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Conserved domains on  [gi|221329602|ref|NP_726675|]
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silver, isoform H [Drosophila melanogaster]

Protein Classification

carboxypeptidase D( domain architecture ID 10133713)

carboxypeptidase D (CPD), an M14 family zinc carboxypeptidase, 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

CATH:  3.40.630.10
EC:  3.4.17.-
Gene Ontology:  GO:0006508|GO:0004181|GO:0008270
MEROPS:  M14

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
35-332 8.23e-164

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: 493.30  E-value: 8.23e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAptgESKNGDLLRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd03868     1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISD---NVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQ 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPDRLEQSHVHqlRAQSRQP 194
Cdd:cd03868    78 YLLENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDPGYGGRENANNVDLNRNFPDQFEDSDDR--LLEGRQP 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  195 ETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNECCEESLTPDDRVFKQLAHTYSDNHPIMRKGNNC-NDSFSGG 273
Cdd:cd03868   156 ETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCcEDSFKDG 235
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  274 ITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd03868   236 ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
454-757 1.94e-159

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: 481.77  E-value: 1.94e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANAHGIDLNRNFPDQYGTDRFNKVT-EPEVAAVMNWT 612
Cdd:cd03858    81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVYSDNNPrQPETKAVMNWL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  613 LSLPFVLSANLHGGSLVANYPFDDNENdfndpfMRLRNSSingrkpnPTEDNALFKHLAGIYSNAHPTMYLGQPCELFQN 692
Cdd:cd03858   161 ESIPFVLSANLHGGALVANYPYDDTRS------GKSTEYS-------PSPDDAVFRMLARSYSDAHPTMSMGKPCCCDDD 227
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221329602  693 EFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd03858   228 ENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
336-414 1.63e-26

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: 103.76  E-value: 1.63e-26
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  336 GIKGLVTDASGFPIADANVYVAGLEeKPMRTSKRGEYWRLLTPGLYSVHASAFGYQTSApQQVRVTNdNQEALRLDFKL 414
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGIN-HDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVT-KTVTVPN-NFSATVVNFTL 76
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
761-837 3.66e-24

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: 97.21  E-value: 3.66e-24
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602  761 GIHGFVHSTIGTPIAGAVVRLDGANHSTYSQVFGDYWKLALPGRHNLTVLGDNYAPLRMEVEVPDVhPFEMRMDITL 837
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFTL 76
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1221-1299 2.47e-09

Carboxypeptidase regulatory-like domain;


:

Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 55.36  E-value: 2.47e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  1221 SIAGVVLDESNHPVRNAKVSVV---GQTQLRNFTGSMGQYRISAVPLGTITLKVEAPRHLEATRQMHLIQGGlATENVVF 1297
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVTntdTGTVRTTTTDADGRYRFPGLPPGTYTVTVSAPGFKTATRTGVTVTAG-QTTTLDV 79

                   ..
gi 221329602  1298 HL 1299
Cdd:pfam13620   80 TL 81
Peptidase_M14NE-CP-C_like super family cl21470
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
1122-1188 1.35e-03

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.


The actual alignment was detected with superfamily member cd11308:

Pssm-ID: 473874 [Multi-domain]  Cd Length: 76  Bit Score: 38.66  E-value: 1.35e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602 1122 GVSGLVQNDKGQPLREAYVRLLEHDRIINVTKNVARFQLMLPhGLYGLEVTAPNYESQMIKVDVEDG 1188
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLP-GTYNVTASAPGYQPVTKTVTVPNN 66
 
Name Accession Description Interval E-value
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
35-332 8.23e-164

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: 493.30  E-value: 8.23e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAptgESKNGDLLRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd03868     1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISD---NVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQ 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPDRLEQSHVHqlRAQSRQP 194
Cdd:cd03868    78 YLLENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDPGYGGRENANNVDLNRNFPDQFEDSDDR--LLEGRQP 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  195 ETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNECCEESLTPDDRVFKQLAHTYSDNHPIMRKGNNC-NDSFSGG 273
Cdd:cd03868   156 ETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCcEDSFKDG 235
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  274 ITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd03868   236 ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
454-757 1.94e-159

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: 481.77  E-value: 1.94e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANAHGIDLNRNFPDQYGTDRFNKVT-EPEVAAVMNWT 612
Cdd:cd03858    81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVYSDNNPrQPETKAVMNWL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  613 LSLPFVLSANLHGGSLVANYPFDDNENdfndpfMRLRNSSingrkpnPTEDNALFKHLAGIYSNAHPTMYLGQPCELFQN 692
Cdd:cd03858   161 ESIPFVLSANLHGGALVANYPYDDTRS------GKSTEYS-------PSPDDAVFRMLARSYSDAHPTMSMGKPCCCDDD 227
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221329602  693 EFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd03858   228 ENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
460-749 2.16e-93

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 303.07  E-value: 2.16e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   460 MESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYMLERYGND 539
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   540 DRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANA-----HGIDLNRNFPDQYGTDRFNKVT------------E 602
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNAngsscIGVDLNRNFPDHWNEVGASSNPcsetyrgpapfsE 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   603 PEVAAVMNWTLSL-PFVLSANLHGGSLVANYPFDDNENdfndpfmrlrnssingrkpNPTEDNALFKHLAGIYSNAHPTM 681
Cdd:pfam00246  161 PETRAVADFIRSKkPFVLYISLHSYSQVLLYPYGYTRD-------------------EPPPDDEELKSLARAAAKALQKM 221
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 221329602   682 YLGQpcelfqneFFPDGITNGAQWYSVTGGMQDWNYVRAGC-LELTIEMGCDK----FPKAAELSRYWEDHRE 749
Cdd:pfam00246  222 VRGT--------SYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWE 286
Zn_pept smart00631
Zn_pept domain;
454-743 4.12e-87

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 285.00  E-value: 4.12e-87
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGshvPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    534 ERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRA---NAHGIDLNRNFPDQYGTDR---------FNKVT 601
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGnpcsetyagPSPFS 157
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    602 EPEVAAVMNWTLS-LPFVLSANLHGGSLVANYPFDDNENDFNdpfmrlrnssingrkPNPTEDNALFKHLAGIYSNAHPT 680
Cdd:smart00631  158 EPETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLP---------------PNVDDLDAVAKALAKALASVHGT 222
                           250       260       270       280       290       300
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602    681 MYlgqpcelfqneffPDGITNGAQWYsVTGGMQDWNYVRAG-CLELTIEMGCD-----KFPKAAELSRY 743
Cdd:smart00631  223 RY-------------TYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
47-325 6.15e-82

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 270.71  E-value: 6.15e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    47 QLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNGdllRPMVKLVANIQGDEAVGRQMVLYMAEYLATHYDGDPKV 126
Cdd:pfam00246    7 ALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPG---KPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPEI 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   127 QALLNLTEIHFLPTCNPDGFAKAKEGNCeslPNYVGRGNAA-----NIDLNRDFPDRLEQ-----SHVHQLRAQSR---Q 193
Cdd:pfam00246   84 TELLDDTDIYILPVVNPDGYEYTHTTDR---LWRKNRSNANgssciGVDLNRNFPDHWNEvgassNPCSETYRGPApfsE 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   194 PETAALVNWIVS-KPFVLSANFHGGAVVASYPYDNSlahneccEESLTPDDRVFKQLAHTYSDNHPIMRKGNNcndsFSG 272
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYT-------RDEPPPDDEELKSLARAAAKALQKMVRGTS----YTY 229
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602   273 GITNGAHWYELSGGMQDFNYAFSNC-FELTIELSCCK----YPAASTLPQEWQRNKAS 325
Cdd:pfam00246  230 GITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
35-318 2.15e-68

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 231.84  E-value: 2.15e-68
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602     35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKngdllrPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGSHDK------PAIFIDAGIHAREWIGPATALYLIN 74
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPDRLEQS-----HVHQLRA 189
Cdd:smart00631   75 QLLENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSPNSNCRGVDLNRNFPFHWGETgnpcsETYAGPS 154
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    190 QSRQPETAALVNWIVSK-PFVLSANFHGGAVVASYPYDNSLAHNeccEESLTPDDRVFKQLAHTYSDNHPImrkgnncnd 268
Cdd:smart00631  155 PFSEPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDL---PPNVDDLDAVAKALAKALASVHGT--------- 222
                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 221329602    269 SFSGGITNGAHWYeLSGGMQDFNYAFSN-CFELTIELSCC-----KYPAASTLPQE 318
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
450-640 1.33e-32

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 130.19  E-value: 1.33e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  450 TKYEHHnftamESYLRAISSSyPSLTRLYSIGKSVQGRDLWVLEIfatpGSHVPGVPEFKYVANMHGNEVVGKELLLILT 529
Cdd:COG2866    20 YTYEEL-----LALLAKLAAA-SPLVELESIGKSVEGRPIYLLKI----GDPAEGKPKVLLNAQQHGNEWTGTEALLGLL 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  530 KYMLERYgnDDRITKLVNGTRMHFLYSMNPDGYEISiegdrtggvGRANAHGIDLNRNFPDQYgtdrfnkVTEPEVAAVM 609
Cdd:COG2866    90 EDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERN---------TRTNANGVDLNRDWPAPW-------LSEPETRALR 151
                         170       180       190
                  ....*....|....*....|....*....|.
gi 221329602  610 NWTLSLPFVLSANLHGGSLVANYPFDDNEND 640
Cdd:COG2866   152 DLLDEHDPDFVLDLHGQGELFYWFVGTTEPT 182
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
35-228 1.81e-31

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 127.11  E-value: 1.81e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDyPDLAQTYTIGKSLEDRPIYALALsaptGESKNGdllRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:COG2866    19 YYTYEELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKI----GDPAEG---KPKVLLNAQQHGNEWTGTEALLGLLE 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDgdPKVQALLNLTEIHFLPTCNPDGFAKAkegnceslpnyvGRGNAANIDLNRDFPDRLEQshvhqlraqsrQP 194
Cdd:COG2866    91 DLLDNYD--PLIRALLDNVTLYIVPMLNPDGAERN------------TRTNANGVDLNRDWPAPWLS-----------EP 145
                         170       180       190
                  ....*....|....*....|....*....|....
gi 221329602  195 ETAALVNWIVSKPFVLSANFHGGAVVASYPYDNS 228
Cdd:COG2866   146 ETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTT 179
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
336-414 1.63e-26

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: 103.76  E-value: 1.63e-26
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  336 GIKGLVTDASGFPIADANVYVAGLEeKPMRTSKRGEYWRLLTPGLYSVHASAFGYQTSApQQVRVTNdNQEALRLDFKL 414
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGIN-HDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVT-KTVTVPN-NFSATVVNFTL 76
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
761-837 3.66e-24

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: 97.21  E-value: 3.66e-24
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602  761 GIHGFVHSTIGTPIAGAVVRLDGANHSTYSQVFGDYWKLALPGRHNLTVLGDNYAPLRMEVEVPDVhPFEMRMDITL 837
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFTL 76
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
336-414 3.37e-15

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 71.93  E-value: 3.37e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   336 GIKGLVTDASGFPIADANVYVAGLEEKPMR---TSKRGEYW-RLLTPGLYSVHASAFGYQTSAPQQVRVTNDnqEALRLD 411
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVTNTDTGTVRtttTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAG--QTTTLD 78

                   ...
gi 221329602   412 FKL 414
Cdd:pfam13620   79 VTL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1221-1299 2.47e-09

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 55.36  E-value: 2.47e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  1221 SIAGVVLDESNHPVRNAKVSVV---GQTQLRNFTGSMGQYRISAVPLGTITLKVEAPRHLEATRQMHLIQGGlATENVVF 1297
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVTntdTGTVRTTTTDADGRYRFPGLPPGTYTVTVSAPGFKTATRTGVTVTAG-QTTTLDV 79

                   ..
gi 221329602  1298 HL 1299
Cdd:pfam13620   80 TL 81
PRK10602 PRK10602
murein tripeptide amidase MpaA;
550-591 1.76e-06

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 50.80  E-value: 1.76e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 221329602  550 RMHFLYSMNPDGYEISIegdrtggvgRANAHGIDLNRNFPDQ 591
Cdd:PRK10602   72 RHHVVLAVNPDGCQLGL---------RANANGVDLNRNFPAA 104
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
761-837 2.92e-06

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 46.50  E-value: 2.92e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   761 GIHGFVHSTIGTPIAGAVVRL----DGANHSTYSQVFGDYWKLAL-PGRHNLTVLGDNYAPLR---MEVEVPDVhpfeMR 832
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdTGTVRTTTTDADGRYRFPGLpPGTYTVTVSAPGFKTATrtgVTVTAGQT----TT 76

                   ....*
gi 221329602   833 MDITL 837
Cdd:pfam13620   77 LDVTL 81
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
1122-1188 1.35e-03

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: 38.66  E-value: 1.35e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602 1122 GVSGLVQNDKGQPLREAYVRLLEHDRIINVTKNVARFQLMLPhGLYGLEVTAPNYESQMIKVDVEDG 1188
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLP-GTYNVTASAPGYQPVTKTVTVPNN 66
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
1222-1299 1.81e-03

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: 38.27  E-value: 1.81e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602 1222 IAGVVLDESNHPVRNAKVSVVGQTQlRNFTGSMGQYRISAVPlGTITLKVEAPRHLEATRQMHLIQGGLATEnVVFHL 1299
Cdd:cd11308     2 IKGFVTDATGNPIANATISVEGINH-DVTTAKDGDYWRLLLP-GTYNVTASAPGYQPVTKTVTVPNNFSATV-VNFTL 76
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1122-1193 7.33e-03

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 36.87  E-value: 7.33e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  1122 GVSGLVQNDKGQPLREAYVRLLEHDRiiNVTKNVA-----RFQLM-LPHGLYGLEVTAPNYESQMIK-VDVEDGRVTEL 1193
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVTNTDT--GTVRTTTtdadgRYRFPgLPPGTYTVTVSAPGFKTATRTgVTVTAGQTTTL 77
 
Name Accession Description Interval E-value
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
35-332 8.23e-164

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: 493.30  E-value: 8.23e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAptgESKNGDLLRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd03868     1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISD---NVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQ 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPDRLEQSHVHqlRAQSRQP 194
Cdd:cd03868    78 YLLENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDPGYGGRENANNVDLNRNFPDQFEDSDDR--LLEGRQP 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  195 ETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNECCEESLTPDDRVFKQLAHTYSDNHPIMRKGNNC-NDSFSGG 273
Cdd:cd03868   156 ETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCcEDSFKDG 235
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  274 ITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd03868   236 ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
454-757 1.94e-159

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: 481.77  E-value: 1.94e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANAHGIDLNRNFPDQYGTDRFNKVT-EPEVAAVMNWT 612
Cdd:cd03858    81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVYSDNNPrQPETKAVMNWL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  613 LSLPFVLSANLHGGSLVANYPFDDNENdfndpfMRLRNSSingrkpnPTEDNALFKHLAGIYSNAHPTMYLGQPCELFQN 692
Cdd:cd03858   161 ESIPFVLSANLHGGALVANYPYDDTRS------GKSTEYS-------PSPDDAVFRMLARSYSDAHPTMSMGKPCCCDDD 227
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221329602  693 EFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd03858   228 ENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
35-332 5.15e-138

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: 425.14  E-value: 5.15e-138
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKngdLLRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHE---PGEPEFKYVANMHGNEVVGRELLLLLAE 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCeslPNYVGRGNAANIDLNRDFPDRLEQSHvhqLRAQSRQP 194
Cdd:cd03858    78 YLCENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDC---GGLIGRNNANGVDLNRNFPDQFFQVY---SDNNPRQP 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  195 ETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHnECCEESLTPDDRVFKQLAHTYSDNHPIMRKGNNC----NDSF 270
Cdd:cd03858   152 ETKAVMNWLESIPFVLSANLHGGALVANYPYDDTRSG-KSTEYSPSPDDAVFRMLARSYSDAHPTMSMGKPCccddDENF 230
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 221329602  271 SGGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd03858   231 PNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
455-757 4.56e-135

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: 417.03  E-value: 4.56e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  455 HNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYMLE 534
Cdd:cd03868     2 HNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLLE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  535 RYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGD---RTGGVGRANAHGIDLNRNFPDQYGT--DRFNKVTEPEVAAVM 609
Cdd:cd03868    82 NYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDcsgDPGYGGRENANNVDLNRNFPDQFEDsdDRLLEGRQPETLAMM 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  610 NWTLSLPFVLSANLHGGSLVANYPFDDNendfndpfmrlRNSSINGRKpNPTEDNALFKHLAGIYSNAHPTMYLGQPCel 689
Cdd:cd03868   162 KWIVENPFVLSANLHGGSVVASYPFDDS-----------PSHIECGVY-SKSPDDAVFRHLAHTYADNHPTMHKGNNC-- 227
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602  690 fQNEFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd03868   228 -CEDSFKDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
447-757 1.97e-129

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: 402.40  E-value: 1.97e-129
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  447 LTPTKYEHHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLL 526
Cdd:cd03863     1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  527 ILTKYMLERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANAHGIDLNRNFPDQYgtDRFNKVTEPEVA 606
Cdd:cd03863    81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQF--FQITDPPQPETL 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  607 AVMNWTLSLPFVLSANLHGGSLVANYPFDDNENDFndpfmrlrnsSINGRKPnpteDNALFKHLAGIYSNAHPTMYLGQP 686
Cdd:cd03863   159 AVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGL----------ATYSKSP----DDAVFQQLALSYSKENSKMYQGSP 224
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 221329602  687 C-ELFQNEFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd03863   225 CkELYPNEYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
454-757 2.12e-111

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: 352.94  E-value: 2.12e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03866     1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANAHGIDLNRNFPDQYGTDrfNKVTEPEVAAVMNWTL 613
Cdd:cd03866    81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEEN--NVQRQPETRAVMDWIK 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  614 SLPFVLSANLHGGSLVANYPFDDNENDFNdpfmRLRNSSIngrkpnpTEDNALFKHLAGIYSNAHPTMYLGQPCELFQNe 693
Cdd:cd03866   159 NETFVLSANLHGGALVASYPFDNGNSGTG----QLGYYSV-------SPDDDVFIYLAKTYSYNHTNMYKGIECSNSQS- 226
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 221329602  694 fFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd03866   227 -FPGGITNGYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
454-757 1.93e-100

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: 323.81  E-value: 1.93e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03864     1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERY-GNDDRITKLVNGTRMHFLYSMNPDGYEISI-EGDRTGG--VGRANAHGIDLNRNFPD---------QYG------- 593
Cdd:cd03864    81 EEYrNGNERITRLIQDTRIHILPSMNPDGYEVAArQGPEFNGylVGRNNANGVDLNRNFPDlntlmyyneKYGgpnhhlp 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  594 -TDRFNKVTEPEVAAVMNWTLSLPFVLSANLHGGSLVANYPFDDNEndfnDPFMRLRNSSINgrkpNPTEDNALFKHLAG 672
Cdd:cd03864   161 lPDNWKSQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSR----EPRVRGFRRTAY----SPTPDDKLFQKLAK 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  673 IYSNAHPTMYLGQPCelfqNEFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLL 752
Cdd:cd03864   233 TYSYAHGWMHKGWNC----GDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALI 308

                  ....*
gi 221329602  753 QFIEQ 757
Cdd:cd03864   309 SYMEQ 313
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
35-332 9.71e-100

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: 320.97  E-value: 9.71e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNGdllRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd03866     1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIG---IPEFKYVANMHGDEVVGRELLLHLIE 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCeslpNY-VGRGNAANIDLNRDFPDRLEQSHVhqlraqSRQ 193
Cdd:cd03866    78 FLVTSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDC----YYtKGRYNKNGYDLNRNFPDAFEENNV------QRQ 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  194 PETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNECCEE-SLTPDDRVFKQLAHTYSDNHPIMRKGNNCND--SF 270
Cdd:cd03866   148 PETRAVMDWIKNETFVLSANLHGGALVASYPFDNGNSGTGQLGYySVSPDDDVFIYLAKTYSYNHTNMYKGIECSNsqSF 227
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 221329602  271 SGGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd03866   228 PGGITNGYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
455-757 2.92e-95

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: 307.97  E-value: 2.92e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  455 HNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGvPEFKYVANMHGNEVVGKELLLILTKYMLE 534
Cdd:cd18173     5 PTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEAE-PEFKYTSTMHGDETTGYELMLRLIDYLLT 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  535 RYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVgRANAHGIDLNRNFPD-QYGTDRFNKVTEPEVAAVMNWTL 613
Cdd:cd18173    84 NYGTDPRITNLVDNTEIWINPLANPDGTYAGGNNTVSGAT-RYNANGVDLNRNFPDpVDGDHPDGNGWQPETQAMMNFAD 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  614 SLPFVLSANLHGGSLVANYPFDdnendfndpfmrlrnssingRKPNPTEDNALFKHLAGIYS-NAH---PTMYLGQpcel 689
Cdd:cd18173   163 EHNFVLSANFHGGAEVVNYPWD--------------------TWYSRHPDDDWFQDISREYAdTNQansPPMYMSE---- 218
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602  690 fqnefFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd18173   219 -----FNNGITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
460-749 2.16e-93

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 303.07  E-value: 2.16e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   460 MESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYMLERYGND 539
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   540 DRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANA-----HGIDLNRNFPDQYGTDRFNKVT------------E 602
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNAngsscIGVDLNRNFPDHWNEVGASSNPcsetyrgpapfsE 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   603 PEVAAVMNWTLSL-PFVLSANLHGGSLVANYPFDDNENdfndpfmrlrnssingrkpNPTEDNALFKHLAGIYSNAHPTM 681
Cdd:pfam00246  161 PETRAVADFIRSKkPFVLYISLHSYSQVLLYPYGYTRD-------------------EPPPDDEELKSLARAAAKALQKM 221
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 221329602   682 YLGQpcelfqneFFPDGITNGAQWYSVTGGMQDWNYVRAGC-LELTIEMGCDK----FPKAAELSRYWEDHRE 749
Cdd:pfam00246  222 VRGT--------SYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWE 286
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
454-757 9.53e-92

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: 299.98  E-value: 9.53e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03865     1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERY--GNDDrITKLVNGTRMHFLYSMNPDGYEISIEGD---RTGGVGRANAHGIDLNRNFPDqygTDRFNKVTE------ 602
Cdd:cd03865    81 NEYqkGNET-IINLIHSTRIHIMPSLNPDGFEKAASQPgelKDWFVGRSNAQGIDLNRNFPD---LDRIVYVNEkeggpn 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  603 ------------------PEVAAVMNWTLSLPFVLSANLHGGSLVANYPFDDNendfndpfmrlRNSSINGRKPNPteDN 664
Cdd:cd03865   157 nhllknmkkavdqntklaPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDET-----------RSGSAHEYSSCP--DD 223
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  665 ALFKHLAGIYSNAHPTMYLGQ--PCELFQNEF-FPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELS 741
Cdd:cd03865   224 AIFQSLARAYSSLNPAMSDPNrpPCRKNDDDSsFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLK 303
                         330
                  ....*....|....*.
gi 221329602  742 RYWEDHREPLLQFIEQ 757
Cdd:cd03865   304 GYWEDNKNSLINYIEQ 319
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
454-756 1.95e-90

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: 294.32  E-value: 1.95e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGShVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd18172     1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGE-DETEPAFKFVGNMHGDEPVGRELLLRLADWLC 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERY-GNDDRITKLVNGTRMHFLYSMNPDGYEIsiegdRTggvgRANAHGIDLNRNFPDQY---GTDRFNKVTEPEVAAVM 609
Cdd:cd18172    80 ANYkAKDPLAAKIVENAHLHLVPTMNPDGFAR-----RR----RNNANNVDLNRDFPDQFfpkNLRNDLAARQPETLAVM 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  610 NWTLSLPFVLSANLHGGSLVANYPFDDNENDFNdpfmrlrnssingrKPNPTEDNALFKHLAGIYSNAHPTMYLgqPCEl 689
Cdd:cd18172   151 NWSRSVRFTASANLHEGALVANYPWDGNADGRT--------------KYSASPDDATFRRLASVYAQAHPNMAK--SKE- 213
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602  690 fqnefFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIE 756
Cdd:cd18172   214 -----FPGGITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALAA 275
Zn_pept smart00631
Zn_pept domain;
454-743 4.12e-87

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 285.00  E-value: 4.12e-87
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGshvPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    534 ERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRA---NAHGIDLNRNFPDQYGTDR---------FNKVT 601
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGnpcsetyagPSPFS 157
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    602 EPEVAAVMNWTLS-LPFVLSANLHGGSLVANYPFDDNENDFNdpfmrlrnssingrkPNPTEDNALFKHLAGIYSNAHPT 680
Cdd:smart00631  158 EPETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLP---------------PNVDDLDAVAKALAKALASVHGT 222
                           250       260       270       280       290       300
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602    681 MYlgqpcelfqneffPDGITNGAQWYsVTGGMQDWNYVRAG-CLELTIEMGCD-----KFPKAAELSRY 743
Cdd:smart00631  223 RY-------------TYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
454-756 1.80e-85

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: 282.16  E-value: 1.80e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03867     1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERY-GNDDRITKLVNGTRMHFLYSMNPDGYEISIE-GDRTGG--VGRANAHGIDLNRNFPD------------QYGTDR- 596
Cdd:cd03867    81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEeGAGYNGwtSGRQNAQNLDLNRNFPDltseayrlartrGARLDHi 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  597 -------FNKVTePEVAAVMNWTLSLPFVLSANLHGGSLVANYPFDDNENDFNDPFMrlrnssingrkpNPTEDNALFKH 669
Cdd:cd03867   161 pipqsywWGKVA-PETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMF------------SPTPDEKMFKL 227
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  670 LAGIYSNAHPTMYLGQPCELFQNEFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHRE 749
Cdd:cd03867   228 LAKAYADAHPMMSDRSENRCGGNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKE 307

                  ....*..
gi 221329602  750 PLLQFIE 756
Cdd:cd03867   308 ALLNFME 314
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
454-757 6.11e-85

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: 280.95  E-value: 6.11e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd03869     1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERY--GNDdRITKLVNGTRMHFLYSMNPDGYEISIE-GDRTGG--VGRANAHGIDLNRNFPD----QYGT---------- 594
Cdd:cd03869    81 QEYlaGNP-RIRHLVEETRIHLLPSVNPDGYEKAYEaGSELGGwsLGRWTSDGIDINHNFPDlnslLWEAedrkwvprkv 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  595 --------DRF---NKVTEPEVAAVMNWTLSLPFVLSANLHGGSLVANYPFDdnendfndpfmrLRNSSINGRKPNPTED 663
Cdd:cd03869   160 pnhhipipEWYlseNATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYD------------MTRTPWKTQEYTPTPD 227
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  664 NALFKHLAGIYSNAHPTMYLG--QPC--ELFQNEffpDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAE 739
Cdd:cd03869   228 DHVFRWLAYSYASTHRLMTDAsrRPChtEDFQKE---DGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESE 304
                         330
                  ....*....|....*...
gi 221329602  740 LSRYWEDHREPLLQFIEQ 757
Cdd:cd03869   305 LPEEWENNRESLLVFMEQ 322
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
33-332 6.99e-85

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: 279.08  E-value: 6.99e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   33 PHYLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNgdllRPMVKLVANIQGDEAVGRQMVLYM 112
Cdd:cd18173     2 DSYPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA----EPEFKYTSTMHGDETTGYELMLRL 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  113 AEYLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAkeGNceslpNYVG---RGNAANIDLNRDFPDRLEQSHVhqlRA 189
Cdd:cd18173    78 IDYLLTNYGTDPRITNLVDNTEIWINPLANPDGTYAG--GN-----NTVSgatRYNANGVDLNRNFPDPVDGDHP---DG 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  190 QSRQPETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSlahnecceESLTPDDRVFKQLAHTYSDNhPIMRKGNNCNDS 269
Cdd:cd18173   148 NGWQPETQAMMNFADEHNFVLSANFHGGAEVVNYPWDTW--------YSRHPDDDWFQDISREYADT-NQANSPPMYMSE 218
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 221329602  270 FSGGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd18173   219 FNNGITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
34-332 7.63e-85

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: 279.52  E-value: 7.63e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   34 HYLKNEEIgdLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNGDllrPMVKLVANIQGDEAVGRQMVLYMA 113
Cdd:cd03863     9 HHFSDMEI--FLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGE---PEFKYIGNMHGNEVVGRELLLNLI 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  114 EYLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLpnyVGRGNAANIDLNRDFPDRLEQShvhqlrAQSRQ 193
Cdd:cd03863    84 EYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGT---VGRNNSNNYDLNRNFPDQFFQI------TDPPQ 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  194 PETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLahNECCEESLTPDDRVFKQLAHTYSDNHPIMRKGNNC-----ND 268
Cdd:cd03863   155 PETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDE--QGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCkelypNE 232
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 221329602  269 SFSGGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd03863   233 YFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
35-330 6.26e-83

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: 273.13  E-value: 6.26e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNgdllRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd18172     1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDET----EPAFKFVGNMHGDEPVGRELLLRLAD 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDG-DPKVQALLNLTEIHFLPTCNPDGFAKAKegnceslpnyvgRGNAANIDLNRDFPDRL-EQSHVHQLRAqsR 192
Cdd:cd18172    77 WLCANYKAkDPLAAKIVENAHLHLVPTMNPDGFARRR------------RNNANNVDLNRDFPDQFfPKNLRNDLAA--R 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  193 QPETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNECCEESltPDDRVFKQLAHTYSDNHPIMRKGNncndSFSG 272
Cdd:cd18172   143 QPETLAVMNWSRSVRFTASANLHEGALVANYPWDGNADGRTKYSAS--PDDATFRRLASVYAQAHPNMAKSK----EFPG 216
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602  273 GITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLL 330
Cdd:cd18172   217 GITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALA 274
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
47-325 6.15e-82

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 270.71  E-value: 6.15e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    47 QLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNGdllRPMVKLVANIQGDEAVGRQMVLYMAEYLATHYDGDPKV 126
Cdd:pfam00246    7 ALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPG---KPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPEI 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   127 QALLNLTEIHFLPTCNPDGFAKAKEGNCeslPNYVGRGNAA-----NIDLNRDFPDRLEQ-----SHVHQLRAQSR---Q 193
Cdd:pfam00246   84 TELLDDTDIYILPVVNPDGYEYTHTTDR---LWRKNRSNANgssciGVDLNRNFPDHWNEvgassNPCSETYRGPApfsE 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   194 PETAALVNWIVS-KPFVLSANFHGGAVVASYPYDNSlahneccEESLTPDDRVFKQLAHTYSDNHPIMRKGNNcndsFSG 272
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYT-------RDEPPPDDEELKSLARAAAKALQKMVRGTS----YTY 229
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602   273 GITNGAHWYELSGGMQDFNYAFSNC-FELTIELSCCK----YPAASTLPQEWQRNKAS 325
Cdd:pfam00246  230 GITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
454-757 1.44e-79

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: 263.92  E-value: 1.44e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  454 HHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYML 533
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  534 ERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANAHGIDLNRNFPDQYGtdRFNKVTEPEVAAVMNWTL 613
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNAN--NRSGAAQPETKAIMDWLK 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  614 SLPFVLSANLHGGSLVANYPFDDNendfndpfmrlrNSSingrkpnpTEDNALFKHLAGIYSNAHPTMYLGQP-CELFQN 692
Cdd:cd06245   159 EKDFTLSVALDGGSLVVTYPYDKP------------VQT--------VENKETLKHLAKVYANNHPTMHAGDPgCCSNSD 218
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221329602  693 EFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFPKAAELSRYWEDHREPLLQFIEQ 757
Cdd:cd06245   219 ENFTNGVIRASEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
53-332 4.61e-79

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: 263.72  E-value: 4.61e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   53 PDLAQTYTIGKSLEDRPIYALALSAPTGESkngDLLRPMVKLVANIQGDEAVGRQMVLYMAEYLATHY-DGDPKVQALLN 131
Cdd:cd03864    19 PYITRIYSIGRSVEGRHLYVLEFSDNPGIH---EPLEPEFKYVGNMHGNEVLGRELLIQLSEFLCEEYrNGNERITRLIQ 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  132 LTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPD-----RLEQSHV---HQL------RAQSrQPETA 197
Cdd:cd03864    96 DTRIHILPSMNPDGYEVAARQGPEFNGYLVGRNNANGVDLNRNFPDlntlmYYNEKYGgpnHHLplpdnwKSQV-EPETL 174
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  198 ALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHN----ECCEESLTPDDRVFKQLAHTYSDNHPIMRKGNNCNDSFSGG 273
Cdd:cd03864   175 AVIQWMQNYNFVLSANLHGGAVVANYPYDKSREPRvrgfRRTAYSPTPDDKLFQKLAKTYSYAHGWMHKGWNCGDYFDEG 254
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  274 ITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd03864   255 ITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
55-330 1.41e-78

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: 262.51  E-value: 1.41e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   55 LAQTYTIGKSLEDRPIYALALSAPTGESkngDLLRPMVKLVANIQGDEAVGRQMVLYMAEYLATHY-DGDPKVQALLNLT 133
Cdd:cd03867    21 IARTYSIGRSFEGKDLLVIEFSSNPGQH---ELLEPEVKYIGNMHGNEVVGREMLIYLAQYLCSEYlLGNPRIQTLINTT 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  134 EIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPDRleQSHVHQLRAQSR-----------------QPET 196
Cdd:cd03867    98 RIHLLPSMNPDGYEVAAEEGAGYNGWTSGRQNAQNLDLNRNFPDL--TSEAYRLARTRGarldhipipqsywwgkvAPET 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  197 AALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNECCEESLTPDDRVFKQLAHTYSDNHPIM--RKGNNCNDSF--SG 272
Cdd:cd03867   176 KAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMFSPTPDEKMFKLLAKAYADAHPMMsdRSENRCGGNFlkRG 255
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602  273 GITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLL 330
Cdd:cd03867   256 GIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFM 313
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
35-332 2.70e-78

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: 261.84  E-value: 2.70e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNGDllrPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd03865     1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGE---PEFKYVGNMHGNEAVGRELLIFLAQ 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHY-DGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPD---------RLEQSHV 184
Cdd:cd03865    78 YLCNEYqKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDldrivyvneKEGGPNN 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  185 HQLRAQSRQ--------PETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSL---AHneccEESLTPDDRVFKQLAHTY 253
Cdd:cd03865   158 HLLKNMKKAvdqntklaPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRsgsAH----EYSSCPDDAIFQSLARAY 233
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  254 SDNHPIM--------RKgNNCNDSFSGGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKAS 325
Cdd:cd03865   234 SSLNPAMsdpnrppcRK-NDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNS 312

                  ....*..
gi 221329602  326 LLQLLRQ 332
Cdd:cd03865   313 LINYIEQ 319
Zn_pept smart00631
Zn_pept domain;
35-318 2.15e-68

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 231.84  E-value: 2.15e-68
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602     35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKngdllrPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGSHDK------PAIFIDAGIHAREWIGPATALYLIN 74
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPDRLEQS-----HVHQLRA 189
Cdd:smart00631   75 QLLENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSPNSNCRGVDLNRNFPFHWGETgnpcsETYAGPS 154
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602    190 QSRQPETAALVNWIVSK-PFVLSANFHGGAVVASYPYDNSLAHNeccEESLTPDDRVFKQLAHTYSDNHPImrkgnncnd 268
Cdd:smart00631  155 PFSEPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDL---PPNVDDLDAVAKALAKALASVHGT--------- 222
                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 221329602    269 SFSGGITNGAHWYeLSGGMQDFNYAFSN-CFELTIELSCC-----KYPAASTLPQE 318
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
39-332 4.10e-67

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: 229.72  E-value: 4.10e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   39 EEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNGDllrPMVKLVANIQGDEAVGRQMVLYMAEYLAT 118
Cdd:cd03869     5 KDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGE---PEFRYVAGAHGNEVLGRELLLLLMQFLCQ 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  119 HY-DGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANIDLNRDFPD----------------RLEQ 181
Cdd:cd03869    82 EYlAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGGWSLGRWTSDGIDINHNFPDlnsllweaedrkwvprKVPN 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  182 SHV-----HQLRAQSRQPETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNECCEESLTPDDRVFKQLAHTYSDN 256
Cdd:cd03869   162 HHIpipewYLSENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYAST 241
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  257 HPIM----RKGNNCND-SFSGGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLR 331
Cdd:cd03869   242 HRLMtdasRRPCHTEDfQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFME 321

                  .
gi 221329602  332 Q 332
Cdd:cd03869   322 Q 322
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
40-332 5.14e-66

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: 225.02  E-value: 5.14e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   40 EIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESkngDLLRPMVKLVANIQGDEAVGRQMVLYMAEYLATH 119
Cdd:cd06245     6 QLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNES---EPSEPKILFVGGIHGNAPVGTELLLLLAHFLCHN 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  120 YDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLpnyVGRGNAANIDLNRDFPDRLEQshvhqlRAQSRQPETAAL 199
Cdd:cd06245    83 YKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSK---IGEKNANGVDLDTDFESNANN------RSGAAQPETKAI 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  200 VNWIVSKPFVLSANFHGGAVVASYPYDNSlahnecceESLTPDDRVFKQLAHTYSDNHPIMRKG-----NNCNDSFSGGI 274
Cdd:cd06245   154 MDWLKEKDFTLSVALDGGSLVVTYPYDKP--------VQTVENKETLKHLAKVYANNHPTMHAGdpgccSNSDENFTNGV 225
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602  275 TNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQEWQRNKASLLQLLRQ 332
Cdd:cd06245   226 IRASEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
455-735 4.17e-39

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: 147.79  E-value: 4.17e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  455 HNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHvPGVPEFKYVANMHGNEVVGKELLLILTKYMLE 534
Cdd:cd03859     5 HTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDED-EDEPEVLFMGLHHAREWISLEVALYFADYLLE 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  535 RYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDrTGGVGRAN----------AHGIDLNRNFPDQYGTDRFNKVT--- 601
Cdd:cd03859    84 NYGTDPRITNLVDNREIWIIPVVNPDGYEYNRETG-GGRLWRKNrrpnngnnpgSDGVDLNRNYGYHWGGDNGGSSPdps 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  602 -----------EPEVAAVMNWTLSLPFVLSANLHG-GSLVaNYPFddnendfndpfmrlrnssiNGRKPNPTEDNALFKH 669
Cdd:cd03859   163 setyrgpapfsEPETQAIRDLVESHDFKVAISYHSyGELV-LYPW-------------------GYTSDAPTPDEDVFEE 222
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 221329602  670 LAGIYSNAHPTMYLGQPcelfqneffpdgitnGAQWYSVTGGMQDWNYVRAGCLELTIEMGCDKFP 735
Cdd:cd03859   223 LAEEMASYNGGGYTPQQ---------------SSDLYPTNGDTDDWMYGEKGIIAFTPELGPEFYP 273
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
510-751 8.22e-39

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: 144.52  E-value: 8.22e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  510 YVANMHGNEVVGKELLLILTKYMLERYGNDDrITKLVNGTRMHFLYSMNPDGYEISIegdrtGGVGRANAHGIDLNRNFP 589
Cdd:cd00596     3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVI-----DSGGRKNANGVDLNRNFP 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  590 -------DQYGTDRFNKVT----EPEVAAVMNWTLSLPFVLSANLHGGSLVANYPFddnendfndpfmrlrnssinGRKP 658
Cdd:cd00596    77 ynwgkdgTSGPSSPTYRGPapfsEPETQALRDLAKSHRFDLAVSYHSSSEAILYPY--------------------GYTN 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  659 NPTEDNALFKHLAGIYSNAHPtmylgqpcelfqneFFPDGITNGAQWYSVTGGMQDWNYVRAGCLELTIEMGC-DKFPKA 737
Cdd:cd00596   137 EPPPDFSEFQELAAGLARALG--------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTaDYPLPG 202
                         250
                  ....*....|....
gi 221329602  738 AELSRYWEDHREPL 751
Cdd:cd00596   203 TLLDRRLERNLAAL 216
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
92-326 4.80e-35

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: 133.74  E-value: 4.80e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   92 VKLVANIQGDEAVGRQMVLYMAEYLATHYdGDPKVQALLNLTEIHFLPTCNPDGFAKAKegnceslpNYVGRGNAANIDL 171
Cdd:cd00596     1 ILITGGIHGNEVIGVELALALIEYLLENY-GNDPLKRLLDNVELWIVPLVNPDGFARVI--------DSGGRKNANGVDL 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  172 NRDFPDRLEQSHVHQLRAQSR-------QPETAALVNWIVSKPFVLSANFHGGAVVASYPYdnslahneCCEESLTPDDR 244
Cdd:cd00596    72 NRNFPYNWGKDGTSGPSSPTYrgpapfsEPETQALRDLAKSHRFDLAVSYHSSSEAILYPY--------GYTNEPPPDFS 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  245 VFKQLAHTYSDNHPimrkgnncndSFSGGITNGAHWYELSGGMQDFNYAFSNCFELTIELSCCKYPAASTLPQ-EWQRNK 323
Cdd:cd00596   144 EFQELAAGLARALG----------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTLLDrRLERNL 213

                  ...
gi 221329602  324 ASL 326
Cdd:cd00596   214 AAL 216
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
39-322 1.38e-34

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: 134.69  E-value: 1.38e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   39 EEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNgdllRPMVKLVANIQGDEAVGRQMVLYMAEYLAT 118
Cdd:cd03859     8 AELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDEDED----EPEVLFMGLHHAREWISLEVALYFADYLLE 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  119 HYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEG------------NCESLPNYVGrgnaanIDLNRDFP-----DRLEQ 181
Cdd:cd03859    84 NYGTDPRITNLVDNREIWIIPVVNPDGYEYNRETgggrlwrknrrpNNGNNPGSDG------VDLNRNYGyhwggDNGGS 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  182 SHVHQ------LRAQSrQPETAALVNWIVSKPFVLSANFHGGAVVASYPYDNSLAHNecceeslTPDDRVFKQLAHTysd 255
Cdd:cd03859   158 SPDPSsetyrgPAPFS-EPETQAIRDLVESHDFKVAISYHSYGELVLYPWGYTSDAP-------TPDEDVFEELAEE--- 226
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 221329602  256 nhpiMRKGNNcndsfsGGITNGAHW--YELSGGMQDFNYAFSNCFELTIEL---SCCKYPAASTLPQEWQRN 322
Cdd:cd03859   227 ----MASYNG------GGYTPQQSSdlYPTNGDTDDWMYGEKGIIAFTPELgpeFYPFYPPPSQIDPLAEEN 288
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
450-640 1.33e-32

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 130.19  E-value: 1.33e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  450 TKYEHHnftamESYLRAISSSyPSLTRLYSIGKSVQGRDLWVLEIfatpGSHVPGVPEFKYVANMHGNEVVGKELLLILT 529
Cdd:COG2866    20 YTYEEL-----LALLAKLAAA-SPLVELESIGKSVEGRPIYLLKI----GDPAEGKPKVLLNAQQHGNEWTGTEALLGLL 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  530 KYMLERYgnDDRITKLVNGTRMHFLYSMNPDGYEISiegdrtggvGRANAHGIDLNRNFPDQYgtdrfnkVTEPEVAAVM 609
Cdd:COG2866    90 EDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERN---------TRTNANGVDLNRDWPAPW-------LSEPETRALR 151
                         170       180       190
                  ....*....|....*....|....*....|.
gi 221329602  610 NWTLSLPFVLSANLHGGSLVANYPFDDNEND 640
Cdd:COG2866   152 DLLDEHDPDFVLDLHGQGELFYWFVGTTEPT 182
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
35-228 1.81e-31

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 127.11  E-value: 1.81e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDyPDLAQTYTIGKSLEDRPIYALALsaptGESKNGdllRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:COG2866    19 YYTYEELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKI----GDPAEG---KPKVLLNAQQHGNEWTGTEALLGLLE 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDgdPKVQALLNLTEIHFLPTCNPDGFAKAkegnceslpnyvGRGNAANIDLNRDFPDRLEQshvhqlraqsrQP 194
Cdd:COG2866    91 DLLDNYD--PLIRALLDNVTLYIVPMLNPDGAERN------------TRTNANGVDLNRDWPAPWLS-----------EP 145
                         170       180       190
                  ....*....|....*....|....*....|....
gi 221329602  195 ETAALVNWIVSKPFVLSANFHGGAVVASYPYDNS 228
Cdd:COG2866   146 ETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTT 179
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
447-728 4.48e-31

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: 126.58  E-value: 4.48e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  447 LTPTKYehHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPEFKYVANMHGNEVVGKELLL 526
Cdd:cd06905     1 LAFDRY--YTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVAL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  527 ILTKYMLERYGNDDRITKLVNGTRMHFLYSMNPDG--------------------------------------------- 561
Cdd:cd06905    79 YLAEYLLTNYGKDPEITRLLDTRTFYILPRLNPDGaeayklktersgrssprdddrdgdgdedgpedlngdglitqmrvk 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  562 --------------------------YEISIEGDRTGGVGRAN---AHGIDLNRNFP-------DQYGTDRFnKVTEPEV 605
Cdd:cd06905   159 dptgtwkvdpddprlmvdrekgekgfYRLYPEGIDNDGDGRYNedgPGGVDLNRNFPynwqpfyVQPGAGPY-PLSEPET 237
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  606 AAVMNWTLSLPFVLSANLHGgslvanypfddNENDFNdpfmrLRNSSINGRKPNPTEDNALFKHLAgiysnAHPTMYLGQ 685
Cdd:cd06905   238 RAVADFLLAHPNIAAVLTFH-----------TSGGMI-----LRPPGTGPDSDMPPADRRVYDAIG-----KKGVELTGY 296
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 221329602  686 PCELFQNEFFPDgiTNGAQwysvTGGMQDWNYVRAGCLELTIE 728
Cdd:cd06905   297 PVSSVYKDFYTV--PGGPL----DGDFFDWAYFHLGIPSFSTE 333
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
336-414 1.63e-26

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: 103.76  E-value: 1.63e-26
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  336 GIKGLVTDASGFPIADANVYVAGLEeKPMRTSKRGEYWRLLTPGLYSVHASAFGYQTSApQQVRVTNdNQEALRLDFKL 414
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGIN-HDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVT-KTVTVPN-NFSATVVNFTL 76
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
761-837 3.66e-24

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: 97.21  E-value: 3.66e-24
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602  761 GIHGFVHSTIGTPIAGAVVRLDGANHSTYSQVFGDYWKLALPGRHNLTVLGDNYAPLRMEVEVPDVhPFEMRMDITL 837
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFTL 76
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
34-180 3.35e-23

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: 103.08  E-value: 3.35e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   34 HYLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESkngDLLRPMVKLVANIQGDEAVGRQMVLYMA 113
Cdd:cd06905     5 RYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGP---ADEKPALWVDGNIHGNEVTGSEVALYLA 81
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602  114 EYLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKakegnceSLPNYVGRGNAANIDLNRDFpDRLE 180
Cdd:cd06905    82 EYLLTNYGKDPEITRLLDTRTFYILPRLNPDGAEA-------YKLKTERSGRSSPRDDDRDG-DGDE 140
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
455-616 1.30e-22

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: 99.91  E-value: 1.30e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  455 HNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGShvPGVPEFKYVANMHGNEVVGKELLLILTKYMLE 534
Cdd:cd03860     2 HPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGGK--GGKPAIVIHGGQHAREWISTSTVEYLAHQLLS 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  535 RYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDR--------TGGvgrANAHGIDLNRNFP---DQYGTDR------- 596
Cdd:cd03860    80 GYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDRlwrknrqpTGG---SSCVGIDLNRNWGykwGGPGASTnpcsety 156
                         170       180
                  ....*....|....*....|....*
gi 221329602  597 -----FNkvtEPEVAAVMNWTLSLP 616
Cdd:cd03860   157 rgpsaFS---APETKALADFINALA 178
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
39-207 1.11e-18

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: 88.35  E-value: 1.11e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   39 EEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKngdllRPMVKLVANIQGDEAVGRQMVLYMAEYLAT 118
Cdd:cd03860     5 DDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGGKGG-----KPAIVIHGGQHAREWISTSTVEYLAHQLLS 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  119 HYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGN--------CESLPNYVGrgnaanIDLNRDFPDRLEQ--------S 182
Cdd:cd03860    80 GYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDrlwrknrqPTGGSSCVG------IDLNRNWGYKWGGpgastnpcS 153
                         170       180
                  ....*....|....*....|....*.
gi 221329602  183 HVHQ-LRAQSrQPETAALVNWIVSKP 207
Cdd:cd03860   154 ETYRgPSAFS-APETKALADFINALA 178
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
60-331 2.26e-15

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: 76.55  E-value: 2.26e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   60 TIGKSLEDRPIYALalsaptgesKNGDLLRPMVKLVANIQGDEAVGRQMVLYMAEYLATHydgdpkvQALLNLTeIHFLP 139
Cdd:cd06904     3 VYGTSVKGRPILAY---------KFGPGSRARILIIGGIHGDEPEGVSLVEHLLRWLKNH-------PASGDFH-IVVVP 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  140 TCNPDGFAKAKegnceslpnyvgRGNAANIDLNRDFPDRLEQSHVHQLRAQSR--------QPETAALVN--------WI 203
Cdd:cd06904    66 CLNPDGLAAGT------------RTNANGVDLNRNFPTKNWEPDARKPKDPRYypgpkpasEPETRALVElierfkpdRI 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  204 VS--KPFVLsaNFHGGAvvasypyDNSLAHnecceesltpddrvfkqlahtysdnhpIMRKGNNCNDSFSGGITNGahwy 281
Cdd:cd06904   134 ISlhAPYLV--NYDGPA-------KSLLAE---------------------------KLAQATGYPVVGDVGYTPG---- 173
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 221329602  282 elSGGmqdfNYA--FSNCFELTIELscckyPAASTLPQEWQRNKASLLQLLR 331
Cdd:cd06904   174 --SLG----TYAgiERNIPVITLEL-----PEAVSIDELWQDLKRALIEAIK 214
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
336-414 3.37e-15

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 71.93  E-value: 3.37e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   336 GIKGLVTDASGFPIADANVYVAGLEEKPMR---TSKRGEYW-RLLTPGLYSVHASAFGYQTSAPQQVRVTNDnqEALRLD 411
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVTNTDTGTVRtttTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAG--QTTTLD 78

                   ...
gi 221329602   412 FKL 414
Cdd:pfam13620   79 VTL 81
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
510-624 2.42e-13

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: 71.22  E-value: 2.42e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  510 YVANMHGNEVVGKELLLILTKYMLERYGNDDRIT-----KLVNGTRMHFLYSMNPDGYEISIEG---------------- 568
Cdd:cd06229     3 YNASFHAREYITTLLLMKFIEDYAKAYVNKSYIRgkdvgELLNKVTLHIVPMVNPDGVEISQNGsnainpyylrlvawnk 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 221329602  569 DRTGGVG-RANAHGIDLNRNFP----------DQYGTDRFNK----VTEPEVAAVMNWTLSLPFVLSANLH 624
Cdd:cd06229    83 KGTDFTGwKANIRGVDLNRNFPagwekekrlgPKAPGPRDYPgkepLSEPETKAMAALTRQNDFDLVLAYH 153
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
89-199 4.05e-12

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: 67.33  E-value: 4.05e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   89 RPMVKLVANIQGDEAVGRQMVLYMAEYLAthydGDPKVQALLNLTEIHFLPTCNPDGFAKAKegnceslpnyvgRGNAAN 168
Cdd:cd06242     1 KPTVLLVGQQHGNEPAGREAALALARDLA----FGDDARELLEKVNVLVVPRANPDGRAANT------------RGNANG 64
                          90       100       110
                  ....*....|....*....|....*....|.
gi 221329602  169 IDLNRDFpdrleqshvHQLraqsRQPETAAL 199
Cdd:cd06242    65 VDLNRDH---------LLL----STPETRAL 82
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
510-657 5.54e-12

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: 66.33  E-value: 5.54e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  510 YVANMHGNEVVGKELLLILTKYMLeryGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVG----RANAHGIDLN 585
Cdd:cd03857     4 LAAQIHGNETTGTEALMELIRDLA---SESDEAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGlpgtRYNANGIDLN 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 221329602  586 RNFPDQygtdrfnkvTEPEVAA----VMNWTLSLpFVLSANLHGGSlvanYPFDDNENDFNDPFMRLRNSSINGRK 657
Cdd:cd03857    81 RDHVKL---------TQPETQAvaenFIHWWPDI-FIDLHEQVGAS----IPYPTPPDAPNYNLVDLRSDAENGQE 142
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
488-699 2.50e-11

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: 65.94  E-value: 2.50e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  488 DLWVLEIF---ATPGShvpGVPEFKYVANMHGNEVVGKELLLILTKYMLERYGNDDRITKLVNGTRMHFLYSMNPDGYEI 564
Cdd:cd06226     1 DIRALKLTnkqATPPG---EKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKI 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  565 SIEG-------DRTGGVGRANAHGIDLNRNFPDQYG-----TDRFNKV-------TEPEVAAVMNWTLSL-----PFVLS 620
Cdd:cd06226    78 AETGllwrkntNTTPCPASSPTYGVDLNRNSSFKWGgagagGSACSETyrgpsaaSEPETQAIENYVKQLfpdqrGPGLT 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  621 A-----------NLHGGSLVANYPFDDNEN-DFNDPFMR---LRNSSINGRKPNP---------TEDNALFKHLaGIysn 676
Cdd:cd06226   158 DpapddtsgiyiDIHSYGNLVLYPWGWTGTpAPNAAGLRtlgRKFAYFNGYTPQQavalyptdgTTDDFAYGTL-GV--- 233
                         250       260
                  ....*....|....*....|....*..
gi 221329602  677 AHPTMYLG----QPCELFQNEFFPDGI 699
Cdd:cd06226   234 AAYTFELGtaffESCSYFENTILPDNL 260
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
70-203 8.78e-11

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: 64.40  E-value: 8.78e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   70 IYALALS----APTGEskngdllRPMVKLVANIQGDEAVGRQMVLYMAEYLATHYDGDPKVQALLNLTEIHFLPTCNPDG 145
Cdd:cd06226     2 IRALKLTnkqaTPPGE-------KPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDG 74
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602  146 FAKAKEGnceslpnYVGRGNAAN-----------IDLNRDFPDRLEQ--------SHVHQLRAQSRQPETAALVNWI 203
Cdd:cd06226    75 RKIAETG-------LLWRKNTNTtpcpassptygVDLNRNSSFKWGGagaggsacSETYRGPSAASEPETQAIENYV 144
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
39-225 9.12e-10

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: 61.68  E-value: 9.12e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   39 EEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSapTGESKngdllRPMVKLVANIQGDEAVGRQMVLYMAEYLAT 118
Cdd:cd03870    10 EEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFS--TGGEE-----RPAIWIDAGIHSREWVTQASAIWTAEKIVS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  119 HYDGDPKVQALLNLTEIHFLPTCNPDGFA----------KAKEGNCESLpnYVGrgnaanIDLNR----DFPDRLEQSH- 183
Cdd:cd03870    83 DYGKDPSITSILDTMDIFLEIVTNPDGYVfthssnrlwrKTRSVNPGSL--CIG------VDPNRnwdaGFGGPGASSNp 154
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 221329602  184 ----VHQLRAQSrQPETAALVNWIVS----KPFVlsaNFHGGAVVASYPY 225
Cdd:cd03870   155 csetYHGPHANS-EVEVKSIVDFIQShgnfKAFI---SIHSYSQLLMYPY 200
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
47-215 9.16e-10

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: 60.66  E-value: 9.16e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   47 QLAKDYPdlAQTYTIGKSLEDRPIYALALSAPTGeskngdllRPMVKLvaniqgdeaVGRQ---------MVLYMAEYLA 117
Cdd:cd06237     9 SLAKKPF--VKRSTIGKSVEGRPIEALTIGNPDS--------KELVVL---------LGRQhppevtgalAMQAFVETLL 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  118 ThyDgDPKVQALLNLTEIHFLPTCNPDGFAkakEGNCeslpnyvgRGNAANIDLNRD---FpdrleqshvhqlraqsRQP 194
Cdd:cd06237    70 A--D-TELAKAFRARFRVLVVPLLNPDGVD---LGHW--------RHNAGGVDLNRDwgpF----------------TQP 119
                         170       180
                  ....*....|....*....|....*..
gi 221329602  195 ETAALVNWIVSKP------FVLSANFH 215
Cdd:cd06237   120 ETRAVRDFLLELVeepggkVVFGLDFH 146
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
35-344 1.32e-09

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: 60.93  E-value: 1.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNgdllRPMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd06248     1 YHSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRSTNSEDTS----KPTIMIEGGINPREWISPPAALYAIH 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDGDPKvqaLLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAAN-----IDLNRDF----------PDRL 179
Cdd:cd06248    77 KLVEDVETQSD---LLNNFDWIILPVANPDGYVFTHTNDREWTKNRSTNSNPLGqicfgVNINRNFdyqwnpvlssESPC 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  180 eqSHVHQLRAQSRQPETAALVNWIVSK--PFVLSANFHGGAVVASYPYDNSLAhnecceeslTPDDRVFKQLAHTYsdnh 257
Cdd:cd06248   154 --SELYAGPSAFSEAESRAIRDILHEHgnRIHLYISFHSGGSFILYPWGYDGS---------TSSNARQLHLAGVA---- 218
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  258 piMRKGNNCNDSFSGGITNGAHW-YELSGGMQDFNYAFSNcFELTIELSCCKYPAASTLPqewqrnKASLLQLLRQAHIG 336
Cdd:cd06248   219 --AAAAISSNNGRPYVVGQSSVLlYRAAGTSSDYAMGIAG-IDYTYELPGYSSGDPFYVP------PAYIEQVVREAWEG 289

                  ....*...
gi 221329602  337 IKGLVTDA 344
Cdd:cd06248   290 IVVGARAA 297
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1221-1299 2.47e-09

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 55.36  E-value: 2.47e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  1221 SIAGVVLDESNHPVRNAKVSVV---GQTQLRNFTGSMGQYRISAVPLGTITLKVEAPRHLEATRQMHLIQGGlATENVVF 1297
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVTntdTGTVRTTTTDADGRYRFPGLPPGTYTVTVSAPGFKTATRTGVTVTAG-QTTTLDV 79

                   ..
gi 221329602  1298 HL 1299
Cdd:pfam13620   80 TL 81
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
480-755 2.81e-09

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: 58.83  E-value: 2.81e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  480 IGKSVQGRDLWVLEifatpgshvPGVPEFKYV---ANMHGNEVVGKELLLILTKYMLerygNDDRITKLvngtRMHFLYS 556
Cdd:cd06904     4 YGTSVKGRPILAYK---------FGPGSRARIliiGGIHGDEPEGVSLVEHLLRWLK----NHPASGDF----HIVVVPC 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  557 MNPDGYEISIegdrtggvgRANAHGIDLNRNFPDQygtdrfnkvtepevaavmNWTLSLPFVLSANLHGGSLVANYPfdd 636
Cdd:cd06904    67 LNPDGLAAGT---------RTNANGVDLNRNFPTK------------------NWEPDARKPKDPRYYPGPKPASEP--- 116
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  637 nENDFndpFMRLrnssINGRKPNPtednalfkhlagIYSnahptmyLGQPcelFQNEFFPDGITNGAQWYSVTGGMQDWN 716
Cdd:cd06904   117 -ETRA---LVEL----IERFKPDR------------IIS-------LHAP---YLVNYDGPAKSLLAEKLAQATGYPVVG 166
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 221329602  717 YV-------------RAGCLELTIEmgcdkFPKAAELSRYWEDHREPLLQFI 755
Cdd:cd06904   167 DVgytpgslgtyagiERNIPVITLE-----LPEAVSIDELWQDLKRALIEAI 213
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
94-226 2.93e-09

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: 58.63  E-value: 2.93e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   94 LVANIQGDEAVGRQMVLYMAEYLAThyDGDPKVQALLNLTeIHFLPTCNPDGF-AKAKEGNCESLPNYVGRGNAANIDLN 172
Cdd:cd03857     4 LAAQIHGNETTGTEALMELIRDLAS--ESDEAAKLLDNIV-ILLVPQLNPDGAeLFVNFYLDSMNGLPGTRYNANGIDLN 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 221329602  173 RDFpdrleqshvhqlrAQSRQPETAALV-NWIVSKPFVLsANFHgGAVVASYPYD 226
Cdd:cd03857    81 RDH-------------VKLTQPETQAVAeNFIHWWPDIF-IDLH-EQVGASIPYP 120
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
453-611 1.04e-08

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: 58.45  E-value: 1.04e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  453 EHHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIfatpGSHVPGVPEFKYV-ANMHGNEVVGKELLLILTKY 531
Cdd:cd03872     1 VYHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIdCGIHAREWIGPAFCQWFVKE 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  532 MLERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRAN-----AHGIDLNRNFPDQYGTDRFN-------- 598
Cdd:cd03872    77 AINSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKnsrfqCRGVDANRNWKVKWCDEGASlhpcddty 156
                         170
                  ....*....|....*..
gi 221329602  599 ----KVTEPEVAAVMNW 611
Cdd:cd03872   157 cgpfPESEPEVKAVAQF 173
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
92-227 5.08e-08

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: 55.42  E-value: 5.08e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   92 VKLVANIQGDEAVGRQMVLYMAEYLATHYD-----GDPKVQALLNLTEIHFLPTCNPDG-------FAKAKEGNCESLPN 159
Cdd:cd06229     1 VLYNASFHAREYITTLLLMKFIEDYAKAYVnksyiRGKDVGELLNKVTLHIVPMVNPDGveisqngSNAINPYYLRLVAW 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  160 YVGR-------GNAANIDLNRDFPDRLEQSHVHQLRAQS----------RQPETAALVNWIVSKPFVLSANFHGGAVVAS 222
Cdd:cd06229    81 NKKGtdftgwkANIRGVDLNRNFPAGWEKEKRLGPKAPGprdypgkeplSEPETKAMAALTRQNDFDLVLAYHSQGEEIY 160

                  ....*
gi 221329602  223 YPYDN 227
Cdd:cd06229   161 WGYNG 165
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
510-610 5.36e-07

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: 51.92  E-value: 5.36e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  510 YVANMHGNEVVGKELLLILTKYMLerygNDDRITKLVNGTRMHFLYSMNPDGYEIsiegDRtggvgRANAHGIDLNRNfp 589
Cdd:cd06242     6 LVGQQHGNEPAGREAALALARDLA----FGDDARELLEKVNVLVVPRANPDGRAA----NT-----RGNANGVDLNRD-- 70
                          90       100
                  ....*....|....*....|.
gi 221329602  590 dqygtdrFNKVTEPEVAAVMN 610
Cdd:cd06242    71 -------HLLLSTPETRALAR 84
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
31-175 9.07e-07

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: 52.50  E-value: 9.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   31 ESPHYLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNGDLLRpmvklvANIQGDEAVGRQMVL 110
Cdd:cd06246     1 YYEQYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGKEQTAKNAIWID------CGIHAREWISPAFCL 74
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602  111 YMAEYLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKEGNCESLPNYVGRGNAANI--DLNRDF 175
Cdd:cd06246    75 WFIGHASYFYGIIGQHTNLLNLVDFYVMPVVNVDGYDYSWKKNRMWRKNRSKHANNRCIgtDLNRNF 141
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
97-216 9.07e-07

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: 9.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   97 NIQGDEAVGRQMVLYMAEYLAThyDGDPKVQALLNLTEIHFLPTCNPDG---FAKAKEGNCESLPNY------------V 161
Cdd:cd06238     9 SIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGrerFVNWFNQNRGAVGDPdpqsmehnepwpG 86
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 221329602  162 GRGNAANIDLNRDFpdrLEQShvhqlraqsrQPETAALVNWIVS-KPFVLsANFHG 216
Cdd:cd06238    87 GRTNHYLFDLNRDW---LAQT----------QPESRARAAAIHRwRPQVV-VDFHE 128
PRK10602 PRK10602
murein tripeptide amidase MpaA;
550-591 1.76e-06

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 50.80  E-value: 1.76e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 221329602  550 RMHFLYSMNPDGYEISIegdrtggvgRANAHGIDLNRNFPDQ 591
Cdd:PRK10602   72 RHHVVLAVNPDGCQLGL---------RANANGVDLNRNFPAA 104
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
450-588 1.98e-06

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: 51.30  E-value: 1.98e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  450 TKYehHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIfATPGSHVPGVpeFkYVANMHGNEVVGKELLLILT 529
Cdd:cd03871     4 EKY--NNWETIEAWTEQVASKNPDLVSRSQIGTTFEGRPIYLLKV-GKPGSNKKAI--F-MDCGFHAREWISPAFCQWFV 77
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 221329602  530 KYMLERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRA-----NAHGIDLNRNF 588
Cdd:cd03871    78 REAVRTYGKEKIMTKLLDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSpnagsSCIGTDPNRNF 141
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
39-146 2.50e-06

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: 51.13  E-value: 2.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   39 EEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALsaptgeSKNGDLLRPMVKLVANIQGDEAVGRQMVLYMAEYLAT 118
Cdd:cd03872     6 EEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL------GKRSRSYKKAVWIDCGIHAREWIGPAFCQWFVKEAIN 79
                          90       100
                  ....*....|....*....|....*...
gi 221329602  119 HYDGDPKVQALLNLTEIHFLPTCNPDGF 146
Cdd:cd03872    80 SYQTDPAMKKMLNQLYFYVMPVFNVDGY 107
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
337-416 2.52e-06

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: 46.82  E-value: 2.52e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   337 IKGLVTDA-SGFPIADANVYVAGLEEKpMRTSKRGEY-WRLLTPGLYSVHASAFGYQTsapQQVRVTNDNQEALRLDFKL 414
Cdd:pfam13715    1 ISGTVVDEnTGEPLPGATVYVKGTTKG-TVTDADGNFeLKNLPAGTYTLVVSFVGYKT---QEKKVTVSNDNTLDVNFLL 76

                   ..
gi 221329602   415 AP 416
Cdd:pfam13715   77 KE 78
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
35-206 2.81e-06

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: 51.00  E-value: 2.81e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   35 YLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPTGESKNgdllrpMVKLVANIQGDEAVGRQMVLYMAE 114
Cdd:cd06247     4 YHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIGWPSDKPKK------IIWMDCGIHAREWIAPAFCQWFVK 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  115 YLATHYDGDPKVQALLNLTEIHFLPTCNPDGFA---------KAKEGNCESlpnyvgrGNAANIDLNRDF--------PD 177
Cdd:cd06247    78 EILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIyswttdrlwRKSRSPHNN-------GTCYGTDLNRNFnsqwcsigAS 150
                         170       180
                  ....*....|....*....|....*....
gi 221329602  178 RLEQSHVHQLRAQSRQPETAALVNWIVSK 206
Cdd:cd06247   151 RNCCSIIFCGTGPESEPETKAVADLIEKK 179
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
761-837 2.92e-06

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 46.50  E-value: 2.92e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   761 GIHGFVHSTIGTPIAGAVVRL----DGANHSTYSQVFGDYWKLAL-PGRHNLTVLGDNYAPLR---MEVEVPDVhpfeMR 832
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdTGTVRTTTTDADGRYRFPGLpPGTYTVTVSAPGFKTATrtgVTVTAGQT----TT 76

                   ....*
gi 221329602   833 MDITL 837
Cdd:pfam13620   77 LDVTL 81
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
69-215 3.01e-06

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: 50.00  E-value: 3.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   69 PIYALAlsaptgeSKNGDLLRPMVKLVANIQGDEAVGRQMVLYMAEYLATHYDGDpkvqalLNLteiHFLPTCNPDGFAK 148
Cdd:cd06231    29 PLFALK-------SPNPRGDKPRVLISAGIHGDEPAGVEALLRFLESLAEKYLRR------VNL---LVLPCVNPWGFER 92
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602  149 AKegnceslpnyvgRGNAANIDLNRDFpdrleqshvhqlRAQSRQPETAALVNWIVS-KPFVLSANFH 215
Cdd:cd06231    93 NT------------RENADGIDLNRSF------------LKDSPSPEVRALMEFLASlGRFDLHLDLH 136
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
510-663 3.37e-06

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: 50.46  E-value: 3.37e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  510 YVANMHGNEVVGKELLLILTKYMLERYGND------------DRITKLVNGTRMHFLYSMNPDGYEISIEGDR------- 570
Cdd:cd06228     5 FIGGVHAREWGSPDILIYFAADLLEAYTNNtgltyggktftaAQVKSILENVDLVVFPLVNPDGRWYSQTSESmwrknrn 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  571 -TGGVGRANAHGIDLNRN------FPDQYGTDRFNKVT--------------EPEVAAVMNWTLSLP----FVlsaNLHG 625
Cdd:cd06228    85 pASAGDGGSCIGVDINRNfdflwdFPRYFDPGRVPASTspcsetyhgpsafsEPETRNVVWLFDAYPnirwFV---DVHS 161
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 221329602  626 GSLVANYPFDDNENDFNDPFMRLRNSSINGRKPNPTED 663
Cdd:cd06228   162 ASELILYSWGDDENQSTDPAMNFLNPAYDGKRGIAGDT 199
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
450-608 3.57e-06

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: 50.62  E-value: 3.57e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  450 TKYehHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIfatpgSHVPGVPE--FKYVANMHGNEVVGKELLLI 527
Cdd:cd06247     2 TKY--HPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKI-----GWPSDKPKkiIWMDCGIHAREWIAPAFCQW 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  528 LTKYMLERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRANAH-----GIDLNRNFPDQYGT-------- 594
Cdd:cd06247    75 FVKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLWRKSRSPHNngtcyGTDLNRNFNSQWCSigasrncc 154
                         170
                  ....*....|....*...
gi 221329602  595 -DRFN---KVTEPEVAAV 608
Cdd:cd06247   155 sIIFCgtgPESEPETKAV 172
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
453-611 3.92e-06

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: 50.58  E-value: 3.92e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  453 EHHNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIFATPGSHVPGVPefkYVANMHGNEVVGKELLLILTKYM 532
Cdd:cd06246     4 QYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGKEQTAKNAIW---IDCGIHAREWISPAFCLWFIGHA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  533 LERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGD---RTGGVGRANAH--GIDLNRNFPDQYGT-----DRFNKV-- 600
Cdd:cd06246    81 SYFYGIIGQHTNLLNLVDFYVMPVVNVDGYDYSWKKNrmwRKNRSKHANNRciGTDLNRNFDAGWCGkgassDSCSETyc 160
                         170
                  ....*....|....*.
gi 221329602  601 -----TEPEVAAVMNW 611
Cdd:cd06246   161 gpypeSEPEVKAVASF 176
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
54-232 1.77e-05

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: 47.95  E-value: 1.77e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   54 DLAQTYTIGKSLEDRPIYALALSAPTGESKNgdllrpmVKLVAniqgdeavgRQ-----MVLYMAEYLATHY--DGDPKV 126
Cdd:cd06234    17 PGVRLEVLGQTLDGRDIDLLTIGDPGTGKKK-------VWIIA---------RQhpgetMAEWFMEGLLDRLldEDDPVS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  127 QALLNLTEIHFLPTCNPDGfakAKEGNCeslpnyvgRGNAANIDLNR--DFPDrleqshvhqlraQSRQPETAALVNWIV 204
Cdd:cd06234    81 RALLEKAVFYVVPNMNPDG---SVRGNL--------RTNAAGVNLNRewANPS------------LERSPEVFAVRQAMD 137
                         170       180
                  ....*....|....*....|....*...
gi 221329602  205 SKPFVLSANFHGgavvasypyDNSLAHN 232
Cdd:cd06234   138 ATGVDFFLDVHG---------DEALPYN 156
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
558-624 4.42e-05

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: 46.53  E-value: 4.42e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602  558 NPDGYEisiegDRTggvgRANAHGIDLNRNFpdqygtdrFNKVTEPEVAAVMNWTLSLP-FVLSANLH 624
Cdd:cd06231    86 NPWGFE-----RNT----RENADGIDLNRSF--------LKDSPSPEVRALMEFLASLGrFDLHLDLH 136
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
514-625 5.74e-05

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: 45.48  E-value: 5.74e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  514 MHGNEVVGKELLLILTKYMlerYGNDDRITKLVNGTRMHFLYSMNPDGYEIsiegdrtggVGRANAHGIDLNRnfpdqyg 593
Cdd:cd06239     8 MHGNEPTGTEALLDLISYL---RRERQEFEKILERLTLVAIPMLNPDGAEL---------FTRHNAEGIDLNR------- 68
                          90       100       110
                  ....*....|....*....|....*....|..
gi 221329602  594 tdRFNKVTEPEVAAVMNWTLSLPFVLSANLHG 625
Cdd:cd06239    69 --DARALQTPESRALKAVLDSFSPKFAFNLHD 98
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
452-729 6.01e-05

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: 46.40  E-value: 6.01e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  452 YEHH-NFTAmesylRAISSSypsLTRLYSIGKSVQGRDLWVLeIFATPGSHVPGVpefkYV-ANMHGNE------VVGke 523
Cdd:cd06234     3 YERHlDLVA-----RAQASP---GVRLEVLGQTLDGRDIDLL-TIGDPGTGKKKV----WIiARQHPGEtmaewfMEG-- 67
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  524 llliltkyMLERY--GNDDRITKLVNGTRMHFLYSMNPDGyeiSIegdrtGGVGRANAHGIDLNRNF--PDqygtdrfnK 599
Cdd:cd06234    68 --------LLDRLldEDDPVSRALLEKAVFYVVPNMNPDG---SV-----RGNLRTNAAGVNLNREWanPS--------L 123
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  600 VTEPEVAAVMNWTLSLPFVLSANLHGgslvanypfdDNENDFNdpFMrlrnSSINGrKPNPTED-NALFKHLAGIYSNAH 678
Cdd:cd06234   124 ERSPEVFAVRQAMDATGVDFFLDVHG----------DEALPYN--FI----AGAEG-IPSWTPRlAALEAAFKAALAAAS 186
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 221329602  679 PTmylgqpcelFQNEF-FPDGITNGAQWYSVtggmqdWNYV--RAGCLELTIEM 729
Cdd:cd06234   187 PD---------FQTEHgYPPDAPGEANLTIA------SNWVaeRFGCLAMTLEM 225
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
511-636 8.33e-05

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: 45.73  E-value: 8.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  511 VANMHGNEVVGKELLLIL------TKYMLERYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGD---RTggvgraNAHG 581
Cdd:cd06227     7 VFGEHARELISVESALRLlrqlcgGLQEPAASALRELAREILDNVELKIIPNANPDGRRLVESGDycwRG------NENG 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221329602  582 IDLNRNFP---DQYGTDRFNKV-------TEPEVAAVMNWTLSLPFVLSANLHGGSLVANYPFDD 636
Cdd:cd06227    81 VDLNRNWGvdwGKGEKGAPSEEypgpkpfSEPETRALRDLALSFKPHAFVSVHSGMLAIYTPYAY 145
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
126-228 1.38e-04

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: 44.96  E-value: 1.38e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  126 VQALLNLTEIHFLPTCNPDGFAKAKEGN-CEslpnyvgRGNAANIDLNRDFPDRLEQSHVHQLRAQSR------QPETAA 198
Cdd:cd06227    44 AREILDNVELKIIPNANPDGRRLVESGDyCW-------RGNENGVDLNRNWGVDWGKGEKGAPSEEYPgpkpfsEPETRA 116
                          90       100       110
                  ....*....|....*....|....*....|
gi 221329602  199 LVNWIVSKPFVLSANFHGGAVVASYPYDNS 228
Cdd:cd06227   117 LRDLALSFKPHAFVSVHSGMLAIYTPYAYS 146
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
97-216 1.45e-04

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: 44.75  E-value: 1.45e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   97 NIQGDEAVGRQMVLYMAEYLATHYDG--------------DPKVQALLNLTEIHFLPTCNPDGFAKAKegnceslpnyvg 162
Cdd:cd06244     7 NIHGNEVEGVDALLEFLEMLATEPNVtyntlvkyykvenvDLEVKDLLDDVFFIVVPTENPDGRVANT------------ 74
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 221329602  163 RGNAANIDLNRDFPdrleqshvhqlrAQSrQPETAALVNWIVSKPFVLSANFHG 216
Cdd:cd06244    75 RTNANGFDLNRDNA------------YQT-QPETRAMQELISKWNPVTFLDMHG 115
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
89-201 2.33e-04

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: 44.17  E-value: 2.33e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   89 RPMVKLVANIQGDEAVGRQMVLYMAEYLAthydgDPKVQALLNLTEIHFLPTCNPDG---FAKAKEGNcESLPNYVG-RG 164
Cdd:cd06241     1 KPVVLIQAGIHPGEVEGKEASLMLLRDIA-----QGGKKHLLDNLILLFVPIFNADGndrRSKGNRPN-QNGPLEVGwRT 74
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 221329602  165 NAANIDLNRDFpdrleqshvhqLRAQSrqPETAALVN 201
Cdd:cd06241    75 NAQGLDLNRDF-----------MKLEA--PETRALAK 98
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
455-729 3.39e-04

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: 44.37  E-value: 3.39e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  455 HNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEIfATPGSHVPGVPEFKYVANMHGNEVVGKELLLILTKYMLE 534
Cdd:cd06248     2 HSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRI-RSTNSEDTSKPTIMIEGGINPREWISPPAALYAIHKLVE 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  535 RygnDDRITKLVNGTRMHFLYSMNPDGYEISIEGDR--TGGVgRANAH-------GIDLNRNFPDQY------------- 592
Cdd:cd06248    81 D---VETQSDLLNNFDWIILPVANPDGYVFTHTNDRewTKNR-STNSNplgqicfGVNINRNFDYQWnpvlssespcsel 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  593 --GTDRFnkvTEPEVAAVMNWTLS--LPFVLSANLHGGSLVANYPFddnendfndpfmrlrnsSINGRKPNptedNALFK 668
Cdd:cd06248   157 yaGPSAF---SEAESRAIRDILHEhgNRIHLYISFHSGGSFILYPW-----------------GYDGSTSS----NARQL 212
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 221329602  669 HLAGIYSNAHPTMYLGQPCELFQneffpdgitNGAQWYSVTGGMQDWNYVRAGcLELTIEM 729
Cdd:cd06248   213 HLAGVAAAAAISSNNGRPYVVGQ---------SSVLLYRAAGTSSDYAMGIAG-IDYTYEL 263
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
32-232 3.48e-04

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: 44.37  E-value: 3.48e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   32 SPHYLKNEEIGDLFSQLAKDYPDLAQTYTIGKSLEDRPIYALALSAPtGESKNGdllrpmVKLVANIQGDEAVGRQMVLY 111
Cdd:cd03871     3 YEKYNNWETIEAWTEQVASKNPDLVSRSQIGTTFEGRPIYLLKVGKP-GSNKKA------IFMDCGFHAREWISPAFCQW 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  112 MAEYLATHYDGDPKVQALLNLTEIHFLPTCNPDGFA----------KAKEGNCESlpNYVGrgnaanIDLNRDF------ 175
Cdd:cd03871    76 FVREAVRTYGKEKIMTKLLDRLDFYILPVLNIDGYVytwtknrmwrKTRSPNAGS--SCIG------TDPNRNFnagwct 147
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 221329602  176 --PDRLEQSHVHQLRAQSRQPETAALVNWIVSKPFVLSA--NFHGGAVVASYP--YDNSLAHN 232
Cdd:cd03871   148 vgASSNPCSETYCGSAPESEKETKALANFIRNNLSSIKAylTIHSYSQMLLYPysYTYKLAPN 210
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
513-611 3.61e-04

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: 43.50  E-value: 3.61e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  513 NMHGNEVVGKELLLILTKYMLEryGNDDRITKLVNGTRMHFLYSMNPDGYE------------------ISIEGDRTGGV 574
Cdd:cd06238     9 SIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRErfvnwfnqnrgavgdpdpQSMEHNEPWPG 86
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 221329602  575 GRANAHGIDLNRNFPDQygtdrfnkvTEPEVAAVMNW 611
Cdd:cd06238    87 GRTNHYLFDLNRDWLAQ---------TQPESRARAAA 114
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
455-614 3.66e-04

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: 44.35  E-value: 3.66e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  455 HNFTAMESYLRAISSSYPSLTRLYSIGKSVQGRDLWVLEiFATPGSHVPgvpEFKYVANMHGNEVVGKELLLILTKYMLE 534
Cdd:cd03870     7 HTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLK-FSTGGEERP---AIWIDAGIHSREWVTQASAIWTAEKIVS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  535 RYGNDDRITKLVNGTRMHFLYSMNPDGYEISIEGDRTGGVGRA-----NAHGIDLNRNFPDQYGTDRFNK---------- 599
Cdd:cd03870    83 DYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNRLWRKTRSvnpgsLCIGVDPNRNWDAGFGGPGASSnpcsetyhgp 162
                         170
                  ....*....|....*..
gi 221329602  600 --VTEPEVAAVMNWTLS 614
Cdd:cd03870   163 haNSEVEVKSIVDFIQS 179
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
513-608 4.46e-04

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: 43.21  E-value: 4.46e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  513 NMHGNEVVGKELLL-ILTKYMLERYGNDDRITKLVNGTRMH-----------FLYSM--NPDGYEISIegdrtggvgRAN 578
Cdd:cd06244     7 NIHGNEVEGVDALLeFLEMLATEPNVTYNTLVKYYKVENVDlevkdllddvfFIVVPteNPDGRVANT---------RTN 77
                          90       100       110
                  ....*....|....*....|....*....|
gi 221329602  579 AHGIDLNRNFPDQygtdrfnkvTEPEVAAV 608
Cdd:cd06244    78 ANGFDLNRDNAYQ---------TQPETRAM 98
M14-like cd03862
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
90-203 8.01e-04

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: 42.80  E-value: 8.01e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602   90 PMVKLVANIQGDEAVGRQMVLYMAEYLATHYDGDPKVQALLNLTEIHFLPTCNPDGFAKAKegnceslpnyvgRGNAANI 169
Cdd:cd03862     1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGGMALKT------------RSNPNGV 68
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 221329602  170 DLNRDFPDRLEQShVHQLRAQSR--------------QPETAALVNWI 203
Cdd:cd03862    69 DLMRNAPVEAVEK-VPFLVGGQRisphlpwyrgrnglETESQALIRYV 115
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
1222-1271 9.69e-04

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: 39.50  E-value: 9.69e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 221329602  1222 IAGVVLDE-SNHPVRNAKVSVVGqTQLRNFTGSMGQYRISAVPLGTITLKV 1271
Cdd:pfam13715    1 ISGTVVDEnTGEPLPGATVYVKG-TTKGTVTDADGNFELKNLPAGTYTLVV 50
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
1122-1188 1.35e-03

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: 38.66  E-value: 1.35e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221329602 1122 GVSGLVQNDKGQPLREAYVRLLEHDRIINVTKNVARFQLMLPhGLYGLEVTAPNYESQMIKVDVEDG 1188
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLP-GTYNVTASAPGYQPVTKTVTVPNN 66
ClfA COG4932
Clumping factor A-related surface protein, MSCRAMM (microbial surface components recognizing ...
1111-1274 1.69e-03

Clumping factor A-related surface protein, MSCRAMM (microbial surface components recognizing adhesive matrix molecules) family, DEv-IgG fold [Cell wall/membrane/envelope biogenesis];


Pssm-ID: 443959 [Multi-domain]  Cd Length: 689  Bit Score: 43.04  E-value: 1.69e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602 1111 KIKNFLALVKTGVSGLVQN-DKGQPLREAYVRLLEHDRIINVTKNVAR------FQLM-LPHGLYGL-EVTAPN-YE--S 1178
Cdd:COG4932   252 TLKNTPKYTKGSVTVTKTDaDTGEPLAGATFTLTDADGNTVVTTTVTVtdadgsYTFTdLPPGTYTVtETKAPAgYDldG 331
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602 1179 QMIKVDVEDGRVTELGIIrmhpftlirgvvlelPNNDNRATTSIAGVVLDESNH--PVRNAKVSVV---GQTQLRNFTGS 1253
Cdd:COG4932   332 EAVKVTITAGQTTTVTVT---------------NGNNEVKTGSVTLTKVDADDGeaPLAGAEFTLTdadGTVVATITTDA 396
                         170       180
                  ....*....|....*....|..
gi 221329602 1254 MGQYRISAVPLGTITLK-VEAP 1274
Cdd:COG4932   397 DGTASFKGLAPGTYTLTeTKAP 418
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
1222-1299 1.81e-03

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: 38.27  E-value: 1.81e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 221329602 1222 IAGVVLDESNHPVRNAKVSVVGQTQlRNFTGSMGQYRISAVPlGTITLKVEAPRHLEATRQMHLIQGGLATEnVVFHL 1299
Cdd:cd11308     2 IKGFVTDATGNPIANATISVEGINH-DVTTAKDGDYWRLLLP-GTYNVTASAPGYQPVTKTVTVPNNFSATV-VNFTL 76
M14-like cd06232
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
480-625 1.88e-03

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: 41.99  E-value: 1.88e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  480 IGKSVQGRDLWVLEIFA-TPGSHVPG------VPEFKYVANMHGNEVVGKELLLILTKYMLErygNDDRITKLVNGTrmh 552
Cdd:cd06232     2 EARSYQGRDIWAREFTEpSTSEFVSQaklslyKPTILISARHHANEVSSTNAALRLAELLAT---DPPEILKKVNLV--- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  553 fLYSM-NPDGYEISIEGDRTG-----GVGRANAHGIDlnrnfpdqYGTDRFNKVTE-PEvAAVMN--WTLSLPFVlSANL 623
Cdd:cd06232    76 -IIPLeNPDGYALHEELQKDNpehklHAARYNALGDE--------YAYEYFNDDPRfPE-AEVRPraWERWLPDI-HVDL 144

                  ..
gi 221329602  624 HG 625
Cdd:cd06232   145 HG 146
M14-like cd03862
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
506-589 6.85e-03

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: 40.10  E-value: 6.85e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221329602  506 PEFKYVANMHGNEVVGKELLLILTKYMLERYGNDDRITKLVNGTRMHFLYSMNPDGYEISiegdrtggvGRANAHGIDLN 585
Cdd:cd03862     1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGGMALK---------TRSNPNGVDLM 71

                  ....
gi 221329602  586 RNFP 589
Cdd:cd03862    72 RNAP 75
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1122-1193 7.33e-03

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 36.87  E-value: 7.33e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221329602  1122 GVSGLVQNDKGQPLREAYVRLLEHDRiiNVTKNVA-----RFQLM-LPHGLYGLEVTAPNYESQMIK-VDVEDGRVTEL 1193
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVTNTDT--GTVRTTTtdadgRYRFPgLPPGTYTVTVSAPGFKTATRTgVTVTAGQTTTL 77
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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