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 545746276  861 QQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLR 940
Cdd:cd06906     1 SQIYYRQQTLCETLGGNSCPVLTITAMPESNNEEHICQFRNRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276  941 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMY 1020
Cdd:cd06906    81 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLRSIGRLPLVYCDYHGHSRKKNVFMY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276 1021 GCSIKETVWHTHDNSASCDIVEDMGYRTLPKILSHIAPAFCMSSCSFVVEKSKESTARVVVWREIGVQRSYTMESTLCGC 1100
Cdd:cd06906   161 GCSPKESWSHGDTNNPSGDIVEDLGYRTLPKLLSHFAPAFSLSSCSFVVEKSKESTARVVVWREIGVLRSYTMESTYCGC 240

                         250       260       270
                  ....*....|....*....|....*....|.
gi 545746276 1101 DQGRYKGLQIGTRELEEMGAKFCVGLLRLKR 1131
Cdd:cd06906   241 DQGKYKGLHIGTRELEEMGARFCEALLRLKR 271

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 545746276  861 QQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLR 940
Cdd:cd06906     1 SQIYYRQQTLCETLGGNSCPVLTITAMPESNNEEHICQFRNRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276  941 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMY 1020
Cdd:cd06906    81 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLRSIGRLPLVYCDYHGHSRKKNVFMY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276 1021 GCSIKETVWHTHDNSASCDIVEDMGYRTLPKILSHIAPAFCMSSCSFVVEKSKESTARVVVWREIGVQRSYTMESTLCGC 1100
Cdd:cd06906   161 GCSPKESWSHGDTNNPSGDIVEDLGYRTLPKLLSHFAPAFSLSSCSFVVEKSKESTARVVVWREIGVLRSYTMESTYCGC 240

                         250       260       270
                  ....*....|....*....|....*....|.
gi 545746276 1101 DQGRYKGLQIGTRELEEMGAKFCVGLLRLKR 1131
Cdd:cd06906   241 DQGKYKGLHIGTRELEEMGARFCEALLRLKR 271

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 545746276   704 FNSKFESGNLRKVIQIRKSEYDLILNSDINSNHyHQWFYFEVSGMRpGVAYRFNIINCekSNSQFNYGMQPLMYSVQEal 783
Cdd:pfam18027    1 ISSNFDSGNIEVVSASDPDAIRLRIRPDNGSEH-FQWFYFRVSGAR-GRPLTFVIENA--GEASYPDGWTGYRVVASY-- 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 545746276   784 nARPWWIRMGTDicyYKNHfsrssvaaggqkgksyytiTFTVNFPHKDDVCYFAY 838
Cdd:pfam18027   75 -DRENWFRVPTE---YDGG-------------------VLTITHTPEADTVYFAY 106

Zinc carboxypeptidase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276   900 RTRPYIFLSARVHPGETNASWVMKGTLEYLMSN---SPTAQSLRESYIFKIVPMLNPDGVING------------NHRCS 964
Cdd:pfam00246   44 PGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygrDPEITELLDDTDIYILPVVNPDGYEYThttdrlwrknrsNANGS 123

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 545746276   965 L-SGEDLNRQWQS------------------PNPELHPtiyHAKGLLQYLAAVKRLpLVYCDYHGHSRkknVFMY 1020
Cdd:pfam00246  124 ScIGVDLNRNFPDhwnevgassnpcsetyrgPAPFSEP---ETRAVADFIRSKKPF-VLYISLHSYSQ---VLLY 191

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 545746276  861 QQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLR 940
Cdd:cd06906     1 SQIYYRQQTLCETLGGNSCPVLTITAMPESNNEEHICQFRNRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276  941 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMY 1020
Cdd:cd06906    81 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLRSIGRLPLVYCDYHGHSRKKNVFMY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276 1021 GCSIKETVWHTHDNSASCDIVEDMGYRTLPKILSHIAPAFCMSSCSFVVEKSKESTARVVVWREIGVQRSYTMESTLCGC 1100
Cdd:cd06906   161 GCSPKESWSHGDTNNPSGDIVEDLGYRTLPKLLSHFAPAFSLSSCSFVVEKSKESTARVVVWREIGVLRSYTMESTYCGC 240

                         250       260       270
                  ....*....|....*....|....*....|.
gi 545746276 1101 DQGRYKGLQIGTRELEEMGAKFCVGLLRLKR 1131
Cdd:cd06906   241 DQGKYKGLHIGTRELEEMGARFCEALLRLKR 271

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 545746276  864 YFRKDVLCETLSGNICPLVTITAmPESNYYEhicqFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLRESY 943
Cdd:cd06907     4 YCKRRVLCRTLAGNSVYVLTITS-PSSNPEE----AKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276  944 IFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAvKRLPLVYCDYHGHSRKKNVFMYGCs 1023
Cdd:cd06907    79 VFKIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLE-EREVILYCDLHGHSRKQNVFMYGC- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276 1024 iketvwhTHDNSASCDIVEdmgyRTLPKILSHIAPA-FCMSSCSFVVEKSKESTARVVVWREiGVQRSYTMESTLCGCDQ 1102
Cdd:cd06907   157 -------ENRKNPEKPLKE----RVFPLMLSKNAPDkFSFESCKFKVQKSKEGTGRVVMWRE-GILNSYTLEATFCGSTL 224

                         250       260
                  ....*....|....*....|....*
gi 545746276 1103 GRYKGLQIGTRELEEMGAKFCVGLL 1127
Cdd:cd06907   225 GRRKGTHFNTLDFEAMGYHFCDTLL 249

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 545746276  860 PQQIYFRKDVLCETLSGNICPLVTITA-----MPESNYYEHIC---------QFRTRPYIFLSARVHPGETNASWVMKGT 925
Cdd:cd06236     4 ESDIYYHRELLCYSLEGRRVDLLTITSchgvtEEREERLPNLFpdtskprphKFEGKKVVFISARVHPGETPSSFVFNGF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276  926 LEYLMS-NSPTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLaavkrlplv 1004
Cdd:cd06236    84 LEFLLRpDDPRAIALRRLFVFKLIPMLNPDGVARGHYRTDTRGVNLNRVYLNPDPELHPSIYAAKALLFYI--------- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276 1005 ycDYHGHSRKKNVFMYGCSIKETVWHthdnsascdiVEDMGYrtlPKILSHIAPAFCMSSCSFvVEK-----------SK 1073
Cdd:cd06236   155 --DLHAHASKRGCFIYGNALEDEEQQ----------VENLLY---PKLISLNSAHFDFDACNF-SEKnmysrdkrdglSK 218

                         250       260
                  ....*....|....*....|.
gi 545746276 1074 ESTARVVVWREIGVQRSYTME 1094
Cdd:cd06236   219 EGSGRVALYKATGIVHSYTLE 239

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 545746276  846 TLQMHLQKLESAhnPQQIYFRKDVLCETLSGNICPLVTITAMPESnyyehicqfrtRPYIFLSARVHPGETNASWVMKGT 925
Cdd:cd06234     2 SYERHLDLVARA--QASPGVRLEVLGQTLDGRDIDLLTIGDPGTG-----------KKKVWIIARQHPGETMAEWFMEGL 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276  926 LEYLMSNS-PTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKgllqylAAVKRLPL- 1003
Cdd:cd06234    69 LDRLLDEDdPVSRALLEKAVFYVVPNMNPDGSVRGNLRTNAAGVNLNREWANPSLERSPEVFAVR------QAMDATGVd 142

                         170
                  ....*....|....*....
gi 545746276 1004 VYCDYHGHSRKKNVFMYGC 1022
Cdd:cd06234   143 FFLDVHGDEALPYNFIAGA 161

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 545746276  903 PY-IFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSP-NPE 980
Cdd:cd18429    40 PHrVFLRARAHPWEAGGNWVVEGLVERLLQNDEEAKRFLKRYCVYILPMANKDGVARGRTRFNANGKDLNREWDKPaDPV 119

                          90       100
                  ....*....|....*....|....*....
gi 545746276  981 LHPTIYHAKGLLQYLAAVKRLPLVYCDYH 1009
Cdd:cd18429   120 LAPENFALEKWLEEMIKAGKKPDLAIELH 148

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 545746276   704 FNSKFESGNLRKVIQIRKSEYDLILNSDINSNHyHQWFYFEVSGMRpGVAYRFNIINCekSNSQFNYGMQPLMYSVQEal 783
Cdd:pfam18027    1 ISSNFDSGNIEVVSASDPDAIRLRIRPDNGSEH-FQWFYFRVSGAR-GRPLTFVIENA--GEASYPDGWTGYRVVASY-- 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 545746276   784 nARPWWIRMGTDicyYKNHfsrssvaaggqkgksyytiTFTVNFPHKDDVCYFAY 838
Cdd:pfam18027   75 -DRENWFRVPTE---YDGG-------------------VLTITHTPEADTVYFAY 106

Zinc carboxypeptidase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276   900 RTRPYIFLSARVHPGETNASWVMKGTLEYLMSN---SPTAQSLRESYIFKIVPMLNPDGVING------------NHRCS 964
Cdd:pfam00246   44 PGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygrDPEITELLDDTDIYILPVVNPDGYEYThttdrlwrknrsNANGS 123

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 545746276   965 L-SGEDLNRQWQS------------------PNPELHPtiyHAKGLLQYLAAVKRLpLVYCDYHGHSRkknVFMY 1020
Cdd:pfam00246  124 ScIGVDLNRNFPDhwnevgassnpcsetyrgPAPFSEP---ETRAVADFIRSKKPF-VLYISLHSYSQ---VLLY 191

Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family includes Francisella tularensis protein rapid encystment phenotype 34 (REP34) which is a zinc-containing monomeric protein demonstrating carboxypeptidase B-like activity. REP34 possesses a novel topology with its substrate binding pocket deviating from the canonical M14 peptidases with a possible catalytic role for a conserved tyrosine and distinct S1' recognition site. Thus, REP34, identified as an active carboxypeptidase and a potential key F. tularensis effector protein, may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells. A functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545746276  902 RPYIFLSARVHPGETNASWvmkGTLEYLMSNsptAQSLRESYIFKIVPMLNPDGVINgNHRCSLSGEDLNRQWQ--SPNP 979
Cdd:cd06231    42 KPRVLISAGIHGDEPAGVE---ALLRFLESL---AEKYLRRVNLLVLPCVNPWGFER-NTRENADGIDLNRSFLkdSPSP 114

                          90       100
                  ....*....|....*....|.
gi 545746276  980 ElhptiyhAKGLLQYLAAVKR 1000
Cdd:cd06231   115 E-------VRALMEFLASLGR 128

Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.

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gi 545746276  900 RTRPYIFLSARVHPGEtnasWVMKGTLEYLMS-------NSPTAQSLRESYIFKIVPMLNPDGVI--------------- 957
Cdd:cd03860    48 GGKPAIVIHGGQHARE----WISTSTVEYLAHqllsgygSDATITALLDKFDFYIIPVVNPDGYVytwttdrlwrknrqp 123

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gi 545746276  958 NGNHRCslSGEDLNR----QWQSPNPELHPT--IYH---------AKGLLQYLAAVKRLP--LVYCDYH 1009
Cdd:cd03860   124 TGGSSC--VGIDLNRnwgyKWGGPGASTNPCseTYRgpsafsapeTKALADFINALAAGQgiKGFIDLH 190

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate 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.

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gi 545746276  905 IFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLRESYIFKIVPMLNPDGvINGNHRCSLSGEDLNR 972
Cdd:cd06239     2 VLLWSQMHGNEPTGTEALLDLISYLRRERQEFEKILERLTLVAIPMLNPDG-AELFTRHNAEGIDLNR 68