NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|315138990|ref|NP_001186704|]
View 

carboxypeptidase D isoform 2 [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

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

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 ...
 249-544 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: 668.19  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  249 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 328
Cdd:cd03863     1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  329 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAV 408
Cdd:cd03863    81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  409 MSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITN 488
Cdd:cd03863   161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  489 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd03863   241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 686-963 1.52e-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: 479.63  E-value: 1.52e-161
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTNNAS------QPETKAIIENLIQK 839
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  840 qDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEWHSHLGSMK 919
Cdd:cd06245   161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 315138990  920 DYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 963
Cdd:cd06245   240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
Peptidase_M14_like super family cl11393
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 2-131 1.18e-78

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: 260.25  E-value: 1.18e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    2 RFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCpgdeDETFKDGITNGAHWY 81
Cdd:cd03868   168 PFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDGITNGAEWY 243

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990   82 DVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 131
Cdd:cd03868   244 DVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYME 293
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 548-623 6.07e-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: 130.34  E-value: 6.07e-36
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  548 GVRGFVLDATdGRGILNATISVAEINHPVTTYKTGDYWRLLVPGTYKITASARGYNPVTKNVTVKSE-GAIQVNFTL 623
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, ...
 136-212 6.82e-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: 116.08  E-value: 6.82e-31
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  136 GVKGFVKDSiTGSGLENATISVAGINHNITTGRFGDFYRLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDFSL 212
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, ...
 967-1041 2.05e-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: 94.90  E-value: 2.05e-23
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  967 GVHGFVKDKTGKPISKAVIVLNEG-IKVQTKEGGYFHVLLAPGVHNIIAIADGYQQQHSQVFVHHDaASSVVIVFD 1041
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 ...
 249-544 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: 668.19  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  249 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 328
Cdd:cd03863     1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  329 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAV 408
Cdd:cd03863    81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  409 MSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITN 488
Cdd:cd03863   161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  489 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd03863   241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 686-963 1.52e-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: 479.63  E-value: 1.52e-161
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTNNAS------QPETKAIIENLIQK 839
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  840 qDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEWHSHLGSMK 919
Cdd:cd06245   161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 315138990  920 DYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 963
Cdd:cd06245   240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
262-537 5.94e-100

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 317.70  E-value: 5.94e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   262 MEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTD 341
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   342 PEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSN-----NFDLNRNFPDQFVQI---TDPT-----------Q 402
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFPDHWNEVgasSNPCsetyrgpapfsE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   403 PETIAVMSWMKS-YPFVLSANLHGGSLVVNYPFDDDEQglatySKSPDDAVFQQIALSYSKENSQMFQGRpcknmypneY 481
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-----EPPPDDEELKSLARAAAKALQKMVRGT---------S 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 315138990   482 FPHGITNGASWYNVPGGMQDWNYLQTNC-FEVTIELGCVK----YPLEKELPNFWEQNRRS 537
Cdd:pfam00246  227 YTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
256-529 4.59e-94

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 301.56  E-value: 4.59e-94
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    336 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN---NSNNFDLNRNFPDQFVQITDP-----------T 401
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGNPcsetyagpspfS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    402 QPETIAVMSWMKSY-PFVLSANLHGGSLVVNYPFDDDEQGLATYSKSpDDAVFQQIALSYSKENsqmfqgrpcknmypNE 480
Cdd:smart00631  158 EPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALASVH--------------GT 222

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 315138990    481 YFPHGITNGASWYnVPGGMQDWNYLQTN-CFEVTIELGCV-----KYPLEKELPN 529
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPT 276
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 2-131 1.18e-78

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: 260.25  E-value: 1.18e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    2 RFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCpgdeDETFKDGITNGAHWY 81
Cdd:cd03868   168 PFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDGITNGAEWY 243

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990   82 DVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 131
Cdd:cd03868   244 DVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYME 293
Zn_pept smart00631
Zn_pept domain;
686-941 1.09e-55

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 194.86  E-value: 1.09e-55
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGG---SHDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIG---QTNARGKDLDTDFTNN-----------------AS 825
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNrspNSNCRGVDLNRNFPFHwgetgnpcsetyagpspFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    826 QPETKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQTV-----ENKETLKHLASLYANNHPSMHMGQPSCpnksden 900
Cdd:smart00631  158 EPETKAVRDFIRSNRRFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGTRYTYGISN------- 230

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|..
gi 315138990    901 ipggvmrGAEWHSHlGSMKDYS-VTYGHCPEITVYTSCCYFP 941
Cdd:smart00631  231 -------GAIYPAS-GGSDDWAyGVLGIPFSFTLELRDDGRY 264
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
694-956 5.13e-48

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 173.25  E-value: 5.13e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   694 EFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPA 773
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   774 VTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNAR-----GKDLDTDF--------------------TNNASQPE 828
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFpdhwnevgassnpcsetyrgPAPFSEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   829 TKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQT-VENKETLKHLASLYANNHPSMHMGQpscpnksdeNIPGGVMR 907
Cdd:pfam00246  163 TRAVADFIRSKKPFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 315138990   908 GAEWHSHLGSMKDYSVTYGHCP-EITVYTSCC----YFPSAARLPSLWADNKRS 956
Cdd:pfam00246  234 GATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
239-499 5.48e-38

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 145.60  E-value: 5.48e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  239 LSGTSSSYQPIQPKD-FHHHHfpDMEIFLRRFANEyPNITRLYSLGKSVESRELYVMEISDnpgvHEPGEPEFKYIGNMH 317
Cdd:COG2866     3 LLILPATYKEVSSYDrYYTYE--ELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQH 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  318 GNEVVGRELLLNLIEYLCKNFgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQFVqi 397
Cdd:COG2866    76 GNEWTGTEALLGLLEDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWL-- 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  398 tdpTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDD---AVFQQIALSYSKENSQMFQGRPCK 474
Cdd:COG2866   143 ---SEPETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEereAFAEELNFEGIILAGSAFLGAGAA 219

                         250       260
                  ....*....|....*....|....*
gi 315138990  475 NMYPNEYFPHGITNGASWYNVPGGM 499
Cdd:COG2866   220 GTLLISAPRQTFLFAAALDIGGGGD 244
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 548-623 6.07e-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: 130.34  E-value: 6.07e-36
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  548 GVRGFVLDATdGRGILNATISVAEINHPVTTYKTGDYWRLLVPGTYKITASARGYNPVTKNVTVKSE-GAIQVNFTL 623
Cdd:cd11308     1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
2-125 1.09e-31

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 125.87  E-value: 1.09e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990     2 RFVLSGNLHGGSVVASYPFDDSPEhkatgiySKTSDDEVFKYLAKAYASNHPIMKTGEphcpgdedeTFKDGITNGAHWY 81
Cdd:pfam00246  175 PFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITNGATIY 238

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 315138990    82 DVEGGMQDYNYVWANC-FEITLELSCCK----YPPASQLRQEWENNRES 125
Cdd:pfam00246  239 PASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 136-212 6.82e-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: 116.08  E-value: 6.82e-31
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  136 GVKGFVKDSiTGSGLENATISVAGINHNITTGRFGDFYRLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDFSL 212
Cdd:cd11308     1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
Zn_pept smart00631
Zn_pept domain;
2-118 3.22e-25

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 106.65  E-value: 3.22e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990      2 RFVLSGNLHGGSVVASYPFDDSPEHKATGIyskTSDDEVFKYLAKAYASNHPImktgephcpgdedeTFKDGITNGAHWY 81
Cdd:smart00631  173 RFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVAKALAKALASVHGT--------------RYTYGISNGAIYP 235

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|...
gi 315138990     82 dVEGGMQDYNYVWAN-CFEITLELSCC-----KYPPASQLRQE 118
Cdd:smart00631  236 -ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 967-1041 2.05e-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: 94.90  E-value: 2.05e-23
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  967 GVHGFVKDKTGKPISKAVIVLNEG-IKVQTKEGGYFHVLLAPGVHNIIAIADGYQQQHSQVFVHHDaASSVVIVFD 1041
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFT 75
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
685-862 1.32e-22

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 100.53  E-value: 1.32e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  685 RYHSYKDLSEFLRGLVMNYPHITnLTNLGQSTEYRHIWSLEISNKpnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 764
Cdd:COG2866    18 RYYTYEELLALLAKLAAASPLVE-LESIGKSVEGRPIYLLKIGDP----AEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  765 CLNYkkNPAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDF-TNNASQPETKAIIEnLIQKQDFS 843
Cdd:COG2866    93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWpAPWLSEPETRALRD-LLDEHDPD 160

                         170       180
                  ....*....|....*....|.
gi 315138990  844 LSVAL--DGGSMLVTYPYDKP 862
Cdd:COG2866   161 FVLDLhgQGELFYWFVGTTEP 181
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
136-212 1.86e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 69.62  E-value: 1.86e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   136 GVKGFVKDSiTGSGLENATISVA----GINHNITTGRFGDFY-RLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDF 210
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 315138990   211 SL 212
Cdd:pfam13620   80 TL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
548-623 3.02e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 68.85  E-value: 3.02e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   548 GVRGFVLDATdGRGILNATISVA----EINHPVTTYKTGDYW-RLLVPGTYKITASARGYNPVTK-NVTVKSEGAIQVNF 621
Cdd:pfam13620    1 TISGTVTDPS-GAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRtGVTVTAGQTTTLDV 79


                   ..
gi 315138990   622 TL 623
Cdd:pfam13620   80 TL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
967-1039 1.85e-06

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 46.89  E-value: 1.85e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   967 GVHGFVKDKTGKPISKAVIVL-----NEGIKVQTKEGGYFHV-LLAPGVHNIIAIADGYQQQH-SQVFVHHDAASSVVIV 1039
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRFpGLPPGTYTVTVSAPGFKTATrTGVTVTAGQTTTLDVT 80
PRK10602 PRK10602
murein tripeptide amidase MpaA;
352-393 1.67e-03

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 41.55  E-value: 1.67e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 315138990  352 RIHLMPSMNPDGyekSQEGDsisvigRNNSNNFDLNRNFPDQ 393
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 ...
 249-544 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: 668.19  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  249 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 328
Cdd:cd03863     1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  329 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAV 408
Cdd:cd03863    81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  409 MSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITN 488
Cdd:cd03863   161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  489 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
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 ...
 256-544 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: 566.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  336 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQI---TDPTQPETIAVMSWM 412
Cdd:cd03858    81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVysdNNPRQPETKAVMNWL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  413 KSYPFVLSANLHGGSLVVNYPFDDDEQG-LATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNmYPNEYFPHGITNGAS 491
Cdd:cd03858   161 ESIPFVLSANLHGGALVANYPYDDTRSGkSTEYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGAA 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 315138990  492 WYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd03858   240 WYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 686-963 1.52e-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: 479.63  E-value: 1.52e-161
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTNNAS------QPETKAIIENLIQK 839
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  840 qDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEWHSHLGSMK 919
Cdd:cd06245   161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 315138990  920 DYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 963
Cdd:cd06245   240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 254-544 9.26e-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: 454.78  E-value: 9.26e-152
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  254 FHHHHfpDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 333
Cdd:cd03868     1 YHNYD--ELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  334 LCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGD---SISVIGRNNSNNFDLNRNFPDQFV----QITDPTQPETI 406
Cdd:cd03868    79 LLENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDcsgDPGYGGRENANNVDLNRNFPDQFEdsddRLLEGRQPETL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  407 AVMSWMKSYPFVLSANLHGGSLVVNYPFDD----DEQGlaTYSKSPDDAVFQQIALSYSKENSQMFQGRPCKnmypNEYF 482
Cdd:cd03868   159 AMMKWIVENPFVLSANLHGGSVVASYPFDDspshIECG--VYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSF 232

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 315138990  483 PHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
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 ...
 686-963 5.73e-129

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: 395.10  E-value: 5.73e-129
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFT---------NNASQPETKAIIENL 836
Cdd:cd03858    81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPdqffqvysdNNPRQPETKAVMNWL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  837 IQKqDFSLSVALDGGSMLVTYPYDKP-------VQTVENKETLKHLASLYANNHPSMHMGQPSCPnKSDENIPGGVMRGA 909
Cdd:cd03858   161 ESI-PFVLSANLHGGALVANYPYDDTrsgksteYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGA 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 315138990  910 EWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 963
Cdd:cd03858   239 AWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 256-544 5.27e-124

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


Pssm-ID: 349438  Cd Length: 289  Bit Score: 381.83  E-value: 5.27e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:cd03866     1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  336 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAVMSWMKSY 415
Cdd:cd03866    81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEENNVQRQPETRAVMDWIKNE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  416 PFVLSANLHGGSLVVNYPFDD---DEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMypnEYFPHGITNGASW 492
Cdd:cd03866   161 TFVLSANLHGGALVASYPFDNgnsGTGQLGYYSVSPDDDVFIYLAKTYSYNHTNMYKGIECSNS---QSFPGGITNGYQW 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 315138990  493 YNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd03866   238 YPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 256-544 7.90e-117

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: 363.87  E-value: 7.90e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:cd03864     1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  336 KNFGTDPE-VTDLVHNTRIHLMPSMNPDGYE-KSQEGDSIS--VIGRNNSNNFDLNRNFPD---------------QFVQ 396
Cdd:cd03864    81 EEYRNGNErITRLIQDTRIHILPSMNPDGYEvAARQGPEFNgyLVGRNNANGVDLNRNFPDlntlmyynekyggpnHHLP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  397 ITD----PTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQ------GLATYSKSPDDAVFQQIALSYSKENSQ 466
Cdd:cd03864   161 LPDnwksQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREprvrgfRRTAYSPTPDDKLFQKLAKTYSYAHGW 240

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 315138990  467 MFQGRPCknmypNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd03864   241 MHKGWNC-----GDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 257-544 1.60e-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: 356.50  E-value: 1.60e-114
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  257 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 336
Cdd:cd18173     5 PTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA-EPEFKYTSTMHGDETTGYELMLRLIDYLLT 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  337 NFGTDPEVTDLVHNTRIHLMPSMNPDGYeksQEGDSISVIG--RNNSNNFDLNRNFPDqFVQITDPT----QPETIAVMS 410
Cdd:cd18173    84 NYGTDPRITNLVDNTEIWINPLANPDGT---YAGGNNTVSGatRYNANGVDLNRNFPD-PVDGDHPDgngwQPETQAMMN 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  411 WMKSYPFVLSANLHGGSLVVNYPFDddeqglATYSKSPDDAVFQQIALSYSKENSQmfqgrPCKNMYpNEYFPHGITNGA 490
Cdd:cd18173   160 FADEHNFVLSANFHGGAEVVNYPWD------TWYSRHPDDDWFQDISREYADTNQA-----NSPPMY-MSEFNNGITNGY 227

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 315138990  491 SWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd18173   228 DWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 256-544 3.80e-112

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: 3.80e-112
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:cd03865     1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  336 KNFGTDPE-VTDLVHNTRIHLMPSMNPDGYEKS-QEGDSIS--VIGRNNSNNFDLNRNFPD------------------- 392
Cdd:cd03865    81 NEYQKGNEtIINLIHSTRIHIMPSLNPDGFEKAaSQPGELKdwFVGRSNAQGIDLNRNFPDldrivyvnekeggpnnhll 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  393 ----QFVQITDPTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLA-TYSKSPDDAVFQQIALSYSKENSQM 467
Cdd:cd03865   161 knmkKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAhEYSSCPDDAIFQSLARAYSSLNPAM 240

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 315138990  468 FQG--RPCKNMYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd03865   241 SDPnrPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 256-544 8.51e-103

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: 326.79  E-value: 8.51e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:cd03869     1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  336 KNF-GTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISV---IGRNNSNNFDLNRNFPD------------------- 392
Cdd:cd03869    81 QEYlAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGgwsLGRWTSDGIDINHNFPDlnsllweaedrkwvprkvp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  393 -------QFVQITDPT-QPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLAT--YSKSPDDAVFQQIALSYSK 462
Cdd:cd03869   161 nhhipipEWYLSENATvAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTqeYTPTPDDHVFRWLAYSYAS 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  463 ENSQMFQG--RPCKnmYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQ 540
Cdd:cd03869   241 THRLMTDAsrRPCH--TEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLV 318


                  ....
gi 315138990  541 FMKQ 544
Cdd:cd03869   319 FMEQ 322
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
262-537 5.94e-100

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 317.70  E-value: 5.94e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   262 MEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTD 341
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   342 PEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSN-----NFDLNRNFPDQFVQI---TDPT-----------Q 402
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFPDHWNEVgasSNPCsetyrgpapfsE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   403 PETIAVMSWMKS-YPFVLSANLHGGSLVVNYPFDDDEQglatySKSPDDAVFQQIALSYSKENSQMFQGRpcknmypneY 481
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-----EPPPDDEELKSLARAAAKALQKMVRGT---------S 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 315138990   482 FPHGITNGASWYNVPGGMQDWNYLQTNC-FEVTIELGCVK----YPLEKELPNFWEQNRRS 537
Cdd:pfam00246  227 YTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 276-540 4.94e-98

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: 312.42  E-value: 4.94e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  276 ITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNF-GTDPEVTDLVHNTRIH 354
Cdd:cd18172    21 ISRLIVIGSSVNGFPLWALEISDGPGEDET-EPAFKFVGNMHGDEPVGRELLLRLADWLCANYkAKDPLAAKIVENAHLH 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  355 LMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQFVQITDPT-----QPETIAVMSWMKSYPFVLSANLHGGSLV 429
Cdd:cd18172   100 LVPTMNPDGFARRR---------RNNANNVDLNRDFPDQFFPKNLRNdlaarQPETLAVMNWSRSVRFTASANLHEGALV 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  430 VNYPFDDDEQGLATYSKSPDDAVFQQIALSYSKENsqmfqgrpcKNMYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNC 509
Cdd:cd18172   171 ANYPWDGNADGRTKYSASPDDATFRRLASVYAQAH---------PNMAKSKEFPGGITNGAQWYPLYGGMQDWNYLHTGC 241

                         250       260       270
                  ....*....|....*....|....*....|.
gi 315138990  510 FEVTIELGCVKYPLEKELPNFWEQNRRSLIQ 540
Cdd:cd18172   242 MDLTLEVNDNKWPPEDRLVQIWAEHRKAMLA 272
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 256-543 1.06e-95

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: 1.06e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:cd03867     1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  336 KNF-GTDPEVTDLVHNTRIHLMPSMNPDGYEKSQE---GDSISVIGRNNSNNFDLNRNFPD----------------QFV 395
Cdd:cd03867    81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEegaGYNGWTSGRQNAQNLDLNRNFPDltseayrlartrgarlDHI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  396 QITD-----PTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLA--TYSKSPDDAVFQQIALSYSKENsQMF 468
Cdd:cd03867   161 PIPQsywwgKVAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEekMFSPTPDEKMFKLLAKAYADAH-PMM 239

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 315138990  469 QGRPCKNMYPNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMK 543
Cdd:cd03867   240 SDRSENRCGGNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314
Zn_pept smart00631
Zn_pept domain;
256-529 4.59e-94

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 301.56  E-value: 4.59e-94
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    336 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN---NSNNFDLNRNFPDQFVQITDP-----------T 401
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGNPcsetyagpspfS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    402 QPETIAVMSWMKSY-PFVLSANLHGGSLVVNYPFDDDEQGLATYSKSpDDAVFQQIALSYSKENsqmfqgrpcknmypNE 480
Cdd:smart00631  158 EPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALASVH--------------GT 222

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 315138990    481 YFPHGITNGASWYnVPGGMQDWNYLQTN-CFEVTIELGCV-----KYPLEKELPN 529
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPT 276
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 256-544 3.62e-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: 263.92  E-value: 3.62e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 335
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  336 KNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNFDLNRNFPDQFVQITDPTQPETIAVMSWMKSY 415
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANNRSGAAQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  416 PFVLSANLHGGSLVVNYPFDDDEQglatysKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITNGASWYNV 495
Cdd:cd06245   161 DFTLSVALDGGSLVVTYPYDKPVQ------TVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSH 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 315138990  496 PGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQ 544
Cdd:cd06245   235 KGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 2-131 1.18e-78

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: 260.25  E-value: 1.18e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    2 RFVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCpgdeDETFKDGITNGAHWY 81
Cdd:cd03868   168 PFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDGITNGAEWY 243

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990   82 DVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 131
Cdd:cd03868   244 DVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYME 293
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 686-959 5.91e-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: 249.85  E-value: 5.91e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03868     1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTS---KIGQTNARGKDLDTDF----------TNNASQPETKAI 832
Cdd:cd03868    81 ENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGdpgYGGRENANNVDLNRNFpdqfedsddrLLEGRQPETLAM 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  833 IeNLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENK--------ETLKHLASLYANNHPSMHMGQPSCpnksDENIPGG 904
Cdd:cd03868   161 M-KWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGvyskspddAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDG 235

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 315138990  905 VMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLS 959
Cdd:cd03868   236 ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLS 290
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
 2-132 8.76e-68

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: 229.85  E-value: 8.76e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    2 RFVLSGNLHGGSVVASYPFDDSPEHKATgIYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCPgDEDETFKDGITNGAHWY 81
Cdd:cd03858   164 PFVLSANLHGGALVANYPYDDTRSGKST-EYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGAAWY 241

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 315138990   82 DVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 132
Cdd:cd03858   242 SVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 684-961 5.06e-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: 210.96  E-value: 5.06e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  684 YRYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEF 763
Cdd:cd03863     6 FRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  764 LCLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTN------NASQPETKAIIeNLI 837
Cdd:cd03863    86 LCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDqffqitDPPQPETLAVM-SWL 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  838 QKQDFSLSVALDGGSMLVTYPYDKPVQTV------ENKETLKHLASLYANNHPSMHMGQPSCPNKSDENIPGGVMRGAEW 911
Cdd:cd03863   165 KTYPFVLSANLHGGSLVVNYPFDDDEQGLatysksPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITNGAQW 244

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990  912 HSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 961
Cdd:cd03863   245 YNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFI 294
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 686-961 5.49e-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: 207.72  E-value: 5.49e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03866     1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDF-----TNNAS-QPETKAIIeNLIQK 839
Cdd:cd03866    81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFpdafeENNVQrQPETRAVM-DWIKN 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  840 QDFSLSVALDGGSMLVTYPYDKPVQTVE---------NKETLKHLASLYANNHPSMHMGQpSCPNKsdENIPGGVMRGAE 910
Cdd:cd03866   160 ETFVLSANLHGGALVASYPFDNGNSGTGqlgyysvspDDDVFIYLAKTYSYNHTNMYKGI-ECSNS--QSFPGGITNGYQ 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 315138990  911 WHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 961
Cdd:cd03866   237 WYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYI 287
Zn_pept smart00631
Zn_pept domain;
686-941 1.09e-55

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 194.86  E-value: 1.09e-55
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGG---SHDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIG---QTNARGKDLDTDFTNN-----------------AS 825
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNrspNSNCRGVDLNRNFPFHwgetgnpcsetyagpspFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    826 QPETKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQTV-----ENKETLKHLASLYANNHPSMHMGQPSCpnksden 900
Cdd:smart00631  158 EPETKAVRDFIRSNRRFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGTRYTYGISN------- 230

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|..
gi 315138990    901 ipggvmrGAEWHSHlGSMKDYS-VTYGHCPEITVYTSCCYFP 941
Cdd:smart00631  231 -------GAIYPAS-GGSDDWAyGVLGIPFSFTLELRDDGRY 264
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 3-132 2.80e-54

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: 191.16  E-value: 2.80e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    3 FVLSGNLHGGSVVASYPFDDS-PEHKATGIYSKTSDDEVFKYLAKAYASNHPIMKTGEpHCPgdEDETFKDGITNGAHWY 81
Cdd:cd03866   162 FVLSANLHGGALVASYPFDNGnSGTGQLGYYSVSPDDDVFIYLAKTYSYNHTNMYKGI-ECS--NSQSFPGGITNGYQWY 238

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 315138990   82 DVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 132
Cdd:cd03866   239 PLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 257-538 1.71e-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: 183.23  E-value: 1.71e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  257 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVhEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 336
Cdd:cd03859     5 HTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLLE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  337 NFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN---NSNNF------DLNRNFPDQFVQI--------TD 399
Cdd:cd03859    84 NYGTDPRITNLVDNREIWIIPVVNPDGYEYNRETGGGRLWRKNrrpNNGNNpgsdgvDLNRNYGYHWGGDnggsspdpSS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  400 PT--------QPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFdddeqGLATYSKSPDDAVFQQIALSYSKENsqmfqgr 471
Cdd:cd03859   164 ETyrgpapfsEPETQAIRDLVESHDFKVAISYHSYGELVLYPW-----GYTSDAPTPDEDVFEELAEEMASYN------- 231

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 315138990  472 pcknmypneyfPHGITNGASW--YNVPGGMQDWNYLQTNCFEVTIELG---CVKYPLEKELPNFWEQNRRSL 538
Cdd:cd03859   232 -----------GGGYTPQQSSdlYPTNGDTDDWMYGEKGIIAFTPELGpefYPFYPPPSQIDPLAEENLPAA 292
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 686-961 4.31e-50

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: 178.76  E-value: 4.31e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEePKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd18172     1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDETE-PAFKFVGNMHGDEPVGRELLLRLADWLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYK-KNPAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDF-----------TNNASQPETKAII 833
Cdd:cd18172    80 ANYKaKDPLAAKIVENAHLHLVPTMNPDGFARRR---------RNNANNVDLNRDFpdqffpknlrnDLAARQPETLAVM 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  834 eNLIQKQDFSLSVALDGGSMLVTYPYD------KPVQTVENKETLKHLASLYANNHPSMHmgqpscpnKSDEnIPGGVMR 907
Cdd:cd18172   151 -NWSRSVRFTASANLHEGALVANYPWDgnadgrTKYSASPDDATFRRLASVYAQAHPNMA--------KSKE-FPGGITN 220

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 315138990  908 GAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 961
Cdd:cd18172   221 GAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALA 274
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 685-961 1.87e-49

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: 177.00  E-value: 1.87e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  685 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEePKIRFVAGIHGNAPVGTELLLALAEFL 764
Cdd:cd18173     3 SYPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEAE-PEFKYTSTMHGDETTGYELMLRLIDYL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  765 CLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIgQTNARGKDLDTDF---------TNNASQPETKAIIeN 835
Cdd:cd18173    82 LTNYGTDPRITNLVDNTEIWINPLANPDGTYAGGNNTVSGAT-RYNANGVDLNRNFpdpvdgdhpDGNGWQPETQAMM-N 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  836 LIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYA----NNHPSMHMGQpscpnksdenIPGGVMRGAEW 911
Cdd:cd18173   160 FADEHNFVLSANFHGGAEVVNYPWDTWYSRHPDDDWFQDISREYAdtnqANSPPMYMSE----------FNNGITNGYDW 229

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990  912 HSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 961
Cdd:cd18173   230 YEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYI 279
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 312-538 1.07e-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: 172.64  E-value: 1.07e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  312 YIGNMHGNEVVGRELLLNLIEYLCKNFGTDPeVTDLVHNTRIHLMPSMNPDGYEKSQEGDsisviGRNNSNNFDLNRNFP 391
Cdd:cd00596     3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVIDSG-----GRKNANGVDLNRNFP 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  392 DQFVQITDP-------------TQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDdeqglaTYSKSPDDAVFQQIAL 458
Cdd:cd00596    77 YNWGKDGTSgpssptyrgpapfSEPETQALRDLAKSHRFDLAVSYHSSSEAILYPYGY------TNEPPPDFSEFQELAA 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  459 SYSKENSqmfqgrpcknmypneYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPN-FWEQNRRS 537
Cdd:cd00596   151 GLARALG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTLLDrRLERNLAA 215


                  .
gi 315138990  538 L 538
Cdd:cd00596   216 L 216
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
694-956 5.13e-48

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 173.25  E-value: 5.13e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   694 EFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPA 773
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   774 VTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQTNAR-----GKDLDTDF--------------------TNNASQPE 828
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFpdhwnevgassnpcsetyrgPAPFSEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   829 TKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQT-VENKETLKHLASLYANNHPSMHMGQpscpnksdeNIPGGVMR 907
Cdd:pfam00246  163 TRAVADFIRSKKPFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 315138990   908 GAEWHSHLGSMKDYSVTYGHCP-EITVYTSCC----YFPSAARLPSLWADNKRS 956
Cdd:pfam00246  234 GATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 686-961 6.96e-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: 168.09  E-value: 6.96e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03869     1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKK-NPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTS---KIGQTNARGKDLDTDF--------------------- 820
Cdd:cd03869    81 QEYLAgNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELggwSLGRWTSDGIDINHNFpdlnsllweaedrkwvprkvp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  821 -----------TNNAS-QPETKAIIeNLIQKQDFSLSVALDGGSMLVTYPYDK---PVQTVENKETLKH-----LASLYA 880
Cdd:cd03869   161 nhhipipewylSENATvAPETRAVI-AWMEKIPFVLGGNLQGGELVVSYPYDMtrtPWKTQEYTPTPDDhvfrwLAYSYA 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  881 NNHpsMHMGQPS---CpNKSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSL 957
Cdd:cd03869   240 STH--RLMTDASrrpC-HTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESL 316


                  ....
gi 315138990  958 LSML 961
Cdd:cd03869   317 LVFM 320
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 3-132 1.33e-45

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: 167.08  E-value: 1.33e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    3 FVLSGNLHGGSVVASYPFDDSpEHKATGIYSKTSDDEVFKYLAKAYASNHPIMK-TGEPHC-PGDEDETFKDGITNGAHW 80
Cdd:cd03865   189 FVLSANLHGGDLVANYPYDET-RSGSAHEYSSCPDDAIFQSLARAYSSLNPAMSdPNRPPCrKNDDDSSFVDGTTNGGAW 267

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 315138990   81 YDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 132
Cdd:cd03865   268 YSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 686-961 2.20e-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: 2.20e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03865     1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKK-NPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSK---IGQTNARGKDLDTDF---------------TNN--- 823
Cdd:cd03865    81 NEYQKgNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKdwfVGRSNAQGIDLNRNFpdldrivyvnekeggPNNhll 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  824 -----------ASQPETKAIIeNLIQKQDFSLSVALDGGSMLVTYPYDKP-------VQTVENKETLKHLASLYANNHPS 885
Cdd:cd03865   161 knmkkavdqntKLAPETKAVI-HWIMDIPFVLSANLHGGDLVANYPYDETrsgsaheYSSCPDDAIFQSLARAYSSLNPA 239

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 315138990  886 MH-MGQPSC-PNKSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 961
Cdd:cd03865   240 MSdPNRPPCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYI 317
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 3-132 2.99e-44

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: 163.18  E-value: 2.99e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    3 FVLSGNLHGGSVVASYPFDDSPEHKATGI----YSKTSDDEVFKYLAKAYASNHPIMKTGEpHCpGDedeTFKDGITNGA 78
Cdd:cd03864   185 FVLSANLHGGAVVANYPYDKSREPRVRGFrrtaYSPTPDDKLFQKLAKTYSYAHGWMHKGW-NC-GD---YFDEGITNGA 259

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 315138990   79 HWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 132
Cdd:cd03864   260 SWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 3-132 4.26e-43

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: 159.34  E-value: 4.26e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    3 FVLSGNLHGGSVVASYPFDDSPEHKATgiYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCPGDEDETFKDGITNGAHWYD 82
Cdd:cd03863   169 FVLSANLHGGSLVVNYPFDDDEQGLAT--YSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITNGAQWYN 246

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990   83 VEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 132
Cdd:cd03863   247 VPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 686-963 1.33e-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: 155.48  E-value: 1.33e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03864     1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKK-NPAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSK---IGQTNARGKDLDTDF--------------------- 820
Cdd:cd03864    81 EEYRNgNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNgylVGRNNANGVDLNRNFpdlntlmyynekyggpnhhlp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  821 --TNNASQ--PETKAIIEnLIQKQDFSLSVALDGGSMLVTYPYDKPVQ------------TVENKETLKHLASLYANNHP 884
Cdd:cd03864   161 lpDNWKSQvePETLAVIQ-WMQNYNFVLSANLHGGAVVANYPYDKSREprvrgfrrtaysPTPDDKLFQKLAKTYSYAHG 239

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 315138990  885 SMHMGQpSCPNKSDEnipgGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSMLVE 963
Cdd:cd03864   240 WMHKGW-NCGDYFDE----GITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 686-961 2.15e-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: 155.04  E-value: 2.15e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03867     1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNY-KKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKDC---TSKIGQTNARGKDLDTDFTNNASQ--------------- 826
Cdd:cd03867    81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAgynGWTSGRQNAQNLDLNRNFPDLTSEayrlartrgarldhi 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  827 ------------PETKAIIEnLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKE--------TLKHLASLYANNHPSM 886
Cdd:cd03867   161 pipqsywwgkvaPETKAVMK-WMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMfsptpdekMFKLLAKAYADAHPMM 239

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 315138990  887 HMGQPSCPNkSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSLLSML 961
Cdd:cd03867   240 SDRSENRCG-GNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFM 313
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 2-131 4.18e-40

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: 149.87  E-value: 4.18e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    2 RFVLSGNLHGGSVVASYPFDDSPEHKATgiYSKTSDDEVFKYLAKAYASNHPIMKtgephcpgdEDETFKDGITNGAHWY 81
Cdd:cd18172   157 RFTASANLHEGALVANYPWDGNADGRTK--YSASPDDATFRRLASVYAQAHPNMA---------KSKEFPGGITNGAQWY 225

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990   82 DVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 131
Cdd:cd18172   226 PLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALAA 275
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
239-499 5.48e-38

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 145.60  E-value: 5.48e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  239 LSGTSSSYQPIQPKD-FHHHHfpDMEIFLRRFANEyPNITRLYSLGKSVESRELYVMEISDnpgvHEPGEPEFKYIGNMH 317
Cdd:COG2866     3 LLILPATYKEVSSYDrYYTYE--ELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQH 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  318 GNEVVGRELLLNLIEYLCKNFgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQFVqi 397
Cdd:COG2866    76 GNEWTGTEALLGLLEDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWL-- 142

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  398 tdpTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDD---AVFQQIALSYSKENSQMFQGRPCK 474
Cdd:COG2866   143 ---SEPETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEereAFAEELNFEGIILAGSAFLGAGAA 219

                         250       260
                  ....*....|....*....|....*
gi 315138990  475 NMYPNEYFPHGITNGASWYNVPGGM 499
Cdd:COG2866   220 GTLLISAPRQTFLFAAALDIGGGGD 244
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 3-132 9.83e-38

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: 144.59  E-value: 9.83e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    3 FVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCPGDEDETFKDGITNGAHWYD 82
Cdd:cd03869   193 FVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYASTHRLMTDASRRPCHTEDFQKEDGTVNGASWHT 272

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 315138990   83 VEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 132
Cdd:cd03869   273 VAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFMEQ 322
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 3-131 1.11e-36

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: 141.18  E-value: 1.11e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    3 FVLSGNLHGGSVVASYPFDDSPEHKATGIYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCPGDEDETfKDGITNGAHWYD 82
Cdd:cd03867   187 FVLSASLHGGDLVVSYPYDFSKHPLEEKMFSPTPDEKMFKLLAKAYADAHPMMSDRSENRCGGNFLK-RGGIINGAEWYS 265

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 315138990   83 VEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 131
Cdd:cd03867   266 FTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 548-623 6.07e-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: 130.34  E-value: 6.07e-36
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  548 GVRGFVLDATdGRGILNATISVAEINHPVTTYKTGDYWRLLVPGTYKITASARGYNPVTKNVTVKSE-GAIQVNFTL 623
Cdd:cd11308     1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 1-131 1.99e-35

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: 136.55  E-value: 1.99e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    1 MRFVLSGNLHGGSVVASYPFDDspehkatgIYSKTSDDEVFKYLAKAYASnhpimkTGEPHCPGDEDETFKDGITNGAHW 80
Cdd:cd18173   164 HNFVLSANFHGGAEVVNYPWDT--------WYSRHPDDDWFQDISREYAD------TNQANSPPMYMSEFNNGITNGYDW 229

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 315138990   81 YDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 131
Cdd:cd18173   230 YEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIE 280
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
2-125 1.09e-31

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 125.87  E-value: 1.09e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990     2 RFVLSGNLHGGSVVASYPFDDSPEhkatgiySKTSDDEVFKYLAKAYASNHPIMKTGEphcpgdedeTFKDGITNGAHWY 81
Cdd:pfam00246  175 PFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITNGATIY 238

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 315138990    82 DVEGGMQDYNYVWANC-FEITLELSCCK----YPPASQLRQEWENNRES 125
Cdd:pfam00246  239 PASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 3-130 2.74e-31

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: 124.48  E-value: 2.74e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    3 FVLSGNLHGGSVVASYPFDDSPEhkatgiysKTSDDEVFKYLAKAYASNHPIMKTGEPHCPGDEDETFKDGITNGAHWYD 82
Cdd:cd06245   162 FTLSVALDGGSLVVTYPYDKPVQ--------TVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHS 233

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 315138990   83 VEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLI 130
Cdd:cd06245   234 HKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMI 281
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 253-516 5.87e-31

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


Pssm-ID: 349476 [Multi-domain]  Cd Length: 359  Bit Score: 125.81  E-value: 5.87e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  253 DFHHHH-FPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLI 331
Cdd:cd06905     2 AFDRYYtYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  332 EYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQE----------------------------GD-SISVI------ 376
Cdd:cd06905    82 EYLLTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYKLktersgrssprdddrdgdgdedgpedlnGDgLITQMrvkdpt 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  377 ------------------------------------GRNN---SNNFDLNRNFPDQFVqiTDPTQ----------PETIA 407
Cdd:cd06905   162 gtwkvdpddprlmvdrekgekgfyrlypegidndgdGRYNedgPGGVDLNRNFPYNWQ--PFYVQpgagpyplsePETRA 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  408 VMSWMKSYPFVLSANLHGGSLVVNY----PFDDDEQGLAtyskspDDAVFQQIAlsyskENSQMFQGRPCKNMYPNEYFP 483
Cdd:cd06905   240 VADFLLAHPNIAAVLTFHTSGGMILrppgTGPDSDMPPA------DRRVYDAIG-----KKGVELTGYPVSSVYKDFYTV 308

                         330       340       350
                  ....*....|....*....|....*....|...
gi 315138990  484 HGitnGASwynvPGGMQDWNYLQTNCFEVTIEL 516
Cdd:cd06905   309 PG---GPL----DGDFFDWAYFHLGIPSFSTEL 334
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 136-212 6.82e-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: 116.08  E-value: 6.82e-31
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  136 GVKGFVKDSiTGSGLENATISVAGINHNITTGRFGDFYRLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDFSL 212
Cdd:cd11308     1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
Zn_pept smart00631
Zn_pept domain;
2-118 3.22e-25

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 106.65  E-value: 3.22e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990      2 RFVLSGNLHGGSVVASYPFDDSPEHKATGIyskTSDDEVFKYLAKAYASNHPImktgephcpgdedeTFKDGITNGAHWY 81
Cdd:smart00631  173 RFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVAKALAKALASVHGT--------------RYTYGISNGAIYP 235

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|...
gi 315138990     82 dVEGGMQDYNYVWAN-CFEITLELSCC-----KYPPASQLRQE 118
Cdd:smart00631  236 -ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 686-859 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: 105.42  E-value: 1.08e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVsEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03859     4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQE--------KDCTSKIG-QTNARGKDL----DTDFTNNA-------- 824
Cdd:cd03859    83 ENYGTDPRITNLVDNREIWIIPVVNPDGYEYNREtgggrlwrKNRRPNNGnNPGSDGVDLnrnyGYHWGGDNggsspdps 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 315138990  825 ----------SQPETKAiIENLIQKQDFSLSVALDGGSMLVTYPY 859
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, ...
 967-1041 2.05e-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: 94.90  E-value: 2.05e-23
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  967 GVHGFVKDKTGKPISKAVIVLNEG-IKVQTKEGGYFHVLLAPGVHNIIAIADGYQQQHSQVFVHHDaASSVVIVFD 1041
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFT 75
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
685-862 1.32e-22

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 100.53  E-value: 1.32e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  685 RYHSYKDLSEFLRGLVMNYPHITnLTNLGQSTEYRHIWSLEISNKpnvsEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 764
Cdd:COG2866    18 RYYTYEELLALLAKLAAASPLVE-LESIGKSVEGRPIYLLKIGDP----AEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  765 CLNYkkNPAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDF-TNNASQPETKAIIEnLIQKQDFS 843
Cdd:COG2866    93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWpAPWLSEPETRALRD-LLDEHDPD 160

                         170       180
                  ....*....|....*....|.
gi 315138990  844 LSVAL--DGGSMLVTYPYDKP 862
Cdd:COG2866   161 FVLDLhgQGELFYWFVGTTEP 181
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 685-820 1.58e-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: 100.77  E-value: 1.58e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  685 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 764
Cdd:cd06905     5 RYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYL 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  765 CLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKdcTSKIGQTNARGKDLDTDF 820
Cdd:cd06905    85 LTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYKLK--TERSGRSSPRDDDRDGDG 138
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 742-957 1.07e-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: 91.75  E-value: 1.07e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  742 FVAGIHGNAPVGTELLLALAEFLCLNYKKNPaVTQLVDRTRIVIVPSLNPDGRERAQEKDctskiGQTNARGKDLDTDFT 821
Cdd:cd00596     3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVIDSG-----GRKNANGVDLNRNFP 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  822 NN-------------------ASQPETKAIIEnLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANN 882
Cdd:cd00596    77 YNwgkdgtsgpssptyrgpapFSEPETQALRD-LAKSHRFDLAVSYHSSSEAILYPYGYTNEPPPDFSEFQELAAGLARA 155

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  883 HPsmhmgqpscpnksdeNIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCC-YFPSAARLPSLWADNKRSL 957
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 ...
 257-414 3.95e-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: 3.95e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  257 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 336
Cdd:cd03860     2 HPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGG--KGGKPAIVIHGGQHAREWISTSTVEYLAHQLLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  337 NFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDsisvigR-------NNSNNF----DLNRNFPDQFVQI---TDPT- 401
Cdd:cd03860    80 GYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTD------RlwrknrqPTGGSScvgiDLNRNWGYKWGGPgasTNPCs 153

                         170       180
                  ....*....|....*....|...
gi 315138990  402 ----------QPETIAVMSWMKS 414
Cdd:cd03860   154 etyrgpsafsAPETKALADFINA 176
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 312-538 2.58e-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: 85.47  E-value: 2.58e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  312 YIGNMHGNEVVGRELLLNLIEYLCKN-------FGTDPEvtDLVHNTRIHLMPSMNPDGYEKSQEG-----------DSI 373
Cdd:cd06229     3 YNASFHAREYITTLLLMKFIEDYAKAyvnksyiRGKDVG--ELLNKVTLHIVPMVNPDGVEISQNGsnainpyylrlVAW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  374 SVIGRN------NSNNFDLNRNFPDQF-----VQITDP-----------TQPETIAVMSWMKSYPFVLSANLHGGSLVVN 431
Cdd:cd06229    81 NKKGTDftgwkaNIRGVDLNRNFPAGWekekrLGPKAPgprdypgkeplSEPETKAMAALTRQNDFDLVLAYHSQGEEIY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  432 YPFDDDEQGLATyskspddavfqQIALSYSKENSqmfqgrpcknmypneYFPHGITNGASWynvpGGMQDWNYLQTNCFE 511
Cdd:cd06229   161 WGYNGLEPEESK-----------AMAEKFASVSG---------------YEPVEAEAIDSY----GGFKDWFIYEFKKPS 210

                         250       260
                  ....*....|....*....|....*...
gi 315138990  512 VTIELGCVKYPL-EKELPNFWEQNRRSL 538
Cdd:cd06229   211 FTIETGKGNNPLpISQFDEIYEKNKGVL 238
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 282-543 8.21e-17

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: 80.40  E-value: 8.21e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  282 LGKSVESRELYVMEISDNPG--VHepgepefkYIGNMHGNEVVGRELLLNLIEYLcknfGTDPEVTDLvhntRIHLMPSM 359
Cdd:cd06904     4 YGTSVKGRPILAYKFGPGSRarIL--------IIGGIHGDEPEGVSLVEHLLRWL----KNHPASGDF----HIVVVPCL 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  360 NPDGYEKSQegdsisvigRNNSNNFDLNRNFPDQ-----FVQITDP---------TQPETIAVMSWMKSYP--FVLSanL 423
Cdd:cd06904    68 NPDGLAAGT---------RTNANGVDLNRNFPTKnwepdARKPKDPryypgpkpaSEPETRALVELIERFKpdRIIS--L 136

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  424 HgGSLVVNYpFDDDEQGLAtyskspddavfqqialsyskensqmfQGRPCKNMYPNEYFPhGITngaswynvPGGMQDWN 503
Cdd:cd06904   137 H-APYLVNY-DGPAKSLLA--------------------------EKLAQATGYPVVGDV-GYT--------PGSLGTYA 179

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 315138990  504 YLQTNCFEVTIELgcvkyPLEKELPNFWEQNRRSLIQFMK 543
Cdd:cd06904   180 GIERNIPVITLEL-----PEAVSIDELWQDLKRALIEAIK 214
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 290-517 1.48e-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: 1.48e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  290 ELYVMEISdNPGVHEPGE-PEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQ 368
Cdd:cd06226     1 DIRALKLT-NKQATPPGEkPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  369 EGdsisVIGRNNSNN-----------FDLNRNFPDQF---VQITDP-----------TQPETIAVMSWMKSY-----PFV 418
Cdd:cd06226    80 TG----LLWRKNTNTtpcpassptygVDLNRNSSFKWggaGAGGSAcsetyrgpsaaSEPETQAIENYVKQLfpdqrGPG 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  419 LSA-----------NLHGGSLVVNYPFDDdeqglaTYSKSPDDAVFQQIALSYSKENSqmFQGRPCKNMYPneyfphgiT 487
Cdd:cd06226   156 LTDpapddtsgiyiDIHSYGNLVLYPWGW------TGTPAPNAAGLRTLGRKFAYFNG--YTPQQAVALYP--------T 219

                         250       260       270
                  ....*....|....*....|....*....|
gi 315138990  488 NGASwynvpggmQDWNYLQTNCFEVTIELG 517
Cdd:cd06226   220 DGTT--------DDFAYGTLGVAAYTFELG 241
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
136-212 1.86e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 69.62  E-value: 1.86e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   136 GVKGFVKDSiTGSGLENATISVA----GINHNITTGRFGDFY-RLLVPGTYNLTVVLTGYMPLTVTNVVVKEGPATEVDF 210
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 315138990   211 SL 212
Cdd:pfam13620   80 TL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
548-623 3.02e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 68.85  E-value: 3.02e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   548 GVRGFVLDATdGRGILNATISVA----EINHPVTTYKTGDYW-RLLVPGTYKITASARGYNPVTK-NVTVKSEGAIQVNF 621
Cdd:pfam13620    1 TISGTVTDPS-GAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRtGVTVTAGQTTTLDV 79


                   ..
gi 315138990   622 TL 623
Cdd:pfam13620   80 TL 81
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 312-499 2.05e-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: 70.18  E-value: 2.05e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  312 YIGNMHGNEVVGRELLLNLIeylcKNFGTDP-EVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIG----RNNSNNFDL 386
Cdd:cd03857     4 LAAQIHGNETTGTEALMELI----RDLASESdEAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGlpgtRYNANGIDL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  387 NRNFPDQfvqitdpTQPETIAVMS-WMKSYPFVLsANLHggslvvnypfdDDEQGLATYSKSPDDAVFQQIALSYSKENS 465
Cdd:cd03857    80 NRDHVKL-------TQPETQAVAEnFIHWWPDIF-IDLH-----------EQVGASIPYPTPPDAPNYNLVDLRSDAENG 140

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 315138990  466 QMfQGRPCKNMYPNE---YFPHGITNGASWYNVPGGM 499
Cdd:cd03857   141 QE-HIRLIAGEGSGElgkYFSPMRGGFDDSTGGNGIG 176
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
 686-859 9.82e-12

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: 9.82e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03860     1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSG--GKGGKPAIVIHGGQHAREWISTSTVEYLAHQLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKIGQTNARGKDLDTDF-----TNNASQ--------- 826
Cdd:cd03860    79 SGYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDrlwrkNRQPTGGSSCVGIDLNRNWgykwgGPGASTnpcsetyrg 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 315138990  827 ------PETKAI---IENLIQKQDFSLSVALDGGSMLVTYPY 859
Cdd:cd03860   159 psafsaPETKALadfINALAAGQGIKGFIDLHSYSQLILYPY 200
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 316-425 3.54e-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: 3.54e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  316 MHGNEVVGRELLLNLIEYLCKnfgTDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNfpdqfv 395
Cdd:cd06239     8 MHGNEPTGTEALLDLISYLRR---ERQEFEKILERLTLVAIPMLNPDGAELFT---------RHNAEGIDLNRD------ 69

                          90       100       110
                  ....*....|....*....|....*....|
gi 315138990  396 qITDPTQPETIAVMSWMKSYPFVLSANLHG 425
Cdd:cd06239    70 -ARALQTPESRALKAVLDSFSPKFAFNLHD 98
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 315-425 1.10e-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: 349463 [Multi-domain]  Cd Length: 223  Bit Score: 62.85  E-value: 1.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  315 NMHGNEVVGRELLLNLIEYLCKN--------------FGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNN 380
Cdd:cd06244     7 NIHGNEVEGVDALLEFLEMLATEpnvtyntlvkyykvENVDLEVKDLLDDVFFIVVPTENPDGRVANT---------RTN 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 315138990  381 SNNFDLNRNFPDQfvqitdpTQPETIAVMSWMKSYPFVLSANLHG 425
Cdd:cd06244    78 ANGFDLNRDNAYQ-------TQPETRAMQELISKWNPVTFLDMHG 115
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 314-419 2.14e-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: 61.60  E-value: 2.14e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  314 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVHNTRIHLMPSMNPDGYEK-----SQEGDSISVI------------ 376
Cdd:cd06238     8 YSIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRERfvnwfNQNRGAVGDPdpqsmehnepwp 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 315138990  377 -GRNNSNNFDLNRnfpDQFVQitdpTQPETIAVMSWMKSY-PFVL 419
Cdd:cd06238    86 gGRTNHYLFDLNR---DWLAQ----TQPESRARAAAIHRWrPQVV 123
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
 256-527 2.14e-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: 63.29  E-value: 2.14e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNpgvhepgEPEFKYI----GNMHGNEVVGRELLLNLI 331
Cdd:cd06246     5 YHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGK-------EQTAKNAiwidCGIHAREWISPAFCLWFI 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  332 EYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSI-----SVIGRNNSNNFDLNRNFPDQFV------QITDP 400
Cdd:cd06246    78 GHASYFYGIIGQHTNLLNLVDFYVMPVVNVDGYDYSWKKNRMwrknrSKHANNRCIGTDLNRNFDAGWCgkgassDSCSE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  401 T--------QPETIAVMSWMKSYPFVLSA--NLHGGSLVVNYPFDddeqglATYSKSPDDAVFQQIAlsysKENSQMFqg 470
Cdd:cd06246   158 TycgpypesEPEVKAVASFLRRHKDTIKAyiSMHSYSQMVLFPYS------YTRNKSKDHDELSLLA----KEAVTAI-- 225

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 315138990  471 rpcKNMYPNEYfPHGitNGA-SWYNVPGGMQDWNYlqtncfevtiELGcVKYPLEKEL 527
Cdd:cd06246   226 ---RKTSRNRY-TYG--PGAeTIYLAPGGSDDWAY----------DLG-IKYSFTFEL 266
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
 315-436 2.23e-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: 61.90  E-value: 2.23e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  315 NMHGNEVVGRELLLNLIEYLC--KNFGTDPEVTDLVH----NTRIHLMPSMNPDGYEKSQEGDsisVIGRNNSNNFDLNR 388
Cdd:cd06227     9 GEHARELISVESALRLLRQLCggLQEPAASALRELAReildNVELKIIPNANPDGRRLVESGD---YCWRGNENGVDLNR 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  389 NFPD--QFVQITDPTQ----------PETIAVMSWMKSYPFVLSANLHGGSLVVNYPFDD 436
Cdd:cd06227    86 NWGVdwGKGEKGAPSEeypgpkpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAY 145
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 312-515 3.04e-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: 3.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  312 YI-GNMHGNEVVGRELLLNLIEylcknfgTDPEvtDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNF 390
Cdd:cd06231    46 LIsAGIHGDEPAGVEALLRFLE-------SLAE--KYLRRVNLLVLPCVNPWGFERNT---------RENADGIDLNRSF 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  391 pdqfvqITDPTQPETIAVMSWMKSYP-FVLSANLHGgslvvnypfDDDEQGLATYSKSPDDAVFQQI-----ALSYSKEN 464
Cdd:cd06231   108 ------LKDSPSPEVRALMEFLASLGrFDLHLDLHE---------DWDSDGFYLYELGPALKAGRDGlqavdAVIPPDPI 172

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 315138990  465 SQMFQGRPcknmypneyFPHG-ITNGASWYNVPGG-MQDWNYLQTNCFEVTIE 515
Cdd:cd06231   173 SLTIDGSP---------APDGvILRPDDPAERPGWpFAIYLVANGAVRTYTTE 216
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 686-887 3.19e-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: 62.84  E-value: 3.19e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKPnvsePEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03870     6 YHTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKIGQTNARGKDL----DTDFTNNA------------ 824
Cdd:cd03870    82 SDYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNrlwrkTRSVNPGSLCIGVDPnrnwDAGFGGPGassnpcsetyhg 161

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  825 ----SQPETKAIIENLIQKQDFSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMH 887
Cdd:cd03870   162 phanSEVEVKSIVDFIQSHGNFKAFISIHSYSQLLMYPYGYTVEKAPDQEELDEVAKKAVKALASLH 228
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 312-409 4.51e-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: 60.78  E-value: 4.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  312 YIGNMHGNEVVGRELLLNLIEYLCKnfgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQegdsisvigRNNSNNFDLNRNFp 391
Cdd:cd06242     6 LVGQQHGNEPAGREAALALARDLAF----GDDARELLEKVNVLVVPRANPDGRAANT---------RGNANGVDLNRDH- 71

                          90
                  ....*....|....*...
gi 315138990  392 dqfvqiTDPTQPETIAVM 409
Cdd:cd06242    72 ------LLLSTPETRALA 83
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 257-434 6.33e-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: 6.33e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  257 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 336
Cdd:cd06248     2 HSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRSTNSEDTS-KPTIMIEGGINPREWISPPAALYAIHKLVE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  337 NfgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSI---SVIGRNNSNNF-----DLNRNFPDQFVQI---TDP----- 400
Cdd:cd06248    81 D---VETQSDLLNNFDWIILPVANPDGYVFTHTNDREwtkNRSTNSNPLGQicfgvNINRNFDYQWNPVlssESPcsely 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 315138990  401 ------TQPETIAVMSWMKSY--PFVLSANLHGGSLVVNYPF 434
Cdd:cd06248   158 agpsafSEAESRAIRDILHEHgnRIHLYISFHSGGSFILYPW 199
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 686-891 2.93e-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: 2.93e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNkPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd06248     1 YHSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRS-TNSEDTSKPTIMIEGGINPREWISPPAALYAIHKLV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNykkNPAVTQLVDRTRIVIVPSLNPDG------------RERAQEKDCTSKIgqtnARGKDLDTDF---------TNNA 824
Cdd:cd06248    80 ED---VETQSDLLNNFDWIILPVANPDGyvfthtndrewtKNRSTNSNPLGQI----CFGVNINRNFdyqwnpvlsSESP 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  825 -----------SQPETKAiIENLIQKQD--FSLSVALDGGSMLVTYPYDKPVQTVENKETLkHLASLYANNHPSMHMGQP 891
Cdd:cd06248   153 cselyagpsafSEAESRA-IRDILHEHGnrIHLYISFHSGGSFILYPWGYDGSTSSNARQL-HLAGVAAAAAISSNNGRP 230
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 274-440 1.92e-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: 56.42  E-value: 1.92e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  274 PNITRLySLGKSVESRELYVMEIsdnpgvHEPGEPEFKY-IGNMHGNEVVGRELLLNLIEYLCknfGTDPEVTDLVHNTR 352
Cdd:cd06237    14 PFVKRS-TIGKSVEGRPIEALTI------GNPDSKELVVlLGRQHPPEVTGALAMQAFVETLL---ADTELAKAFRARFR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  353 IHLMPSMNPDGYEKsqegdsisviG--RNNSNNFDLNR---NFpdqfvqitdpTQPETIAVMSWMKSYpfvlsANLHGGS 427
Cdd:cd06237    84 VLVVPLLNPDGVDL----------GhwRHNAGGVDLNRdwgPF----------TQPETRAVRDFLLEL-----VEEPGGK 138

                         170       180
                  ....*....|....*....|....
gi 315138990  428 LV-----------VNYPFDDDEQG 440
Cdd:cd06237   139 VVfgldfhstwedVFYTQPDDEKT 162
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 268-516 3.28e-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: 56.31  E-value: 3.28e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  268 RFANEYPNITRLYSLGKSVESRELYVMEISdNPGVHEPGepEFKYIGnMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDL 347
Cdd:cd03871    18 QVASKNPDLVSRSQIGTTFEGRPIYLLKVG-KPGSNKKA--IFMDCG-FHAREWISPAFCQWFVREAVRTYGKEKIMTKL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  348 VHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNN-----FDLNRNFPDQFVQI---TDP-----------TQPETIAV 408
Cdd:cd03871    94 LDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSPNAGsscigTDPNRNFNAGWCTVgasSNPcsetycgsapeSEKETKAL 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  409 MSWMKSYPFVLSANL--HGGSLVVNYPFDddeqglATYSKSPDDAVFQQIALSYSKEnsqmfqgrpCKNMYPNEYfPHGi 486
Cdd:cd03871   174 ANFIRNNLSSIKAYLtiHSYSQMLLYPYS------YTYKLAPNHEELNSIAKGAVKE---------LSSLYGTKY-TYG- 236

                         250       260       270
                  ....*....|....*....|....*....|
gi 315138990  487 TNGASWYNVPGGMQDWNYLQTNCFEVTIEL 516
Cdd:cd03871   237 PGATTIYPAAGGSDDWAYDQGIKYSFTFEL 266
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 744-839 5.27e-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: 5.27e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  744 AGIHGNAPVGTELLLALAEFLCLNYKknpAVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKIGQT----NARGKDLDTD 819
Cdd:cd03857     6 AQIHGNETTGTEALMELIRDLASESD---EAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGLPgtryNANGIDLNRD 82

                          90       100
                  ....*....|....*....|
gi 315138990  820 FTnNASQPETKAIIENLIQK 839
Cdd:cd03857    83 HV-KLTQPETQAVAENFIHW 101
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
 549-631 1.60e-07

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


Pssm-ID: 433425 [Multi-domain]  Cd Length: 88  Bit Score: 49.90  E-value: 1.60e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   549 VRGFVLDATDGRGILNATISVAEINHPVTTYKTGDY-WRLLVPGTYKITASARGYNPVTKNVTVKSEGAIQVNFTLVRSS 627
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTDADGNFeLKNLPAGTYTLVVSFVGYKTQEKKVTVSNDNTLDVNFLLKEDA 80


                   ....
gi 315138990   628 TDSN 631
Cdd:pfam13715   81 LLLD 84
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 709-848 2.50e-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: 2.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  709 LTNLGQSTEYRHIWSLEISNKPNvsePEEPKIRFVAGIHGNAPVGtelllalaeflclnykknP---------AVTQLVD 779
Cdd:cd06231    17 VRELGEVGYQGYPLFALKSPNPR---GDKPRVLISAGIHGDEPAG------------------VeallrflesLAEKYLR 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 315138990  780 RTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDFTNNASQPETKAIIENLIQKQDFSLSVAL 848
Cdd:cd06231    76 RVNLLVLPCVNPWGFERNT---------RENADGIDLNRSFLKDSPSPEVRALMEFLASLGRFDLHLDL 135
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 712-961 2.75e-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: 52.66  E-value: 2.75e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  712 LGQSTEYRHIWSLEISNKPNvsepeePKIRFVAGIHGNAPVGTELLLALAeflclNYKKNPAVTQLVdrtRIVIVPSLNP 791
Cdd:cd06904     4 YGTSVKGRPILAYKFGPGSR------ARILIIGGIHGDEPEGVSLVEHLL-----RWLKNHPASGDF---HIVVVPCLNP 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  792 DGRERAQekdctskigQTNARGKDLDTDF-TNN-------------------ASQPETKAIIeNLIQKQDFSLSVALDGG 851
Cdd:cd06904    70 DGLAAGT---------RTNANGVDLNRNFpTKNwepdarkpkdpryypgpkpASEPETRALV-ELIERFKPDRIISLHAP 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  852 SMLVTYPYDKPvqtvenkETLKHLASlyANNHPsmHMGQPscpnksdENIPGGvmrgaewhshLGsmkdysvTYG----H 927
Cdd:cd06904   140 YLVNYDGPAKS-------LLAEKLAQ--ATGYP--VVGDV-------GYTPGS----------LG-------TYAgierN 184

                         250       260       270
                  ....*....|....*....|....*....|....
gi 315138990  928 CPEITVytsccYFPSAARLPSLWADNKRSLLSML 961
Cdd:cd06904   185 IPVITL-----ELPEAVSIDELWQDLKRALIEAI 213
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
 276-425 5.79e-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: 5.79e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  276 ITRLYSLGKSVESRELYVMEISDNPG----------VHePGEPEFKYIgnMHGnevvgrelllnLIEYLCKNfgTDPEVT 345
Cdd:cd06234    18 GVRLEVLGQTLDGRDIDLLTIGDPGTgkkkvwiiarQH-PGETMAEWF--MEG-----------LLDRLLDE--DDPVSR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  346 DLVHNTRIHLMPSMNPDGyeksqegdsiSVIG--RNNSNNFDLNRNF--PDQfvqitdPTQPETIAVMSWMKSYPFVLSA 421
Cdd:cd06234    82 ALLEKAVFYVVPNMNPDG----------SVRGnlRTNAAGVNLNREWanPSL------ERSPEVFAVRQAMDATGVDFFL 145


                  ....
gi 315138990  422 NLHG 425
Cdd:cd06234   146 DVHG 149
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 738-850 1.15e-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: 50.76  E-value: 1.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  738 PKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPavtqLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLD 817
Cdd:cd06242     2 PTVLLVGQQHGNEPAGREAALALARDLAFGDDARE----LLEKVNVLVVPRANPDGRAANT---------RGNANGVDLN 68

                          90       100       110
                  ....*....|....*....|....*....|...
gi 315138990  818 TDFTnNASQPETKAIIENLiqkQDFSLSVALDG 850
Cdd:cd06242    69 RDHL-LLSTPETRALARVL---RDYRPEVVIDA 97
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
 256-414 1.18e-06

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 carboxypeptidase (CP) O (CPO, also known as metallocarboxypeptidase C; EC 3.4.17.) belongs to the carboxypeptidase A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPO has not been well characterized as yet, and little is known about it. Based on modeling studies, CPO has been suggested to have specificity for acidic residues rather than aliphatic/aromatic residues as in A-like enzymes or basic residues as in B-like enzymes. It remains to be demonstrated that CPO is functional as an MCP.


Pssm-ID: 349466 [Multi-domain]  Cd Length: 298  Bit Score: 51.77  E-value: 1.18e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEI---SDNPgvhepgepefKYIGNM----HGNEVVGRELLL 328
Cdd:cd06247     4 YHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKP----------KKIIWMdcgiHAREWIAPAFCQ 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  329 NLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNN-----FDLNRNFPDQFVQI------ 397
Cdd:cd06247    74 WFVKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLWRKSRSPHNNgtcygTDLNRNFNSQWCSIgasrnc 153

                         170       180
                  ....*....|....*....|....*
gi 315138990  398 -------TDP-TQPETIAVMSWMKS 414
Cdd:cd06247   154 csiifcgTGPeSEPETKAVADLIEK 178
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 721-832 1.72e-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: 1.72e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  721 IWSLEISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERA--- 797
Cdd:cd06226     2 IRALKLTNKQATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAetg 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 315138990  798 --QEKDCTSKIGQT--NARGKDLDTDFT--------------------NNASQPETKAI 832
Cdd:cd06226    82 llWRKNTNTTPCPAssPTYGVDLNRNSSfkwggagaggsacsetyrgpSAASEPETQAI 140
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
967-1039 1.85e-06

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 46.89  E-value: 1.85e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   967 GVHGFVKDKTGKPISKAVIVL-----NEGIKVQTKEGGYFHV-LLAPGVHNIIAIADGYQQQH-SQVFVHHDAASSVVIV 1039
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRFpGLPPGTYTVTVSAPGFKTATrTGVTVTAGQTTTLDVT 80
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 257-394 2.20e-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: 50.90  E-value: 2.20e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  257 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPgvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 336
Cdd:cd03870     7 HTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIVS 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 315138990  337 NFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRN-NSNNF----DLNRNFPDQF 394
Cdd:cd03870    83 DYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNRLWRKTRSvNPGSLcigvDPNRNWDAGF 145
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 779-849 5.43e-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: 49.10  E-value: 5.43e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 315138990  779 DRTRIVIVPSLNPDGRERaqekdctskiG--QTNARGKDLDTDFtNNASQPETKAI---IENLIQKQDFSLSVALD 849
Cdd:cd06237    80 ARFRVLVVPLLNPDGVDL----------GhwRHNAGGVDLNRDW-GPFTQPETRAVrdfLLELVEEPGGKVVFGLD 144
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 2-126 6.33e-06

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: 48.61  E-value: 6.33e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990    2 RFVLSGNLHGGSVVASYPFDDSPEhkatgiysKTSDDEVFKYLAKAYASNHPimktgephcpgdedeTFKDGITNGAHWY 81
Cdd:cd00596   114 RFDLAVSYHSSSEAILYPYGYTNE--------PPPDFSEFQELAAGLARALG---------------AGEYGYGYSYTWY 170

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 315138990   82 DVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQ-EWENNRESL 126
Cdd:cd00596   171 STTGTADDWLYGELGILAFTVELGTADYPLPGTLLDrRLERNLAAL 216
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
 256-390 1.25e-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: 1.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  256 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEIsdnpGVHEPGEPEFKYIG-NMHGNEVVGRELLLNLIEYL 334
Cdd:cd03872     2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIDcGIHAREWIGPAFCQWFVKEA 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 315138990  335 CKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIGRNNSNNF-----DLNRNF 390
Cdd:cd03872    78 INSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKNSRFqcrgvDANRNW 138
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 312-438 1.37e-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: 1.37e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  312 YIGNMHGNEVVGRELLLNLIE-------------YLCKNFGTDpEVTDLVHNTRIHLMPSMNPDGYEKSQE--------- 369
Cdd:cd06228     5 FIGGVHAREWGSPDILIYFAAdlleaytnntgltYGGKTFTAA-QVKSILENVDLVVFPLVNPDGRWYSQTsesmwrknr 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  370 -----GDSISVIGRNNSNNFDLNRNFPDQF-----VQITDP-----------TQPETIAVMSWMKSYP----FVlsaNLH 424
Cdd:cd06228    84 npasaGDGGSCIGVDINRNFDFLWDFPRYFdpgrvPASTSPcsetyhgpsafSEPETRNVVWLFDAYPnirwFV---DVH 160

                         170
                  ....*....|....
gi 315138990  425 GGSLVVNYPFDDDE 438
Cdd:cd06228   161 SASELILYSWGDDE 174
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 772-839 1.73e-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: 47.44  E-value: 1.73e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 315138990  772 PAVTQLVDRTRIVIVPSLNPDGRERAQekdctskigQTNARGKDLDTDFTnNASQPETKAIIEnLIQK 839
Cdd:cd06244    48 LEVKDLLDDVFFIVVPTENPDGRVANT---------RTNANGFDLNRDNA-YQTQPETRAMQE-LISK 104
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 740-849 1.51e-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: 44.64  E-value: 1.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  740 IRFVAGIHGNAPVGTELLLALAEFLCLNYKKN-----PAVTQLVDRTRIVIVPSLNPDG----------------RERAQ 798
Cdd:cd06229     1 VLYNASFHAREYITTLLLMKFIEDYAKAYVNKsyirgKDVGELLNKVTLHIVPMVNPDGveisqngsnainpyylRLVAW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 315138990  799 EKDCTSKIG-QTNARGKDLDTDF--------TNNA--------------SQPETKAIIeNLIQKQDFSLSVALD 849
Cdd:cd06229    81 NKKGTDFTGwKANIRGVDLNRNFpagwekekRLGPkapgprdypgkeplSEPETKAMA-ALTRQNDFDLVLAYH 153
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
 137-218 3.00e-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: 40.65  E-value: 3.00e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990   137 VKGFVKDSITGSGLENATISVAGINHNITT---GRFgdFYRLLVPGTYNLTVVLTGYMPLTVTnVVVKEGPATEVDFSLR 213
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTdadGNF--ELKNLPAGTYTLVVSFVGYKTQEKK-VTVSNDNTLDVNFLLK 77


                   ....*
gi 315138990   214 PTVTS 218
Cdd:pfam13715   78 EDALL 82
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 777-840 4.84e-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: 4.84e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  777 LVDRTRIVIVPSLNPDGRERAQEKDCTSKIG------QTNARGKDLDTDFTnNASQPETKAIIENLIQKQ 840
Cdd:cd06241    36 LLDNLILLFVPIFNADGNDRRSKGNRPNQNGplevgwRTNAQGLDLNRDFM-KLEAPETRALAKLFNQWD 104
M14-like cd06240
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 314-366 7.23e-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: 7.23e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 315138990  314 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVHNTRIHLMPSMNPDGYEK 366
Cdd:cd06240     8 GGLHATEVAGSQMLPELAYRLAT--SDDEEVRRILDNVILLLVPSANPDGQDL 58
M14_Nna1-like cd18429
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 261-437 9.24e-04

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: 42.44  E-value: 9.24e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  261 DMEIFLRRFA-NEYPNITRLyslGKSVESRELYVMEISDNPGVH-----------EPGepefkyignmhGNEVVGrelll 328
Cdd:cd18429     1 DLDRLLAKIRkNPLVEITTI---GKTVEGRPLEIIRIGNESAPHrvflrarahpwEAG-----------GNWVVE----- 61

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  329 NLIEYLCKNfgtDPEVTDLVHNTRIHLMPSMNPDGYEKSQEgdsisvigRNNSNNFDLNRN--FPdqfvqiTDPT-QPET 405
Cdd:cd18429    62 GLVERLLQN---DEEAKRFLKRYCVYILPMANKDGVARGRT--------RFNANGKDLNREwdKP------ADPVlAPEN 124

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 315138990  406 IAVMSWM------KSYPFvLSANLH---GGSLVVNYPFDDD 437
Cdd:cd18429   125 FALEKWLeemikaGKKPD-LAIELHndgGGNLHVSRPPVDG 164
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
 685-881 9.67e-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: 42.53  E-value: 9.67e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  685 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEI---SNKPNvsepeepKIRFV-AGIHGNAPVGTELLLAL 760
Cdd:cd06247     3 KYHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKPK-------KIIWMdCGIHAREWIAPAFCQWF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  761 AEFLCLNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKIGQTNARGKDLDTDFTNN------------ 823
Cdd:cd06247    76 VKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDrlwrkSRSPHNNGTCYGTDLNRNFNSQwcsigasrnccs 155

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315138990  824 --------ASQPETKAIIENLIQKQDFSLS-VALDGGSMLVTYPYDKPVQTVENKETLKHLASLYAN 881
Cdd:cd06247   156 iifcgtgpESEPETKAVADLIEKKKSDILCyLTIHSYGQLILLPYGYTKEPSPNHEEMMEVGEKAAA 222
M14_Nna1-like cd03856
Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related ...
 776-909 1.12e-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: 42.19  E-value: 1.12e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  776 QLVDRTRIVIVPSLNPDGRERAQEKdctskigqTNARGKDLDTDFTNNA--SQPET---KAIIENLIQKQ---DFSLSVA 847
Cdd:cd03856    79 QLRAEYNFYIIPMVNPDGVARGHWR--------TNSRGMDLNRDWHAPDalLSPETyavAAALAERVQSPegvVLALDLH 150

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 315138990  848 LDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQpscpnKSDENIPGGVMRGA 909
Cdd:cd03856   151 GDNRNVFLTGPDNKDESTNHNPDKLNSLLTETDRRLPDYNTEA-----SPGDNPGGTVGKQW 207
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 685-883 1.41e-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: 42.06  E-value: 1.41e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  685 RYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISnKPNVSEPeepKIRFVAGIHGNAPVGTELLLALAEFL 764
Cdd:cd03871     5 KYNNWETIEAWTEQVASKNPDLVSRSQIGTTFEGRPIYLLKVG-KPGSNKK---AIFMDCGFHAREWISPAFCQWFVREA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  765 CLNYKKNPAVTQLVDRTRIVIVPSLNPDG------RERAQEKDcTSKIGQTNARGKDLDTDF---------TNNA----- 824
Cdd:cd03871    81 VRTYGKEKIMTKLLDRLDFYILPVLNIDGyvytwtKNRMWRKT-RSPNAGSSCIGTDPNRNFnagwctvgaSSNPcsety 159

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 315138990  825 ------SQPETKAiIENLIQKQDFSLSVALD--GGSMLVTYPYDKPVQTVEN--------KETLKHLASLYANNH 883
Cdd:cd03871   160 cgsapeSEKETKA-LANFIRNNLSSIKAYLTihSYSQMLLYPYSYTYKLAPNheelnsiaKGAVKELSSLYGTKY 233
M14-like cd03862
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 308-391 1.64e-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: 41.64  E-value: 1.64e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  308 PEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGyeksqegdsISVIGRNNSNNFDLN 387
Cdd:cd03862     1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGG---------MALKTRSNPNGVDLM 71


                  ....
gi 315138990  388 RNFP 391
Cdd:cd03862    72 RNAP 75
PRK10602 PRK10602
murein tripeptide amidase MpaA;
352-393 1.67e-03

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 41.55  E-value: 1.67e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 315138990  352 RIHLMPSMNPDGyekSQEGDsisvigRNNSNNFDLNRNFPDQ 393
Cdd:PRK10602   72 RHHVVLAVNPDG---CQLGL------RANANGVDLNRNFPAA 104
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 313-390 2.42e-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: 2.42e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  313 IGNMHGNEVVGRELLLNLIEYLCknFGtdpEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIG------RNNSNNFDL 386
Cdd:cd06241     7 QAGIHPGEVEGKEASLMLLRDIA--QG---GKKHLLDNLILLFVPIFNADGNDRRSKGNRPNQNGplevgwRTNAQGLDL 81


                  ....
gi 315138990  387 NRNF 390
Cdd:cd06241    82 NRDF 85
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
 686-868 2.92e-03

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: 41.12  E-value: 2.92e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  686 YHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLEISNKpnvSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 765
Cdd:cd03872     2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKLGKR---SRSYKKAVWIDCGIHAREWIGPAFCQWFVKEAI 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315138990  766 LNYKKNPAVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKIGQTNARGKDLDTDFTNN----------------- 823
Cdd:cd03872    79 NSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDrfwrkTRSKNSRFQCRGVDANRNWKVKwcdegaslhpcddtycg 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 315138990  824 ---ASQPETKAIIENLI-QKQDFSLSVALDGGSMLVTYPYDKPVQTVEN 868
Cdd:cd03872   159 pfpESEPEVKAVAQFLRkHRKHVRAYLSFHAYAQMLLYPYSYKYATIPN 207
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH