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Conserved domains on  [gi|150378501|ref|NP_031780|]
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carboxypeptidase D precursor [Mus musculus]

Protein Classification

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

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

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 495-790 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: 652.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  495 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 574
Cdd:cd03863     1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  575 NLIEYLCKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNNFDLNRNFPDQFVPITEPTQPETIAV 654
Cdd:cd03863    81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  655 MSWVKAYPFVLSANLHGGSLVVNYPYDDNEQGVATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKDMYLNEYFPHGITN 734
Cdd:cd03863   161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501  735 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd03863   241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 930-1207 2.94e-159

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: 2.94e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNAHGKDLDTDFTSNAS------QPETKAIIENLIQK 1083
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1084 qDFSLSIALDGGSVLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNNSDENIPGGVMRGAEWHSHLGSMK 1163
Cdd:cd06245   161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 150378501 1164 DYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSMLVE 1207
Cdd:cd06245   240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
Peptidase_M14_like super family cl11393
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 86-377 6.37e-153

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: 463.64  E-value: 6.37e-153
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGLGPPPtaaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd03868    23 KLHSIGKSVQGRELWVLEISDNVNRRE-------------PGKPMFKYVANMHGDETVGRQLLIYLAQYLLENYGK-DER 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCglgdSGPPGTSGRDNSRGRDLNRSFPDQFSTGEPPSLDE-VPEVRALIDWI 244
Cdd:cd03868    89 VTRLVNSTDIHLMPSMNPDGFENSKEGDC----SGDPGYGGRENANNVDLNRNFPDQFEDSDDRLLEGrQPETLAMMKWI 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  245 RRNKFVLSGNLHGGSVVASYPFDDSPEHKTTGLYSKTSDDEVFRYLAKAYASNHPIMKTGEPHCpgdeDETFKDGITNGA 324
Cdd:cd03868   165 VENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDGITNGA 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  325 HWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 377
Cdd:cd03868   241 EWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYME 293
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 794-869 3.78e-35

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: 128.41  E-value: 3.78e-35
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  794 GVKGFVLDATdGRGILNATLSVAEINHPVTTYKAGDYWRLLVPGTYKITASARGYNPVTKNVTVRSE-GAVQVNFTL 869
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, ...
 382-458 1.25e-28

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: 109.92  E-value: 1.25e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501  382 GIKGFVKDSvTGSGLENATISVAGINHNITTGRFGDFHRLLVPGTYNLTALSTGYMPLTiNNIMVKEGP-ATEMDFSL 458
Cdd:cd11308     1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVT-KTVTVPNNFsATVVNFTL 76
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 1211-1285 7.67e-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: 93.36  E-value: 7.67e-23
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501 1211 GVHGLVKDKAGKPISKAVIVLNEG-IKVYTKEGGYFHVLLAPGVHNINAIADGYQQQHTQVFVHHDaASSVVIVFD 1285
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 ...
 495-790 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: 652.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  495 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 574
Cdd:cd03863     1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  575 NLIEYLCKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNNFDLNRNFPDQFVPITEPTQPETIAV 654
Cdd:cd03863    81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  655 MSWVKAYPFVLSANLHGGSLVVNYPYDDNEQGVATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKDMYLNEYFPHGITN 734
Cdd:cd03863   161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501  735 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd03863   241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 930-1207 2.94e-159

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: 2.94e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNAHGKDLDTDFTSNAS------QPETKAIIENLIQK 1083
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1084 qDFSLSIALDGGSVLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNNSDENIPGGVMRGAEWHSHLGSMK 1163
Cdd:cd06245   161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 150378501 1164 DYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSMLVE 1207
Cdd:cd06245   240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 86-377 6.37e-153

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: 463.64  E-value: 6.37e-153
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGLGPPPtaaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd03868    23 KLHSIGKSVQGRELWVLEISDNVNRRE-------------PGKPMFKYVANMHGDETVGRQLLIYLAQYLLENYGK-DER 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCglgdSGPPGTSGRDNSRGRDLNRSFPDQFSTGEPPSLDE-VPEVRALIDWI 244
Cdd:cd03868    89 VTRLVNSTDIHLMPSMNPDGFENSKEGDC----SGDPGYGGRENANNVDLNRNFPDQFEDSDDRLLEGrQPETLAMMKWI 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  245 RRNKFVLSGNLHGGSVVASYPFDDSPEHKTTGLYSKTSDDEVFRYLAKAYASNHPIMKTGEPHCpgdeDETFKDGITNGA 324
Cdd:cd03868   165 VENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDGITNGA 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  325 HWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 377
Cdd:cd03868   241 EWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYME 293
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
508-783 3.36e-99

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 318.86  E-value: 3.36e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   508 MEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTD 587
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   588 PEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSN-----NFDLNRNFPDQF-------VPITEP-------TQ 648
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFPDHWnevgassNPCSETyrgpapfSE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   649 PETIAVMSWV-KAYPFVLSANLHGGSLVVNYPYDDNEQgvatySKSPDDAVFQQIALSYSKENSQMFQGRpckdmylneY 727
Cdd:pfam00246  161 PETRAVADFIrSKKPFVLYISLHSYSQVLLYPYGYTRD-----EPPPDDEELKSLARAAAKALQKMVRGT---------S 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 150378501   728 FPHGITNGASWYNVPGGMQDWNYLQTNC-FEVTIELGCVK----YPFENELPKYWEQNRRS 783
Cdd:pfam00246  227 YTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
502-776 7.74e-94

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 303.49  E-value: 7.74e-94
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    582 KNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRN---NSNNFDLNRNFPDQFVPITEP-----------T 647
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGNPcsetyagpspfS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    648 QPETIAVMSWVKAY-PFVLSANLHGGSLVVNYPYDDNEQGVATYSKSpDDAVFQQIALSYSKENsqmfqgrpckdmylNE 726
Cdd:smart00631  158 EPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALASVH--------------GT 222

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501    727 YFPHGITNGASWYnVPGGMQDWNYLQTN-CFEVTIELGCV-----KYPFENELPKY 776
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
86-371 2.00e-80

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 266.47  E-value: 2.00e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    86 RLFSIGSSVEGRPLWVLRLTAGlgppptaaagldaAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:pfam00246   17 RLVSIGKSVEGRPLKVLKISSG-------------PGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGR-DPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   166 LVRLLNTTDVYLLPSLNPDGFERAREGDcglgdsgPPGTSGRDNSR-----GRDLNRSFPDQF-----------STGEPP 229
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTD-------RLWRKNRSNANgssciGVDLNRNFPDHWnevgassnpcsETYRGP 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   230 SLDEVPEVRALIDWIRR-NKFVLSGNLHGGSVVASYPFDDSPEhkttglySKTSDDEVFRYLAKAYASNHPIMKTGephc 308
Cdd:pfam00246  156 APFSEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAKALQKMVRG---- 224

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501   309 pgdedETFKDGITNGAHWYDVEGGMQDYNYVWANC-FEITLELSCCK----YPPASQLRQEWENNRES 371
Cdd:pfam00246  225 -----TSYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
86-364 3.18e-78

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 259.58  E-value: 3.18e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501     86 RLFSIGSSVEGRPLWVLRLTaglgppptaaagldaaGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:smart00631   23 RLVSIGKSVEGRPIWVLKIS----------------NGGSHDKPAIFIDAGIHAREWIGPATALYLINQLLENYGR-DPR 85

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDsgppGTSGRDNSRGRDLNRSFPDQFS--------TGEPPSLDEVPEV 237
Cdd:smart00631   86 VTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRK----NRSPNSNCRGVDLNRNFPFHWGetgnpcseTYAGPSPFSEPET 161

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    238 RALIDWIRRN-KFVLSGNLHGGSVVASYPFDDSPEHKTTGLyskTSDDEVFRYLAKAYASNHPImktgephcpgdedeTF 316
Cdd:smart00631  162 KAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVAKALAKALASVHGT--------------RY 224

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....
gi 150378501    317 KDGITNGAHWYdVEGGMQDYNYVWAN-CFEITLELSCC-----KYPPASQLRQE 364
Cdd:smart00631  225 TYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
Zn_pept smart00631
Zn_pept domain;
930-1192 1.89e-58

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 202.95  E-value: 1.89e-58
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPnisEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGG---SHDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHT---NAHGKDLDTDFTSN-----------------AS 1069
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHwgetgnpcsetyagpspFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   1070 QPETKAIIENLIQKQDFSLSIALDGGSVLVTYPYDKPVQTV-----ENKETLKHLASLYANNHPSMHMGQPSCpnnsden 1144
Cdd:smart00631  158 EPETKAVRDFIRSNRRFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGTRYTYGISN------- 230

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|....*....
gi 150378501   1145 ipggvmrGAEWHSHlGSMKDYS-VTYGHCPEITVYTSCCYFpSAAQLPA 1192
Cdd:smart00631  231 -------GAIYPAS-GGSDDWAyGVLGIPFSFTLELRDDGR-YGFLLPP 270
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
938-1200 1.28e-50

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 180.96  E-value: 1.28e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   938 EFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKRNPV 1017
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  1018 VTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNA-----HGKDLDTDF--------------------TSNASQPE 1072
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNAngsscIGVDLNRNFpdhwnevgassnpcsetyrgPAPFSEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  1073 TKAIIENLIQKQDFSLSIALDGGSVLVTYPYDKPVQT-VENKETLKHLASLYANNHPSMHMGQpscpnnsdeNIPGGVMR 1151
Cdd:pfam00246  163 TRAVADFIRSKKPFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 150378501  1152 GAEWHSHLGSMKDYSVTYGHCP-EITVYTSCC----YFPSAAQLPALWAENKKS 1200
Cdd:pfam00246  234 GATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
507-745 1.83e-37

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 144.45  E-value: 1.83e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  507 DMEIFLRRFANEyPNITRLYSLGKSVESRELYVMEISDnpgvHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFgt 586
Cdd:COG2866    24 ELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNY-- 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  587 DPEVTDLVRSTRIHLMPSMNPDGYEKSQegdsisvvgRNNSNNFDLNRNFPDQFVpitepTQPETIAVMSWVKAYPFVLS 666
Cdd:COG2866    97 DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWL-----SEPETRALRDLLDEHDPDFV 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  667 ANLHGGSLVVNYPYDDNEQGVATYSKSPDD---AVFQQIALSYSKENSQMFQGRPCKDMYLNEYFPHGITNGASWYNVPG 743
Cdd:COG2866   163 LDLHGQGELFYWFVGTTEPTGSFLAPSYDEereAFAEELNFEGIILAGSAFLGAGAAGTLLISAPRQTFLFAAALDIGGG 242


                  ..
gi 150378501  744 GM 745
Cdd:COG2866   243 GD 244
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 794-869 3.78e-35

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: 128.41  E-value: 3.78e-35
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  794 GVKGFVLDATdGRGILNATLSVAEINHPVTTYKAGDYWRLLVPGTYKITASARGYNPVTKNVTVRSE-GAVQVNFTL 869
Cdd:cd11308     1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
86-390 1.31e-30

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 124.42  E-value: 1.31e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLtaglgppptaaagldaaGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYrrgDPR 165
Cdd:COG2866    40 ELESIGKSVEGRPIYLLKI-----------------GDPAEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNY---DPL 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERARegdcglgdsgppgtsgRDNSRGRDLNRSFPDqfstgepPSLDEvPEVRALIDWIR 245
Cdd:COG2866   100 IRALLDNVTLYIVPMLNPDGAERNT----------------RTNANGVDLNRDWPA-------PWLSE-PETRALRDLLD 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  246 RNKFVLSGNLHGGSVVASYPFDDSPEhktTGLYSKTSDDEVFRYLAKAYASNHPIMKTGephcpGDEDETFKDGITNGAH 325
Cdd:COG2866   156 EHDPDFVLDLHGQGELFYWFVGTTEP---TGSFLAPSYDEEREAFAEELNFEGIILAGS-----AFLGAGAAGTLLISAP 227

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 150378501  326 WYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEKVHIGIKGFVKDS 390
Cdd:COG2866   228 RQTFLFAAALDIGGGGDVSAGELVAGTLLTAGGAGLGLELLVVRGTSALSLVLKLVGAKTAELES 292
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 382-458 1.25e-28

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: 109.92  E-value: 1.25e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501  382 GIKGFVKDSvTGSGLENATISVAGINHNITTGRFGDFHRLLVPGTYNLTALSTGYMPLTiNNIMVKEGP-ATEMDFSL 458
Cdd:cd11308     1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVT-KTVTVPNNFsATVVNFTL 76
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
929-1104 9.65e-24

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 104.39  E-value: 9.65e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  929 RYHSYKDLSEFLRGLVMNYPHITnLTTLGQSVEYRHIWSLEISNKpnisEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1008
Cdd:COG2866    18 RYYTYEELLALLAKLAAASPLVE-LESIGKSVEGRPIYLLKIGDP----AEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1009 CLNYkrNPVVTQLVDRTRIVIVPSLNPDGRERAQEkdctsktghTNAHGKDLDTDF-TSNASQPETKAIIEnLIQKQDFS 1087
Cdd:COG2866    93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNTR---------TNANGVDLNRDWpAPWLSEPETRALRD-LLDEHDPD 160

                         170
                  ....*....|....*..
gi 150378501 1088 LSIALDGGSVLVTYPYD 1104
Cdd:COG2866   161 FVLDLHGQGELFYWFVG 177
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 1211-1285 7.67e-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: 93.36  E-value: 7.67e-23
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501 1211 GVHGLVKDKAGKPISKAVIVLNEG-IKVYTKEGGYFHVLLAPGVHNINAIADGYQQQHTQVFVHHDaASSVVIVFD 1285
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFT 75
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
794-869 8.96e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 67.69  E-value: 8.96e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   794 GVKGFVLDATdGRGILNATLSVA----EINHPVTTYKAGDYW-RLLVPGTYKITASARGYNPVTK-NVTVRSEGAVQVNF 867
Cdd:pfam13620    1 TISGTVTDPS-GAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRtGVTVTAGQTTTLDV 79


                   ..
gi 150378501   868 TL 869
Cdd:pfam13620   80 TL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
382-458 2.95e-13

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 66.15  E-value: 2.95e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   382 GIKGFVKDSvTGSGLENATISVA----GINHNITTGRFGDFH-RLLVPGTYNLTALSTGYMPLTINNIMVKEGPATEMDF 456
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 150378501   457 SL 458
Cdd:pfam13620   80 TL 81
PRK10602 PRK10602
murein tripeptide amidase MpaA;
91-252 2.43e-07

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 53.49  E-value: 2.43e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   91 GSSVEGRPLwvLRLTAglgPPPTAAAGLDAAGpllpgrpqvklvgnMHGDETVSRQVLVYLARELASGYRRgdprlvrll 170
Cdd:PRK10602   21 GRSLLGAPL--LWFPA---PAASRESGLILAG--------------THGDETASVVTLSCALRTLTPSLRR--------- 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  171 ntTDVYLlpSLNPDGferaregdCGLGDsgppgtsgRDNSRGRDLNRSFPDQ---------------------FSTGEPP 229
Cdd:PRK10602   73 --HHVVL--AVNPDG--------CQLGL--------RANANGVDLNRNFPAAnwkegetvyrwnsaaeerdvvLLTGDKP 132

                         170       180
                  ....*....|....*....|....*
gi 150378501  230 SLDevPEVRALIDWIRRNK--FVLS 252
Cdd:PRK10602  133 GSE--PETQALCQLIHRLQpaWVVS 155
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1211-1283 4.78e-05

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 43.04  E-value: 4.78e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  1211 GVHGLVKDKAGKPISKAVIVL-----NEGIKVYTKEGGYFHV-LLAPGVHNINAIADGYQQQH-TQVFVHHDAASSVVIV 1283
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRFpGLPPGTYTVTVSAPGFKTATrTGVTVTAGQTTTLDVT 80
PRK10602 PRK10602
murein tripeptide amidase MpaA;
598-639 2.08e-03

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 41.55  E-value: 2.08e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 150378501  598 RIHLMPSMNPDGyekSQEGDsisvvgRNNSNNFDLNRNFPDQ 639
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 ...
 495-790 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: 652.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  495 IQPKDFHHHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 574
Cdd:cd03863     1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  575 NLIEYLCKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNNFDLNRNFPDQFVPITEPTQPETIAV 654
Cdd:cd03863    81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  655 MSWVKAYPFVLSANLHGGSLVVNYPYDDNEQGVATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKDMYLNEYFPHGITN 734
Cdd:cd03863   161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501  735 GASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
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 ...
 502-790 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: 559.58  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  582 KNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNNFDLNRNFPDQFVPI---TEPTQPETIAVMSWV 658
Cdd:cd03858    81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVysdNNPRQPETKAVMNWL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  659 KAYPFVLSANLHGGSLVVNYPYDDNEQGVAT-YSKSPDDAVFQQIALSYSKENSQMFQGRPCKDmYLNEYFPHGITNGAS 737
Cdd:cd03858   161 ESIPFVLSANLHGGALVANYPYDDTRSGKSTeYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGAA 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  738 WYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd03858   240 WYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 930-1207 2.94e-159

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: 2.94e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNAHGKDLDTDFTSNAS------QPETKAIIENLIQK 1083
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANnrsgaaQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1084 qDFSLSIALDGGSVLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNNSDENIPGGVMRGAEWHSHLGSMK 1163
Cdd:cd06245   161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 150378501 1164 DYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSMLVE 1207
Cdd:cd06245   240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 86-377 6.37e-153

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: 463.64  E-value: 6.37e-153
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGLGPPPtaaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd03868    23 KLHSIGKSVQGRELWVLEISDNVNRRE-------------PGKPMFKYVANMHGDETVGRQLLIYLAQYLLENYGK-DER 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCglgdSGPPGTSGRDNSRGRDLNRSFPDQFSTGEPPSLDE-VPEVRALIDWI 244
Cdd:cd03868    89 VTRLVNSTDIHLMPSMNPDGFENSKEGDC----SGDPGYGGRENANNVDLNRNFPDQFEDSDDRLLEGrQPETLAMMKWI 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  245 RRNKFVLSGNLHGGSVVASYPFDDSPEHKTTGLYSKTSDDEVFRYLAKAYASNHPIMKTGEPHCpgdeDETFKDGITNGA 324
Cdd:cd03868   165 VENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDGITNGA 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  325 HWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 377
Cdd:cd03868   241 EWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYME 293
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 500-790 1.05e-150

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The first carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain I. CPD differs from all other metallocarboxypeptidases in that it contains multiple CP-like domains. CPD belongs to the N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs).The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPD is a single-chain protein containing a signal peptide, three tandem repeats of CP-like domains separated by short bridge regions, followed by a transmembrane domain, and a C-terminal cytosolic tail. The first two CP-like domains of CPD contain all of the essential active site and substrate-binding residues, the third CP-like domain lacks critical residues necessary for enzymatic activity and is inactive towards standard CP substrates. Domain I is optimally active at pH 6.3-7.5 and prefers substrates with C-terminal Arg, whereas domain II is active at pH 5.0-6.5 and prefers substrates with C-terminal Lys. This Domain I family contains two contiguous surface cysteines that may become palmitoylated and target the enzyme to membranes, thus regulating intracellular trafficking. CPD functions in the processing of proteins that transit the secretory pathway, and is present in all vertebrates as well as Drosophila. It is broadly distributed in all tissue types. Within cells, CPD is present in the trans Golgi network and immature secretory vesicles, but is excluded from mature vesicles. It is thought to play a role in the processing of proteins that are initially processed by furin or related endopeptidases present in the trans Golgi network, such as growth factors and receptors. CPD is implicated in the pathogenesis of lupus erythematosus (LE), it is regulated by TGF-beta in various cell types of murine and human origin and is significantly down-regulated in CD14 positive cells isolated from patients with LE. As down-regulation of CPD leads to down-modulation of TGF-beta, CPD may have a role in a positive feedback loop. In D. melanogaster, the CPD variant 1B short (DmCPD1Bs) is necessary and sufficient for viability of the fruit fly.


Pssm-ID: 349440  Cd Length: 294  Bit Score: 457.48  E-value: 1.05e-150
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  500 FHHHHfpDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 579
Cdd:cd03868     1 YHNYD--ELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  580 LCKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGD---SISVVGRNNSNNFDLNRNFPDQFV----PITEPTQPETI 652
Cdd:cd03868    79 LLENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDcsgDPGYGGRENANNVDLNRNFPDQFEdsddRLLEGRQPETL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  653 AVMSWVKAYPFVLSANLHGGSLVVNYPYDD----NEQGVatYSKSPDDAVFQQIALSYSKENSQMFQGRPCkdmyLNEYF 728
Cdd:cd03868   159 AMMKWIVENPFVLSANLHGGSVVASYPFDDspshIECGV--YSKSPDDAVFRHLAHTYADNHPTMHKGNNC----CEDSF 232

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 150378501  729 PHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
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 ...
 86-378 2.16e-125

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: 390.09  E-value: 2.16e-125
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTaglgppptaaaglDAAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd03858    23 RLYSIGKSVEGRELWVLEIS-------------DNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLCENYGK-DPR 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGlgdsgppGTSGRDNSRGRDLNRSFPDQFSTGEPPSLDEVPEVRALIDWIR 245
Cdd:cd03858    89 VTQLVNSTRIHIMPSMNPDGYEKAQEGDCG-------GLIGRNNANGVDLNRNFPDQFFQVYSDNNPRQPETKAVMNWLE 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  246 RNKFVLSGNLHGGSVVASYPFDDSPEHKTTgLYSKTSDDEVFRYLAKAYASNHPIMKTGEPHCPgDEDETFKDGITNGAH 325
Cdd:cd03858   162 SIPFVLSANLHGGALVANYPYDDTRSGKST-EYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGAA 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  326 WYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 378
Cdd:cd03858   240 WYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
 930-1207 1.97e-124

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: 387.78  E-value: 1.97e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03858     1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNAHGKDLDTDFTSNAS---------QPETKAIIENL 1080
Cdd:cd03858    81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFqvysdnnprQPETKAVMNWL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1081 IQKqDFSLSIALDGGSVLVTYPYDKP-------VQTVENKETLKHLASLYANNHPSMHMGQPSCPNNsDENIPGGVMRGA 1153
Cdd:cd03858   161 ESI-PFVLSANLHGGALVANYPYDDTrsgksteYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCCDD-DENFPNGITNGA 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 150378501 1154 EWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSMLVE 1207
Cdd:cd03858   239 AWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 502-790 1.17e-120

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: 377.60  E-value: 1.17e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:cd03866     1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  582 KNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNNFDLNRNFPDQFVPITEPTQPETIAVMSWVKAY 661
Cdd:cd03866    81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEENNVQRQPETRAVMDWIKNE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  662 PFVLSANLHGGSLVVNYPYDDNEQGVAT---YSKSPDDAVFQQIALSYSKENSQMFQGRPCKDMylnEYFPHGITNGASW 738
Cdd:cd03866   161 TFVLSANLHGGALVASYPFDNGNSGTGQlgyYSVSPDDDVFIYLAKTYSYNHTNMYKGIECSNS---QSFPGGITNGYQW 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 150378501  739 YNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd03866   238 YPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 503-790 7.20e-115

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: 361.51  E-value: 7.20e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  503 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 582
Cdd:cd18173     5 PTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA-EPEFKYTSTMHGDETTGYELMLRLIDYLLT 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  583 NFGTDPEVTDLVRSTRIHLMPSMNPDGYeksQEGDSISVVG--RNNSNNFDLNRNFPDQFV---PITEPTQPETIAVMSW 657
Cdd:cd18173    84 NYGTDPRITNLVDNTEIWINPLANPDGT---YAGGNNTVSGatRYNANGVDLNRNFPDPVDgdhPDGNGWQPETQAMMNF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  658 VKAYPFVLSANLHGGSLVVNYPYDdneqgvATYSKSPDDAVFQQIALSYSKENSQmfqgrPCKDMYLNEyFPHGITNGAS 737
Cdd:cd18173   161 ADEHNFVLSANFHGGAEVVNYPWD------TWYSRHPDDDWFQDISREYADTNQA-----NSPPMYMSE-FNNGITNGYD 228

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  738 WYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd18173   229 WYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 502-790 1.18e-114

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: 362.33  E-value: 1.18e-114
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:cd03864     1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  582 KNFGTDPE-VTDLVRSTRIHLMPSMNPDGYE-KSQEGDSIS--VVGRNNSNNFDLNRNFPD---------------QFVP 642
Cdd:cd03864    81 EEYRNGNErITRLIQDTRIHILPSMNPDGYEvAARQGPEFNgyLVGRNNANGVDLNRNFPDlntlmyynekyggpnHHLP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  643 ITE----PTQPETIAVMSWVKAYPFVLSANLHGGSLVVNYPYDDNEQ------GVATYSKSPDDAVFQQIALSYSKENSQ 712
Cdd:cd03864   161 LPDnwksQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREprvrgfRRTAYSPTPDDKLFQKLAKTYSYAHGW 240

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501  713 MFQGRPCKDmylneYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd03864   241 MHKGWNCGD-----YFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 502-790 6.94e-111

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: 352.36  E-value: 6.94e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:cd03865     1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  582 KNFGTDPE-VTDLVRSTRIHLMPSMNPDGYEKS-QEGDSIS--VVGRNNSNNFDLNRNFPD--QFVPITE---------- 645
Cdd:cd03865    81 NEYQKGNEtIINLIHSTRIHIMPSLNPDGFEKAaSQPGELKdwFVGRSNAQGIDLNRNFPDldRIVYVNEkeggpnnhll 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  646 -----------PTQPETIAVMSWVKAYPFVLSANLHGGSLVVNYPYDDNEQGVA-TYSKSPDDAVFQQIALSYSKENSQM 713
Cdd:cd03865   161 knmkkavdqntKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAhEYSSCPDDAIFQSLARAYSSLNPAM 240

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 150378501  714 FQG--RPCKDMYLNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd03865   241 SDPnrPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 502-790 9.53e-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: 329.87  E-value: 9.53e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:cd03869     1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  582 KNF-GTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISV---VGRNNSNNFDLNRNFPD------------------- 638
Cdd:cd03869    81 QEYlAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGgwsLGRWTSDGIDINHNFPDlnsllweaedrkwvprkvp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  639 -QFVPITE-------PTQPETIAVMSWVKAYPFVLSANLHGGSLVVNYPYDDNEQGVAT--YSKSPDDAVFQQIALSYSK 708
Cdd:cd03869   161 nHHIPIPEwylsenaTVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTqeYTPTPDDHVFRWLAYSYAS 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  709 ENSQMFQG--RPCKDMYLNEYfpHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQ 786
Cdd:cd03869   241 THRLMTDAsrRPCHTEDFQKE--DGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLV 318


                  ....
gi 150378501  787 FMKQ 790
Cdd:cd03869   319 FMEQ 322
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
508-783 3.36e-99

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 318.86  E-value: 3.36e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   508 MEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTD 587
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   588 PEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSN-----NFDLNRNFPDQF-------VPITEP-------TQ 648
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANgssciGVDLNRNFPDHWnevgassNPCSETyrgpapfSE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   649 PETIAVMSWV-KAYPFVLSANLHGGSLVVNYPYDDNEQgvatySKSPDDAVFQQIALSYSKENSQMFQGRpckdmylneY 727
Cdd:pfam00246  161 PETRAVADFIrSKKPFVLYISLHSYSQVLLYPYGYTRD-----EPPPDDEELKSLARAAAKALQKMVRGT---------S 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 150378501   728 FPHGITNGASWYNVPGGMQDWNYLQTNC-FEVTIELGCVK----YPFENELPKYWEQNRRS 783
Cdd:pfam00246  227 YTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 87-378 5.37e-99

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: 318.28  E-value: 5.37e-99
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   87 LFSIGSSVEGRPLWVLrltaGLGPPPTAAagldaagplLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPRL 166
Cdd:cd03866    24 LHSIGKSVEGRDLWVL----VLGRFPTKH---------RIGIPEFKYVANMHGDEVVGRELLLHLIEFLVTSYGS-DPVI 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  167 VRLLNTTDVYLLPSLNPDGFERAREGDCGlgdsgppGTSGRDNSRGRDLNRSFPDQFSTGEPPSLdevPEVRALIDWIRR 246
Cdd:cd03866    90 TRLINSTRIHIMPSMNPDGFEATKKPDCY-------YTKGRYNKNGYDLNRNFPDAFEENNVQRQ---PETRAVMDWIKN 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  247 NKFVLSGNLHGGSVVASYPFDDS-PEHKTTGLYSKTSDDEVFRYLAKAYASNHPIMKTGEpHCPgdEDETFKDGITNGAH 325
Cdd:cd03866   160 ETFVLSANLHGGALVASYPFDNGnSGTGQLGYYSVSPDDDVFIYLAKTYSYNHTNMYKGI-ECS--NSQSFPGGITNGYQ 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  326 WYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 378
Cdd:cd03866   237 WYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 522-786 2.80e-96

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


Pssm-ID: 349482 [Multi-domain]  Cd Length: 276  Bit Score: 310.50  E-value: 2.80e-96
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  522 ITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNF-GTDPEVTDLVRSTRIH 600
Cdd:cd18172    21 ISRLIVIGSSVNGFPLWALEISDGPGEDET-EPAFKFVGNMHGDEPVGRELLLRLADWLCANYkAKDPLAAKIVENAHLH 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  601 LMPSMNPDGYEKSQegdsisvvgRNNSNNFDLNRNFPDQFVPITEPT-----QPETIAVMSWVKAYPFVLSANLHGGSLV 675
Cdd:cd18172   100 LVPTMNPDGFARRR---------RNNANNVDLNRDFPDQFFPKNLRNdlaarQPETLAVMNWSRSVRFTASANLHEGALV 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  676 VNYPYDDNEQGVATYSKSPDDAVFQQIALSYSKENsqmfqgrpcKDMYLNEYFPHGITNGASWYNVPGGMQDWNYLQTNC 755
Cdd:cd18172   171 ANYPWDGNADGRTKYSASPDDATFRRLASVYAQAH---------PNMAKSKEFPGGITNGAQWYPLYGGMQDWNYLHTGC 241

                         250       260       270
                  ....*....|....*....|....*....|.
gi 150378501  756 FEVTIELGCVKYPFENELPKYWEQNRRSLIQ 786
Cdd:cd18172   242 MDLTLEVNDNKWPPEDRLVQIWAEHRKAMLA 272
Zn_pept smart00631
Zn_pept domain;
502-776 7.74e-94

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 303.49  E-value: 7.74e-94
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    582 KNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRN---NSNNFDLNRNFPDQFVPITEP-----------T 647
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGNPcsetyagpspfS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    648 QPETIAVMSWVKAY-PFVLSANLHGGSLVVNYPYDDNEQGVATYSKSpDDAVFQQIALSYSKENsqmfqgrpckdmylNE 726
Cdd:smart00631  158 EPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALASVH--------------GT 222

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501    727 YFPHGITNGASWYnVPGGMQDWNYLQTN-CFEVTIELGCV-----KYPFENELPKY 776
Cdd:smart00631  223 RYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 502-789 4.96e-93

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: 302.96  E-value: 4.96e-93
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:cd03867     1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  582 KNF-GTDPEVTDLVRSTRIHLMPSMNPDGYEKSQE---GDSISVVGRNNSNNFDLNRNFPD----------------QFV 641
Cdd:cd03867    81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEegaGYNGWTSGRQNAQNLDLNRNFPDltseayrlartrgarlDHI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  642 PITE-----PTQPETIAVMSWVKAYPFVLSANLHGGSLVVNYPYD--DNEQGVATYSKSPDDAVFQQIALSYSKENSQMF 714
Cdd:cd03867   161 PIPQsywwgKVAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDfsKHPLEEKMFSPTPDEKMFKLLAKAYADAHPMMS 240

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  715 --QGRPCKDMYLNEyfpHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMK 789
Cdd:cd03867   241 drSENRCGGNFLKR---GGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 86-377 1.28e-86

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


Pssm-ID: 349482 [Multi-domain]  Cd Length: 276  Bit Score: 283.53  E-value: 1.28e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGLGPPPTaaagldaagpllpgRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDPR 165
Cdd:cd18172    23 RLIVIGSSVNGFPLWALEISDGPGEDET--------------EPAFKFVGNMHGDEPVGRELLLRLADWLCANYKAKDPL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERARegdcglgdsgppgtsgRDNSRGRDLNRSFPDQFST-GEPPSLD-EVPEVRALIDW 243
Cdd:cd18172    89 AAKIVENAHLHLVPTMNPDGFARRR----------------RNNANNVDLNRDFPDQFFPkNLRNDLAaRQPETLAVMNW 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  244 IRRNKFVLSGNLHGGSVVASYPFDDSPEHKTTglYSKTSDDEVFRYLAKAYASNHPIMKtgephcpgdEDETFKDGITNG 323
Cdd:cd18172   153 SRSVRFTASANLHEGALVANYPWDGNADGRTK--YSASPDDATFRRLASVYAQAHPNMA---------KSKEFPGGITNG 221

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 150378501  324 AHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 377
Cdd:cd18172   222 AQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALAA 275
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 86-378 1.79e-84

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The second carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain II. CPD differs from all other metallocarboxypeptidases in that it contains multiple CP-like domains. CPD belongs to the N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs).The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPD is a single-chain protein containing a signal peptide, three tandem repeats of CP-like domains separated by short bridge regions, followed by a transmembrane domain, and a C-terminal cytosolic tail. The first two CP-like domains of CPD contain all of the essential active site and substrate-binding residues, while the third CP-like domain lacks critical residues necessary for enzymatic activity and is inactive towards standard CP substrates. Domain I is optimally active at pH 6.3-7.5 and prefers substrates with C-terminal Arg, whereas domain II is active at pH 5.0-6.5 and prefers substrates with C-terminal Lys. CPD functions in the processing of proteins that transit the secretory pathway, and is present in all vertebrates as well as Drosophila. It is broadly distributed in all tissue types. Within cells, CPD is present in the trans-Golgi network and immature secretory vesicles, but is excluded from mature vesicles. It is thought to play a role in the processing of proteins that are initially processed by furin or related endopeptidases present in the trans-Golgi network, such as growth factors and receptors. CPD is implicated in the pathogenesis of lupus erythematosus (LE), it is regulated by TGF-beta in various cell types of murine and human origin and is significantly down-regulated in CD14 positive cells isolated from patients with LE. As down -regulation of CPD leads to down-modulation of TGF-beta, CPD may have a role in a positive feedback loop.


Pssm-ID: 349435 [Multi-domain]  Cd Length: 296  Bit Score: 278.37  E-value: 1.79e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTaglgppptaaaglDAAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd03863    30 RLYSVGKSVELRELYVMEIS-------------DNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGT-DPE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGlgdsgppGTSGRDNSRGRDLNRSFPDQF-STGEPPSldevPEVRALIDWI 244
Cdd:cd03863    96 VTDLVQNTRIHIMPSMNPDGYEKSQEGDRG-------GTVGRNNSNNYDLNRNFPDQFfQITDPPQ----PETLAVMSWL 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  245 RRNKFVLSGNLHGGSVVASYPFDDSPEHKTTglYSKTSDDEVFRYLAKAYASNHPIMKTGEPHCPGDEDETFKDGITNGA 324
Cdd:cd03863   165 KTYPFVLSANLHGGSLVVNYPFDDDEQGLAT--YSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITNGA 242

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 150378501  325 HWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 378
Cdd:cd03863   243 QWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 86-378 2.35e-83

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: 275.66  E-value: 2.35e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTaglgppptaaaglDAAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDPR 165
Cdd:cd03864    23 RIYSIGRSVEGRHLYVLEFS-------------DNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLCEEYRNGNER 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAregdcglGDSGP--PG-TSGRDNSRGRDLNRSFPDQFST-------GEP----PSL 231
Cdd:cd03864    90 ITRLIQDTRIHILPSMNPDGYEVA-------ARQGPefNGyLVGRNNANGVDLNRNFPDLNTLmyynekyGGPnhhlPLP 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  232 DE-----VPEVRALIDWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKTTGL----YSKTSDDEVFRYLAKAYASNHPIMK 302
Cdd:cd03864   163 DNwksqvEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREPRVRGFrrtaYSPTPDDKLFQKLAKTYSYAHGWMH 242

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501  303 TGEpHCpGDedeTFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 378
Cdd:cd03864   243 KGW-NC-GD---YFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 86-378 3.99e-83

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


Pssm-ID: 349437 [Multi-domain]  Cd Length: 319  Bit Score: 275.32  E-value: 3.99e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTaglgppptaaaglDAAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDPR 165
Cdd:cd03865    23 RIYTVGRSFEGRELLVIEVS-------------DNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLCNEYQKGNET 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDsgppGTSGRDNSRGRDLNRSFPD----------------------QF 223
Cdd:cd03865    90 IINLIHSTRIHIMPSLNPDGFEKAASQPGELKD----WFVGRSNAQGIDLNRNFPDldrivyvnekeggpnnhllknmKK 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  224 STGEPPSLdeVPEVRALIDWIRRNKFVLSGNLHGGSVVASYPFDDSpEHKTTGLYSKTSDDEVFRYLAKAYASNHPIMK- 302
Cdd:cd03865   166 AVDQNTKL--APETKAVIHWIMDIPFVLSANLHGGDLVANYPYDET-RSGSAHEYSSCPDDAIFQSLARAYSSLNPAMSd 242

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  303 TGEPHC-PGDEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 378
Cdd:cd03865   243 PNRPPCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
86-371 2.00e-80

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 266.47  E-value: 2.00e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    86 RLFSIGSSVEGRPLWVLRLTAGlgppptaaagldaAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:pfam00246   17 RLVSIGKSVEGRPLKVLKISSG-------------PGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGR-DPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   166 LVRLLNTTDVYLLPSLNPDGFERAREGDcglgdsgPPGTSGRDNSR-----GRDLNRSFPDQF-----------STGEPP 229
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTD-------RLWRKNRSNANgssciGVDLNRNFPDHWnevgassnpcsETYRGP 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   230 SLDEVPEVRALIDWIRR-NKFVLSGNLHGGSVVASYPFDDSPEhkttglySKTSDDEVFRYLAKAYASNHPIMKTGephc 308
Cdd:pfam00246  156 APFSEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAKALQKMVRG---- 224

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501   309 pgdedETFKDGITNGAHWYDVEGGMQDYNYVWANC-FEITLELSCCK----YPPASQLRQEWENNRES 371
Cdd:pfam00246  225 -----TSYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 502-790 6.79e-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: 264.69  E-value: 6.79e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 581
Cdd:cd06245     1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  582 KNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNNFDLNRNFPDQFVPITEPTQPETIAVMSWVKAY 661
Cdd:cd06245    81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANNRSGAAQPETKAIMDWLKEK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  662 PFVLSANLHGGSLVVNYPYDDNEQGVAtyskspDDAVFQQIALSYSKENSQMFQGRPCKDMYLNEYFPHGITNGASWYNV 741
Cdd:cd06245   161 DFTLSVALDGGSLVVTYPYDKPVQTVE------NKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSH 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 150378501  742 PGGMQDWNYLQTNCFEVTIELGCVKYPFENELPKYWEQNRRSLIQFMKQ 790
Cdd:cd06245   235 KGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
Zn_pept smart00631
Zn_pept domain;
86-364 3.18e-78

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 259.58  E-value: 3.18e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501     86 RLFSIGSSVEGRPLWVLRLTaglgppptaaagldaaGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:smart00631   23 RLVSIGKSVEGRPIWVLKIS----------------NGGSHDKPAIFIDAGIHAREWIGPATALYLINQLLENYGR-DPR 85

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDsgppGTSGRDNSRGRDLNRSFPDQFS--------TGEPPSLDEVPEV 237
Cdd:smart00631   86 VTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRK----NRSPNSNCRGVDLNRNFPFHWGetgnpcseTYAGPSPFSEPET 161

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    238 RALIDWIRRN-KFVLSGNLHGGSVVASYPFDDSPEHKTTGLyskTSDDEVFRYLAKAYASNHPImktgephcpgdedeTF 316
Cdd:smart00631  162 KAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVAKALAKALASVHGT--------------RY 224

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....
gi 150378501    317 KDGITNGAHWYdVEGGMQDYNYVWAN-CFEITLELSCC-----KYPPASQLRQE 364
Cdd:smart00631  225 TYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
 930-1203 1.67e-77

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: 258.33  E-value: 1.67e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03868     1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTS---KTGHTNAHGKDLDTDF----------TSNASQPETKAI 1076
Cdd:cd03868    81 ENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGdpgYGGRENANNVDLNRNFpdqfedsddrLLEGRQPETLAM 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1077 IeNLIQKQDFSLSIALDGGSVLVTYPYDKPVQTVENK--------ETLKHLASLYANNHPSMHMGQPSCpnnsDENIPGG 1148
Cdd:cd03868   161 M-KWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGvyskspddAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDG 235

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 150378501 1149 VMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLS 1203
Cdd:cd03868   236 ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLS 290
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 86-377 3.10e-75

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


Pssm-ID: 349483 [Multi-domain]  Cd Length: 281  Bit Score: 251.34  E-value: 3.10e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGlgpPPTAAAgldaagpllpgRPQVKLVGNMHGDETVSRQVLVYLARELASGYRrGDPR 165
Cdd:cd18173    26 RLVSIGTSVQGRKLLALKISDN---VNTEEA-----------EPEFKYTSTMHGDETTGYELMLRLIDYLLTNYG-TDPR 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAregdcglGDSGPPGTSgRDNSRGRDLNRSFPDQFSTGEPPSLDEVPEVRALIDWIR 245
Cdd:cd18173    91 ITNLVDNTEIWINPLANPDGTYAG-------GNNTVSGAT-RYNANGVDLNRNFPDPVDGDHPDGNGWQPETQAMMNFAD 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  246 RNKFVLSGNLHGGSVVASYPFDdspehkTTglYSKTSDDEVFRYLAKAYASnhpimkTGEPHCPGDEDETFKDGITNGAH 325
Cdd:cd18173   163 EHNFVLSANFHGGAEVVNYPWD------TW--YSRHPDDDWFQDISREYAD------TNQANSPPMYMSEFNNGITNGYD 228

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 150378501  326 WYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 377
Cdd:cd18173   229 WYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIE 280
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 86-377 3.83e-75

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: 252.50  E-value: 3.83e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTaglgppptaaaglDAAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDPR 165
Cdd:cd03867    23 RTYSIGRSFEGKDLLVIEFS-------------SNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLCSEYLLGNPR 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDSgppgTSGRDNSRGRDLNRSFPD----QFSTGEPPS--LDEV----- 234
Cdd:cd03867    90 IQTLINTTRIHLLPSMNPDGYEVAAEEGAGYNGW----TSGRQNAQNLDLNRNFPDltseAYRLARTRGarLDHIpipqs 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  235 -------PEVRALIDWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKTTGLYSKTSDDEVFRYLAKAYASNHPIMKTGEPH 307
Cdd:cd03867   166 ywwgkvaPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMFSPTPDEKMFKLLAKAYADAHPMMSDRSEN 245

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  308 CPGDEDETfKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIE 377
Cdd:cd03867   246 RCGGNFLK-RGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 86-378 6.14e-68

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


Pssm-ID: 349441  Cd Length: 322  Bit Score: 232.03  E-value: 6.14e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTaglgppptaaaglDAAGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDPR 165
Cdd:cd03869    23 RIYNIGKSYQGLKLYAMEIS-------------DNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLCQEYLAGNPR 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDsgppGTSGRDNSRGRDLNRSFPD--------QFSTGEP--------- 228
Cdd:cd03869    90 IRHLVEETRIHLLPSVNPDGYEKAYEAGSELGG----WSLGRWTSDGIDINHNFPDlnsllweaEDRKWVPrkvpnhhip 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  229 -------PSLDEVPEVRALIDWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKTTGLYSKTSDDEVFRYLAKAYASNHPIM 301
Cdd:cd03869   166 ipewylsENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYASTHRLM 245

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  302 KTGEPHCPGDEDETFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEK 378
Cdd:cd03869   246 TDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFMEQ 322
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
 86-376 4.41e-65

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: 222.32  E-value: 4.41e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLtaGLGPPPTAaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd06245    23 NLTSLGQSVEKRDIWVLEI--GNKPNESE-----------PSEPKILFVGGIHGNAPVGTELLLLLAHFLCHNYKK-DSA 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDCGlgdsgppGTSGRDNSRGRDLNRSFPDQFStgEPPSLDEvPEVRALIDWIR 245
Cdd:cd06245    89 ITKLLNRTRIHIVPSLNPDGAEKAEEKKCT-------SKIGEKNANGVDLDTDFESNAN--NRSGAAQ-PETKAIMDWLK 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  246 RNKFVLSGNLHGGSVVASYPFDDspehkttgLYSKTSDDEVFRYLAKAYASNHPIMKTGEPHCPGDEDETFKDGITNGAH 325
Cdd:cd06245   159 EKDFTLSVALDGGSLVVTYPYDK--------PVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASE 230

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 150378501  326 WYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLI 376
Cdd:cd06245   231 WHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMI 281
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
 928-1205 4.96e-61

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The second carboxypeptidase (CP)-like domain of Carboxypeptidase D (CPD; EC 3.4.17.22), domain II. CPD differs from all other metallocarboxypeptidases in that it contains multiple CP-like domains. CPD belongs to the N/E-like subfamily of the M14 family of metallocarboxypeptidases (MCPs).The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPD is a single-chain protein containing a signal peptide, three tandem repeats of CP-like domains separated by short bridge regions, followed by a transmembrane domain, and a C-terminal cytosolic tail. The first two CP-like domains of CPD contain all of the essential active site and substrate-binding residues, while the third CP-like domain lacks critical residues necessary for enzymatic activity and is inactive towards standard CP substrates. Domain I is optimally active at pH 6.3-7.5 and prefers substrates with C-terminal Arg, whereas domain II is active at pH 5.0-6.5 and prefers substrates with C-terminal Lys. CPD functions in the processing of proteins that transit the secretory pathway, and is present in all vertebrates as well as Drosophila. It is broadly distributed in all tissue types. Within cells, CPD is present in the trans-Golgi network and immature secretory vesicles, but is excluded from mature vesicles. It is thought to play a role in the processing of proteins that are initially processed by furin or related endopeptidases present in the trans-Golgi network, such as growth factors and receptors. CPD is implicated in the pathogenesis of lupus erythematosus (LE), it is regulated by TGF-beta in various cell types of murine and human origin and is significantly down-regulated in CD14 positive cells isolated from patients with LE. As down -regulation of CPD leads to down-modulation of TGF-beta, CPD may have a role in a positive feedback loop.


Pssm-ID: 349435 [Multi-domain]  Cd Length: 296  Bit Score: 211.34  E-value: 4.96e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  928 YRYHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEF 1007
Cdd:cd03863     6 FRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1008 LCLNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNAHGKDLDTDF------TSNASQPETKAIIeNLI 1081
Cdd:cd03863    86 LCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFpdqffqITDPPQPETLAVM-SWL 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1082 QKQDFSLSIALDGGSVLVTYPYDKPVQTV------ENKETLKHLASLYANNHPSMHMGQPSCPNNSDENIPGGVMRGAEW 1155
Cdd:cd03863   165 KTYPFVLSANLHGGSLVVNYPFDDDEQGLatysksPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITNGAQW 244

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 150378501 1156 HSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSML 1205
Cdd:cd03863   245 YNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFI 294
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
 930-1205 6.30e-61

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: 210.81  E-value: 6.30e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03866     1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNAHGKDLDTDF------TSNASQPETKAIIeNLIQK 1083
Cdd:cd03866    81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFpdafeeNNVQRQPETRAVM-DWIKN 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1084 QDFSLSIALDGGSVLVTYPYDKPVQTVE---------NKETLKHLASLYANNHPSMHMGQpSCPNNsdENIPGGVMRGAE 1154
Cdd:cd03866   160 ETFVLSANLHGGALVASYPFDNGNSGTGqlgyysvspDDDVFIYLAKTYSYNHTNMYKGI-ECSNS--QSFPGGITNGYQ 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 150378501 1155 WHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSML 1205
Cdd:cd03866   237 WYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYI 287
Zn_pept smart00631
Zn_pept domain;
930-1192 1.89e-58

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 202.95  E-value: 1.89e-58
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501    930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPnisEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGG---SHDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHT---NAHGKDLDTDFTSN-----------------AS 1069
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHwgetgnpcsetyagpspFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   1070 QPETKAIIENLIQKQDFSLSIALDGGSVLVTYPYDKPVQTV-----ENKETLKHLASLYANNHPSMHMGQPSCpnnsden 1144
Cdd:smart00631  158 EPETKAVRDFIRSNRRFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGTRYTYGISN------- 230

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|....*....
gi 150378501   1145 ipggvmrGAEWHSHlGSMKDYS-VTYGHCPEITVYTSCCYFpSAAQLPA 1192
Cdd:smart00631  231 -------GAIYPAS-GGSDDWAyGVLGIPFSFTLELRDDGR-YGFLLPP 270
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 503-784 1.56e-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: 183.61  E-value: 1.56e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  503 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVhEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 582
Cdd:cd03859     5 HTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLLE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  583 NFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRN---NSNNF------DLNRNFPDQF---------VPIT 644
Cdd:cd03859    84 NYGTDPRITNLVDNREIWIIPVVNPDGYEYNRETGGGRLWRKNrrpNNGNNpgsdgvDLNRNYGYHWggdnggsspDPSS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  645 E----PTQ---PETIAVMSWVKAYPFVLSANLHGGSLVVNYPYddneqGVATYSKSPDDAVFQQIALSYSKENsqmfqgr 717
Cdd:cd03859   164 EtyrgPAPfsePETQAIRDLVESHDFKVAISYHSYGELVLYPW-----GYTSDAPTPDEDVFEELAEEMASYN------- 231

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 150378501  718 pckdmylneyfPHGITNGASW--YNVPGGMQDWNYLQTNCFEVTIELGCVKYPF---ENELPKYWEQNRRSL 784
Cdd:cd03859   232 -----------GGGYTPQQSSdlYPTNGDTDDWMYGEKGIIAFTPELGPEFYPFyppPSQIDPLAEENLPAA 292
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
 929-1205 2.01e-51

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: 183.16  E-value: 2.01e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  929 RYHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEePKIRFVAGIHGNAPVGTELLLALAEFL 1008
Cdd:cd18173     3 SYPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEAE-PEFKYTSTMHGDETTGYELMLRLIDYL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1009 CLNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAqekDCTSKTGHT--NAHGKDLDTDF---------TSNASQPETKAII 1077
Cdd:cd18173    82 LTNYGTDPRITNLVDNTEIWINPLANPDGTYAG---GNNTVSGATryNANGVDLNRNFpdpvdgdhpDGNGWQPETQAMM 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1078 eNLIQKQDFSLSIALDGGSVLVTYPYDKPVQTVENKETLKHLASLYA----NNHPSMHMGQpscpnnsdenIPGGVMRGA 1153
Cdd:cd18173   159 -NFADEHNFVLSANFHGGAEVVNYPWDTWYSRHPDDDWFQDISREYAdtnqANSPPMYMSE----------FNNGITNGY 227

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 150378501 1154 EWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSML 1205
Cdd:cd18173   228 DWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYI 279
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
938-1200 1.28e-50

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 180.96  E-value: 1.28e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   938 EFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKRNPV 1017
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  1018 VTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHTNA-----HGKDLDTDF--------------------TSNASQPE 1072
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNAngsscIGVDLNRNFpdhwnevgassnpcsetyrgPAPFSEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  1073 TKAIIENLIQKQDFSLSIALDGGSVLVTYPYDKPVQT-VENKETLKHLASLYANNHPSMHMGQpscpnnsdeNIPGGVMR 1151
Cdd:pfam00246  163 TRAVADFIRSKKPFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRGT---------SYTYGITN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 150378501  1152 GAEWHSHLGSMKDYSVTYGHCP-EITVYTSCC----YFPSAAQLPALWAENKKS 1200
Cdd:pfam00246  234 GATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
 930-1205 4.36e-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: 179.15  E-value: 4.36e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEePKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd18172     1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDETE-PAFKFVGNMHGDEPVGRELLLRLADWLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRN-PVVTQLVDRTRIVIVPSLNPDGRERAQEKdctsktghtNAHGKDLDTDF-----------TSNASQPETKAII 1077
Cdd:cd18172    80 ANYKAKdPLAAKIVENAHLHLVPTMNPDGFARRRRN---------NANNVDLNRDFpdqffpknlrnDLAARQPETLAVM 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1078 eNLIQKQDFSLSIALDGGSVLVTYPYD------KPVQTVENKETLKHLASLYANNHPSMHmgqpscpnNSDEnIPGGVMR 1151
Cdd:cd18172   151 -NWSRSVRFTASANLHEGALVANYPWDgnadgrTKYSASPDDATFRRLASVYAQAHPNMA--------KSKE-FPGGITN 220

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 150378501 1152 GAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSML 1205
Cdd:cd18172   221 GAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALA 274
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 558-784 1.01e-47

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: 169.95  E-value: 1.01e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  558 YIGNMHGNEVVGRELLLNLIEYLCKNFGTDPeVTDLVRSTRIHLMPSMNPDGYEKSQEgdsisVVGRNNSNNFDLNRNFP 637
Cdd:cd00596     3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVID-----SGGRKNANGVDLNRNFP 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  638 ------------DQFVPITEP-TQPETIAVMSWVKAYPFVLSANLHGGSLVVNYPYDDneqgvaTYSKSPDDAVFQQIAL 704
Cdd:cd00596    77 ynwgkdgtsgpsSPTYRGPAPfSEPETQALRDLAKSHRFDLAVSYHSSSEAILYPYGY------TNEPPPDFSEFQELAA 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  705 SYSKensqmfqgrpckdmyLNEYFPHGITNGASWYNVPGGMQDWNYLQTNCFEVTIELGCVKYPFENELP-KYWEQNRRS 783
Cdd:cd00596   151 GLAR---------------ALGAGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTLLdRRLERNLAA 215


                  .
gi 150378501  784 L 784
Cdd:cd00596   216 L 216
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
 930-1205 5.54e-44

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: 163.08  E-value: 5.54e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03869     1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKR-NPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTS---KTGHTNAHGKDLDTDF--------------------- 1064
Cdd:cd03869    81 QEYLAgNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELggwSLGRWTSDGIDINHNFpdlnsllweaedrkwvprkvp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1065 -----------TSNAS-QPETKAIIeNLIQKQDFSLSIALDGGSVLVTYPYDK---PVQTVENKETLKH-----LASLYA 1124
Cdd:cd03869   161 nhhipipewylSENATvAPETRAVI-AWMEKIPFVLGGNLQGGELVVSYPYDMtrtPWKTQEYTPTPDDhvfrwLAYSYA 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1125 NNHpsMHMGQPS---CpNNSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSL 1201
Cdd:cd03869   240 STH--RLMTDASrrpC-HTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESL 316


                  ....
gi 150378501 1202 LSML 1205
Cdd:cd03869   317 LVFM 320
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
 930-1205 2.11e-43

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: 161.30  E-value: 2.11e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03865     1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKR-NPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSK---TGHTNAHGKDLDTDFTS-------NASQ-------- 1070
Cdd:cd03865    81 NEYQKgNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKdwfVGRSNAQGIDLNRNFPDldrivyvNEKEggpnnhll 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1071 --------------PETKAIIeNLIQKQDFSLSIALDGGSVLVTYPYDKP-------VQTVENKETLKHLASLYANNHPS 1129
Cdd:cd03865   161 knmkkavdqntklaPETKAVI-HWIMDIPFVLSANLHGGDLVANYPYDETrsgsaheYSSCPDDAIFQSLARAYSSLNPA 239

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501 1130 MH-MGQPSC-PNNSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSML 1205
Cdd:cd03865   240 MSdPNRPPCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYI 317
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
 930-1207 7.26e-43

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: 159.33  E-value: 7.26e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03864     1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKR-NPVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSK---TGHTNAHGKDLDTDFTS------------------- 1066
Cdd:cd03864    81 EEYRNgNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNgylVGRNNANGVDLNRNFPDlntlmyynekyggpnhhlp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1067 ------NASQPETKAIIEnLIQKQDFSLSIALDGGSVLVTYPYDKPVQ------------TVENKETLKHLASLYANNHP 1128
Cdd:cd03864   161 lpdnwkSQVEPETLAVIQ-WMQNYNFVLSANLHGGAVVANYPYDKSREprvrgfrrtaysPTPDDKLFQKLAKTYSYAHG 239

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 150378501 1129 SMHMGQpscpnNSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSMLVE 1207
Cdd:cd03864   240 WMHKGW-----NCGDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
 930-1205 4.59e-41

Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase M14-like domain of carboxypeptidase (CP) Z (CPZ), CPZ belongs to the N/E subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPZ is a secreted Zn-dependent enzyme whose biological function is largely unknown. Unlike other members of the N/E subfamily, CPZ has a bipartite structure, which consists of an N-terminal cysteine-rich domain (CRD) whose sequence is similar to Wnt-binding proteins, and a C-terminal CP catalytic domain that removes C-terminal Arg residues from substrates. CPZ is enriched in the extracellular matrix and is widely distributed during early embryogenesis. That the CRD of CPZ can bind to Wnt4 suggests that CPZ plays a role in Wnt signaling.


Pssm-ID: 349439  Cd Length: 315  Bit Score: 154.27  E-value: 4.59e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03867     1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNY-KRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKDC---TSKTGHTNAHGKDLDTDF---TSNASQ------------ 1070
Cdd:cd03867    81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAgynGWTSGRQNAQNLDLNRNFpdlTSEAYRlartrgarldhi 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1071 ------------PETKAIIEnLIQKQDFSLSIALDGGSVLVTYPYDKPVQTVENKE--------TLKHLASLYANNHPSM 1130
Cdd:cd03867   161 pipqsywwgkvaPETKAVMK-WMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMfsptpdekMFKLLAKAYADAHPMM 239

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 150378501 1131 HMGQPSCpNNSDENIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAENKKSLLSML 1205
Cdd:cd03867   240 SDRSENR-CGGNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFM 313
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
507-745 1.83e-37

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 144.45  E-value: 1.83e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  507 DMEIFLRRFANEyPNITRLYSLGKSVESRELYVMEISDnpgvHEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFgt 586
Cdd:COG2866    24 ELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNY-- 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  587 DPEVTDLVRSTRIHLMPSMNPDGYEKSQegdsisvvgRNNSNNFDLNRNFPDQFVpitepTQPETIAVMSWVKAYPFVLS 666
Cdd:COG2866    97 DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWL-----SEPETRALRDLLDEHDPDFV 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  667 ANLHGGSLVVNYPYDDNEQGVATYSKSPDD---AVFQQIALSYSKENSQMFQGRPCKDMYLNEYFPHGITNGASWYNVPG 743
Cdd:COG2866   163 LDLHGQGELFYWFVGTTEPTGSFLAPSYDEereAFAEELNFEGIILAGSAFLGAGAAGTLLISAPRQTFLFAAALDIGGG 242


                  ..
gi 150378501  744 GM 745
Cdd:COG2866   243 GD 244
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 794-869 3.78e-35

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: 128.41  E-value: 3.78e-35
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  794 GVKGFVLDATdGRGILNATLSVAEINHPVTTYKAGDYWRLLVPGTYKITASARGYNPVTKNVTVRSE-GAVQVNFTL 869
Cdd:cd11308     1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 131-372 3.53e-34

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


Pssm-ID: 349427 [Multi-domain]  Cd Length: 216  Bit Score: 131.04  E-value: 3.53e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  131 VKLVGNMHGDETVSRQVLVYLARELASGYRRGDprLVRLLNTTDVYLLPSLNPDGFERARegdcglgdsgppGTSGRDNS 210
Cdd:cd00596     1 ILITGGIHGNEVIGVELALALIEYLLENYGNDP--LKRLLDNVELWIVPLVNPDGFARVI------------DSGGRKNA 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  211 RGRDLNRSFPdqFSTGEPPSLDEV------------PEVRALIDWIRRNKFVLSGNLHGGSVVASYPFDDSPEhkttgly 278
Cdd:cd00596    67 NGVDLNRNFP--YNWGKDGTSGPSsptyrgpapfsePETQALRDLAKSHRFDLAVSYHSSSEAILYPYGYTNE------- 137

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  279 sKTSDDEVFRYLAKAYASNHPimktgephcpgdedeTFKDGITNGAHWYDVEGGMQDYNYVWANCFEITLELSCCKYPPA 358
Cdd:cd00596   138 -PPPDFSEFQELAAGLARALG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLP 201

                         250
                  ....*....|....*
gi 150378501  359 SQLRQ-EWENNRESL 372
Cdd:cd00596   202 GTLLDrRLERNLAAL 216
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 499-780 3.72e-31

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


Pssm-ID: 349476 [Multi-domain]  Cd Length: 359  Bit Score: 126.58  E-value: 3.72e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  499 DFHHHH-FPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLI 577
Cdd:cd06905     2 AFDRYYtYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  578 EYLCKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSisvvGRNNSNN---------------------------- 629
Cdd:cd06905    82 EYLLTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYKLKTE----RSGRSSPrdddrdgdgdedgpedlngdglitqmrv 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  630 --------------------------------------------------FDLNRNFPDQFVPitEPTQ----------P 649
Cdd:cd06905   158 kdptgtwkvdpddprlmvdrekgekgfyrlypegidndgdgrynedgpggVDLNRNFPYNWQP--FYVQpgagpyplseP 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  650 ETIAVMSWVKAYPFVLSANLHGGSLVVNY-PYddneQGVATYSKSPDD-AVFQQIAlsyskENSQMFQGRPCKDMYlNEY 727
Cdd:cd06905   236 ETRAVADFLLAHPNIAAVLTFHTSGGMILrPP----GTGPDSDMPPADrRVYDAIG-----KKGVELTGYPVSSVY-KDF 305

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  728 FPHgiTNGASwynvPGGMQDWNYLQTNCFEVTIEL-------GCVKYPFENELPKYWEQN 780
Cdd:cd06905   306 YTV--PGGPL----DGDFFDWAYFHLGIPSFSTELwdlpefaGKKKEGTVEEAERLRWAD 359
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
86-390 1.31e-30

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 124.42  E-value: 1.31e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLtaglgppptaaagldaaGPLLPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYrrgDPR 165
Cdd:COG2866    40 ELESIGKSVEGRPIYLLKI-----------------GDPAEGKPKVLLNAQQHGNEWTGTEALLGLLEDLLDNY---DPL 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERARegdcglgdsgppgtsgRDNSRGRDLNRSFPDqfstgepPSLDEvPEVRALIDWIR 245
Cdd:COG2866   100 IRALLDNVTLYIVPMLNPDGAERNT----------------RTNANGVDLNRDWPA-------PWLSE-PETRALRDLLD 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  246 RNKFVLSGNLHGGSVVASYPFDDSPEhktTGLYSKTSDDEVFRYLAKAYASNHPIMKTGephcpGDEDETFKDGITNGAH 325
Cdd:COG2866   156 EHDPDFVLDLHGQGELFYWFVGTTEP---TGSFLAPSYDEEREAFAEELNFEGIILAGS-----AFLGAGAAGTLLISAP 227

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 150378501  326 WYDVEGGMQDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEKVHIGIKGFVKDS 390
Cdd:COG2866   228 RQTFLFAAALDIGGGGDVSAGELVAGTLLTAGGAGLGLELLVVRGTSALSLVLKLVGAKTAELES 292
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 382-458 1.25e-28

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: 109.92  E-value: 1.25e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501  382 GIKGFVKDSvTGSGLENATISVAGINHNITTGRFGDFHRLLVPGTYNLTALSTGYMPLTiNNIMVKEGP-ATEMDFSL 458
Cdd:cd11308     1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVT-KTVTVPNNFsATVVNFTL 76
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 86-372 7.99e-28

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: 115.05  E-value: 7.99e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGLGPPptaaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd03859    26 KLISIGKSVEGRPIWAVKISDNPDED--------------EDEPEVLFMGLHHAREWISLEVALYFADYLLENYGT-DPR 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREgdcglGDSGP-------PGTSGRDNSRGRDLNRSFPDQF------STGEPPSld 232
Cdd:cd03859    91 ITNLVDNREIWIIPVVNPDGYEYNRE-----TGGGRlwrknrrPNNGNNPGSDGVDLNRNYGYHWggdnggSSPDPSS-- 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  233 EV---------PEVRALIDWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKTTglysktsDDEVFRYLAKAYASnhPIMKT 303
Cdd:cd03859   164 ETyrgpapfsePETQAIRDLVESHDFKVAISYHSYGELVLYPWGYTSDAPTP-------DEDVFEELAEEMAS--YNGGG 234

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 150378501  304 GEPHCPGDedetfkdgitngahWYDVEGGMQDYNYVWANCFEITLEL---SCCKYPPASQLRQEWENNRESL 372
Cdd:cd03859   235 YTPQQSSD--------------LYPTNGDTDDWMYGEKGIIAFTPELgpeFYPFYPPPSQIDPLAEENLPAA 292
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
 930-1103 1.52e-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: 1.52e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNIsEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03859     4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQE--------KDCTSKTGHTNAH-GKDL---------------DTDFT 1065
Cdd:cd03859    83 ENYGTDPRITNLVDNREIWIIPVVNPDGYEYNREtgggrlwrKNRRPNNGNNPGSdGVDLnrnygyhwggdnggsSPDPS 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 150378501 1066 SNA-------SQPETKAiIENLIQKQDFSLSIALDGGSVLVTYPY 1103
Cdd:cd03859   163 SETyrgpapfSEPETQA-IRDLVESHDFKVAISYHSYGELVLYPW 206
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
929-1104 9.65e-24

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 104.39  E-value: 9.65e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  929 RYHSYKDLSEFLRGLVMNYPHITnLTTLGQSVEYRHIWSLEISNKpnisEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1008
Cdd:COG2866    18 RYYTYEELLALLAKLAAASPLVE-LESIGKSVEGRPIYLLKIGDP----AEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1009 CLNYkrNPVVTQLVDRTRIVIVPSLNPDGRERAQEkdctsktghTNAHGKDLDTDF-TSNASQPETKAIIEnLIQKQDFS 1087
Cdd:COG2866    93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNTR---------TNANGVDLNRDWpAPWLSEPETRALRD-LLDEHDPD 160

                         170
                  ....*....|....*..
gi 150378501 1088 LSIALDGGSVLVTYPYD 1104
Cdd:COG2866   161 FVLDLHGQGELFYWFVG 177
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
 1211-1285 7.67e-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: 93.36  E-value: 7.67e-23
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501 1211 GVHGLVKDKAGKPISKAVIVLNEG-IKVYTKEGGYFHVLLAPGVHNINAIADGYQQQHTQVFVHHDaASSVVIVFD 1285
Cdd:cd11308     1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFT 75
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 929-1044 4.08e-22

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


Pssm-ID: 349476 [Multi-domain]  Cd Length: 359  Bit Score: 99.61  E-value: 4.08e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  929 RYHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1008
Cdd:cd06905     5 RYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYL 84

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 150378501 1009 CLNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEK 1044
Cdd:cd06905    85 LTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYKLK 120
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
 503-774 4.72e-19

Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.


Pssm-ID: 349433 [Multi-domain]  Cd Length: 300  Bit Score: 89.51  E-value: 4.72e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  503 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGvhEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 582
Cdd:cd03860     2 HPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGG--KGGKPAIVIHGGQHAREWISTSTVEYLAHQLLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  583 NFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDsisvvgR-------NNSNNF----DLNRNFPDQFVPITEPTQP-- 649
Cdd:cd03860    80 GYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTD------RlwrknrqPTGGSScvgiDLNRNWGYKWGGPGASTNPcs 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  650 ------------ETIAVMSWVKAYP----FVLSANLHGGSLVVNYPYddneqGVATYSKSPDDAVFQQIALSYSKEnsqm 713
Cdd:cd03860   154 etyrgpsafsapETKALADFINALAagqgIKGFIDLHSYSQLILYPY-----GYSCDAVPPDLENLMELALGAAKA---- 224

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501  714 fqgrpckdMYLneyfPHGI--TNGASW---YNVPGGMQDWNYlqtncfevtiELGCVKYPFENELP 774
Cdd:cd03860   225 --------IRA----VHGTtyTVGPACstlYPASGSSLDWAY----------DVAKIKYSYTIELR 268
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 558-784 4.78e-19

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: 87.78  E-value: 4.78e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  558 YIGNMHGNEVVGRELLLNLIEYLCKN-------FGTDPEvtDLVRSTRIHLMPSMNPDGYEKSQEG-----------DSI 619
Cdd:cd06229     3 YNASFHAREYITTLLLMKFIEDYAKAyvnksyiRGKDVG--ELLNKVTLHIVPMVNPDGVEISQNGsnainpyylrlVAW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  620 SVVGRN------NSNNFDLNRNFPDQF-----VPITEP-----------TQPETIAVMSWVKAYPFVLSANLHGGSLVVN 677
Cdd:cd06229    81 NKKGTDftgwkaNIRGVDLNRNFPAGWekekrLGPKAPgprdypgkeplSEPETKAMAALTRQNDFDLVLAYHSQGEEIY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  678 YPYDDNEQGVATyskspddavfqQIALSYSKensqmfqgrpckdmyLNEYFPHGITNGASWynvpGGMQDWNYLQTNCFE 757
Cdd:cd06229   161 WGYNGLEPEESK-----------AMAEKFAS---------------VSGYEPVEAEAIDSY----GGFKDWFIYEFKKPS 210

                         250       260
                  ....*....|....*....|....*...
gi 150378501  758 VTIELGCVKYPFEN-ELPKYWEQNRRSL 784
Cdd:cd06229   211 FTIETGKGNNPLPIsQFDEIYEKNKGVL 238
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
 986-1197 7.68e-19

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: 86.74  E-value: 7.68e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  986 FVAGIHGNAPVGTELLLALAEFLCLNYKRNPvVTQLVDRTRIVIVPSLNPDGRERAQekdctSKTGHTNAHGKDLDTDFT 1065
Cdd:cd00596     3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVI-----DSGGRKNANGVDLNRNFP 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1066 SN-------------------ASQPETKAIIEnLIQKQDFSLSIALDGGSVLVTYPYDKPVQTVENKETLKHLASLYANN 1126
Cdd:cd00596    77 YNwgkdgtsgpssptyrgpapFSEPETQALRD-LAKSHRFDLAVSYHSSSEAILYPYGYTNEPPPDFSEFQELAAGLARA 155

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 150378501 1127 HPsmhmgqpscpnnsdeNIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAAQLPALWAEN 1197
Cdd:cd00596   156 LG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTLLDRRLER 211
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
 86-248 2.36e-18

Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.


Pssm-ID: 349433 [Multi-domain]  Cd Length: 300  Bit Score: 87.20  E-value: 2.36e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGLGPpptaaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd03860    23 EIFTIGKSYEGRDITGIHIWGSGGK---------------GGKPAIVIHGGQHAREWISTSTVEYLAHQLLSGYGS-DAT 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERAREGDcglgdsgppgtsgR---------DNS--RGRDLNRSFPDQFSTGEPPS---- 230
Cdd:cd03860    87 ITALLDKFDFYIIPVVNPDGYVYTWTTD-------------RlwrknrqptGGSscVGIDLNRNWGYKWGGPGASTnpcs 153

                         170       180
                  ....*....|....*....|....*.
gi 150378501  231 --------LDEvPEVRALIDWIRRNK 248
Cdd:cd03860   154 etyrgpsaFSA-PETKALADFINALA 178
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 86-257 2.52e-17

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: 85.36  E-value: 2.52e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGLGPPPTAaagldaagpllpgRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPR 165
Cdd:cd06905    28 RLESIGKSYEGRDIWLLTITNGETGPADE-------------KPALWVDGNIHGNEVTGSEVALYLAEYLLTNYGK-DPE 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGFERA----------------REGDcGLGD-------------------SGP--------- 201
Cdd:cd06905    94 ITRLLDTRTFYILPRLNPDGAEAYklktersgrssprdddRDGD-GDEDgpedlngdglitqmrvkdpTGTwkvdpddpr 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  202 ------PG--------TSGRDN----------SRGRDLNRSFP-------DQFSTGEPPsLDEvPEVRALIDWIRRNKFV 250
Cdd:cd06905   173 lmvdreKGekgfyrlyPEGIDNdgdgrynedgPGGVDLNRNFPynwqpfyVQPGAGPYP-LSE-PETRAVADFLLAHPNI 250


                  ....*..
gi 150378501  251 LSGNLHG 257
Cdd:cd06905   251 AAVLTFH 257
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 133-288 9.06e-17

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


Pssm-ID: 349430 [Multi-domain]  Cd Length: 203  Bit Score: 80.20  E-value: 9.06e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  133 LVGNMHGDETVSRQVLVYLARELASgyrRGDPrLVRLLNTTDVYLLPSLNPDGFERAREGDcglGDSGPPGTSGRDNSRG 212
Cdd:cd03857     4 LAAQIHGNETTGTEALMELIRDLAS---ESDE-AAKLLDNIVILLVPQLNPDGAELFVNFY---LDSMNGLPGTRYNANG 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501  213 RDLNRSFPDQfstgeppsldEVPEVRALIDWIRRNKFVLSGNLHgGSVVASYPFDDSPEHKTTGLYSKTSDDEVFR 288
Cdd:cd03857    77 IDLNRDHVKL----------TQPETQAVAENFIHWWPDIFIDLH-EQVGASIPYPTPPDAPNYNLVDLRSDAENGQ 141
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 536-785 1.81e-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: 1.81e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  536 ELYVMEISdNPGVHEPGE-PEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQ 614
Cdd:cd06226     1 DIRALKLT-NKQATPPGEkPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  615 EGDSisvvGRNNSNN-----------FDLNRNFPDQF-------VPITE----PT---QPETIAVMSWVKAY-----PFV 664
Cdd:cd06226    80 TGLL----WRKNTNTtpcpassptygVDLNRNSSFKWggagaggSACSEtyrgPSaasEPETQAIENYVKQLfpdqrGPG 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  665 LSA-----------NLHGGSLVVNYPYDDNEQgvatysKSPDDAVFQQIALSYSkensqmfqgrpckdmYLNEYFPHgit 733
Cdd:cd06226   156 LTDpapddtsgiyiDIHSYGNLVLYPWGWTGT------PAPNAAGLRTLGRKFA---------------YFNGYTPQ--- 211

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  734 NGASWYNVPGGMQDWNYLQTNCFEVTIELG-----CVKYpFENELpkyWEQNRRSLI 785
Cdd:cd06226   212 QAVALYPTDGTTDDFAYGTLGVAAYTFELGtaffeSCSY-FENTI---LPDNLPALY 264
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 528-789 3.08e-14

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: 73.08  E-value: 3.08e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  528 LGKSVESRELYVMEISDNPG--VHepgepefkYIGNMHGNEVVGRELLLNLIEYLcknfGTDPEVTDLvrstRIHLMPSM 605
Cdd:cd06904     4 YGTSVKGRPILAYKFGPGSRarIL--------IIGGIHGDEPEGVSLVEHLLRWL----KNHPASGDF----HIVVVPCL 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  606 NPDGYEKSQegdsisvvgRNNSNNFDLNRNFP-------------DQFVPITEP-TQPETIAVMSWVKAYP--FVLSanL 669
Cdd:cd06904    68 NPDGLAAGT---------RTNANGVDLNRNFPtknwepdarkpkdPRYYPGPKPaSEPETRALVELIERFKpdRIIS--L 136

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  670 HGGSLVVnypYDDNEQGVatyskspddavfqqIALSYSKENSQMFQGRPckdmylneyfphGITngaswynvPGGMQDWN 749
Cdd:cd06904   137 HAPYLVN---YDGPAKSL--------------LAEKLAQATGYPVVGDV------------GYT--------PGSLGTYA 179

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 150378501  750 YLQTNCFEVTIELgcvkyPFENELPKYWEQNRRSLIQFMK 789
Cdd:cd06904   180 GIERNIPVITLEL-----PEAVSIDELWQDLKRALIEAIK 214
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 558-745 3.52e-14

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: 72.88  E-value: 3.52e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  558 YIGNMHGNEVVGRELLLNLIeylcKNFGTDP-EVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVG----RNNSNNFDL 632
Cdd:cd03857     4 LAAQIHGNETTGTEALMELI----RDLASESdEAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGlpgtRYNANGIDL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  633 NRNFPDQfvpitepTQPETIAVMSWV-KAYPFVLsANLHggslvvnypydDNEQGVATYSKSPDDAVFQQIALSYSKENS 711
Cdd:cd03857    80 NRDHVKL-------TQPETQAVAENFiHWWPDIF-IDLH-----------EQVGASIPYPTPPDAPNYNLVDLRSDAENG 140

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 150378501  712 QMfQGRPCKDMYLNE---YFPHGITNGASWYNVPGGM 745
Cdd:cd03857   141 QE-HIRLIAGEGSGElgkYFSPMRGGFDDSTGGNGIG 176
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
 128-271 7.57e-14

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: 72.30  E-value: 7.57e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  128 RPQVKLVGNMHGDETVSRQVLVYLARELASGY-----RRGDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGLgdsgpp 202
Cdd:cd06227     1 KPRVLLVFGEHARELISVESALRLLRQLCGGLqepaaSALRELAREILDNVELKIIPNANPDGRRLVESGDYCW------ 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 150378501  203 gtsgRDNSRGRDLNRSFPDQFSTGEPPSLDEV---------PEVRALIDWIRRNKFVLSGNLHGGSVVASYPFDDSPE 271
Cdd:cd06227    75 ----RGNENGVDLNRNWGVDWGKGEKGAPSEEypgpkpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAYSAS 148
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
794-869 8.96e-14

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 67.69  E-value: 8.96e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   794 GVKGFVLDATdGRGILNATLSVA----EINHPVTTYKAGDYW-RLLVPGTYKITASARGYNPVTK-NVTVRSEGAVQVNF 867
Cdd:pfam13620    1 TISGTVTDPS-GAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRtGVTVTAGQTTTLDV 79


                   ..
gi 150378501   868 TL 869
Cdd:pfam13620   80 TL 81
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
382-458 2.95e-13

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 66.15  E-value: 2.95e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   382 GIKGFVKDSvTGSGLENATISVA----GINHNITTGRFGDFH-RLLVPGTYNLTALSTGYMPLTINNIMVKEGPATEMDF 456
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 150378501   457 SL 458
Cdd:pfam13620   80 TL 81
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
 930-1103 1.53e-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: 69.86  E-value: 1.53e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPeePKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03860     1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGGKGGK--PAIVIHGGQHAREWISTSTVEYLAHQLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKTGHTNAHGKDLDTDF-------------------- 1064
Cdd:cd03860    79 SGYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDrlwrkNRQPTGGSSCVGIDLNRNWgykwggpgastnpcsetyrg 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 150378501 1065 TSNASQPETKAI---IENLIQKQDFSLSIALDGGSVLVTYPY 1103
Cdd:cd03860   159 PSAFSAPETKALadfINALAAGQGIKGFIDLHSYSQLILYPY 200
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 90-376 2.46e-12

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


Pssm-ID: 349475 [Multi-domain]  Cd Length: 214  Bit Score: 67.69  E-value: 2.46e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   90 IGSSVEGRPLWVLRltaglgPPPTAaagldaagpllpgRPQVKLVGNMHGDETVSrqvlVYLARELAsgyrrgdprlvRL 169
Cdd:cd06904     4 YGTSVKGRPILAYK------FGPGS-------------RARILIIGGIHGDEPEG----VSLVEHLL-----------RW 49

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  170 LNTTD------VYLLPSLNPDGFERaregdcglgdsgppGTsgRDNSRGRDLNRSFP-------------DQFSTGEPPs 230
Cdd:cd06904    50 LKNHPasgdfhIVVVPCLNPDGLAA--------------GT--RTNANGVDLNRNFPtknwepdarkpkdPRYYPGPKP- 112

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  231 LDEvPEVRALIDWIRRNK--FVLSgnLHGGSVVasyPFDDSPEHKTTGLYSKtsddevfrylakayASNHPIMKtgephc 308
Cdd:cd06904   113 ASE-PETRALVELIERFKpdRIIS--LHAPYLV---NYDGPAKSLLAEKLAQ--------------ATGYPVVG------ 166

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 150378501  309 pgdedetfKDGITNGAhwydveGGMqdynyvWA----NCFEITLELscckyPPASQLRQEWENNRESLITLI 376
Cdd:cd06904   167 --------DVGYTPGS------LGT------YAgierNIPVITLEL-----PEAVSIDELWQDLKRALIEAI 213
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
 516-773 1.43e-11

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: 67.14  E-value: 1.43e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  516 ANEYPNITRLYSLGKSVESRELYVMEISDNpgvhepgEPEFKYI----GNMHGNEVVGRELLLNLIEYLCKNFGTDPEVT 591
Cdd:cd06246    19 TERHPDMLTKIHIGSSFEKYPLYVLKVSGK-------EQTAKNAiwidCGIHAREWISPAFCLWFIGHASYFYGIIGQHT 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  592 DLVRSTRIHLMPSMNPDGYEKSQEGDSI-----SVVGRNNSNNFDLNRNFP----------DQFVPI---TEP-TQPETI 652
Cdd:cd06246    92 NLLNLVDFYVMPVVNVDGYDYSWKKNRMwrknrSKHANNRCIGTDLNRNFDagwcgkgassDSCSETycgPYPeSEPEVK 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  653 AVMSWVKAYPFVLSA--NLHGGSLVVNYPYDdneqgvATYSKSPDDAVFQQIAlsysKENSQMFQGrpckdmYLNEYFPH 730
Cdd:cd06246   172 AVASFLRRHKDTIKAyiSMHSYSQMVLFPYS------YTRNKSKDHDELSLLA----KEAVTAIRK------TSRNRYTY 235

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 150378501  731 GitNGA-SWYNVPGGMQDWNYlqtncfevtiELGcVKYPFENEL 773
Cdd:cd06246   236 G--PGAeTIYLAPGGSDDWAY----------DLG-IKYSFTFEL 266
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 131-256 2.35e-11

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: 65.44  E-value: 2.35e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  131 VKLVGNMHGDETVSRQVLVYLARELASGYRRG----DPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGLGD-------- 198
Cdd:cd06229     1 VLYNASFHAREYITTLLLMKFIEDYAKAYVNKsyirGKDVGELLNKVTLHIVPMVNPDGVEISQNGSNAINPyylrlvaw 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 150378501  199 --SGPPGTSGRDNSRGRDLNRSFPDQF---STGEP--PS---------LDEvPEVRALIDWIRRNKFVLSGNLH 256
Cdd:cd06229    81 nkKGTDFTGWKANIRGVDLNRNFPAGWekeKRLGPkaPGprdypgkepLSE-PETKAMAALTRQNDFDLVLAYH 153
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 128-240 4.23e-11

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


Pssm-ID: 349461 [Multi-domain]  Cd Length: 220  Bit Score: 64.25  E-value: 4.23e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  128 RPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDprlvrLLNTTDVYLLPSLNPDGFERARegdcglgdsgppgtsgR 207
Cdd:cd06242     1 KPTVLLVGQQHGNEPAGREAALALARDLAFGDDARE-----LLEKVNVLVVPRANPDGRAANT----------------R 59

                          90       100       110
                  ....*....|....*....|....*....|...
gi 150378501  208 DNSRGRDLNRsfpDQfstgeppSLDEVPEVRAL 240
Cdd:cd06242    60 GNANGVDLNR---DH-------LLLSTPETRAL 82
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 92-256 8.31e-11

Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family includes Francisella tularensis protein rapid encystment phenotype 34 (REP34) which is a zinc-containing monomeric protein demonstrating carboxypeptidase B-like activity. REP34 possesses a novel topology with its substrate binding pocket deviating from the canonical M14 peptidases with a possible catalytic role for a conserved tyrosine and distinct S1' recognition site. Thus, REP34, identified as an active carboxypeptidase and a potential key F. tularensis effector protein, may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells. A functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate cleavages. They contain an extra C-terminal transthyretin-like domain, thought to be involved in folding or formation of oligomers. MCPs can also be classified based on their involvement in specific physiological processes; the pancreatic MCPs participate only in alimentary digestion and include carboxypeptidase A and B (A/B subfamily), while others, namely regulatory MCPs or the N/E subfamily, are involved in more selective reactions, mainly in non-digestive tissues and fluids, acting on blood coagulation/fibrinolysis, inflammation and local anaphylaxis, pro-hormone and neuropeptide processing, cellular response and others. Another MCP subfamily, is that of succinylglutamate desuccinylase /aspartoacylase, which hydrolyzes N-acetyl-L-aspartate (NAA), and deficiency in which is the established cause of Canavan disease. Another subfamily (referred to as subfamily C) includes an exceptional type of activity in the MCP family, that of dipeptidyl-peptidase activity of gamma-glutamyl-(L)-meso-diaminopimelate peptidase I which is involved in bacterial cell wall metabolism.


Pssm-ID: 349450 [Multi-domain]  Cd Length: 239  Bit Score: 63.87  E-value: 8.31e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   92 SSVEGRPLWVLRL--TAGLGPPPTAaagLDAAGPLlPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGdprlVRL 169
Cdd:cd06231     8 ERLGARRFKVRELgeVGYQGYPLFA---LKSPNPR-GDKPRVLISAGIHGDEPAGVEALLRFLESLAEKYLRR----VNL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  170 LnttdvyLLPSLNPDGFERaregdcglgdsgppGTsgRDNSRGRDLNRSFpdqfsTGEPPSldevPEVRALIDWIR-RNK 248
Cdd:cd06231    80 L------VLPCVNPWGFER--------------NT--RENADGIDLNRSF-----LKDSPS----PEVRALMEFLAsLGR 128


                  ....*...
gi 150378501  249 FVLSGNLH 256
Cdd:cd06231   129 FDLHLDLH 136
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 127-246 8.92e-11

Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins; Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT)-like proteins. This group belongs to the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPT exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues and C-terminal positively charged residues. However, CPT does not belong to this CPT-like group.


Pssm-ID: 349445 [Multi-domain]  Cd Length: 267  Bit Score: 64.01  E-value: 8.92e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  127 GRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDSGPPGTSG 206
Cdd:cd06226    17 EKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGT-DADATWLLDYTELHLVPQVNPDGRKIAETGLLWRKNTNTTPCPA 95

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  207 RDNSRGRDLNRSFPdqFSTGEPPSLDEV-------------PEVRALIDWIRR 246
Cdd:cd06226    96 SSPTYGVDLNRNSS--FKWGGAGAGGSAcsetyrgpsaasePETQAIENYVKQ 146
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 558-655 1.30e-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: 62.70  E-value: 1.30e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  558 YIGNMHGNEVVGRELLLNLIEYLCKnfgtDPEVTDLVRSTRIHLMPSMNPDGYEKSQegdsisvvgRNNSNNFDLNRNFp 637
Cdd:cd06242     6 LVGQQHGNEPAGREAALALARDLAF----GDDARELLEKVNVLVVPRANPDGRAANT---------RGNANGVDLNRDH- 71

                          90
                  ....*....|....*...
gi 150378501  638 dqfvpiTEPTQPETIAVM 655
Cdd:cd06242    72 ------LLLSTPETRALA 83
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 503-680 1.76e-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: 63.63  E-value: 1.76e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  503 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPgEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 582
Cdd:cd06248     2 HSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRSTNSEDTS-KPTIMIEGGINPREWISPPAALYAIHKLVE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  583 NfgtDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSI---SVVGRNNSNNF-----DLNRNFPDQFVPI--TEP------ 646
Cdd:cd06248    81 D---VETQSDLLNNFDWIILPVANPDGYVFTHTNDREwtkNRSTNSNPLGQicfgvNINRNFDYQWNPVlsSESpcsely 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 150378501  647 ------TQPETIAVMSWVKAY--PFVLSANLHGGSLVVNYPY 680
Cdd:cd06248   158 agpsafSEAESRAIRDILHEHgnRIHLYISFHSGGSFILYPW 199
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 558-761 2.04e-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: 62.71  E-value: 2.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  558 YI-GNMHGNEVVGRELLLNLIEylcknfgTDPEvtDLVRSTRIHLMPSMNPDGYEKSQegdsisvvgRNNSNNFDLNRNF 636
Cdd:cd06231    46 LIsAGIHGDEPAGVEALLRFLE-------SLAE--KYLRRVNLLVLPCVNPWGFERNT---------RENADGIDLNRSF 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  637 pdqfvpITEPTQPETIAVMSWVKAYP-FVLSANLHGgslvvnypyDDNEQGVATYSKSPDDAVFQQI-----ALSYSKEN 710
Cdd:cd06231   108 ------LKDSPSPEVRALMEFLASLGrFDLHLDLHE---------DWDSDGFYLYELGPALKAGRDGlqavdAVIPPDPI 172

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  711 SQMFQGRPCKDmylneyfphG-ITNGASWYNVPGG-MQDWNYLQTNCFEVTIE 761
Cdd:cd06231   173 SLTIDGSPAPD---------GvILRPDDPAERPGWpFAIYLVANGAVRTYTTE 216
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 562-671 2.59e-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: 349458 [Multi-domain]  Cd Length: 194  Bit Score: 61.28  E-value: 2.59e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  562 MHGNEVVGRELLLNLIEYLCKnfgTDPEVTDLVRSTRIHLMPSMNPDGYEKSQegdsisvvgRNNSNNFDLNRNFPDQfv 641
Cdd:cd06239     8 MHGNEPTGTEALLDLISYLRR---ERQEFEKILERLTLVAIPMLNPDGAELFT---------RHNAEGIDLNRDARAL-- 73

                          90       100       110
                  ....*....|....*....|....*....|
gi 150378501  642 pitepTQPETIAVMSWVKAYPFVLSANLHG 671
Cdd:cd06239    74 -----QTPESRALKAVLDSFSPKFAFNLHD 98
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
 561-682 2.88e-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: 2.88e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  561 NMHGNEVVGRELLLNLIEYLC--KNFGTDPEVTDLVRSTR----IHLMPSMNPDGYEKSQEGDsisVVGRNNSNNFDLNR 634
Cdd:cd06227     9 GEHARELISVESALRLLRQLCggLQEPAASALRELAREILdnveLKIIPNANPDGRRLVESGD---YCWRGNENGVDLNR 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  635 NFPD--QFVPITEPTQ----------PETIAVMSWVKAYPFVLSANLHGGSLVVNYPYDD 682
Cdd:cd06227    86 NWGVdwGKGEKGAPSEeypgpkpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAY 145
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 561-671 5.67e-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: 60.93  E-value: 5.67e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  561 NMHGNEVVGRELLLNLIEYLCKN--------------FGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQegdsisvvgRNN 626
Cdd:cd06244     7 NIHGNEVEGVDALLEFLEMLATEpnvtyntlvkyykvENVDLEVKDLLDDVFFIVVPTENPDGRVANT---------RTN 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 150378501  627 SNNFDLNRNFPDQfvpitepTQPETIAVMSWVKAYPFVLSANLHG 671
Cdd:cd06244    78 ANGFDLNRDNAYQ-------TQPETRAMQELISKWNPVTFLDMHG 115
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 90-320 6.38e-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: 62.07  E-value: 6.38e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   90 IGSSVEGRPLWVLRLTAGLgppptaaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPRLVRL 169
Cdd:cd03870    32 IGSSFENRPMYVLKFSTGG-----------------EERPAIWIDAGIHSREWVTQASAIWTAEKIVSDYGK-DPSITSI 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  170 LNTTDVYLLPSLNPDGF----------ERARegdcglgdSGPPGTSgrdnSRGRDLNR----SFPDQFSTGEP------- 228
Cdd:cd03870    94 LDTMDIFLEIVTNPDGYvfthssnrlwRKTR--------SVNPGSL----CIGVDPNRnwdaGFGGPGASSNPcsetyhg 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  229 PSLDEVPEVRALIDWIRRN-KFVLSGNLHGGSVVASYPFDdspeHKTTGLYSKTSDDEVFRYLAKAYASNH-------PI 300
Cdd:cd03870   162 PHANSEVEVKSIVDFIQSHgNFKAFISIHSYSQLLMYPYG----YTVEKAPDQEELDEVAKKAVKALASLHgteykvgSI 237

                         250       260
                  ....*....|....*....|
gi 150378501  301 MKTGEPHCPGDEDETFKDGI 320
Cdd:cd03870   238 STTIYQASGSSIDWAYDNGI 257
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 930-1131 1.26e-09

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 Carboxypeptidase (CP) A (CPA) belongs to the A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPA enzymes generally favor hydrophobic residues. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. This subfamily includes CPA1, CPA2 and CPA4 forms. Within these A forms, there are slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer.


Pssm-ID: 349442 [Multi-domain]  Cd Length: 301  Bit Score: 61.30  E-value: 1.26e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPnisePEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03870     6 YHTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKTGHTNAHGKDL----DTDFTSNA------------ 1068
Cdd:cd03870    82 SDYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNrlwrkTRSVNPGSLCIGVDPnrnwDAGFGGPGassnpcsetyhg 161

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501 1069 ----SQPETKAIIENLIQKQDFSLSIALDGGSVLVTYPYDKPVQTVENKETLKHLASLYANNHPSMH 1131
Cdd:cd03870   162 phanSEVEVKSIVDFIQSHGNFKAFISIHSYSQLLMYPYGYTVEKAPDQEELDEVAKKAVKALASLH 228
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
 954-1083 6.86e-09

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


Pssm-ID: 349475 [Multi-domain]  Cd Length: 214  Bit Score: 57.67  E-value: 6.86e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  954 TTLGQSVEYRHIWSLEISNKPNisepeePKIRFVAGIHGNAPVGTELLLalaeflclNYKRNPVVTQLVDRTRIVIVPSL 1033
Cdd:cd06904     2 KVYGTSVKGRPILAYKFGPGSR------ARILIIGGIHGDEPEGVSLVE--------HLLRWLKNHPASGDFHIVVVPCL 67

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1034 NPDGRERAQEkdctsktghTNAHGKDLDTDF-TSN-------------------ASQPETKAIIeNLIQK 1083
Cdd:cd06904    68 NPDGLAAGTR---------TNANGVDLNRNFpTKNwepdarkpkdpryypgpkpASEPETRALV-ELIER 127
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 930-1146 8.32e-09

Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 carboxypeptidases found specifically in insects, including B-type carboxypeptidase of H. zea (CPBHz, insect gut carboxypeptidase-3) that is insensitive to potato carboxypeptidase inhibitor (PCI) in corn earworm, and midgut procarboxypeptidase A (PCPAHa, insect gut carboxypeptidase-1) from Helicoverpa armigera larva, a devastating pest of crops. PCPAHa preferentially cleaves aliphatic and aromatic residues. The peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.


Pssm-ID: 349467 [Multi-domain]  Cd Length: 297  Bit Score: 58.62  E-value: 8.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKPNISEPeEPKIRFVAGIHGNAPVGTELLLALAeflc 1009
Cdd:cd06248     1 YHSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRSTNSEDTS-KPTIMIEGGINPREWISPPAALYAI---- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 lnYK---RNPVVTQLVDRTRIVIVPSLNPDGRE--RAQEKDCTsKTGHTNAH-------GKDLDTDF------------- 1064
Cdd:cd06248    76 --HKlveDVETQSDLLNNFDWIILPVANPDGYVftHTNDREWT-KNRSTNSNplgqicfGVNINRNFdyqwnpvlssesp 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1065 -------TSNASQPETKAiIENLIQKQD--FSLSIALDGGSVLVTYPYDKPVQTVENKETLkHLASLYANNHPSMHMGQP 1135
Cdd:cd06248   153 cselyagPSAFSEAESRA-IRDILHEHGnrIHLYISFHSGGSFILYPWGYDGSTSSNARQL-HLAGVAAAAAISSNNGRP 230

                         250
                  ....*....|.
gi 150378501 1136 SCPNNSDENIP 1146
Cdd:cd06248   231 YVVGQSSVLLY 241
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 560-665 1.78e-08

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: 56.21  E-value: 1.78e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  560 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVRSTRIHLMPSMNPDGYEK-----SQEGDSISVV------------ 622
Cdd:cd06238     8 YSIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRERfvnwfNQNRGAVGDPdpqsmehnepwp 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 150378501  623 -GRNNSNNFDLNRNFPDQfvpitepTQPETIAVMSWVKAY-PFVL 665
Cdd:cd06238    86 gGRTNHYLFDLNRDWLAQ-------TQPESRARAAAIHRWrPQVV 123
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 514-773 2.87e-08

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 Carboxypeptidase B (CPB) belongs to the carboxypeptidase A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Carboxypeptidase B (CPB) enzymes only cleave the basic residues lysine or arginine. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients. this subfamily also includes thrombin activatable fibrinolysis inhibitor (TAFIa), a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help in prevention of thrombosis.


Pssm-ID: 349443 [Multi-domain]  Cd Length: 300  Bit Score: 57.08  E-value: 2.87e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  514 RFANEYPNITRLYSLGKSVESRELYVMEISdNPGVHEPGepEFKYIGnMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDL 593
Cdd:cd03871    18 QVASKNPDLVSRSQIGTTFEGRPIYLLKVG-KPGSNKKA--IFMDCG-FHAREWISPAFCQWFVREAVRTYGKEKIMTKL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  594 VRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNN-----FDLNRNFPDQFVPI---TEP-----------TQPETIAV 654
Cdd:cd03871    94 LDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSPNAGsscigTDPNRNFNAGWCTVgasSNPcsetycgsapeSEKETKAL 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  655 MSWVKAYPFVLSANL--HGGSLVVNYPYDdneqgvATYSKSPDDAVFQQIALSYSKENSQMFQGRpckdmylneyFPHGi 732
Cdd:cd03871   174 ANFIRNNLSSIKAYLtiHSYSQMLLYPYS------YTYKLAPNHEELNSIAKGAVKELSSLYGTK----------YTYG- 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 150378501  733 TNGASWYNVPGGMQDWNYlqtncfevtiELGcVKYPFENEL 773
Cdd:cd03871   237 PGATTIYPAAGGSDDWAY----------DQG-IKYSFTFEL 266
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
 953-1092 4.49e-08

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: 55.39  E-value: 4.49e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  953 LTTLGQSVEYRHIWSLEISNKPNisePEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYkrnpvvtqlVDRTRIVIVPS 1032
Cdd:cd06231    17 VRELGEVGYQGYPLFALKSPNPR---GDKPRVLISAGIHGDEPAGVEALLRFLESLAEKY---------LRRVNLLVLPC 84

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 150378501 1033 LNPDGRERaqekdctsktgHT--NAHGKDLDTDFTSNASQPETKAIIENLIQKQDFSLSIAL 1092
Cdd:cd06231    85 VNPWGFER-----------NTreNADGIDLNRSFLKDSPSPEVRALMEFLASLGRFDLHLDL 135
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
 86-350 1.50e-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: 54.11  E-value: 1.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRltagLGPPPTaaagldaagpllpGRPQVKLVGNMHGDETVSRQVLVYLARELASGYrrgDPR 165
Cdd:cd06234    20 RLEVLGQTLDGRDIDLLT----IGDPGT-------------GKKKVWIIARQHPGETMAEWFMEGLLDRLLDED---DPV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVRLLNTTDVYLLPSLNPDGferaregdCGLGDSgppgtsgRDNSRGRDLNRSFpdqfstgEPPSLDEVPEVRALIDWIR 245
Cdd:cd06234    80 SRALLEKAVFYVVPNMNPDG--------SVRGNL-------RTNAAGVNLNREW-------ANPSLERSPEVFAVRQAMD 137

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  246 RNKFVLSGNLHGGSVVAsYPFDDSPEhkttGLySKTSD--DEVFRYLAKAYASNHPIMKTG---EPHCPGDEDETFKDgi 320
Cdd:cd06234   138 ATGVDFFLDVHGDEALP-YNFIAGAE----GI-PSWTPrlAALEAAFKAALAAASPDFQTEhgyPPDAPGEANLTIAS-- 209

                         250       260       270
                  ....*....|....*....|....*....|..
gi 150378501  321 tngahwydveggmqdyNYVWA--NCFEITLEL 350
Cdd:cd06234   210 ----------------NWVAErfGCLAMTLEM 225
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
 929-1105 1.89e-07

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


Pssm-ID: 349466 [Multi-domain]  Cd Length: 298  Bit Score: 54.47  E-value: 1.89e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  929 RYHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEI---SNKPNisepeepKIRFV-AGIHGNAPVGTELLLAL 1004
Cdd:cd06247     3 KYHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKPK-------KIIWMdCGIHAREWIAPAFCQWF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1005 AEFLCLNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKD---CTSKTGHTNA--HGKDLDTDFTSN------------ 1067
Cdd:cd06247    76 VKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDrlwRKSRSPHNNGtcYGTDLNRNFNSQwcsigasrnccs 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 150378501 1068 --------ASQPETKAIIENLIQKQD---FSLSIALDGGSVLVTYPYDK 1105
Cdd:cd06247   156 iifcgtgpESEPETKAVADLIEKKKSdilCYLTIHSYGQLILLPYGYTK 204
PRK10602 PRK10602
murein tripeptide amidase MpaA;
91-252 2.43e-07

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 53.49  E-value: 2.43e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   91 GSSVEGRPLwvLRLTAglgPPPTAAAGLDAAGpllpgrpqvklvgnMHGDETVSRQVLVYLARELASGYRRgdprlvrll 170
Cdd:PRK10602   21 GRSLLGAPL--LWFPA---PAASRESGLILAG--------------THGDETASVVTLSCALRTLTPSLRR--------- 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  171 ntTDVYLlpSLNPDGferaregdCGLGDsgppgtsgRDNSRGRDLNRSFPDQ---------------------FSTGEPP 229
Cdd:PRK10602   73 --HHVVL--AVNPDG--------CQLGL--------RANANGVDLNRNFPAAnwkegetvyrwnsaaeerdvvLLTGDKP 132

                         170       180
                  ....*....|....*....|....*
gi 150378501  230 SLDevPEVRALIDWIRRNK--FVLS 252
Cdd:PRK10602  133 GSE--PETQALCQLIHRLQpaWVVS 155
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 89-320 2.46e-07

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 Carboxypeptidase B (CPB) belongs to the carboxypeptidase A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Carboxypeptidase B (CPB) enzymes only cleave the basic residues lysine or arginine. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients. this subfamily also includes thrombin activatable fibrinolysis inhibitor (TAFIa), a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help in prevention of thrombosis.


Pssm-ID: 349443 [Multi-domain]  Cd Length: 300  Bit Score: 54.00  E-value: 2.46e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   89 SIGSSVEGRPLWVLRltagLGPPPTAaagldaagpllpgRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRgDPRLVR 168
Cdd:cd03871    31 QIGTTFEGRPIYLLK----VGKPGSN-------------KKAIFMDCGFHAREWISPAFCQWFVREAVRTYGK-EKIMTK 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  169 LLNTTDVYLLPSLNPDGFERAREGDCGLGDSGPPGTSGrdNSRGRDLNRSFP----DQFSTGEP-------PSLDEVPEV 237
Cdd:cd03871    93 LLDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSPNAGS--SCIGTDPNRNFNagwcTVGASSNPcsetycgSAPESEKET 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  238 RALIDWIRRNKFVLSGNL--HGGSVVASYPF----DDSPEHKTTGLYSKTSDDEvfryLAKAYASNH---PIMKTGEPHC 308
Cdd:cd03871   171 KALANFIRNNLSSIKAYLtiHSYSQMLLYPYsytyKLAPNHEELNSIAKGAVKE----LSSLYGTKYtygPGATTIYPAA 246

                         250
                  ....*....|..
gi 150378501  309 PGDEDETFKDGI 320
Cdd:cd03871   247 GGSDDWAYDQGI 258
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
 988-1106 2.50e-07

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: 52.85  E-value: 2.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  988 AGIHGNAPVGTELLLALAEFLCLNYKrnpVVTQLVDRTRIVIVPSLNPDGRERAQEKDCTSKTGHT----NAHGKDLDTD 1063
Cdd:cd03857     6 AQIHGNETTGTEALMELIRDLASESD---EAAKLLDNIVILLVPQLNPDGAELFVNFYLDSMNGLPgtryNANGIDLNRD 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 150378501 1064 FTsNASQPETKAIIENLIqkqDFSLSIALD-----GGSVLVTYPYDKP 1106
Cdd:cd03857    83 HV-KLTQPETQAVAENFI---HWWPDIFIDlheqvGASIPYPTPPDAP 126
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 520-675 3.46e-07

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: 52.95  E-value: 3.46e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  520 PNITRLySLGKSVESRELYVMEIsdnpgvHEPGEPEFKY-IGNMHGNEVVGRELLLNLIEYLCKNfgtdpevTDLVRSTR 598
Cdd:cd06237    14 PFVKRS-TIGKSVEGRPIEALTI------GNPDSKELVVlLGRQHPPEVTGALAMQAFVETLLAD-------TELAKAFR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  599 ----IHLMPSMNPDGyeksqegdsisVVG---RNNSNNFDLNR---NFpdqfvpitepTQPETIAVMSWVKAYpfvlsAN 668
Cdd:cd06237    80 arfrVLVVPLLNPDG-----------VDLghwRHNAGGVDLNRdwgPF----------TQPETRAVRDFLLEL-----VE 133


                  ....*..
gi 150378501  669 LHGGSLV 675
Cdd:cd06237   134 EPGGKVV 140
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
 503-680 4.64e-07

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 Carboxypeptidase (CP) A (CPA) belongs to the A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPA enzymes generally favor hydrophobic residues. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. This subfamily includes CPA1, CPA2 and CPA4 forms. Within these A forms, there are slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer.


Pssm-ID: 349442 [Multi-domain]  Cd Length: 301  Bit Score: 53.21  E-value: 4.64e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  503 HHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPgvhePGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 582
Cdd:cd03870     7 HTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIVS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  583 NFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSI-----SVVGRNNSNNFDLNRNFPDQFV-------PITEP---- 646
Cdd:cd03870    83 DYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNRLwrktrSVNPGSLCIGVDPNRNWDAGFGgpgassnPCSETyhgp 162

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 150378501  647 ---TQPETIAVMSWVKAY-PFVLSANLHGGSLVVNYPY 680
Cdd:cd03870   163 hanSEVEVKSIVDFIQSHgNFKAFISIHSYSQLLMYPY 200
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 1023-1093 1.05e-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: 51.41  E-value: 1.05e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501 1023 DRTRIVIVPSLNPDGRERaqekdctsktGH--TNAHGKDLDTDFtSNASQPETKAI---IENLIQKQDFSLSIALD 1093
Cdd:cd06237    80 ARFRVLVVPLLNPDGVDL----------GHwrHNAGGVDLNRDW-GPFTQPETRAVrdfLLELVEEPGGKVVFGLD 144
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
 90-298 1.54e-06

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 Carboxypeptidase (CP) B2 (CPB2, also known as plasma carboxypeptidase B, carboxypeptidase U, and CPU), belongs to the carboxpeptidase A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPB2 enzyme displays B-like activity; it only cleaves the basic residues lysine or arginine. It is produced and secreted by the liver as the inactive precursor, procarboxypeptidase U or PCPB2, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). It circulates in plasma as a zymogen bound to plasminogen, and the active enzyme, TAFIa, inhibits fibrinolysis. It is highly regulated, increased TAFI concentrations are thought to increase the risk of thrombosis and coronary artery disease by reducing fibrinolytic activity while low TAFI levels have been correlated with chronic liver disease.


Pssm-ID: 349465 [Multi-domain]  Cd Length: 300  Bit Score: 51.73  E-value: 1.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   90 IGSSVEGRPLWVLRLTAGLGPPPTAaagldaagpllpgrpqVKLVGNMHGDETVSRQVLVYLaRELASGYRRGDPRLVRL 169
Cdd:cd06246    31 IGSSFEKYPLYVLKVSGKEQTAKNA----------------IWIDCGIHAREWISPAFCLWF-IGHASYFYGIIGQHTNL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  170 LNTTDVYLLPSLNPDGFERAREGDCGLGDSGppgtSGRDNSR--GRDLNRSFpDQFSTGEPPSLDEV------------P 235
Cdd:cd06246    94 LNLVDFYVMPVVNVDGYDYSWKKNRMWRKNR----SKHANNRciGTDLNRNF-DAGWCGKGASSDSCsetycgpypeseP 168

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 150378501  236 EVRALIDWIRRNKFVLSG--NLHGGSVVA----SYPFDDSPEHKTTGLYSKTSDDEVFRYLAKAYASNH 298
Cdd:cd06246   169 EVKAVASFLRRHKDTIKAyiSMHSYSQMVlfpySYTRNKSKDHDELSLLAKEAVTAIRKTSRNRYTYGP 237
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
 87-248 1.55e-06

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


Pssm-ID: 349444 [Multi-domain]  Cd Length: 300  Bit Score: 51.52  E-value: 1.55e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   87 LFSIGSSVEGRPLWVLRLtaglgppptaaaGLDAagpllpgRPQVKLV---GNMHGDETVSRQVLVYLARELASGYRRgD 163
Cdd:cd03872    25 MFSIGKSYEGRSLYVLKL------------GKRS-------RSYKKAVwidCGIHAREWIGPAFCQWFVKEAINSYQT-D 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  164 PRLVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDSGPPGTsgRDNSRGRDLNRSFP----DQFSTGEP-------PSLD 232
Cdd:cd03872    85 PAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKNS--RFQCRGVDANRNWKvkwcDEGASLHPcddtycgPFPE 162

                         170
                  ....*....|....*.
gi 150378501  233 EVPEVRALIDWIRRNK 248
Cdd:cd03872   163 SEPEVKAVAQFLRKHR 178
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 982-1094 2.05e-06

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


Pssm-ID: 349461 [Multi-domain]  Cd Length: 220  Bit Score: 50.38  E-value: 2.05e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  982 PKIRFVAGIHGNAPVGTELLLALAEFLCLNYKRNPvvtqLVDRTRIVIVPSLNPDGRERAQEkdctsktghTNAHGKDLD 1061
Cdd:cd06242     2 PTVLLVGQQHGNEPAGREAALALARDLAFGDDARE----LLEKVNVLVVPRANPDGRAANTR---------GNANGVDLN 68

                          90       100       110
                  ....*....|....*....|....*....|...
gi 150378501 1062 TDFTsNASQPETKAIIENLiqkQDFSLSIALDG 1094
Cdd:cd06242    69 RDHL-LLSTPETRALARVL---RDYRPEVVIDA 97
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 137-257 2.24e-06

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


Pssm-ID: 349458 [Multi-domain]  Cd Length: 194  Bit Score: 49.72  E-value: 2.24e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  137 MHGDETVSRQVLVYLARELasgyRRGDPRLVRLLNTTDVYLLPSLNPDGFERARegdcglgdsgppgtsgRDNSRGRDLN 216
Cdd:cd06239     8 MHGNEPTGTEALLDLISYL----RRERQEFEKILERLTLVAIPMLNPDGAELFT----------------RHNAEGIDLN 67

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 150378501  217 RsfpDQFSTGEPpsldevpEVRALIDWIRRNKFVLSGNLHG 257
Cdd:cd06239    68 R---DARALQTP-------ESRALKAVLDSFSPKFAFNLHD 98
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
 965-1076 2.50e-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: 50.53  E-value: 2.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  965 IWSLEISNKPNISEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKRNPVVTQLVDRTRIVIVPSLNPDGRERA--- 1041
Cdd:cd06226     2 IRALKLTNKQATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAetg 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 150378501 1042 --QEKDCTSKTGHT--NAHGKDLDTDFT--------------------SNASQPETKAI 1076
Cdd:cd06226    82 llWRKNTNTTPCPAssPTYGVDLNRNSSfkwggagaggsacsetyrgpSAASEPETQAI 140
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 135-246 3.64e-06

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


Pssm-ID: 349457  Cd Length: 217  Bit Score: 49.66  E-value: 3.64e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  135 GNMHGDETVSRQVLVYLARELASGyrrGDPRLVRLLNTTDVYLLPSLNPDGFER------AREGDCGLGDS-----GPPG 203
Cdd:cd06238     8 YSIHGNELSGSEAAMQVAYHLAAG---QDEATRALLENTVIVIDPNQNPDGRERfvnwfnQNRGAVGDPDPqsmehNEPW 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 150378501  204 TSGRDNSRGRDLNRsfpDQFSTGEppsldevPEVRALIDWIRR 246
Cdd:cd06238    85 PGGRTNHYLFDLNR---DWLAQTQ-------PESRARAAAIHR 117
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 558-684 4.54e-06

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


Pssm-ID: 349447  Cd Length: 294  Bit Score: 50.08  E-value: 4.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  558 YIGNMHGNEVVGRELLLNLIE-------------YLCKNFGTDpEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSI----- 619
Cdd:cd06228     5 FIGGVHAREWGSPDILIYFAAdlleaytnntgltYGGKTFTAA-QVKSILENVDLVVFPLVNPDGRWYSQTSESMwrknr 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  620 ---SVVGRNNSNNFDLNRN------FPDQFVPITEPT----------------QPETIAVMSWVKAYP----FVlsaNLH 670
Cdd:cd06228    84 npaSAGDGGSCIGVDINRNfdflwdFPRYFDPGRVPAstspcsetyhgpsafsEPETRNVVWLFDAYPnirwFV---DVH 160

                         170
                  ....*....|....
gi 150378501  671 GGSLVVNYPYDDNE 684
Cdd:cd06228   161 SASELILYSWGDDE 174
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
 502-660 5.00e-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: 49.85  E-value: 5.00e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEI---SDNPgvhepgepefKYIGNM----HGNEVVGRELLL 574
Cdd:cd06247     4 YHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKP----------KKIIWMdcgiHAREWIAPAFCQ 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  575 NLIEYLCKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNN-----FDLNRNFPDQFVPI------ 643
Cdd:cd06247    74 WFVKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLWRKSRSPHNNgtcygTDLNRNFNSQWCSIgasrnc 153

                         170       180
                  ....*....|....*....|....*
gi 150378501  644 -------TEP-TQPETIAVMSWVKA 660
Cdd:cd06247   154 csiifcgTGPeSEPETKAVADLIEK 178
M14_Nna1-like cd18429
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 90-246 5.50e-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: 349485  Cd Length: 253  Bit Score: 49.38  E-value: 5.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   90 IGSSVEGRPLWVLRltagLGPPPTaaagldaagpllPGRpqVKLVGNMHGDETVSRQVLVYLARELAsgyrRGDPRLVRL 169
Cdd:cd18429    20 IGKTVEGRPLEIIR----IGNESA------------PHR--VFLRARAHPWEAGGNWVVEGLVERLL----QNDEEAKRF 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 150378501  170 LNTTDVYLLPSLNPDGFERAREgdcglgdsgppgtsgRDNSRGRDLNRSFpdqfstGEPPSLDEVPEVRALIDWIRR 246
Cdd:cd18429    78 LKRYCVYILPMANKDGVARGRT---------------RFNANGKDLNREW------DKPADPVLAPENFALEKWLEE 133
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
 795-869 7.42e-06

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


Pssm-ID: 433425 [Multi-domain]  Cd Length: 88  Bit Score: 45.66  E-value: 7.42e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 150378501   795 VKGFVLDATDGRGILNATLSVAEINHPVTTYKAGDY-WRLLVPGTYKITASARGYNPVTKNVTVRSEGAVQVNFTL 869
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTDADGNFeLKNLPAGTYTLVVSFVGYKTQEKKVTVSNDNTLDVNFLL 76
M14-like cd06244
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 1013-1083 8.41e-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: 349463 [Multi-domain]  Cd Length: 223  Bit Score: 48.60  E-value: 8.41e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 150378501 1013 KRNPVVTQLVDRTRIVIVPSLNPDGRERAQEkdctsktghTNAHGKDLDTDFTsNASQPETKAIIEnLIQK 1083
Cdd:cd06244    45 NVDLEVKDLLDDVFFIVVPTENPDGRVANTR---------TNANGFDLNRDNA-YQTQPETRAMQE-LISK 104
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
 502-680 8.91e-06

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


Pssm-ID: 349444 [Multi-domain]  Cd Length: 300  Bit Score: 49.21  E-value: 8.91e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  502 HHHFPDMEIFLRRFANEYPNITRLYSLGKSVESRELYVMEIsdnpGVHEPGEPEFKYIG-NMHGNEVVGRELLLNLIEYL 580
Cdd:cd03872     2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIDcGIHAREWIGPAFCQWFVKEA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  581 CKNFGTDPEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVGRNNSNNF-----DLNRNFPDQFV-------------- 641
Cdd:cd03872    78 INSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKNSRFqcrgvDANRNWKVKWCdegaslhpcddtyc 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 150378501  642 -PITEpTQPETIAVMSW-------VKAYpfvlsANLHGGSLVVNYPY 680
Cdd:cd03872   158 gPFPE-SEPEVKAVAQFlrkhrkhVRAY-----LSFHAYAQMLLYPY 198
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 86-246 9.66e-06

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


Pssm-ID: 349456 [Multi-domain]  Cd Length: 239  Bit Score: 48.72  E-value: 9.66e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   86 RLFSIGSSVEGRPLWVLRLTAGlgppptaaagldaagpllPGRPQVKLVGNMHGDETVSRQVLVYLARELASgyrrgDPR 165
Cdd:cd06237    17 KRSTIGKSVEGRPIEALTIGNP------------------DSKELVVLLGRQHPPEVTGALAMQAFVETLLA-----DTE 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  166 LVR-LLNTTDVYLLPSLNPDGFERaregdcglgdsgppgtsG--RDNSRGRDLNR---SFpDQfstgeppsldevPEVRA 239
Cdd:cd06237    74 LAKaFRARFRVLVVPLLNPDGVDL-----------------GhwRHNAGGVDLNRdwgPF-TQ------------PETRA 123


                  ....*..
gi 150378501  240 LIDWIRR 246
Cdd:cd06237   124 VRDFLLE 130
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 129-232 1.04e-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: 48.92  E-value: 1.04e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  129 PQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDP-----------RLVRLLNTTDVYLLPSLNPDGFERAREGDCGLG 197
Cdd:cd06228     1 PGVYFIGGVHAREWGSPDILIYFAADLLEAYTNNTGltyggktftaaQVKSILENVDLVVFPLVNPDGRWYSQTSESMWR 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 150378501  198 DSGPPGTSGRDNSR-GRDLNRS------FPDQFSTGEPPSLD 232
Cdd:cd06228    81 KNRNPASAGDGGSCiGVDINRNfdflwdFPRYFDPGRVPAST 122
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 128-241 1.33e-05

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


Pssm-ID: 349460 [Multi-domain]  Cd Length: 215  Bit Score: 47.64  E-value: 1.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  128 RPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGdprlvrLLNTTDVYLLPSLNPDGFERAREGDcGLGDSGPPGTSGR 207
Cdd:cd06241     1 KPVVLIQAGIHPGEVEGKEASLMLLRDIAQGGKKH------LLDNLILLFVPIFNADGNDRRSKGN-RPNQNGPLEVGWR 73

                          90       100       110
                  ....*....|....*....|....*....|....
gi 150378501  208 DNSRGRDLNRSFPDQfstgeppsldEVPEVRALI 241
Cdd:cd06241    74 TNAQGLDLNRDFMKL----------EAPETRALA 97
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
 522-671 1.79e-05

Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar to Pseudomonas aerugnosa CCP (PaCCP); A bacterial subgroup of the Peptidase M14-like domain of Nna-1 (Nervous system Nuclear protein induced by Axotomy), also known as ATP/GTP binding protein (AGTPBP-1) and cytosolic carboxypeptidase (CCP)-like proteins. This subgroup includes PaCCP from Pseudomonas aeruginosa, a carboxypeptidase homologous to M14D subfamily of human CCPs. Structural complexes with well-known inhibitors of metallocarboxypeptidases indicate that PaCCP might only possess C-terminal hydrolase activity against cellular substrates of particular specificity. The Peptidase M14 family of metallocarboxypeptidases are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Nna1-like proteins are active metallopeptidases that are thought to act on cytosolic proteins (such as alpha-tubulin in eukaryotes) to remove a C-terminal tyrosine. Nna1-like proteins from the different phyla are highly diverse, but they all contain a unique N-terminal conserved domain right before the CP domain. It has been suggested that this N-terminal domain might act as a folding domain.


Pssm-ID: 349453 [Multi-domain]  Cd Length: 256  Bit Score: 47.95  E-value: 1.79e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  522 ITRLYSLGKSVESRELYVMEISDNPG----------VHePGEPEFKYIgnMHGnevvgrelllnLIEYLCKNfgTDPEVT 591
Cdd:cd06234    18 GVRLEVLGQTLDGRDIDLLTIGDPGTgkkkvwiiarQH-PGETMAEWF--MEG-----------LLDRLLDE--DDPVSR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  592 DLVRSTRIHLMPSMNPDGyeksqegdsiSVVG--RNNSNNFDLNRNF--PDqfvpitEPTQPETIAVMSWVKAYPFVLSA 667
Cdd:cd06234    82 ALLEKAVFYVVPNMNPDG----------SVRGnlRTNAAGVNLNREWanPS------LERSPEVFAVRQAMDATGVDFFL 145


                  ....
gi 150378501  668 NLHG 671
Cdd:cd06234   146 DVHG 149
M14_Nna1-like cd03856
Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related ...
 87-283 1.93e-05

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: 47.96  E-value: 1.93e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   87 LFSIGSSVEGRPLWVLRLTAGLGPPptaaagldaagpllpGRPQVKLVGNMHGDETVSRQVLVYLARELASGyrrgDPRL 166
Cdd:cd03856    17 LLEIGVTEQGREIQALQSLRTERSD---------------DKSWLFLIARQHPGETTGAWVFFGFLDQLLSD----DDPA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  167 VRLLNTTDVYLLPSLNPDGFERAREgdcglgdsgppgtsgRDNSRGRDLNRSFpdqfstgEPPSLDEVPEVRALIDWI-- 244
Cdd:cd03856    78 QQLRAEYNFYIIPMVNPDGVARGHW---------------RTNSRGMDLNRDW-------HAPDALLSPETYAVAAALae 135

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 150378501  245 ---RRNKFVLSGNLHGGSVVASYPFDDSPEHKTTGLYSKTSD 283
Cdd:cd03856   136 rvqSPEGVVLALDLHGDNRNVFLTGPDNKDESTNHNPDKLNS 177
M14-like cd06240
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 128-211 2.89e-05

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


Pssm-ID: 349459  Cd Length: 212  Bit Score: 46.88  E-value: 2.89e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  128 RPQVKLVGNMHGDETVSRQVLVYLARELASgyrRGDPRLVRLLNTTDVYLLPSLNPDGFERA-----REGDCGLGDSGPP 202
Cdd:cd06240     1 KAVVWIDGGLHATEVAGSQMLPELAYRLAT---SDDEEVRRILDNVILLLVPSANPDGQDLVvdwymRYKDTPKEGSRLP 77

                          90
                  ....*....|...
gi 150378501  203 GT----SGRDNSR 211
Cdd:cd06240    78 WLyqkyVGHDNNR 90
COG3608 COG3608
Predicted deacylase [General function prediction only];
126-221 3.06e-05

Predicted deacylase [General function prediction only];


Pssm-ID: 442826 [Multi-domain]  Cd Length: 296  Bit Score: 47.53  E-value: 3.06e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  126 PGrPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGdpRLVrllnttdvyLLPSLNPDGFERAregdcglgdsgppgts 205
Cdd:COG3608    25 PG-PTLLITAGIHGDELNGIEALRRLLRELDPGELRG--TVI---------LVPVANPPGFLQG---------------- 76

                          90
                  ....*....|....*..
gi 150378501  206 GRDNSR-GRDLNRSFPD 221
Cdd:COG3608    77 SRYLPIdGRDLNRSFPG 93
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
 1011-1093 3.40e-05

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: 46.95  E-value: 3.40e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1011 NYKRNPVVTQLVDRTRIVIVPSLNPDG----------------RERAQEKDCTSKTG-HTNAHGKDLDTDF--------T 1065
Cdd:cd06229    33 SYIRGKDVGELLNKVTLHIVPMVNPDGveisqngsnainpyylRLVAWNKKGTDFTGwKANIRGVDLNRNFpagwekekR 112

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 150378501 1066 SNA--------------SQPETKAIIeNLIQKQDFSLSIALD 1093
Cdd:cd06229   113 LGPkapgprdypgkeplSEPETKAMA-ALTRQNDFDLVLAYH 153
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
1211-1283 4.78e-05

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 43.04  E-value: 4.78e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  1211 GVHGLVKDKAGKPISKAVIVL-----NEGIKVYTKEGGYFHV-LLAPGVHNINAIADGYQQQH-TQVFVHHDAASSVVIV 1283
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRFpGLPPGTYTVTVSAPGFKTATrTGVTVTAGQTTTLDVT 80
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
 91-350 1.37e-04

Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 carboxypeptidases found specifically in insects, including B-type carboxypeptidase of H. zea (CPBHz, insect gut carboxypeptidase-3) that is insensitive to potato carboxypeptidase inhibitor (PCI) in corn earworm, and midgut procarboxypeptidase A (PCPAHa, insect gut carboxypeptidase-1) from Helicoverpa armigera larva, a devastating pest of crops. PCPAHa preferentially cleaves aliphatic and aromatic residues. The peptidase M14 Carboxypeptidase (CP) A/B subfamily is one of two main M14 CP subfamilies defined by sequence and structural homology, the other being the N/E subfamily. CPs hydrolyze single, C-terminal amino acids from polypeptide chains. They have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. There are nine members in the A/B family: CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPB, CPO and CPU. CPA1, CPA2 and CPB are produced by the pancreas. The A forms have slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA3 is found in secretory granules of mast cells and functions in inflammatory processes. CPA4 is detected in hormone-regulated tissues, and is thought to play a role in prostate cancer. CPA5 is present in discrete regions of pituitary and other tissues, and cleaves aliphatic C-terminal residues. CPA6 is highly expressed in embryonic brain and optic muscle, suggesting that it may play a specific role in cell migration and axonal guidance. CPU (also called CPB2) is produced and secreted by the liver as the inactive precursor, PCPU, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). Little is known about CPO but it has been suggested to have specificity for acidic residues.


Pssm-ID: 349467 [Multi-domain]  Cd Length: 297  Bit Score: 45.53  E-value: 1.37e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   91 GSSVEGRPLWVLRLTAGlgppptaaAGLDAAgpllpgRPQVKLVGNMHGDETVSRQVLVYLARELASGYRRGDPrlvrLL 170
Cdd:cd06248    28 GYTFEGRPIKYVRIRST--------NSEDTS------KPTIMIEGGINPREWISPPAALYAIHKLVEDVETQSD----LL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  171 NTTDVYLLPSLNPDGFERAREGDCGLGDSGPPGTSGRDNS-RGRDLNRSFPDQF----STGEP-------PSLDEVPEVR 238
Cdd:cd06248    90 NNFDWIILPVANPDGYVFTHTNDREWTKNRSTNSNPLGQIcFGVNINRNFDYQWnpvlSSESPcselyagPSAFSEAESR 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  239 ALIDWI--RRNKFVLSGNLHGGSVVASYPFDDSPehkttglysKTSDDEVFRYLAKAYASNHPIMKTGEPHCPGdedetf 316
Cdd:cd06248   170 AIRDILheHGNRIHLYISFHSGGSFILYPWGYDG---------STSSNARQLHLAGVAAAAAISSNNGRPYVVG------ 234

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 150378501  317 kdgitNGAHW-YDVEGGMQDYNYVWANcFEITLEL 350
Cdd:cd06248   235 -----QSSVLlYRAAGTSSDYAMGIAG-IDYTYEL 263
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
 929-1127 1.71e-04

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 Carboxypeptidase B (CPB) belongs to the carboxypeptidase A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Carboxypeptidase B (CPB) enzymes only cleave the basic residues lysine or arginine. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients. this subfamily also includes thrombin activatable fibrinolysis inhibitor (TAFIa), a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help in prevention of thrombosis.


Pssm-ID: 349443 [Multi-domain]  Cd Length: 300  Bit Score: 45.14  E-value: 1.71e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  929 RYHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISnKPNisePEEPKIRFVAGIHGNAPVGTELLLALAEFL 1008
Cdd:cd03871     5 KYNNWETIEAWTEQVASKNPDLVSRSQIGTTFEGRPIYLLKVG-KPG---SNKKAIFMDCGFHAREWISPAFCQWFVREA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1009 CLNYKRNPVVTQLVDRTRIVIVPSLNPDG------RERAQEKDcTSKTGHTNAHGKDLDTDF---------TSNA----- 1068
Cdd:cd03871    81 VRTYGKEKIMTKLLDRLDFYILPVLNIDGyvytwtKNRMWRKT-RSPNAGSSCIGTDPNRNFnagwctvgaSSNPcsety 159

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 150378501 1069 ------SQPETKAiIENLIQKQDFSLS--IALDGGSVLVTYPYDKPVQTVEN--------KETLKHLASLYANNH 1127
Cdd:cd03871   160 cgsapeSEKETKA-LANFIRNNLSSIKayLTIHSYSQMLLYPYSYTYKLAPNheelnsiaKGAVKELSSLYGTKY 233
M14-like cd03862
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
 554-637 3.36e-04

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


Pssm-ID: 349434  Cd Length: 245  Bit Score: 43.96  E-value: 3.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  554 PEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVRSTRIHLMPSMNPDGyeksqegdsISVVGRNNSNNFDLN 633
Cdd:cd03862     1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGG---------MALKTRSNPNGVDLM 71


                  ....
gi 150378501  634 RNFP 637
Cdd:cd03862    72 RNAP 75
AstE_AspA pfam04952
Succinylglutamate desuccinylase / Aspartoacylase family; This family includes ...
 129-234 4.08e-04

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


Pssm-ID: 428216 [Multi-domain]  Cd Length: 289  Bit Score: 43.88  E-value: 4.08e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501   129 PQVKLVGNMHGDETVSRQVLVYLARELASGYRRGdprlvrllnttDVYLLPSLNPDGFERARegdcglgdsgppgtsgRD 208
Cdd:pfam04952    3 PTLLLSAGIHGNETNGVELLRRLLRQLDPGDIAG-----------ERTLVPLANPPAFRAGS----------------RY 55

                           90       100
                   ....*....|....*....|....*.
gi 150378501   209 NSrgRDLNRSFPDQFSTGEPPSLDEV 234
Cdd:pfam04952   56 IP--RDLNRSFPGRALGASSDEPYRA 79
M14_ASTE_ASPA_like cd06230
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA) subfamily; The ...
 133-266 7.84e-04

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


Pssm-ID: 349449 [Multi-domain]  Cd Length: 177  Bit Score: 41.91  E-value: 7.84e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  133 LVGNMHGDETVSRQVLVYLARELASGYRRGdpRLVrllnttdvyLLPSLNPDGFERAREGdcglgdsgppgtsgrDNSRG 212
Cdd:cd06230     3 ILAGVHGDEYEGVEAIRRLLAELDPSELKG--TVV---------LVPVANPPAFEAGTRY---------------TPLDG 56

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 150378501  213 RDLNRSFPdqfstGEPPSLDEVPEVRALIDWIRRN-KFVLSgnLHGGSVVASYPF 266
Cdd:cd06230    57 LDLNRIFP-----GDPDGSPTERLAHELTELILKHaDALID--LHSGGTGRLVPY 104
M14_Nna1-like cd18429
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
 507-683 7.88e-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: 42.83  E-value: 7.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  507 DMEIFLRRFA-NEYPNITRLyslGKSVESRELYVMEISDNPGVH-----------EPGepefkyignmhGNEVVGrelll 574
Cdd:cd18429     1 DLDRLLAKIRkNPLVEITTI---GKTVEGRPLEIIRIGNESAPHrvflrarahpwEAG-----------GNWVVE----- 61

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  575 NLIEYLCKNfgtDPEVTDLVRSTRIHLMPSMNPDGYEKSQEgdsisvvgRNNSNNFDLNRNFPDqfvPITEPTQPETIAV 654
Cdd:cd18429    62 GLVERLLQN---DEEAKRFLKRYCVYILPMANKDGVARGRT--------RFNANGKDLNREWDK---PADPVLAPENFAL 127

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 150378501  655 MSWV------KAYPFvLSANLH---GGSLVVNYPYDDN 683
Cdd:cd18429   128 EKWLeemikaGKKPD-LAIELHndgGGNLHVSRPPVDG 164
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
 929-1121 1.68e-03

Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 Carboxypeptidase (CP) B2 (CPB2, also known as plasma carboxypeptidase B, carboxypeptidase U, and CPU), belongs to the carboxpeptidase A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPB2 enzyme displays B-like activity; it only cleaves the basic residues lysine or arginine. It is produced and secreted by the liver as the inactive precursor, procarboxypeptidase U or PCPB2, commonly referred to as thrombin-activatable fibrinolysis inhibitor (TAFI). It circulates in plasma as a zymogen bound to plasminogen, and the active enzyme, TAFIa, inhibits fibrinolysis. It is highly regulated, increased TAFI concentrations are thought to increase the risk of thrombosis and coronary artery disease by reducing fibrinolytic activity while low TAFI levels have been correlated with chronic liver disease.


Pssm-ID: 349465 [Multi-domain]  Cd Length: 300  Bit Score: 42.10  E-value: 1.68e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  929 RYHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKpniSEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1008
Cdd:cd06246     4 QYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGK---EQTAKNAIWIDCGIHAREWISPAFCLWFIGHA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1009 CLNYKRNPVVTQLVDRTRIVIVPSLNPDG-----RERAQEKDCTSKTGHTNAHGKDLDTDFTSN---------------- 1067
Cdd:cd06246    81 SYFYGIIGQHTNLLNLVDFYVMPVVNVDGydyswKKNRMWRKNRSKHANNRCIGTDLNRNFDAGwcgkgassdscsetyc 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 150378501 1068 ----ASQPETKAIIENLIQKQD-FSLSIALDGGSVLVTYPYDKPVQTVENKETLKHLAS 1121
Cdd:cd06246   161 gpypESEPEVKAVASFLRRHKDtIKAYISMHSYSQMVLFPYSYTRNKSKDHDELSLLAK 219
M14_ASTE_ASPA-like cd06254
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 126-301 2.06e-03

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


Pssm-ID: 349472  Cd Length: 198  Bit Score: 41.03  E-value: 2.06e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  126 PGrPQVKLVGNMHGDETVSRQVLVYLARELasgyrrgDPRLVRllntTDVYLLPSLNPDGFERARegdcglgdsgpPGTS 205
Cdd:cd06254    10 PG-PTLLITAGIHGGEYPGILAAIRLAREL-------DPADVK----GTLIIVHIANVSGFEART-----------PFVV 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  206 GRDnsrGRDLNRSFPdqfstGEPP-SLDEvpevrALIDWIRRNKFVLSG---NLHGGSVV-ASYPFddspehkttGLYSK 280
Cdd:cd06254    67 PED---GKNLNRVFP-----GDPDgTLTE-----RIAYFLTREIISRADfliDLHGGDANeALTPF---------VYYPG 124

                         170       180
                  ....*....|....*....|..
gi 150378501  281 TSDDEVF-RYLAKAYASNHPIM 301
Cdd:cd06254   125 GASEEVNdISRAAAQALGLPYI 146
PRK10602 PRK10602
murein tripeptide amidase MpaA;
598-639 2.08e-03

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 41.55  E-value: 2.08e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 150378501  598 RIHLMPSMNPDGyekSQEGDsisvvgRNNSNNFDLNRNFPDQ 639
Cdd:PRK10602   72 RHHVVLAVNPDG---CQLGL------RANANGVDLNRNFPAA 104
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
 930-1112 2.24e-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: 41.89  E-value: 2.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  930 YHSYKDLSEFLRGLVMNYPHITNLTTLGQSVEYRHIWSLEISNKpniSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1009
Cdd:cd03872     2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKLGKR---SRSYKKAVWIDCGIHAREWIGPAFCQWFVKEAI 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1010 LNYKRNPVVTQLVDRTRIVIVPSLNPDGRERAQEKD-----CTSKTGHTNAHGKDLDTDFTSN----------------- 1067
Cdd:cd03872    79 NSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDrfwrkTRSKNSRFQCRGVDANRNWKVKwcdegaslhpcddtycg 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 150378501 1068 ---ASQPETKAIIENLI-QKQDFSLSIALDGGSVLVTYPYDKPVQTVEN 1112
Cdd:cd03872   159 pfpESEPEVKAVAQFLRkHRKHVRAYLSFHAYAQMLLYPYSYKYATIPN 207
M14_Nna1-like cd03856
Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related ...
 1020-1153 3.73e-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: 40.65  E-value: 3.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1020 QLVDRTRIVIVPSLNPDGRERaqekdctsktGH--TNAHGKDLDTDFTSNA--SQPET---KAIIENLIQKQ---DFSLS 1089
Cdd:cd03856    79 QLRAEYNFYIIPMVNPDGVAR----------GHwrTNSRGMDLNRDWHAPDalLSPETyavAAALAERVQSPegvVLALD 148

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 150378501 1090 IALDGGSVLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQpscpnNSDENIPGGVMRGA 1153
Cdd:cd03856   149 LHGDNRNVFLTGPDNKDESTNHNPDKLNSLLTETDRRLPDYNTEA-----SPGDNPGGTVGKQW 207
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 559-681 4.60e-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: 39.93  E-value: 4.60e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  559 IGNMHGNEVVGRELLLNLIEYLCknFGtdpEVTDLVRSTRIHLMPSMNPDGYEKSQEGDSISVVG------RNNSNNFDL 632
Cdd:cd06241     7 QAGIHPGEVEGKEASLMLLRDIA--QG---GKKHLLDNLILLFVPIFNADGNDRRSKGNRPNQNGplevgwRTNAQGLDL 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 150378501  633 NRNFpdqfvpiTEPTQPETIAVMSWVKAYPFVLSANLH--GGSlvvNYPYD 681
Cdd:cd06241    82 NRDF-------MKLEAPETRALAKLFNQWDPDLFIDTHttDGS---DHQYD 122
M14-like cd06240
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 560-612 5.47e-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 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: 39.95  E-value: 5.47e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 150378501  560 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVRSTRIHLMPSMNPDGYEK 612
Cdd:cd06240     8 GGLHATEVAGSQMLPELAYRLAT--SDDEEVRRILDNVILLLVPSANPDGQDL 58
M14_CPO cd06247
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase O subgroup; Peptidase M14 ...
 137-225 6.24e-03

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: 40.22  E-value: 6.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  137 MHGDETVSRQVLVYLARELASGYRRgDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGLGDSGPPGTSGrdNSRGRDLN 216
Cdd:cd06247    61 IHAREWIAPAFCQWFVKEILQNYKT-DSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLWRKSRSPHNNG--TCYGTDLN 137


                  ....*....
gi 150378501  217 RSFPDQFST 225
Cdd:cd06247   138 RNFNSQWCS 146
M14_ASTE_ASPA-like cd06251
Peptidase M14 Succinylglutamate desuccinylase (ASTE)/aspartoacylase (ASPA)-like; ...
 126-233 6.57e-03

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


Pssm-ID: 349469 [Multi-domain]  Cd Length: 195  Bit Score: 39.45  E-value: 6.57e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501  126 PGrPQVKLVGNMHGDE----TVSRQVLVYLARELASGyrrgdprlvrllnttDVYLLPSLNPDGFERaregdcglgdsgp 201
Cdd:cd06251    11 PG-PTLLLTAAIHGDElngiEVIQRLLEDLDPSKLRG---------------TLIAIPVVNPLGFEN------------- 61

                          90       100       110
                  ....*....|....*....|....*....|..
gi 150378501  202 pgTSGRDNSRGRDLNRSFPDqfstGEPPSLDE 233
Cdd:cd06251    62 --NSRYLPDDGRDLNRSFPG----SEKGSLAS 87
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
 1021-1084 9.78e-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: 39.16  E-value: 9.78e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 150378501 1021 LVDRTRIVIVPSLNPDGRERAQEKDCTSKTG------HTNAHGKDLDTDFTsNASQPETKAIIENLIQKQ 1084
Cdd:cd06241    36 LLDNLILLFVPIFNADGNDRRSKGNRPNQNGplevgwRTNAQGLDLNRDFM-KLEAPETRALAKLFNQWD 104
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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