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 568917265  231 FESRFESGNLQKAVRVGIYEYELTLRTDlYTDKHTQWFYFRVQNTRkDATYRFTIVNLlkPKSLYAVGMKPLmysQLDAT 310
Cdd:pfam18027   1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGAR-GRPLTFVIENA--GEASYPDGWTGY---RVVAS 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 568917265  311 IYNIGWRREGREikyYKNNVddgqqplycLTWTtqFPHDQDTCFFAHF 358
Cdd:pfam18027  74 YDRENWFRVPTE---YDGGV---------LTIT--HTPEADTVYFAYF 107

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 568917265  231 FESRFESGNLQKAVRVGIYEYELTLRTDlYTDKHTQWFYFRVQNTRkDATYRFTIVNLlkPKSLYAVGMKPLmysQLDAT 310
Cdd:pfam18027   1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGAR-GRPLTFVIENA--GEASYPDGWTGY---RVVAS 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 568917265  311 IYNIGWRREGREikyYKNNVddgqqplycLTWTtqFPHDQDTCFFAHF 358
Cdd:pfam18027  74 YDRENWFRVPTE---YDGGV---------LTIT--HTPEADTVYFAYF 107

Zn_pept domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265   361 YTYTDLQCYLLSVANNPiqSQFCKLRALCRSLAGNTVYLLTITNPSRtpqeaAAKKAVVLSARVHPGESNSSWIMNGFLD 440
Cdd:smart00631   2 HSYEEIEAWLKELAARY--PDLVRLVSIGKSVEGRPIWVLKISNGGS-----HDKPAIFIDAGIHAREWIGPATALYLIN 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265   441 FILSNSPDAQLLRDI---FVFKVIPMLNPDGVIVG-----------NYRCSLAGRDLNRHYKTVL-KDSFPCIWY----- 500
Cdd:smart00631  75 QLLENYGRDPRVTNLldkTDIYIVPVLNPDGYEYThtgdrlwrknrSPNSNCRGVDLNRNFPFHWgETGNPCSETyagps 154

                          170       180       190
                   ....*....|....*....|....*....|.
gi 568917265   501 ------TKNMIKRLLEEREVLLYCDFHGHSR 525
Cdd:smart00631 155 pfsepeTKAVRDFIRSNRRFKLYIDLHSYSQ 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 568917265 381 QFCKLRALCRSLAGNTVYLLTITNPSRT-----PQEAAAKKAVVLSARVHPGESNSSWIMNGFLDFILSNSPDAQLLRDI 455
Cdd:cd06235    1 IYFEREVLCHSLDGRKLDLLTITSPNNKklgpyPREFAGKKVVFLSGRVHPGETPASFVMKGFLDFLLSNDPRAQLLREH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 456 FVFKVIPMLNPDGVIVGNYRCSLAGRDLNRHYKTVLKDSFPCIWYTKNMIKRLLE--EREVLLYCDFHGHSRKNNIFLYG 533
Cdd:cd06235   81 FVFKIVPMLNPDGVIRGNYRCSLNGFNLNRHYKNPDPELHPTIYGAKKVIDYLQKtyKRRVLMYCDFHGHSSKSNGFMYG 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 534 CHSNNRKHWLHERVFPLMLSKNAPDKFSFDSCNFKVQKCKEGTGRVVMWRM-GIINSYTMESTFGGSTLGSK-RDTHFTI 611
Cdd:cd06235  161 NSFPDTVQFHWNMVFPKILSLNAPDFFSSSCCSFGVMKSKEGTGRVVFGRRlIHSHSYTLESTFFSNNRGNIdGACGYTE 240

                        250
                 ....*....|....*.
gi 568917265 612 EDLKSLGYHVCDTLLD 627
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 568917265 388 LCRSLAGNTVYLLTITNPSRTPQEAAAKKAVV-LSARVHPGESNSSWIMNGFLDFILSNSPDAQLLRDIFVFKVIPMLNP 466
Cdd:cd06908    8 LGKSVQQRRLDLLTITDPVNKHLTVEKKKKVVfITARVHPGETPSSFVCQGLIDFLVSNHPVAKVLRDHLVFKIVPMLNP 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 467 DGVIVGNYRCSLAGRDLNRHYKTVLKDSFPCIWYTKNMIKRLLEEREVLL--YCDFHGHSRKNNIFLYGCHSNNRKHWLH 544
Cdd:cd06908   88 DGVFLGNYRCSLMGFDLNRHWHEPSPWAHPTLYAVKNLLRELDNDPTVQLdfYIDIHAHSTLMNGFMYGNIYDDVYRFER 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 545 ERVFPLMLSKNAPDkFSFDSCNFKVQKCKEGTGRVVMWRMGIINS--YTME-STFGGSTLGSKRDTHFTIEDLKSLGYHV 621
Cdd:cd06908  168 QAVFPKLLCQNAED-FSLSNTVFNRDPVKAGTGRRFLGGLLDDTAncYTLEvSFYSYRLSDSSSATPYTEEGYMKLGRNM 246

                 ....*..
gi 568917265 622 CDTLLDF 628
Cdd:cd06908  247 ARALLDY 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 568917265 369 YLLSVANNPIQSqfckLRALCRSLAGNTVYLLTITNPSRTPqeaaAKKAVVLSARVHPGESNSSWIMNGFLDFILSNSPD 448
Cdd:cd03856    5 WLNLIATQPLVQ----LLEIGVTEQGREIQALQSLRTERSD----DKSWLFLIARQHPGETTGAWVFFGFLDQLLSDDDP 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 449 AQLLRDIFVFKVIPMLNPDGVIVGNYRCSLAGRDLNRHYKTVLKDSFPCIWYTKN-MIKRLLEEREVLLYCDFHGHSRkn 527
Cdd:cd03856   77 AQQLRAEYNFYIIPMVNPDGVARGHWRTNSRGMDLNRDWHAPDALLSPETYAVAAaLAERVQSPEGVVLALDLHGDNR-- 154

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568917265 528 NIFLYGCHSNNRKhwlHERVFPLMLSKNApDKFSFDScNFKVQKCKE-----GTGRVVMWRM-GIINSYTMESTF 596
Cdd:cd03856  155 NVFLTGPDNKDES---TNHNPDKLNSLLT-ETDRRLP-DYNTEASPGdnpggTVGKQWIADVyQITHSVTLEVGD 224

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 568917265  231 FESRFESGNLQKAVRVGIYEYELTLRTDlYTDKHTQWFYFRVQNTRkDATYRFTIVNLlkPKSLYAVGMKPLmysQLDAT 310
Cdd:pfam18027   1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGAR-GRPLTFVIENA--GEASYPDGWTGY---RVVAS 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 568917265  311 IYNIGWRREGREikyYKNNVddgqqplycLTWTtqFPHDQDTCFFAHF 358
Cdd:pfam18027  74 YDRENWFRVPTE---YDGGV---------LTIT--HTPEADTVYFAYF 107

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 568917265 379 QSQFCKLRALCRSLAGNTVYLLTITNPSrtpqeaaAKKAVVLSARVHPGESNSSWIMNGFLDFILSNSPDAQLLRDIFVF 458
Cdd:cd06237   12 KKPFVKRSTIGKSVEGRPIEALTIGNPD-------SKELVVLLGRQHPPEVTGALAMQAFVETLLADTELAKAFRARFRV 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 459 KVIPMLNPDGVIVGNYRCSLAGRDLNRhyktvlkDsfpciW--YT-------KNMIKRLLEE--REVLLYCDFhgHSRKN 527
Cdd:cd06237   85 LVVPLLNPDGVDLGHWRHNAGGVDLNR-------D-----WgpFTqpetravRDFLLELVEEpgGKVVFGLDF--HSTWE 150

                 ...
gi 568917265 528 NIF 530
Cdd:cd06237  151 DVF 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 568917265 365 DLQCYLLSVANNPIQSqfckLRALCRSLAGNTVYLLTITNPSrtpqeaaAKKAVVLSARVHPGESNSSWIMNGFLDFILS 444
Cdd:cd18429    1 DLDRLLAKIRKNPLVE----ITTIGKTVEGRPLEIIRIGNES-------APHRVFLRARAHPWEAGGNWVVEGLVERLLQ 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 568917265 445 NSPDAQLLRDIFVFKVIPMLNPDGVIVGNYRCSLAGRDLNRHY 487
Cdd:cd18429   70 NDEEAKRFLKRYCVYILPMANKDGVARGRTRFNANGKDLNREW 112

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 354 FFAHFYpyTYTDLQCYLLSVA-NNPiqsQFCKLRALCRSLAGNTVYLLTITNPSRTPqeAAAKKAVVLSARVHPGESNSS 432
Cdd:cd06905    2 AFDRYY--TYAELTARLKALAeAYP---NLVRLESIGKSYEGRDIWLLTITNGETGP--ADEKPALWVDGNIHGNEVTGS 74

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 568917265 433 WIMNGFLDFILSN---SPDAQLLRDIFVFKVIPMLNPDG 468
Cdd:cd06905   75 EVALYLAEYLLTNygkDPEITRLLDTRTFYILPRLNPDG 113

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 568917265 418 VVLSARVHPGESNSSWIMNGFLDFILSN---SPDAQLL--RDIFVfkvIPMLNPDGVIVGNYRCS---LAGRDLNR---H 486
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALIEYLLENygnDPLKRLLdnVELWI---VPLVNPDGFARVIDSGGrknANGVDLNRnfpY 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568917265 487 YKTVLKDSFPCIWY-----------TKNMIKrLLEEREVLLYCDFHGhSRKNNIFLYGCHSNNRKHWLHERVF-PLMLSK 554
Cdd:cd00596   78 NWGKDGTSGPSSPTyrgpapfsepeTQALRD-LAKSHRFDLAVSYHS-SSEAILYPYGYTNEPPPDFSEFQELaAGLARA 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568917265 555 NAPDKFSFDSCNFKVQKckegTGRVVMW---RMGIInSYTMESTFGGSTLGSKRDTHFTIEDLKSL 617
Cdd:cd00596  156 LGAGEYGYGYSYTWYST----TGTADDWlygELGIL-AFTVELGTADYPLPGTLLDRRLERNLAAL 216

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 568917265 418 VVLSARVHPGESNSSWIMNGFLDFILSNSPD---------AQLLRDIFVFKVIPMLNPDG---VIVGNY--RCSLAGRDL 483
Cdd:cd06227    4 VLLVFGEHARELISVESALRLLRQLCGGLQEpaasalrelAREILDNVELKIIPNANPDGrrlVESGDYcwRGNENGVDL 83

                 ....*
gi 568917265 484 NRHYK 488
Cdd:cd06227   84 NRNWG 88