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 1907094258  803 QQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLR 882
Cdd:cd06906      1 SQIYYRQQTLCETLGGNSCPVLTITAMPESNNEEHICQFRNRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  883 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMY 962
Cdd:cd06906     81 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLRSIGRLPLVYCDYHGHSRKKNVFMY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  963 GCSIKETVWHTHDNSASCDIVEDMGYRTLPKILSHIAPAFCMSSCSFVVEKSKESTARVVVWREIGVQRSYTMESTLCGC 1042
Cdd:cd06906    161 GCSPKESWSHGDTNNPSGDIVEDLGYRTLPKLLSHFAPAFSLSSCSFVVEKSKESTARVVVWREIGVLRSYTMESTYCGC 240

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1907094258 1043 DQGRYKGLQIGTRELEEMGAKFCVGLLRLKR 1073
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 1907094258  803 QQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLR 882
Cdd:cd06906      1 SQIYYRQQTLCETLGGNSCPVLTITAMPESNNEEHICQFRNRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  883 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMY 962
Cdd:cd06906     81 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLRSIGRLPLVYCDYHGHSRKKNVFMY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  963 GCSIKETVWHTHDNSASCDIVEDMGYRTLPKILSHIAPAFCMSSCSFVVEKSKESTARVVVWREIGVQRSYTMESTLCGC 1042
Cdd:cd06906    161 GCSPKESWSHGDTNNPSGDIVEDLGYRTLPKLLSHFAPAFSLSSCSFVVEKSKESTARVVVWREIGVLRSYTMESTYCGC 240

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1907094258 1043 DQGRYKGLQIGTRELEEMGAKFCVGLLRLKR 1073
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 1907094258  646 FNSKFESGNLRKVIQIRKSEYDLILNSDINSNHyHQWFYFEVSGMRpGVAYRFNIINCekSNSQFNYGMQPLMYSVQEal 725
Cdd:pfam18027    1 ISSNFDSGNIEVVSASDPDAIRLRIRPDNGSEH-FQWFYFRVSGAR-GRPLTFVIENA--GEASYPDGWTGYRVVASY-- 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907094258  726 nARPWWIRMGTDicyYKNHfsrssvaaggqkgksyytiTFTVNFPHKDDVCYFAY 780
Cdd:pfam18027   75 -DRENWFRVPTE---YDGG-------------------VLTITHTPEADTVYFAY 106

Zinc carboxypeptidase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  842 RTRPYIFLSARVHPGETNASWVMKGTLEYLMSN---SPTAQSLRESYIFKIVPMLNPDGVING------------NHRCS 906
Cdd:pfam00246   44 PGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygrDPEITELLDDTDIYILPVVNPDGYEYThttdrlwrknrsNANGS 123

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907094258  907 L-SGEDLNRQWQS------------------PNPELHPtiyHAKGLLQYLAAVKRLpLVYCDYHGHSRkknVFMY 962
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 1907094258  803 QQIYFRKDVLCETLSGNICPLVTITAMPESNYYEHICQFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLR 882
Cdd:cd06906      1 SQIYYRQQTLCETLGGNSCPVLTITAMPESNNEEHICQFRNRPYIFLSARVHPGESNASWVMKGTLDFLLSSSPAAQSLR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  883 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAVKRLPLVYCDYHGHSRKKNVFMY 962
Cdd:cd06906     81 ESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRRWLNPNPELHPTIYHTKGLLQYLRSIGRLPLVYCDYHGHSRKKNVFMY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  963 GCSIKETVWHTHDNSASCDIVEDMGYRTLPKILSHIAPAFCMSSCSFVVEKSKESTARVVVWREIGVQRSYTMESTLCGC 1042
Cdd:cd06906    161 GCSPKESWSHGDTNNPSGDIVEDLGYRTLPKLLSHFAPAFSLSSCSFVVEKSKESTARVVVWREIGVLRSYTMESTYCGC 240

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1907094258 1043 DQGRYKGLQIGTRELEEMGAKFCVGLLRLKR 1073
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 1907094258  806 YFRKDVLCETLSGNICPLVTITAmPESNYYEhicqFRTRPYIFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLRESY 885
Cdd:cd06907      4 YCKRRVLCRTLAGNSVYVLTITS-PSSNPEE----AKAKKAVVLTARVHPGETNASWMMKGFLDFLTGSSPDAKLLRDNF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  886 IFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLAAvKRLPLVYCDYHGHSRKKNVFMYGCs 965
Cdd:cd06907     79 VFKIVPMLNPDGVIVGNYRCSLAGRDLNRNYKTPLKESFPTIWHTKMMIKRLLE-EREVILYCDLHGHSRKQNVFMYGC- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  966 iketvwhTHDNSASCDIVEdmgyRTLPKILSHIAPA-FCMSSCSFVVEKSKESTARVVVWREiGVQRSYTMESTLCGCDQ 1044
Cdd:cd06907    157 -------ENRKNPEKPLKE----RVFPLMLSKNAPDkFSFESCKFKVQKSKEGTGRVVMWRE-GILNSYTLEATFCGSTL 224

                          250       260
                   ....*....|....*....|....*
gi 1907094258 1045 GRYKGLQIGTRELEEMGAKFCVGLL 1069
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 1907094258  802 PQQIYFRKDVLCETLSGNICPLVTITA-----MPESNYYEHIC---------QFRTRPYIFLSARVHPGETNASWVMKGT 867
Cdd:cd06236      4 ESDIYYHRELLCYSLEGRRVDLLTITSchgvtEEREERLPNLFpdtskprphKFEGKKVVFISARVHPGETPSSFVFNGF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  868 LEYLMS-NSPTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKGLLQYLaavkrlplv 946
Cdd:cd06236     84 LEFLLRpDDPRAIALRRLFVFKLIPMLNPDGVARGHYRTDTRGVNLNRVYLNPDPELHPSIYAAKALLFYI--------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  947 ycDYHGHSRKKNVFMYGCSIKETVWHthdnsascdiVEDMGYrtlPKILSHIAPAFCMSSCSFvVEK-----------SK 1015
Cdd:cd06236    155 --DLHAHASKRGCFIYGNALEDEEQQ----------VENLLY---PKLISLNSAHFDFDACNF-SEKnmysrdkrdglSK 218

                          250       260
                   ....*....|....*....|.
gi 1907094258 1016 ESTARVVVWREIGVQRSYTME 1036
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 1907094258  788 TLQMHLQKLESAhnPQQIYFRKDVLCETLSGNICPLVTITAMPESnyyehicqfrtRPYIFLSARVHPGETNASWVMKGT 867
Cdd:cd06234      2 SYERHLDLVARA--QASPGVRLEVLGQTLDGRDIDLLTIGDPGTG-----------KKKVWIIARQHPGETMAEWFMEGL 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  868 LEYLMSNS-PTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSPNPELHPTIYHAKgllqylAAVKRLPL- 945
Cdd:cd06234     69 LDRLLDEDdPVSRALLEKAVFYVVPNMNPDGSVRGNLRTNAAGVNLNREWANPSLERSPEVFAVR------QAMDATGVd 142

                          170
                   ....*....|....*....
gi 1907094258  946 VYCDYHGHSRKKNVFMYGC 964
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 1907094258  845 PY-IFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLRESYIFKIVPMLNPDGVINGNHRCSLSGEDLNRQWQSP-NPE 922
Cdd:cd18429     40 PHrVFLRARAHPWEAGGNWVVEGLVERLLQNDEEAKRFLKRYCVYILPMANKDGVARGRTRFNANGKDLNREWDKPaDPV 119

                           90       100
                   ....*....|....*....|....*....
gi 1907094258  923 LHPTIYHAKGLLQYLAAVKRLPLVYCDYH 951
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 1907094258  646 FNSKFESGNLRKVIQIRKSEYDLILNSDINSNHyHQWFYFEVSGMRpGVAYRFNIINCekSNSQFNYGMQPLMYSVQEal 725
Cdd:pfam18027    1 ISSNFDSGNIEVVSASDPDAIRLRIRPDNGSEH-FQWFYFRVSGAR-GRPLTFVIENA--GEASYPDGWTGYRVVASY-- 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907094258  726 nARPWWIRMGTDicyYKNHfsrssvaaggqkgksyytiTFTVNFPHKDDVCYFAY 780
Cdd:pfam18027   75 -DRENWFRVPTE---YDGG-------------------VLTITHTPEADTVYFAY 106

Zinc carboxypeptidase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907094258  842 RTRPYIFLSARVHPGETNASWVMKGTLEYLMSN---SPTAQSLRESYIFKIVPMLNPDGVING------------NHRCS 906
Cdd:pfam00246   44 PGKPAVFIDGGIHAREWIGPATALYLIHQLLTNygrDPEITELLDDTDIYILPVVNPDGYEYThttdrlwrknrsNANGS 123

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907094258  907 L-SGEDLNRQWQS------------------PNPELHPtiyHAKGLLQYLAAVKRLpLVYCDYHGHSRkknVFMY 962
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 1907094258  844 RPYIFLSARVHPGETNASWvmkGTLEYLMSNsptAQSLRESYIFKIVPMLNPDGVINgNHRCSLSGEDLNRQWQ--SPNP 921
Cdd:cd06231     42 KPRVLISAGIHGDEPAGVE---ALLRFLESL---AEKYLRRVNLLVLPCVNPWGFER-NTRENADGIDLNRSFLkdSPSP 114

                           90       100
                   ....*....|....*....|.
gi 1907094258  922 ElhptiyhAKGLLQYLAAVKR 942
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 1907094258  842 RTRPYIFLSARVHPGEtnasWVMKGTLEYLMS-------NSPTAQSLRESYIFKIVPMLNPDGVI--------------- 899
Cdd:cd03860     48 GGKPAIVIHGGQHARE----WISTSTVEYLAHqllsgygSDATITALLDKFDFYIIPVVNPDGYVytwttdrlwrknrqp 123

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gi 1907094258  900 NGNHRCslSGEDLNR----QWQSPNPELHPT--IYH---------AKGLLQYLAAVKRLP--LVYCDYH 951
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 1907094258  847 IFLSARVHPGETNASWVMKGTLEYLMSNSPTAQSLRESYIFKIVPMLNPDGvINGNHRCSLSGEDLNR 914
Cdd:cd06239      2 VLLWSQMHGNEPTGTEALLDLISYLRRERQEFEKILERLTLVAIPMLNPDG-AELFTRHNAEGIDLNR 68

Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like domain of Gamma-D-glutamyl-L-diamino acid endopeptidase 1 (also known as Gamma-D-glutamyl-meso-diaminopimelate peptidase I, and Endopeptidase I (ENP1); EC 3.4.19.11). ENP1 is a member of the M14 family of metallocarboxypeptidases (MCPs), and is classified as belonging to subfamily C. However it has an exceptional type of activity of hydrolyzing the gamma-D-Glu-(L)meso-diaminopimelic acid (gamma-D-Glu-Dap) bond of L-Ala-gamma-D-Glu-(L)meso-diaminopimelic acid and L-Ala-gamma-D-Glu-(L)meso-diaminopimelic acid(L)-D-Ala peptides. ENP1 has a different substrate specificity and cellular role than MpaA (MpaA does not belong to this group). ENP1 hydrolyzes the gamma-D-Glu-Dap bond of MurNAc-tripeptide and MurNAc-tetrapeptide, as well as the amide bond of free tripeptide and tetrapeptide. ENP1 is active on spore cortex peptidoglycan, and is produced at stage IV of sporulation in forespore and spore integuments.

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gi 1907094258  847 IFLSARVHPGET-NASWVMKGTLEYLMS----NSPTAQSLRE---SYIFKIVPMLNPDGV---ING-------------- 901
Cdd:cd06229      1 VLYNASFHAREYiTTLLLMKFIEDYAKAyvnkSYIRGKDVGEllnKVTLHIVPMVNPDGVeisQNGsnainpyylrlvaw 80

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gi 1907094258  902 NHRCS--------LSGEDLNRQW 916
Cdd:cd06229     81 NKKGTdftgwkanIRGVDLNRNF 103