NCBI Conserved Domain Search

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The second carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain II. 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, while 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. 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.

Pssm-ID: 349435 [Multi-domain] Cd Length: 296 Bit Score: 642.00 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  467 IQPQEFRHHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLL 546
Cdd:cd03863      1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  547 NLIEYLCRNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNYDLNRNFPDRFKLITDPIQPETLAV 626
Cdd:cd03863     81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  627 MNWSKNYSFVLSANLHGGSLVVNYPFDDNLEDVIGYSKSPDDAVFRMVALAYSQENSEMHEGHPCKEMsSYPEYFQDGIT 706
Cdd:cd03863    161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKEL-YPNEYFPHGIT 239

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866  707 NGAAWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd03863    240 NGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296

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.

Pssm-ID: 349440 Cd Length: 294 Bit Score: 532.21 E-value: 2.32e-179

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDISAADgTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03868      1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRRE-PGKPMFKYVANMHGDETVGRQLLIYLAQYL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKDE--GRHNAKNIDLNRSFPDQFEE--IHLNAEDIPEVTA 201
Cdd:cd03868     80 LENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDPGygGRENANNVDLNRNFPDQFEDsdDRLLEGRQPETLA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  202 VIKWILENKFVLSGNLHGGTVVASYPYDDSAGHSTDGTYSRSPDDALFRHLALVYAENNPVMKTGQPKCEDNvnesFPDG 281
Cdd:cd03868    160 MMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCCEDS----FKDG 235

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207194866  282 ITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYMEQ 340
Cdd:cd03868    236 ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349431 [Multi-domain] Cd Length: 292 Bit Score: 522.21 E-value: 1.46e-175

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:cd03858      1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  554 RNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNYDLNRNFPDRFKLI---TDPIQPETLAVMNWS 630
Cdd:cd03858     81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVysdNNPRQPETKAVMNWL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  631 KNYSFVLSANLHGGSLVVNYPFDDNLEDVIG-YSKSPDDAVFRMVALAYSQENSEMHEGHPCKEMSsyPEYFQDGITNGA 709
Cdd:cd03858    161 ESIPFVLSANLHGGALVANYPYDDTRSGKSTeYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCCDD--DENFPNGITNGA 238

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207194866  710 AWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd03858    239 AWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; The third carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain III. 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. 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.

Pssm-ID: 349464 [Multi-domain] Cd Length: 283 Bit Score: 455.75 E-value: 2.32e-150

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd06245      1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDGRELAKERDCTSTVGMTNVHGKDLDTDFIvGNASQRVSEPQPETRAVMNLIQE 1055
Cdd:cd06245     81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFE-SNANNRSGAAQPETKAIMDWLKE 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1056 RGFTLSVALDGGSLLVTYPYDKPVQTVENDDTLRYLATVYADHHPTMHLGNTGCPNSVQSNIPGGVLRAAVWHSHMGSMK 1135
Cdd:cd06245    160 KDFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1207194866 1136 DFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSMLVE 1179
Cdd:cd06245    240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283

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.

Pssm-ID: 349440 Cd Length: 294 Bit Score: 446.31 E-value: 1.13e-146

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  475 HRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLCR 554
Cdd:cd03868      2 HNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLLE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  555 NYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEG---IKGRNNSKNYDLNRNFPDRFK----LITDPIQPETLAVM 627
Cdd:cd03868     82 NYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGdpgYGGRENANNVDLNRNFPDQFEdsddRLLEGRQPETLAMM 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  628 NWSKNYSFVLSANLHGGSLVVNYPFDDNLEDVI--GYSKSPDDAVFRMVALAYSQENSEMHEGHPCKEmssypEYFQDGI 705
Cdd:cd03868    162 KWIVENPFVLSANLHGGSVVASYPFDDSPSHIEcgVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCCE-----DSFKDGI 236

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207194866  706 TNGAAWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd03868    237 TNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349431 [Multi-domain] Cd Length: 292 Bit Score: 444.02 E-value: 8.81e-146

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTkDISAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03858      1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEIS-DNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKdEGRHNAKNIDLNRSFPDQFEEIHLNAEDI-PEVTAVIK 204
Cdd:cd03858     80 CENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGL-IGRNNANGVDLNRNFPDQFFQVYSDNNPRqPETKAVMN 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  205 WILENKFVLSGNLHGGTVVASYPYDDSAGHSTdGTYSRSPDDALFRHLALVYAENNPVMKTGQPKCEDNvNESFPDGITN 284
Cdd:cd03858    159 WLESIPFVLSANLHGGALVANYPYDDTRSGKS-TEYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCCDD-DENFPNGITN 236

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207194866  285 GAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYMEQ 340
Cdd:cd03858    237 GAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 Carboxypeptidase (CP) M (CPM) belongs to the N/E 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. CPM is an extracellular glycoprotein, bound to cell membranes via a glycosyl-phosphatidylinositol on the C-terminus of the protein. It specifically removes C-terminal basic residues such as lysine and arginine from peptides and proteins. The highest levels of CPM have been found in human lung and placenta, but significant amounts are present in kidney, blood vessels, intestine, brain, and peripheral nerves. CPM has also been found in soluble form in various body fluids, including amniotic fluid, seminal plasma and urine. Due to its wide distribution in a variety of tissues, it is believed that it plays an important role in the control of peptide hormones and growth factor activity on the cell surface and in the membrane-localized degradation of extracellular proteins, for example it hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. CPM is a required processing enzyme that generates specific agonists for the B1 receptor.

Pssm-ID: 349438 Cd Length: 289 Bit Score: 381.06 E-value: 3.25e-122

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:cd03866      1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  554 RNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNYDLNRNFPDRFKLITDPIQPETLAVMNWSKNY 633
Cdd:cd03866     81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEENNVQRQPETRAVMDWIKNE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  634 SFVLSANLHGGSLVVNYPFDDNLEDVI---GYSKSPDDAVFRMVALAYSQENSEMHEGHPCKEMSSypeyFQDGITNGAA 710
Cdd:cd03866    161 TFVLSANLHGGALVASYPFDNGNSGTGqlgYYSVSPDDDVFIYLAKTYSYNHTNMYKGIECSNSQS----FPGGITNGYQ 236

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207194866  711 WYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd03866    237 WYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349431 [Multi-domain] Cd Length: 292 Bit Score: 361.97 E-value: 4.52e-115

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03858      1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDGRELAKERDCTSTVGMTNVHGKDLDTDF--IVGNASQRVSEPQPETRAVMNLI 1053
Cdd:cd03858     81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFpdQFFQVYSDNNPRQPETKAVMNWL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1054 QERGFTLSVALDGGSLLVTYPYDKP-------VQTVENDDTLRYLATVYADHHPTMHLGNTGCPNSvQSNIPGGVLRAAV 1126
Cdd:cd03858    161 ESIPFVLSANLHGGALVANYPYDDTrsgksteYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCCDD-DENFPNGITNGAA 239

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207194866 1127 WHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSMLVE 1179
Cdd:cd03858    240 WYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 Carboxypeptidase N (CPN, also known as kininase I, creatine kinase conversion factor, plasma carboxypeptidase B, arginine carboxypeptidase, and protaminase; EC 3.4.17.3) is an extracellular glycoprotein synthesized in the liver and released into the blood, where it is present in high concentrations. CPN belongs to the N/E subfamily 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. CPN plays an important role in protecting the body from excessive buildup of potentially deleterious peptides that normally act as local autocrine or paracrine hormones. It specifically removes C-terminal basic residues. As CPN can cleave lysine more avidly than arginine residues it is also called lysine carboxypeptidase. CPN substrates include peptides found in the bloodstream, such as kinins (e.g. bradykinin, kalinin, met-lys-bradykinin), complement anaphylatoxins and creatine kinase MM (CK-MM). By removing just one amino acid, CPN can alter peptide activity and receptor binding. For example Bradykinin, a nine-residue peptide released from kiningen in response to tissue injury which is inactivated by CPN, anaphylatoxins which are regulated by CPN by the cleaving and removal of their C-terminal arginines resulting in a reduction in their biological activities of 10-100-fold, and creatine kinase MM, a cytosolic enzyme that catalyzes the reversible transfer of a phosphate group from ATP to creatine, and is regulated by CPN by the cleavage of C-terminal lysines. Like the other N/E subfamily members, two surface loops surrounding the active-site groove restrict access to the catalytic center, thus restricting larger protein carboxypeptidase inhibitors from inhibiting CPN.

Pssm-ID: 349436 [Multi-domain] Cd Length: 313 Bit Score: 359.63 E-value: 6.66e-114

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:cd03864      1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  554 RNYGTDPE-VTQLVDTTRIHIMPSMNPDGYEVS--QKGDVEG-IKGRNNSKNYDLNRNFPDRFKLI-------------- 615
Cdd:cd03864     81 EEYRNGNErITRLIQDTRIHILPSMNPDGYEVAarQGPEFNGyLVGRNNANGVDLNRNFPDLNTLMyynekyggpnhhlp 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  616 -----TDPIQPETLAVMNWSKNYSFVLSANLHGGSLVVNYPFDDNLEDVI------GYSKSPDDAVFRMVALAYSQENSE 684
Cdd:cd03864    161 lpdnwKSQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREPRVrgfrrtAYSPTPDDKLFQKLAKTYSYAHGW 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207194866  685 MHEGHPCKemssypEYFQDGITNGAAWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd03864    241 MHKGWNCG------DYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313

bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial carboxypeptidase (CP) members of the M14 family of metallocarboxypeptidases (MCPs), mostly of which have yet to be characterized. 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349483 [Multi-domain] Cd Length: 281 Bit Score: 354.19 E-value: 2.10e-112

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  475 HRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHElGEPEFKYIGNMHGNEVVGRELLLNLIEYLCR 554
Cdd:cd18173      5 PTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEE-AEPEFKYTSTMHGDETTGYELMLRLIDYLLT 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  555 NYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKgRNNSKNYDLNRNFPDRFKLI---TDPIQPETLAVMNWSK 631
Cdd:cd18173     84 NYGTDPRITNLVDNTEIWINPLANPDGTYAGGNNTVSGAT-RYNANGVDLNRNFPDPVDGDhpdGNGWQPETQAMMNFAD 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  632 NYSFVLSANLHGGSLVVNYPFDDNledvigYSKSPDDAVFRMVALAYSQENsemHEGHPckemSSYPEYFQDGITNGAAW 711
Cdd:cd18173    163 EHNFVLSANFHGGAEVVNYPWDTW------YSRHPDDDWFQDISREYADTN---QANSP----PMYMSEFNNGITNGYDW 229

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207194866  712 YNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd18173    230 YEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 Carboxypeptidase (CP) M (CPM) belongs to the N/E 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. CPM is an extracellular glycoprotein, bound to cell membranes via a glycosyl-phosphatidylinositol on the C-terminus of the protein. It specifically removes C-terminal basic residues such as lysine and arginine from peptides and proteins. The highest levels of CPM have been found in human lung and placenta, but significant amounts are present in kidney, blood vessels, intestine, brain, and peripheral nerves. CPM has also been found in soluble form in various body fluids, including amniotic fluid, seminal plasma and urine. Due to its wide distribution in a variety of tissues, it is believed that it plays an important role in the control of peptide hormones and growth factor activity on the cell surface and in the membrane-localized degradation of extracellular proteins, for example it hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. CPM is a required processing enzyme that generates specific agonists for the B1 receptor.

Pssm-ID: 349438 Cd Length: 289 Bit Score: 345.24 E-value: 7.00e-109

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDISAADgTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03866      1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHR-IGIPEFKYVANMHGDEVVGRELLLHLIEFL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKdEGRHNAKNIDLNRSFPDQFEEIHLNAEdiPEVTAVIKW 205
Cdd:cd03866     80 VTSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYT-KGRYNKNGYDLNRNFPDAFEENNVQRQ--PETRAVMDW 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  206 ILENKFVLSGNLHGGTVVASYPYDDS-AGHSTDGTYSRSPDDALFRHLALVYAENNPVMKTGQpKCEDNvnESFPDGITN 284
Cdd:cd03866    157 IKNETFVLSANLHGGALVASYPFDNGnSGTGQLGYYSVSPDDDVFIYLAKTYSYNHTNMYKGI-ECSNS--QSFPGGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207194866  285 GAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYMEQ 340
Cdd:cd03866    234 GYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The second carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain II. 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, while 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. 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.

Pssm-ID: 349435 [Multi-domain] Cd Length: 296 Bit Score: 334.61 E-value: 6.30e-105

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   45 KYYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTkDISAADGTGKPKFKYVGNMHGDETVSRQVLVYLLED 124
Cdd:cd03863      7 RHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEIS-DNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  125 LLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKdEGRHNAKNIDLNRSFPDQFEEIHLNAEdiPEVTAVIK 204
Cdd:cd03863     86 LCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGT-VGRNNSNNYDLNRNFPDQFFQITDPPQ--PETLAVMS 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  205 WILENKFVLSGNLHGGTVVASYPYDDSagHSTDGTYSRSPDDALFRHLALVYAENNPVMKTGQPKCEDNVNESFPDGITN 284
Cdd:cd03863    163 WLKTYPFVLSANLHGGSLVVNYPFDDD--EQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207194866  285 GAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYMEQ 340
Cdd:cd03863    241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296

Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes only plant members of the carboxypeptidase (CP) N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs). It includes Arabidopsis thaliana SOL1 carboxypeptidase D which is known to possess enzymatic activity to remove the C-terminal arginine residue of CLE19 proprotein in vitro, and SOL1-dependent cleavage of the C-terminal arginine residue is necessary for CLE19 activity in vivo. 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349482 [Multi-domain] Cd Length: 276 Bit Score: 329.37 E-value: 2.73e-103

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  479 DMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHElGEPEFKYIGNMHGNEVVGRELLLNLIEYLCRNY-G 557
Cdd:cd18172      6 ELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDE-TEPAFKFVGNMHGDEPVGRELLLRLADWLCANYkA 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  558 TDPEVTQLVDTTRIHIMPSMNPDGYEvsqkgdvegIKGRNNSKNYDLNRNFPDRFKLI-----TDPIQPETLAVMNWSKN 632
Cdd:cd18172     85 KDPLAAKIVENAHLHLVPTMNPDGFA---------RRRRNNANNVDLNRDFPDQFFPKnlrndLAARQPETLAVMNWSRS 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  633 YSFVLSANLHGGSLVVNYPFDDNLEDVIGYSKSPDDAVFRMVALAYSQENSEMHEGHPckemssypeyFQDGITNGAAWY 712
Cdd:cd18172    156 VRFTASANLHEGALVANYPWDGNADGRTKYSASPDDATFRRLASVYAQAHPNMAKSKE----------FPGGITNGAQWY 225

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207194866  713 NVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIH 762
Cdd:cd18172    226 PLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALAA 275

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 Carboxypeptidase (CP) E (CPE, also known as carboxypeptidase H, and enkephalin convertase; EC 3.4.17.10) belongs to the N/E 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. CPE is an important enzyme responsible for the proteolytic processing of prohormone intermediates (such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin-releasing hormone) by specifically removing C-terminal basic residues. In addition, it has been proposed that the regulated secretory pathway (RSP) of the nervous and endocrine systems utilizes membrane-bound CPE as a sorting receptor. A naturally occurring point mutation in CPE reduces the stability of the enzyme and causes its degradation, leading to an accumulation of numerous neuroendocrine peptides that result in obesity and hyperglycemia. Reduced CPE enzyme and receptor activity could underlie abnormal placental phenotypes from the observation that CPE is down-regulated in enlarged placentas of interspecific hybrid (interspecies hybrid placental dysplasia, IHPD) and cloned mice.

Pssm-ID: 349437 [Multi-domain] Cd Length: 319 Bit Score: 326.17 E-value: 1.70e-101

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:cd03865      1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  554 RNYGTDPE-VTQLVDTTRIHIMPSMNPDGYE--VSQKGDVEG-IKGRNNSKNYDLNRNFPDRFKLI-------------- 615
Cdd:cd03865     81 NEYQKGNEtIINLIHSTRIHIMPSLNPDGFEkaASQPGELKDwFVGRSNAQGIDLNRNFPDLDRIVyvnekeggpnnhll 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  616 ---------TDPIQPETLAVMNWSKNYSFVLSANLHGGSLVVNYPFDDNLE-DVIGYSKSPDDAVFRMVALAYSQENSEM 685
Cdd:cd03865    161 knmkkavdqNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSgSAHEYSSCPDDAIFQSLARAYSSLNPAM 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  686 HEGH--PCKEmSSYPEYFQDGITNGAAWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd03865    241 SDPNrpPCRK-NDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319

bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial carboxypeptidase (CP) members of the M14 family of metallocarboxypeptidases (MCPs), mostly of which have yet to be characterized. 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349483 [Multi-domain] Cd Length: 281 Bit Score: 316.06 E-value: 1.89e-98

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   43 YNKYYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDISAADGtgKPKFKYVGNMHGDETVSRQVLVYLL 122
Cdd:cd18173      1 WDSYPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA--EPEFKYTSTMHGDETTGYELMLRLI 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  123 EDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSveGDCLGKDEGRHNAKNIDLNRSFPDQFEEIHLNAEDI-PEVTA 201
Cdd:cd18173     79 DYLLTNYGTDPRITNLVDNTEIWINPLANPDGTYAG--GNNTVSGATRYNANGVDLNRNFPDPVDGDHPDGNGWqPETQA 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  202 VIKWILENKFVLSGNLHGGTVVASYPYDDsaghstdgTYSRSPDDALFRHLALVYAENNpvmktgQPKCEDNVNESFPDG 281
Cdd:cd18173    157 MMNFADEHNFVLSANFHGGAEVVNYPWDT--------WYSRHPDDDWFQDISREYADTN------QANSPPMYMSEFNNG 222

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207194866  282 ITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYMEQ 340
Cdd:cd18173    223 ITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 Carboxypeptidase (CP) E (CPE, also known as carboxypeptidase H, and enkephalin convertase; EC 3.4.17.10) belongs to the N/E 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. CPE is an important enzyme responsible for the proteolytic processing of prohormone intermediates (such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin-releasing hormone) by specifically removing C-terminal basic residues. In addition, it has been proposed that the regulated secretory pathway (RSP) of the nervous and endocrine systems utilizes membrane-bound CPE as a sorting receptor. A naturally occurring point mutation in CPE reduces the stability of the enzyme and causes its degradation, leading to an accumulation of numerous neuroendocrine peptides that result in obesity and hyperglycemia. Reduced CPE enzyme and receptor activity could underlie abnormal placental phenotypes from the observation that CPE is down-regulated in enlarged placentas of interspecific hybrid (interspecies hybrid placental dysplasia, IHPD) and cloned mice.

Pssm-ID: 349437 [Multi-domain] Cd Length: 319 Bit Score: 315.00 E-value: 2.03e-97

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTkDISAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03865      1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVS-DNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGE-DQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKD--EGRHNAKNIDLNRSFPDQFEEIHLNAED------- 195
Cdd:cd03865     80 CNEYQKgNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDwfVGRSNAQGIDLNRNFPDLDRIVYVNEKEggpnnhl 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  196 --------------IPEVTAVIKWILENKFVLSGNLHGGTVVASYPYDDSAGHSTDgTYSRSPDDALFRHLALVYAENNP 261
Cdd:cd03865    160 lknmkkavdqntklAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAH-EYSSCPDDAIFQSLARAYSSLNP 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  262 VMK-TGQPKCEDNVNE-SFPDGITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYME 339
Cdd:cd03865    239 AMSdPNRPPCRKNDDDsSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIE 318


                   .
gi 1207194866  340 Q 340
Cdd:cd03865    319 Q 319

Zinc carboxypeptidase;

Pssm-ID: 459730 [Multi-domain] Cd Length: 287 Bit Score: 302.68 E-value: 1.72e-93

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  480 MELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLCRNYGTD 559
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  560 PEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNY-----DLNRNFPDRFKLI---TDPI-----------Q 620
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANGSscigvDLNRNFPDHWNEVgasSNPCsetyrgpapfsE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  621 PETLAVMNWSKN-YSFVLSANLHGGSLVVNYPFDDnledvIGYSKSPDDAVFRMVALAYSQENSEMHEGhpckemssypE 699
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGY-----TRDEPPPDDEELKSLARAAAKALQKMVRG----------T 225

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207194866  700 YFQDGITNGAAWYNVHGGMQDWNYMNTNC-FEVTIELGCHK----YPPVADLQKYWEQNRKS 756
Cdd:pfam00246  226 SYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase M14-like domain of carboxypeptidase (CP)-like protein X (CPX), CPX forms a distinct subgroup of the N/E 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. Proteins belonging to this subgroup include CP-like protein X1 (CPX1), CP-like protein X2 (CPX2), and aortic CP-like protein (ACLP) and its isoform adipocyte enhancer binding protein-1 (AEBP1). AEBP1 is a truncated form of ACLP, which may arise from alternative splicing of the gene. These proteins are inactive towards standard CP substrates because they lack one or more critical active site and substrate-binding residues that are necessary for activity. They may function as binding proteins rather than as active CPs or display catalytic activity toward other substrates. Proteins in this subgroup also contain an N-terminal discoidin domain. The CP domain is important for the function of AEBP1 as a transcriptional repressor. AEBP1 is involved in several biological processes including adipogenesis, macrophage cholesterol homeostasis, and inflammation. In macrophages, AEBP1 promotes the expression of IL-6, TNF-alpha, MCP-1, and iNOS whose expression is tightly regulated by NF-kappaB activity. ACLP, a secreted protein that associates with the extracellular matrix, is essential for abdominal wall development and contributes to dermal wound healing.

Pssm-ID: 349441 Cd Length: 322 Bit Score: 303.68 E-value: 2.71e-93

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:cd03869      1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  554 RNY-GTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVE---GIKGRNNSKNYDLNRNFPDRFKLITD------------ 617
Cdd:cd03869     81 QEYlAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSElggWSLGRWTSDGIDINHNFPDLNSLLWEaedrkwvprkvp 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  618 ----PI-----------QPETLAVMNWSKNYSFVLSANLHGGSLVVNYPFD--DNLEDVIGYSKSPDDAVFRMVALAYSQ 680
Cdd:cd03869    161 nhhiPIpewylsenatvAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDmtRTPWKTQEYTPTPDDHVFRWLAYSYAS 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  681 ENSEMHEGH--PCkemssYPEYFQ--DGITNGAAWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKS 756
Cdd:cd03869    241 THRLMTDASrrPC-----HTEDFQkeDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRES 315


                   ....*..
gi 1207194866  757 LLQFIHQ 763
Cdd:cd03869    316 LLVFMEQ 322

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 Carboxypeptidase N (CPN, also known as kininase I, creatine kinase conversion factor, plasma carboxypeptidase B, arginine carboxypeptidase, and protaminase; EC 3.4.17.3) is an extracellular glycoprotein synthesized in the liver and released into the blood, where it is present in high concentrations. CPN belongs to the N/E subfamily 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. CPN plays an important role in protecting the body from excessive buildup of potentially deleterious peptides that normally act as local autocrine or paracrine hormones. It specifically removes C-terminal basic residues. As CPN can cleave lysine more avidly than arginine residues it is also called lysine carboxypeptidase. CPN substrates include peptides found in the bloodstream, such as kinins (e.g. bradykinin, kalinin, met-lys-bradykinin), complement anaphylatoxins and creatine kinase MM (CK-MM). By removing just one amino acid, CPN can alter peptide activity and receptor binding. For example Bradykinin, a nine-residue peptide released from kiningen in response to tissue injury which is inactivated by CPN, anaphylatoxins which are regulated by CPN by the cleaving and removal of their C-terminal arginines resulting in a reduction in their biological activities of 10-100-fold, and creatine kinase MM, a cytosolic enzyme that catalyzes the reversible transfer of a phosphate group from ATP to creatine, and is regulated by CPN by the cleavage of C-terminal lysines. Like the other N/E subfamily members, two surface loops surrounding the active-site groove restrict access to the catalytic center, thus restricting larger protein carboxypeptidase inhibitors from inhibiting CPN.

Pssm-ID: 349436 [Multi-domain] Cd Length: 313 Bit Score: 295.69 E-value: 1.62e-90

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTkDISAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03864      1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFS-DNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKY-GEDQRVTELVNTTDIYILPSMNPDGFERSVEG--DCLGKDEGRHNAKNIDLNRSFPD------QFEEI-----HL 191
Cdd:cd03864     80 CEEYrNGNERITRLIQDTRIHILPSMNPDGYEVAARQgpEFNGYLVGRNNANGVDLNRNFPDlntlmyYNEKYggpnhHL 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  192 NAED------IPEVTAVIKWILENKFVLSGNLHGGTVVASYPYDDSAGHSTDG----TYSRSPDDALFRHLALVYAENNP 261
Cdd:cd03864    160 PLPDnwksqvEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREPRVRGfrrtAYSPTPDDKLFQKLAKTYSYAHG 239

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207194866  262 VMKTGQpkcedNVNESFPDGITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYMEQ 340
Cdd:cd03864    240 WMHKGW-----NCGDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase M14-like domain of carboxypeptidase (CP) Z (CPZ), CPZ belongs to the N/E 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. CPZ is a secreted Zn-dependent enzyme whose biological function is largely unknown. Unlike other members of the N/E subfamily, CPZ has a bipartite structure, which consists of an N-terminal cysteine-rich domain (CRD) whose sequence is similar to Wnt-binding proteins, and a C-terminal CP catalytic domain that removes C-terminal Arg residues from substrates. CPZ is enriched in the extracellular matrix and is widely distributed during early embryogenesis. That the CRD of CPZ can bind to Wnt4 suggests that CPZ plays a role in Wnt signaling.

Pssm-ID: 349439 Cd Length: 315 Bit Score: 293.33 E-value: 1.08e-89

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:cd03867      1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  554 RNY-GTDPEVTQLVDTTRIHIMPSMNPDGYEVSQK---GDVEGIKGRNNSKNYDLNRNFPD----RFKLITDP------- 618
Cdd:cd03867     81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEegaGYNGWTSGRQNAQNLDLNRNFPDltseAYRLARTRgarldhi 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  619 ----------IQPETLAVMNWSKNYSFVLSANLHGGSLVVNYPFDDN---LEDVIgYSKSPDDAVFRMVALAYSQENSEM 685
Cdd:cd03867    161 pipqsywwgkVAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSkhpLEEKM-FSPTPDEKMFKLLAKAYADAHPMM 239

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207194866  686 HEGHPCKEMSSYPEyfQDGITNGAAWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFI 761
Cdd:cd03867    240 SDRSENRCGGNFLK--RGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFM 313

Zn_pept domain;

Pssm-ID: 214748 [Multi-domain] Cd Length: 277 Bit Score: 291.16 E-value: 1.75e-89

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVhelGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGSH---DKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   554 RNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNY---DLNRNFPDRFKLITDPI----------- 619
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSPNSNCrgvDLNRNFPFHWGETGNPCsetyagpspfs 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   620 QPETLAVMNWSKNYS-FVLSANLHGGSLVVNYPFDDNLEDVIGYSKSpDDAVFRMVALAYSqensemheghpckemSSYP 698
Cdd:smart00631  158 EPETKAVRDFIRSNRrFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALA---------------SVHG 221

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866   699 EYFQDGITNGAAWYnVHGGMQDWNYMNTN-CFEVTIELGCH-----KYPPVADLQKY 749
Cdd:smart00631  222 TRYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277

Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes only plant members of the carboxypeptidase (CP) N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs). It includes Arabidopsis thaliana SOL1 carboxypeptidase D which is known to possess enzymatic activity to remove the C-terminal arginine residue of CLE19 proprotein in vitro, and SOL1-dependent cleavage of the C-terminal arginine residue is necessary for CLE19 activity in vivo. 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349482 [Multi-domain] Cd Length: 276 Bit Score: 290.85 E-value: 2.59e-89

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDISAADGtgKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd18172      1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDET--EPAFKFVGNMHGDEPVGRELLLRLADWL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGE-DQRVTELVNTTDIYILPSMNPDGFERSVegdclgkdegRHNAKNIDLNRSFPDQF----EEIHLNAEDiPEVT 200
Cdd:cd18172     79 CANYKAkDPLAAKIVENAHLHLVPTMNPDGFARRR----------RNNANNVDLNRDFPDQFfpknLRNDLAARQ-PETL 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  201 AVIKWILENKFVLSGNLHGGTVVASYPYDDSAGHSTdgTYSRSPDDALFRHLALVYAENNPVMKTgqpkcednvNESFPD 280
Cdd:cd18172    148 AVMNWSRSVRFTASANLHEGALVANYPWDGNADGRT--KYSASPDDATFRRLASVYAQAHPNMAK---------SKEFPG 216

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207194866  281 GITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYME 339
Cdd:cd18172    217 GITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALAA 275

Zn_pept domain;

Pssm-ID: 214748 [Multi-domain] Cd Length: 277 Bit Score: 280.76 E-value: 1.04e-85

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866    46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDisaaDGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNG----GSHDKPAIFIDAGIHAREWIGPATALYLINQL 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   126 LEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKD--EGRHNAKNIDLNRSFPDQFEEI---------HLNAE 194
Cdd:smart00631   77 LENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKnrSPNSNCRGVDLNRNFPFHWGETgnpcsetyaGPSPF 156

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   195 DIPEVTAVIKWILEN-KFVLSGNLHGGTVVASYPYDDSAGHSTDGTYSrspDDALFRHLALVYAENNPVmktgqpkcedn 273
Cdd:smart00631  157 SEPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD---LDAVAKALAKALASVHGT----------- 222

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207194866   274 vneSFPDGITNGAKWYdVPGGMQDFNYL-KGNCLEITMELSCC-----KYPPSSQLKTE 326
Cdd:smart00631  223 ---RYTYGISNGAIYP-ASGGSDDWAYGvLGIPFSFTLELRDDgrygfLLPPSQIIPTG 277

Zinc carboxypeptidase;

Pssm-ID: 459730 [Multi-domain] Cd Length: 287 Bit Score: 277.26 E-value: 2.25e-84

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   52 LTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDiSAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDLLEKYGE 131
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSG-PGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  132 DQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKdEGRHNAK-----NIDLNRSFPDQFEEIHL------------NAE 194
Cdd:pfam00246   80 DPEITELLDDTDIYILPVVNPDGYEYTHTTDRLWR-KNRSNANgssciGVDLNRNFPDHWNEVGAssnpcsetyrgpAPF 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  195 DIPEVTAVIKWILE-NKFVLSGNLHGGTVVASYPYDDSAghstdgtYSRSPDDALFRHLALVYAENNPVMKTGQpkcedn 273
Cdd:pfam00246  159 SEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTR-------DEPPPDDEELKSLARAAAKALQKMVRGT------ 225

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207194866  274 vneSFPDGITNGAKWYDVPGGMQDFNYLKGNC-LEITMELSCCK----YPPSSQLKTEWENNRDA 333
Cdd:pfam00246  226 ---SYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287

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.

Pssm-ID: 349440 Cd Length: 294 Bit Score: 266.42 E-value: 1.85e-80

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03868      1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDGRELAKERDCTST---VGMTNVHGKDLDTDF---IVGNASQRVSEPQPETRAV 1049
Cdd:cd03868     81 ENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDpgyGGRENANNVDLNRNFpdqFEDSDDRLLEGRQPETLAM 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1050 MNLIQERGFTLSVALDGGSLLVTYPYDKPVQTVEN--------DDTLRYLATVYADHHPTMHLGNTGCPNsvqsNIPGGV 1121
Cdd:cd03868    161 MKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECgvyskspdDAVFRHLAHTYADNHPTMHKGNNCCED----SFKDGI 236

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207194866 1122 LRAAVWHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLS 1175
Cdd:cd03868    237 TNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLS 290

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase M14-like domain of carboxypeptidase (CP) Z (CPZ), CPZ belongs to the N/E 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. CPZ is a secreted Zn-dependent enzyme whose biological function is largely unknown. Unlike other members of the N/E subfamily, CPZ has a bipartite structure, which consists of an N-terminal cysteine-rich domain (CRD) whose sequence is similar to Wnt-binding proteins, and a C-terminal CP catalytic domain that removes C-terminal Arg residues from substrates. CPZ is enriched in the extracellular matrix and is widely distributed during early embryogenesis. That the CRD of CPZ can bind to Wnt4 suggests that CPZ plays a role in Wnt signaling.

Pssm-ID: 349439 Cd Length: 315 Bit Score: 264.06 E-value: 3.04e-79

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMrvtkDISAADGTG---KPKFKYVGNMHGDETVSRQVLVYLL 122
Cdd:cd03867      1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVI----EFSSNPGQHellEPEVKYIGNMHGNEVVGREMLIYLA 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  123 EDLLEKYGE-DQRVTELVNTTDIYILPSMNPDGFERSVE--GDCLGKDEGRHNAKNIDLNRSFPDQFEEIHLNAED---- 195
Cdd:cd03867     77 QYLCSEYLLgNPRIQTLINTTRIHLLPSMNPDGYEVAAEegAGYNGWTSGRQNAQNLDLNRNFPDLTSEAYRLARTrgar 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  196 ---------------IPEVTAVIKWILENKFVLSGNLHGGTVVASYPYDDSAGHSTDGTYSRSPDDALFRHLALVYAENN 260
Cdd:cd03867    157 ldhipipqsywwgkvAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMFSPTPDEKMFKLLAKAYADAH 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  261 PVMK-TGQPKCEDNVNESfpDGITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYME 339
Cdd:cd03867    237 PMMSdRSENRCGGNFLKR--GGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; The third carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain III. 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. 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.

Pssm-ID: 349464 [Multi-domain] Cd Length: 283 Bit Score: 257.37 E-value: 2.67e-77

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDISAADgTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd06245      1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESE-PSEPKILFVGGIHGNAPVGTELLLLLAHFL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKDeGRHNAKNIDLNRSFPDQFEEIHLNAEdiPEVTAVIKW 205
Cdd:cd06245     80 CHNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKI-GEKNANGVDLDTDFESNANNRSGAAQ--PETKAIMDW 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  206 ILENKFVLSGNLHGGTVVASYPYDDsaghstdGTYSRSPDDALfRHLALVYAENNPVMKTGQPKCEDNVNESFPDGITNG 285
Cdd:cd06245    157 LKEKDFTLSVALDGGSLVVTYPYDK-------PVQTVENKETL-KHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRA 228

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207194866  286 AKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDALLAYMEQ 340
Cdd:cd06245    229 SEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; The third carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain III. 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. 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.

Pssm-ID: 349464 [Multi-domain] Cd Length: 283 Bit Score: 255.83 E-value: 8.04e-77

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 553
Cdd:cd06245      1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  554 RNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNYDLNRNFPDRFKLITDPIQPETLAVMNWSKNY 633
Cdd:cd06245     81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANNRSGAAQPETKAIMDWLKEK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  634 SFVLSANLHGGSLVVNYPFDDNLEDVigysksPDDAVFRMVALAYSQENSEMHEGHPCKEMSSyPEYFQDGITNGAAWYN 713
Cdd:cd06245    161 DFTLSVALDGGSLVVTYPYDKPVQTV------ENKETLKHLAKVYANNHPTMHAGDPGCCSNS-DENFTNGVIRASEWHS 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207194866  714 VHGGMQDWNYMNTNCFEVTIELGCHKYPPVADLQKYWEQNRKSLLQFIHQ 763
Cdd:cd06245    234 HKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase M14-like domain of carboxypeptidase (CP)-like protein X (CPX), CPX forms a distinct subgroup of the N/E 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. Proteins belonging to this subgroup include CP-like protein X1 (CPX1), CP-like protein X2 (CPX2), and aortic CP-like protein (ACLP) and its isoform adipocyte enhancer binding protein-1 (AEBP1). AEBP1 is a truncated form of ACLP, which may arise from alternative splicing of the gene. These proteins are inactive towards standard CP substrates because they lack one or more critical active site and substrate-binding residues that are necessary for activity. They may function as binding proteins rather than as active CPs or display catalytic activity toward other substrates. Proteins in this subgroup also contain an N-terminal discoidin domain. The CP domain is important for the function of AEBP1 as a transcriptional repressor. AEBP1 is involved in several biological processes including adipogenesis, macrophage cholesterol homeostasis, and inflammation. In macrophages, AEBP1 promotes the expression of IL-6, TNF-alpha, MCP-1, and iNOS whose expression is tightly regulated by NF-kappaB activity. ACLP, a secreted protein that associates with the extracellular matrix, is essential for abdominal wall development and contributes to dermal wound healing.

Pssm-ID: 349441 Cd Length: 322 Bit Score: 253.21 E-value: 2.22e-75

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTkDISAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03869      1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEIS-DNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKY-GEDQRVTELVNTTDIYILPSMNPDGFERSVEG--DCLGKDEGRHNAKNIDLNRSFPD------QFEE-------- 188
Cdd:cd03869     80 CQEYlAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAgsELGGWSLGRWTSDGIDINHNFPDlnsllwEAEDrkwvprkv 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  189 -----------IHLNAEDIPEVTAVIKWILENKFVLSGNLHGGTVVASYPYDDSAGHSTDGTYSRSPDDALFRHLALVYA 257
Cdd:cd03869    160 pnhhipipewyLSENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYA 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  258 ENNPVMK-TGQPKC--EDNVNEsfpDGITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQLKTEWENNRDAL 334
Cdd:cd03869    240 STHRLMTdASRRPChtEDFQKE---DGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESL 316


                   ....*.
gi 1207194866  335 LAYMEQ 340
Cdd:cd03869    317 LVFMEQ 322

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 Carboxypeptidase (CP) M (CPM) belongs to the N/E 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. CPM is an extracellular glycoprotein, bound to cell membranes via a glycosyl-phosphatidylinositol on the C-terminus of the protein. It specifically removes C-terminal basic residues such as lysine and arginine from peptides and proteins. The highest levels of CPM have been found in human lung and placenta, but significant amounts are present in kidney, blood vessels, intestine, brain, and peripheral nerves. CPM has also been found in soluble form in various body fluids, including amniotic fluid, seminal plasma and urine. Due to its wide distribution in a variety of tissues, it is believed that it plays an important role in the control of peptide hormones and growth factor activity on the cell surface and in the membrane-localized degradation of extracellular proteins, for example it hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. CPM is a required processing enzyme that generates specific agonists for the B1 receptor.

Pssm-ID: 349438 Cd Length: 289 Bit Score: 237.00 E-value: 4.53e-70

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03866      1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDGRELAKERDCTSTVGMTNVHGKDLDTDFIVGNASQRVSEpQPETRAVMNLIQE 1055
Cdd:cd03866     81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEENNVQR-QPETRAVMDWIKN 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1056 RGFTLSVALDGGSLLVTYPYDKPVQTVE---------NDDTLRYLATVYADHHPTMHLGNTgCPNSvqSNIPGGVLRAAV 1126
Cdd:cd03866    160 ETFVLSANLHGGALVASYPFDNGNSGTGqlgyysvspDDDVFIYLAKTYSYNHTNMYKGIE-CSNS--QSFPGGITNGYQ 236

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207194866 1127 WHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSML 1177
Cdd:cd03866    237 WYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYI 287

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The second carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain II. 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, while 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. 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.

Pssm-ID: 349435 [Multi-domain] Cd Length: 296 Bit Score: 224.82 E-value: 1.00e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  894 FRYQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAES 973
Cdd:cd03863      6 FRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  974 LCVNYGKNAAINRLINETRIVILPSINPDGRELAKERDCTSTVGMTNVHGKDLDTDFiVGNASQRVSEPQPETRAVMNLI 1053
Cdd:cd03863     86 LCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNF-PDQFFQITDPPQPETLAVMSWL 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1054 QERGFTLSVALDGGSLLVTYPYDKPVQTV------ENDDTLRYLATVYADHHPTMHLGNTGCPNSVQSNIPGGVLRAAVW 1127
Cdd:cd03863    165 KTYPFVLSANLHGGSLVVNYPFDDDEQGLatysksPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITNGAQW 244

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1128 HSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSML 1177
Cdd:cd03863    245 YNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFI 294

bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial carboxypeptidase (CP) members of the M14 family of metallocarboxypeptidases (MCPs), mostly of which have yet to be characterized. 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349483 [Multi-domain] Cd Length: 281 Bit Score: 202.04 E-value: 5.26e-58

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  895 RYQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPsKPKIRFVAGIHGNAPVGTELLLEFAESL 974
Cdd:cd18173      3 SYPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA-EPEFKYTSTMHGDETTGYELMLRLIDYL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  975 CVNYGKNAAINRLINETRIVILPSINPDGRelakERDCTSTVGM---TNVHGKDLDTDFIVGNASQRVSEP--QPETRAV 1049
Cdd:cd18173     82 LTNYGTDPRITNLVDNTEIWINPLANPDGT----YAGGNNTVSGatrYNANGVDLNRNFPDPVDGDHPDGNgwQPETQAM 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1050 MNLIQERGFTLSVALDGGSLLVTYPYDKPVQTVENDDTLRYLATVYADHhptmhlGNTGCPNSVQSNIPGGVLRAAVWHS 1129
Cdd:cd18173    158 MNFADEHNFVLSANFHGGAEVVNYPWDTWYSRHPDDDWFQDISREYADT------NQANSPPMYMSEFNNGITNGYDWYE 231

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1207194866 1130 HMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSML 1177
Cdd:cd18173    232 VYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYI 279

Zinc carboxypeptidase;

Pssm-ID: 459730 [Multi-domain] Cd Length: 287 Bit Score: 198.68 E-value: 7.30e-57

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  904 EFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLCVNYGKNAA 983
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  984 INRLINETRIVILPSINPDGRELAKERDCTSTVGMTNV-----HGKDLDTDF-----IVGNASQRVSEP--------QPE 1045
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNAngsscIGVDLNRNFpdhwnEVGASSNPCSETyrgpapfsEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1046 TRAVMNLIQERG-FTLSVALDGGSLLVTYPYDKPVQT-VENDDTLRYLATVYADHHPTMHLGntgcpnsvqSNIPGGVLR 1123
Cdd:pfam00246  163 TRAVADFIRSKKpFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRG---------TSYTYGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207194866 1124 AAVWHSHMGSMKDFSVDFGHCP-EITVYTSCC----LFPSAEMLPSLWAENRKS 1172
Cdd:pfam00246  234 GATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287

Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes only plant members of the carboxypeptidase (CP) N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs). It includes Arabidopsis thaliana SOL1 carboxypeptidase D which is known to possess enzymatic activity to remove the C-terminal arginine residue of CLE19 proprotein in vitro, and SOL1-dependent cleavage of the C-terminal arginine residue is necessary for CLE19 activity in vivo. 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. The N/E subfamily includes eight members, of which five (CPN, CPE, CPM, CPD, CPZ) are considered enzymatically active, while the other three are non-active (CPX1, PCX2, ACLP/AEBP1) and lack the critical active site and substrate-binding residues considered necessary for CP activity. These non-active members may function as binding proteins or display catalytic activity towards other substrates. Unlike the A/B CP subfamily, enzymes belonging to the N/E subfamily are not produced as inactive precursors that require proteolysis to produce the active form; rather, they rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell. In addition, all members of the N/E subfamily contain an extra C-terminal domain that is not present in the A/B subfamily. This domain has structural homology to transthyretin and other proteins and has been proposed to function as a folding domain. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation.

Pssm-ID: 349482 [Multi-domain] Cd Length: 276 Bit Score: 194.55 E-value: 1.60e-55

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPsKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd18172      1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDET-EPAFKFVGNMHGDEPVGRELLLRLADWLC 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNY-GKNAAINRLINETRIVILPSINPDGRElAKERDctstvgmtNVHGKDLDTDF----IVGNASQRVSEPQPETRAVM 1050
Cdd:cd18172     80 ANYkAKDPLAAKIVENAHLHLVPTMNPDGFA-RRRRN--------NANNVDLNRDFpdqfFPKNLRNDLAARQPETLAVM 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1051 NLIQERGFTLSVALDGGSLLVTYPYD------KPVQTVENDDTLRYLATVYADHHPTMHLgntgcpnsvQSNIPGGVLRA 1124
Cdd:cd18172    151 NWSRSVRFTASANLHEGALVANYPWDgnadgrTKYSASPDDATFRRLASVYAQAHPNMAK---------SKEFPGGITNG 221

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207194866 1125 AVWHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSML 1177
Cdd:cd18172    222 AQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALA 274

Zn_pept domain;

Pssm-ID: 214748 [Multi-domain] Cd Length: 277 Bit Score: 189.47 E-value: 9.91e-54

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPkvqEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGG---SHDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   976 VNYGKNAAINRLINETRIVILPSINPDGRELAKERDCTSTVG---MTNVHGKDLDTDFIVGNASQRV----------SEP 1042
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNrspNSNCRGVDLNRNFPFHWGETGNpcsetyagpsPFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  1043 QPETRAVMNLIQERG-FTLSVALDGGSLLVTYPYDKPVQTV-----ENDDTLRYLATVYADHHPTmhlgntgcpnsvqsN 1116
Cdd:smart00631  158 EPETKAVRDFIRSNRrFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGT--------------R 223

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1207194866  1117 IPGGVLRAAVWHSHmGSMKDFSVDF-GHCPEITVYTSCC-----LFPSAEMLP 1163
Cdd:smart00631  224 YTYGISNGAIYPAS-GGSDDWAYGVlGIPFSFTLELRDDgrygfLLPPSQIIP 275

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase M14-like domain of carboxypeptidase (CP) Z (CPZ), CPZ belongs to the N/E 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. CPZ is a secreted Zn-dependent enzyme whose biological function is largely unknown. Unlike other members of the N/E subfamily, CPZ has a bipartite structure, which consists of an N-terminal cysteine-rich domain (CRD) whose sequence is similar to Wnt-binding proteins, and a C-terminal CP catalytic domain that removes C-terminal Arg residues from substrates. CPZ is enriched in the extracellular matrix and is widely distributed during early embryogenesis. That the CRD of CPZ can bind to Wnt4 suggests that CPZ plays a role in Wnt signaling.

Pssm-ID: 349439 Cd Length: 315 Bit Score: 185.47 E-value: 7.10e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03867      1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNY-GKNAAINRLINETRIVILPSINPDGRELAKERDC---TSTVGMTNVHGKDLDTDF------------IVGNASQRV 1039
Cdd:cd03867     81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAgynGWTSGRQNAQNLDLNRNFpdltseayrlarTRGARLDHI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1040 SEPQ--------PETRAVMNLIQERGFTLSVALDGGSLLVTYPYD--------KPVQTVENDDTLRYLATVYADHHPTMH 1103
Cdd:cd03867    161 PIPQsywwgkvaPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDfskhpleeKMFSPTPDEKMFKLLAKAYADAHPMMS 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207194866 1104 LGNTGCPNSvQSNIPGGVLRAAVWHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSML 1177
Cdd:cd03867    241 DRSENRCGG-NFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFM 313

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 Carboxypeptidase N (CPN, also known as kininase I, creatine kinase conversion factor, plasma carboxypeptidase B, arginine carboxypeptidase, and protaminase; EC 3.4.17.3) is an extracellular glycoprotein synthesized in the liver and released into the blood, where it is present in high concentrations. CPN belongs to the N/E subfamily 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. CPN plays an important role in protecting the body from excessive buildup of potentially deleterious peptides that normally act as local autocrine or paracrine hormones. It specifically removes C-terminal basic residues. As CPN can cleave lysine more avidly than arginine residues it is also called lysine carboxypeptidase. CPN substrates include peptides found in the bloodstream, such as kinins (e.g. bradykinin, kalinin, met-lys-bradykinin), complement anaphylatoxins and creatine kinase MM (CK-MM). By removing just one amino acid, CPN can alter peptide activity and receptor binding. For example Bradykinin, a nine-residue peptide released from kiningen in response to tissue injury which is inactivated by CPN, anaphylatoxins which are regulated by CPN by the cleaving and removal of their C-terminal arginines resulting in a reduction in their biological activities of 10-100-fold, and creatine kinase MM, a cytosolic enzyme that catalyzes the reversible transfer of a phosphate group from ATP to creatine, and is regulated by CPN by the cleavage of C-terminal lysines. Like the other N/E subfamily members, two surface loops surrounding the active-site groove restrict access to the catalytic center, thus restricting larger protein carboxypeptidase inhibitors from inhibiting CPN.

Pssm-ID: 349436 [Multi-domain] Cd Length: 313 Bit Score: 182.44 E-value: 6.89e-51

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03864      1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNY-GKNAAINRLINETRIVILPSINPDGRELAKERDCTST---VGMTNVHGKDLDTDFIVGNA----SQRVSEP----- 1042
Cdd:cd03864     81 EEYrNGNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNgylVGRNNANGVDLNRNFPDLNTlmyyNEKYGGPnhhlp 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1043 ---------QPETRAVMNLIQERGFTLSVALDGGSLLVTYPYDKP-----------VQTVENDDTL-RYLATVYADHHPT 1101
Cdd:cd03864    161 lpdnwksqvEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSreprvrgfrrtAYSPTPDDKLfQKLAKTYSYAHGW 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207194866 1102 MHLGnTGCpnsvQSNIPGGVLRAAVWHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSMLVE 1179
Cdd:cd03864    241 MHKG-WNC----GDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase M14-like domain of carboxypeptidase (CP)-like protein X (CPX), CPX forms a distinct subgroup of the N/E 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. Proteins belonging to this subgroup include CP-like protein X1 (CPX1), CP-like protein X2 (CPX2), and aortic CP-like protein (ACLP) and its isoform adipocyte enhancer binding protein-1 (AEBP1). AEBP1 is a truncated form of ACLP, which may arise from alternative splicing of the gene. These proteins are inactive towards standard CP substrates because they lack one or more critical active site and substrate-binding residues that are necessary for activity. They may function as binding proteins rather than as active CPs or display catalytic activity toward other substrates. Proteins in this subgroup also contain an N-terminal discoidin domain. The CP domain is important for the function of AEBP1 as a transcriptional repressor. AEBP1 is involved in several biological processes including adipogenesis, macrophage cholesterol homeostasis, and inflammation. In macrophages, AEBP1 promotes the expression of IL-6, TNF-alpha, MCP-1, and iNOS whose expression is tightly regulated by NF-kappaB activity. ACLP, a secreted protein that associates with the extracellular matrix, is essential for abdominal wall development and contributes to dermal wound healing.

Pssm-ID: 349441 Cd Length: 322 Bit Score: 181.18 E-value: 2.33e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03869      1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGK-NAAINRLINETRIVILPSINPDGRELAKERDCTS---TVGMTNVHGKDLDTDF-----IVGNASQRVSEPQ--- 1043
Cdd:cd03869     81 QEYLAgNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELggwSLGRWTSDGIDINHNFpdlnsLLWEAEDRKWVPRkvp 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1044 ------------------PETRAVMNLIQERGFTLSVALDGGSLLVTYPYDK---PVQTVE-----NDDTLRYLATVYAD 1097
Cdd:cd03869    161 nhhipipewylsenatvaPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMtrtPWKTQEytptpDDHVFRWLAYSYAS 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1098 HHPTMHLGNTGCPNSVQSNIPGGVLRAAVWHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSML 1177
Cdd:cd03869    241 THRLMTDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFM 320

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 Carboxypeptidase (CP) E (CPE, also known as carboxypeptidase H, and enkephalin convertase; EC 3.4.17.10) belongs to the N/E 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. CPE is an important enzyme responsible for the proteolytic processing of prohormone intermediates (such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin-releasing hormone) by specifically removing C-terminal basic residues. In addition, it has been proposed that the regulated secretory pathway (RSP) of the nervous and endocrine systems utilizes membrane-bound CPE as a sorting receptor. A naturally occurring point mutation in CPE reduces the stability of the enzyme and causes its degradation, leading to an accumulation of numerous neuroendocrine peptides that result in obesity and hyperglycemia. Reduced CPE enzyme and receptor activity could underlie abnormal placental phenotypes from the observation that CPE is down-regulated in enlarged placentas of interspecific hybrid (interspecies hybrid placental dysplasia, IHPD) and cloned mice.

Pssm-ID: 349437 [Multi-domain] Cd Length: 319 Bit Score: 180.95 E-value: 3.31e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03865      1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGK-NAAINRLINETRIVILPSINPDGRELAKERDCTST---VGMTNVHGKDLDTDF-------------------IV 1032
Cdd:cd03865     81 NEYQKgNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKdwfVGRSNAQGIDLNRNFpdldrivyvnekeggpnnhLL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1033 GNASQRVSE-PQ--PETRAVMNLIQERGFTLSVALDGGSLLVTYPYDKP-------VQTVENDDTLRYLATVYADHHPTM 1102
Cdd:cd03865    161 KNMKKAVDQnTKlaPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETrsgsaheYSSCPDDAIFQSLARAYSSLNPAM 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866 1103 HLGNTG-C-PNSVQSNIPGGVLRAAVWHSHMGSMKDFSVDFGHCPEITVYTSCCLFPSAEMLPSLWAENRKSLLSML 1177
Cdd:cd03865    241 SDPNRPpCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYI 317

Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) T (CPT), CPT belongs to 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. CPT has moderate similarity to CPA and CPB, and exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues like CPA and C-terminal positively charged residues like CPB. CPA and CPB are M14 family peptidases but do not belong to this CPT group. The substrate specificity difference between CPT and CPA and CPB is ascribed to a few amino acid substitutions at the substrate-binding pocket while the spatial organization of the binding site remains the same as in all Zn-CPs. CPT has increased thermal stability in presence of Ca2+ ions, and two disulfide bridges which give an additional stabilization factor.

Pssm-ID: 349432 [Multi-domain] Cd Length: 292 Bit Score: 177.06 E-value: 2.67e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  475 HRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHElGEPEFKYIGNMHGNEVVGRELLLNLIEYLCR 554
Cdd:cd03859      5 HTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDEDE-DEPEVLFMGLHHAREWISLEVALYFADYLLE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  555 NYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGI--KGRNNSKNY-------DLNRNFPDRFKLI-----TDPI- 619
Cdd:cd03859     84 NYGTDPRITNLVDNREIWIIPVVNPDGYEYNRETGGGRLwrKNRRPNNGNnpgsdgvDLNRNYGYHWGGDnggssPDPSs 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  620 ----------QPETLAVMNWSKNYSFVLSANLHGGSLVVNYPFddnledviGYSKS---PDDAVFRmvalaysqensEMH 686
Cdd:cd03859    164 etyrgpapfsEPETQAIRDLVESHDFKVAISYHSYGELVLYPW--------GYTSDaptPDEDVFE-----------ELA 224

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207194866  687 EghpckEMSSYPEYfqdGITNGAAW--YNVHGGMQDWNYMNTNCFEVTIELG---CHKYPPVADLQKYWEQNRKSL 757
Cdd:cd03859    225 E-----EMASYNGG---GYTPQQSSdlYPTNGDTDDWMYGEKGIIAFTPELGpefYPFYPPPSQIDPLAEENLPAA 292

M14 family of metallocarboxypeptidases and related proteins; The M14 family of metallocarboxypeptidases (MCPs), also known as funnelins, are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

Pssm-ID: 349427 [Multi-domain] Cd Length: 216 Bit Score: 168.02 E-value: 4.83e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  530 YIGNMHGNEVVGRELLLNLIEYLCRNYGTDPeVTQLVDTTRIHIMPSMNPDGYEVsqkgdVEGIKGRNNSKNYDLNRNFP 609
Cdd:cd00596      3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFAR-----VIDSGGRKNANGVDLNRNFP 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  610 DRFKLITDPI-------------QPETLAVMNWSKNYSFVLSANLHGGSLVVNYPFDDNLEDVigysksPDDAVFRMVAL 676
Cdd:cd00596     77 YNWGKDGTSGpssptyrgpapfsEPETQALRDLAKSHRFDLAVSYHSSSEAILYPYGYTNEPP------PDFSEFQELAA 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  677 AYSQENSemheghpckemssypeYFQDGITNGAAWYNVHGGMQDWNYMNTNCFEVTIELGCHKYPPVAD-LQKYWEQNRK 755
Cdd:cd00596    151 GLARALG----------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTlLDRRLERNLA 214


                   ..
gi 1207194866  756 SL 757
Cdd:cd00596    215 AL 216

Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) T (CPT), CPT belongs to 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. CPT has moderate similarity to CPA and CPB, and exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues like CPA and C-terminal positively charged residues like CPB. CPA and CPB are M14 family peptidases but do not belong to this CPT group. The substrate specificity difference between CPT and CPA and CPB is ascribed to a few amino acid substitutions at the substrate-binding pocket while the spatial organization of the binding site remains the same as in all Zn-CPs. CPT has increased thermal stability in presence of Ca2+ ions, and two disulfide bridges which give an additional stabilization factor.

Pssm-ID: 349432 [Multi-domain] Cd Length: 292 Bit Score: 152.03 E-value: 1.38e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDisAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03859      4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDN--PDEDEDEPEVLFMGLHHAREWISLEVALYFADYL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGdclGKDEG-RHNAKN----------IDLNRSF------------ 182
Cdd:cd03859     82 LENYGTDPRITNLVDNREIWIIPVVNPDGYEYNRET---GGGRLwRKNRRPnngnnpgsdgVDLNRNYgyhwggdnggss 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  183 ----------PDQFEEihlnaediPEVTAVIKWILENKFVLSGNLHGGTVVASYPYddsaGHSTDGTysrSPDDALFRHL 252
Cdd:cd03859    159 pdpssetyrgPAPFSE--------PETQAIRDLVESHDFKVAISYHSYGELVLYPW----GYTSDAP---TPDEDVFEEL 223

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  253 ALVYAENNPVmktgqpkcednvnesfpdGITNGAKW--YDVPGGMQDFNYLKGNCLEITMEL---SCCKYPPSSQLKTEW 327
Cdd:cd03859    224 AEEMASYNGG------------------GYTPQQSSdlYPTNGDTDDWMYGEKGIIAFTPELgpeFYPFYPPPSQIDPLA 285


                   ....*..
gi 1207194866  328 ENNRDAL 334
Cdd:cd03859    286 EENLPAA 292

Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442113 [Multi-domain] Cd Length: 337 Bit Score: 142.52 E-value: 9.25e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   43 YNKYYNYDELTELLKSLAVKHPsIANLTSIGRSVEGRELWVMRVTKDisaadGTGKPKFKYVGNMHGDETVSRQVLVYLL 122
Cdd:COG2866     16 YDRYYTYEELLALLAKLAAASP-LVELESIGKSVEGRPIYLLKIGDP-----AEGKPKVLLNAQQHGNEWTGTEALLGLL 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  123 EDLLEKYGEDqrVTELVNTTDIYILPSMNPDGFERSvegdclgkdeGRHNAKNIDLNRSFPDQFeeihlnaEDIPEVTAV 202
Cdd:COG2866     90 EDLLDNYDPL--IRALLDNVTLYIVPMLNPDGAERN----------TRTNANGVDLNRDWPAPW-------LSEPETRAL 150

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207194866  203 IKWILENKFVLSGNLHGGTVVASYPYDDSAGHSTDGTYSRSPDDALFRHL 252
Cdd:COG2866    151 RDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEEREAFAEE 200

Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442113 [Multi-domain] Cd Length: 337 Bit Score: 141.75 E-value: 1.78e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  465 LTIQPQEFR----HHRYI---DMELFMKKFSSEySSITRLYSIGKSVQKRLLWVMEISNNPGvhelGEPEFKYIGNMHGN 537
Cdd:COG2866      3 LLILPATYKevssYDRYYtyeELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGDPAE----GKPKVLLNAQQHGN 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  538 EVVGRELLLNLIEYLCRNYgtDPEVTQLVDTTRIHIMPSMNPDGYEVSQkgdvegikgRNNSKNYDLNRNFPDRFKLitd 617
Cdd:COG2866     78 EWTGTEALLGLLEDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWLS--- 143

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207194866  618 piQPETLAVMNWSKNYSFVLSANLHGGSLVVNYPFDDNLEDVIGYSKSPDDAVFRMVAL 676
Cdd:COG2866    144 --EPETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEEREAFAEE 200

M14 family of metallocarboxypeptidases and related proteins; The M14 family of metallocarboxypeptidases (MCPs), also known as funnelins, are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

Pssm-ID: 349427 [Multi-domain] Cd Length: 216 Bit Score: 136.05 E-value: 6.98e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  103 YVGNMHGDETVSRQVLVYLLEDLLEKYGEDqRVTELVNTTDIYILPSMNPDGFERsVEGDClgkdeGRHNAKNIDLNRSF 182
Cdd:cd00596      3 ITGGIHGNEVIGVELALALIEYLLENYGND-PLKRLLDNVELWIVPLVNPDGFAR-VIDSG-----GRKNANGVDLNRNF 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  183 PDQFEEIHLNAEDI-----------PEVTAVIKWILENKFVLSGNLHGGTVVASYPYddsaghstDGTYSRSPDDALFRH 251
Cdd:cd00596     76 PYNWGKDGTSGPSSptyrgpapfsePETQALRDLAKSHRFDLAVSYHSSSEAILYPY--------GYTNEPPPDFSEFQE 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  252 LALVYAENNPVmktgqpkcednvnesFPDGITNGAKWYDVPGGMQDFNYLKGNCLEITMELSCCKYPPSSQ-LKTEWENN 330
Cdd:cd00596    148 LAAGLARALGA---------------GEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTlLDRRLERN 212


                   ....
gi 1207194866  331 RDAL 334
Cdd:cd00596    213 LAAL 216

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.

Pssm-ID: 349476 [Multi-domain] Cd Length: 359 Bit Score: 136.59 E-value: 1.27e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   42 TYNKYYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDISAADGTgKPKFKYVGNMHGDETVSRQVLVYL 121
Cdd:cd06905      2 AFDRYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADE-KPALWVDGNIHGNEVTGSEVALYL 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1207194866  122 LEDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERS 158
Cdd:cd06905     81 AEYLLTNYGKDPEITRLLDTRTFYILPRLNPDGAEAY 117

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.

Pssm-ID: 349476 [Multi-domain] Cd Length: 359 Bit Score: 130.43 E-value: 1.90e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  473 RHHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYL 552
Cdd:cd06905      5 RYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYL 84

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1207194866  553 CRNYGTDPEVTQLVDTTRIHIMPSMNPDGYE 583
Cdd:cd06905     85 LTNYGKDPEITRLLDTRTFYILPRLNPDGAE 115

Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) T (CPT), CPT belongs to 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. CPT has moderate similarity to CPA and CPB, and exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues like CPA and C-terminal positively charged residues like CPB. CPA and CPB are M14 family peptidases but do not belong to this CPT group. The substrate specificity difference between CPT and CPA and CPB is ascribed to a few amino acid substitutions at the substrate-binding pocket while the spatial organization of the binding site remains the same as in all Zn-CPs. CPT has increased thermal stability in presence of Ca2+ ions, and two disulfide bridges which give an additional stabilization factor.

Pssm-ID: 349432 [Multi-domain] Cd Length: 292 Bit Score: 127.76 E-value: 3.65e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKvQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03859      4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPD-EDEDEPEVLFMGLHHAREWISLEVALYFADYLL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDG----RELAKER----------DCTSTVGmtnvhGKDLDTDF-------IVGN 1034
Cdd:cd03859     83 ENYGTDPRITNLVDNREIWIIPVVNPDGyeynRETGGGRlwrknrrpnnGNNPGSD-----GVDLNRNYgyhwggdNGGS 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207194866 1035 ASQRVSE----PQ----PETRAVMNLIQERGFTLSVALDGGSLLVTYPY 1075
Cdd:cd03859    158 SPDPSSEtyrgPApfsePETQAIRDLVESHDFKVAISYHSYGELVLYPW 206

Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain; This domain is found C-terminal to the M14 carboxypeptidase (CP) N/E subfamily containing zinc-binding enzymes that 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. The N/E subfamily includes enzymatically active members (carboxypeptidase N, E, M, D, and Z), as well as non-active members (carboxypeptidase-like protein 1, -2, aortic CP-like protein, and adipocyte enhancer binding protein-1) which lack the critical active site and substrate-binding residues considered necessary for activity. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation. For M14 CPs, it has been suggested that this domain may assist in folding of the CP domain, regulate enzyme activity, or be involved in interactions with other proteins or with membranes; for carboxypeptidase M, it may interact with the bradykinin 1 receptor at the cell surface. This domain may also be found in other peptidase families.

Pssm-ID: 200604 [Multi-domain] Cd Length: 76 Bit Score: 111.08 E-value: 4.88e-29

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207194866  344 GVRGFVRAAkNEAPIADAVIMVADIKHNVSTSRFGDYYRLLLPGTYSITAVAPGYIPMTVaGVEVKEG-KATVLNITL 420
Cdd:cd11308      1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTK-TVTVPNNfSATVVNFTL 76

Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain; This domain is found C-terminal to the M14 carboxypeptidase (CP) N/E subfamily containing zinc-binding enzymes that 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. The N/E subfamily includes enzymatically active members (carboxypeptidase N, E, M, D, and Z), as well as non-active members (carboxypeptidase-like protein 1, -2, aortic CP-like protein, and adipocyte enhancer binding protein-1) which lack the critical active site and substrate-binding residues considered necessary for activity. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation. For M14 CPs, it has been suggested that this domain may assist in folding of the CP domain, regulate enzyme activity, or be involved in interactions with other proteins or with membranes; for carboxypeptidase M, it may interact with the bradykinin 1 receptor at the cell surface. This domain may also be found in other peptidase families.

Pssm-ID: 200604 [Multi-domain] Cd Length: 76 Bit Score: 110.31 E-value: 8.91e-29

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866  767 GVKGMVIDsKDGSGIPNATITVETIHHQVTSSSLGDYWRLLVPGKYKLTASAQGYMSDSSSVTVPKD-GLEIVNFTL 842
Cdd:cd11308      1 GIKGFVTD-ATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76

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.

Pssm-ID: 349476 [Multi-domain] Cd Length: 359 Bit Score: 118.49 E-value: 2.21e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  895 RYQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESL 974
Cdd:cd06905      5 RYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYL 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1207194866  975 CVNYGKNAAINRLINETRIVILPSINPDGRELAK---ERDCTSTV 1016
Cdd:cd06905     85 LTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYKlktERSGRSSP 129

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.

Pssm-ID: 349433 [Multi-domain] Cd Length: 300 Bit Score: 116.47 E-value: 2.96e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTkdiSAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd03860      1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIW---GSGGKGGKPAIVIHGGQHAREWISTSTVEYLAHQL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGD--------------CLGkdegrhnaknIDLNRSFPDQFEEIH- 190
Cdd:cd03860     78 LSGYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDrlwrknrqptggssCVG----------IDLNRNWGYKWGGPGa 147

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1207194866  191 -----------LNAEDIPEVTAVIKWILENK 210
Cdd:cd03860    148 stnpcsetyrgPSAFSAPETKALADFINALA 178

Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442113 [Multi-domain] Cd Length: 337 Bit Score: 113.25 E-value: 9.40e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  895 RYQQYGEVSEFLRGLTLNfPEITSLRSLGQSVEIRNIWALEISNnpkvQEPSKPKIRFVAGIHGNAPVGTELLLEFAESL 974
Cdd:COG2866     18 RYYTYEELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  975 CVNYgkNAAINRLINETRIVILPSINPDGRELAKeRdctstvgmTNVHGKDLDTDFIVGNASqrvsepQPETRAVMNLIQ 1054
Cdd:COG2866     93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT-R--------TNANGVDLNRDWPAPWLS------EPETRALRDLLD 155

                          170       180
                   ....*....|....*....|....*.
gi 1207194866 1055 ERGFTLSVAL--DGGSLLVTYPYDKP 1078
Cdd:COG2866    156 EHDPDFVLDLhgQGELFYWFVGTTEP 181

M14 family of metallocarboxypeptidases and related proteins; The M14 family of metallocarboxypeptidases (MCPs), also known as funnelins, are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavage. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.

Pssm-ID: 349427 [Multi-domain] Cd Length: 216 Bit Score: 102.15 E-value: 3.29e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  952 FVAGIHGNAPVGTELLLEFAESLCVNYGKNaAINRLINETRIVILPSINPDGRELAKERDctstvGMTNVHGKDL----D 1027
Cdd:cd00596      3 ITGGIHGNEVIGVELALALIEYLLENYGND-PLKRLLDNVELWIVPLVNPDGFARVIDSG-----GRKNANGVDLnrnfP 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1028 TDFIVGNASQRVSE--------PQPETRAVMNLIQERGFTLSVALDGGSLLVTYPYDKPVQTVENDDTLRYLATVYADHH 1099
Cdd:cd00596     77 YNWGKDGTSGPSSPtyrgpapfSEPETQALRDLAKSHRFDLAVSYHSSSEAILYPYGYTNEPPPDFSEFQELAAGLARAL 156

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207194866 1100 PtmhlgntgcpnsvqsNIPGGVLRAAVWHSHMGSMKDFSVDFGHCPEITVYTSCCL-FPSAEMLPSLWAENRKSL 1173
Cdd:cd00596    157 G---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADyPLPGTLLDRRLERNLAAL 216

Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain; This domain is found C-terminal to the M14 carboxypeptidase (CP) N/E subfamily containing zinc-binding enzymes that 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. The N/E subfamily includes enzymatically active members (carboxypeptidase N, E, M, D, and Z), as well as non-active members (carboxypeptidase-like protein 1, -2, aortic CP-like protein, and adipocyte enhancer binding protein-1) which lack the critical active site and substrate-binding residues considered necessary for activity. The active N/E enzymes fulfill a variety of cellular functions, including prohormone processing, regulation of peptide hormone activity, alteration of protein-protein or protein-cell interactions and transcriptional regulation. For M14 CPs, it has been suggested that this domain may assist in folding of the CP domain, regulate enzyme activity, or be involved in interactions with other proteins or with membranes; for carboxypeptidase M, it may interact with the bradykinin 1 receptor at the cell surface. This domain may also be found in other peptidase families.

Pssm-ID: 200604 [Multi-domain] Cd Length: 76 Bit Score: 87.96 E-value: 6.30e-21

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207194866 1183 GVRGIVKDKNGKPIVGAAIVLNGG-VRVYTSEGGYFHALLAPGLHSIEAVADGYQQQSQKVSVSqfEAASSIIIEFDM 1259
Cdd:cd11308      1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVP--NNFSATVVNFTL 76

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.

Pssm-ID: 349433 [Multi-domain] Cd Length: 300 Bit Score: 90.66 E-value: 1.91e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  475 HRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGVHelGEPEFKYIGNMHGNEVVGRELLLNLIEYLCR 554
Cdd:cd03860      2 HPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGGKG--GKPAIVIHGGQHAREWISTSTVEYLAHQLLS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  555 NYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDvegikgR----NNSKNY-------DLNRNFPDRFKLI---TDPI- 619
Cdd:cd03860     80 GYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTD------RlwrkNRQPTGgsscvgiDLNRNWGYKWGGPgasTNPCs 153

                          170       180
                   ....*....|....*....|...
gi 1207194866  620 ----------QPETLAVMNWSKN 632
Cdd:cd03860    154 etyrgpsafsAPETKALADFINA 176

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.

Pssm-ID: 349448 [Multi-domain] Cd Length: 238 Bit Score: 85.08 E-value: 4.40e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  530 YIGNMHGNEVVGRELLLNLIEYLCRNY-----GTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKG----------DVEGIK 594
Cdd:cd06229      3 YNASFHAREYITTLLLMKFIEDYAKAYvnksyIRGKDVGELLNKVTLHIVPMVNPDGVEISQNGsnainpyylrLVAWNK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  595 GRNNSKNY-------DLNRNFPDRFKL-----ITDPI-----------QPETLAVMNWSKNYSFVLSANLHGGSLVVNYP 651
Cdd:cd06229     83 KGTDFTGWkanirgvDLNRNFPAGWEKekrlgPKAPGprdypgkeplsEPETKAMAALTRQNDFDLVLAYHSQGEEIYWG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  652 FDDNLEDVIgyskspdDAVFRMVAlaysqensemheghpckEMSSYPEYFQDGITNGaawynvhGGMQDWNYMNTNCFEV 731
Cdd:cd06229    163 YNGLEPEES-------KAMAEKFA-----------------SVSGYEPVEAEAIDSY-------GGFKDWFIYEFKKPSF 211

                          250       260
                   ....*....|....*....|....
gi 1207194866  732 TIELGCHKYP-PVADLQKYWEQNR 754
Cdd:cd06229    212 TIETGKGNNPlPISQFDEIYEKNK 235

Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 carboxypeptidases found specifically in insects, including B-type carboxypeptidase of H. zea (CPBHz, insect gut carboxypeptidase-3) that is insensitive to potato carboxypeptidase inhibitor (PCI) in corn earworm, and midgut procarboxypeptidase A (PCPAHa, insect gut carboxypeptidase-1) from Helicoverpa armigera larva, a devastating pest of crops. PCPAHa preferentially cleaves aliphatic and aromatic residues. 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.

Pssm-ID: 349467 [Multi-domain] Cd Length: 297 Bit Score: 75.19 E-value: 2.64e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISnNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd06248      1 YHSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIR-STNSEDTSKPTIMIEGGINPREWISPPAALYAIHKLV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNygkNAAINRLINETRIVILPSINPDG--------RELAKERDCTSTVGMTNVHGKDLDTDF-IVGNASQRVSEP---- 1042
Cdd:cd06248     80 ED---VETQSDLLNNFDWIILPVANPDGyvfthtndREWTKNRSTNSNPLGQICFGVNINRNFdYQWNPVLSSESPcsel 156

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207194866 1043 --------QPETRAVMNLIQERG--FTLSVALDGGSLLVTYPYDKPVQTVENDDTlRYLATVYA 1096
Cdd:cd06248    157 yagpsafsEAESRAIRDILHEHGnrIHLYISFHSGGSFILYPWGYDGSTSSNARQ-LHLAGVAA 219

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.

Pssm-ID: 349433 [Multi-domain] Cd Length: 300 Bit Score: 74.87 E-value: 3.18e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPkvQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03860      1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSG--GKGGKPAIVIHGGQHAREWISTSTVEYLAHQLL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDGRELAKERD-----CTSTVGMTNVHGKDLDTDF----IVGNASqrvSEPQ--- 1043
Cdd:cd03860     79 SGYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDrlwrkNRQPTGGSSCVGIDLNRNWgykwGGPGAS---TNPCset 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207194866 1044 ---------PETRAVMNLIQERGFTLSVA--LDGGS--LLVTYPY 1075
Cdd:cd03860    156 yrgpsafsaPETKALADFINALAAGQGIKgfIDLHSysQLILYPY 200

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 Carboxypeptidase (CP) B2 (CPB2, also known as plasma carboxypeptidase B, carboxypeptidase U, and CPU), belongs to the carboxpeptidase 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. CPB2 enzyme displays B-like activity; it only cleaves the basic residues lysine or arginine. It is produced and secreted by the liver as the inactive precursor, procarboxypeptidase U or PCPB2, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). It circulates in plasma as a zymogen bound to plasminogen, and the active enzyme, TAFIa, inhibits fibrinolysis. It is highly regulated, increased TAFI concentrations are thought to increase the risk of thrombosis and coronary artery disease by reducing fibrinolytic activity while low TAFI levels have been correlated with chronic liver disease.

Pssm-ID: 349465 [Multi-domain] Cd Length: 300 Bit Score: 74.46 E-value: 5.54e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   43 YNKYYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVtkdiSAADGTGKPKFKYVGNMHGDETVSRQVLVYLL 122
Cdd:cd06246      2 YEQYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKV----SGKEQTAKNAIWIDCGIHAREWISPAFCLWFI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  123 EDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKDEGRHNAKN----IDLNRSF----------PDQFEE 188
Cdd:cd06246     78 GHASYFYGIIGQHTNLLNLVDFYVMPVVNVDGYDYSWKKNRMWRKNRSKHANNrcigTDLNRNFdagwcgkgasSDSCSE 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  189 IH--LNAEDIPEVTAVIKWILENKFVLSG--NLHGGTVVASYPYddsaghstDGTYSRSPDdalfrHLALVYAENNPVmk 264
Cdd:cd06246    158 TYcgPYPESEPEVKAVASFLRRHKDTIKAyiSMHSYSQMVLFPY--------SYTRNKSKD-----HDELSLLAKEAV-- 222

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207194866  265 TGQPKCEDNVNESFPdgitnGAK-WYDVPGGMQDFNYLKGNCLEITMEL 312
Cdd:cd06246    223 TAIRKTSRNRYTYGP-----GAEtIYLAPGGSDDWAYDLGIKYSFTFEL 266

Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins; Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins. This group belongs to 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. CPT exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues and C-terminal positively charged residues. However, CPT does not belong to this CPT-like group.

Pssm-ID: 349445 [Multi-domain] Cd Length: 267 Bit Score: 73.26 E-value: 7.82e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  509 LWVMEISNNPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLCRNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQkg 588
Cdd:cd06226      2 IRALKLTNKQATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAE-- 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  589 dvEGIKGRNNSKN-----------YDLNRNFPdrFKLITDPI----------------QPETLAVMNWSK 631
Cdd:cd06226     80 --TGLLWRKNTNTtpcpassptygVDLNRNSS--FKWGGAGAggsacsetyrgpsaasEPETQAIENYVK 145

Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 carboxypeptidases found specifically in insects, including B-type carboxypeptidase of H. zea (CPBHz, insect gut carboxypeptidase-3) that is insensitive to potato carboxypeptidase inhibitor (PCI) in corn earworm, and midgut procarboxypeptidase A (PCPAHa, insect gut carboxypeptidase-1) from Helicoverpa armigera larva, a devastating pest of crops. PCPAHa preferentially cleaves aliphatic and aromatic residues. 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.

Pssm-ID: 349467 [Multi-domain] Cd Length: 297 Bit Score: 73.65 E-value: 8.95e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDISaaDGTGKPKFKYVGNMHGDETVSRQVLVYLLEDL 125
Cdd:cd06248      1 YHSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRSTNS--EDTSKPTIMIEGGINPREWISPPAALYAIHKL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  126 LEkygEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCL---GKDEGRHNAKNI----DLNRSFPDQFEEIH-------- 190
Cdd:cd06248     79 VE---DVETQSDLLNNFDWIILPVANPDGYVFTHTNDREwtkNRSTNSNPLGQIcfgvNINRNFDYQWNPVLssespcse 155

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207194866  191 ----LNAEDIPEVTAVIKWILE--NKFVLSGNLHGGTVVASYPYddsaGHStdgtySRSPDDALFRHLALVYA 257
Cdd:cd06248    156 lyagPSAFSEAESRAIRDILHEhgNRIHLYISFHSGGSFILYPW----GYD-----GSTSSNARQLHLAGVAA 219

Carboxypeptidase regulatory-like domain;

Pssm-ID: 433354 [Multi-domain] Cd Length: 81 Bit Score: 67.69 E-value: 9.22e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  344 GVRGFVRAAKNeAPIADAVIMVAD----IKHNVSTSRFGDYY-RLLLPGTYSITAVAPGYIPMTVAGVEVKEGKATVLNI 418
Cdd:pfam13620    1 TISGTVTDPSG-APVPGATVTVTNtdtgTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 1207194866  419 TL 420
Cdd:pfam13620   80 TL 81

Carboxypeptidase regulatory-like domain;

Pssm-ID: 433354 [Multi-domain] Cd Length: 81 Bit Score: 64.22 E-value: 1.42e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  767 GVKGMVIDSkDGSGIPNATITVET----IHHQVTSSSLGDYW-RLLVPGKYKLTASAQGYMSDS-SSVTVPKDGLEIVNF 840
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTNtdtgTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATrTGVTVTAGQTTTLDV 79


                   ..
gi 1207194866  841 TL 842
Cdd:pfam13620   80 TL 81

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.

Pssm-ID: 349453 [Multi-domain] Cd Length: 256 Bit Score: 69.13 E-value: 1.80e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   47 YNYDELTELLkSLAVKHPsIANLTSIGRSVEGRELWVMRVTKDisaadGTGKPKFKYVGNMHGDETVSRqvlvYLLEDLL 126
Cdd:cd06234      1 YSYERHLDLV-ARAQASP-GVRLEVLGQTLDGRDIDLLTIGDP-----GTGKKKVWIIARQHPGETMAE----WFMEGLL 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  127 EKY--GEDQRVTELVNTTDIYILPSMNPDGferSVEGDClgkdegRHNAKNIDLNRSF--PDqfeeihlnAEDIPEVTAV 202
Cdd:cd06234     70 DRLldEDDPVSRALLEKAVFYVVPNMNPDG---SVRGNL------RTNAAGVNLNREWanPS--------LERSPEVFAV 132

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207194866  203 IKWILENKFVLSGNLHGGTVVasyPYDDSAGhsTDGTYSRSPD-DALFRHLALVYAENNPVMKT--GQPKCE 271
Cdd:cd06234    133 RQAMDATGVDFFLDVHGDEAL---PYNFIAG--AEGIPSWTPRlAALEAAFKAALAAASPDFQTehGYPPDA 199

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.

Pssm-ID: 349430 [Multi-domain] Cd Length: 203 Bit Score: 67.48 E-value: 2.24e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  103 YVGNMHGDETVSRQVLVYLLEDLLekyGEDQRVTELVNTTDIYILPSMNPDGFERSVE---GDCLGKDEGRHNAKNIDLN 179
Cdd:cd03857      4 LAAQIHGNETTGTEALMELIRDLA---SESDEAAKLLDNIVILLVPQLNPDGAELFVNfylDSMNGLPGTRYNANGIDLN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  180 RSFPDQF-EEIHLNAEDipevtaVIKWILEnkFVLsgNLHgGTVVASYPYDDSAGHSTDGTYSRSPDDALFR-HLALVYA 257
Cdd:cd03857     81 RDHVKLTqPETQAVAEN------FIHWWPD--IFI--DLH-EQVGASIPYPTPPDAPNYNLVDLRSDAENGQeHIRLIAG 149


                   ..
gi 1207194866  258 EN 259
Cdd:cd03857    150 EG 151

Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A (MpaA) and related proteins. MpaA is a member of the M14 family of metallocarboxypeptidases (MCPs), however it has an exceptional type of activity, it hydrolyzes the gamma-D-glutamyl-meso-diaminopimelic acid (gamma-D-Glu-Dap) bond in murein peptides. MpaA is specific for cleavage of the gamma-D-Glu-Dap bond of free murein tripeptide; it may also cleave murein tetrapeptide. MpaA has a different substrate specificity and cellular role than endopeptidase I, ENP1 (ENP1 does not belong to this group). MpaA works on free murein peptide in the recycling pathway.

Pssm-ID: 349475 [Multi-domain] Cd Length: 214 Bit Score: 67.30 E-value: 2.99e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  922 LGQSVEIRNIWALEISNNPKvqepskPKIRFVAGIHGNAPVGTELLLEFAESLcvnygknaAINRLINETRIVILPSINP 1001
Cdd:cd06904      4 YGTSVKGRPILAYKFGPGSR------ARILIIGGIHGDEPEGVSLVEHLLRWL--------KNHPASGDFHIVVVPCLNP 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1002 DGReLAKERdctstvgmTNVHGKDLDTDFIVGN---ASQRVSEP----------QPETRAVMNLIQERGFTLSVALDGGS 1068
Cdd:cd06904     70 DGL-AAGTR--------TNANGVDLNRNFPTKNwepDARKPKDPryypgpkpasEPETRALVELIERFKPDRIISLHAPY 140

                          170
                   ....*....|.
gi 1207194866 1069 LLVTYPYDKPV 1079
Cdd:cd06904    141 LVNYDGPAKSL 151

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 Carboxypeptidase B (CPB) 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. Carboxypeptidase B (CPB) enzymes only cleave the basic residues lysine or arginine. A/B subfamily enzymes 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 procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients. this subfamily also includes thrombin activatable fibrinolysis inhibitor (TAFIa), a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help in prevention of thrombosis.

Pssm-ID: 349443 [Multi-domain] Cd Length: 300 Bit Score: 68.25 E-value: 5.67e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   42 TYNKYYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKdisaaDGTGKPKFKYVGNMHGDETVSRQVLVYL 121
Cdd:cd03871      2 SYEKYNNWETIEAWTEQVASKNPDLVSRSQIGTTFEGRPIYLLKVGK-----PGSNKKAIFMDCGFHAREWISPAFCQWF 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207194866  122 LEDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKDEGRHNAKN----IDLNRSF 182
Cdd:cd03871     77 VREAVRTYGKEKIMTKLLDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSPNAGSscigTDPNRNF 141

Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A (MpaA) and related proteins. MpaA is a member of the M14 family of metallocarboxypeptidases (MCPs), however it has an exceptional type of activity, it hydrolyzes the gamma-D-glutamyl-meso-diaminopimelic acid (gamma-D-Glu-Dap) bond in murein peptides. MpaA is specific for cleavage of the gamma-D-Glu-Dap bond of free murein tripeptide; it may also cleave murein tetrapeptide. MpaA has a different substrate specificity and cellular role than endopeptidase I, ENP1 (ENP1 does not belong to this group). MpaA works on free murein peptide in the recycling pathway.

Pssm-ID: 349475 [Multi-domain] Cd Length: 214 Bit Score: 64.99 E-value: 2.06e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  500 IGKSVQKR--LLWVMEISNNPGVHelgepefkYIGNMHGNEVVGRELLLNLIEYLcrnyGTDPEVTQLvdttRIHIMPSM 577
Cdd:cd06904      4 YGTSVKGRpiLAYKFGPGSRARIL--------IIGGIHGDEPEGVSLVEHLLRWL----KNHPASGDF----HIVVVPCL 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  578 NPDGYEVSQkgdvegikgRNNSKNYDLNRNFP-------------DRFKLITDPI-QPETLAVMNWSKNYS--FVLSanL 641
Cdd:cd06904     68 NPDGLAAGT---------RTNANGVDLNRNFPtknwepdarkpkdPRYYPGPKPAsEPETRALVELIERFKpdRIIS--L 136

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  642 HGGSLVvnypfddnleDVIGYSKSPddavfrmVALAYSQENsemheGHPckemssYPEYFqdGITNGA--AWYNVHggmq 719
Cdd:cd06904    137 HAPYLV----------NYDGPAKSL-------LAEKLAQAT-----GYP------VVGDV--GYTPGSlgTYAGIE---- 182

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1207194866  720 dwnymnTNCFEVTIELgchkyPPVADLQKYWEQNRKSLLQFIH 762
Cdd:cd06904    183 ------RNIPVITLEL-----PEAVSIDELWQDLKRALIEAIK 214

Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A (MpaA) and related proteins. MpaA is a member of the M14 family of metallocarboxypeptidases (MCPs), however it has an exceptional type of activity, it hydrolyzes the gamma-D-glutamyl-meso-diaminopimelic acid (gamma-D-Glu-Dap) bond in murein peptides. MpaA is specific for cleavage of the gamma-D-Glu-Dap bond of free murein tripeptide; it may also cleave murein tetrapeptide. MpaA has a different substrate specificity and cellular role than endopeptidase I, ENP1 (ENP1 does not belong to this group). MpaA works on free murein peptide in the recycling pathway.

Pssm-ID: 349475 [Multi-domain] Cd Length: 214 Bit Score: 64.22 E-value: 3.56e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   70 TSIGRSVEGRELWVMRVtkdisaadGTGKPKFKYV-GNMHGDETVSrqvlVYLLEDLLEKYGEDQRVTELvnttDIYILP 148
Cdd:cd06904      2 KVYGTSVKGRPILAYKF--------GPGSRARILIiGGIHGDEPEG----VSLVEHLLRWLKNHPASGDF----HIVVVP 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  149 SMNPDGFERSVegdclgkdegRHNAKNIDLNRSFPDQ-FEEIHLNAEDI-----------PEVTAVIKWILENK--FVLS 214
Cdd:cd06904     66 CLNPDGLAAGT----------RTNANGVDLNRNFPTKnWEPDARKPKDPryypgpkpasePETRALVELIERFKpdRIIS 135

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  215 gnLHGGTVVasyPYDDSAGhstdgtysrspdDALFRHLALvyaennpvmKTGQPKcEDNVnesfpdGITngakwydvPGG 294
Cdd:cd06904    136 --LHAPYLV---NYDGPAK------------SLLAEKLAQ---------ATGYPV-VGDV------GYT--------PGS 174

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1207194866  295 MQDFNYLKGNCLEITMELscckyPPSSQLKTEWENNRDALLAYM 338
Cdd:cd06904    175 LGTYAGIERNIPVITLEL-----PEAVSIDELWQDLKRALIEAI 213

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 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.

Pssm-ID: 349461 [Multi-domain] Cd Length: 220 Bit Score: 63.47 E-value: 7.92e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  947 KPKIRFVAGIHGNAPVGTELLLEFAESLCVNYGKNAainrLINETRIVILPSINPDGRElAKERdctstvgmTNVHGKDL 1026
Cdd:cd06242      1 KPTVLLVGQQHGNEPAGREAALALARDLAFGDDARE----LLEKVNVLVVPRANPDGRA-ANTR--------GNANGVDL 67

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1207194866 1027 DTDFIvgnasqRVSepQPETRAVMNLIQErgFTLSVALDG 1066
Cdd:cd06242     68 NRDHL------LLS--TPETRALARVLRD--YRPEVVIDA 97

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.

Pssm-ID: 349450 [Multi-domain] Cd Length: 239 Bit Score: 63.87 E-value: 7.98e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   48 NYDELTELLKSLAVKhpsianLTSIGRsVEGRELWVMRVTkdiSAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDLLE 127
Cdd:cd06231      2 YLRDVAERLGARRFK------VRELGE-VGYQGYPLFALK---SPNPRGDKPRVLISAGIHGDEPAGVEALLRFLESLAE 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  128 KYGEDQRVTelvnttdiyILPSMNPDGFERSVegdclgkdegRHNAKNIDLNRSFpdqfeeiHLNAEDiPEVTAVIKWIL 207
Cdd:cd06231     72 KYLRRVNLL---------VLPCVNPWGFERNT----------RENADGIDLNRSF-------LKDSPS-PEVRALMEFLA 124

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  208 E-NKFVLSGNLHggtvvasypyDDSAGHSTDGtYSRSPDDALFRhlALVYAENnpvmKTGQPKCEDNVNESFP--DG-IT 283
Cdd:cd06231    125 SlGRFDLHLDLH----------EDWDSDGFYL-YELGPALKAGR--DGLQAVD----AVIPPDPISLTIDGSPapDGvIL 187

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866  284 NGAKWYDVPGG-MQDFNYLKGNCLEITMELscckyPPSSQLKTEWENNRDALLAYME 339
Cdd:cd06231    188 RPDDPAERPGWpFAIYLVANGAVRTYTTET-----PSDFPLERRVAAHLAAIRTALE 239

Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins; Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins. This group belongs to 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. CPT exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues and C-terminal positively charged residues. However, CPT does not belong to this CPT-like group.

Pssm-ID: 349445 [Multi-domain] Cd Length: 267 Bit Score: 63.63 E-value: 1.19e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  930 NIWALEISNNPKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAESLCVNYGKNAAINRLINETRIVILPSINPDGRELAKE 1009
Cdd:cd06226      1 DIRALKLTNKQATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAET 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1010 ----RDCTSTVG---MTNVHGKDLDTDFI-----VGNASQRVSE--------PQPETRAVMNLIQ-----ERGFTLS--- 1061
Cdd:cd06226     81 gllwRKNTNTTPcpaSSPTYGVDLNRNSSfkwggAGAGGSACSEtyrgpsaaSEPETQAIENYVKqlfpdQRGPGLTdpa 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207194866 1062 ------VALDGGSL--LVTYPYDKPVQTVENDDTLRYLATVYA 1096
Cdd:cd06226    161 pddtsgIYIDIHSYgnLVLYPWGWTGTPAPNAAGLRTLGRKFA 203

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.

Pssm-ID: 349448 [Multi-domain] Cd Length: 238 Bit Score: 63.13 E-value: 1.32e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  103 YVGNMHGDETVSRQVLVYLLEDLLEKY-----GEDQRVTELVNTTDIYILPSMNPDGFERSVEG---------------- 161
Cdd:cd06229      3 YNASFHAREYITTLLLMKFIEDYAKAYvnksyIRGKDVGELLNKVTLHIVPMVNPDGVEISQNGsnainpyylrlvawnk 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  162 DCLGKDEGRHNAKNIDLNRSFPDQFEEIH--------------LNAEDIPEVTAVIKWILENKFVLSGNLHGGTVVASYP 227
Cdd:cd06229     83 KGTDFTGWKANIRGVDLNRNFPAGWEKEKrlgpkapgprdypgKEPLSEPETKAMAALTRQNDFDLVLAYHSQGEEIYWG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  228 YDDsaghstdgtysRSPDDAlfRHLALVYAEnnpvmKTGQPKCEdnvnesfPDGITNGAKWYDvpggmqDFNYlKGNCLE 307
Cdd:cd06229    163 YNG-----------LEPEES--KAMAEKFAS-----VSGYEPVE-------AEAIDSYGGFKD------WFIY-EFKKPS 210

                          250       260
                   ....*....|....*....|....*...
gi 1207194866  308 ITMELSCCKYP-PSSQLKTEWENNRDAL 334
Cdd:cd06229    211 FTIETGKGNNPlPISQFDEIYEKNKGVL 238

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 Carboxypeptidase (CP) A (CPA) belongs to the 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. CPA enzymes generally favor hydrophobic residues. A/B subfamily enzymes 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 procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. This subfamily includes CPA1, CPA2 and CPA4 forms. Within these A forms, there are slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer.

Pssm-ID: 349442 [Multi-domain] Cd Length: 301 Bit Score: 63.61 E-value: 1.84e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   43 YNKYYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDisaadGTGKPKFKYVGNMHGDETVSRQVLVYLL 122
Cdd:cd03870      3 YAAYHTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTG-----GEERPAIWIDAGIHSREWVTQASAIWTA 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  123 EDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKDEGRHNAKN----IDLNRSFPDQF-----------E 187
Cdd:cd03870     78 EKIVSDYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNRLWRKTRSVNPGSlcigVDPNRNWDAGFggpgassnpcsE 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866  188 EIH---LNAEdiPEVTAVIKWILENkfvlsGN------LHGGTVVASYPYddsaGHSTdgtySRSPD 245
Cdd:cd03870    158 TYHgphANSE--VEVKSIVDFIQSH-----GNfkafisIHSYSQLLMYPY----GYTV----EKAPD 209

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.

Pssm-ID: 349450 [Multi-domain] Cd Length: 239 Bit Score: 62.32 E-value: 2.76e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  919 LRSLGQSVEIRNIWALEISNNPkvqEPSKPKIRFVAGIHGNAPVGTELLLEFAESLcvnygknaaINRLINETRIVILPS 998
Cdd:cd06231     17 VRELGEVGYQGYPLFALKSPNP---RGDKPRVLISAGIHGDEPAGVEALLRFLESL---------AEKYLRRVNLLVLPC 84

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866  999 INPDGRElAKERdctstvgmTNVHGKDLDTDFivgnasqRVSEPQPETRAVMNLIQERG-FTLSVAL 1064
Cdd:cd06231     85 VNPWGFE-RNTR--------ENADGIDLNRSF-------LKDSPSPEVRALMEFLASLGrFDLHLDL 135

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.

Pssm-ID: 349458 [Multi-domain] Cd Length: 194 Bit Score: 60.12 E-value: 6.30e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  534 MHGNEVVGRELLLNLIEYLCRnygTDPEVTQLVDTTRIHIMPSMNPDGYEVSQkgdvegikgRNNSKNYDLNRnfpDRFK 613
Cdd:cd06239      8 MHGNEPTGTEALLDLISYLRR---ERQEFEKILERLTLVAIPMLNPDGAELFT---------RHNAEGIDLNR---DARA 72

                           90       100       110
                   ....*....|....*....|....*....|
gi 1207194866  614 LITdpiqPETLAVMNWSKNYSFVLSANLHG 643
Cdd:cd06239     73 LQT----PESRALKAVLDSFSPKFAFNLHD 98

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.

Pssm-ID: 349457 Cd Length: 217 Bit Score: 60.06 E-value: 9.44e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  955 GIHGNAPVGTELLLEFAESLCVnyGKNAAINRLINETRIVILPSINPDGRE------------------LAKERDCTSTV 1016
Cdd:cd06238      9 SIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRErfvnwfnqnrgavgdpdpQSMEHNEPWPG 86

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1207194866 1017 GMTNVHGKDLDTDFIVGNasqrvsepQPETRAVMNLIQE 1055
Cdd:cd06238     87 GRTNHYLFDLNRDWLAQT--------QPESRARAAAIHR 117

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 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.

Pssm-ID: 349461 [Multi-domain] Cd Length: 220 Bit Score: 60.01 E-value: 1.08e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  530 YIGNMHGNEVVGRELLLNLIEYLCRnygtDPEVTQLVDTTRIHIMPSMNPDGYEVSQkgdvegikgRNNSKNYDLNRnfp 609
Cdd:cd06242      6 LVGQQHGNEPAGREAALALARDLAF----GDDARELLEKVNVLVVPRANPDGRAANT---------RGNANGVDLNR--- 69

                           90
                   ....*....|....*....
gi 1207194866  610 DRFKLITdpiqPETLAVMN 628
Cdd:cd06242     70 DHLLLST----PETRALAR 84

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.

Pssm-ID: 349446 [Multi-domain] Cd Length: 224 Bit Score: 59.98 E-value: 1.17e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  533 NMHGNEVVGRELLLNLIEYLCRNYgTDPE-------VTQLVDTTRIHIMPSMNPDGYEVSQKGDVegiKGRNNSKNYDLN 605
Cdd:cd06227      9 GEHARELISVESALRLLRQLCGGL-QEPAasalrelAREILDNVELKIIPNANPDGRRLVESGDY---CWRGNENGVDLN 84

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207194866  606 RNFPDRFKLITDPIQ------------PETLAVMNWSKNYSFVLSANLHGGSLVVNYPFDD 654
Cdd:cd06227     85 RNWGVDWGKGEKGAPseeypgpkpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAY 145

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.

Pssm-ID: 349446 [Multi-domain] Cd Length: 224 Bit Score: 59.21 E-value: 2.41e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   98 KPKFKYVGNMHGDETVSRQVLVYLLEDLLEKY------GEDQRVTELVNTTDIYILPSMNPDGFERSVEGD-CLgkdegR 170
Cdd:cd06227      1 KPRVLLVFGEHARELISVESALRLLRQLCGGLqepaasALRELAREILDNVELKIIPNANPDGRRLVESGDyCW-----R 75

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207194866  171 HNAKNIDLNRSFPDQFEEIHLNAED----------IPEVTAVIKWILENKFVLSGNLHGGTVVASYPYDDSA 232
Cdd:cd06227     76 GNENGVDLNRNWGVDWGKGEKGAPSeeypgpkpfsEPETRALRDLALSFKPHAFVSVHSGMLAIYTPYAYSA 147

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.

Pssm-ID: 349466 [Multi-domain] Cd Length: 298 Bit Score: 59.86 E-value: 3.31e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   43 YNKYYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRvtkdISAADGTGKPKFKYVGNMHGDETVSRQVLVYLL 122
Cdd:cd06247      1 YTKYHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLK----IGWPSDKPKKIIWMDCGIHAREWIAPAFCQWFV 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  123 EDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCL-GKDEGRHN---AKNIDLNRSFPDQFEEIHLN------ 192
Cdd:cd06247     77 KEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLwRKSRSPHNngtCYGTDLNRNFNSQWCSIGASrnccsi 156

                          170       180
                   ....*....|....*....|
gi 1207194866  193 ------AEDIPEVTAVIKWI 206
Cdd:cd06247    157 ifcgtgPESEPETKAVADLI 176

Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins; Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins. This group belongs to 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. CPT exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues and C-terminal positively charged residues. However, CPT does not belong to this CPT-like group.

Pssm-ID: 349445 [Multi-domain] Cd Length: 267 Bit Score: 59.00 E-value: 4.86e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   80 ELWVMRVTKDiSAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSV 159
Cdd:cd06226      1 DIRALKLTNK-QATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAE 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1207194866  160 EGdcLGKdegRHNAKN-----------IDLNRSFP 183
Cdd:cd06226     80 TG--LLW---RKNTNTtpcpassptygVDLNRNSS 109

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.

Pssm-ID: 349430 [Multi-domain] Cd Length: 203 Bit Score: 57.85 E-value: 4.96e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  954 AGIHGNAPVGTELLLEFAESLCvnyGKNAAINRLINETRIVILPSINPDGRELAKERDCTSTVGMT----NVHGKDLDTD 1029
Cdd:cd03857      6 AQIHGNETTGTEALMELIRDLA---SESDEAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGLPgtryNANGIDLNRD 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207194866 1030 FivgnasqrVSEPQPETRAVMNLIqeRGFTLSVALD-----GGSLLVTYPYDKP 1078
Cdd:cd03857     83 H--------VKLTQPETQAVAENF--IHWWPDIFIDlheqvGASIPYPTPPDAP 126

Carboxypeptidase regulatory-like domain;

Pssm-ID: 433354 [Multi-domain] Cd Length: 81 Bit Score: 54.21 E-value: 5.85e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207194866 1183 GVRGIVKDKNGKPIVGAAIVL-----NGGVRVYTSEGGYFH-ALLAPGLHSIEAVADGYQQQSQK 1241
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRT 65

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.

Pssm-ID: 349466 [Multi-domain] Cd Length: 298 Bit Score: 57.93 E-value: 1.50e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  895 RYQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEI---SNNPKvqepskpKIRFV-AGIHGNAPVGTELLLEF 970
Cdd:cd06247      3 KYHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKPK-------KIIWMdCGIHAREWIAPAFCQWF 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  971 AESLCVNYGKNAAINRLINETRIVILPSINPDG--------RELAKERdctSTVGMTNVHGKDLDTDF------------ 1030
Cdd:cd06247     76 VKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGyiyswttdRLWRKSR---SPHNNGTCYGTDLNRNFnsqwcsigasrn 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1031 ---IVGNASQRVSEpqPETRAVMNLIQERGFTLSVALDGGSL--LVTYPYDKPVQTVENDDTLRYLATVYADHHPTMHlg 1105
Cdd:cd06247    153 ccsIIFCGTGPESE--PETKAVADLIEKKKSDILCYLTIHSYgqLILLPYGYTKEPSPNHEEMMEVGEKAAAALKEKH-- 228

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207194866 1106 ntGCPNSVQSNipggvlrAAVWHSHMGSMKDFSVDFG 1142
Cdd:cd06247    229 --GTSYRVGSS-------ADILYSNSGSSRDWARDIG 256

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; Carboxypeptidase (CP) A6 (CPA6, also known as CPAH; EC 3.4.17.1), 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. CPA6 prefers large hydrophobic C-terminal amino acids as well as histidine, while peptides with a penultimate glycine or proline are very poorly cleaved. Several neuropeptides are processed by CPA6, including Met- and Leu-enkephalin, angiotensin I, and neurotensin. CPA6 converts enkephalin and neurotensin into forms known to be inactive toward their receptors, but converts inactive angiotensin I into the biologically active angiotensin II. Thus, CPA6 plays a possible role in the regulation of neuropeptides in the extracellular environment within the olfactory bulb where it is highly expressed. It is also broadly expressed in embryonic tissue, being found in neuronal tissues, bone, skin as well as the lateral rectus eye muscle. A disruption in the CPA6 gene is linked to Duane syndrome, a defect in the abducens nerve/lateral rectus muscle connection.

Pssm-ID: 349444 [Multi-domain] Cd Length: 300 Bit Score: 57.68 E-value: 1.82e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   46 YYNYDELTELLKSLAVKHPSIANLTSIGRSVEGRELWVMRVTKDisaadgtGKPKFKYV---GNMHGDETVSRQVLVYLL 122
Cdd:cd03872      2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKLGKR-------SRSYKKAVwidCGIHAREWIGPAFCQWFV 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  123 EDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVEGDCLGKDEGRHNAK----NIDLNRSFP----DQFEEIHLN-- 192
Cdd:cd03872     75 KEAINSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKNSRfqcrGVDANRNWKvkwcDEGASLHPCdd 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207194866  193 ------AEDIPEVTAVIKWILENKFVLSGNL--HGGTVVASYPY 228
Cdd:cd03872    155 tycgpfPESEPEVKAVAQFLRKHRKHVRAYLsfHAYAQMLLYPY 198

Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related proteins; Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP), and related proteins. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. This subfamily includes the human AGTPBP-1 and AGBL -2, -3, -4, and -5, and the mouse Nna1/CCP-1 and CCP -2 through -6. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Nna1 is widely expressed in the developing and adult nervous systems, including cerebellar Purkinje and granule neurons, miral cells of the olfactory bulb and retinal photoreceptors. Nna1 is also induced in axotomized motor neurons. Mutations in Nna1 cause Purkinje cell degeneration (pcd). The Nna1 CP domain is required to prevent the retinal photoreceptor loss and cerebellar ataxia phenotypes of pcd mice, and a functional zinc-binding domain is needed for Nna-1 to support neuron survival in these mice. Nna1-like proteins from the different phyla are highly diverse, but they all contain a characteristic N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

Pssm-ID: 349429 Cd Length: 252 Bit Score: 56.44 E-value: 2.43e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   69 LTSIGRSVEGRELwvmRVTKDISAADGTGKPKFKYVGNMHGDETVSRQVLVYLLEDLLEKYGEDQRVTELVNttdIYILP 148
Cdd:cd03856     17 LLEIGVTEQGREI---QALQSLRTERSDDKSWLFLIARQHPGETTGAWVFFGFLDQLLSDDDPAQQLRAEYN---FYIIP 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  149 SMNPDGferSVEGDClgkdegRHNAKNIDLNRSFPDQFEEIHlnaediPEVTAVIKWILENkfvlsgNLHGGTVVASYpy 228
Cdd:cd03856     91 MVNPDG---VARGHW------RTNSRGMDLNRDWHAPDALLS------PETYAVAAALAER------VQSPEGVVLAL-- 147

                          170       180
                   ....*....|....*....|....*.
gi 1207194866  229 dDSAGHSTDGTY--SRSPDDALFRHL 252
Cdd:cd03856    148 -DLHGDNRNVFLtgPDNKDESTNHNP 172

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 Carboxypeptidase (CP) B2 (CPB2, also known as plasma carboxypeptidase B, carboxypeptidase U, and CPU), belongs to the carboxpeptidase 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. CPB2 enzyme displays B-like activity; it only cleaves the basic residues lysine or arginine. It is produced and secreted by the liver as the inactive precursor, procarboxypeptidase U or PCPB2, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). It circulates in plasma as a zymogen bound to plasminogen, and the active enzyme, TAFIa, inhibits fibrinolysis. It is highly regulated, increased TAFI concentrations are thought to increase the risk of thrombosis and coronary artery disease by reducing fibrinolytic activity while low TAFI levels have been correlated with chronic liver disease.

Pssm-ID: 349465 [Multi-domain] Cd Length: 300 Bit Score: 57.13 E-value: 2.48e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  473 RHHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNpgvhelgEPEFKYI----GNMHGNEVVGRELLLNL 548
Cdd:cd06246      4 QYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGK-------EQTAKNAiwidCGIHAREWISPAFCLWF 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207194866  549 IEYLCRNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNY-----DLNRNF 608
Cdd:cd06246     77 IGHASYFYGIIGQHTNLLNLVDFYVMPVVNVDGYDYSWKKNRMWRKNRSKHANNrcigtDLNRNF 141

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.

Pssm-ID: 349430 [Multi-domain] Cd Length: 203 Bit Score: 55.16 E-value: 4.15e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  530 YIGNMHGNEVVGRELLLNLIeylcRNYGTDP-EVTQLVDTTRIHIMPSMNPDGYE----VSQKGDVEGIKGRNNSKNYDL 604
Cdd:cd03857      4 LAAQIHGNETTGTEALMELI----RDLASESdEAAKLLDNIVILLVPQLNPDGAElfvnFYLDSMNGLPGTRYNANGIDL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  605 NRnfpDRFKLitdpIQPETLAVmNWSKNYSFVLS-ANLH---GGSlvvnypfddnledvIGYSKSPDDAVFRMVALAYSQ 680
Cdd:cd03857     80 NR---DHVKL----TQPETQAV-AENFIHWWPDIfIDLHeqvGAS--------------IPYPTPPDAPNYNLVDLRSDA 137

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207194866  681 ENSEMHEGHPCKEMSSY-PEYFQDGITNGAAWYNVHGGMQDWNYMN 725
Cdd:cd03857    138 ENGQEHIRLIAGEGSGElGKYFSPMRGGFDDSTGGNGIGRTSGFHG 183

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 Carboxypeptidase (CP) A (CPA) belongs to the 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. CPA enzymes generally favor hydrophobic residues. A/B subfamily enzymes 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 procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. This subfamily includes CPA1, CPA2 and CPA4 forms. Within these A forms, there are slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer.

Pssm-ID: 349442 [Multi-domain] Cd Length: 301 Bit Score: 56.29 E-value: 4.69e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPkvqePSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03870      6 YHTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDG--------RELAKERDCTSTVGMTNVH-GKDLDTDF-IVGNASQRVSE---- 1041
Cdd:cd03870     82 SDYGKDPSITSILDTMDIFLEIVTNPDGyvfthssnRLWRKTRSVNPGSLCIGVDpNRNWDAGFgGPGASSNPCSEtyhg 161

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866 1042 ----PQPETRAVMNLIQERG-FTLSVALDGGSLLVTYPYDKPVQTVENDDTLRYLAT 1093
Cdd:cd03870    162 phanSEVEVKSIVDFIQSHGnFKAFISIHSYSQLLMYPYGYTVEKAPDQEELDEVAK 218

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 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.

Pssm-ID: 349461 [Multi-domain] Cd Length: 220 Bit Score: 54.23 E-value: 1.01e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   98 KPKFKYVGNMHGDETVSRQVLVYLLEDLLEkyGEDQRvtELVNTTDIYILPSMNPDGFERSVegdclgkdegRHNAKNID 177
Cdd:cd06242      1 KPTVLLVGQQHGNEPAGREAALALARDLAF--GDDAR--ELLEKVNVLVVPRANPDGRAANT----------RGNANGVD 66


                   ...
gi 1207194866  178 LNR 180
Cdd:cd06242     67 LNR 69

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.

Pssm-ID: 349456 [Multi-domain] Cd Length: 239 Bit Score: 54.11 E-value: 1.53e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   56 LKSLAvKHPSIAnLTSIGRSVEGRELWVMRVTkdisaaDGTGKPKFKYVGNMHGDETVSRQVLVYLLEDLLekyGEDQRV 135
Cdd:cd06237      7 IDSLA-KKPFVK-RSTIGKSVEGRPIEALTIG------NPDSKELVVLLGRQHPPEVTGALAMQAFVETLL---ADTELA 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1207194866  136 TELVNTTDIYILPSMNPDGFersvegdclgkDEG--RHNAKNIDLNR 180
Cdd:cd06237     76 KAFRARFRVLVVPLLNPDGV-----------DLGhwRHNAGGVDLNR 111

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 Carboxypeptidase B (CPB) 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. Carboxypeptidase B (CPB) enzymes only cleave the basic residues lysine or arginine. A/B subfamily enzymes 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 procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients. this subfamily also includes thrombin activatable fibrinolysis inhibitor (TAFIa), a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help in prevention of thrombosis.

Pssm-ID: 349443 [Multi-domain] Cd Length: 300 Bit Score: 54.77 E-value: 1.59e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  892 SSFRYQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNnpkvQEPSKPKIRFVAGIHGNAPVGTELLLEFA 971
Cdd:cd03871      2 SYEKYNNWETIEAWTEQVASKNPDLVSRSQIGTTFEGRPIYLLKVGK----PGSNKKAIFMDCGFHAREWISPAFCQWFV 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  972 ESLCVNYGKNAAINRLINETRIVILPSINPDG--------RELAKERdctSTVGMTNVHGKDLDTDF-----IVGNASQR 1038
Cdd:cd03871     78 REAVRTYGKEKIMTKLLDRLDFYILPVLNIDGyvytwtknRMWRKTR---SPNAGSSCIGTDPNRNFnagwcTVGASSNP 154

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207194866 1039 VS--------EPQPETRAVMNLIQERGFTLSVALD--GGSLLVTYPYDKPVQTVENDDTLRYLA 1092
Cdd:cd03871    155 CSetycgsapESEKETKALANFIRNNLSSIKAYLTihSYSQMLLYPYSYTYKLAPNHEELNSIA 218

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.

Pssm-ID: 349456 [Multi-domain] Cd Length: 239 Bit Score: 53.34 E-value: 2.54e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  917 TSLRSLGQSVEIRNIWALEISNNpkvqePSKPKIRFVAGIHgnaP---VGTELLLEFAESLCvnyGKNAAINRLINETRI 993
Cdd:cd06237     16 VKRSTIGKSVEGRPIEALTIGNP-----DSKELVVLLGRQH---PpevTGALAMQAFVETLL---ADTELAKAFRARFRV 84

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207194866  994 VILPSINPDGRELAKERdctstvgmTNVHGKDLDTDFivGNASqrvsepQPETRAVMNLIQER 1056
Cdd:cd06237     85 LVVPLLNPDGVDLGHWR--------HNAGGVDLNRDW--GPFT------QPETRAVRDFLLEL 131

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.

Pssm-ID: 349448 [Multi-domain] Cd Length: 238 Bit Score: 53.11 E-value: 2.66e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  950 IRFVAGIHGNAPVGTELLLEFAESLCVNYGKNAAIN-----RLINETRIVILPSINPDG----------------RELAK 1008
Cdd:cd06229      1 VLYNASFHAREYITTLLLMKFIEDYAKAYVNKSYIRgkdvgELLNKVTLHIVPMVNPDGveisqngsnainpyylRLVAW 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207194866 1009 ERDCTSTVGM-TNVHGKDLDTDFIVG---NASQRVSEP------------QPETRAVMNLIQERGFTLSVALD 1065
Cdd:cd06229     81 NKKGTDFTGWkANIRGVDLNRNFPAGwekEKRLGPKAPgprdypgkeplsEPETKAMAALTRQNDFDLVLAYH 153

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 Carboxypeptidase (CP) B2 (CPB2, also known as plasma carboxypeptidase B, carboxypeptidase U, and CPU), belongs to the carboxpeptidase 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. CPB2 enzyme displays B-like activity; it only cleaves the basic residues lysine or arginine. It is produced and secreted by the liver as the inactive precursor, procarboxypeptidase U or PCPB2, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). It circulates in plasma as a zymogen bound to plasminogen, and the active enzyme, TAFIa, inhibits fibrinolysis. It is highly regulated, increased TAFI concentrations are thought to increase the risk of thrombosis and coronary artery disease by reducing fibrinolytic activity while low TAFI levels have been correlated with chronic liver disease.

Pssm-ID: 349465 [Multi-domain] Cd Length: 300 Bit Score: 54.04 E-value: 2.83e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQY---GEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISnnpKVQEPSKPKIRFVAGIHGNAPVGTELLLEFAE 972
Cdd:cd06246      2 YEQYhslNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVS---GKEQTAKNAIWIDCGIHAREWISPAFCLWFIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  973 SLCVNYGKNAAINRLINETRIVILPSINPDGRELAKE-----RDCTSTVGMTNVHGKDLDTDFIVGNASQRVS------- 1040
Cdd:cd06246     79 HASYFYGIIGQHTNLLNLVDFYVMPVVNVDGYDYSWKknrmwRKNRSKHANNRCIGTDLNRNFDAGWCGKGASsdscset 158

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1041 ------EPQPETRAVMNLIQERGFT--LSVALDGGSLLVTYPYDKPVQTVENDDTLRYLA 1092
Cdd:cd06246    159 ycgpypESEPEVKAVASFLRRHKDTikAYISMHSYSQMVLFPYSYTRNKSKDHDELSLLA 218

CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, and is approximately 90 amino acids in length. The family is found in association with pfam07715 and pfam00593.

Pssm-ID: 433425 [Multi-domain] Cd Length: 88 Bit Score: 49.13 E-value: 3.69e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207194866  768 VKGMVIDSKDGSGIPNATITVETIHHQVTSSSLGDY-WRLLVPGKYKLTASAQGYMSDSSSVTVPKDGLEIVNFTL 842
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTDADGNFeLKNLPAGTYTLVVSFVGYKTQEKKVTVSNDNTLDVNFLL 76

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 Carboxypeptidase (CP) A (CPA) belongs to the 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. CPA enzymes generally favor hydrophobic residues. A/B subfamily enzymes 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 procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. This subfamily includes CPA1, CPA2 and CPA4 forms. Within these A forms, there are slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer.

Pssm-ID: 349442 [Multi-domain] Cd Length: 301 Bit Score: 52.82 E-value: 5.63e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  475 HRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNPGvhelGEPEFKYIGNMHGNEVVGRELLLNLIEYLCR 554
Cdd:cd03870      7 HTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGGE----ERPAIWIDAGIHSREWVTQASAIWTAEKIVS 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207194866  555 NYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRnnSKN-------YDLNRNF 608
Cdd:cd03870     83 DYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNRLWRKTR--SVNpgslcigVDPNRNW 141

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; Carboxypeptidase (CP) A6 (CPA6, also known as CPAH; EC 3.4.17.1), 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. CPA6 prefers large hydrophobic C-terminal amino acids as well as histidine, while peptides with a penultimate glycine or proline are very poorly cleaved. Several neuropeptides are processed by CPA6, including Met- and Leu-enkephalin, angiotensin I, and neurotensin. CPA6 converts enkephalin and neurotensin into forms known to be inactive toward their receptors, but converts inactive angiotensin I into the biologically active angiotensin II. Thus, CPA6 plays a possible role in the regulation of neuropeptides in the extracellular environment within the olfactory bulb where it is highly expressed. It is also broadly expressed in embryonic tissue, being found in neuronal tissues, bone, skin as well as the lateral rectus eye muscle. A disruption in the CPA6 gene is linked to Duane syndrome, a defect in the abducens nerve/lateral rectus muscle connection.

Pssm-ID: 349444 [Multi-domain] Cd Length: 300 Bit Score: 52.67 E-value: 6.27e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  474 HHRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNNpgvhelGEPEFKYIG---NMHGNEVVGRELLLNLIE 550
Cdd:cd03872      2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKLGKR------SRSYKKAVWidcGIHAREWIGPAFCQWFVK 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207194866  551 YLCRNYGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNY-----DLNRNF 608
Cdd:cd03872     76 EAINSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKNSRFqcrgvDANRNW 138

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.

Pssm-ID: 349457 Cd Length: 217 Bit Score: 51.20 E-value: 8.71e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  532 GNMHGNEVVGRELLLNLIEYLCRnyGTDPEVTQLVDTTRIHIMPSMNPDGYE--VSQ----KGDVEGI------------ 593
Cdd:cd06238      8 YSIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRErfVNWfnqnRGAVGDPdpqsmehnepwp 85

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1207194866  594 KGRNNSKNYDLNRnfpDRFKLitdpIQPETLAVMNW 629
Cdd:cd06238     86 GGRTNHYLFDLNR---DWLAQ----TQPESRARAAA 114

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.

Pssm-ID: 349485 Cd Length: 253 Bit Score: 51.30 E-value: 1.25e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  479 DMELFMKKF-SSEYSSITRlysIGKSVQKRLLWVMEISNNPGVHELgepefkYI-GNMHGNEVVGRELLLNLIEYLCRNy 556
Cdd:cd18429      1 DLDRLLAKIrKNPLVEITT---IGKTVEGRPLEIIRIGNESAPHRV------FLrARAHPWEAGGNWVVEGLVERLLQN- 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  557 gtDPEVTQLVDTTRIHIMPSMNPDGyevsqkgdVEGIKGRNNSKNYDLNRN--FPdrfkliTDP-IQPETLAVMNW---- 629
Cdd:cd18429     71 --DEEAKRFLKRYCVYILPMANKDG--------VARGRTRFNANGKDLNREwdKP------ADPvLAPENFALEKWleem 134

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1207194866  630 -SKNYSFVLSANLH---GGSLVVNYPFDDNLE 657
Cdd:cd18429    135 iKAGKKPDLAIELHndgGGNLHVSRPPVDGLE 166

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.

Pssm-ID: 349447 Cd Length: 294 Bit Score: 51.62 E-value: 1.65e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  103 YVGNMHGDETVSRQVLVYLLEDLLE--------KYGE-----DQrVTELVNTTDIYILPSMNPDGFERSVE--------- 160
Cdd:cd06228      5 FIGGVHAREWGSPDILIYFAADLLEaytnntglTYGGktftaAQ-VKSILENVDLVVFPLVNPDGRWYSQTsesmwrknr 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1207194866  161 --------GDCLGKDEGRhnakNIDLNRSFPDQFEEIHLNAEDIP 197
Cdd:cd06228     84 npasagdgGSCIGVDINR----NFDFLWDFPRYFDPGRVPASTSP 124

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.

Pssm-ID: 349450 [Multi-domain] Cd Length: 239 Bit Score: 50.77 E-value: 1.76e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  530 YI-GNMHGNEVVGRELLLNLIEYLCRNYGTDpevtqlvdtTRIHIMPSMNPDGYEVSQkgdvegikgRNNSKNYDLNRNF 608
Cdd:cd06231     46 LIsAGIHGDEPAGVEALLRFLESLAEKYLRR---------VNLLVLPCVNPWGFERNT---------RENADGIDLNRSF 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  609 pdrfklITDPIQPETLAVMNWSKNY-SFVLSANLHGgslvvnypfDDNLEDVIGYSKSPDDAVFRmvalaYSQENSEMHE 687
Cdd:cd06231    108 ------LKDSPSPEVRALMEFLASLgRFDLHLDLHE---------DWDSDGFYLYELGPALKAGR-----DGLQAVDAVI 167

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207194866  688 GHPCKEMSSYPEYFQDG-ITNG-AAWYNVHGGMQDWNYMNTNCFEVTIELgchkyPPVADLQK 748
Cdd:cd06231    168 PPDPISLTIDGSPAPDGvILRPdDPAERPGWPFAIYLVANGAVRTYTTET-----PSDFPLER 225

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 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.

Pssm-ID: 349463 [Multi-domain] Cd Length: 223 Bit Score: 49.37 E-value: 4.43e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  533 NMHGNEVVGRELLLNLIE-----------YLCRNY---GTDPEVTQLVDTTRIHIMPSMNPDGYEVSQkgdvegikgRNN 598
Cdd:cd06244      7 NIHGNEVEGVDALLEFLEmlatepnvtynTLVKYYkveNVDLEVKDLLDDVFFIVVPTENPDGRVANT---------RTN 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1207194866  599 SKNYDLNRNFpdrfkliTDPIQPETLAVMNWSKNYSFVLSANLHG 643
Cdd:cd06244     78 ANGFDLNRDN-------AYQTQPETRAMQELISKWNPVTFLDMHG 115

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.

Pssm-ID: 349458 [Multi-domain] Cd Length: 194 Bit Score: 48.57 E-value: 5.50e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  107 MHGDETVSrqvlVYLLEDLLE-KYGEDQRVTELVNTTDIYILPSMNPDGFERSVegdclgkdegRHNAKNIDLNRsfpdq 185
Cdd:cd06239      8 MHGNEPTG----TEALLDLISyLRRERQEFEKILERLTLVAIPMLNPDGAELFT----------RHNAEGIDLNR----- 68

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1207194866  186 feeihlNAEDI--PEVTAVIKWILENKFVLSGNLHG 219
Cdd:cd06239     69 ------DARALqtPESRALKAVLDSFSPKFAFNLHD 98

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.

Pssm-ID: 349447 Cd Length: 294 Bit Score: 49.69 E-value: 5.97e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  530 YIGNMHGNEVVGRELLLNLIEYLCRNY--GTD----------PEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRN 597
Cdd:cd06228      5 FIGGVHAREWGSPDILIYFAADLLEAYtnNTGltyggktftaAQVKSILENVDLVVFPLVNPDGRWYSQTSESMWRKNRN 84

                           90
                   ....*....|....*....
gi 1207194866  598 --------NSKNYDLNRNF 608
Cdd:cd06228     85 pasagdggSCIGVDINRNF 103

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 Carboxypeptidase B (CPB) 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. Carboxypeptidase B (CPB) enzymes only cleave the basic residues lysine or arginine. A/B subfamily enzymes 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 procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients. this subfamily also includes thrombin activatable fibrinolysis inhibitor (TAFIa), a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help in prevention of thrombosis.

Pssm-ID: 349443 [Multi-domain] Cd Length: 300 Bit Score: 49.37 E-value: 8.41e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  485 KKFSSEYSSITRLYSIGKSVQKRLLWVMEI----SNNPGVhelgepeFKYIGnMHGNEVVGRELLLNLIEYLCRNYGTDP 560
Cdd:cd03871     17 EQVASKNPDLVSRSQIGTTFEGRPIYLLKVgkpgSNKKAI-------FMDCG-FHAREWISPAFCQWFVREAVRTYGKEK 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  561 EVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKN-----YDLNRNFPDRFKLI---TDPI-----------QP 621
Cdd:cd03871     89 IMTKLLDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSPNAGsscigTDPNRNFNAGWCTVgasSNPCsetycgsapesEK 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  622 ETLAVMNWSKNYSFVLSANL--HGGSLVVNYPFDdnledvIGYSKSPDDAVFRMVALAYSQENSEMHEghpckemSSYpe 699
Cdd:cd03871    169 ETKALANFIRNNLSSIKAYLtiHSYSQMLLYPYS------YTYKLAPNHEELNSIAKGAVKELSSLYG-------TKY-- 233

                          250       260
                   ....*....|....*....|....*..
gi 1207194866  700 yfqdgiTNG---AAWYNVHGGMQDWNY 723
Cdd:cd03871    234 ------TYGpgaTTIYPAAGGSDDWAY 254

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.

Pssm-ID: 349434 Cd Length: 245 Bit Score: 48.58 E-value: 8.59e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  948 PKIRFVAGIHGNAPVGTELLLEFAESLCVNYGKNAAINRLINETRIVILPSINPDGReLAKERDCTSTVGM-----TNVH 1022
Cdd:cd03862      1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGGM-ALKTRSNPNGVDLmrnapVEAV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1023 GKdldTDFIVGnaSQRVSE--P--------QPETRAVMNLIQERGF--TLSVALD-----GGSLLVTYPYDKPVQTVEND 1085
Cdd:cd03862     80 EK---VPFLVG--GQRISPhlPwyrgrnglETESQALIRYVNEHLLesKMSISLDchsgfGLVDRIWFPYAHTTEPFPNL 154

                          170
                   ....*....|....*
gi 1207194866 1086 DTLRYLATVYADHHP 1100
Cdd:cd03862    155 AEIFALIQLFRTSYP 169

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.

Pssm-ID: 349456 [Multi-domain] Cd Length: 239 Bit Score: 48.33 E-value: 9.72e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  479 DMELFMKKFSSEYSsiTRLYSIGKSVQKRLLWVMEISNNPGvhelgePEFKY-IGNMHGNEVVGRELLLNLIEYLCrnyG 557
Cdd:cd06237      2 DYDAWIDSLAKKPF--VKRSTIGKSVEGRPIEALTIGNPDS------KELVVlLGRQHPPEVTGALAMQAFVETLL---A 70

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207194866  558 TDPEVTQLVDTTRIHIMPSMNPDGyevsqkgdVEGikG--RNNSKNYDLNRNFpDRFKlitdpiQPETLAVMNW 629
Cdd:cd06237     71 DTELAKAFRARFRVLVVPLLNPDG--------VDL--GhwRHNAGGVDLNRDW-GPFT------QPETRAVRDF 127

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.

Pssm-ID: 349447 Cd Length: 294 Bit Score: 47.76 E-value: 2.64e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  948 PKIRFVAGIHGNAPVGTELLLEFAESLC--------VNYGK----NAAINRLINETRIVILPSINPDGRELA-------- 1007
Cdd:cd06228      1 PGVYFIGGVHAREWGSPDILIYFAADLLeaytnntgLTYGGktftAAQVKSILENVDLVVFPLVNPDGRWYSqtsesmwr 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866 1008 KERDCTSTVGMTNVHGKDLDT------DFIVGNASQRVS---------------EPQPETRAVMNLI 1053
Cdd:cd06228     81 KNRNPASAGDGGSCIGVDINRnfdflwDFPRYFDPGRVPastspcsetyhgpsaFSEPETRNVVWLF 147

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.

Pssm-ID: 349485 Cd Length: 253 Bit Score: 47.07 E-value: 3.18e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   51 ELTELLKSLAvKHPsIANLTSIGRSVEGRELWVMRvtkdISAADGtgkPKFKYV-GNMHGDETVSRQVLVYLLEDLLEKY 129
Cdd:cd18429      1 DLDRLLAKIR-KNP-LVEITTIGKTVEGRPLEIIR----IGNESA---PHRVFLrARAHPWEAGGNWVVEGLVERLLQND 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  130 GEDQRVTELVNttdIYILPSMNPDGFERsvegdclGKDegRHNAKNIDLNRSFPDQFEEIHlnaedIPEVTAVIKWILE- 208
Cdd:cd18429     72 EEAKRFLKRYC---VYILPMANKDGVAR-------GRT--RFNANGKDLNREWDKPADPVL-----APENFALEKWLEEm 134

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207194866  209 ----NKFVLSGNLHggtvvasypyDDSAG--HstdgtYSRSPDDALFRHLA 253
Cdd:cd18429    135 ikagKKPDLAIELH----------NDGGGnlH-----VSRPPVDGLERYLA 170

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 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.

Pssm-ID: 349463 [Multi-domain] Cd Length: 223 Bit Score: 46.67 E-value: 3.52e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  952 FVAGIHGNAPVGTELLLEFAESL----------CVNYGK----NAAINRLINETRIVILPSINPDGRELAKErdctstvg 1017
Cdd:cd06244      4 VYNNIHGNEVEGVDALLEFLEMLatepnvtyntLVKYYKvenvDLEVKDLLDDVFFIVVPTENPDGRVANTR-------- 75

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1207194866 1018 mTNVHGKDLDTDfivgNASQrvsePQPETRAVMNLIQER 1056
Cdd:cd06244     76 -TNANGFDLNRD----NAYQ----TQPETRAMQELISKW 105

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.

Pssm-ID: 349434 Cd Length: 245 Bit Score: 45.50 E-value: 9.80e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   99 PKFKYVGNMHGDETVSRQVLVYLLEDLLEKYGEDQRVTELVNTTDIYILPSMNPDGFERSVegdclgkdegRHNAKNIDL 178
Cdd:cd03862      1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGGMALKT----------RSNPNGVDL 70


                   ....*
gi 1207194866  179 NRSFP 183
Cdd:cd03862     71 MRNAP 75

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.

Pssm-ID: 349457 Cd Length: 217 Bit Score: 45.04 E-value: 9.96e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  105 GNMHGDETVSRQVLVYLLEDLLEkyGEDQRVTELVNTTDIYILPSMNPDGFERSVE------GDCLGKD----------- 167
Cdd:cd06238      8 YSIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRERFVNwfnqnrGAVGDPDpqsmehnepwp 85

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1207194866  168 EGRHNAKNIDLNRsfpDQFEEIHlnaediPEVTAVIKWILE 208
Cdd:cd06238     86 GGRTNHYLFDLNR---DWLAQTQ------PESRARAAAIHR 117

Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 carboxypeptidases found specifically in insects, including B-type carboxypeptidase of H. zea (CPBHz, insect gut carboxypeptidase-3) that is insensitive to potato carboxypeptidase inhibitor (PCI) in corn earworm, and midgut procarboxypeptidase A (PCPAHa, insect gut carboxypeptidase-1) from Helicoverpa armigera larva, a devastating pest of crops. PCPAHa preferentially cleaves aliphatic and aromatic residues. 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.

Pssm-ID: 349467 [Multi-domain] Cd Length: 297 Bit Score: 45.91 E-value: 1.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  475 HRYIDMELFMKKFSSEYSSITRLYSIGKSVQKRLLWVMEISNnPGVHELGEPEFKYIGNMHGNEVVGRELLLNLIEYLCR 554
Cdd:cd06248      2 HSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRS-TNSEDTSKPTIMIEGGINPREWISPPAALYAIHKLVE 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207194866  555 NygtDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGRNNSKNY--------DLNRNF 608
Cdd:cd06248     81 D---VETQSDLLNNFDWIILPVANPDGYVFTHTNDREWTKNRSTNSNPlgqicfgvNINRNF 139

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.

Pssm-ID: 349434 Cd Length: 245 Bit Score: 44.34 E-value: 2.36e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  526 PEFKYIGNMHGNEVVGRELLLNLIEYLCRNYGTDPEVTQLVDTTRIHIMPSMNPDGYevsqkgdveGIKGRNNSKNYDLN 605
Cdd:cd03862      1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGGM---------ALKTRSNPNGVDLM 71


                   ....
gi 1207194866  606 RNFP 609
Cdd:cd03862     72 RNAP 75

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; Carboxypeptidase (CP) A6 (CPA6, also known as CPAH; EC 3.4.17.1), 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. CPA6 prefers large hydrophobic C-terminal amino acids as well as histidine, while peptides with a penultimate glycine or proline are very poorly cleaved. Several neuropeptides are processed by CPA6, including Met- and Leu-enkephalin, angiotensin I, and neurotensin. CPA6 converts enkephalin and neurotensin into forms known to be inactive toward their receptors, but converts inactive angiotensin I into the biologically active angiotensin II. Thus, CPA6 plays a possible role in the regulation of neuropeptides in the extracellular environment within the olfactory bulb where it is highly expressed. It is also broadly expressed in embryonic tissue, being found in neuronal tissues, bone, skin as well as the lateral rectus eye muscle. A disruption in the CPA6 gene is linked to Duane syndrome, a defect in the abducens nerve/lateral rectus muscle connection.

Pssm-ID: 349444 [Multi-domain] Cd Length: 300 Bit Score: 44.59 E-value: 3.10e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  896 YQQYGEVSEFLRGLTLNFPEITSLRSLGQSVEIRNIWALEISNNPKvqePSKPKIRFVAGIHGNAPVGTELLLEFAESLC 975
Cdd:cd03872      2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKLGKRSR---SYKKAVWIDCGIHAREWIGPAFCQWFVKEAI 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  976 VNYGKNAAINRLINETRIVILPSINPDGRELAKERD-----CTSTVGMTNVHGKDLDTDFIVGNASQRVS---------- 1040
Cdd:cd03872     79 NSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDrfwrkTRSKNSRFQCRGVDANRNWKVKWCDEGASlhpcddtycg 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207194866 1041 ---EPQPETRAVMNLI--QERGFTLSVALDGGSLLVTYPYDKPVQTVEN 1084
Cdd:cd03872    159 pfpESEPEVKAVAQFLrkHRKHVRAYLSFHAYAQMLLYPYSYKYATIPN 207

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 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.

Pssm-ID: 349459 Cd Length: 212 Bit Score: 43.41 E-value: 4.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207194866  954 AGIHGNAPVGTELLLEFAESLcVNyGKNAAINRLINETRIVILPSINPDGREL 1006
Cdd:cd06240      8 GGLHATEVAGSQMLPELAYRL-AT-SDDEEVRRILDNVILLLVPSANPDGQDL 58

Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related proteins; Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP), and related proteins. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. This subfamily includes the human AGTPBP-1 and AGBL -2, -3, -4, and -5, and the mouse Nna1/CCP-1 and CCP -2 through -6. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Nna1 is widely expressed in the developing and adult nervous systems, including cerebellar Purkinje and granule neurons, miral cells of the olfactory bulb and retinal photoreceptors. Nna1 is also induced in axotomized motor neurons. Mutations in Nna1 cause Purkinje cell degeneration (pcd). The Nna1 CP domain is required to prevent the retinal photoreceptor loss and cerebellar ataxia phenotypes of pcd mice, and a functional zinc-binding domain is needed for Nna-1 to support neuron survival in these mice. Nna1-like proteins from the different phyla are highly diverse, but they all contain a characteristic N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

Pssm-ID: 349429 Cd Length: 252 Bit Score: 43.34 E-value: 4.81e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  918 SLRSLGQSVEIRNIWALEIsnnPKVQEPSKPKIRFVAG-IHGNAPVGTELLLEFAESLCVNygkNAAINRLINETRIVIL 996
Cdd:cd03856     16 QLLEIGVTEQGREIQALQS---LRTERSDDKSWLFLIArQHPGETTGAWVFFGFLDQLLSD---DDPAQQLRAEYNFYII 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  997 PSINPDGRELAKERdctstvgmTNVHGKDLDTDFIVGNAsqrvsEPQPETRAVMNLIQER-------GFTLSVALDGGSL 1069
Cdd:cd03856     90 PMVNPDGVARGHWR--------TNSRGMDLNRDWHAPDA-----LLSPETYAVAAALAERvqspegvVLALDLHGDNRNV 156

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207194866 1070 LVTYPYDKPVQTVENDDTLRYLATVYADHHPTMHLGntgcpNSVQSNIPGGVLRAAV 1126
Cdd:cd03856    157 FLTGPDNKDESTNHNPDKLNSLLTETDRRLPDYNTE-----ASPGDNPGGTVGKQWI 208

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.

Pssm-ID: 349446 [Multi-domain] Cd Length: 224 Bit Score: 42.64 E-value: 6.36e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  947 KPKIRFVAGIHGNAPVGTELLLEFAESLCVNYGKNAA------INRLINETRIVILPSINPDGRELAKERD-CTStvgmT 1019
Cdd:cd06227      1 KPRVLLVFGEHARELISVESALRLLRQLCGGLQEPAAsalrelAREILDNVELKIIPNANPDGRRLVESGDyCWR----G 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866 1020 NVHGKDL----DTDFIVGNASQRVSE---PQ----PETRAVMNLIQERGFTLSVALDGGSLLVTYPYD----KPVQTVEN 1084
Cdd:cd06227     77 NENGVDLnrnwGVDWGKGEKGAPSEEypgPKpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAysasVPRPNRAA 156


                   .
gi 1207194866 1085 D 1085
Cdd:cd06227    157 D 157

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.

Pssm-ID: 349460 [Multi-domain] Cd Length: 215 Bit Score: 42.63 E-value: 6.92e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  531 IGNMHGNEVVGRELLLNLIeylcRNYgTDPEVTQLVDTTRIHIMPSMNPDGYE-------VSQKGDVE-GIkgRNNSKNY 602
Cdd:cd06241      7 QAGIHPGEVEGKEASLMLL----RDI-AQGGKKHLLDNLILLFVPIFNADGNDrrskgnrPNQNGPLEvGW--RTNAQGL 79

                           90       100
                   ....*....|....*....|....*.
gi 1207194866  603 DLNRNFpdrFKLITdpiqPETLAVMN 628
Cdd:cd06241     80 DLNRDF---MKLEA----PETRALAK 98

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.

Pssm-ID: 349466 [Multi-domain] Cd Length: 298 Bit Score: 42.91 E-value: 8.65e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  483 FMKKFSSEYSSITRLYSIGKSVQKRLLWVMEI---SNNPgvhelgepefKYIGNM----HGNEVVGRELLLNLIEYLCRN 555
Cdd:cd06247     13 WMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKP----------KKIIWMdcgiHAREWIAPAFCQWFVKEILQN 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207194866  556 YGTDPEVTQLVDTTRIHIMPSMNPDGYEVSQKGDVEGIKGR---NNSKNY--DLNRNF 608
Cdd:cd06247     83 YKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLWRKSRsphNNGTCYgtDLNRNF 140

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 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.

Pssm-ID: 349459 Cd Length: 212 Bit Score: 42.26 E-value: 9.18e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207194866  532 GNMHGNEVVGRELLLNLIEYLCRnyGTDPEVTQLVDTTRIHIMPSMNPDGYE 583
Cdd:cd06240      8 GGLHATEVAGSQMLPELAYRLAT--SDDEEVRRILDNVILLLVPSANPDGQD 57

Peptidase M14-like domain of ATP/GTP binding protein AGBL-4 and related proteins; Peptidase M14-like domain of ATP/GTP binding protein_like (AGBL)-4, and related proteins. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. This eukaryotic subgroup includes the human AGBL4 and the mouse cytosolic carboxypeptidase (CCP)-6. ATP/GTP binding protein (AGTPBP-1/Nna1)-like proteins are active metallopeptidases that are thought to act on cytosolic proteins such as alpha-tubulin, to remove a C-terminal tyrosine. Mutations in AGTPBP-1/Nna1 cause Purkinje cell degeneration (pcd). AGTPBP-1/Nna1 however does not belong to this subgroup. AGTPBP-1/Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.

Pssm-ID: 349479 Cd Length: 254 Bit Score: 42.29 E-value: 1.12e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  500 IGKSVQKRLLWVMEISNNPGVHELGEPEFKYI---GNMHGNEVVGRELLLNLIEYLCRNygtDPEVTQLVDTTRIHIMPS 576
Cdd:cd06908      8 LGKSVQQRRLDLLTITDPVNKHLTVEKKKKVVfitARVHPGETPSSFVCQGLIDFLVSN---HPVAKVLRDHLVFKIVPM 84

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207194866  577 MNPDGYEVSQKgdvegikgRNNSKNYDLNRNFPDRfkliTDPIQPETLAVMNWSKNYS 634
Cdd:cd06908     85 LNPDGVFLGNY--------RCSLMGFDLNRHWHEP----SPWAHPTLYAVKNLLRELD 130

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.

Pssm-ID: 349460 [Multi-domain] Cd Length: 215 Bit Score: 41.09 E-value: 2.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  947 KPKIRFVAGIHGNAPVGTELLLEFAESLcVNYGKNAAINRLInetrIVILPSINPDGRELAKERDCTSTVGM------TN 1020
Cdd:cd06241      1 KPVVLIQAGIHPGEVEGKEASLMLLRDI-AQGGKKHLLDNLI----LLFVPIFNADGNDRRSKGNRPNQNGPlevgwrTN 75

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1207194866 1021 VHGKDLDTDFIVGNAsqrvsepqPETRAVMNLIQE 1055
Cdd:cd06241     76 AQGLDLNRDFMKLEA--------PETRALAKLFNQ 102

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.

Pssm-ID: 349453 [Multi-domain] Cd Length: 256 Bit Score: 40.63 E-value: 3.71e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  548 LIEYLCRNygTDPEVTQLVDTTRIHIMPSMNPDGyevsqkgdveGIKG--RNNSKNYDLNRNF--PDRFKlitdpiQPET 623
Cdd:cd06234     68 LLDRLLDE--DDPVSRALLEKAVFYVVPNMNPDG----------SVRGnlRTNAAGVNLNREWanPSLER------SPEV 129

                           90       100
                   ....*....|....*....|
gi 1207194866  624 LAVMNWSKNYSFVLSANLHG 643
Cdd:cd06234    130 FAVRQAMDATGVDFFLDVHG 149

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 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.

Pssm-ID: 349451 Cd Length: 276 Bit Score: 40.83 E-value: 3.94e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  923 GQSVEIRNIWALEIsNNPKVQEP--------SKPKIRFVAGIHGNAPVGTELLLEFAESLcvnygkNAAINRLINETRIV 994
Cdd:cd06232      3 ARSYQGRDIWAREF-TEPSTSEFvsqaklslYKPTILISARHHANEVSSTNAALRLAELL------ATDPPEILKKVNLV 75

                           90
                   ....*....|....*
gi 1207194866  995 ILPSINPDGRELAKE 1009
Cdd:cd06232     76 IIPLENPDGYALHEE 90

Predicted deacylase [General function prediction only];

Pssm-ID: 442826 [Multi-domain] Cd Length: 296 Bit Score: 40.22 E-value: 7.06e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866  104 VGNMHGDETVSRQVLVYLLEDLLEKygedqrvtELVNTtdIYILPSMNPDGFERSvegdclgkdeGRHNAK-NIDLNRSF 182
Cdd:COG3608     32 TAGIHGDELNGIEALRRLLRELDPG--------ELRGT--VILVPVANPPGFLQG----------SRYLPIdGRDLNRSF 91


                   ..
gi 1207194866  183 PD 184
Cdd:COG3608     92 PG 93

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.

Pssm-ID: 349471 Cd Length: 211 Bit Score: 39.12 E-value: 8.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207194866   95 GTGKPKFKYVGNMHGDEtVSRQVLVYLLEDLLEKYGEdqrvTELVNTTDIYILPSMNPDGF---ERSVEGDclgkdegrh 171
Cdd:cd06253     19 GNAEPRIAIVAGIHGDE-LNGLYVCSRLIRFLKELEE----GGYKLKGKVLVIPAVNPLGInsgTRFWPFD--------- 84

                           90
                   ....*....|..
gi 1207194866  172 nakNIDLNRSFP 183
Cdd:cd06253     85 ---NLDMNRMFP 93