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 386764376  282 FESRFESGNLAKAVQITPTYYELYLRPDlYTSRSKQWFYFRVRRTRRKMlYRFSIVNLvkSDSLYNDGMQPvmYSTlGAK 361
Cdd:pfam18027   1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGARGRP-LTFVIENA--GEASYPDGWTG--YRV-VAS 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 386764376  362 EKSEGWRRCGdniCYYRNDdesasssaneddednstytlTFTIEFEHDDDTVFFAH 417
Cdd:pfam18027  74 YDRENWFRVP---TEYDGG--------------------VLTITHTPEADTVYFAY 106

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 421 YTYSDLQDYLMEIQRhpvKSKFCKLRLLCRTLAGNNVYYLTVTAPSSNeenmrrKKSIVVSARVHPSETPASWMMKGLMD 500
Cdd:COG2866   20 YTYEELLALLAKLAA---ASPLVELESIGKSVEGRPIYLLKIGDPAEG------KPKVLLNAQQHGNEWTGTEALLGLLE 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 501 FI-TGDTTVAKRLRHKFIFKLVPMLNPDGVIVgNTRNSLTGKDLNRQYRTVIrETYPSiwyTKAMiRRLIEECGVAMYCD 579
Cdd:COG2866   91 DLlDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAPW-LSEPE---TRAL-RDLLDEHDPDFVLD 164

                 ..
gi 386764376 580 MH 581
Cdd:COG2866  165 LH 166

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 386764376  282 FESRFESGNLAKAVQITPTYYELYLRPDlYTSRSKQWFYFRVRRTRRKMlYRFSIVNLvkSDSLYNDGMQPvmYSTlGAK 361
Cdd:pfam18027   1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGARGRP-LTFVIENA--GEASYPDGWTG--YRV-VAS 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 386764376  362 EKSEGWRRCGdniCYYRNDdesasssaneddednstytlTFTIEFEHDDDTVFFAH 417
Cdd:pfam18027  74 YDRENWFRVP---TEYDGG--------------------VLTITHTPEADTVYFAY 106

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 386764376 442 FCKLRLLCRTLAGNNVYYLTVTAPSSNEENMR-----RKKSIVVSARVHPSETPASWMMKGLMDFITGDTTVAKRLRHKF 516
Cdd:cd06235    2 YFEREVLCHSLDGRKLDLLTITSPNNKKLGPYprefaGKKVVFLSGRVHPGETPASFVMKGFLDFLLSNDPRAQLLREHF 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 517 IFKLVPMLNPDGVIVGNTRNSLTGKDLNRQYRTVIRETYPSIWYTKAMIRRLIE--ECGVAMYCDMHAHSRKHNIFIYGC 594
Cdd:cd06235   82 VFKIVPMLNPDGVIRGNYRCSLNGFNLNRHYKNPDPELHPTIYGAKKVIDYLQKtyKRRVLMYCDFHGHSSKSNGFMYGN 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 595 ENKrNPEKKLTEQVFPLMLHKNSADRFSFESCKFKIQRSKEGTGRIVVW-MLGITNSYTIEASFGGSSLG-SRKGTHFNT 672
Cdd:cd06235  162 SFP-DTVQFHWNMVFPKILSLNAPDFFSSSCCSFGVMKSKEGTGRVVFGrRLIHSHSYTLESTFFSNNRGnIDGACGYTE 240

                        250
                 ....*....|....*.
gi 386764376 673 QDYEHMGRAFCETLLD 688
Cdd:cd06235  241 ENLEDLGYSVASTLLD 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 386764376 447 LLCRTLAGNNVYYLTVTAPSSNEENMR-RKKSIVVSARVHPSETPASWMMKGLMDFITGDTTVAKRLRHKFIFKLVPMLN 525
Cdd:cd06908    7 LLGKSVQQRRLDLLTITDPVNKHLTVEkKKKVVFITARVHPGETPSSFVCQGLIDFLVSNHPVAKVLRDHLVFKIVPMLN 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 526 PDGVIVGNTRNSLTGKDLNRQYRTVIRETYPSIWYTKAMIRRLIEE--CGVAMYCDMHAHSRKHNIFIYGceNKRNPEKK 603
Cdd:cd06908   87 PDGVFLGNYRCSLMGFDLNRHWHEPSPWAHPTLYAVKNLLRELDNDptVQLDFYIDIHAHSTLMNGFMYG--NIYDDVYR 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 604 LTEQ-VFPLMLHKNSADrFSFESCKFKIQRSKEGTGRIVVWMLGITNS--YTIEASFGGSSLGSRKG-THFNTQDYEHMG 679
Cdd:cd06908  165 FERQaVFPKLLCQNAED-FSLSNTVFNRDPVKAGTGRRFLGGLLDDTAncYTLEVSFYSYRLSDSSSaTPYTEEGYMKLG 243

                        250
                 ....*....|
gi 386764376 680 RAFCETLLDY 689
Cdd:cd06908  244 RNMARALLDY 253

Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related proteins; 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 subfamily includes the human 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 characteristic 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 386764376 475 KKSIVVSARVHPSETPASWMMKGLMDFITGDTTVAKRLRHKFIFKLVPMLNPDGVIVGNTRNSLTGKDLNRQYRTVIRET 554
Cdd:cd03856   43 KSWLFLIARQHPGETTGAWVFFGFLDQLLSDDDPAQQLRAEYNFYIIPMVNPDGVARGHWRTNSRGMDLNRDWHAPDALL 122

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 555 YPSIWYTKA-MIRRLIEECGVAMYCDMHAHSRkhNIFIYGCENKRNPekklTEQVFPLMLHKNSaDRFSFEScKFKIQRS 633
Cdd:cd03856  123 SPETYAVAAaLAERVQSPEGVVLALDLHGDNR--NVFLTGPDNKDES----TNHNPDKLNSLLT-ETDRRLP-DYNTEAS 194

                        170       180       190
                 ....*....|....*....|....*....|
gi 386764376 634 KEGTGRIVV---WM---LGITNSYTIEASF 657
Cdd:cd03856  195 PGDNPGGTVgkqWIadvYQITHSVTLEVGD 224

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 421 YTYSDLQDYLMEIQRhpvKSKFCKLRLLCRTLAGNNVYYLTVTAPSSNeenmrrKKSIVVSARVHPSETPASWMMKGLMD 500
Cdd:COG2866   20 YTYEELLALLAKLAA---ASPLVELESIGKSVEGRPIYLLKIGDPAEG------KPKVLLNAQQHGNEWTGTEALLGLLE 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 501 FI-TGDTTVAKRLRHKFIFKLVPMLNPDGVIVgNTRNSLTGKDLNRQYRTVIrETYPSiwyTKAMiRRLIEECGVAMYCD 579
Cdd:COG2866   91 DLlDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAPW-LSEPE---TRAL-RDLLDEHDPDFVLD 164

                 ..
gi 386764376 580 MH 581
Cdd:COG2866  165 LH 166

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 386764376 424 SDLQDYLMEIQRHPvkskFCKLRLLCRTLAGNNVYYLTVTAPSSneenmrrKKSIVVSARVHPSETPASWMMKGLMDFIT 503
Cdd:cd06237    1 ADYDAWIDSLAKKP----FVKRSTIGKSVEGRPIEALTIGNPDS-------KELVVLLGRQHPPEVTGALAMQAFVETLL 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 504 GDTTVAKRLRHKFIFKLVPMLNPDGVIVGNTRNSLTGKDLNRQyrtviretypsiWY------TKAM---IRRLIEECGV 574
Cdd:cd06237   70 ADTELAKAFRARFRVLVVPLLNPDGVDLGHWRHNAGGVDLNRD------------WGpftqpeTRAVrdfLLELVEEPGG 137

                        170
                 ....*....|....*.
gi 386764376 575 AMYCDMHAHSRKHNIF 590
Cdd:cd06237  138 KVVFGLDFHSTWEDVF 153

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 386764376 425 DLQDYLMEIQrhpvKSKFCKLRLLCRTLAGNNVYYLTVTAPSSneenmrrKKSIVVSARVHPSETPASWMMKGLMDFITG 504
Cdd:cd18429    1 DLDRLLAKIR----KNPLVEITTIGKTVEGRPLEIIRIGNESA-------PHRVFLRARAHPWEAGGNWVVEGLVERLLQ 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 386764376 505 DTTVAKRLRHKFIFKLVPMLNPDGVIVGNTRNSLTGKDLNRQY 547
Cdd:cd18429   70 NDEEAKRFLKRYCVYILPMANKDGVARGRTRFNANGKDLNREW 112

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 386764376 478 IVVSARVHPSETPASwmmKGLMDFI----TGDTTVAKRLRhKFIFKLVPMLNPDG------------VIVGNTRNSLTGK 541
Cdd:cd03857    2 VLLAAQIHGNETTGT---EALMELIrdlaSESDEAAKLLD-NIVILLVPQLNPDGaelfvnfyldsmNGLPGTRYNANGI 77

                         90       100       110
                 ....*....|....*....|....*....|
gi 386764376 542 DLNR-----------QYRTVIRETYPSIWY 560
Cdd:cd03857   78 DLNRdhvkltqpetqAVAENFIHWWPDIFI 107

Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular 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. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 422 TYSDLQDYLMEIQ-RHPvksKFCKLRLLCRTLAGNNVYYLTVTAPSSNEEnmrrKKSIVVSARVHPSE--TPAS--WMMK 496
Cdd:cd03860    3 PLDDIVQWLDDLAaAFP---DNVEIFTIGKSYEGRDITGIHIWGSGGKGG----KPAIVIHGGQHAREwiSTSTveYLAH 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 497 GLMDFITGDTTVAKRLRhKFIFKLVPMLNPDGVIVGNTRNSL-------------TGKDLNRQY----------RTVIRE 553
Cdd:cd03860   76 QLLSGYGSDATITALLD-KFDFYIIPVVNPDGYVYTWTTDRLwrknrqptggsscVGIDLNRNWgykwggpgasTNPCSE 154

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 386764376 554 TYP-----SIWYTKAM---IRRLIEECGVAMYCDMHAHS 584
Cdd:cd03860  155 TYRgpsafSAPETKALadfINALAAGQGIKGFIDLHSYS 193

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 478 IVVSARVHPSETPASWMMKGLMDFITGD--TTVAKRLRHKFIFKLVPMLNPDG---VIVGNTRNSLTGKDLNRQYRT--- 549
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALIEYLLENygNDPLKRLLDNVELWIVPLVNPDGfarVIDSGGRKNANGVDLNRNFPYnwg 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 550 VIRETYPSIWYTK----------AMIRRLIEECGVAMYCDMhaHSRKHNIFI-YGCENKRNPEKKLTEQVFPLMLHKNSA 618
Cdd:cd00596   81 KDGTSGPSSPTYRgpapfsepetQALRDLAKSHRFDLAVSY--HSSSEAILYpYGYTNEPPPDFSEFQELAAGLARALGA 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 386764376 619 DRFSFESCKFKIQRSkeGTGRIvvWMLGITN--SYTIEasfGGSSLGSRKGTHFN 671
Cdd:cd00596  159 GEYGYGYSYTWYSTT--GTADD--WLYGELGilAFTVE---LGTADYPLPGTLLD 206

Peptidase M14-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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764376 421 YTYSDLQDYLMEIQR-HPvksKFCKLRLLCRTLAGNNVYYLTVTAPssNEENMRRKKSIVVSARVHPSETPAS----WMM 495
Cdd:cd06905    7 YTYAELTARLKALAEaYP---NLVRLESIGKSYEGRDIWLLTITNG--ETGPADEKPALWVDGNIHGNEVTGSevalYLA 81

                         90       100       110
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gi 386764376 496 KGLMDFITGDTTVAKRLRHKFIFkLVPMLNPDG 528
Cdd:cd06905   82 EYLLTNYGKDPEITRLLDTRTFY-ILPRLNPDG 113