Peptidase M14-like domain of ATP/GTP binding protein AGBL-2 and AGBL-3, and related proteins; Peptidase M14-like domain of ATP/GTP binding protein_like (AGBL)-2, 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 subgroup includes the human AGBL-2, and -3, and the mouse cytosolic carboxypeptidase (CCPs)-2, and -3. 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 120300909  319 RSKFCKIRVLCHTLARNMVYVLTITTPLK--TSDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIF 396
Cdd:cd06907     1 RSQYCKRRVLCRTLAGNSVYVLTITSPSSnpEEAKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNFVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  397 KVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRLMEKREVILYCDLHGHSRKQNIFMYGCDGSS 476
Cdd:cd06907    81 KIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLEEREVILYCDLHGHSRKQNVFMYGCENRK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  477 RSKTKglyLQQRIFPLMLSKNCPNIFSFSACKFNVQKSKEGTGRVVMWKMGIRNSFTLEATFCGSTLGNKRGTHFGTKDL 556
Cdd:cd06907   161 NPEKP---LKERVFPLMLSKNAPDKFSFESCKFKVQKSKEGTGRVVMWREGILNSYTLEATFCGSTLGRRKGTHFNTLDF 237

                         250
                  ....*....|....*
gi 120300909  557 ESMGYHFCDSLLDYC 571
Cdd:cd06907   238 EAMGYHFCDTLLDYC 252

Peptidase M14-like domain of ATP/GTP binding protein AGBL-2 and AGBL-3, and related proteins; Peptidase M14-like domain of ATP/GTP binding protein_like (AGBL)-2, 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 subgroup includes the human AGBL-2, and -3, and the mouse cytosolic carboxypeptidase (CCPs)-2, and -3. 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 120300909  319 RSKFCKIRVLCHTLARNMVYVLTITTPLK--TSDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIF 396
Cdd:cd06907     1 RSQYCKRRVLCRTLAGNSVYVLTITSPSSnpEEAKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNFVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  397 KVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRLMEKREVILYCDLHGHSRKQNIFMYGCDGSS 476
Cdd:cd06907    81 KIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLEEREVILYCDLHGHSRKQNVFMYGCENRK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  477 RSKTKglyLQQRIFPLMLSKNCPNIFSFSACKFNVQKSKEGTGRVVMWKMGIRNSFTLEATFCGSTLGNKRGTHFGTKDL 556
Cdd:cd06907   161 NPEKP---LKERVFPLMLSKNAPDKFSFESCKFKVQKSKEGTGRVVMWREGILNSYTLEATFCGSTLGRRKGTHFNTLDF 237

                         250
                  ....*....|....*
gi 120300909  557 ESMGYHFCDSLLDYC 571
Cdd:cd06907   238 EAMGYHFCDTLLDYC 252

Zn_pept domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909    301 YTYSNLQEYLSGINSDpvRSKFCKIRVLCHTLARNMVYVLTITTPLKTSdskRKAVILTARVHPGETNSSWIMKGFLDYI 380
Cdd:smart00631    2 HSYEEIEAWLKELAAR--YPDLVRLVSIGKSVEGRPIWVLKISNGGSHD---KPAIFIDAGIHAREWIGPATALYLINQL 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909    381 L-GDSSDARL--LRDTFIFKVVPMLNPDGVIVG-----------NYRCSLAGRDLNRNYTSLLKES---FPSVWY----- 438
Cdd:smart00631   77 LeNYGRDPRVtnLLDKTDIYIVPVLNPDGYEYThtgdrlwrknrSPNSNCRGVDLNRNFPFHWGETgnpCSETYAgpspf 156

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909    439 ----TRNMINRLMEKREVILYCDLHGHSRKqniFMYGCDGSSRSKTKGLYLQQRIFPLM---LSKNCPNIFSFsACKFNV 511
Cdd:smart00631  157 sepeTKAVRDFIRSNRRFKLYIDLHSYSQL---ILYPYGYTKNDLPPNVDDLDAVAKALakaLASVHGTRYTY-GISNGA 232

                           250       260       270
                    ....*....|....*....|....*....|
gi 120300909    512 QKSKEGTGRV-VMWKMGIRNSFTLEATFCG 540
Cdd:smart00631  233 IYPASGGSDDwAYGVLGIPFSFTLELRDDG 262

Zinc carboxypeptidase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909   334 RNMvYVLTITTPLKTSDSKRKAVILTARVHPGETNSSWIMKGFLDYIL---GDSSDARLLRDTFIFKVVPMLNPDGVIVG 410
Cdd:pfam00246   28 RPL-KVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLtnyGRDPEITELLDDTDIYILPVVNPDGYEYT 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909   411 ------------NYRCSLA-GRDLNRNYTSLLKE--------------SFP-SVWYTRNMINRLMEKREVILYCDLHGHS 462
Cdd:pfam00246  107 httdrlwrknrsNANGSSCiGVDLNRNFPDHWNEvgassnpcsetyrgPAPfSEPETRAVADFIRSKKPFVLYISLHSYS 186

                          170       180
                   ....*....|....*....|....
gi 120300909   463 RKQNiFMYGCDGSSRSKTKGLYLQ 486
Cdd:pfam00246  187 QVLL-YPYGYTRDEPPPDDEELKS 209

Peptidase M14-like domain of ATP/GTP binding protein AGBL-2 and AGBL-3, and related proteins; Peptidase M14-like domain of ATP/GTP binding protein_like (AGBL)-2, 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 subgroup includes the human AGBL-2, and -3, and the mouse cytosolic carboxypeptidase (CCPs)-2, and -3. 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 120300909  319 RSKFCKIRVLCHTLARNMVYVLTITTPLK--TSDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIF 396
Cdd:cd06907     1 RSQYCKRRVLCRTLAGNSVYVLTITSPSSnpEEAKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNFVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  397 KVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRLMEKREVILYCDLHGHSRKQNIFMYGCDGSS 476
Cdd:cd06907    81 KIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLEEREVILYCDLHGHSRKQNVFMYGCENRK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  477 RSKTKglyLQQRIFPLMLSKNCPNIFSFSACKFNVQKSKEGTGRVVMWKMGIRNSFTLEATFCGSTLGNKRGTHFGTKDL 556
Cdd:cd06907   161 NPEKP---LKERVFPLMLSKNAPDKFSFESCKFKVQKSKEGTGRVVMWREGILNSYTLEATFCGSTLGRRKGTHFNTLDF 237

                         250
                  ....*....|....*
gi 120300909  557 ESMGYHFCDSLLDYC 571
Cdd:cd06907   238 EAMGYHFCDTLLDYC 252

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP), and related proteins. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. This eukaryotic subgroup includes the mouse Nna1/CCP-1, and -4 proteins, and the human Nna1/AGTPBP-1 protein. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Nna1 is widely expressed in the developing and adult nervous systems, including cerebellar Purkinje and granule neurons, miral cells of the olfactory bulb and retinal photoreceptors. Nna1 is also induced in axotomized motor neurons. Mutations in Nna1 cause Purkinje cell degeneration (pcd). The Nna1 CP domain is required to prevent the retinal photoreceptor loss and cerebellar ataxia phenotypes of pcd mice, and a functional zinc-binding domain is needed for Nna-1 to support neuron survival in these mice. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  327 VLCHTLARNMVYVLTITTPLKTSDSK-------RKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKVV 399
Cdd:cd06906     9 TLCETLGGNSCPVLTITAMPESNNEEhicqfrnRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLRESYIFKIV 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  400 PMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRL-MEKREVILYCDLHGHSRKQNIFMYGCDGS--- 475
Cdd:cd06906    89 PMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLrSIGRLPLVYCDYHGHSRKKNVFMYGCSPKesw 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  476 ---SRSKTKGLYLQQ---RIFPLMLSKNCPnIFSFSACKFNVQKSKEGTGRVVMWKM-GIRNSFTLEATFCGSTLGNKRG 548
Cdd:cd06906   169 shgDTNNPSGDIVEDlgyRTLPKLLSHFAP-AFSLSSCSFVVEKSKESTARVVVWREiGVLRSYTMESTYCGCDQGKYKG 247

                         250       260
                  ....*....|....*....|
gi 120300909  549 THFGTKDLESMGYHFCDSLL 568
Cdd:cd06906   248 LHIGTRELEEMGARFCEALL 267

Peptidase M14-like domain of ATP/GTP binding protein (AGBL)-5 and related proteins; Peptidase M14-like domain of ATP/GTP binding protein_like (AGBL)-5, 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 AGBL5 and the mouse cytosolic carboxypeptidase (CCP)-5. 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 120300909  327 VLCHTLARNMVYVLTITTPLKTSDS---------------------KRKAVILTARVHPGETNSSWIMKGFLDYILG-DS 384
Cdd:cd06236    13 LLCYSLEGRRVDLLTITSCHGVTEEreerlpnlfpdtskprphkfeGKKVVFISARVHPGETPSSFVFNGFLEFLLRpDD 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  385 SDARLLRDTFIFKVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTrnminrlmekREVILYCDLHGHSRK 464
Cdd:cd06236    93 PRAIALRRLFVFKLIPMLNPDGVARGHYRTDTRGVNLNRVYLNPDPELHPSIYAA----------KALLFYIDLHAHASK 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  465 QNIFMYGcdgsSRSKTKGLYLQQRIFPLMLSKNCPNiFSFSACKFNVQ----------KSKEGTGRVVMWK-MGIRNSFT 533
Cdd:cd06236   163 RGCFIYG----NALEDEEQQVENLLYPKLISLNSAH-FDFDACNFSEKnmysrdkrdgLSKEGSGRVALYKaTGIVHSYT 237

                  ....*.
gi 120300909  534 LEATFC 539
Cdd:cd06236   238 LECNYH 243

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar to Pseudomonas aerugnosa CCP (PaCCP); 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. This subgroup includes PaCCP from Pseudomonas aeruginosa, a carboxypeptidase homologous to M14D subfamily of human CCPs. Structural complexes with well-known inhibitors of metallocarboxypeptidases indicate that PaCCP might only possess C-terminal hydrolase activity against cellular substrates of particular specificity. 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 120300909  320 SKFCKIRVLCHTLA-RNMVyVLTITTPlktsDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDS-SDARLLRDTFIFK 397
Cdd:cd06234    16 SPGVRLEVLGQTLDgRDID-LLTIGDP----GTGKKKVWIIARQHPGETMAEWFMEGLLDRLLDEDdPVSRALLEKAVFY 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  398 VVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMinrlMEKREVILYCDLHGHSRKQNIFMYGCDGSSr 477
Cdd:cd06234    91 VVPNMNPDGSVRGNLRTNAAGVNLNREWANPSLERSPEVFAVRQA----MDATGVDFFLDVHGDEALPYNFIAGAEGIP- 165

                         170       180
                  ....*....|....*....|..
gi 120300909  478 SKTKGLYLQQRIFPLMLSKNCP 499
Cdd:cd06234   166 SWTPRLAALEAAFKAALAAASP 187

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 120300909  319 RSKFCKIRVLCHTLARNMVYVLTITTPlktsdSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKV 398
Cdd:cd06237    12 KKPFVKRSTIGKSVEGRPIEALTIGNP-----DSKELVVLLGRQHPPEVTGALAMQAFVETLLADTELAKAFRARFRVLV 86

                          90       100
                  ....*....|....*....|....*..
gi 120300909  399 VPMLNPDGVIVGNYRCSLAGRDLNRNY 425
Cdd:cd06237    87 VPLLNPDGVDLGHWRHNAGGVDLNRDW 113

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 120300909   171 FEARFESGNLQKVVKVADHEYELTVRPDlFTNKHTQWYYFQVTNTQAEIvYRFTIVNFTKpaSLYNRGMKPL--FYSEke 248
Cdd:pfam18027    1 ISSNFDSGNIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGARGRP-LTFVIENAGE--ASYPDGWTGYrvVASY-- 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 120300909   249 aktHNIGWQRIGDQikyYKNNlgqdgrhffslTWTFQFPHSQDTCYFAH 297
Cdd:pfam18027   75 ---DRENWFRVPTE---YDGG-----------VLTITHTPEADTVYFAY 106

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 120300909  354 KAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKVVPMLNPDGVIVGNYRCSLAGRDLNRNY-----TSL 428
Cdd:cd18429    41 HRVFLRARAHPWEAGGNWVVEGLVERLLQNDEEAKRFLKRYCVYILPMANKDGVARGRTRFNANGKDLNREWdkpadPVL 120

                          90       100       110
                  ....*....|....*....|....*....|.
gi 120300909  429 LKESFPSVWYTRNMINRlmeKREVILYCDLH 459
Cdd:cd18429   121 APENFALEKWLEEMIKA---GKKPDLAIELH 148

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 120300909  356 VILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKVVPMLNPDG-VIVGNYRCSLA-----------GRDLNR 423
Cdd:cd03857     2 VLLAAQIHGNETTGTEALMELIRDLASESDEAAKLLDNIVILLVPQLNPDGaELFVNFYLDSMnglpgtrynanGIDLNR 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 120300909  424 NYTSLLKESfpsvwytRNMINRLMEKREVILYCDLHG 460
Cdd:cd03857    82 DHVKLTQPE-------TQAVAENFIHWWPDIFIDLHE 111

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 120300909  356 VILTARVHPGETNSSWIMKGFLDYILGDSSD---------ARLLRDTFIFKVVPMLNPDG---VIVGNY--RCSLAGRDL 421
Cdd:cd06227     4 VLLVFGEHARELISVESALRLLRQLCGGLQEpaasalrelAREILDNVELKIIPNANPDGrrlVESGDYcwRGNENGVDL 83

                  ....
gi 120300909  422 NRNY 425
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 120300909  354 KAVILTARVHPGETNSSWIMKGFLDYIlgdssDARLLRDTFIfkVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESF 433
Cdd:cd06251    13 PTLLLTAAIHGDELNGIEVIQRLLEDL-----DPSKLRGTLI--AIPVVNPLGFENNSRYLPDDGRDLNRSFPGSEKGSL 85

                          90       100
                  ....*....|....*....|....*.
gi 120300909  434 PSVwYTRNMINRLMEKREVILycDLH 459
Cdd:cd06251    86 ASR-LAHLLWNEIVKKADYVI--DLH 108

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The first carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain I. CPD differs from all other metallocarboxypeptidases in that it contains multiple CP-like domains. CPD belongs to the N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs).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. CPD is a single-chain protein containing a signal peptide, three tandem repeats of CP-like domains separated by short bridge regions, followed by a transmembrane domain, and a C-terminal cytosolic tail. The first two CP-like domains of CPD contain all of the essential active site and substrate-binding residues, the third CP-like domain lacks critical residues necessary for enzymatic activity and is inactive towards standard CP substrates. Domain I is optimally active at pH 6.3-7.5 and prefers substrates with C-terminal Arg, whereas domain II is active at pH 5.0-6.5 and prefers substrates with C-terminal Lys. This Domain I family contains two contiguous surface cysteines that may become palmitoylated and target the enzyme to membranes, thus regulating intracellular trafficking. CPD functions in the processing of proteins that transit the secretory pathway, and is present in all vertebrates as well as Drosophila. It is broadly distributed in all tissue types. Within cells, CPD is present in the trans Golgi network and immature secretory vesicles, but is excluded from mature vesicles. It is thought to play a role in the processing of proteins that are initially processed by furin or related endopeptidases present in the trans Golgi network, such as growth factors and receptors. CPD is implicated in the pathogenesis of lupus erythematosus (LE), it is regulated by TGF-beta in various cell types of murine and human origin and is significantly down-regulated in CD14 positive cells isolated from patients with LE. As down-regulation of CPD leads to down-modulation of TGF-beta, CPD may have a role in a positive feedback loop. In D. melanogaster, the CPD variant 1B short (DmCPD1Bs) is necessary and sufficient for viability of the fruit fly.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  334 RNMvYVLTITTPLKTSDSKRKAVILTARVHPGETNSSWIMKGFLDYILG----DSSDARLLRDTFIFkVVPMLNPDG--- 406
Cdd:cd03868    34 REL-WVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLLEnygkDERVTRLVNSTDIH-LMPSMNPDGfen 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  407 ----------VIVGnyRCSLAGRDLNRNYTSLLKESFPSVWY-----TRNMINRLMEKREViLYCDLHGHSRKQNifmYG 471
Cdd:cd03868   112 skegdcsgdpGYGG--RENANNVDLNRNFPDQFEDSDDRLLEgrqpeTLAMMKWIVENPFV-LSANLHGGSVVAS---YP 185

                         170
                  ....*....|...
gi 120300909  472 CDGSSRSKTKGLY 484
Cdd:cd03868   186 FDDSPSHIECGVY 198

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 carboxypeptidase (CP) O (CPO, also known as metallocarboxypeptidase C; EC 3.4.17.) belongs to the carboxypeptidase A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). 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. CPO has not been well characterized as yet, and little is known about it. Based on modeling studies, CPO has been suggested to have specificity for acidic residues rather than aliphatic/aromatic residues as in A-like enzymes or basic residues as in B-like enzymes. It remains to be demonstrated that CPO is functional as an MCP.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  334 RNMvYVLTITTPlktSDSKRKAVILTARVHPGEtnssWIMKGFLDY----ILG----DSSDARLLRDtFIFKVVPMLNPD 405
Cdd:cd06247    37 RPM-YYLKIGWP---SDKPKKIIWMDCGIHARE----WIAPAFCQWfvkeILQnyktDSRLNKLLKN-LDFYVLPVLNID 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 120300909  406 GVIVG---------------NYRCSlaGRDLNRNYTSllkeSFPSVWYTRN------------------MINRLMEKREV 452
Cdd:cd06247   108 GYIYSwttdrlwrksrsphnNGTCY--GTDLNRNFNS----QWCSIGASRNccsiifcgtgpesepetkAVADLIEKKKS 181

                         170       180
                  ....*....|....*....|
gi 120300909  453 ILYCDLHGHSRKQNIFM-YG 471
Cdd:cd06247   182 DILCYLTIHSYGQLILLpYG 201