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Conserved domains on  [gi|22202611|ref|NP_001295|]
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carboxypeptidase D isoform 1 precursor [Homo sapiens]

Protein Classification

M14 family carboxypeptidase N/E( domain architecture ID 10301804)

M14 family zinc carboxypeptidase N/E relies on its substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages that would otherwise damage the cell; it contains an extra C-terminal domain which may assist in folding of the carboxypeptidase domain, regulate enzyme activity, or be involved in interactions with other proteins or with membranes

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 496-791 0e+00

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: 671.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  496 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 575
Cdd:cd03863    1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  576 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAV 655
Cdd:cd03863   81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  656 MSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITN 735
Cdd:cd03863  161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611  736 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03863  241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 933-1210 3.59e-161

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: 484.64  E-value: 3.59e-161
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTNNAS------QPETKAIIENLIQK 1086
Cdd:cd06245   81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1087 qDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEWHSHLGSMK 1166
Cdd:cd06245  161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 22202611 1167 DYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 1210
Cdd:cd06245  240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
Peptidase_M14_like super family cl11393
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 58-378 1.97e-152

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.


The actual alignment was detected with superfamily member cd03868:

Pssm-ID: 472171  Cd Length: 294  Bit Score: 462.10  E-value: 1.97e-152
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   58 YYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTAglgslipEGDAGPdaagpdaagpllPGRPQVKLVGN 137
Cdd:cd03868    1 YHNYDELTDLLHKLAETYPNIA-KLHSIGKSVQGRELWVLEISD-------NVNRRE------------PGKPMFKYVAN 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  138 MHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGfgdgGPSGASGRDNSRGRDLN 217
Cdd:cd03868   61 MHGDETVGRQLLIYLAQYLLENYGK-DERVTRLVNSTDIHLMPSMNPDGFENSKEGDCS----GDPGYGGRENANNVDLN 135

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  218 RSFPDQFSTGEPPALDE-VPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYA 296
Cdd:cd03868  136 RNFPDQFEDSDDRLLEGrQPETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYA 215

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  297 SNHPIMKTGEPHCpgdeDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITL 376
Cdd:cd03868  216 DNHPTMHKGNNCC----EDSFKDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSY 291


                 ..
gi 22202611  377 IE 378
Cdd:cd03868  292 ME 293
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 795-870 3.79e-36

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: 131.49  E-value: 3.79e-36
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611  795 GVRGFVLDATdGRGILNATISVAEINHPVTTYKTGDYWRLLVPGTYKITASARGYNPVTKNVTVKSE-GAIQVNFTL 870
Cdd:cd11308    1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 383-459 4.52e-31

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: 116.85  E-value: 4.52e-31
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611  383 GVKGFVKDSiTGSGLENATISVAGINHNITTGRFGDFYRLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDFSL 459
Cdd:cd11308    1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 1214-1288 1.53e-23

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: 95.28  E-value: 1.53e-23
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611 1214 GVHGFVKDKTGKPISKAVIVLNEG-IKVQTKEGGYFHVLLAPGVHNIIAIADGYQQQHSQVFVHHDaASSVVIVFD 1288
Cdd:cd11308    1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFT 75
 
Name Accession Description Interval E-value
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 496-791 0e+00

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: 671.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  496 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 575
Cdd:cd03863    1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  576 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAV 655
Cdd:cd03863   81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  656 MSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITN 735
Cdd:cd03863  161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611  736 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03863  241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 933-1210 3.59e-161

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: 484.64  E-value: 3.59e-161
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTNNAS------QPETKAIIENLIQK 1086
Cdd:cd06245   81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1087 qDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEWHSHLGSMK 1166
Cdd:cd06245  161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 22202611 1167 DYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 1210
Cdd:cd06245  240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 58-378 1.97e-152

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: 462.10  E-value: 1.97e-152
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   58 YYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTAglgslipEGDAGPdaagpdaagpllPGRPQVKLVGN 137
Cdd:cd03868    1 YHNYDELTDLLHKLAETYPNIA-KLHSIGKSVQGRELWVLEISD-------NVNRRE------------PGKPMFKYVAN 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  138 MHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGfgdgGPSGASGRDNSRGRDLN 217
Cdd:cd03868   61 MHGDETVGRQLLIYLAQYLLENYGK-DERVTRLVNSTDIHLMPSMNPDGFENSKEGDCS----GDPGYGGRENANNVDLN 135

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  218 RSFPDQFSTGEPPALDE-VPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYA 296
Cdd:cd03868  136 RNFPDQFEDSDDRLLEGrQPETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYA 215

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  297 SNHPIMKTGEPHCpgdeDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITL 376
Cdd:cd03868  216 DNHPTMHKGNNCC----EDSFKDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSY 291


                 ..
gi 22202611  377 IE 378
Cdd:cd03868  292 ME 293
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
509-784 6.15e-99

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 318.09  E-value: 6.15e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    509 MEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTD 588
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    589 PEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSN-----NFDLNRNFPDQFVQI---TDPT-----------Q 649
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFPDHWNEVgasSNPCsetyrgpapfsE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    650 PETIAVMSWMKS-YPFVLSANLHGGSLVVNYPFDDDEQglatySKSPDDAVFQQIALSYSKENSQMFQGRpcknmypneY 728
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-----EPPPDDEELKSLARAAAKALQKMVRGT---------S 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 22202611    729 FPHGITNGASWYNVPGGMQDWNYLQTNC-FEVTIELGCVK----YPLEKELPNFWEQNRRS 784
Cdd:pfam00246  227 YTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
503-776 2.43e-93

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 302.33  E-value: 2.43e-93
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     583 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN---NSNNFDLNRNFPDQFVQITDP-----------T 648
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGNPcsetyagpspfS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     649 QPETIAVMSWMKSY-PFVLSANLHGGSLVVNYPFDDDEQGLATYSKSpDDAVFQQIALSYSKENsqmfqgrpcknmypNE 727
Cdd:smart00631  158 EPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALASVH--------------GT 222

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 22202611     728 YFPHGITNGASWYnVPGGMQDWNYLQTN-CFEVTIELGCV-----KYPLEKELPN 776
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPT 276
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
81-372 4.29e-79

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 262.62  E-value: 4.29e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     81 RLFSIGRSVEGRPLWVLRLTAGlgslipegdagpdaagpdaAGPLLPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:pfam00246   17 RLVSIGKSVEGRPLKVLKISSG-------------------PGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    161 RRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGfgdggpsGASGRDNSR-----GRDLNRSFPDQF----------- 224
Cdd:pfam00246   78 GR-DPEITELLDDTDIYILPVVNPDGYEYTHTTDRL-------WRKNRSNANgssciGVDLNRNFPDHWnevgassnpcs 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    225 STGEPPALDEVPEVRALIEWIRR-NKFVLSGNLHGGSVVASYPFDDSPEhkatgiySKTSDDEVFKYLAKAYASNHPIMK 303
Cdd:pfam00246  150 ETYRGPAPFSEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAKALQKMV 222

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22202611    304 TGephcpgdedETFKDGITNGAHWYDVEGGMQDYNYVWANC-FEITLELSCCK----YPPASQLRQEWENNRES 372
Cdd:pfam00246  223 RG---------TSYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
58-365 2.94e-78

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 259.96  E-value: 2.94e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611      58 YYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpdaaGPLLPGRPQVKLVGN 137
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLV-RLVSIGKSVEGRPIWVLKIS----------------------NGGSHDKPAIFIDAG 57

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     138 MHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCgfgdGGPSGASGRDNSRGRDLN 217
Cdd:smart00631   58 IHAREWIGPATALYLINQLLENYGR-DPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDR----LWRKNRSPNSNCRGVDLN 132

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     218 RSFPDQFS--------TGEPPALDEVPEVRALIEWIRRN-KFVLSGNLHGGSVVASYPFDDSPEHKATGIyskTSDDEVF 288
Cdd:smart00631  133 RNFPFHWGetgnpcseTYAGPSPFSEPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVA 209

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     289 KYLAKAYASNHPImktgephcpgdedeTFKDGITNGAHWYdVEGGMQDYNYVWAN-CFEITLELSCC-----KYPPASQL 362
Cdd:smart00631  210 KALAKALASVHGT--------------RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQII 274


                    ...
gi 22202611     363 RQE 365
Cdd:smart00631  275 PTG 277
Zn_pept smart00631
Zn_pept domain;
933-1188 1.29e-55

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 194.86  E-value: 1.29e-55
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGG---SHDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIG---QTNARGKDLDTDFTNN-----------------AS 1072
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNrspNSNCRGVDLNRNFPFHwgetgnpcsetyagpspFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    1073 QPETKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQTV-----ENKETLKHLASLYANNHPSMHMGQPSCpnksden 1147
Cdd:smart00631  158 EPETKAVRDFIRSNRRFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGTRYTYGISN------- 230

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|..
gi 22202611    1148 ipggvmrGAEWHSHlGSMKDYS-VTYGHCPEITVYTSCCYFP 1188
Cdd:smart00631  231 -------GAIYPAS-GGSDDWAyGVLGIPFSFTLELRDDGRY 264
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
941-1203 6.42e-48

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 173.25  E-value: 6.42e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    941 EFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPA 1020
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   1021 VTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNAR-----GKDLDTDF--------------------TNNASQPE 1075
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFpdhwnevgassnpcsetyrgPAPFSEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   1076 TKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQT-VENKETLKHLASLYANNHPSMHMGQpscpnksdeNIPGGVMR 1154
Cdd:pfam00246  163 TRAVADFIRSKKPFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 22202611   1155 GAEWHSHLGSMKDYSVTYGHCP-EITVYTSCC----YFPSAARLPSLWADNKRS 1203
Cdd:pfam00246  234 GATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
486-746 7.73e-38

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 145.60  E-value: 7.73e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  486 LSGTSSSYQPIQPKD-FHHHHfpDMEIFLRRFANEyPNITRLYSLGKSVESRELYVMEISDnpgvHEPGEPEFKYIGNMH 564
Cdd:COG2866    3 LLILPATYKEVSSYDrYYTYE--ELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQH 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  565 GNEVVGRELLLNLIEYLCKNFgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQFVqi 644
Cdd:COG2866   76 GNEWTGTEALLGLLEDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWL-- 142

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  645 tdpTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDD---AVFQQIALSYSKENSQMFQGRPCK 721
Cdd:COG2866  143 ---SEPETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEereAFAEELNFEGIILAGSAFLGAGAA 219

                        250       260
                 ....*....|....*....|....*
gi 22202611  722 NMYPNEYFPHGITNGASWYNVPGGM 746
Cdd:COG2866  220 GTLLISAPRQTFLFAAALDIGGGGD 244
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 795-870 3.79e-36

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: 131.49  E-value: 3.79e-36
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611  795 GVRGFVLDATdGRGILNATISVAEINHPVTTYKTGDYWRLLVPGTYKITASARGYNPVTKNVTVKSE-GAIQVNFTL 870
Cdd:cd11308    1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
54-291 5.02e-32

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 128.65  E-value: 5.02e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   54 QFDRYYHEEELESALREAAAAGLPGlaRLFSIGRSVEGRPLWVLRLtaglgslipegdagpdaagpdaaGPLLPGRPQVK 133
Cdd:COG2866   15 SYDRYYTYEELLALLAKLAAASPLV--ELESIGKSVEGRPIYLLKI-----------------------GDPAEGKPKVL 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  134 LVGNMHGDETVSRQVLIYLARELAAGYrrgDPRLVRLLNTTDVYLLPSLNPDGFERARegdcgfgdggpsgasgRDNSRG 213
Cdd:COG2866   70 LNAQQHGNEWTGTEALLGLLEDLLDNY---DPLIRALLDNVTLYIVPMLNPDGAERNT----------------RTNANG 130

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  214 RDLNRSFPDqfstgepPALDEvPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYL 291
Cdd:COG2866  131 VDLNRDWPA-------PWLSE-PETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEEREAFAEE 200
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 383-459 4.52e-31

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: 116.85  E-value: 4.52e-31
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611  383 GVKGFVKDSiTGSGLENATISVAGINHNITTGRFGDFYRLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDFSL 459
Cdd:cd11308    1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 1214-1288 1.53e-23

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: 95.28  E-value: 1.53e-23
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611 1214 GVHGFVKDKTGKPISKAVIVLNEG-IKVQTKEGGYFHVLLAPGVHNIIAIADGYQQQHSQVFVHHDaASSVVIVFD 1288
Cdd:cd11308    1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFT 75
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
932-1109 1.94e-22

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 100.15  E-value: 1.94e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  932 RYHSYKDLSEFLRGLVMNYPHITnLTNLGQSTEYRHIWSLEISNKpnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1011
Cdd:COG2866   18 RYYTYEELLALLAKLAAASPLVE-LESIGKSVEGRPIYLLKIGDP----AEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1012 CLNYkkNPAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDF-TNNASQPETKAIIEnLIQKQDFS 1090
Cdd:COG2866   93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWpAPWLSEPETRALRD-LLDEHDPD 160

                        170       180
                 ....*....|....*....|.
gi 22202611 1091 LSVAL--DGGSMLVTYPYDKP 1109
Cdd:COG2866  161 FVLDLhgQGELFYWFVGTTEP 181
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
383-459 2.41e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 69.62  E-value: 2.41e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    383 GVKGFVKDSiTGSGLENATISVA----GINHNITTGRFGDFY-RLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDF 457
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 22202611    458 SL 459
Cdd:pfam13620   80 TL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
795-870 3.88e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 68.85  E-value: 3.88e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    795 GVRGFVLDATdGRGILNATISVA----EINHPVTTYKTGDYW-RLLVPGTYKITASARGYNPVTK-NVTVKSEGAIQVNF 868
Cdd:pfam13620    1 TISGTVTDPS-GAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRtGVTVTAGQTTTLDV 79


                   ..
gi 22202611    869 TL 870
Cdd:pfam13620   80 TL 81
PRK10602 PRK10602
murein tripeptide amidase MpaA;
139-253 2.26e-06

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 50.41  E-value: 2.26e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   139 HGDETVSRQVLIYLARELAAGYRRgdprlvrllntTDVYLlpSLNPDGferaregdCGFGDggpsgasgRDNSRGRDLNR 218
Cdd:PRK10602   49 HGDETASVVTLSCALRTLTPSLRR-----------HHVVL--AVNPDG--------CQLGL--------RANANGVDLNR 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611   219 SFPDQ---------------------FSTGEPPALDevPEVRALIEWIRRNK--FVLS 253
Cdd:PRK10602  100 NFPAAnwkegetvyrwnsaaeerdvvLLTGDKPGSE--PETQALCQLIHRLQpaWVVS 155
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1214-1286 2.33e-06

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 46.89  E-value: 2.33e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   1214 GVHGFVKDKTGKPISKAVIVL-----NEGIKVQTKEGGYFHV-LLAPGVHNIIAIADGYQQQH-SQVFVHHDAASSVVIV 1286
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRFpGLPPGTYTVTVSAPGFKTATrTGVTVTAGQTTTLDVT 80
PRK10602 PRK10602
murein tripeptide amidase MpaA;
599-640 2.08e-03

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 41.55  E-value: 2.08e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 22202611   599 RIHLMPSMNPDGyekSQEGDsisvigRNNSNNFDLNRNFPDQ 640
Cdd:PRK10602   72 RHHVVLAVNPDG---CQLGL------RANANGVDLNRNFPAA 104
 
Name Accession Description Interval E-value
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 496-791 0e+00

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: 671.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  496 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 575
Cdd:cd03863    1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  576 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAV 655
Cdd:cd03863   81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  656 MSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITN 735
Cdd:cd03863  161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611  736 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03863  241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
 503-791 0e+00

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: 569.21  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:cd03858    1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  583 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQI---TDPTQPETIAVMSWM 659
Cdd:cd03858   81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVysdNNPRQPETKAVMNWL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  660 KSYPFVLSANLHGGSLVVNYPFDDDEQG-LATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNmYPNEYFPHGITNGAS 738
Cdd:cd03858  161 ESIPFVLSANLHGGALVANYPYDDTRSGkSTEYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGAA 239

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 22202611  739 WYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03858  240 WYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 933-1210 3.59e-161

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: 484.64  E-value: 3.59e-161
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTNNAS------QPETKAIIENLIQK 1086
Cdd:cd06245   81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1087 qDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEWHSHLGSMK 1166
Cdd:cd06245  161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 22202611 1167 DYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 1210
Cdd:cd06245  240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 58-378 1.97e-152

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: 462.10  E-value: 1.97e-152
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   58 YYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTAglgslipEGDAGPdaagpdaagpllPGRPQVKLVGN 137
Cdd:cd03868    1 YHNYDELTDLLHKLAETYPNIA-KLHSIGKSVQGRELWVLEISD-------NVNRRE------------PGKPMFKYVAN 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  138 MHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGfgdgGPSGASGRDNSRGRDLN 217
Cdd:cd03868   61 MHGDETVGRQLLIYLAQYLLENYGK-DERVTRLVNSTDIHLMPSMNPDGFENSKEGDCS----GDPGYGGRENANNVDLN 135

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  218 RSFPDQFSTGEPPALDE-VPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYA 296
Cdd:cd03868  136 RNFPDQFEDSDDRLLEGrQPETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYA 215

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  297 SNHPIMKTGEPHCpgdeDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITL 376
Cdd:cd03868  216 DNHPTMHKGNNCC----EDSFKDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSY 291


                 ..
gi 22202611  377 IE 378
Cdd:cd03868  292 ME 293
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 501-791 1.43e-150

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: 457.48  E-value: 1.43e-150
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  501 FHHHHfpDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 580
Cdd:cd03868    1 YHNYD--ELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQY 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  581 LCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGD---SISVIGRNNSNNFDLNRNFPDQFV----QITDPTQPETI 653
Cdd:cd03868   79 LLENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDcsgDPGYGGRENANNVDLNRNFPDQFEdsddRLLEGRQPETL 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  654 AVMSWMKSYPFVLSANLHGGSLVVNYPFDD----DEQGlaTYSKSPDDAVFQQIALSYSKENSQMFQGRPCKnmypNEYF 729
Cdd:cd03868  159 AMMKWIVENPFVLSANLHGGSVVASYPFDDspshIECG--VYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSF 232

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22202611  730 PHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03868  233 KDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
 933-1210 6.54e-128

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: 397.02  E-value: 6.54e-128
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03858    1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFT---------NNASQPETKAIIENL 1083
Cdd:cd03858   81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPdqffqvysdNNPRQPETKAVMNWL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1084 IQKqDFSLSVALDGGSMLVTYPYDKP-------VQTVENKETLKHLASLYANNHPSMHMGQPSCPnKSDENIPGGVMRGA 1156
Cdd:cd03858  161 ESI-PFVLSANLHGGALVANYPYDDTrsgksteYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGA 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 22202611 1157 EWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 1210
Cdd:cd03858  239 AWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
 58-379 3.36e-126

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: 392.40  E-value: 3.36e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   58 YYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpDAAGPLLPGRPQVKLVGN 137
Cdd:cd03858    1 HHNYEELEEFLKQVAKRYPNIT-RLYSIGKSVEGRELWVLEIS-------------------DNPGVHEPGEPEFKYVAN 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  138 MHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGfgdggpsGASGRDNSRGRDLN 217
Cdd:cd03858   61 MHGNEVVGRELLLLLAEYLCENYGK-DPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCG-------GLIGRNNANGVDLN 132

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  218 RSFPDQFSTGEPPALDEVPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATgIYSKTSDDEVFKYLAKAYAS 297
Cdd:cd03858  133 RNFPDQFFQVYSDNNPRQPETKAVMNWLESIPFVLSANLHGGALVANYPYDDTRSGKST-EYSPSPDDAVFRMLARSYSD 211

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  298 NHPIMKTGEPHCPgDEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLI 377
Cdd:cd03858  212 AHPTMSMGKPCCC-DDDENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFL 290


                 ..
gi 22202611  378 EK 379
Cdd:cd03858  291 EQ 292
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 503-791 1.37e-123

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: 385.30  E-value: 1.37e-123
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:cd03866    1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  583 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAVMSWMKSY 662
Cdd:cd03866   81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEENNVQRQPETRAVMDWIKNE 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  663 PFVLSANLHGGSLVVNYPFDD---DEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMypnEYFPHGITNGASW 739
Cdd:cd03866  161 TFVLSANLHGGALVASYPFDNgnsGTGQLGYYSVSPDDDVFIYLAKTYSYNHTNMYKGIECSNS---QSFPGGITNGYQW 237

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 22202611  740 YNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03866  238 YPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 503-791 1.54e-115

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: 364.64  E-value: 1.54e-115
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:cd03864    1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  583 KNFGTDPE-VTDLVHNTRIHLMPSMNPDGYE-KSQEGDSIS--VIGRNNSNNFDLNRNFPD---------------QFVQ 643
Cdd:cd03864   81 EEYRNGNErITRLIQDTRIHILPSMNPDGYEvAARQGPEFNgyLVGRNNANGVDLNRNFPDlntlmyynekyggpnHHLP 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  644 ITD----PTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQ------GLATYSKSPDDAVFQQIALSYSKENSQ 713
Cdd:cd03864  161 LPDnwksQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREprvrgfRRTAYSPTPDDKLFQKLAKTYSYAHGW 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  714 MFQGRPCknmypNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03864  241 MHKGWNC-----GDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 504-791 6.44e-114

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: 358.81  E-value: 6.44e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  504 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 583
Cdd:cd18173    5 PTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA-EPEFKYTSTMHGDETTGYELMLRLIDYLLT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  584 NFGTDPEVTDLVHNTRIHLMPSMNPDGYeksQEGDSISVIG--RNNSNNFDLNRNFPDqFVQITDPT----QPETIAVMS 657
Cdd:cd18173   84 NYGTDPRITNLVDNTEIWINPLANPDGT---YAGGNNTVSGatRYNANGVDLNRNFPD-PVDGDHPDgngwQPETQAMMN 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  658 WMKSYPFVLSANLHGGSLVVNYPFDddeqglATYSKSPDDAVFQQIALSYSKENSQmfqgrPCKNMYpNEYFPHGITNGA 737
Cdd:cd18173  160 FADEHNFVLSANFHGGAEVVNYPWD------TWYSRHPDDDWFQDISREYADTNQA-----NSPPMY-MSEFNNGITNGY 227

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 22202611  738 SWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd18173  228 DWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 503-791 1.02e-110

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: 351.59  E-value: 1.02e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  583 KNFGTDPE-VTDLVHNTRIHLMPSMNPDGYEKS-QEGDSIS--VIGRNNSNNFDLNRNFPD------------------- 639
Cdd:cd03865   81 NEYQKGNEtIINLIHSTRIHIMPSLNPDGFEKAaSQPGELKdwFVGRSNAQGIDLNRNFPDldrivyvnekeggpnnhll 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  640 ----QFVQITDPTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLA-TYSKSPDDAVFQQIALSYSKENSQM 714
Cdd:cd03865  161 knmkKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAhEYSSCPDDAIFQSLARAYSSLNPAM 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22202611  715 FQG--RPCKNMYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd03865  241 SDPnrPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 503-791 7.20e-102

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: 327.56  E-value: 7.20e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:cd03869    1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  583 KNF-GTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISV---IGRNNSNNFDLNRNFPD------------------- 639
Cdd:cd03869   81 QEYlAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGgwsLGRWTSDGIDINHNFPDlnsllweaedrkwvprkvp 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  640 -------QFVQITDPT-QPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLAT--YSKSPDDAVFQQIALSYSK 709
Cdd:cd03869  161 nhhipipEWYLSENATvAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTqeYTPTPDDHVFRWLAYSYAS 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  710 ENSQMFQG--RPCKnmYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQ 787
Cdd:cd03869  241 THRLMTDAsrRPCH--TEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLV 318


                 ....
gi 22202611  788 FMKQ 791
Cdd:cd03869  319 FMEQ 322
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
509-784 6.15e-99

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 318.09  E-value: 6.15e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    509 MEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTD 588
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    589 PEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSN-----NFDLNRNFPDQFVQI---TDPT-----------Q 649
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFPDHWNEVgasSNPCsetyrgpapfsE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    650 PETIAVMSWMKS-YPFVLSANLHGGSLVVNYPFDDDEQglatySKSPDDAVFQQIALSYSKENSQMFQGRpcknmypneY 728
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-----EPPPDDEELKSLARAAAKALQKMVRGT---------S 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 22202611    729 FPHGITNGASWYNVPGGMQDWNYLQTNC-FEVTIELGCVK----YPLEKELPNFWEQNRRS 784
Cdd:pfam00246  227 YTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 58-379 1.51e-98

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: 317.12  E-value: 1.51e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   58 YYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLtaglgSLIPEGDagpdaagpdaagplLPGRPQVKLVGN 137
Cdd:cd03866    1 YHNQEQMETYLKDVNKNYPSIT-HLHSIGKSVEGRDLWVLVL-----GRFPTKH--------------RIGIPEFKYVAN 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  138 MHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFgdggpsgASGRDNSRGRDLN 217
Cdd:cd03866   61 MHGDEVVGRELLLHLIEFLVTSYGS-DPVITRLINSTRIHIMPSMNPDGFEATKKPDCYY-------TKGRYNKNGYDLN 132

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  218 RSFPDQFSTGEPPaldEVPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDS-PEHKATGIYSKTSDDEVFKYLAKAYA 296
Cdd:cd03866  133 RNFPDAFEENNVQ---RQPETRAVMDWIKNETFVLSANLHGGALVASYPFDNGnSGTGQLGYYSVSPDDDVFIYLAKTYS 209

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  297 SNHPIMKTGEpHCPgdEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITL 376
Cdd:cd03866  210 YNHTNMYKGI-ECS--NSQSFPGGITNGYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEY 286


                 ...
gi 22202611  377 IEK 379
Cdd:cd03866  287 IKQ 289
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 523-787 2.86e-96

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: 310.50  E-value: 2.86e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  523 ITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNF-GTDPEVTDLVHNTRIH 601
Cdd:cd18172   21 ISRLIVIGSSVNGFPLWALEISDGPGEDET-EPAFKFVGNMHGDEPVGRELLLRLADWLCANYkAKDPLAAKIVENAHLH 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  602 LMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQFVQITDPT-----QPETIAVMSWMKSYPFVLSANLHGGSLV 676
Cdd:cd18172  100 LVPTMNPDGFARRR---------RNNANNVDLNRDFPDQFFPKNLRNdlaarQPETLAVMNWSRSVRFTASANLHEGALV 170

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  677 VNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENsqmfqgrpcKNMYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNC 756
Cdd:cd18172  171 ANYPWDGNADGRTKYSASPDDATFRRLASVYAQAH---------PNMAKSKEFPGGITNGAQWYPLYGGMQDWNYLHTGC 241

                        250       260       270
                 ....*....|....*....|....*....|.
gi 22202611  757 FEVTIELGCVKYPLEKELPNFWEQNRRSLIQ 787
Cdd:cd18172  242 MDLTLEVNDNKWPPEDRLVQIWAEHRKAMLA 272
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 503-790 1.03e-94

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: 307.58  E-value: 1.03e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:cd03867    1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  583 KNF-GTDPEVTDLVHNTRIHLMPSMNPDGYEKSQE---GDSISVIGRNNSNNFDLNRNFPD----------------QFV 642
Cdd:cd03867   81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEegaGYNGWTSGRQNAQNLDLNRNFPDltseayrlartrgarlDHI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  643 QITD-----PTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLA--TYSKSPDDAVFQQIALSYSKENsQMF 715
Cdd:cd03867  161 PIPQsywwgKVAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEekMFSPTPDEKMFKLLAKAYADAH-PMM 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22202611  716 QGRPCKNMYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMK 790
Cdd:cd03867  240 SDRSENRCGGNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314
Zn_pept smart00631
Zn_pept domain;
503-776 2.43e-93

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 302.33  E-value: 2.43e-93
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     583 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN---NSNNFDLNRNFPDQFVQITDP-----------T 648
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGNPcsetyagpspfS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     649 QPETIAVMSWMKSY-PFVLSANLHGGSLVVNYPFDDDEQGLATYSKSpDDAVFQQIALSYSKENsqmfqgrpcknmypNE 727
Cdd:smart00631  158 EPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALASVH--------------GT 222

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 22202611     728 YFPHGITNGASWYnVPGGMQDWNYLQTN-CFEVTIELGCV-----KYPLEKELPN 776
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPT 276
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 58-378 4.97e-86

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: 281.61  E-value: 4.97e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   58 YYHEEELESALrEAAAAGLPGLARLFSIGRSVEGRPLWVLRLTAGlgsliPEGDAGpdaagpdaagpllpgRPQVKLVGN 137
Cdd:cd18172    1 YHSNAELEDAL-KAFTRRCGAISRLIVIGSSVNGFPLWALEISDG-----PGEDET---------------EPAFKFVGN 59

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  138 MHGDETVSRQVLIYLARELAAGYRRGDPRLVRLLNTTDVYLLPSLNPDGFERARegdcgfgdggpsgasgRDNSRGRDLN 217
Cdd:cd18172   60 MHGDEPVGRELLLRLADWLCANYKAKDPLAAKIVENAHLHLVPTMNPDGFARRR----------------RNNANNVDLN 123

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  218 RSFPDQFST-GEPPALD-EVPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATgiYSKTSDDEVFKYLAKAY 295
Cdd:cd18172  124 RDFPDQFFPkNLRNDLAaRQPETLAVMNWSRSVRFTASANLHEGALVANYPWDGNADGRTK--YSASPDDATFRRLASVY 201

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  296 ASNHPIMKtgephcpgdEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLIT 375
Cdd:cd18172  202 AQAHPNMA---------KSKEFPGGITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLA 272


                 ...
gi 22202611  376 LIE 378
Cdd:cd18172  273 LAA 275
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 57-379 4.78e-84

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: 276.83  E-value: 4.78e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   57 RYYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpDAAGPLLPGRPQVKLVG 136
Cdd:cd03863    7 RHHHFSDMEIFLRRYANEYPSIT-RLYSVGKSVELRELYVMEIS-------------------DNPGVHEPGEPEFKYIG 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  137 NMHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGfgdggpsGASGRDNSRGRDL 216
Cdd:cd03863   67 NMHGNEVVGRELLLNLIEYLCKNFGT-DPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRG-------GTVGRNNSNNYDL 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  217 NRSFPDQF-STGEPPAldevPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATgiYSKTSDDEVFKYLAKAY 295
Cdd:cd03863  139 NRNFPDQFfQITDPPQ----PETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLAT--YSKSPDDAVFQQLALSY 212

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  296 ASNHPIMKTGEPHCPGDEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLIT 375
Cdd:cd03863  213 SKENSKMYQGSPCKELYPNEYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQ 292


                 ....
gi 22202611  376 LIEK 379
Cdd:cd03863  293 FIKQ 296
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 81-379 5.66e-84

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: 277.58  E-value: 5.66e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpDAAGPLLPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd03864   23 RIYSIGRSVEGRHLYVLEFS-------------------DNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLCEEY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RRGDPRLVRLLNTTDVYLLPSLNPDGFERAregdcgfGDGGPSGAS---GRDNSRGRDLNRSFPDQFST-------GEP- 229
Cdd:cd03864   84 RNGNERITRLIQDTRIHILPSMNPDGYEVA-------ARQGPEFNGylvGRNNANGVDLNRNFPDLNTLmyynekyGGPn 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  230 ---PALDE-----VPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGI----YSKTSDDEVFKYLAKAYAS 297
Cdd:cd03864  157 hhlPLPDNwksqvEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREPRVRGFrrtaYSPTPDDKLFQKLAKTYSY 236

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  298 NHPIMKTGEpHCpGDedeTFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLI 377
Cdd:cd03864  237 AHGWMHKGW-NC-GD---YFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYM 311


                 ..
gi 22202611  378 EK 379
Cdd:cd03864  312 EQ 313
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 81-379 2.20e-83

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: 276.09  E-value: 2.20e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpDAAGPLLPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd03865   23 RIYTVGRSFEGRELLVIEVS-------------------DNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLCNEY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RRGDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFGDGgpsgASGRDNSRGRDLNRSFPD-------QFSTGEP---- 229
Cdd:cd03865   84 QKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDW----FVGRSNAQGIDLNRNFPDldrivyvNEKEGGPnnhl 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  230 -----PALDE----VPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSpEHKATGIYSKTSDDEVFKYLAKAYASNHP 300
Cdd:cd03865  160 lknmkKAVDQntklAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDET-RSGSAHEYSSCPDDAIFQSLARAYSSLNP 238

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  301 IMK-TGEPHC-PGDEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 378
Cdd:cd03865  239 AMSdPNRPPCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIE 318


                 .
gi 22202611  379 K 379
Cdd:cd03865  319 Q 319
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 503-791 1.35e-80

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: 266.62  E-value: 1.35e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 582
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  583 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAVMSWMKSY 662
Cdd:cd06245   81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANNRSGAAQPETKAIMDWLKEK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  663 PFVLSANLHGGSLVVNYPFDDDEQglatysKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITNGASWYNV 742
Cdd:cd06245  161 DFTLSVALDGGSLVVTYPYDKPVQ------TVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSH 234

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 22202611  743 PGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 791
Cdd:cd06245  235 KGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
81-372 4.29e-79

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 262.62  E-value: 4.29e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     81 RLFSIGRSVEGRPLWVLRLTAGlgslipegdagpdaagpdaAGPLLPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:pfam00246   17 RLVSIGKSVEGRPLKVLKISSG-------------------PGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    161 RRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGfgdggpsGASGRDNSR-----GRDLNRSFPDQF----------- 224
Cdd:pfam00246   78 GR-DPEITELLDDTDIYILPVVNPDGYEYTHTTDRL-------WRKNRSNANgssciGVDLNRNFPDHWnevgassnpcs 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    225 STGEPPALDEVPEVRALIEWIRR-NKFVLSGNLHGGSVVASYPFDDSPEhkatgiySKTSDDEVFKYLAKAYASNHPIMK 303
Cdd:pfam00246  150 ETYRGPAPFSEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAKALQKMV 222

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22202611    304 TGephcpgdedETFKDGITNGAHWYDVEGGMQDYNYVWANC-FEITLELSCCK----YPPASQLRQEWENNRES 372
Cdd:pfam00246  223 RG---------TSYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
58-365 2.94e-78

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 259.96  E-value: 2.94e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611      58 YYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpdaaGPLLPGRPQVKLVGN 137
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLV-RLVSIGKSVEGRPIWVLKIS----------------------NGGSHDKPAIFIDAG 57

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     138 MHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCgfgdGGPSGASGRDNSRGRDLN 217
Cdd:smart00631   58 IHAREWIGPATALYLINQLLENYGR-DPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDR----LWRKNRSPNSNCRGVDLN 132

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     218 RSFPDQFS--------TGEPPALDEVPEVRALIEWIRRN-KFVLSGNLHGGSVVASYPFDDSPEHKATGIyskTSDDEVF 288
Cdd:smart00631  133 RNFPFHWGetgnpcseTYAGPSPFSEPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVA 209

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     289 KYLAKAYASNHPImktgephcpgdedeTFKDGITNGAHWYdVEGGMQDYNYVWAN-CFEITLELSCC-----KYPPASQL 362
Cdd:smart00631  210 KALAKALASVHGT--------------RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQII 274


                    ...
gi 22202611     363 RQE 365
Cdd:smart00631  275 PTG 277
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 81-378 6.83e-76

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: 254.43  E-value: 6.83e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpDAAGPLLPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd03867   23 RTYSIGRSFEGKDLLVIEFS-------------------SNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLCSEY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RRGDPRLVRLLNTTDVYLLPSLNPDGFERAREgdcgFGDGGPSGASGRDNSRGRDLNRSFPDQFS-----TGEPPA-LDE 234
Cdd:cd03867   84 LLGNPRIQTLINTTRIHLLPSMNPDGYEVAAE----EGAGYNGWTSGRQNAQNLDLNRNFPDLTSeayrlARTRGArLDH 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  235 V------------PEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYASNHPIM 302
Cdd:cd03867  160 IpipqsywwgkvaPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMFSPTPDEKMFKLLAKAYADAHPMM 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611  303 KTGEPHCPGDEDETfKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 378
Cdd:cd03867  240 SDRSENRCGGNFLK-RGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 933-1206 4.94e-75

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: 251.39  E-value: 4.94e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03868    1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTS---KIGQTNARGKDLDTDF----------TNNASQPETKAI 1079
Cdd:cd03868   81 ENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGdpgYGGRENANNVDLNRNFpdqfedsddrLLEGRQPETLAM 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1080 IeNLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENK--------ETLKHLASLYANNHPSMHMGQPSCpnksDENIPGG 1151
Cdd:cd03868  161 M-KWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGvyskspddAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDG 235

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 22202611 1152 VMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLS 1206
Cdd:cd03868  236 ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLS 290
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 81-378 8.75e-75

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: 250.19  E-value: 8.75e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTAGLGSLIPEgdagpdaagpdaagpllpgrPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd18173   26 RLVSIGTSVQGRKLLALKISDNVNTEEAE--------------------PEFKYTSTMHGDETTGYELMLRLIDYLLTNY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RrGDPRLVRLLNTTDVYLLPSLNPDGFERAregdcgfGDGGPSGASgRDNSRGRDLNRSFPDQFSTGEPPALDEVPEVRA 240
Cdd:cd18173   86 G-TDPRITNLVDNTEIWINPLANPDGTYAG-------GNNTVSGAT-RYNANGVDLNRNFPDPVDGDHPDGNGWQPETQA 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  241 LIEWIRRNKFVLSGNLHGGSVVASYPFDDspehkatgIYSKTSDDEVFKYLAKAYASnhpimkTGEPHCPGDEDETFKDG 320
Cdd:cd18173  157 MMNFADEHNFVLSANFHGGAEVVNYPWDT--------WYSRHPDDDWFQDISREYAD------TNQANSPPMYMSEFNNG 222

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  321 ITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 378
Cdd:cd18173  223 ITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIE 280
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 81-379 6.47e-68

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: 232.03  E-value: 6.47e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTaglgslipegdagpdaagpDAAGPLLPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd03869   23 RIYNIGKSYQGLKLYAMEIS-------------------DNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLCQEY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RRGDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFGdggpSGASGRDNSRGRDLNRSFPD--------QFSTGEP--- 229
Cdd:cd03869   84 LAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELG----GWSLGRWTSDGIDINHNFPDlnsllweaEDRKWVPrkv 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  230 -------------PALDEVPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYA 296
Cdd:cd03869  160 pnhhipipewylsENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYA 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  297 SNHPIMKTGEPHCPGDEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITL 376
Cdd:cd03869  240 STHRLMTDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVF 319


                 ...
gi 22202611  377 IEK 379
Cdd:cd03869  320 MEQ 322
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 81-377 2.57e-63

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: 217.31  E-value: 2.57e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLtaglgslipegdaGPDAAGPDaagpllPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd06245   23 NLTSLGQSVEKRDIWVLEI-------------GNKPNESE------PSEPKILFVGGIHGNAPVGTELLLLLAHFLCHNY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCgfgdggpSGASGRDNSRGRDLNRSFPDQFStgEPPALDEvPEVRA 240
Cdd:cd06245   84 KK-DSAITKLLNRTRIHIVPSLNPDGAEKAEEKKC-------TSKIGEKNANGVDLDTDFESNAN--NRSGAAQ-PETKA 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  241 LIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEhkatgiysKTSDDEVFKYLAKAYASNHPIMKTGEPHCPGDEDETFKDG 320
Cdd:cd06245  153 IMDWLKEKDFTLSVALDGGSLVVTYPYDKPVQ--------TVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNG 224

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611  321 ITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLI 377
Cdd:cd06245  225 VIRASEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMI 281
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 931-1208 3.41e-61

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: 211.73  E-value: 3.41e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  931 YRYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEF 1010
Cdd:cd03863    6 FRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1011 LCLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTN------NASQPETKAIIeNLI 1084
Cdd:cd03863   86 LCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDqffqitDPPQPETLAVM-SWL 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1085 QKQDFSLSVALDGGSMLVTYPYDKPVQTV------ENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEW 1158
Cdd:cd03863  165 KTYPFVLSANLHGGSLVVNYPFDDDEQGLatysksPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITNGAQW 244

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 22202611 1159 HSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 1208
Cdd:cd03863  245 YNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFI 294
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 933-1208 1.62e-60

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: 209.65  E-value: 1.62e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03866    1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDF-----TNNAS-QPETKAIIeNLIQK 1086
Cdd:cd03866   81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFpdafeENNVQrQPETRAVM-DWIKN 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1087 QDFSLSVALDGGSMLVTYPYDKPVQTVE---------NKETLKHLASLYANNHPSMHMGQpSCPNKsdENIPGGVMRGAE 1157
Cdd:cd03866  160 ETFVLSANLHGGALVASYPFDNGNSGTGqlgyysvspDDDVFIYLAKTYSYNHTNMYKGI-ECSNS--QSFPGGITNGYQ 236

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 22202611 1158 WHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 1208
Cdd:cd03866  237 WYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYI 287
Zn_pept smart00631
Zn_pept domain;
933-1188 1.29e-55

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 194.86  E-value: 1.29e-55
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611     933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGG---SHDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIG---QTNARGKDLDTDFTNN-----------------AS 1072
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNrspNSNCRGVDLNRNFPFHwgetgnpcsetyagpspFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    1073 QPETKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQTV-----ENKETLKHLASLYANNHPSMHMGQPSCpnksden 1147
Cdd:smart00631  158 EPETKAVRDFIRSNRRFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGTRYTYGISN------- 230

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|..
gi 22202611    1148 ipggvmrGAEWHSHlGSMKDYS-VTYGHCPEITVYTSCCYFP 1188
Cdd:smart00631  231 -------GAIYPAS-GGSDDWAyGVLGIPFSFTLELRDDGRY 264
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 504-785 1.18e-51

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: 184.00  E-value: 1.18e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  504 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVhEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 583
Cdd:cd03859    5 HTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLLE 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  584 NFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN---NSNNF------DLNRNFPDQFVQI--------TD 646
Cdd:cd03859   84 NYGTDPRITNLVDNREIWIIPVVNPDGYEYNRETGGGRLWRKNrrpNNGNNpgsdgvDLNRNYGYHWGGDnggsspdpSS 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  647 PT--------QPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFdddeqGLATYSKSPDDAVFQQIALSYSKENsqmfqgr 718
Cdd:cd03859  164 ETyrgpapfsEPETQAIRDLVESHDFKVAISYHSYGELVLYPW-----GYTSDAPTPDEDVFEELAEEMASYN------- 231

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22202611  719 pcknmypneyfPHGITNGASW--YNVPGGMQDWNYLQTNCFEVTIELG---CVKYPLEKELPNFWEQNRRSL 785
Cdd:cd03859  232 -----------GGGYTPQQSSdlYPTNGDTDDWMYGEKGIIAFTPELGpefYPFYPPPSQIDPLAEENLPAA 292
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 932-1208 9.88e-50

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: 178.16  E-value: 9.88e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  932 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEePKIRFVAGIHGNAPVGTELLLALAEFL 1011
Cdd:cd18173    3 SYPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEAE-PEFKYTSTMHGDETTGYELMLRLIDYL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1012 CLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIgQTNARGKDLDTDF---------TNNASQPETKAIIeN 1082
Cdd:cd18173   82 LTNYGTDPRITNLVDNTEIWINPLANPDGTYAGGNNTVSGAT-RYNANGVDLNRNFpdpvdgdhpDGNGWQPETQAMM-N 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1083 LIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYA----NNHPSMHMGQpscpnksdenIPGGVMRGAEW 1158
Cdd:cd18173  160 FADEHNFVLSANFHGGAEVVNYPWDTWYSRHPDDDWFQDISREYAdtnqANSPPMYMSE----------FNNGITNGYDW 229

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 22202611 1159 HSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 1208
Cdd:cd18173  230 YEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYI 279
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 933-1208 1.44e-49

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: 177.60  E-value: 1.44e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEePKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd18172    1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDETE-PAFKFVGNMHGDEPVGRELLLRLADWLC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYK-KNPAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDF-----------TNNASQPETKAII 1080
Cdd:cd18172   80 ANYKaKDPLAAKIVENAHLHLVPTMNPDGFARRR---------RNNANNVDLNRDFpdqffpknlrnDLAARQPETLAVM 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1081 eNLIQKQDFSLSVALDGGSMLVTYPYD------KPVQTVENKETLKHLASLYANNHPSMHmgqpscpnKSDEnIPGGVMR 1154
Cdd:cd18172  151 -NWSRSVRFTASANLHEGALVANYPWDgnadgrTKYSASPDDATFRRLASVYAQAHPNMA--------KSKE-FPGGITN 220

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 22202611 1155 GAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 1208
Cdd:cd18172  221 GAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALA 274
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 559-785 2.21e-48

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: 171.87  E-value: 2.21e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  559 YIGNMHGNEVVGRELLLNLIEYLCKNFGTDPeVTDLVHNTRIHLMPSMNPDGYEKSQEGDsisviGRNNSNNFDLNRNFP 638
Cdd:cd00596    3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVIDSG-----GRKNANGVDLNRNFP 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  639 DQFVQITDP-------------TQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDdeqglaTYSKSPDDAVFQQIAL 705
Cdd:cd00596   77 YNWGKDGTSgpssptyrgpapfSEPETQALRDLAKSHRFDLAVSYHSSSEAILYPYGY------TNEPPPDFSEFQELAA 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  706 SYSKENSqmfqgrpcknmypneYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPN-FWEQNRRS 784
Cdd:cd00596  151 GLARALG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTLLDrRLERNLAA 215


                 .
gi 22202611  785 L 785
Cdd:cd00596  216 L 216
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
941-1203 6.42e-48

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 173.25  E-value: 6.42e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    941 EFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPA 1020
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   1021 VTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNAR-----GKDLDTDF--------------------TNNASQPE 1075
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFpdhwnevgassnpcsetyrgPAPFSEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   1076 TKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQT-VENKETLKHLASLYANNHPSMHMGQpscpnksdeNIPGGVMR 1154
Cdd:pfam00246  163 TRAVADFIRSKKPFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 22202611   1155 GAEWHSHLGSMKDYSVTYGHCP-EITVYTSCC----YFPSAARLPSLWADNKRS 1203
Cdd:pfam00246  234 GATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 933-1208 7.29e-46

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: 168.47  E-value: 7.29e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03869    1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKK-NPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTS---KIGQTNARGKDLDTDF--------------------- 1067
Cdd:cd03869   81 QEYLAgNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELggwSLGRWTSDGIDINHNFpdlnsllweaedrkwvprkvp 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1068 -----------TNNAS-QPETKAIIeNLIQKQDFSLSVALDGGSMLVTYPYDK---PVQTVENKETLKH-----LASLYA 1127
Cdd:cd03869  161 nhhipipewylSENATvAPETRAVI-AWMEKIPFVLGGNLQGGELVVSYPYDMtrtPWKTQEYTPTPDDhvfrwLAYSYA 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1128 NNHpsMHMGQPS---CpNKSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSL 1204
Cdd:cd03869  240 STH--RLMTDASrrpC-HTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESL 316


                 ....
gi 22202611 1205 LSML 1208
Cdd:cd03869  317 LVFM 320
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 933-1208 3.19e-44

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: 163.61  E-value: 3.19e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKK-NPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSK---IGQTNARGKDLDTDF---------------TNN--- 1070
Cdd:cd03865   81 NEYQKgNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKdwfVGRSNAQGIDLNRNFpdldrivyvnekeggPNNhll 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1071 -----------ASQPETKAIIeNLIQKQDFSLSVALDGGSMLVTYPYDKP-------VQTVENKETLKHLASLYANNHPS 1132
Cdd:cd03865  161 knmkkavdqntKLAPETKAVI-HWIMDIPFVLSANLHGGDLVANYPYDETrsgsaheYSSCPDDAIFQSLARAYSSLNPA 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611 1133 MH-MGQPSC-PNKSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 1208
Cdd:cd03865  240 MSdPNRPPCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYI 317
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 933-1210 1.37e-41

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: 155.86  E-value: 1.37e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03864    1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKK-NPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSK---IGQTNARGKDLDTDF--------------------- 1067
Cdd:cd03864   81 EEYRNgNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNgylVGRNNANGVDLNRNFpdlntlmyynekyggpnhhlp 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1068 --TNNASQ--PETKAIIEnLIQKQDFSLSVALDGGSMLVTYPYDKPVQ-------------TVENKeTLKHLASLYANNH 1130
Cdd:cd03864  161 lpDNWKSQvePETLAVIQ-WMQNYNFVLSANLHGGAVVANYPYDKSREprvrgfrrtayspTPDDK-LFQKLAKTYSYAH 238

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1131 PSMHMGQpSCPNKSDEnipgGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 1210
Cdd:cd03864  239 GWMHKGW-NCGDYFDE----GITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 933-1208 3.02e-41

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: 154.66  E-value: 3.02e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03867    1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNY-KKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDC---TSKIGQTNARGKDLDTDFTNNASQ--------------- 1073
Cdd:cd03867   81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAgynGWTSGRQNAQNLDLNRNFPDLTSEayrlartrgarldhi 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1074 ------------PETKAIIEnLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKE--------TLKHLASLYANNHPSM 1133
Cdd:cd03867  161 pipqsywwgkvaPETKAVMK-WMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMfsptpdekMFKLLAKAYADAHPMM 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22202611 1134 HMGQPSCPNkSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 1208
Cdd:cd03867  240 SDRSENRCG-GNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFM 313
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
486-746 7.73e-38

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 145.60  E-value: 7.73e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  486 LSGTSSSYQPIQPKD-FHHHHfpDMEIFLRRFANEyPNITRLYSLGKSVESRELYVMEISDnpgvHEPGEPEFKYIGNMH 564
Cdd:COG2866    3 LLILPATYKEVSSYDrYYTYE--ELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQH 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  565 GNEVVGRELLLNLIEYLCKNFgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQFVqi 644
Cdd:COG2866   76 GNEWTGTEALLGLLEDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWL-- 142

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  645 tdpTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDD---AVFQQIALSYSKENSQMFQGRPCK 721
Cdd:COG2866  143 ---SEPETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEereAFAEELNFEGIILAGSAFLGAGAA 219

                        250       260
                 ....*....|....*....|....*
gi 22202611  722 NMYPNEYFPHGITNGASWYNVPGGM 746
Cdd:COG2866  220 GTLLISAPRQTFLFAAALDIGGGGD 244
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 795-870 3.79e-36

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: 131.49  E-value: 3.79e-36
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611  795 GVRGFVLDATdGRGILNATISVAEINHPVTTYKTGDYWRLLVPGTYKITASARGYNPVTKNVTVKSE-GAIQVNFTL 870
Cdd:cd11308    1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 132-373 4.05e-34

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: 130.66  E-value: 4.05e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  132 VKLVGNMHGDETVSRQVLIYLARELAAGYRRGDprLVRLLNTTDVYLLPSLNPDGFERARegdcgfgdggpsGASGRDNS 211
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALIEYLLENYGNDP--LKRLLDNVELWIVPLVNPDGFARVI------------DSGGRKNA 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  212 RGRDLNRSFPdqFSTGEPPALDEV------------PEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEhkatgiy 279
Cdd:cd00596   67 NGVDLNRNFP--YNWGKDGTSGPSsptyrgpapfsePETQALRDLAKSHRFDLAVSYHSSSEAILYPYGYTNE------- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  280 sKTSDDEVFKYLAKAYASNHPimktgephcpgdedeTFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPA 359
Cdd:cd00596  138 -PPPDFSEFQELAAGLARALG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLP 201

                        250
                 ....*....|....*
gi 22202611  360 SQLRQ-EWENNRESL 373
Cdd:cd00596  202 GTLLDrRLERNLAAL 216
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
54-291 5.02e-32

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 128.65  E-value: 5.02e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   54 QFDRYYHEEELESALREAAAAGLPGlaRLFSIGRSVEGRPLWVLRLtaglgslipegdagpdaagpdaaGPLLPGRPQVK 133
Cdd:COG2866   15 SYDRYYTYEELLALLAKLAAASPLV--ELESIGKSVEGRPIYLLKI-----------------------GDPAEGKPKVL 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  134 LVGNMHGDETVSRQVLIYLARELAAGYrrgDPRLVRLLNTTDVYLLPSLNPDGFERARegdcgfgdggpsgasgRDNSRG 213
Cdd:COG2866   70 LNAQQHGNEWTGTEALLGLLEDLLDNY---DPLIRALLDNVTLYIVPMLNPDGAERNT----------------RTNANG 130

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  214 RDLNRSFPDqfstgepPALDEvPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYL 291
Cdd:COG2866  131 VDLNRDWPA-------PWLSE-PETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEEREAFAEE 200
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 383-459 4.52e-31

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: 116.85  E-value: 4.52e-31
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611  383 GVKGFVKDSiTGSGLENATISVAGINHNITTGRFGDFYRLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDFSL 459
Cdd:cd11308    1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 500-763 3.71e-30

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: 123.50  E-value: 3.71e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  500 DFHHHH-FPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLI 578
Cdd:cd06905    2 AFDRYYtYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  579 EYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQE----------------------------GD-SISVI------ 623
Cdd:cd06905   82 EYLLTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYKLktersgrssprdddrdgdgdedgpedlnGDgLITQMrvkdpt 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  624 ------------------------------------GRNN---SNNFDLNRNFPDQFVqiTDPTQ----------PETIA 654
Cdd:cd06905  162 gtwkvdpddprlmvdrekgekgfyrlypegidndgdGRYNedgPGGVDLNRNFPYNWQ--PFYVQpgagpyplsePETRA 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  655 VMSWMKSYPFVLSANLHGGSLVVNY----PFDDDEQGLAtyskspDDAVFQQIAlsyskENSQMFQGRPCKNMYPNEYFP 730
Cdd:cd06905  240 VADFLLAHPNIAAVLTFHTSGGMILrppgTGPDSDMPPA------DRRVYDAIG-----KKGVELTGYPVSSVYKDFYTV 308

                        330       340       350
                 ....*....|....*....|....*....|...
gi 22202611  731 HGitnGASwynvPGGMQDWNYLQTNCFEVTIEL 763
Cdd:cd06905  309 PG---GPL----DGDFFDWAYFHLGIPSFSTEL 334
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 81-373 1.83e-26

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: 111.19  E-value: 1.83e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTAGlgsliPEGDagpdaagpdaagpllPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd03859   26 KLISIGKSVEGRPIWAVKISDN-----PDED---------------EDEPEVLFMGLHHAREWISLEVALYFADYLLENY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGdcgfGDGG-------PSGASGrDNSRGRDLNRSFPDQF------STG 227
Cdd:cd03859   86 GT-DPRITNLVDNREIWIIPVVNPDGYEYNRET----GGGRlwrknrrPNNGNN-PGSDGVDLNRNYGYHWggdnggSSP 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  228 EPPalDEV---------PEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKATgiysktsDDEVFKYLAKAYASn 298
Cdd:cd03859  160 DPS--SETyrgpapfsePETQAIRDLVESHDFKVAISYHSYGELVLYPWGYTSDAPTP-------DEDVFEELAEEMAS- 229

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  299 hPIMKTGEPHCPGDedetfkdgitngahWYDVEGGMQDYNYVWANCFEITLEL---SCCKYPPASQLRQEWENNRESL 373
Cdd:cd03859  230 -YNGGGYTPQQSSD--------------LYPTNGDTDDWMYGEKGIIAFTPELgpeFYPFYPPPSQIDPLAEENLPAA 292
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 933-1106 1.08e-24

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: 105.80  E-value: 1.08e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVsEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03859    4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQE--------KDCTSKIG-QTNARGKDL----DTDFTNNA-------- 1071
Cdd:cd03859   83 ENYGTDPRITNLVDNREIWIIPVVNPDGYEYNREtgggrlwrKNRRPNNGnNPGSDGVDLnrnyGYHWGGDNggsspdps 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 22202611 1072 ----------SQPETKAiIENLIQKQDFSLSVALDGGSMLVTYPY 1106
Cdd:cd03859  163 setyrgpapfSEPETQA-IRDLVESHDFKVAISYHSYGELVLYPW 206
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 1214-1288 1.53e-23

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: 95.28  E-value: 1.53e-23
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611 1214 GVHGFVKDKTGKPISKAVIVLNEG-IKVQTKEGGYFHVLLAPGVHNIIAIADGYQQQHSQVFVHHDaASSVVIVFD 1288
Cdd:cd11308    1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFT 75
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
932-1109 1.94e-22

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 100.15  E-value: 1.94e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  932 RYHSYKDLSEFLRGLVMNYPHITnLTNLGQSTEYRHIWSLEISNKpnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1011
Cdd:COG2866   18 RYYTYEELLALLAKLAAASPLVE-LESIGKSVEGRPIYLLKIGDP----AEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1012 CLNYkkNPAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDF-TNNASQPETKAIIEnLIQKQDFS 1090
Cdd:COG2866   93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWpAPWLSEPETRALRD-LLDEHDPD 160

                        170       180
                 ....*....|....*....|.
gi 22202611 1091 LSVAL--DGGSMLVTYPYDKP 1109
Cdd:COG2866  161 FVLDLhgQGELFYWFVGTTEP 181
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 932-1067 4.88e-22

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: 99.61  E-value: 4.88e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  932 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1011
Cdd:cd06905    5 RYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYL 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611 1012 CLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKdcTSKIGQTNARGKDLDTDF 1067
Cdd:cd06905   85 LTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYKLK--TERSGRSSPRDDDRDGDG 138
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 989-1204 2.04e-20

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: 91.37  E-value: 2.04e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  989 FVAGIHGNAPVGTELLLALAEFLCLNYKKNPaVTQLVDRTRIVIVPSLNPDGRERAQEKDctskiGQTNARGKDLDTDFT 1068
Cdd:cd00596    3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVIDSG-----GRKNANGVDLNRNFP 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1069 NN-------------------ASQPETKAIIEnLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANN 1129
Cdd:cd00596   77 YNwgkdgtsgpssptyrgpapFSEPETQALRD-LAKSHRFDLAVSYHSSSEAILYPYGYTNEPPPDFSEFQELAAGLARA 155

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611 1130 HPsmhmgqpscpnksdeNIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCC-YFPSAARLPSLWADNKRSL 1204
Cdd:cd00596  156 LG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTAdYPLPGTLLDRRLERNLAAL 216
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
 504-661 4.12e-19

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: 89.51  E-value: 4.12e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  504 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 583
Cdd:cd03860    2 HPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGG--KGGKPAIVIHGGQHAREWISTSTVEYLAHQLLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  584 NFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDsisvigR-------NNSNNF----DLNRNFPDQFVQI---TDPT- 648
Cdd:cd03860   80 GYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTD------RlwrknrqPTGGSScvgiDLNRNWGYKWGGPgasTNPCs 153

                        170       180
                 ....*....|....*....|...
gi 22202611  649 ----------QPETIAVMSWMKS 661
Cdd:cd03860  154 etyrgpsafsAPETKALADFINA 176
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 55-258 7.19e-19

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: 89.98  E-value: 7.19e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   55 FDRYYHEEELESALREAAAAGLPGLaRLFSIGRSVEGRPLWVLRLTAglgslipeGDAGPDAAgpdaagpllpgRPQVKL 134
Cdd:cd06905    3 FDRYYTYAELTARLKALAEAYPNLV-RLESIGKSYEGRDIWLLTITN--------GETGPADE-----------KPALWV 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  135 VGNMHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERA----------------REGDcGFG 198
Cdd:cd06905   63 DGNIHGNEVTGSEVALYLAEYLLTNYGK-DPEITRLLDTRTFYILPRLNPDGAEAYklktersgrssprdddRDGD-GDE 140

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  199 DGG----------------PSGA--------------------------SGRDN----------SRGRDLNRSFP----- 221
Cdd:cd06905  141 DGPedlngdglitqmrvkdPTGTwkvdpddprlmvdrekgekgfyrlypEGIDNdgdgrynedgPGGVDLNRNFPynwqp 220

                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 22202611  222 --DQFSTGEPPaLDEvPEVRALIEWIRRNKFVLSGNLHG 258
Cdd:cd06905  221 fyVQPGAGPYP-LSE-PETRAVADFLLAHPNIAAVLTFH 257
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 559-785 1.62e-18

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: 86.24  E-value: 1.62e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  559 YIGNMHGNEVVGRELLLNLIEYLCKN-------FGTDPEvtDLVHNTRIHLMPSMNPDGYEKSQEG-----------DSI 620
Cdd:cd06229    3 YNASFHAREYITTLLLMKFIEDYAKAyvnksyiRGKDVG--ELLNKVTLHIVPMVNPDGVEISQNGsnainpyylrlVAW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  621 SVIGRN------NSNNFDLNRNFPDQF-----VQITDP-----------TQPETIAVMSWMKSYPFVLSANLHGGSLVVN 678
Cdd:cd06229   81 NKKGTDftgwkaNIRGVDLNRNFPAGWekekrLGPKAPgprdypgkeplSEPETKAMAALTRQNDFDLVLAYHSQGEEIY 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  679 YPFDDDEQGLATyskspddavfqQIALSYSKENSqmfqgrpcknmypneYFPHGITNGASWynvpGGMQDWNYLQTNCFE 758
Cdd:cd06229  161 WGYNGLEPEESK-----------AMAEKFASVSG---------------YEPVEAEAIDSY----GGFKDWFIYEFKKPS 210

                        250       260
                 ....*....|....*....|....*...
gi 22202611  759 VTIELGCVKYPL-EKELPNFWEQNRRSL 785
Cdd:cd06229  211 FTIETGKGNNPLpISQFDEIYEKNKGVL 238
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
 81-249 1.62e-17

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: 84.89  E-value: 1.62e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTaglgslipeGDAGPdaagpdaagpllPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd03860   23 EIFTIGKSYEGRDITGIHIW---------GSGGK------------GGKPAIVIHGGQHAREWISTSTVEYLAHQLLSGY 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 RRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDcgfgdggpsgasgR---------DNS--RGRDLNRSFPDQFSTGEP 229
Cdd:cd03860   82 GS-DATITALLDKFDFYIIPVVNPDGYVYTWTTD-------------RlwrknrqptGGSscVGIDLNRNWGYKWGGPGA 147

                        170       180       190
                 ....*....|....*....|....*....|..
gi 22202611  230 P------------ALDEvPEVRALIEWIRRNK 249
Cdd:cd03860  148 StnpcsetyrgpsAFSA-PETKALADFINALA 178
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 134-287 1.19e-16

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: 80.20  E-value: 1.19e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  134 LVGNMHGDETVSRQVLIYLARELAAgyrRGDPrLVRLLNTTDVYLLPSLNPDGFERAREgdcGFGDGGPSGASGRDNSRG 213
Cdd:cd03857    4 LAAQIHGNETTGTEALMELIRDLAS---ESDE-AAKLLDNIVILLVPQLNPDGAELFVN---FYLDSMNGLPGTRYNANG 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22202611  214 RDLNRSFPDQfstgeppaldEVPEVRALIEWIRRNKFVLSGNLHgGSVVASYPFDDSPEHKATGIYSKTSDDEV 287
Cdd:cd03857   77 IDLNRDHVKL----------TQPETQAVAENFIHWWPDIFIDLH-EQVGASIPYPTPPDAPNYNLVDLRSDAEN 139
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 529-790 1.73e-16

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: 79.63  E-value: 1.73e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  529 LGKSVESRELYVMEISDNPG--VHepgepefkYIGNMHGNEVVGRELLLNLIEYLcknfGTDPEVTDLvhntRIHLMPSM 606
Cdd:cd06904    4 YGTSVKGRPILAYKFGPGSRarIL--------IIGGIHGDEPEGVSLVEHLLRWL----KNHPASGDF----HIVVVPCL 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  607 NPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQ-----FVQITDP---------TQPETIAVMSWMKSYP--FVLSanL 670
Cdd:cd06904   68 NPDGLAAGT---------RTNANGVDLNRNFPTKnwepdARKPKDPryypgpkpaSEPETRALVELIERFKpdRIIS--L 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  671 HgGSLVVNYpFDDDEQGLAtyskspddavfqqialsyskensqmfQGRPCKNMYPNEYFPhGITngaswynvPGGMQDWN 750
Cdd:cd06904  137 H-APYLVNY-DGPAKSLLA--------------------------EKLAQATGYPVVGDV-GYT--------PGSLGTYA 179

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 22202611  751 YLQTNCFEVTIELgcvkyPLEKELPNFWEQNRRSLIQFMK 790
Cdd:cd06904  180 GIERNIPVITLEL-----PEAVSIDELWQDLKRALIEAIK 214
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 537-764 1.87e-14

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: 75.18  E-value: 1.87e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  537 ELYVMEISdNPGVHEPGE-PEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQ 615
Cdd:cd06226    1 DIRALKLT-NKQATPPGEkPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  616 EGdsisVIGRNNSNN-----------FDLNRNFPDQF---VQITDP-----------TQPETIAVMSWMKSY-----PFV 665
Cdd:cd06226   80 TG----LLWRKNTNTtpcpassptygVDLNRNSSFKWggaGAGGSAcsetyrgpsaaSEPETQAIENYVKQLfpdqrGPG 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  666 LSA-----------NLHGGSLVVNYPFDDdeqglaTYSKSPDDAVFQQIALSYSKENSqmFQGRPCKNMYPneyfphgiT 734
Cdd:cd06226  156 LTDpapddtsgiyiDIHSYGNLVLYPWGW------TGTPAPNAAGLRTLGRKFAYFNG--YTPQQAVALYP--------T 219

                        250       260       270
                 ....*....|....*....|....*....|
gi 22202611  735 NGASwynvpggmQDWNYLQTNCFEVTIELG 764
Cdd:cd06226  220 DGTT--------DDFAYGTLGVAAYTFELG 241
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
383-459 2.41e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 69.62  E-value: 2.41e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    383 GVKGFVKDSiTGSGLENATISVA----GINHNITTGRFGDFY-RLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDF 457
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 22202611    458 SL 459
Cdd:pfam13620   80 TL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
795-870 3.88e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 68.85  E-value: 3.88e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    795 GVRGFVLDATdGRGILNATISVA----EINHPVTTYKTGDYW-RLLVPGTYKITASARGYNPVTK-NVTVKSEGAIQVNF 868
Cdd:pfam13620    1 TISGTVTDPS-GAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRtGVTVTAGQTTTLDV 79


                   ..
gi 22202611    869 TL 870
Cdd:pfam13620   80 TL 81
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 85-377 2.77e-13

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: 70.38  E-value: 2.77e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   85 IGRSVEGRPLWVLRltaglgslipegdagpdaagpdaAGPLlpGRPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGD 164
Cdd:cd06904    4 YGTSVKGRPILAYK-----------------------FGPG--SRARILIIGGIHGDEPEGVSLVEHLLRWLKNHPASGD 58

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  165 PRLVrllnttdvyLLPSLNPDGFERARegdcgfgdggpsgasgRDNSRGRDLNRSFP-------------DQFSTGEPPA 231
Cdd:cd06904   59 FHIV---------VVPCLNPDGLAAGT----------------RTNANGVDLNRNFPtknwepdarkpkdPRYYPGPKPA 113

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  232 LDevPEVRALIEWIRRNK--FVLSgnLHGGSVVasyPFDDSPEHKATGIYSKTSDDEVFKYLakayasnhpimktgephc 309
Cdd:cd06904  114 SE--PETRALVELIERFKpdRIIS--LHAPYLV---NYDGPAKSLLAEKLAQATGYPVVGDV------------------ 168

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22202611  310 pgdedetfkdGITNGAhwydveGGMqdynyvWA----NCFEITLELscckyPPASQLRQEWENNRESLITLI 377
Cdd:cd06904  169 ----------GYTPGS------LGT------YAgierNIPVITLEL-----PEAVSIDELWQDLKRALIEAI 213
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 559-746 3.37e-13

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: 69.80  E-value: 3.37e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  559 YIGNMHGNEVVGRELLLNLIeylcKNFGTDP-EVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIG----RNNSNNFDL 633
Cdd:cd03857    4 LAAQIHGNETTGTEALMELI----RDLASESdEAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGlpgtRYNANGIDL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  634 NRNFPDQfvqitdpTQPETIAVMS-WMKSYPFVLsANLHggslvvnypfdDDEQGLATYSKSPDDAVFQQIALSYSKENS 712
Cdd:cd03857   80 NRDHVKL-------TQPETQAVAEnFIHWWPDIF-IDLH-----------EQVGASIPYPTPPDAPNYNLVDLRSDAENG 140

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 22202611  713 QMfQGRPCKNMYPNE---YFPHGITNGASWYNVPGGM 746
Cdd:cd03857  141 QE-HIRLIAGEGSGElgkYFSPMRGGFDDSTGGNGIG 176
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
 129-272 3.23e-12

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: 67.68  E-value: 3.23e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  129 RPQVKLVGNMHGDETVSRQVLIYLARELAAGY-----RRGDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFgdggps 203
Cdd:cd06227    1 KPRVLLVFGEHARELISVESALRLLRQLCGGLqepaaSALRELAREILDNVELKIIPNANPDGRRLVESGDYCW------ 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  204 gasgRDNSRGRDLNRSFPDQFSTGEPPALDEV---------PEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPE 272
Cdd:cd06227   75 ----RGNENGVDLNRNWGVDWGKGEKGAPSEEypgpkpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAYSAS 148
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 132-257 7.81e-12

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: 66.59  E-value: 7.81e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  132 VKLVGNMHGDETVSRQVLIYLARELAAGYRRG----DPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFGD-------- 199
Cdd:cd06229    1 VLYNASFHAREYITTLLLMKFIEDYAKAYVNKsyirGKDVGELLNKVTLHIVPMVNPDGVEISQNGSNAINPyylrlvaw 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22202611  200 --GGPSGASGRDNSRGRDLNRSFPDQF---STGEPP-----------ALDEvPEVRALIEWIRRNKFVLSGNLH 257
Cdd:cd06229   81 nkKGTDFTGWKANIRGVDLNRNFPAGWekeKRLGPKapgprdypgkePLSE-PETKAMAALTRQNDFDLVLAYH 153
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 129-247 9.31e-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: 66.17  E-value: 9.31e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  129 RPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGDprlvrLLNTTDVYLLPSLNPDGFERARegdcgfgdggpsgasgR 208
Cdd:cd06242    1 KPTVLLVGQQHGNEPAGREAALALARDLAFGDDARE-----LLEKVNVLVVPRANPDGRAANT----------------R 59

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 22202611  209 DNSRGRDLNRsfpDQFstgeppALDEvPEVRALIEWIRR 247
Cdd:cd06242   60 GNANGVDLNR---DHL------LLST-PETRALARVLRD 88
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 127-257 1.03e-11

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: 66.56  E-value: 1.03e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  127 PGRPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGdprlVRLLnttdvyLLPSLNPDGFERARegdcgfgdggpsgas 206
Cdd:cd06231   40 GDKPRVLISAGIHGDEPAGVEALLRFLESLAEKYLRR----VNLL------VLPCVNPWGFERNT--------------- 94

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 22202611  207 gRDNSRGRDLNRSFpdqfsTGEPPAldevPEVRALIEWIR-RNKFVLSGNLH 257
Cdd:cd06231   95 -RENADGIDLNRSF-----LKDSPS----PEVRALMEFLAsLGRFDLHLDLH 136
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
 933-1106 1.29e-11

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: 67.17  E-value: 1.29e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03860    1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSG--GKGGKPAIVIHGGQHAREWISTSTVEYLAHQLL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKIGQTNARGKDLDTDF-----TNNASQ--------- 1073
Cdd:cd03860   79 SGYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDrlwrkNRQPTGGSSCVGIDLNRNWgykwgGPGASTnpcsetyrg 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 22202611 1074 ------PETKAI---IENLIQKQDFSLSVALDGGSMLVTYPY 1106
Cdd:cd03860  159 psafsaPETKALadfINALAAGQGIKGFIDLHSYSQLILYPY 200
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 563-672 4.40e-11

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: 63.59  E-value: 4.40e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  563 MHGNEVVGRELLLNLIEYLCKnfgTDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNfpdqfv 642
Cdd:cd06239    8 MHGNEPTGTEALLDLISYLRR---ERQEFEKILERLTLVAIPMLNPDGAELFT---------RHNAEGIDLNRD------ 69

                         90       100       110
                 ....*....|....*....|....*....|
gi 22202611  643 qITDPTQPETIAVMSWMKSYPFVLSANLHG 672
Cdd:cd06239   70 -ARALQTPESRALKAVLDSFSPKFAFNLHD 98
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 128-247 5.58e-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: 64.78  E-value: 5.58e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  128 GRPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFGDGGPSGASG 207
Cdd:cd06226   17 EKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGT-DADATWLLDYTELHLVPQVNPDGRKIAETGLLWRKNTNTTPCPA 95

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 22202611  208 RDNSRGRDLNRSFPdqFSTGEPPALDEV-------------PEVRALIEWIRR 247
Cdd:cd06226   96 SSPTYGVDLNRNSS--FKWGGAGAGGSAcsetyrgpsaasePETQAIENYVKQ 146
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 562-672 9.47e-11

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: 63.24  E-value: 9.47e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  562 NMHGNEVVGRELLLNLIEYLCKN--------------FGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNN 627
Cdd:cd06244    7 NIHGNEVEGVDALLEFLEMLATEpnvtyntlvkyykvENVDLEVKDLLDDVFFIVVPTENPDGRVANT---------RTN 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 22202611  628 SNNFDLNRNFPDQfvqitdpTQPETIAVMSWMKSYPFVLSANLHG 672
Cdd:cd06244   78 ANGFDLNRDNAYQ-------TQPETRAMQELISKWNPVTFLDMHG 115
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
 517-774 1.13e-10

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: 64.44  E-value: 1.13e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  517 ANEYPNITRLYSLGKSVESRELYVMEISDNpgvhepgEPEFKYI----GNMHGNEVVGRELLLNLIEYLCKNFGTDPEVT 592
Cdd:cd06246   19 TERHPDMLTKIHIGSSFEKYPLYVLKVSGK-------EQTAKNAiwidCGIHAREWISPAFCLWFIGHASYFYGIIGQHT 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  593 DLVHNTRIHLMPSMNPDGYEKSQEGDSI-----SVIGRNNSNNFDLNRNFPDQFV------QITDPT--------QPETI 653
Cdd:cd06246   92 NLLNLVDFYVMPVVNVDGYDYSWKKNRMwrknrSKHANNRCIGTDLNRNFDAGWCgkgassDSCSETycgpypesEPEVK 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  654 AVMSWMKSYPFVLSA--NLHGGSLVVNYPFDddeqglATYSKSPDDAVFQQIAlsysKENSQMFqgrpcKNMYPNEYfPH 731
Cdd:cd06246  172 AVASFLRRHKDTIKAyiSMHSYSQMVLFPYS------YTRNKSKDHDELSLLA----KEAVTAI-----RKTSRNRY-TY 235

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 22202611  732 GitNGA-SWYNVPGGMQDWNYlqtncfevtiELGcVKYPLEKEL 774
Cdd:cd06246  236 G--PGAeTIYLAPGGSDDWAY----------DLG-IKYSFTFEL 266
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 933-1134 2.82e-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: 63.22  E-value: 2.82e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvsePEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd03870    6 YHTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKIGQTNARGKDL----DTDFTNNA------------ 1071
Cdd:cd03870   82 SDYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNrlwrkTRSVNPGSLCIGVDPnrnwDAGFGGPGassnpcsetyhg 161

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611 1072 ----SQPETKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMH 1134
Cdd:cd03870  162 phanSEVEVKSIVDFIQSHGNFKAFISIHSYSQLLMYPYGYTVEKAPDQEELDEVAKKAVKALASLH 228
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 559-762 3.81e-10

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: 61.94  E-value: 3.81e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  559 YI-GNMHGNEVVGRELLLNLIEylcknfgTDPEvtDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNF 637
Cdd:cd06231   46 LIsAGIHGDEPAGVEALLRFLE-------SLAE--KYLRRVNLLVLPCVNPWGFERNT---------RENADGIDLNRSF 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  638 pdqfvqITDPTQPETIAVMSWMKSYP-FVLSANLHGgslvvnypfDDDEQGLATYSKSPDDAVFQQI-----ALSYSKEN 711
Cdd:cd06231  108 ------LKDSPSPEVRALMEFLASLGrFDLHLDLHE---------DWDSDGFYLYELGPALKAGRDGlqavdAVIPPDPI 172

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 22202611  712 SQMFQGRPcknmypneyFPHG-ITNGASWYNVPGG-MQDWNYLQTNCFEVTIE 762
Cdd:cd06231  173 SLTIDGSP---------APDGvILRPDDPAERPGWpFAIYLVANGAVRTYTTE 216
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 561-666 4.19e-10

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: 61.22  E-value: 4.19e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  561 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVHNTRIHLMPSMNPDGYEK-----SQEGDSISVI------------ 623
Cdd:cd06238    8 YSIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRERfvnwfNQNRGAVGDPdpqsmehnepwp 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 22202611  624 -GRNNSNNFDLNRnfpDQFVQitdpTQPETIAVMSWMKSY-PFVL 666
Cdd:cd06238   86 gGRTNHYLFDLNR---DWLAQ----TQPESRARAAAIHRWrPQVV 123
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
 562-683 4.20e-10

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: 61.52  E-value: 4.20e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  562 NMHGNEVVGRELLLNLIEYLC--KNFGTDPEVTDLVH----NTRIHLMPSMNPDGYEKSQEGDsisVIGRNNSNNFDLNR 635
Cdd:cd06227    9 GEHARELISVESALRLLRQLCggLQEPAASALRELAReildNVELKIIPNANPDGRRLVESGD---YCWRGNENGVDLNR 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  636 NFPD--QFVQITDPTQ----------PETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDD 683
Cdd:cd06227   86 NWGVdwGKGEKGAPSEeypgpkpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAY 145
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 504-681 7.41e-10

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: 61.71  E-value: 7.41e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  504 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 583
Cdd:cd06248    2 HSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRSTNSEDTS-KPTIMIEGGINPREWISPPAALYAIHKLVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  584 NfgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSI---SVIGRNNSNNF-----DLNRNFPDQFVQI---TDP----- 647
Cdd:cd06248   81 D---VETQSDLLNNFDWIILPVANPDGYVFTHTNDREwtkNRSTNSNPLGQicfgvNINRNFDYQWNPVlssESPcsely 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 22202611  648 ------TQPETIAVMSWMKSY--PFVLSANLHGGSLVVNYPF 681
Cdd:cd06248  158 agpsafSEAESRAIRDILHEHgnRIHLYISFHSGGSFILYPW 199
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 559-656 7.60e-10

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


Pssm-ID: 349461 [Multi-domain]  Cd Length: 220  Bit Score: 60.39  E-value: 7.60e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  559 YIGNMHGNEVVGRELLLNLIEYLCKnfgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFp 638
Cdd:cd06242    6 LVGQQHGNEPAGREAALALARDLAF----GDDARELLEKVNVLVVPRANPDGRAANT---------RGNANGVDLNRDH- 71

                         90
                 ....*....|....*...
gi 22202611  639 dqfvqiTDPTQPETIAVM 656
Cdd:cd06242   72 ------LLLSTPETRALA 83
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 933-1138 3.90e-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: 59.78  E-value: 3.90e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  933 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNkPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1012
Cdd:cd06248    1 YHSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRS-TNSEDTSKPTIMIEGGINPREWISPPAALYAIHKLV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1013 LNykkNPAVTQLVDRTRIVIVPSLNPDG------------RERAQEKDCTSKIgqtnARGKDLDTDF---------TNNA 1071
Cdd:cd06248   80 ED---VETQSDLLNNFDWIILPVANPDGyvfthtndrewtKNRSTNSNPLGQI----CFGVNINRNFdyqwnpvlsSESP 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1072 -----------SQPETKAiIENLIQKQD--FSLSVALDGGSMLVTYPYDKPVQTVENKETLkHLASLYANNHPSMHMGQP 1138
Cdd:cd06248  153 cselyagpsafSEAESRA-IRDILHEHGnrIHLYISFHSGGSFILYPWGYDGSTSSNARQL-HLAGVAAAAAISSNNGRP 230
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 515-763 2.15e-08

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: 57.46  E-value: 2.15e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  515 RFANEYPNITRLYSLGKSVESRELYVMEISdNPGVHEPGepEFKYIGnMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDL 594
Cdd:cd03871   18 QVASKNPDLVSRSQIGTTFEGRPIYLLKVG-KPGSNKKA--IFMDCG-FHAREWISPAFCQWFVREAVRTYGKEKIMTKL 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  595 VHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNN-----FDLNRNFPDQFVQI---TDP-----------TQPETIAV 655
Cdd:cd03871   94 LDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSPNAGsscigTDPNRNFNAGWCTVgasSNPcsetycgsapeSEKETKAL 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  656 MSWMKSYPFVLSANL--HGGSLVVNYPFDddeqglATYSKSPDDAVFQQIALSYSKEnsqmfqgrpCKNMYPNEYfPHGi 733
Cdd:cd03871  174 ANFIRNNLSSIKAYLtiHSYSQMLLYPYS------YTYKLAPNHEELNSIAKGAVKE---------LSSLYGTKY-TYG- 236

                        250       260       270
                 ....*....|....*....|....*....|
gi 22202611  734 TNGASWYNVPGGMQDWNYLQTNCFEVTIEL 763
Cdd:cd03871  237 PGATTIYPAAGGSDDWAYDQGIKYSFTFEL 266
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 521-687 3.03e-08

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: 56.04  E-value: 3.03e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  521 PNITRLySLGKSVESRELYVMEIsdnpgvHEPGEPEFKY-IGNMHGNEVVGRELLLNLIEYLCknfGTDPEVTDLVHNTR 599
Cdd:cd06237   14 PFVKRS-TIGKSVEGRPIEALTI------GNPDSKELVVlLGRQHPPEVTGALAMQAFVETLL---ADTELAKAFRARFR 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  600 IHLMPSMNPDGYEKsqegdsisviG--RNNSNNFDLNR---NFpdqfvqitdpTQPETIAVMSWMKSYpfvlsANLHGGS 674
Cdd:cd06237   84 VLVVPLLNPDGVDL----------GhwRHNAGGVDLNRdwgPF----------TQPETRAVRDFLLEL-----VEEPGGK 138

                        170       180
                 ....*....|....*....|....
gi 22202611  675 LV-----------VNYPFDDDEQG 687
Cdd:cd06237  139 VVfgldfhstwedVFYTQPDDEKT 162
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 991-1086 7.98e-08

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: 54.39  E-value: 7.98e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  991 AGIHGNAPVGTELLLALAEFLCLNYKknpAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQT----NARGKDLDTD 1066
Cdd:cd03857    6 AQIHGNETTGTEALMELIRDLASESD---EAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGLPgtryNANGIDLNRD 82

                         90       100
                 ....*....|....*....|
gi 22202611 1067 FTnNASQPETKAIIENLIQK 1086
Cdd:cd03857   83 HV-KLTQPETQAVAENFIHW 101
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
 796-878 9.44e-08

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: 51.05  E-value: 9.44e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    796 VRGFVLDATDGRGILNATISVAEINHPVTTYKTGDY-WRLLVPGTYKITASARGYNPVTKNVTVKSEGAIQVNFTLVRSS 874
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTDADGNFeLKNLPAGTYTLVVSFVGYKTQEKKVTVSNDNTLDVNFLLKEDA 80


                   ....
gi 22202611    875 TDSN 878
Cdd:pfam13715   81 LLLD 84
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 85-321 1.72e-07

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: 54.75  E-value: 1.72e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   85 IGRSVEGRPLWVLRLTAGlgslipegdaGPDaagpdaagpllpgRPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRgD 164
Cdd:cd03870   32 IGSSFENRPMYVLKFSTG----------GEE-------------RPAIWIDAGIHSREWVTQASAIWTAEKIVSDYGK-D 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  165 PRLVRLLNTTDVYLLPSLNPDGF----------ERARegdcgfgdggpSGASGrDNSRGRDLNR----SFPDQFSTGEP- 229
Cdd:cd03870   88 PSITSILDTMDIFLEIVTNPDGYvfthssnrlwRKTR-----------SVNPG-SLCIGVDPNRnwdaGFGGPGASSNPc 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  230 ------PALDEVPEVRALIEWIRRN-KFVLSGNLHGGSVVASYPFDdspeHKATGIYSKTSDDEVFKYLAKAYASNH--- 299
Cdd:cd03870  156 setyhgPHANSEVEVKSIVDFIQSHgNFKAFISIHSYSQLLMYPYG----YTVEKAPDQEELDEVAKKAVKALASLHgte 231

                        250       260
                 ....*....|....*....|....*.
gi 22202611  300 ----PIMKTGEPHCPGDEDETFKDGI 321
Cdd:cd03870  232 ykvgSISTTIYQASGSSIDWAYDNGI 257
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 956-1095 3.12e-07

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: 53.08  E-value: 3.12e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  956 LTNLGQSTEYRHIWSLEISNKPNvsePEEPKIRFVAGIHGNAPVGtelllalaeflclnykknP---------AVTQLVD 1026
Cdd:cd06231   17 VRELGEVGYQGYPLFALKSPNPR---GDKPRVLISAGIHGDEPAG------------------VeallrflesLAEKYLR 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22202611 1027 RTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDFTNNASQPETKAIIENLIQKQDFSLSVAL 1095
Cdd:cd06231   76 RVNLLVLPCVNPWGFERNT---------RENADGIDLNRSFLKDSPSPEVRALMEFLASLGRFDLHLDL 135
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 138-258 4.39e-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: 349458 [Multi-domain]  Cd Length: 194  Bit Score: 52.03  E-value: 4.39e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  138 MHGDETVSRQVLIYLARELaagyRRGDPRLVRLLNTTDVYLLPSLNPDGFERARegdcgfgdggpsgasgRDNSRGRDLN 217
Cdd:cd06239    8 MHGNEPTGTEALLDLISYL----RRERQEFEKILERLTLVAIPMLNPDGAELFT----------------RHNAEGIDLN 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 22202611  218 RSfpdqfstgeppALD-EVPEVRALIEWIRRNKFVLSGNLHG 258
Cdd:cd06239   68 RD-----------ARAlQTPESRALKAVLDSFSPKFAFNLHD 98
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 959-1208 5.82e-07

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: 51.89  E-value: 5.82e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  959 LGQSTEYRHIWSLEISNKPNvsepeePKIRFVAGIHGNAPVGTELLLALAeflclNYKKNPAVTQLVdrtRIVIVPSLNP 1038
Cdd:cd06904    4 YGTSVKGRPILAYKFGPGSR------ARILIIGGIHGDEPEGVSLVEHLL-----RWLKNHPASGDF---HIVVVPCLNP 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1039 DGRERAQekdctskigQTNARGKDLDTDF-TNN-------------------ASQPETKAIIeNLIQKQDFSLSVALDGG 1098
Cdd:cd06904   70 DGLAAGT---------RTNANGVDLNRNFpTKNwepdarkpkdpryypgpkpASEPETRALV-ELIERFKPDRIISLHAP 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1099 SMLVTYPYDKPvqtvenkETLKHLASlyANNHPsmHMGQPscpnksdENIPGGvmrgaewhshLGsmkdysvTYG----H 1174
Cdd:cd06904  140 YLVNYDGPAKS-------LLAEKLAQ--ATGYP--VVGDV-------GYTPGS----------LG-------TYAgierN 184

                        250       260       270
                 ....*....|....*....|....*....|....
gi 22202611 1175 CPEITVytsccYFPSAARLPSLWADNKRSLLSML 1208
Cdd:cd06904  185 IPVITL-----ELPEAVSIDELWQDLKRALIEAI 213
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
 523-672 7.72e-07

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: 52.18  E-value: 7.72e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  523 ITRLYSLGKSVESRELYVMEISDNPG----------VHePGEPEFKYIgnMHGnevvgrelllnLIEYLCKNfgTDPEVT 592
Cdd:cd06234   18 GVRLEVLGQTLDGRDIDLLTIGDPGTgkkkvwiiarQH-PGETMAEWF--MEG-----------LLDRLLDE--DDPVSR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  593 DLVHNTRIHLMPSMNPDGyeksqegdsiSVIG--RNNSNNFDLNRNF--PDQfvqitdPTQPETIAVMSWMKSYPFVLSA 668
Cdd:cd06234   82 ALLEKAVFYVVPNMNPDG----------SVRGnlRTNAAGVNLNREWanPSL------ERSPEVFAVRQAMDATGVDFFL 145


                 ....
gi 22202611  669 NLHG 672
Cdd:cd06234  146 DVHG 149
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
 503-661 7.96e-07

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: 52.54  E-value: 7.96e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEI---SDNPgvhepgepefKYIGNM----HGNEVVGRELLL 575
Cdd:cd06247    4 YHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKP----------KKIIWMdcgiHAREWIAPAFCQ 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  576 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNN-----FDLNRNFPDQFVQI------ 644
Cdd:cd06247   74 WFVKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLWRKSRSPHNNgtcygTDLNRNFNSQWCSIgasrnc 153

                        170       180
                 ....*....|....*....|....*
gi 22202611  645 -------TDP-TQPETIAVMSWMKS 661
Cdd:cd06247  154 csiifcgTGPeSEPETKAVADLIEK 178
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
 81-351 1.06e-06

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: 51.80  E-value: 1.06e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLtaglgslipeGDAGPdaagpdaagpllpGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY 160
Cdd:cd06234   20 RLEVLGQTLDGRDIDLLTI----------GDPGT-------------GKKKVWIIARQHPGETMAEWFMEGLLDRLLDED 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 rrgDPRLVRLLNTTDVYLLPSLNPDGferaregdcgfgdggpsGASG--RDNSRGRDLNRSFpdqfstgEPPALDEVPEV 238
Cdd:cd06234   77 ---DPVSRALLEKAVFYVVPNMNPDG-----------------SVRGnlRTNAAGVNLNREW-------ANPSLERSPEV 129

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  239 RALIEWIRRNKFVLSGNLHGGSVVAsYPFDDSPEhkatGIySKTSD--DEVFKYLAKAYASNHPIMKTG---EPHCPGDE 313
Cdd:cd06234  130 FAVRQAMDATGVDFFLDVHGDEALP-YNFIAGAE----GI-PSWTPrlAALEAAFKAALAAASPDFQTEhgyPPDAPGEA 203

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 22202611  314 DETFKDgitngahwydveggmqdyNYVWA--NCFEITLEL 351
Cdd:cd06234  204 NLTIAS------------------NWVAErfGCLAMTLEM 225
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 985-1097 1.91e-06

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: 50.38  E-value: 1.91e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  985 PKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPavtqLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLD 1064
Cdd:cd06242    2 PTVLLVGQQHGNEPAGREAALALARDLAFGDDARE----LLEKVNVLVVPRANPDGRAANT---------RGNANGVDLN 68

                         90       100       110
                 ....*....|....*....|....*....|...
gi 22202611 1065 TDFTnNASQPETKAIIENLiqkQDFSLSVALDG 1097
Cdd:cd06242   69 RDHL-LLSTPETRALARVL---RDYRPEVVIDA 97
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 504-641 2.09e-06

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: 51.28  E-value: 2.09e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  504 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPgvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 583
Cdd:cd03870    7 HTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIVS 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 22202611  584 NFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN-NSNNF----DLNRNFPDQF 641
Cdd:cd03870   83 DYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNRLWRKTRSvNPGSLcigvDPNRNWDAGF 145
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 968-1079 2.15e-06

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: 50.92  E-value: 2.15e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  968 IWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERA--- 1044
Cdd:cd06226    2 IRALKLTNKQATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAetg 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 22202611 1045 --QEKDCTSKIGQT--NARGKDLDTDFT--------------------NNASQPETKAI 1079
Cdd:cd06226   82 llWRKNTNTTPCPAssPTYGVDLNRNSSfkwggagaggsacsetyrgpSAASEPETQAI 140
PRK10602 PRK10602
murein tripeptide amidase MpaA;
139-253 2.26e-06

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 50.41  E-value: 2.26e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   139 HGDETVSRQVLIYLARELAAGYRRgdprlvrllntTDVYLlpSLNPDGferaregdCGFGDggpsgasgRDNSRGRDLNR 218
Cdd:PRK10602   49 HGDETASVVTLSCALRTLTPSLRR-----------HHVVL--AVNPDG--------CQLGL--------RANANGVDLNR 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611   219 SFPDQ---------------------FSTGEPPALDevPEVRALIEWIRRNK--FVLS 253
Cdd:PRK10602  100 NFPAAnwkegetvyrwnsaaeerdvvLLTGDKPGSE--PETQALCQLIHRLQpaWVVS 155
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1214-1286 2.33e-06

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 46.89  E-value: 2.33e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   1214 GVHGFVKDKTGKPISKAVIVL-----NEGIKVQTKEGGYFHV-LLAPGVHNIIAIADGYQQQH-SQVFVHHDAASSVVIV 1286
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRFpGLPPGTYTVTVSAPGFKTATrTGVTVTAGQTTTLDVT 80
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 136-247 2.45e-06

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: 50.05  E-value: 2.45e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  136 GNMHGDETVSRQVLIYLARELAAGyrrGDPRLVRLLNTTDVYLLPSLNPDGFER------AREGDCGFGD------GGPS 203
Cdd:cd06238    8 YSIHGNELSGSEAAMQVAYHLAAG---QDEATRALLENTVIVIDPNQNPDGRERfvnwfnQNRGAVGDPDpqsmehNEPW 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 22202611  204 GaSGRDNSRGRDLNRsfpDQFSTGEppaldevPEVRALIEWIRR 247
Cdd:cd06238   85 P-GGRTNHYLFDLNR---DWLAQTQ-------PESRARAAAIHR 117
COG3608 COG3608
Predicted deacylase [General function prediction only];
127-222 3.92e-06

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 50.23  E-value: 3.92e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  127 PGrPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGdpRLVrllnttdvyLLPSLNPDGFERAregdcgfgdggpsgas 206
Cdd:COG3608   25 PG-PTLLITAGIHGDELNGIEALRRLLRELDPGELRG--TVI---------LVPVANPPGFLQG---------------- 76

                         90
                 ....*....|....*..
gi 22202611  207 GRDNSR-GRDLNRSFPD 222
Cdd:COG3608   77 SRYLPIdGRDLNRSFPG 93
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 84-321 6.43e-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: 49.76  E-value: 6.43e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   84 SIGRSVEGRPLWVLRLtaglgslipeGDAGPDaagpdaagpllpgRPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRg 163
Cdd:cd03871   31 QIGTTFEGRPIYLLKV----------GKPGSN-------------KKAIFMDCGFHAREWISPAFCQWFVREAVRTYGK- 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  164 DPRLVRLLNTTDVYLLPSLNPDGFE----------RAREGDCGfgdggpsgasgrDNSRGRDLNRSFP----DQFSTGEP 229
Cdd:cd03871   87 EKIMTKLLDRLDFYILPVLNIDGYVytwtknrmwrKTRSPNAG------------SSCIGTDPNRNFNagwcTVGASSNP 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  230 -------PALDEVPEVRALIEWIRRNKFVLSGNL--HGGSVVASYPF----DDSPEHKATGIYSKTSDDEvfkyLAKAYA 296
Cdd:cd03871  155 csetycgSAPESEKETKALANFIRNNLSSIKAYLtiHSYSQMLLYPYsytyKLAPNHEELNSIAKGAVKE----LSSLYG 230

                        250       260
                 ....*....|....*....|....*...
gi 22202611  297 SNH---PIMKTGEPHCPGDEDETFKDGI 321
Cdd:cd03871  231 TKYtygPGATTIYPAAGGSDDWAYDQGI 258
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 1026-1096 7.92e-06

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; uncharacterized bacterial subgroup; A bacterial subgroup of the Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP),-like proteins. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins (such as alpha-tubulin in eukaryotes) to remove a C-terminal tyrosine. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.


Pssm-ID: 349456 [Multi-domain]  Cd Length: 239  Bit Score: 48.72  E-value: 7.92e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22202611 1026 DRTRIVIVPSLNPDGRERaqekdctskiG--QTNARGKDLDTDFtNNASQPETKAI---IENLIQKQDFSLSVALD 1096
Cdd:cd06237   80 ARFRVLVVPLLNPDGVDL----------GhwRHNAGGVDLNRDW-GPFTQPETRAVrdfLLELVEEPGGKVVFGLD 144
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
 503-637 1.56e-05

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: 48.44  E-value: 1.56e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  503 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEIsdnpGVHEPGEPEFKYIG-NMHGNEVVGRELLLNLIEYL 581
Cdd:cd03872    2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIDcGIHAREWIGPAFCQWFVKEA 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 22202611  582 CKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNF-----DLNRNF 637
Cdd:cd03872   78 INSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKNSRFqcrgvDANRNW 138
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 1019-1086 1.63e-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 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: 47.83  E-value: 1.63e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611 1019 PAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDFTnNASQPETKAIIEnLIQK 1086
Cdd:cd06244   48 LEVKDLLDDVFFIVVPTENPDGRVANT---------RTNANGFDLNRDNA-YQTQPETRAMQE-LISK 104
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 130-233 1.69e-05

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: 48.53  E-value: 1.69e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  130 PQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGDP-----------RLVRLLNTTDVYLLPSLNPDGFERAREGDCGF- 197
Cdd:cd06228    1 PGVYFIGGVHAREWGSPDILIYFAADLLEAYTNNTGltyggktftaaQVKSILENVDLVVFPLVNPDGRWYSQTSESMWr 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 22202611  198 GDGGPSGASGRDNSRGRDLNRS------FPDQFSTGEPPALD 233
Cdd:cd06228   81 KNRNPASAGDGGSCIGVDINRNfdflwdFPRYFDPGRVPAST 122
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 559-685 1.95e-05

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: 48.15  E-value: 1.95e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  559 YIGNMHGNEVVGRELLLNLIE-------------YLCKNFGTDpEVTDLVHNTRIHLMPSMNPDGYEKSQE--------- 616
Cdd:cd06228    5 FIGGVHAREWGSPDILIYFAAdlleaytnntgltYGGKTFTAA-QVKSILENVDLVVFPLVNPDGRWYSQTsesmwrknr 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  617 -----GDSISVIGRNNSNNFDLNRNFPDQF-----VQITDP-----------TQPETIAVMSWMKSYP----FVlsaNLH 671
Cdd:cd06228   84 npasaGDGGSCIGVDINRNFDFLWDFPRYFdpgrvPASTSPcsetyhgpsafSEPETRNVVWLFDAYPnirwFV---DVH 160

                        170
                 ....*....|....
gi 22202611  672 GGSLVVNYPFDDDE 685
Cdd:cd06228  161 SASELILYSWGDDE 174
M14_Nna1-like cd18429
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 85-247 3.97e-05

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; uncharacterized bacterial subgroup; A bacterial subgroup of the Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP),-like proteins. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins (such as alpha-tubulin in eukaryotes) to remove a C-terminal tyrosine. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.


Pssm-ID: 349485  Cd Length: 253  Bit Score: 46.68  E-value: 3.97e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   85 IGRSVEGRPLWVLRLtaglgslipegdaGPDAAgpdaagpllPGRpqVKLVGNMHGDETVSRQVLIYLARELAagyrRGD 164
Cdd:cd18429   20 IGKTVEGRPLEIIRI-------------GNESA---------PHR--VFLRARAHPWEAGGNWVVEGLVERLL----QND 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  165 PRLVRLLNTTDVYLLPSLNPDGFERAREgdcgfgdggpsgasgRDNSRGRDLNRSFpdqfstGEPPALDEVPEVRALIEW 244
Cdd:cd18429   72 EEAKRFLKRYCVYILPMANKDGVARGRT---------------RFNANGKDLNREW------DKPADPVLAPENFALEKW 130


                 ...
gi 22202611  245 IRR 247
Cdd:cd18429  131 LEE 133
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 129-242 4.68e-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: 349460 [Multi-domain]  Cd Length: 215  Bit Score: 46.10  E-value: 4.68e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  129 RPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGdprlvrLLNTTDVYLLPSLNPDGFERAREGDcGFGDGGPSGASGR 208
Cdd:cd06241    1 KPVVLIQAGIHPGEVEGKEASLMLLRDIAQGGKKH------LLDNLILLFVPIFNADGNDRRSKGN-RPNQNGPLEVGWR 73

                         90       100       110
                 ....*....|....*....|....*....|....
gi 22202611  209 DNSRGRDLNRSFPDQfstgeppaldEVPEVRALI 242
Cdd:cd06241   74 TNAQGLDLNRDFMKL----------EAPETRALA 97
M14-like cd06240
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 129-186 5.19e-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 cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.


Pssm-ID: 349459  Cd Length: 212  Bit Score: 46.11  E-value: 5.19e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  129 RPQVKLVGNMHGDETVSRQVLIYLARELAAgyrRGDPRLVRLLNTTDVYLLPSLNPDG 186
Cdd:cd06240    1 KAVVWIDGGLHATEVAGSQMLPELAYRLAT---SDDEEVRRILDNVILLLVPSANPDG 55
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 81-247 6.88e-05

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: 46.02  E-value: 6.88e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   81 RLFSIGRSVEGRPLWVLRLTAGlgslipegdagpdaagpdaagpllPGRPQVKLVGNMHGDETVSRQVLIYLARELAAgy 160
Cdd:cd06237   17 KRSTIGKSVEGRPIEALTIGNP------------------------DSKELVVLLGRQHPPEVTGALAMQAFVETLLA-- 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  161 rrgDPRLVR-LLNTTDVYLLPSLNPDGFERaregdcgfgdggpsgasG--RDNSRGRDLNR---SFpDQfstgeppalde 234
Cdd:cd06237   71 ---DTELAKaFRARFRVLVVPLLNPDGVDL-----------------GhwRHNAGGVDLNRdwgPF-TQ----------- 118

                        170
                 ....*....|...
gi 22202611  235 vPEVRALIEWIRR 247
Cdd:cd06237  119 -PETRAVRDFLLE 130
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 134-267 1.01e-04

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily belongs to the M14 family of metallocarboxypeptidases (MCPs), and includes ASTE, which catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-2; EC:3.5.1.15) which cleaves N-acetyl L-aspartic acid (NAA) into aspartate and acetate. NAA is abundant in the brain, and hydrolysis of NAA by ASPA may help maintain white matter. ASPA is an NAA scavenger in other tissues. Mutations in the gene encoding ASPA cause Canavan disease (CD), a fatal progressive neurodegenerative disorder involving dysmyelination and spongiform degeneration of white matter in children. This enzyme binds zinc which is necessary for activity. Measurement of elevated NAA levels in urine is used in the diagnosis of CD.


Pssm-ID: 349449 [Multi-domain]  Cd Length: 177  Bit Score: 44.61  E-value: 1.01e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  134 LVGNMHGDETVSRQVLIYLARELAAGYRRGdpRLVrllnttdvyLLPSLNPDGFERAREGDCGFgdggpsgasgrdnsrG 213
Cdd:cd06230    3 ILAGVHGDEYEGVEAIRRLLAELDPSELKG--TVV---------LVPVANPPAFEAGTRYTPLD---------------G 56

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 22202611  214 RDLNRSFPdqfstGEPPALDEVPEVRALIEWIRRN-KFVLSgnLHGGSVVASYPF 267
Cdd:cd06230   57 LDLNRIFP-----GDPDGSPTERLAHELTELILKHaDALID--LHSGGTGRLVPY 104
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 1014-1096 1.49e-04

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: 45.02  E-value: 1.49e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1014 NYKKNPAVTQLVDRTRIVIVPSLNPDG----------------RERAQEKDCTSKIG-QTNARGKDLDTDF--------T 1068
Cdd:cd06229   33 SYIRGKDVGELLNKVTLHIVPMVNPDGveisqngsnainpyylRLVAWNKKGTDFTGwKANIRGVDLNRNFpagwekekR 112

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 22202611 1069 NNA--------------SQPETKAIIeNLIQKQDFSLSVALD 1096
Cdd:cd06229  113 LGPkapgprdypgkeplSEPETKAMA-ALTRQNDFDLVLAYH 153
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
 384-465 1.66e-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: 41.81  E-value: 1.66e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    384 VKGFVKDSITGSGLENATISVAGINHNITT---GRFgdFYRLLVPGTYNLTVVLTGYMPLTVTnVVVKEGPATEVDFSLR 460
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTdadGNF--ELKNLPAGTYTLVVSFVGYKTQEKK-VTVSNDNTLDVNFLLK 77


                   ....*
gi 22202611    461 PTVTS 465
Cdd:pfam13715   78 EDALL 82
M14_Nna1-like cd03856
Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related ...
 127-258 2.68e-04

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


Pssm-ID: 349429  Cd Length: 252  Bit Score: 44.11  E-value: 2.68e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  127 PGRPQVK----LVGNMHGDETVSRQVLI-YLARELaagyrRGDPRLVRLLNTTDVYLLPSLNPDGFERAREgdcgfgdgg 201
Cdd:cd03856   37 TERSDDKswlfLIARQHPGETTGAWVFFgFLDQLL-----SDDDPAQQLRAEYNFYIIPMVNPDGVARGHW--------- 102

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22202611  202 psgasgRDNSRGRDLNRSFpdqfstgEPPALDEVPEVRALIEWI-----RRNKFVLSGNLHG 258
Cdd:cd03856  103 ------RTNSRGMDLNRDW-------HAPDALLSPETYAVAAALaervqSPEGVVLALDLHG 151
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 130-235 4.63e-04

Succinylglutamate desuccinylase / Aspartoacylase family; This family includes Succinylglutamate desuccinylase EC:3.1.-.- that catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway. The family also include aspartoacylase EC:3.5.1.15 which cleaves acylaspartate into a fatty acid and aspartate. Mutations in Swiss:P45381 lead to Canavan disease. This family is probably structurally related to pfam00246 (Bateman A pers. obs.).


Pssm-ID: 428216 [Multi-domain]  Cd Length: 289  Bit Score: 43.88  E-value: 4.63e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611    130 PQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGdprlvrllnttDVYLLPSLNPDGFERARegdcgfgdggpsgasgRD 209
Cdd:pfam04952    3 PTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAG-----------ERTLVPLANPPAFRAGS----------------RY 55

                           90       100
                   ....*....|....*....|....*.
gi 22202611    210 NSrgRDLNRSFPDQFSTGEPPALDEV 235
Cdd:pfam04952   56 IP--RDLNRSFPGRALGASSDEPYRA 79
M14_ASTE_ASPA-like cd06254
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 127-302 6.34e-04

Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; uncharacterized subgroup; A functionally uncharacterized subgroup of the Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily which is part of the M14 family of metallocarboxypeptidases. ASTE catalyzes the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway, and aspartoacylase (ASPA, also known as aminoacylase 2, and ACY-2; EC:3.5.1.15) cleaves N-acetyl L-aspartic acid (NAA) into aspartate and acetate. NAA is abundant in the brain, and hydrolysis of NAA by ASPA may help maintain white matter. ASPA is an NAA scavenger in other tissues. Mutations in the gene encoding ASPA cause Canavan disease (CD), a fatal progressive neurodegenerative disorder involving dysmyelination and spongiform degeneration of white matter in children. This enzyme binds zinc which is necessary for activity. Measurement of elevated NAA levels in urine is used in the diagnosis of CD.


Pssm-ID: 349472  Cd Length: 198  Bit Score: 42.57  E-value: 6.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  127 PGrPQVKLVGNMHGDETVSRQVLIYLARELaagyrrgDPRLVRllntTDVYLLPSLNPDGFErAREGDCGFGDggpsgas 206
Cdd:cd06254   10 PG-PTLLITAGIHGGEYPGILAAIRLAREL-------DPADVK----GTLIIVHIANVSGFE-ARTPFVVPED------- 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  207 grdnsrGRDLNRSFPdqfstGEPPA-LDEvpEVRALI--EWIRRNKFVLsgNLHGGSVV-ASYPFddspehkatGIYSKT 282
Cdd:cd06254   70 ------GKNLNRVFP-----GDPDGtLTE--RIAYFLtrEIISRADFLI--DLHGGDANeALTPF---------VYYPGG 125

                        170       180
                 ....*....|....*....|.
gi 22202611  283 SDDEVF-KYLAKAYASNHPIM 302
Cdd:cd06254  126 ASEEVNdISRAAAQALGLPYI 146
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 1024-1087 6.71e-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: 42.63  E-value: 6.71e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1024 LVDRTRIVIVPSLNPDGRERAQEKDCTSKIG------QTNARGKDLDTDFTnNASQPETKAIIENLIQKQ 1087
Cdd:cd06241   36 LLDNLILLFVPIFNADGNDRRSKGNRPNQNGplevgwRTNAQGLDLNRDFM-KLEAPETRALAKLFNQWD 104
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
 932-1128 7.18e-04

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: 43.30  E-value: 7.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  932 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEI---SNKPNvsepeepKIRFV-AGIHGNAPVGTELLLAL 1007
Cdd:cd06247    3 KYHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKPK-------KIIWMdCGIHAREWIAPAFCQWF 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1008 AEFLCLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKIGQTNARGKDLDTDFTNN------------ 1070
Cdd:cd06247   76 VKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDrlwrkSRSPHNNGTCYGTDLNRNFNSQwcsigasrnccs 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22202611 1071 --------ASQPETKAIIENLIQKQDFSLS-VALDGGSMLVTYPYDKPVQTVENKETLKHLASLYAN 1128
Cdd:cd06247  156 iifcgtgpESEPETKAVADLIEKKKSDILCyLTIHSYGQLILLPYGYTKEPSPNHEEMMEVGEKAAA 222
M14-like cd06240
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 561-613 8.20e-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: 349459  Cd Length: 212  Bit Score: 42.26  E-value: 8.20e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 22202611  561 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVHNTRIHLMPSMNPDGYEK 613
Cdd:cd06240    8 GGLHATEVAGSQMLPELAYRLAT--SDDEEVRRILDNVILLLVPSANPDGQDL 58
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 932-1130 1.02e-03

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: 42.83  E-value: 1.02e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  932 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISnKPNVSEPeepKIRFVAGIHGNAPVGTELLLALAEFL 1011
Cdd:cd03871    5 KYNNWETIEAWTEQVASKNPDLVSRSQIGTTFEGRPIYLLKVG-KPGSNKK---AIFMDCGFHAREWISPAFCQWFVREA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1012 CLNYKKNPAVTQLVDRTRIVIVPSLNPDG------RERAQEKDcTSKIGQTNARGKDLDTDF---------TNNA----- 1071
Cdd:cd03871   81 VRTYGKEKIMTKLLDRLDFYILPVLNIDGyvytwtKNRMWRKT-RSPNAGSSCIGTDPNRNFnagwctvgaSSNPcsety 159

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22202611 1072 ------SQPETKAiIENLIQKQDFSLSVALD--GGSMLVTYPYDKPVQTVEN--------KETLKHLASLYANNH 1130
Cdd:cd03871  160 cgsapeSEKETKA-LANFIRNNLSSIKAYLTihSYSQMLLYPYSYTYKLAPNheelnsiaKGAVKELSSLYGTKY 233
M14_Nna1-like cd18429
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 508-684 1.27e-03

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; uncharacterized bacterial subgroup; A bacterial subgroup of the Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP),-like proteins. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins (such as alpha-tubulin in eukaryotes) to remove a C-terminal tyrosine. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.


Pssm-ID: 349485  Cd Length: 253  Bit Score: 42.06  E-value: 1.27e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  508 DMEIFLRRFA-NEYPNITRLyslGKSVESRELYVMEISDNPGVH-----------EPGepefkyignmhGNEVVGrelll 575
Cdd:cd18429    1 DLDRLLAKIRkNPLVEITTI---GKTVEGRPLEIIRIGNESAPHrvflrarahpwEAG-----------GNWVVE----- 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  576 NLIEYLCKNfgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQEgdsisvigRNNSNNFDLNRN--FPdqfvqiTDPT-QPET 652
Cdd:cd18429   62 GLVERLLQN---DEEAKRFLKRYCVYILPMANKDGVARGRT--------RFNANGKDLNREwdKP------ADPVlAPEN 124

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 22202611  653 IAVMSWM------KSYPFvLSANLH---GGSLVVNYPFDDD 684
Cdd:cd18429  125 FALEKWLeemikaGKKPD-LAIELHndgGGNLHVSRPPVDG 164
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
 85-313 1.73e-03

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: 42.10  E-value: 1.73e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611   85 IGRSVEGRPLWVLRLTaglgslipegdagpdaagpdaaGPLLPGRPQVKLVGNMHGDETVSRQVLIYLaRELAAGYRRGD 164
Cdd:cd06246   31 IGSSFEKYPLYVLKVS----------------------GKEQTAKNAIWIDCGIHAREWISPAFCLWF-IGHASYFYGII 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  165 PRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFGDGGpsgaSGRDNSR--GRDLNRSFP-------------DQFSTGEP 229
Cdd:cd06246   88 GQHTNLLNLVDFYVMPVVNVDGYDYSWKKNRMWRKNR----SKHANNRciGTDLNRNFDagwcgkgassdscSETYCGPY 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  230 PalDEVPEVRALIEWIRRNKFVLSG--NLHGGSVVASYPFDDSpehkatgiYSKTSD-DEVFKYLAKAYASNHPIMKTGE 306
Cdd:cd06246  164 P--ESEPEVKAVASFLRRHKDTIKAyiSMHSYSQMVLFPYSYT--------RNKSKDhDELSLLAKEAVTAIRKTSRNRY 233


                 ....*..
gi 22202611  307 PHCPGDE 313
Cdd:cd06246  234 TYGPGAE 240
PRK10602 PRK10602
murein tripeptide amidase MpaA;
599-640 2.08e-03

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 41.55  E-value: 2.08e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 22202611   599 RIHLMPSMNPDGyekSQEGDsisvigRNNSNNFDLNRNFPDQ 640
Cdd:PRK10602   72 RHHVVLAVNPDG---CQLGL------RANANGVDLNRNFPAA 104
M14-like cd03862
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 555-638 2.23e-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: 41.26  E-value: 2.23e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  555 PEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGyeksqegdsISVIGRNNSNNFDLN 634
Cdd:cd03862    1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGG---------MALKTRSNPNGVDLM 71


                 ....
gi 22202611  635 RNFP 638
Cdd:cd03862   72 RNAP 75
M14_Nna1-like cd03856
Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related ...
 1023-1156 2.41e-03

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


Pssm-ID: 349429  Cd Length: 252  Bit Score: 41.42  E-value: 2.41e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611 1023 QLVDRTRIVIVPSLNPDGRERAQEKdctskigqTNARGKDLDTDFTNNA--SQPET---KAIIENLIQKQ---DFSLSVA 1094
Cdd:cd03856   79 QLRAEYNFYIIPMVNPDGVARGHWR--------TNSRGMDLNRDWHAPDalLSPETyavAAALAERVQSPegvVLALDLH 150

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22202611 1095 LDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQpscpnKSDENIPGGVMRGA 1156
Cdd:cd03856  151 GDNRNVFLTGPDNKDESTNHNPDKLNSLLTETDRRLPDYNTEA-----SPGDNPGGTVGKQW 207
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 560-637 3.32e-03

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: 40.70  E-value: 3.32e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  560 IGNMHGNEVVGRELLLNLIEYLCknFGtdpEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIG------RNNSNNFDL 633
Cdd:cd06241    7 QAGIHPGEVEGKEASLMLLRDIA--QG---GKKHLLDNLILLFVPIFNADGNDRRSKGNRPNQNGplevgwRTNAQGLDL 81


                 ....
gi 22202611  634 NRNF 637
Cdd:cd06241   82 NRDF 85
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 129-271 9.04e-03

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: 39.75  E-value: 9.04e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22202611  129 RPQVKLVGNMHGDETVSRQVLIYLARELAAGYRRGDPrlvrLLNTTDVYLLPSLNPDGFERAREGDCGFGDGGPSGASGR 208
Cdd:cd06248   51 KPTIMIEGGINPREWISPPAALYAIHKLVEDVETQSD----LLNNFDWIILPVANPDGYVFTHTNDREWTKNRSTNSNPL 126

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22202611  209 DNS-RGRDLNRSFPDQF----STGEP--------PALDEvPEVRALIEWI--RRNKFVLSGNLHGGSVVASYPFDDSP 271
Cdd:cd06248  127 GQIcFGVNINRNFDYQWnpvlSSESPcselyagpSAFSE-AESRAIRDILheHGNRIHLYISFHSGGSFILYPWGYDG 203
 
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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