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 2462614147 171 FEARFESGNLQKVVKVAEYEYQLTVRPDlFTNKHTQWYYFQVTNMRaGIVYRFTIVNFTKpaSLYSRGMRPL--FYSEke 248
Cdd:pfam18027   1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGAR-GRPLTFVIENAGE--ASYPDGWTGYrvVASY-- 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2462614147 249 akaHHIGWQRIGDQikyYRNNpgqdgrhyfslTWTFQFPHNKDTCYFAH 297
Cdd:pfam18027  75 ---DRENWFRVPTE---YDGG-----------VLTITHTPEADTVYFAY 106

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 301 YTYTNLQEYLSGINNdpvRSKFCKIRVLCHT-LARNMvYILTITTPLKNsdsrkRKAVILTARVHPGETNSSWIMKGFLD 379
Cdd:COG2866    20 YTYEELLALLAKLAA---ASPLVELESIGKSvEGRPI-YLLKIGDPAEG-----KPKVLLNAQQHGNEWTGTEALLGLLE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 380 YILGN-SSDAQLLRDTFVFKVVPMLNPDGVIVgNYRCSLAGRDLNRNYtsllkesfPSVWY----TRNMvHRLMEKREVI 454
Cdd:COG2866    91 DLLDNyDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDW--------PAPWLsepeTRAL-RDLLDEHDPD 160

                  ....*..
gi 2462614147 455 LYCDLHG 461
Cdd:COG2866   161 FVLDLHG 167

Zn_pept domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147  301 YTYTNLQEYLSGINNDpvRSKFCKIRVLCHTLARNMVYILTITTPlknsDSRKRKAVILTARVHPGETNSSWIMKGFLDY 380
Cdd:smart00631   2 HSYEEIEAWLKELAAR--YPDLVRLVSIGKSVEGRPIWVLKISNG----GSHDKPAIFIDAGIHAREWIGPATALYLINQ 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147  381 ILGNSSDAQL---LRDTFVFKVVPMLNPDGVIVG-----------NYRCSLAGRDLNRNYTSLLKES---FPSVWY---- 439
Cdd:smart00631  76 LLENYGRDPRvtnLLDKTDIYIVPVLNPDGYEYThtgdrlwrknrSPNSNCRGVDLNRNFPFHWGETgnpCSETYAgpsp 155

                          170       180       190
                   ....*....|....*....|....*....|
gi 2462614147  440 -----TRNMVHRLMEKREVILYCDLHGHSR 464
Cdd:smart00631 156 fsepeTKAVRDFIRSNRRFKLYIDLHSYSQ 185

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 2462614147 322 FCKIRVLCHTLARNMVYILTITTPLKNSDS------RKRKAVILTARVHPGETNSSWIMKGFLDYILGNSSDAQLLRDTF 395
Cdd:cd06235     2 YFEREVLCHSLDGRKLDLLTITSPNNKKLGpyprefAGKKVVFLSGRVHPGETPASFVMKGFLDFLLSNDPRAQLLREHF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 396 VFKVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMVHRLME--KREVILYCDLHGHSRKENIFMYGC 473
Cdd:cd06235    82 VFKIVPMLNPDGVIRGNYRCSLNGFNLNRHYKNPDPELHPTIYGAKKVIDYLQKtyKRRVLMYCDFHGHSSKSNGFMYGN 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 474 DGSDRSKtlYLQQRIFPLMLSKNCPDKFSFSACKFNVQKSKEGTGRVVMWKM-GIRNSFTMEATFCGSTLGNK-RGTHFS 551
Cdd:cd06235   162 SFPDTVQ--FHWNMVFPKILSLNAPDFFSSSCCSFGVMKSKEGTGRVVFGRRlIHSHSYTLESTFFSNNRGNIdGACGYT 239

                         250
                  ....*....|....*..
gi 2462614147 552 TKDLESMGYHFCDSLLD 568
Cdd:cd06235   240 EENLEDLGYSVASTLLD 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 2462614147 327 VLCHTLARNMVYILTITTP--LKNSDSRKRKAVILTARVHPGETNSSWIMKGFLDYILGNSSDAQLLRDTFVFKVVPMLN 404
Cdd:cd06908     7 LLGKSVQQRRLDLLTITDPvnKHLTVEKKKKVVFITARVHPGETPSSFVCQGLIDFLVSNHPVAKVLRDHLVFKIVPMLN 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 405 PDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMVHRLME--KREVILYCDLHGHSRKENIFMYGCDGSDRSKtl 482
Cdd:cd06908    87 PDGVFLGNYRCSLMGFDLNRHWHEPSPWAHPTLYAVKNLLRELDNdpTVQLDFYIDIHAHSTLMNGFMYGNIYDDVYR-- 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 483 YLQQRIFPLMLSKNCPDkFSFSACKFNVQKSKEGTGRVVMWKMGIRNSF--TMEATFCGSTLGNKRG-THFSTKDLESMG 559
Cdd:cd06908   165 FERQAVFPKLLCQNAED-FSLSNTVFNRDPVKAGTGRRFLGGLLDDTANcyTLEVSFYSYRLSDSSSaTPYTEEGYMKLG 243

                         250
                  ....*....|
gi 2462614147 560 YHFCDSLLDY 569
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 2462614147 340 LTITTPLKNSDSRKRKAVILTARVHPGETNSSWIMKGFLDYILGNSSDAQLLRDTFVFKVVPMLNPDGVIVGNYRCSLAG 419
Cdd:cd03856    29 IQALQSLRTERSDDKSWLFLIARQHPGETTGAWVFFGFLDQLLSDDDPAQQLRAEYNFYIIPMVNPDGVARGHWRTNSRG 108

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462614147 420 RDLNRNYTSLLKESFPSVWYTRNMVH-RLMEKREVILYCDLHGHSRkeNIFMYGCDGSDRSKTLYLQ 485
Cdd:cd03856   109 MDLNRDWHAPDALLSPETYAVAAALAeRVQSPEGVVLALDLHGDNR--NVFLTGPDNKDESTNHNPD 173

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 301 YTYTNLQEYLSGINNdpvRSKFCKIRVLCHT-LARNMvYILTITTPLKNsdsrkRKAVILTARVHPGETNSSWIMKGFLD 379
Cdd:COG2866    20 YTYEELLALLAKLAA---ASPLVELESIGKSvEGRPI-YLLKIGDPAEG-----KPKVLLNAQQHGNEWTGTEALLGLLE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 380 YILGN-SSDAQLLRDTFVFKVVPMLNPDGVIVgNYRCSLAGRDLNRNYtsllkesfPSVWY----TRNMvHRLMEKREVI 454
Cdd:COG2866    91 DLLDNyDPLIRALLDNVTLYIVPMLNPDGAER-NTRTNANGVDLNRDW--------PAPWLsepeTRAL-RDLLDEHDPD 160

                  ....*..
gi 2462614147 455 LYCDLHG 461
Cdd:COG2866   161 FVLDLHG 167

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 2462614147 319 RSKFCKIRVLCHTLARNMVYILTITTPlknsdsRKRKAVILTARVHPGETNSSWIMKGFLDYILGNSSDAQLLRDTFVFK 398
Cdd:cd06237    12 KKPFVKRSTIGKSVEGRPIEALTIGNP------DSKELVVLLGRQHPPEVTGALAMQAFVETLLADTELAKAFRARFRVL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 399 VVPMLNPDGVIVGNYRCSLAGRDLNRNytsllkesfpsvWYTRN-----MVHRLME------KREVILYCDLhgHSRKEN 467
Cdd:cd06237    86 VVPLLNPDGVDLGHWRHNAGGVDLNRD------------WGPFTqpetrAVRDFLLelveepGGKVVFGLDF--HSTWED 151

                  ..
gi 2462614147 468 IF 469
Cdd:cd06237   152 VF 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462614147 355 KAVILTARVHPGETNSSWIMKGFLDYILGNSSDAQLLRDTFVFKVVPMLNPDGVIVGNYRCSLAGRDLNRNY 426
Cdd:cd18429    41 HRVFLRARAHPWEAGGNWVVEGLVERLLQNDEEAKRFLKRYCVYILPMANKDGVARGRTRFNANGKDLNREW 112

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 2462614147 357 VILTARVHPGETNSSWIMKGFLDYILGNSSDAQL--LRDTFVFKVVPMLNPDGVIVGNYRCS---LAGRDLNRNYTSLLK 431
Cdd:cd00596     1 ILITGGIHGNEVIGVELALALIEYLLENYGNDPLkrLLDNVELWIVPLVNPDGFARVIDSGGrknANGVDLNRNFPYNWG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462614147 432 E---SFPSVWY-----------TRNMVHrLMEKREVILYCDLHGhSRKENIFMYGCDGSDRSKTLYLQQ 486
Cdd:cd00596    81 KdgtSGPSSPTyrgpapfsepeTQALRD-LAKSHRFDLAVSYHS-SSEAILYPYGYTNEPPPDFSEFQE 147

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 357 VILTARVHPGETNSSWIMKGFLDYILGNSSD---------AQLLRDTFVFKVVPMLNPDG---VIVGNY--RCSLAGRDL 422
Cdd:cd06227     4 VLLVFGEHARELISVESALRLLRQLCGGLQEpaasalrelAREILDNVELKIIPNANPDGrrlVESGDYcwRGNENGVDL 83

                  ....
gi 2462614147 423 NRNY 426
Cdd:cd06227    84 NRNW 87

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; uncharacterized subgroup; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-2; EC:3.5.1.15) cleaves N-acetyl L-aspartic acid (NAA) into aspartate and acetate. NAA is abundant in the brain, and hydrolysis of NAA by ASPA may help maintain white matter. ASPA is an NAA scavenger in other tissues. Mutations in the gene encoding ASPA cause Canavan disease (CD), a fatal progressive neurodegenerative disorder involving dysmyelination and spongiform degeneration of white matter in children. This enzyme binds zinc which is necessary for activity. Measurement of elevated NAA levels in urine is used in the diagnosis of CD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462614147 355 KAVILTARVHPGETNSSWIMKGFLDYIlgnssDAQLLRDTFVfkVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESF 434
Cdd:cd06251    13 PTLLLTAAIHGDELNGIEVIQRLLEDL-----DPSKLRGTLI--AIPVVNPLGFENNSRYLPDDGRDLNRSFPGSEKGSL 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462614147 435 PSVwYTRNMVHRLMEKREVILycDLH-GHSRKENI-FMYGCDGSDRSKTL 482
Cdd:cd06251    86 ASR-LAHLLWNEIVKKADYVI--DLHtASTGRTNLpYVRADLRDPESRRM 132

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 2462614147 342 ITTPLKNSDsrkRKAVILTARVHPGETNSSWIMKGFLdyilgnSSDAQLLRDTFVFKVVPMLNPDGVIVGNyRCSLAGRD 421
Cdd:cd06231    33 LKSPNPRGD---KPRVLISAGIHGDEPAGVEALLRFL------ESLAEKYLRRVNLLVLPCVNPWGFERNT-RENADGID 102

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462614147 422 LNRNYtsLLKESFPSVWYTRNMVHRLmEKREVILycDLH 460
Cdd:cd06231   103 LNRSF--LKDSPSPEVRALMEFLASL-GRFDLHL--DLH 136

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

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gi 2462614147 388 AQLLRDTFvFKVVPMLNPDGViVGNYRCSLAGRDLNRNYTSllkESFPSvwyTRNMVHrLMEKREVILYCDLHG 461
Cdd:cd06244    51 KDLLDDVF-FIVVPTENPDGR-VANTRTNANGFDLNRDNAY---QTQPE---TRAMQE-LISKWNPVTFLDMHG 115

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.

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gi 2462614147 357 VILTARVHPGETNSSWIMKGFLDYIL---GNSSDAQLLRDTFVFKVVPMLNPDG-VIVGNYRCSLA------GRDLNRNY 426
Cdd:cd18173    57 FKYTSTMHGDETTGYELMLRLIDYLLtnyGTDPRITNLVDNTEIWINPLANPDGtYAGGNNTVSGAtrynanGVDLNRNF 136