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 161077807   618 FESRFESGNLAKAVQITPTYYELYLRPDlYTSRSKQWFYFRVRRTRRKMlYRFSIVNLvkSDSLYNDGMQPvmYSTlGAK 697
Cdd:pfam18027    1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGARGRP-LTFVIENA--GEASYPDGWTG--YRV-VAS 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 161077807   698 EKSEGWRRCGdniCYYRNDdesasssaneddednstytlTFTIEFEHDDDTVFFAH 753
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 161077807  757 YTYSDLQDYLMEIQRhpvKSKFCKLRLLCRTLAGNNVYYLTVTAPSSNeenmrrKKSIVVSARVHPSETPASWMMKGLMD 836
Cdd:COG2866    20 YTYEELLALLAKLAA---ASPLVELESIGKSVEGRPIYLLKIGDPAEG------KPKVLLNAQQHGNEWTGTEALLGLLE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  837 FI-TGDTTVAKRLRHKFIFKLVPMLNPDGVIVgNTRNSLTGKDLNRQYRTVIrETYPSiwyTKAMiRRLIEECGVAMYCD 915
Cdd:COG2866    91 DLlDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAPW-LSEPE---TRAL-RDLLDEHDPDFVLD 164

                  ..
gi 161077807  916 MH 917
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 161077807   618 FESRFESGNLAKAVQITPTYYELYLRPDlYTSRSKQWFYFRVRRTRRKMlYRFSIVNLvkSDSLYNDGMQPvmYSTlGAK 697
Cdd:pfam18027    1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGARGRP-LTFVIENA--GEASYPDGWTG--YRV-VAS 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 161077807   698 EKSEGWRRCGdniCYYRNDdesasssaneddednstytlTFTIEFEHDDDTVFFAH 753
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 161077807  778 FCKLRLLCRTLAGNNVYYLTVTAPSSNEENMR-----RKKSIVVSARVHPSETPASWMMKGLMDFITGDTTVAKRLRHKF 852
Cdd:cd06235     2 YFEREVLCHSLDGRKLDLLTITSPNNKKLGPYprefaGKKVVFLSGRVHPGETPASFVMKGFLDFLLSNDPRAQLLREHF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  853 IFKLVPMLNPDGVIVGNTRNSLTGKDLNRQYRTVIRETYPSIWYTKAMIRRLIE--ECGVAMYCDMHAHSRKHNIFIYGC 930
Cdd:cd06235    82 VFKIVPMLNPDGVIRGNYRCSLNGFNLNRHYKNPDPELHPTIYGAKKVIDYLQKtyKRRVLMYCDFHGHSSKSNGFMYGN 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  931 ENKrNPEKKLTEQVFPLMLHKNSADRFSFESCKFKIQRSKEGTGRIVVW-MLGITNSYTIEASFGGSSLG-SRKGTHFNT 1008
Cdd:cd06235   162 SFP-DTVQFHWNMVFPKILSLNAPDFFSSSCCSFGVMKSKEGTGRVVFGrRLIHSHSYTLESTFFSNNRGnIDGACGYTE 240

                         250
                  ....*....|....*.
gi 161077807 1009 QDYEHMGRAFCETLLD 1024
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 161077807  783 LLCRTLAGNNVYYLTVTAPSSNEENMR-RKKSIVVSARVHPSETPASWMMKGLMDFITGDTTVAKRLRHKFIFKLVPMLN 861
Cdd:cd06908     7 LLGKSVQQRRLDLLTITDPVNKHLTVEkKKKVVFITARVHPGETPSSFVCQGLIDFLVSNHPVAKVLRDHLVFKIVPMLN 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  862 PDGVIVGNTRNSLTGKDLNRQYRTVIRETYPSIWYTKAMIRRLIEE--CGVAMYCDMHAHSRKHNIFIYGceNKRNPEKK 939
Cdd:cd06908    87 PDGVFLGNYRCSLMGFDLNRHWHEPSPWAHPTLYAVKNLLRELDNDptVQLDFYIDIHAHSTLMNGFMYG--NIYDDVYR 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  940 LTEQ-VFPLMLHKNSADrFSFESCKFKIQRSKEGTGRIVvwmLG-----ITNSYTIEASFGGSSLGSRKG-THFNTQDYE 1012
Cdd:cd06908   165 FERQaVFPKLLCQNAED-FSLSNTVFNRDPVKAGTGRRF---LGgllddTANCYTLEVSFYSYRLSDSSSaTPYTEEGYM 240

                         250
                  ....*....|...
gi 161077807 1013 HMGRAFCETLLDY 1025
Cdd:cd06908   241 KLGRNMARALLDY 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 161077807  811 KKSIVVSARVHPSETPASWMMKGLMDFITGDTTVAKRLRHKFIFKLVPMLNPDGVIVGNTRNSLTGKDLNRQYRTVIRET 890
Cdd:cd03856    43 KSWLFLIARQHPGETTGAWVFFGFLDQLLSDDDPAQQLRAEYNFYIIPMVNPDGVARGHWRTNSRGMDLNRDWHAPDALL 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  891 YPSIWYTKA-MIRRLIEECGVAMYCDMHAHSRkhNIFIYGCENKRNPekklTEQVFPLMLHKNSaDRFSFEScKFKIQRS 969
Cdd:cd03856   123 SPETYAVAAaLAERVQSPEGVVLALDLHGDNR--NVFLTGPDNKDES----TNHNPDKLNSLLT-ETDRRLP-DYNTEAS 194

                         170       180       190
                  ....*....|....*....|....*....|
gi 161077807  970 KEGTGRIVV---WM---LGITNSYTIEASF 993
Cdd:cd03856   195 PGDNPGGTVgkqWIadvYQITHSVTLEVGD 224

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  757 YTYSDLQDYLMEIQRhpvKSKFCKLRLLCRTLAGNNVYYLTVTAPSSNeenmrrKKSIVVSARVHPSETPASWMMKGLMD 836
Cdd:COG2866    20 YTYEELLALLAKLAA---ASPLVELESIGKSVEGRPIYLLKIGDPAEG------KPKVLLNAQQHGNEWTGTEALLGLLE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  837 FI-TGDTTVAKRLRHKFIFKLVPMLNPDGVIVgNTRNSLTGKDLNRQYRTVIrETYPSiwyTKAMiRRLIEECGVAMYCD 915
Cdd:COG2866    91 DLlDNYDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDWPAPW-LSEPE---TRAL-RDLLDEHDPDFVLD 164

                  ..
gi 161077807  916 MH 917
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 161077807  760 SDLQDYLMEIQRHPvkskFCKLRLLCRTLAGNNVYYLTVTAPSSneenmrrKKSIVVSARVHPSETPASWMMKGLMDFIT 839
Cdd:cd06237     1 ADYDAWIDSLAKKP----FVKRSTIGKSVEGRPIEALTIGNPDS-------KELVVLLGRQHPPEVTGALAMQAFVETLL 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  840 GDTTVAKRLRHKFIFKLVPMLNPDGVIVGNTRNSLTGKDLNRQyrtviretypsiWY------TKAM---IRRLIEECGV 910
Cdd:cd06237    70 ADTELAKAFRARFRVLVVPLLNPDGVDLGHWRHNAGGVDLNRD------------WGpftqpeTRAVrdfLLELVEEPGG 137

                         170
                  ....*....|....*.
gi 161077807  911 AMYCDMHAHSRKHNIF 926
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 161077807  761 DLQDYLMEIQrhpvKSKFCKLRLLCRTLAGNNVYYLTVTAPSSneenmrrKKSIVVSARVHPSETPASWMMKGLMDFITG 840
Cdd:cd18429     1 DLDRLLAKIR----KNPLVEITTIGKTVEGRPLEIIRIGNESA-------PHRVFLRARAHPWEAGGNWVVEGLVERLLQ 69

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 161077807  841 DTTVAKRLRHKFIFKLVPMLNPDGVIVGNTRNSLTGKDLNRQY 883
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 161077807  814 IVVSARVHPSETPASwmmKGLMDFI----TGDTTVAKRLRhKFIFKLVPMLNPDG------------VIVGNTRNSLTGK 877
Cdd:cd03857     2 VLLAAQIHGNETTGT---EALMELIrdlaSESDEAAKLLD-NIVILLVPQLNPDGaelfvnfyldsmNGLPGTRYNANGI 77

                          90       100       110
                  ....*....|....*....|....*....|
gi 161077807  878 DLNR-----------QYRTVIRETYPSIWY 896
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 161077807  758 TYSDLQDYLMEIQ-RHPvksKFCKLRLLCRTLAGNNVYYLTVTAPSSNEEnmrrKKSIVVSARVHPSE--TPAS--WMMK 832
Cdd:cd03860     3 PLDDIVQWLDDLAaAFP---DNVEIFTIGKSYEGRDITGIHIWGSGGKGG----KPAIVIHGGQHAREwiSTSTveYLAH 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  833 GLMDFITGDTTVAKRLRhKFIFKLVPMLNPDGVIVGNTRNSL-------------TGKDLNRQY----------RTVIRE 889
Cdd:cd03860    76 QLLSGYGSDATITALLD-KFDFYIIPVVNPDGYVYTWTTDRLwrknrqptggsscVGIDLNRNWgykwggpgasTNPCSE 154

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 161077807  890 TYP-----SIWYTKAM---IRRLIEECGVAMYCDMHAHS 920
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 161077807  814 IVVSARVHPSETPASWMMKGLMDFITGD--TTVAKRLRHKFIFKLVPMLNPDG---VIVGNTRNSLTGKDLNRQYRT--- 885
Cdd:cd00596     1 ILITGGIHGNEVIGVELALALIEYLLENygNDPLKRLLDNVELWIVPLVNPDGfarVIDSGGRKNANGVDLNRNFPYnwg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161077807  886 VIRETYPSIWYTK----------AMIRRLIEECGVAMYCDMhaHSRKHNIFI-YGCENKRNPEKKLTEQVFPLMLHKNSA 954
Cdd:cd00596    81 KDGTSGPSSPTYRgpapfsepetQALRDLAKSHRFDLAVSY--HSSSEAILYpYGYTNEPPPDFSEFQELAAGLARALGA 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 161077807  955 DRFSFESCKFKIQRSkeGTGRIvvWMLGITN--SYTIEasfGGSSLGSRKGTHFN 1007
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 161077807  757 YTYSDLQDYLMEIQR-HPvksKFCKLRLLCRTLAGNNVYYLTVTAPssNEENMRRKKSIVVSARVHPSETPAS----WMM 831
Cdd:cd06905     7 YTYAELTARLKALAEaYP---NLVRLESIGKSYEGRDIWLLTITNG--ETGPADEKPALWVDGNIHGNEVTGSevalYLA 81

                          90       100       110
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gi 161077807  832 KGLMDFITGDTTVAKRLRHKFIFkLVPMLNPDG 864
Cdd:cd06905    82 EYLLTNYGKDPEITRLLDTRTFY-ILPRLNPDG 113