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 767914974   10 FSSRFDSGNLAHVEkveslssdgegvgggasaltsgiASSPDyEFNVWTRPDcAETEFengnRSWFYFSVRGGmPGKLIK 89
Cdd:pfam18027   1 ISSNFDSGNIEVVS-----------------------ASDPD-AIRLRIRPD-NGSEH----FQWFYFRVSGA-RGRPLT 50

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974   90 INIMNMNKQSklYSQGMAPFVRTLPT-RPRWERIrdrptfemtETQF---VLSFVHRFVegrGATTFFAF 155
Cdd:pfam18027  51 FVIENAGEAS--YPDGWTGYRVVASYdRENWFRV---------PTEYdggVLTITHTPE---ADTVYFAY 106

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 159 FSYSDCQELLNQLDQRFPenhpthsspldtiYYHRELLCYSLDGLRVDLLTITSchglredreprleqlfpdtstprpfR 238
Cdd:COG2866   20 YTYEELLALLAKLAAASP-------------LVELESIGKSVEGRPIYLLKIGD-------------------------P 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 239 FAGKRIFFLSSRVHPGETPSSFVFNGFLDFILRPDDPRAQTLRRLFVFKLIPMLNPDGVVRgHYRTDSRGVNLNRQYLKP 318
Cdd:COG2866   62 AEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAP 140

                 ..
gi 767914974 319 DA 320
Cdd:COG2866  141 WL 142

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974  232 STPRPFRFAGKRIFFLSSRVHPGETPSSFVFNGFLDFILRP--DDPRAQTLRRLFVFKLIPMLNPDGVVRGHY------- 302
Cdd:pfam00246  36 SSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygRDPEITELLDDTDIYILPVVNPDGYEYTHTtdrlwrk 115

                          90
                  ....*....|....*....
gi 767914974  303 -RTDSR-----GVNLNRQY 315
Cdd:pfam00246 116 nRSNANgssciGVDLNRNF 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 767914974 189 IYYHRELLCYSLDGLRVDLLTITSCHGLREdreprleqlfpdtsTPRPFRFAGKRIFFLSSRVHPGETPSSFVFNGFLDF 268
Cdd:cd06235    1 IYFEREVLCHSLDGRKLDLLTITSPNNKKL--------------GPYPREFAGKKVVFLSGRVHPGETPASFVMKGFLDF 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 269 ILRPDdPRAQTLRRLFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKPDAVLHPAIYGAKAVLLYHHVHsrlnsqsss 348
Cdd:cd06235   67 LLSND-PRAQLLREHFVFKIVPMLNPDGVIRGNYRCSLNGFNLNRHYKNPDPELHPTIYGAKKVIDYLQKT--------- 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 349 ehqpssclppdapvsdlekannlqneaqcghsadrhnaeawkqtepaeqklnsvwimpqqsagleesapdtippKESGVA 428
Cdd:cd06235  137 --------------------------------------------------------------------------YKRRVL 142

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 429 YYVDLHGHASKRGCFMYGNSFSDESTQVENMLYPKLISLNSAHFDFQGCNfseknmyarDRRDGQSKEGSGRVAIYKASG 508
Cdd:cd06235  143 MYCDFHGHSSKSNGFMYGNSFPDTVQFHWNMVFPKILSLNAPDFFSSSCC---------SFGVMKSKEGTGRVVFGRRLI 213

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 509 IIHSYTLECNYNTGRSVNSIpAACHdngraspppppafpsrYTVELFEQVGRAMAIAALD 568
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 767914974 190 YYHRELLCYSLDGLRVDLLTITSchglrEDREPRLEQLFpdtstprpfrfagKRIFFLSSRVHPGETPSSFVFNGFLDFI 269
Cdd:cd06908    2 FFTRELLGKSVQQRRLDLLTITD-----PVNKHLTVEKK-------------KKVVFITARVHPGETPSSFVCQGLIDFL 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 270 LRpDDPRAQTLRRLFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKPDAVLHPAIYGAKAVLLyhhvhsRLNSQSSSE 349
Cdd:cd06908   64 VS-NHPVAKVLRDHLVFKIVPMLNPDGVFLGNYRCSLMGFDLNRHWHEPSPWAHPTLYAVKNLLR------ELDNDPTVQ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 350 hqpssclppdapvsdlekannlqneaqcghsadrhnaeawkqtepaeqklnsvwimpqqsagleesapdtippkesgVAY 429
Cdd:cd06908  137 -----------------------------------------------------------------------------LDF 139

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 430 YVDLHGHASKRGCFMYGNSFSDESTQVENMLYPKLISLNSAHFDFQGCNFSeknmyaRDrrdgQSKEGSGRVAIykaSGI 509
Cdd:cd06908  140 YIDIHAHSTLMNGFMYGNIYDDVYRFERQAVFPKLLCQNAEDFSLSNTVFN------RD----PVKAGTGRRFL---GGL 206

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767914974 510 I----HSYTLECN---YNTGRSVNSIPaachdngraspppppafpsrYTVELFEQVGRAMAIAALD 568
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 767914974 188 TIYYHRELLCYSLDGLRVDLLTITSchglredrEPRLEQLFPDTSTP-RPFrfagkriFFLSSRVHPGETPSSFVFNGFL 266
Cdd:cd06906    2 QIYYRQQTLCETLGGNSCPVLTITA--------MPESNNEEHICQFRnRPY-------IFLSARVHPGESNASWVMKGTL 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 267 DFILRpDDPRAQTLRRLFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKPDAVLHPAIYGAKAVLLYhhvhsrlnsqs 346
Cdd:cd06906   67 DFLLS-SSPAAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQY----------- 134

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 347 ssehqpssclppdapvsdlekannlqneaqcghsadrhnaeawkqtepaeqkLNSVWIMPqqsagleesapdtippkesg 426
Cdd:cd06906  135 ----------------------------------------------------LRSIGRLP-------------------- 142

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 427 vAYYVDLHGHASKRGCFMYGNSFSDESTQ----------VENMLY---PKLISLNSAHFDFQGCNFS-EKnmyardrrdg 492
Cdd:cd06906  143 -LVYCDYHGHSRKKNVFMYGCSPKESWSHgdtnnpsgdiVEDLGYrtlPKLLSHFAPAFSLSSCSFVvEK---------- 211

                        330       340
                 ....*....|....*....|....*..
gi 767914974 493 qSKEGSGRVAIYKASGIIHSYTLECNY 519
Cdd:cd06906  212 -SKESTARVVVWREIGVLRSYTMESTY 237

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 159 FSYSDCQELLNQLDQRFPenhpthsspldtiYYHRELLCYSLDGLRVDLLTITSchglredreprleqlfpdtstprpfR 238
Cdd:COG2866   20 YTYEELLALLAKLAAASP-------------LVELESIGKSVEGRPIYLLKIGD-------------------------P 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974 239 FAGKRIFFLSSRVHPGETPSSFVFNGFLDFILRPDDPRAQTLRRLFVFKLIPMLNPDGVVRgHYRTDSRGVNLNRQYLKP 318
Cdd:COG2866   62 AEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAP 140

                 ..
gi 767914974 319 DA 320
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 767914974 240 AGKRIFfLSSRVHPGETPSSFVFNGFLDFILRPDDPRAQTLRRlFVFKLIPMLNPDGVVRGHYRTDSRGVNLNRQYLKP- 318
Cdd:cd18429   39 APHRVF-LRARAHPWEAGGNWVVEGLVERLLQNDEEAKRFLKR-YCVYILPMANKDGVARGRTRFNANGKDLNREWDKPa 116

                 ....*.
gi 767914974 319 DAVLHP 324
Cdd:cd18429  117 DPVLAP 122

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914974  232 STPRPFRFAGKRIFFLSSRVHPGETPSSFVFNGFLDFILRP--DDPRAQTLRRLFVFKLIPMLNPDGVVRGHY------- 302
Cdd:pfam00246  36 SSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygRDPEITELLDDTDIYILPVVNPDGYEYTHTtdrlwrk 115

                          90
                  ....*....|....*....
gi 767914974  303 -RTDSR-----GVNLNRQY 315
Cdd:pfam00246 116 nRSNANgssciGVDLNRNF 134

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 767914974 245 FFLSSRVHPGETPSSFVFNGFLDFIL--RPDDPRAQTL--RRLFVfklIPMLNPDGVVRGHY---RTDSRGVNLNRQY 315
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALIEYLLenYGNDPLKRLLdnVELWI---VPLVNPDGFARVIDsggRKNANGVDLNRNF 75

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 767914974 245 FFLSSRVHPGETPSSFVFNGFLDFILR--PDDPRAQTLRRLFVFKLIPMLNPDG-------VVRGHYRTDSRGVNLNRQY 315
Cdd:cd18173   57 FKYTSTMHGDETTGYELMLRLIDYLLTnyGTDPRITNLVDNTEIWINPLANPDGtyaggnnTVSGATRYNANGVDLNRNF 136

                 ....*....
gi 767914974 316 LKPDAVLHP 324
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 767914974 232 STPRPFRFAGKRIFfLSSRVHpGETPSSfVFnGFLDFIlrpDDPRAQTLRRlFVFKLIPMLNPDGVVRGHyRTDSRGVNL 311
Cdd:cd06231   33 LKSPNPRGDKPRVL-ISAGIH-GDEPAG-VE-ALLRFL---ESLAEKYLRR-VNLLVLPCVNPWGFERNT-RENADGIDL 103

                         90
                 ....*....|....*
gi 767914974 312 NRQYLKPDAVLHPAI 326
Cdd:cd06231  104 NRSFLKDSPSPEVRA 118

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767914974 249 SRVHpGETPSSFvfNGFLDFI--LRPDDPRAQTLRRLFVFKLIPMLNPDGVVRgHYRTDSRGVNLNR 313
Cdd:cd06239    6 SQMH-GNEPTGT--EALLDLIsyLRRERQEFEKILERLTLVAIPMLNPDGAEL-FTRHNAEGIDLNR 68