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 568943126 307 RSKFCKIRVLCHTLARNMVYVLTITTPLK--TSDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIF 384
Cdd:cd06907    1 RSQYCKRRVLCRTLAGNSVYVLTITSPSSnpEEAKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNFVF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 385 KVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRLMEKREVILYCDLHGHSRKQNIFMYGCDGSS 464
Cdd:cd06907   81 KIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLEEREVILYCDLHGHSRKQNVFMYGCENRK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 465 RSKTKglyLQQRIFPLMLSKNCPNIFSFSACKFNVQKSKEGTGRVVMWKMGIRNSFTLEATFCGSTLGNKRGTHFGTKDL 544
Cdd:cd06907  161 NPEKP---LKERVFPLMLSKNAPDKFSFESCKFKVQKSKEGTGRVVMWREGILNSYTLEATFCGSTLGRRKGTHFNTLDF 237

                        250
                 ....*....|....*
gi 568943126 545 ESMGYHFCDSLLDYC 559
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 568943126 307 RSKFCKIRVLCHTLARNMVYVLTITTPLK--TSDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIF 384
Cdd:cd06907    1 RSQYCKRRVLCRTLAGNSVYVLTITSPSSnpEEAKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNFVF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 385 KVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRLMEKREVILYCDLHGHSRKQNIFMYGCDGSS 464
Cdd:cd06907   81 KIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLEEREVILYCDLHGHSRKQNVFMYGCENRK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 465 RSKTKglyLQQRIFPLMLSKNCPNIFSFSACKFNVQKSKEGTGRVVMWKMGIRNSFTLEATFCGSTLGNKRGTHFGTKDL 544
Cdd:cd06907  161 NPEKP---LKERVFPLMLSKNAPDKFSFESCKFKVQKSKEGTGRVVMWREGILNSYTLEATFCGSTLGRRKGTHFNTLDF 237

                        250
                 ....*....|....*
gi 568943126 545 ESMGYHFCDSLLDYC 559
Cdd:cd06907  238 EAMGYHFCDTLLDYC 252

Zn_pept domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126   289 YTYSNLQEYLSGINSDpvRSKFCKIRVLCHTLARNMVYVLTITTPLKTSdskRKAVILTARVHPGETNSSWIMKGFLDYI 368
Cdd:smart00631   2 HSYEEIEAWLKELAAR--YPDLVRLVSIGKSVEGRPIWVLKISNGGSHD---KPAIFIDAGIHAREWIGPATALYLINQL 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126   369 L-GDSSDARL--LRDTFIFKVVPMLNPDGVIVG-----------NYRCSLAGRDLNRNYTSLLKES---FPSVWY----- 426
Cdd:smart00631  77 LeNYGRDPRVtnLLDKTDIYIVPVLNPDGYEYThtgdrlwrknrSPNSNCRGVDLNRNFPFHWGETgnpCSETYAgpspf 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126   427 ----TRNMINRLMEKREVILYCDLHGHSRKqniFMYGCDGSSRSKTKGLYLQQRIFPLM---LSKNCPNIFSFsACKFNV 499
Cdd:smart00631 157 sepeTKAVRDFIRSNRRFKLYIDLHSYSQL---ILYPYGYTKNDLPPNVDDLDAVAKALakaLASVHGTRYTY-GISNGA 232

                          250       260       270
                   ....*....|....*....|....*....|
gi 568943126   500 QKSKEGTGRV-VMWKMGIRNSFTLEATFCG 528
Cdd:smart00631 233 IYPASGGSDDwAYGVLGIPFSFTLELRDDG 262

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 568943126  167 NTLVFEASADHEYELTVRPDlFTNKHTQWYYFQVTNTQAEIvYRFTIVNFTKpaSLYNRGMKPL--FYSEkeaktHNIGW 244
Cdd:pfam18027   9 NIEVVSASDPDAIRLRIRPD-NGSEHFQWFYFRVSGARGRP-LTFVIENAGE--ASYPDGWTGYrvVASY-----DRENW 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568943126  245 QRIGDQikyYKNNlgqdgrhffslTWTFQFPHSQDTCYFAH 285
Cdd:pfam18027  80 FRVPTE---YDGG-----------VLTITHTPEADTVYFAY 106

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 568943126 307 RSKFCKIRVLCHTLARNMVYVLTITTPLK--TSDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIF 384
Cdd:cd06907    1 RSQYCKRRVLCRTLAGNSVYVLTITSPSSnpEEAKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNFVF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 385 KVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRLMEKREVILYCDLHGHSRKQNIFMYGCDGSS 464
Cdd:cd06907   81 KIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLEEREVILYCDLHGHSRKQNVFMYGCENRK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 465 RSKTKglyLQQRIFPLMLSKNCPNIFSFSACKFNVQKSKEGTGRVVMWKMGIRNSFTLEATFCGSTLGNKRGTHFGTKDL 544
Cdd:cd06907  161 NPEKP---LKERVFPLMLSKNAPDKFSFESCKFKVQKSKEGTGRVVMWREGILNSYTLEATFCGSTLGRRKGTHFNTLDF 237

                        250
                 ....*....|....*
gi 568943126 545 ESMGYHFCDSLLDYC 559
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 568943126 315 VLCHTLARNMVYVLTITTPLKTSDSK-------RKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKVV 387
Cdd:cd06906    9 TLCETLGGNSCPVLTITAMPESNNEEhicqfrnRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLRESYIFKIV 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 388 PMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMINRL-MEKREVILYCDLHGHSRKQNIFMYGCDGS--- 463
Cdd:cd06906   89 PMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLrSIGRLPLVYCDYHGHSRKKNVFMYGCSPKesw 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 464 ---SRSKTKGLYLQQ---RIFPLMLSKNCPnIFSFSACKFNVQKSKEGTGRVVMWKM-GIRNSFTLEATFCGSTLGNKRG 536
Cdd:cd06906  169 shgDTNNPSGDIVEDlgyRTLPKLLSHFAP-AFSLSSCSFVVEKSKESTARVVVWREiGVLRSYTMESTYCGCDQGKYKG 247

                        250       260
                 ....*....|....*....|
gi 568943126 537 THFGTKDLESMGYHFCDSLL 556
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 568943126 315 VLCHTLARNMVYVLTITTPLKTSDS---------------------KRKAVILTARVHPGETNSSWIMKGFLDYILG-DS 372
Cdd:cd06236   13 LLCYSLEGRRVDLLTITSCHGVTEEreerlpnlfpdtskprphkfeGKKVVFISARVHPGETPSSFVFNGFLEFLLRpDD 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 373 SDARLLRDTFIFKVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTrnminrlmekREVILYCDLHGHSRK 452
Cdd:cd06236   93 PRAIALRRLFVFKLIPMLNPDGVARGHYRTDTRGVNLNRVYLNPDPELHPSIYAA----------KALLFYIDLHAHASK 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 453 QNIFMYGcdgsSRSKTKGLYLQQRIFPLMLSKNCPNiFSFSACKFNVQ----------KSKEGTGRVVMWK-MGIRNSFT 521
Cdd:cd06236  163 RGCFIYG----NALEDEEQQVENLLYPKLISLNSAH-FDFDACNFSEKnmysrdkrdgLSKEGSGRVALYKaTGIVHSYT 237

                 ....*.
gi 568943126 522 LEATFC 527
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 568943126 308 SKFCKIRVLCHTLA-RNMVyVLTITTPlktsDSKRKAVILTARVHPGETNSSWIMKGFLDYILGDS-SDARLLRDTFIFK 385
Cdd:cd06234   16 SPGVRLEVLGQTLDgRDID-LLTIGDP----GTGKKKVWIIARQHPGETMAEWFMEGLLDRLLDEDdPVSRALLEKAVFY 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 386 VVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESFPSVWYTRNMinrlMEKREVILYCDLHGHSRKQNIFMYGCDGSSr 465
Cdd:cd06234   91 VVPNMNPDGSVRGNLRTNAAGVNLNREWANPSLERSPEVFAVRQA----MDATGVDFFLDVHGDEALPYNFIAGAEGIP- 165

                        170       180
                 ....*....|....*....|..
gi 568943126 466 SKTKGLYLQQRIFPLMLSKNCP 487
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 568943126 307 RSKFCKIRVLCHTLARNMVYVLTITTPlktsdSKRKAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKV 386
Cdd:cd06237   12 KKPFVKRSTIGKSVEGRPIEALTIGNP-----DSKELVVLLGRQHPPEVTGALAMQAFVETLLADTELAKAFRARFRVLV 86

                         90       100
                 ....*....|....*....|....*..
gi 568943126 387 VPMLNPDGVIVGNYRCSLAGRDLNRNY 413
Cdd:cd06237   87 VPLLNPDGVDLGHWRHNAGGVDLNRDW 113

Zinc carboxypeptidase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126  322 RNMvYVLTITTPLKTSDSKRKAVILTARVHPGETNSSWIMKGFLDYIL---GDSSDARLLRDTFIFKVVPMLNPDGVIVG 398
Cdd:pfam00246  28 RPL-KVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLtnyGRDPEITELLDDTDIYILPVVNPDGYEYT 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126  399 ------------NYRCSLA-GRDLNRNYTSLLKESFP---------------SVWYTRNMINRLMEKREVILYCDLHGHS 450
Cdd:pfam00246 107 httdrlwrknrsNANGSSCiGVDLNRNFPDHWNEVGAssnpcsetyrgpapfSEPETRAVADFIRSKKPFVLYISLHSYS 186

                         170       180
                  ....*....|....*....|....
gi 568943126  451 RKQNiFMYGCDGSSRSKTKGLYLQ 474
Cdd:pfam00246 187 QVLL-YPYGYTRDEPPPDDEELKS 209

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 568943126 342 KAVILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKVVPMLNPDGVIVGNYRCSLAGRDLNRNY-----TSL 416
Cdd:cd18429   41 HRVFLRARAHPWEAGGNWVVEGLVERLLQNDEEAKRFLKRYCVYILPMANKDGVARGRTRFNANGKDLNREWdkpadPVL 120

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568943126 417 LKESFPSVWYTRNMINRlmeKREVILYCDLH 447
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 568943126 344 VILTARVHPGETNSSWIMKGFLDYILGDSSDARLLRDTFIFKVVPMLNPDG-VIVGNYRCSLA-----------GRDLNR 411
Cdd:cd03857    2 VLLAAQIHGNETTGTEALMELIRDLASESDEAAKLLDNIVILLVPQLNPDGaELFVNFYLDSMnglpgtrynanGIDLNR 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568943126 412 NYTSLLKESfpsvwytRNMINRLMEKREVILYCDLHG 448
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 568943126 344 VILTARVHPGETNSSWIMKGFLDYILGDSSD---------ARLLRDTFIFKVVPMLNPDG---VIVGNY--RCSLAGRDL 409
Cdd:cd06227    4 VLLVFGEHARELISVESALRLLRQLCGGLQEpaasalrelAREILDNVELKIIPNANPDGrrlVESGDYcwRGNENGVDL 83

                 ....
gi 568943126 410 NRNY 413
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 568943126 342 KAVILTARVHPGETNSSWIMKGFLDYIlgdssDARLLRDTFIfkVVPMLNPDGVIVGNYRCSLAGRDLNRNYTSLLKESF 421
Cdd:cd06251   13 PTLLLTAAIHGDELNGIEVIQRLLEDL-----DPSKLRGTLI--AIPVVNPLGFENNSRYLPDDGRDLNRSFPGSEKGSL 85

                         90       100
                 ....*....|....*....|....*.
gi 568943126 422 PSVwYTRNMINRLMEKREVILycDLH 447
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 568943126 322 RNMvYVLTITTPLKTSDSKRKAVILTARVHPGETNSSWIMKGFLDYILG----DSSDARLLRDTFIFkVVPMLNPDG--- 394
Cdd:cd03868   34 REL-WVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLLEnygkDERVTRLVNSTDIH-LMPSMNPDGfen 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 395 ----------VIVGnyRCSLAGRDLNRNYTSLLKESFPSVWY-----TRNMINRLMEKREViLYCDLHGHSRKQNifmYG 459
Cdd:cd03868  112 skegdcsgdpGYGG--RENANNVDLNRNFPDQFEDSDDRLLEgrqpeTLAMMKWIVENPFV-LSANLHGGSVVAS---YP 185

                        170
                 ....*....|...
gi 568943126 460 CDGSSRSKTKGLY 472
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 568943126 322 RNMvYVLTITTPlktSDSKRKAVILTARVHPGEtnssWIMKGFLDY----ILG----DSSDARLLRDtFIFKVVPMLNPD 393
Cdd:cd06247   37 RPM-YYLKIGWP---SDKPKKIIWMDCGIHARE----WIAPAFCQWfvkeILQnyktDSRLNKLLKN-LDFYVLPVLNID 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568943126 394 GVIVG---------------NYRCSlaGRDLNRNYTSllkeSFPSVWYTRN------------------MINRLMEKREV 440
Cdd:cd06247  108 GYIYSwttdrlwrksrsphnNGTCY--GTDLNRNFNS----QWCSIGASRNccsiifcgtgpesepetkAVADLIEKKKS 181

                        170       180
                 ....*....|....*....|
gi 568943126 441 ILYCDLHGHSRKQNIFM-YG 459
Cdd:cd06247  182 DILCYLTIHSYGQLILLpYG 201

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 568943126 289 YTYSNLQEYLSGINSDpvRSKFCKIRVLCHTL-ARNMvYVLTITTPLKTSDSKRKAVILTARVHPGETNSSWIMKGFLDY 367
Cdd:cd06905    7 YTYAELTARLKALAEA--YPNLVRLESIGKSYeGRDI-WLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEY 83

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568943126 368 IL----GDSSDARLLrDTFIFKVVPMLNPDG 394
Cdd:cd06905   84 LLtnygKDPEITRLL-DTRTFYILPRLNPDG 113