 family of metallocarboxypeptidases (MCPs), mostly of which have yet to be characterized. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 274 FFLSSRVHPGETPSSFVFNGFLDFILR--PDDPRAQTLRRLFVFKLIPMLNPDG-------VVRGHYRTDSRGVNLNRQY 344
Cdd:cd18173   57 FKYTSTMHGDETTGYELMLRLIDYLLTnyGTDPRITNLVDNTEIWINPLANPDGtyaggnnTVSGATRYNANGVDLNRNF 136

                 ....*....
gi 568934051 345 LKPDAVLHP 353
Cdd:cd18173  137 PDPVDGDHP 145

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568934051 263 PRPFRFTGKRIFfLSSRVHpGETPSSfVFnGFLDFIlrpDDPRAQTLRRlFVFKLIPMLNPDGVVRGHyRTDSRGVNLNR 342
Cdd:cd06231   35 SPNPRGDKPRVL-ISAGIH-GDEPAG-VE-ALLRFL---ESLAEKYLRR-VNLLVLPCVNPWGFERNT-RENADGIDLNR 105

                         90
                 ....*....|...
gi 568934051 343 QYLKPDAVLHPAI 355
Cdd:cd06231  106 SFLKDSPSPEVRA 118

Peptidase M14-like domain; uncharacterized subfamily; 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 568934051 273 IFFLSSRVHPGETPSSfvfNGFLDFILR---PDDPRAQTLRRlFVFKLIPMLNPDGVVR------------GHYRTDSRG 337
Cdd:cd03857    1 TVLLAAQIHGNETTGT---EALMELIRDlasESDEAAKLLDN-IVILLVPQLNPDGAELfvnfyldsmnglPGTRYNANG 76

                 ....*....
gi 568934051 338 VNLNRQYLK 346
Cdd:cd03857   77 IDLNRDHVK 85