NCBI Conserved Domain Search

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

Pssm-ID: 349435 [Multi-domain] Cd Length: 296 Bit Score: 683.60 E-value: 0e+00

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   503 VQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLL 582
Cdd:cd03863    1 IQPVDFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   583 NLIEYLCKNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQVTDPPQPETLAV 662
Cdd:cd03863   81 NLIEYLCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   663 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGIAIYSKSPDDAVFQQLALSYSKENKKMYQGSPCKDLYPTEYFPHGITN 742
Cdd:cd03863  161 MSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLATYSKSPDDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITN 240

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 2789654   743 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd03863  241 GAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 296

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: 571.52 E-value: 0e+00

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd03858    1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 KNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQV---TDPPQPETLAVMSWL 666
Cdd:cd03858   81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVysdNNPRQPETKAVMNWL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   667 KTYPFVLSANLHGGSLVVNYPFDDDEQG-IAIYSKSPDDAVFQQLALSYSKENKKMYQGSPCKDlYPTEYFPHGITNGAQ 745
Cdd:cd03858  161 ESIPFVLSANLHGGALVANYPYDDTRSGkSTEYSPSPDDAVFRMLARSYSDAHPTMSMGKPCCC-DDDENFPNGITNGAA 239

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 2789654   746 WYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd03858  240 WYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292

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

Pssm-ID: 349464 [Multi-domain] Cd Length: 283 Bit Score: 507.75 E-value: 6.71e-170

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTSKLGHANAHGRDLDTDFTSNYSRYSGTREPETKAIIENLILK 1093
Cdd:cd06245   81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANNRSGAAQPETKAIMDWLKEK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1094 qDFSLSVALDGGSLLVTYPFDKPAQTVENKDTLKHLASVYANNHPLMHLGQPGCPNKSDENIPGGVIRGSEWHSHLGSMK 1173
Cdd:cd06245  161 -DFTLSVALDGGSLVVTYPYDKPVQTVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSML 239

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 2789654  1174 DFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSMLVE 1217
Cdd:cd06245  240 DFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283

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

Pssm-ID: 349440 Cd Length: 294 Bit Score: 465.18 E-value: 1.44e-153

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   511 HHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 590
Cdd:cd03868    2 HNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLLE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   591 NFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGD---RGGTVGRNNSNNYDLNRNFPDQFFQVTDPP----QPETLAVM 663
Cdd:cd03868   82 NYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDcsgDPGYGGRENANNVDLNRNFPDQFEDSDDRLlegrQPETLAMM 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   664 SWLKTYPFVLSANLHGGSLVVNYPFDDDEQGIA--IYSKSPDDAVFQQLALSYSKENKKMYQGSPCKDlyptEYFPHGIT 741
Cdd:cd03868  162 KWIVENPFVLSANLHGGSVVASYPFDDSPSHIEcgVYSKSPDDAVFRHLAHTYADNHPTMHKGNNCCE----DSFKDGIT 237

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 2789654   742 NGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd03868  238 NGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294

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: 406.63 E-value: 1.75e-131

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    48 YLHAAELGQALRDLvAEAPPGLARLFSIGRSVEGRPLWVLRLTAGlpelPEARQdgekkkkeeeeeeeeegeeggggalP 127
Cdd:cd03868    1 YHNYDELTDLLHKL-AETYPNIAKLHSIGKSVQGRELWVLEISDN----VNRRE-------------------------P 50

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   128 GRPQVKLVGNMHGDEPLARPLLLRLAQELVRGWaGGDERLGRLLNTTDLYLLPSLNPDGFERAREGDCGGGGGGEGGGep 207
Cdd:cd03868   51 GKPMFKYVANMHGDETVGRQLLIYLAQYLLENY-GKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDPGYGGRE-- 127

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   208 ggreNSRGRDLNRSFPDQF-GSAQPDLEP-VPEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPTHRPTGVYSKSAD 285
Cdd:cd03868  128 ----NANNVDLNRNFPDQFeDSDDRLLEGrQPETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPD 203

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   286 DEVFKYLAKAYASHHPIMRTGKPNCpgeeGETFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPTSELQQ 365
Cdd:cd03868  204 DAVFRHLAHTYADNHPTMHKGNNCC----EDSFKDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPK 279

                        330
                 ....*....|....
gi 2789654   366 EWENNRESLLTFIE 379
Cdd:cd03868  280 EWDNNKEALLSYME 293

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: 384.92 E-value: 2.51e-123

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd03866    1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 KNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQVTDPPQPETLAVMSWLKTY 669
Cdd:cd03866   81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEENNVQRQPETRAVMDWIKNE 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   670 PFVLSANLHGGSLVVNYPFDD---DEQGIAIYSKSPDDAVFQQLALSYSKENKKMYQGSPCKDLyptEYFPHGITNGAQW 746
Cdd:cd03866  161 TFVLSANLHGGALVASYPFDNgnsGTGQLGYYSVSPDDDVFIYLAKTYSYNHTNMYKGIECSNS---QSFPGGITNGYQW 237

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 2789654   747 YNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd03866  238 YPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYIKQ 289

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

Pssm-ID: 349431 [Multi-domain] Cd Length: 292 Bit Score: 369.29 E-value: 1.69e-117

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd03858    1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTSKLGHANAHGRDLDTDFTSNYSRY---SGTREPETKAIIENL 1090
Cdd:cd03858   81 ENYGKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDCGGLIGRNNANGVDLNRNFPDQFFQVysdNNPRQPETKAVMNWL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1091 IlKQDFSLSVALDGGSLLVTYPFDKPA-------QTVENKDTLKHLASVYANNHPLMHLGQPgCPNKSDENIPGGVIRGS 1163
Cdd:cd03858  161 E-SIPFVLSANLHGGALVANYPYDDTRsgksteySPSPDDAVFRMLARSYSDAHPTMSMGKP-CCCDDDENFPNGITNGA 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 2789654  1164 EWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSMLVE 1217
Cdd:cd03858  239 AWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292

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

Pssm-ID: 349436 [Multi-domain] Cd Length: 313 Bit Score: 359.63 E-value: 1.09e-113

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd03864    1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 KNFGTDPE-VTDLVQSTRIHIMPSMNPDGYE--KSQEGDRGG-TVGRNNSNNYDLNRNFPD-----QFFQVTDPP----- 655
Cdd:cd03864   81 EEYRNGNErITRLIQDTRIHILPSMNPDGYEvaARQGPEFNGyLVGRNNANGVDLNRNFPDlntlmYYNEKYGGPnhhlp 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   656 ---------QPETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQ------GIAIYSKSPDDAVFQQLALSYSKENKK 720
Cdd:cd03864  161 lpdnwksqvEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREprvrgfRRTAYSPTPDDKLFQKLAKTYSYAHGW 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2789654   721 MYQGSPCKDlypteYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd03864  241 MHKGWNCGD-----YFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313

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

Pssm-ID: 349483 [Multi-domain] Cd Length: 281 Bit Score: 354.58 E-value: 2.91e-112

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   511 HHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAgEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 590
Cdd:cd18173    5 PTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA-EPEFKYTSTMHGDETTGYELMLRLIDYLLT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   591 NFGTDPEVTDLVQSTRIHIMPSMNPDG-YEKSQEGDRGGTvgRNNSNNYDLNRNFPDQFFQVTDPP---QPETLAVMSWL 666
Cdd:cd18173   84 NYGTDPRITNLVDNTEIWINPLANPDGtYAGGNNTVSGAT--RYNANGVDLNRNFPDPVDGDHPDGngwQPETQAMMNFA 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   667 KTYPFVLSANLHGGSLVVNYPFDddeqgiAIYSKSPDDAVFQQLALSYSKENKkmyQGSPckDLYPTEyFPHGITNGAQW 746
Cdd:cd18173  162 DEHNFVLSANFHGGAEVVNYPWD------TWYSRHPDDDWFQDISREYADTNQ---ANSP--PMYMSE-FNNGITNGYDW 229

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 2789654   747 YNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd18173  230 YEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281

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

Pssm-ID: 349437 [Multi-domain] Cd Length: 319 Bit Score: 347.35 E-value: 4.45e-109

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 KNFGTDPE-VTDLVQSTRIHIMPSMNPDGYEK--SQEGD-RGGTVGRNNSNNYDLNRNFPD----------------QFF 649
Cdd:cd03865   81 NEYQKGNEtIINLIHSTRIHIMPSLNPDGFEKaaSQPGElKDWFVGRSNAQGIDLNRNFPDldrivyvnekeggpnnHLL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   650 Q-----VTDPPQ--PETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGIA-IYSKSPDDAVFQQLALSYSKENKKM 721
Cdd:cd03865  161 KnmkkaVDQNTKlaPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAhEYSSCPDDAIFQSLARAYSSLNPAM 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2789654   722 YQGS--PCKDLYPTEYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd03865  241 SDPNrpPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319

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: 345.02 E-value: 1.18e-108

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    48 YLHAAELGQALRDlVAEAPPGLARLFSIGRSVEGRPLWVLRLTaglpELPEARQdgekkkkeeeeeeeeegeeggggalP 127
Cdd:cd03858    1 HHNYEELEEFLKQ-VAKRYPNITRLYSIGKSVEGRELWVLEIS----DNPGVHE-------------------------P 50

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   128 GRPQVKLVGNMHGDEPLARPLLLRLAQELVRGWaGGDERLGRLLNTTDLYLLPSLNPDGFERAregdcggggGGEGGGEP 207
Cdd:cd03858   51 GEPEFKYVANMHGNEVVGRELLLLLAEYLCENY-GKDPRVTQLVNSTRIHIMPSMNPDGYEKA---------QEGDCGGL 120

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   208 GGRENSRGRDLNRSFPDQFGSAQPDLEPV-PEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPTHRpTGVYSKSADD 286
Cdd:cd03858  121 IGRNNANGVDLNRNFPDQFFQVYSDNNPRqPETKAVMNWLESIPFVLSANLHGGALVANYPYDDTRSGK-STEYSPSPDD 199

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   287 EVFKYLAKAYASHHPIMRTGKPNCPGeEGETFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPTSELQQE 366
Cdd:cd03858  200 AVFRMLARSYSDAHPTMSMGKPCCCD-DDENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKY 278

                        330
                 ....*....|....
gi 2789654   367 WENNRESLLTFIEK 380
Cdd:cd03858  279 WEDNKRSLLNFLEQ 292

Zinc carboxypeptidase;

Pssm-ID: 459730 [Multi-domain] Cd Length: 287 Bit Score: 320.78 E-value: 7.88e-100

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     516 MEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTD 595
Cdd:pfam00246    1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     596 PEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNY-----DLNRNFPDQFFQV---TDP-----------PQ 656
Cdd:pfam00246   81 PEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANGSscigvDLNRNFPDHWNEVgasSNPcsetyrgpapfSE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     657 PETLAVMSWLKT-YPFVLSANLHGGSLVVNYPFDDDEQgiaiySKSPDDAVFQQLALSYSKENKKMYQGSpckdlypteY 735
Cdd:pfam00246  161 PETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-----EPPPDDEELKSLARAAAKALQKMVRGT---------S 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2789654     736 FPHGITNGAQWYNVPGGMQDWNYLNTNC-FEVTIELGCVK----YPKAEELPKYWEQNRRS 791
Cdd:pfam00246  227 YTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287

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

Pssm-ID: 349482 [Multi-domain] Cd Length: 276 Bit Score: 317.43 E-value: 7.16e-99

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   530 ITRLYSVGKSVELRELYVMEISDNPGVhEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNF-GTDPEVTDLVQSTRIH 608
Cdd:cd18172   21 ISRLIVIGSSVNGFPLWALEISDGPGE-DETEPAFKFVGNMHGDEPVGRELLLRLADWLCANYkAKDPLAAKIVENAHLH 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   609 IMPSMNPDGYEKSQegdrggtvgRNNSNNYDLNRNFPDQFFQV-----TDPPQPETLAVMSWLKTYPFVLSANLHGGSLV 683
Cdd:cd18172  100 LVPTMNPDGFARRR---------RNNANNVDLNRDFPDQFFPKnlrndLAARQPETLAVMNWSRSVRFTASANLHEGALV 170

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   684 VNYPFDDDEQGIAIYSKSPDDAVFQQLALSYSKENKKMYQGSPckdlypteyFPHGITNGAQWYNVPGGMQDWNYLNTNC 763
Cdd:cd18172  171 ANYPWDGNADGRTKYSASPDDATFRRLASVYAQAHPNMAKSKE---------FPGGITNGAQWYPLYGGMQDWNYLHTGC 241

                        250       260       270
                 ....*....|....*....|....*....|...
gi 2789654   764 FEVTIELGCVKYPKAEELPKYWEQNRRSLLQFI 796
Cdd:cd18172  242 MDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALA 274

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: 319.47 E-value: 7.89e-99

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd03869    1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 KNF-GTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDR---GGTVGRNNSNNYDLNRNFPD------------------- 646
Cdd:cd03869   81 QEYlAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSelgGWSLGRWTSDGIDINHNFPDlnsllweaedrkwvprkvp 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   647 -------QFFQVTDPP-QPETLAVMSWLKTYPFVLSANLHGGSLVVNYPFD--DDEQGIAIYSKSPDDAVFQQLALSYSK 716
Cdd:cd03869  161 nhhipipEWYLSENATvAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDmtRTPWKTQEYTPTPDDHVFRWLAYSYAS 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   717 ENKKMYQGS--PCKdlypTEYFP--HGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSL 792
Cdd:cd03869  241 THRLMTDASrrPCH----TEDFQkeDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESL 316


                 ....*.
gi 2789654   793 LQFIKQ 798
Cdd:cd03869  317 LVFMEQ 322

Zn_pept domain;

Pssm-ID: 214748 [Multi-domain] Cd Length: 277 Bit Score: 313.12 E-value: 3.41e-97

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGvheAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      590 KNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRN---NSNNYDLNRNFPDQFFQVTDP-----------P 655
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNRSpnsNCRGVDLNRNFPFHWGETGNPcsetyagpspfS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      656 QPETLAVMSWLKTY-PFVLSANLHGGSLVVNYPFDDDEQGIAIYSKSpDDAVFQQLALSYSKenkkmyqgspckdLYPTE 734
Cdd:smart00631  158 EPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD-LDAVAKALAKALAS-------------VHGTR 223

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 2789654      735 YfPHGITNGAQWYnVPGGMQDWNYLNTN-CFEVTIELGCV-----KYPKAEELPKY 784
Cdd:smart00631  224 Y-TYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277

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: 4.67e-93

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd03867    1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 KNF-GTDPEVTDLVQSTRIHIMPSMNPDGYEKSQE---GDRGGTVGRNNSNNYDLNRNFPDQFFQV----------TDP- 654
Cdd:cd03867   81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEegaGYNGWTSGRQNAQNLDLNRNFPDLTSEAyrlartrgarLDHi 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   655 --PQ--------PETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGIA--IYSKSPDDAVFQQLALSYSKENKKMY 722
Cdd:cd03867  161 piPQsywwgkvaPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEekMFSPTPDEKMFKLLAKAYADAHPMMS 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2789654   723 QGSP--CKDLYPTEyfpHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIK 797
Cdd:cd03867  241 DRSEnrCGGNFLKR---GGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFME 314

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: 278.75 E-value: 1.37e-84

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    45 ELRYLHAAELGQALRDLVAEAPpGLARLFSIGRSVEGRPLWVLRLTaglpelpearqdgekkkkeeeeeeeeegeEGGGG 124
Cdd:cd03863    5 DFRHHHFSDMEIFLRRYANEYP-SITRLYSVGKSVELRELYVMEIS-----------------------------DNPGV 54

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   125 ALPGRPQVKLVGNMHGDEPLARPLLLRLAQELVRGWaGGDERLGRLLNTTDLYLLPSLNPDGFERAREGDCGGggggegg 204
Cdd:cd03863   55 HEPGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNF-GTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGG------- 126

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   205 gePGGRENSRGRDLNRSFPDQFgsAQPDLEPVPEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSptHRPTGVYSKSA 284
Cdd:cd03863  127 --TVGRNNSNNYDLNRNFPDQF--FQITDPPQPETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDD--EQGLATYSKSP 200

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   285 DDEVFKYLAKAYASHHPIMRTGKPNCPGEEGETFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPTSELQ 364
Cdd:cd03863  201 DDAVFQQLALSYSKENSKMYQGSPCKELYPNEYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELP 280

                        330
                 ....*....|....*.
gi 2789654   365 QEWENNRESLLTFIEK 380
Cdd:cd03863  281 KYWEQNRRSLLQFIKQ 296

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: 273.98 E-value: 4.44e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    48 YLHAAELGQALRDlVAEAPPGLARLFSIGRSVEGRPLWVLRL-------TAGLPELpearqdgekkkkeeeeeeeeegee 120
Cdd:cd03866    1 YHNQEQMETYLKD-VNKNYPSITHLHSIGKSVEGRDLWVLVLgrfptkhRIGIPEF------------------------ 55

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   121 ggggalpgrpqvKLVGNMHGDEPLARPLLLRLAQELVRGWaGGDERLGRLLNTTDLYLLPSLNPDGFERAREGDCGGGGG 200
Cdd:cd03866   56 ------------KYVANMHGDEVVGRELLLHLIEFLVTSY-GSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKG 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   201 GEgggepggreNSRGRDLNRSFPDQFGSAqpDLEPVPEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPT-HRPTGV 279
Cdd:cd03866  123 RY---------NKNGYDLNRNFPDAFEEN--NVQRQPETRAVMDWIKNETFVLSANLHGGALVASYPFDNGNSgTGQLGY 191

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   280 YSKSADDEVFKYLAKAYASHHPIMRTGKpNCPGEEgeTFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPP 359
Cdd:cd03866  192 YSVSPDDDVFIYLAKTYSYNHTNMYKGI-ECSNSQ--SFPGGITNGYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPP 268

                        330       340
                 ....*....|....*....|.
gi 2789654   360 TSELQQEWENNRESLLTFIEK 380
Cdd:cd03866  269 EETLPQFWNDNRVALIEYIKQ 289

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

Pssm-ID: 349464 [Multi-domain] Cd Length: 283 Bit Score: 266.62 E-value: 1.66e-80

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 KNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQVTDPPQPETLAVMSWLKTY 669
Cdd:cd06245   81 HNYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKIGEKNANGVDLDTDFESNANNRSGAAQPETKAIMDWLKEK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   670 PFVLSANLHGGSLVVNYPFDDDEQgiaiysKSPDDAVFQQLALSYSKENKKMYQGSPCKDLYPTEYFPHGITNGAQWYNV 749
Cdd:cd06245  161 DFTLSVALDGGSLVVTYPYDKPVQ------TVENKETLKHLAKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSH 234

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 2789654   750 PGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIKQ 798
Cdd:cd06245  235 KGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283

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: 254.47 E-value: 6.75e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    53 ELGQALRDLVAEAPpGLARLFSIGRSVEGRPLWVLRLT--AGLPELPEarqdgekkkkeeeeeeeeegeeggggalpgrP 130
Cdd:cd03864    6 DLVRALYAVQNECP-YITRIYSIGRSVEGRHLYVLEFSdnPGIHEPLE-------------------------------P 53

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   131 QVKLVGNMHGDEPLARPLLLRLAQELVRGWAGGDERLGRLLNTTDLYLLPSLNPDGFERAregdcgGGGGGEGGGEPGGR 210
Cdd:cd03864   54 EFKYVGNMHGNEVLGRELLIQLSEFLCEEYRNGNERITRLIQDTRIHILPSMNPDGYEVA------ARQGPEFNGYLVGR 127

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   211 ENSRGRDLNRSFPD---------QFGSAQ-----PD---LEPVPEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPT 273
Cdd:cd03864  128 NNANGVDLNRNFPDlntlmyyneKYGGPNhhlplPDnwkSQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSRE 207

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   274 HRPTG----VYSKSADDEVFKYLAKAYASHHPIMRTGKpNCpgeeGETFQDGITNGAQWYDVEGGMQDYNYVWANCFEIT 349
Cdd:cd03864  208 PRVRGfrrtAYSPTPDDKLFQKLAKTYSYAHGWMHKGW-NC----GDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEIT 282

                        330       340       350
                 ....*....|....*....|....*....|.
gi 2789654   350 LELSCCKYPPTSELQQEWENNRESLLTFIEK 380
Cdd:cd03864  283 LELSCDKFPPEEELEREWLGNREALISYMEQ 313

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: 246.39 E-value: 2.73e-73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd03868    1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTS---KLGHANAHGRDLDTDF-----TSNYSRYSGtREPETKA 1085
Cdd:cd03868   81 ENYGKDERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGdpgYGGRENANNVDLNRNFpdqfeDSDDRLLEG-RQPETLA 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1086 IIeNLILKQDFSLSVALDGGSLLVTYPFDKPAQTVENK--------DTLKHLASVYANNHPLMHLGQPGCpnksDENIPG 1157
Cdd:cd03868  160 MM-KWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGvyskspddAVFRHLAHTYADNHPTMHKGNNCC----EDSFKD 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 2789654  1158 GVIRGSEWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLS 1213
Cdd:cd03868  235 GITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLS 290

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: 240.39 E-value: 1.88e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    48 YLHAAELGQALRDLVAEaPPGLARLFSIGRSVEGRPLWVLRLTAGlPELPEARqdgekkkkeeeeeeeeegeeggggalp 127
Cdd:cd18172    1 YHSNAELEDALKAFTRR-CGAISRLIVIGSSVNGFPLWALEISDG-PGEDETE--------------------------- 51

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   128 grPQVKLVGNMHGDEPLARPLLLRLAQELVRGWAGGDERLGRLLNTTDLYLLPSLNPDGFERAREGdcggggggegggep 207
Cdd:cd18172   52 --PAFKFVGNMHGDEPVGRELLLRLADWLCANYKAKDPLAAKIVENAHLHLVPTMNPDGFARRRRN-------------- 115

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   208 ggreNSRGRDLNRSFPDQFgSAQPDLEPV----PEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPTHRptGVYSKS 283
Cdd:cd18172  116 ----NANNVDLNRDFPDQF-FPKNLRNDLaarqPETLAVMNWSRSVRFTASANLHEGALVANYPWDGNADGR--TKYSAS 188

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   284 ADDEVFKYLAKAYASHHPIMRTGKpncpgeegeTFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPTSEL 363
Cdd:cd18172  189 PDDATFRRLASVYAQAHPNMAKSK---------EFPGGITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRL 259

                        330
                 ....*....|....*.
gi 2789654   364 QQEWENNRESLLTFIE 379
Cdd:cd18172  260 VQIWAEHRKAMLALAA 275

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

Pssm-ID: 349437 [Multi-domain] Cd Length: 319 Bit Score: 233.34 E-value: 1.91e-68

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    48 YLHAAELGQALRDLVAEAPpGLARLFSIGRSVEGRPLWVLRLTaglpELPEARQdgekkkkeeeeeeeeegeeggggalP 127
Cdd:cd03865    1 YHRYPELREALVSVWLQCP-AISRIYTVGRSFEGRELLVIEVS----DNPGEHE-------------------------P 50

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   128 GRPQVKLVGNMHGDEPLARPLLLRLAQELVRGWAGGDERLGRLLNTTDLYLLPSLNPDGFERAregdcgGGGGGEGGGEP 207
Cdd:cd03865   51 GEPEFKYVGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIINLIHSTRIHIMPSLNPDGFEKA------ASQPGELKDWF 124

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   208 GGRENSRGRDLNRSFPD---------QFGSAQPDL------------EPVPEVRALIAWMRRNKFLLSGNLHGGSVVASY 266
Cdd:cd03865  125 VGRSNAQGIDLNRNFPDldrivyvneKEGGPNNHLlknmkkavdqntKLAPETKAVIHWIMDIPFVLSANLHGGDLVANY 204

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   267 PYDDS---PTHRptgvYSKSADDEVFKYLAKAYASHHPIMR-TGKPNC-PGEEGETFQDGITNGAQWYDVEGGMQDYNYV 341
Cdd:cd03865  205 PYDETrsgSAHE----YSSCPDDAIFQSLARAYSSLNPAMSdPNRPPCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYL 280

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 2789654   342 WANCFEITLELSCCKYPPTSELQQEWENNRESLLTFIEK 380
Cdd:cd03865  281 SSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319

Zinc carboxypeptidase;

Pssm-ID: 459730 [Multi-domain] Cd Length: 287 Bit Score: 229.88 E-value: 1.12e-67

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      60 DLVAEAPPGLARLFSIGRSVEGRPLWVLRLTAGLPElpearqdgekkkkeeeeeeeeegeeggggALPGRPQVKLVGNMH 139
Cdd:pfam00246    6 DALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGE-----------------------------HNPGKPAVFIDGGIH 56

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     140 GDEPLARPLLLRLAQELVRGWaGGDERLGRLLNTTDLYLLPSLNPDGFERAREGDCGGGGGGEGGGEPGGrensRGRDLN 219
Cdd:pfam00246   57 AREWIGPATALYLIHQLLTNY-GRDPEITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNANGSSC----IGVDLN 131

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     220 RSFPDQFGS------------AQPDLEPVPEVRALIAWMRR-NKFLLSGNLHGGSVVASYPYDDSPThrptgvySKSADD 286
Cdd:pfam00246  132 RNFPDHWNEvgassnpcsetyRGPAPFSEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-------EPPPDD 204

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     287 EVFKYLAKAYASHHPIMRTGKpncpgeegeTFQDGITNGAQWYDVEGGMQDYNYVWANC-FEITLELSCCK----YPPTS 361
Cdd:pfam00246  205 EELKSLARAAAKALQKMVRGT---------SYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPAS 275

                          330
                   ....*....|..
gi 2789654     362 ELQQEWENNRES 373
Cdd:pfam00246  276 QIIPTAEETWEA 287

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: 229.39 E-value: 1.57e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    52 AELGQALRDLvAEAPPGLARLFSIGRSVEGRPLWVLRLTAGlPELPEArqdgekkkkeeeeeeeeegeeggggalpgRPQ 131
Cdd:cd18173    8 EEYEAMMQSF-AANYPNICRLVSIGTSVQGRKLLALKISDN-VNTEEA-----------------------------EPE 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   132 VKLVGNMHGDEPLARPLLLRLAQELVRGWaGGDERLGRLLNTTDLYLLPSLNPDGFERAregdcgggggGEGGGEPGGRE 211
Cdd:cd18173   57 FKYTSTMHGDETTGYELMLRLIDYLLTNY-GTDPRITNLVDNTEIWINPLANPDGTYAG----------GNNTVSGATRY 125

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   212 NSRGRDLNRSFPDQFGSAQPDLEPV-PEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSpthrptgvYSKSADDEVFK 290
Cdd:cd18173  126 NANGVDLNRNFPDPVDGDHPDGNGWqPETQAMMNFADEHNFVLSANFHGGAEVVNYPWDTW--------YSRHPDDDWFQ 197

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   291 YLAKAYASH----HPIMRTGkpncpgeegeTFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPTSELQQE 366
Cdd:cd18173  198 DISREYADTnqanSPPMYMS----------EFNNGITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTY 267

                        330
                 ....*....|...
gi 2789654   367 WENNRESLLTFIE 379
Cdd:cd18173  268 WNYNRESLLNYIE 280

Zn_pept domain;

Pssm-ID: 214748 [Multi-domain] Cd Length: 277 Bit Score: 223.75 E-value: 1.35e-65

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654       48 YLHAAELGQALRDLvAEAPPGLARLFSIGRSVEGRPLWVLRLTAGlpelpearqdgekkkkeeeeeeeeegeeggggALP 127
Cdd:smart00631    1 YHSYEEIEAWLKEL-AARYPDLVRLVSIGKSVEGRPIWVLKISNG--------------------------------GSH 47

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      128 GRPQVKLVGNMHGDEPLARPLLLRLAQELVRGWaGGDERLGRLLNTTDLYLLPSLNPDGFERARegdcggGGGGEGGGEP 207
Cdd:smart00631   48 DKPAIFIDAGIHAREWIGPATALYLINQLLENY-GRDPRVTNLLDKTDIYIVPVLNPDGYEYTH------TGDRLWRKNR 120

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      208 GGRENSRGRDLNRSFPDQFGSAQ---------PDLEPVPEVRALIAWMRRN-KFLLSGNLHGGSVVASYPYDDSPTHRPT 277
Cdd:smart00631  121 SPNSNCRGVDLNRNFPFHWGETGnpcsetyagPSPFSEPETKAVRDFIRSNrRFKLYIDLHSYSQLILYPYGYTKNDLPP 200

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      278 GVyskSADDEVFKYLAKAYASHHpimrtgkpncpgeeGETFQDGITNGAQWYdVEGGMQDYNYVWAN-CFEITLELSCC- 355
Cdd:smart00631  201 NV---DDLDAVAKALAKALASVH--------------GTRYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDg 262

                           330
                    ....*....|....*
gi 2789654      356 ----KYPPTSELQQE 366
Cdd:smart00631  263 rygfLLPPSQIIPTG 277

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: 219.82 E-value: 5.10e-64

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   932 YRYRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEF 1011
Cdd:cd03863    6 FRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1012 LCMNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTSKLGHANAHGRDLDTDFTSNYSRYSGTREPETKAIIeNLI 1091
Cdd:cd03863   86 LCKNFGTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNYDLNRNFPDQFFQITDPPQPETLAVM-SWL 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1092 LKQDFSLSVALDGGSLLVTYPFDKPAQTV------ENKDTLKHLASVYANNHPLMHLGQPgCPNKS-DENIPGGVIRGSE 1164
Cdd:cd03863  165 KTYPFVLSANLHGGSLVVNYPFDDDEQGLatysksPDDAVFQQLALSYSKENSKMYQGSP-CKELYpNEYFPHGITNGAQ 243

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 2789654  1165 WHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd03863  244 WYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFI 294

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: 217.45 E-value: 6.47e-63

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    63 AEAPPGLARLFSIGRSVEGRPLWVLRLTA--GLPELPEarqdgekkkkeeeeeeeeegeeggggalpgrPQVKLVGNMHG 140
Cdd:cd03867   15 AARCAHIARTYSIGRSFEGKDLLVIEFSSnpGQHELLE-------------------------------PEVKYIGNMHG 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   141 DEPLARPLLLRLAQELVRGWAGGDERLGRLLNTTDLYLLPSLNPDGFERAregdcgGGGGGEGGGEPGGRENSRGRDLNR 220
Cdd:cd03867   64 NEVVGREMLIYLAQYLCSEYLLGNPRIQTLINTTRIHLLPSMNPDGYEVA------AEEGAGYNGWTSGRQNAQNLDLNR 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   221 SFPD---------QFGSAQPDLEPVP----------EVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPTHRPTGVYS 281
Cdd:cd03867  138 NFPDltseayrlaRTRGARLDHIPIPqsywwgkvapETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMFS 217

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   282 KSADDEVFKYLAKAYASHHPIMRTGKPNCPGEEGETfQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPTS 361
Cdd:cd03867  218 PTPDEKMFKLLAKAYADAHPMMSDRSENRCGGNFLK-RGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEE 296

                        330
                 ....*....|....*...
gi 2789654   362 ELQQEWENNRESLLTFIE 379
Cdd:cd03867  297 ELYTIWQENKEALLNFME 314

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: 205.45 E-value: 1.25e-58

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    58 LRDLVAEAPPGLARLFSIGRSVEGRPLWVLRLT--AGLPELpearqdgekkkkeeeeeeeeegeeggggalpGRPQVKLV 135
Cdd:cd03869   10 LMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISdnPGEHEV-------------------------------GEPEFRYV 58

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   136 GNMHGDEPLARPLLLRLAQELVRGWAGGDERLGRLLNTTDLYLLPSLNPDGFERAregdcgGGGGGEGGGEPGGRENSRG 215
Cdd:cd03869   59 AGAHGNEVLGRELLLLLMQFLCQEYLAGNPRIRHLVEETRIHLLPSVNPDGYEKA------YEAGSELGGWSLGRWTSDG 132

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   216 RDLNRSFPD----------QFGSA---------------QPDLEPVPEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDD 270
Cdd:cd03869  133 IDINHNFPDlnsllweaedRKWVPrkvpnhhipipewylSENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDM 212

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   271 SPTHRPTGVYSKSADDEVFKYLAKAYASHHPIMRTGKPNCPGEEGETFQDGITNGAQWYDVEGGMQDYNYVWANCFEITL 350
Cdd:cd03869  213 TRTPWKTQEYTPTPDDHVFRWLAYSYASTHRLMTDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSI 292

                        330       340       350
                 ....*....|....*....|....*....|
gi 2789654   351 ELSCCKYPPTSELQQEWENNRESLLTFIEK 380
Cdd:cd03869  293 YLGCDKFPHESELPEEWENNRESLLVFMEQ 322

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

Pssm-ID: 349438 Cd Length: 289 Bit Score: 203.87 E-value: 1.36e-58

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd03866    1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTSKLGHANAHGRDLDTDFTSNYSRYSGTREPETKAIIeNLILK 1093
Cdd:cd03866   81 TSYGSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCYYTKGRYNKNGYDLNRNFPDAFEENNVQRQPETRAVM-DWIKN 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1094 QDFSLSVALDGGSLLVTYPFD---KPAQTVENK------DTLKHLASVYANNHPLMHLGQPgCPNKsdENIPGGVIRGSE 1164
Cdd:cd03866  160 ETFVLSANLHGGALVASYPFDngnSGTGQLGYYsvspddDVFIYLAKTYSYNHTNMYKGIE-CSNS--QSFPGGITNGYQ 236

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 2789654  1165 WHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd03866  237 WYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYI 287

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: 188.23 E-value: 3.84e-53

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   511 HHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEaGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 590
Cdd:cd03859    5 HTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDEDE-DEPEVLFMGLHHAREWISLEVALYFADYLLE 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   591 NFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRN---NSNNY------DLNRNFpDQFFQV------TDPP 655
Cdd:cd03859   84 NYGTDPRITNLVDNREIWIIPVVNPDGYEYNRETGGGRLWRKNrrpNNGNNpgsdgvDLNRNY-GYHWGGdnggssPDPS 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   656 -----------QPETLAVMSWLKTYPFVLSANLHGGSLVVNYPF--DDDEQgiaiyskSPDDAVFQQLALSYSKENKKMY 722
Cdd:cd03859  163 setyrgpapfsEPETQAIRDLVESHDFKVAISYHSYGELVLYPWgyTSDAP-------TPDEDVFEELAEEMASYNGGGY 235

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2789654   723 QGSPCKDLYPTEyfphgitngaqwynvpGGMQDWNYLNTNCFEVTIELG---CVKYPKAEELPKYWEQNRRSL 792
Cdd:cd03859  236 TPQQSSDLYPTN----------------GDTDDWMYGEKGIIAFTPELGpefYPFYPPPSQIDPLAEENLPAA 292

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

Pssm-ID: 349464 [Multi-domain] Cd Length: 283 Bit Score: 185.73 E-value: 2.79e-52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    53 ELGQALRDLVAEAPpGLARLFSIGRSVEGRPLWVLRLtaGLPELPEArqdgekkkkeeeeeeeeegeeggggalPGRPQV 132
Cdd:cd06245    6 QLSKFLRGLNSNYP-TITNLTSLGQSVEKRDIWVLEI--GNKPNESE---------------------------PSEPKI 55

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   133 KLVGNMHGDEPLARPLLLRLaQELVRGWAGGDERLGRLLNTTDLYLLPSLNPDGFERAregdcggggGGEGGGEPGGREN 212
Cdd:cd06245   56 LFVGGIHGNAPVGTELLLLL-AHFLCHNYKKDSAITKLLNRTRIHIVPSLNPDGAEKA---------EEKKCTSKIGEKN 125

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   213 SRGRDLNRSFPDQFGsaQPDLEPVPEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDspthrptGVYSkSADDEVFKYL 292
Cdd:cd06245  126 ANGVDLDTDFESNAN--NRSGAAQPETKAIMDWLKEKDFTLSVALDGGSLVVTYPYDK-------PVQT-VENKETLKHL 195

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   293 AKAYASHHPIMRTGKPNCPGEEGETFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPTSELQQEWENNRE 372
Cdd:cd06245  196 AKVYANNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKK 275


                 ....*.
gi 2789654   373 SLLTFI 378
Cdd:cd06245  276 SLLSMI 281

Zn_pept domain;

Pssm-ID: 214748 [Multi-domain] Cd Length: 277 Bit Score: 184.08 E-value: 8.72e-52

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654      934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEepkIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:smart00631    1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGSHDKPA---IFIDAGIHAREWIGPATALYLINQLL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     1014 MNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTSKLG---HANAHGRDLDTDF-----------TSNYSRYSGTR 1079
Cdd:smart00631   78 ENYGRDPRVTNLLDKTDIYIVPVLNPDGYEYTHTGDRLWRKNrspNSNCRGVDLNRNFpfhwgetgnpcSETYAGPSPFS 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     1080 EPETKAIIENLILKQDFSLSVALDGGSLLVTYPFDKPAQTV-----ENKDTLKHLASVYANNHPLmhlgqpgcpnksdeN 1154
Cdd:smart00631  158 EPETKAVRDFIRSNRRFKLYIDLHSYSQLILYPYGYTKNDLppnvdDLDAVAKALAKALASVHGT--------------R 223

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|....*...
gi 2789654     1155 IPGGVIRGSEWHSHlGSMKDFS-VTFGHCPEITVYTSCCYFpSAGQLP 1201
Cdd:smart00631  224 YTYGISNGAIYPAS-GGSDDWAyGVLGIPFSFTLELRDDGR-YGFLLP 269

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: 175.34 E-value: 1.37e-49

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   566 YIGNMHGNEVVGRELLLNLIEYLCKNFGTDPeVTDLVQSTRIHIMPSMNPDGYEKSQegdrgGTVGRNNSNNYDLNRNFP 645
Cdd:cd00596    3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVI-----DSGGRKNANGVDLNRNFP 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   646 DQFFQVTDPP-------------QPETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDeqgiaiYSKSPDDAVFQQLAL 712
Cdd:cd00596   77 YNWGKDGTSGpssptyrgpapfsEPETQALRDLAKSHRFDLAVSYHSSSEAILYPYGYT------NEPPPDFSEFQELAA 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   713 SYSKENKkmyqgspckdlypteYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPK-AEELPKYWEQNRRS 791
Cdd:cd00596  151 GLARALG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLpGTLLDRRLERNLAA 215


                 .
gi 2789654   792 L 792
Cdd:cd00596  216 L 216

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: 176.06 E-value: 4.05e-49

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEePKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd18172    1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDETE-PAFKFVGNMHGDEPVGRELLLRLADWLC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYK-KNSAVTKLIDRTRIVIVPSLNPDGREiAQERGctsklghaNAHGRDLDTDF-----TSNYSRYSGTREPETKAII 1087
Cdd:cd18172   80 ANYKaKDPLAAKIVENAHLHLVPTMNPDGFA-RRRRN--------NANNVDLNRDFpdqffPKNLRNDLAARQPETLAVM 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1088 eNLILKQDFSLSVALDGGSLLVTYPFD----KPAQTVENKD--TLKHLASVYANNHPLMHlgqpgcpnKSDEnIPGGVIR 1161
Cdd:cd18172  151 -NWSRSVRFTASANLHEGALVANYPWDgnadGRTKYSASPDdaTFRRLASVYAQAHPNMA--------KSKE-FPGGITN 220

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 2789654  1162 GSEWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd18172  221 GAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALA 274

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: 169.63 E-value: 2.69e-46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   937 YKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCMNY 1016
Cdd:cd03869    4 YKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLCQEY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1017 KK-NSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTS---KLGHANAHGRDLDTDFT----------------------- 1069
Cdd:cd03869   84 LAgNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELggwSLGRWTSDGIDINHNFPdlnsllweaedrkwvprkvpnhh 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1070 ----SNYSRYSGTREPETKAIIeNLILKQDFSLSVALDGGSLLVTYPFDK---PAQTVENKDTLKH-----LASVYANNH 1137
Cdd:cd03869  164 ipipEWYLSENATVAPETRAVI-AWMEKIPFVLGGNLQGGELVVSYPYDMtrtPWKTQEYTPTPDDhvfrwLAYSYASTH 242

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2789654  1138 PLMHLGQPGCPNKSDENIPGGVIRGSEWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd03869  243 RLMTDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFM 320

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: 167.76 E-value: 3.31e-46

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   933 RYRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEePKIRFVAGIHGNAPVGTELLLALAEFL 1012
Cdd:cd18173    3 SYPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEAE-PEFKYTSTMHGDETTGYELMLRLIDYL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1013 CMNYKKNSAVTKLIDRTRIVIVPSLNPDGreiAQERGCTSKLGH--ANAHGRDLDTDF---TSNYSRYSGTREPETKAII 1087
Cdd:cd18173   82 LTNYGTDPRITNLVDNTEIWINPLANPDG---TYAGGNNTVSGAtrYNANGVDLNRNFpdpVDGDHPDGNGWQPETQAMM 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1088 eNLILKQDFSLSVALDGGSLLVTYPFDKPAQTVENKDTLKHLASVYANNhplmhlGQPGCPNKSDENIPGGVIRGSEWHS 1167
Cdd:cd18173  159 -NFADEHNFVLSANFHGGAEVVNYPWDTWYSRHPDDDWFQDISREYADT------NQANSPPMYMSEFNNGITNGYDWYE 231

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 2789654  1168 HLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd18173  232 VYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYI 279

Zinc carboxypeptidase;

Pssm-ID: 459730 [Multi-domain] Cd Length: 287 Bit Score: 164.78 E-value: 4.46e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     942 EFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCMNYKKNSA 1021
Cdd:pfam00246    3 AWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGRDPE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    1022 VTKLIDRTRIVIVPSLNPDGREIAQERGCTSKLGHANA-----HGRDLDTDF--------------TSNYSRYSGTREPE 1082
Cdd:pfam00246   83 ITELLDDTDIYILPVVNPDGYEYTHTTDRLWRKNRSNAngsscIGVDLNRNFpdhwnevgassnpcSETYRGPAPFSEPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    1083 TKAIIeNLILKQD-FSLSVALDGGSLLVTYPFDKPAQT-VENKDTLKHLASVYANNHPLMHLGQpgcpnksdeNIPGGVI 1160
Cdd:pfam00246  163 TRAVA-DFIRSKKpFVLYISLHSYSQVLLYPYGYTRDEpPPDDEELKSLARAAAKALQKMVRGT---------SYTYGIT 232

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2789654    1161 RGSEWHSHLGSMKDFSVTFGHCP-EITVYTSCC----YFPSAGQLPGLWADHRKS 1210
Cdd:pfam00246  233 NGATIYPASGGSDDWAYGRLGIKySYTIELRDTgrygFLLPASQIIPTAEETWEA 287

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: 164.00 E-value: 2.55e-44

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYKK-NSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTSK---LGHANAHGRDLDTDFtSNYSR--YSGTRE------- 1080
Cdd:cd03865   81 NEYQKgNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKdwfVGRSNAQGIDLNRNF-PDLDRivYVNEKEggpnnhl 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1081 ---------------PETKAIIeNLILKQDFSLSVALDGGSLLVTYPFDKPA-------QTVENKDTLKHLASVYANNHP 1138
Cdd:cd03865  160 lknmkkavdqntklaPETKAVI-HWIMDIPFVLSANLHGGDLVANYPYDETRsgsaheySSCPDDAIFQSLARAYSSLNP 238

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2789654  1139 LMH-LGQPGC-PNKSDENIPGGVIRGSEWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd03865  239 AMSdPNRPPCrKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYI 317

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: 160.05 E-value: 4.85e-43

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd03867    1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNY-KKNSAVTKLIDRTRIVIVPSLNPDGREIAQERGC---TSKLGHANAHGRDLDTDF---TSNYSRYSGTR------- 1079
Cdd:cd03867   81 SEYlLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAgynGWTSGRQNAQNLDLNRNFpdlTSEAYRLARTRgarldhi 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1080 -----------EPETKAIIEnLILKQDFSLSVALDGGSLLVTYPFDKPAQTVENK--------DTLKHLASVYANNHPLM 1140
Cdd:cd03867  161 pipqsywwgkvAPETKAVMK-WMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKmfsptpdeKMFKLLAKAYADAHPMM 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2789654  1141 HLGQPGCPNkSDENIPGGVIRGSEWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd03867  240 SDRSENRCG-GNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNFM 313

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

Pssm-ID: 349436 [Multi-domain] Cd Length: 313 Bit Score: 158.94 E-value: 1.04e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   937 YKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCMNY 1016
Cdd:cd03864    4 YDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLCEEY 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1017 KK-NSAVTKLIDRTRIVIVPSLNPDGREIAQERGCTSK---LGHANAHGRDLDTDFTS------NYSRYSGTR------- 1079
Cdd:cd03864   84 RNgNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNgylVGRNNANGVDLNRNFPDlntlmyYNEKYGGPNhhlplpd 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1080 ------EPETKAIIEnLILKQDFSLSVALDGGSLLVTYPFDKP-----------AQTVENKDTL-KHLASVYANNHPLMH 1141
Cdd:cd03864  164 nwksqvEPETLAVIQ-WMQNYNFVLSANLHGGAVVANYPYDKSreprvrgfrrtAYSPTPDDKLfQKLAKTYSYAHGWMH 242

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2789654  1142 LGQpGCPNKSDEnipgGVIRGSEWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADHRKSLLSMLVE 1217
Cdd:cd03864  243 KGW-NCGDYFDE----GITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREALISYMEQ 313

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

Pssm-ID: 442113 [Multi-domain] Cd Length: 337 Bit Score: 143.29 E-value: 4.22e-37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   509 RHHHFSDMEIFLRRYANEyPSITRLYSVGKSVELRELYVMEISDnpgvHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYL 588
Cdd:COG2866   18 RYYTYEELLALLAKLAAA-SPLVELESIGKSVEGRPIYLLKIGD----PAEGKPKVLLNAQQHGNEWTGTEALLGLLEDL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   589 CKNFgtDPEVTDLVQSTRIHIMPSMNPDGYEKSQegdrggtvgRNNSNNYDLNRNFPDQFFQvtdppQPETLAVMSWLKT 668
Cdd:COG2866   93 LDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT---------RTNANGVDLNRDWPAPWLS-----EPETRALRDLLDE 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   669 YPFVLSANLHGGSLVVNYPFDDDEQGIAIYSKSPDD---AVFQQLALSYSKENKKMYQGS----PCKDLYPTEYFPHGIT 741
Cdd:COG2866  157 HDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEereAFAEELNFEGIILAGSAFLGAgaagTLLISAPRQTFLFAAA 236

                        250
                 ....*....|
gi 2789654   742 NGAQWYNVPG 751
Cdd:COG2866  237 LDIGGGGDVS 246

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: 127.26 E-value: 1.16e-34

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2789654   802 GIWGFVLDATdGRGILNATISVADINHPVTTYKDGDYWRLLVQGTYKVTASARGYDPVTKTVEVDSK-GGVQVNFTL 877
Cdd:cd11308    1 GIKGFVTDAT-GNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNfSATVVNFTL 76

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

Pssm-ID: 349476 [Multi-domain] Cd Length: 359 Bit Score: 127.73 E-value: 1.48e-31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   506 VDFRHHH-FSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNL 584
Cdd:cd06905    1 LAFDRYYtYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   585 IEYLCKNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKS------------------------------------------- 621
Cdd:cd06905   81 AEYLLTNYGKDPEITRLLDTRTFYILPRLNPDGAEAYklktersgrssprdddrdgdgdedgpedlngdglitqmrvkdp 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   622 -----------------QEGDRG-------GTV----GRNN---SNNYDLNRNFPDQFFQVTDPP--------QPETLAV 662
Cdd:cd06905  161 tgtwkvdpddprlmvdrEKGEKGfyrlypeGIDndgdGRYNedgPGGVDLNRNFPYNWQPFYVQPgagpyplsEPETRAV 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   663 MSWLKTYPFVLSANLHGGSLVVNypfdddeqgIAIYSKSPDDavfqqlalSYSKENKKMYQGSPCKDLYPTEYFPHGITN 742
Cdd:cd06905  241 ADFLLAHPNIAAVLTFHTSGGMI---------LRPPGTGPDS--------DMPPADRRVYDAIGKKGVELTGYPVSSVYK 303

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 2789654   743 GaqWYNVPGG-----MQDWNYLNTNCFEVTIEL-------GCVKYPKAEELPKYWEQN 788
Cdd:cd06905  304 D--FYTVPGGpldgdFFDWAYFHLGIPSFSTELwdlpefaGKKKEGTVEEAERLRWAD 359

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

Pssm-ID: 200604 [Multi-domain] Cd Length: 76 Bit Score: 116.47 E-value: 5.85e-31

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2789654   384 GVKGYVRDAiTGAGLENATIVVAGIAHNITAGKFGDYHRLLVPGTYNVTAVVMGYAPVTKeNIEVKEGD-ATVVDFSL 460
Cdd:cd11308    1 GIKGFVTDA-TGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTK-TVTVPNNFsATVVNFTL 76

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: 109.86 E-value: 8.09e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   132 VKLVGNMHGDEPLARPLLLRLAQELVRGWagGDERLGRLLNTTDLYLLPSLNPDGFERARegdcggggggegggEPGGRE 211
Cdd:cd00596    1 ILITGGIHGNEVIGVELALALIEYLLENY--GNDPLKRLLDNVELWIVPLVNPDGFARVI--------------DSGGRK 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   212 NSRGRDLNRSFPDQFGSAQPDLEPV-----------PEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPTHRPtgvy 280
Cdd:cd00596   65 NANGVDLNRNFPYNWGKDGTSGPSSptyrgpapfsePETQALRDLAKSHRFDLAVSYHSSSEAILYPYGYTNEPPP---- 140

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   281 sksaDDEVFKYLAKAYASHHPimrtgkpncpgeegeTFQDGITNGAQWYDVEGGMQDYNYVWANCFEITLELSCCKYPPT 360
Cdd:cd00596  141 ----DFSEFQELAAGLARALG---------------AGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLP 201

                        250
                 ....*....|....*
gi 2789654   361 SE-LQQEWENNRESL 374
Cdd:cd00596  202 GTlLDRRLERNLAAL 216

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

Pssm-ID: 349432 [Multi-domain] Cd Length: 292 Bit Score: 111.19 E-value: 1.88e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNhSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd03859    4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPD-EDEDEPEVLFMGLHHAREWISLEVALYFADYLL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYKKNSAVTKLIDRTRIVIVPSLNPDG----REIAQER----------GCTSKLGhanahGRDL----------DTDFT 1069
Cdd:cd03859   83 ENYGTDPRITNLVDNREIWIIPVVNPDGyeynRETGGGRlwrknrrpnnGNNPGSD-----GVDLnrnygyhwggDNGGS 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1070 SNYSR---YSGTR---EPETKAiIENLILKQDFSLSVALDGGSLLVTYPFD-KPAQTVENKDTLKHLASVYAN-NHPLMH 1141
Cdd:cd03859  158 SPDPSsetYRGPApfsEPETQA-IRDLVESHDFKVAISYHSYGELVLYPWGyTSDAPTPDEDVFEELAEEMASyNGGGYT 236

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2789654  1142 LGQPGCpnksdenipGGVIRG--SEWhsHLGSMKDFSVTFGHCPEitvytSCCYFPSAGQLPGLWADHRKSL 1211
Cdd:cd03859  237 PQQSSD---------LYPTNGdtDDW--MYGEKGIIAFTPELGPE-----FYPFYPPPSQIDPLAEENLPAA 292

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

Pssm-ID: 442113 [Multi-domain] Cd Length: 337 Bit Score: 101.69 E-value: 6.14e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    47 RYLHAAELGQALRDLVAEapPGLARLFSIGRSVEGRPLWVLRLTAglpelpearqdgekkkkeeeeeeeeegeeggggAL 126
Cdd:COG2866   18 RYYTYEELLALLAKLAAA--SPLVELESIGKSVEGRPIYLLKIGD---------------------------------PA 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   127 PGRPQVKLVGNMHGDEPLARPLLLRLAQELVrgwAGGDERLGRLLNTTDLYLLPSLNPDGFERARegdcggggggeggge 206
Cdd:COG2866   63 EGKPKVLLNAQQHGNEWTGTEALLGLLEDLL---DNYDPLIRALLDNVTLYIVPMLNPDGAERNT--------------- 124

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   207 pggRENSRGRDLNRSFPDQFGSAqpdlepvPEVRALIAWMRRNKFLLSGNLHGGSVVASYPYDDSPTHRPTGVYSKSADD 286
Cdd:COG2866  125 ---RTNANGVDLNRDWPAPWLSE-------PETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGSFLAPSYDEER 194


                 ....*.
gi 2789654   287 EVFKYL 292
Cdd:COG2866  195 EAFAEE 200

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: 97.60 E-value: 8.97e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   511 HHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGvhEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 590
Cdd:cd03860    2 HPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGG--KGGKPAIVIHGGQHAREWISTSTVEYLAHQLLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   591 NFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDR---------GGT--VGRnnsnnyDLNRNFPDQFFQV---TDP-- 654
Cdd:cd03860   80 GYGSDATITALLDKFDFYIIPVVNPDGYVYTWTTDRlwrknrqptGGSscVGI------DLNRNWGYKWGGPgasTNPcs 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   655 -----PQ----PETLAVMSWLKTYP----FVLSANLHGGSLVVNYPFdddeqGIAIYSKSPDDAVFQQLALSYSKE---- 717
Cdd:cd03860  154 etyrgPSafsaPETKALADFINALAagqgIKGFIDLHSYSQLILYPY-----GYSCDAVPPDLENLMELALGAAKAirav 228

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 2789654   718 NKKMYQ-GSPCKDLYPTeyfphgitngaqwynvPGGMQDWNYLNTNC-FEVTIEL 770
Cdd:cd03860  229 HGTTYTvGPACSTLYPA----------------SGSSLDWAYDVAKIkYSYTIEL 267

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: 89.12 E-value: 2.52e-21

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2789654  1221 GVHGFVQDKSGKAISKATIVLNEG-LRVYTKEGGYFHVLLAPGLHNINAIADGYQQKHMKVLVRHDaPSSVFIVFDM 1296
Cdd:cd11308    1 GIKGFVTDATGNPIANATISVEGInHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNN-FSATVVNFTL 76

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: 95.40 E-value: 3.91e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    48 YLHAAELGQALRDLvAEAPPGLARLFSIGRSVEGRPLWVLRLTAGlpelPEARqdgekkkkeeeeeeeeegeeggggalP 127
Cdd:cd03859    4 YHTYAELVAELDQL-AAEYPEITKLISIGKSVEGRPIWAVKISDN----PDED--------------------------E 52

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   128 GRPQVKLVGNMHGDEPLARPLLLRLAQELVRGwAGGDERLGRLLNTTDLYLLPSLNPDGFERAREGDCGGGGGGEGGGEP 207
Cdd:cd03859   53 DEPEVLFMGLHHAREWISLEVALYFADYLLEN-YGTDPRITNLVDNREIWIIPVVNPDGYEYNRETGGGRLWRKNRRPNN 131

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   208 GGRENSRGRDLNRSFPDQFGSAQPDLEPV--------------PEVRALIAWMRRNKFLLSGNLH--GGSVVASYPYDDS 271
Cdd:cd03859  132 GNNPGSDGVDLNRNYGYHWGGDNGGSSPDpssetyrgpapfsePETQAIRDLVESHDFKVAISYHsyGELVLYPWGYTSD 211

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   272 PThrptgvyskSADDEVFKYLAKAYAShhPIMRTGKPNCPgeegetfqdgitngAQWYDVEGGMQDYNYVWANCFEITLE 351
Cdd:cd03859  212 AP---------TPDEDVFEELAEEMAS--YNGGGYTPQQS--------------SDLYPTNGDTDDWMYGEKGIIAFTPE 266

                        330       340
                 ....*....|....*....|....*.
gi 2789654   352 L---SCCKYPPTSELQQEWENNRESL 374
Cdd:cd03859  267 LgpeFYPFYPPPSQIDPLAEENLPAA 292

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

Pssm-ID: 349427 [Multi-domain] Cd Length: 216 Bit Score: 90.98 E-value: 2.92e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   990 FVAGIHGNAPVGTELLLALAEFLCMNYKKNSaVTKLIDRTRIVIVPSLNPDGREIAQERGctsklGHANAHGRDLDTDFT 1069
Cdd:cd00596    3 ITGGIHGNEVIGVELALALIEYLLENYGNDP-LKRLLDNVELWIVPLVNPDGFARVIDSG-----GRKNANGVDLNRNFP 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1070 SN----------YSRYSGTR---EPETKAIIEnLILKQDFSLSVALDGGSLLVTYPFDKPAQTVENKDTLKHLASVYANN 1136
Cdd:cd00596   77 YNwgkdgtsgpsSPTYRGPApfsEPETQALRD-LAKSHRFDLAVSYHSSSEAILYPYGYTNEPPPDFSEFQELAAGLARA 155

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2789654  1137 HPLMHlgqpgcpnksdenipGGVIRGSEWHSHLGSMKDFSVTFGHCPEITVYTSCCYFPSAGQLPGLWADH 1207
Cdd:cd00596  156 LGAGE---------------YGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTADYPLPGTLLDRRLER 211

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

Pssm-ID: 442113 [Multi-domain] Cd Length: 337 Bit Score: 90.52 E-value: 4.41e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   928 KVSPYRYRPYKDLSEFLRGLYLNYPHITnLTSLGQSVEFRQIWSLEISNKpnhsEPEEPKIRFVAGIHGNAPVGTELLLA 1007
Cdd:COG2866   13 VSSYDRYYTYEELLALLAKLAAASPLVE-LESIGKSVEGRPIYLLKIGDP----AEGKPKVLLNAQQHGNEWTGTEALLG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1008 LAEFLCMNYkkNSAVTKLIDRTRIVIVPSLNPDGREIAQeRgctsklghANAHGRDLDTDFTSNYSrysgtREPETKAII 1087
Cdd:COG2866   88 LLEDLLDNY--DPLIRALLDNVTLYIVPMLNPDGAERNT-R--------TNANGVDLNRDWPAPWL-----SEPETRALR 151

                        170       180       190
                 ....*....|....*....|....*....|..
gi 2789654  1088 EnLILKQDFSLSVAL--DGGSLLVTYPFDKPA 1117
Cdd:COG2866  152 D-LLDEHDPDFVLDLhgQGELFYWFVGTTEPT 182

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: 85.79 E-value: 1.69e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   536 VGKSVELRELYVMEISDNPG--VHeagepefkYIGNMHGNEVVGRELLLNLIEYLcknfGTDPEVTDLvqstRIHIMPSM 613
Cdd:cd06904    4 YGTSVKGRPILAYKFGPGSRarIL--------IIGGIHGDEPEGVSLVEHLLRWL----KNHPASGDF----HIVVVPCL 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   614 NPDGYEKSQegdrggtvgRNNSNNYDLNRNFPDQFFQVTDPP--------------QPETLAVMSWLKTYP--FVLSanL 677
Cdd:cd06904   68 NPDGLAAGT---------RTNANGVDLNRNFPTKNWEPDARKpkdpryypgpkpasEPETRALVELIERFKpdRIIS--L 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   678 HGGSLVVnypFDDDEQGIaiyskspddavfqqLALSYSKENKKMYQGSPckdlypteyfphGITngaqwynvPGGMQDWN 757
Cdd:cd06904  137 HAPYLVN---YDGPAKSL--------------LAEKLAQATGYPVVGDV------------GYT--------PGSLGTYA 179

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 2789654   758 YLNTNCFEVTIELgcvkyPKAEELPKYWEQNRRSLLQFIK 797
Cdd:cd06904  180 GIERNIPVITLEL-----PEAVSIDELWQDLKRALIEAIK 214

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: 88.83 E-value: 2.08e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   933 RYRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFL 1012
Cdd:cd06905    5 RYYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYL 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 2789654  1013 CMNYKKNSAVTKLIDRTRIVIVPSLNPDGRE 1043
Cdd:cd06905   85 LTNYGKDPEITRLLDTRTFYILPRLNPDGAE 115

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: 81.35 E-value: 1.54e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   544 ELYVMEISDNPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQE 623
Cdd:cd06226    1 DIRALKLTNKQATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAET 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   624 gdrgGTVGRNNSNN-----------YDLNRNFPDQFFQV---TDP-----------PQPETLAVMSWLKTypfvLSANLH 678
Cdd:cd06226   81 ----GLLWRKNTNTtpcpassptygVDLNRNSSFKWGGAgagGSAcsetyrgpsaaSEPETQAIENYVKQ----LFPDQR 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   679 GGSLvvNYPFDDDEQGIAI----YSK------------SPDDAVFQQLALSYSKENKkmYQGSPCKDLYPTEyfphgitn 742
Cdd:cd06226  153 GPGL--TDPAPDDTSGIYIdihsYGNlvlypwgwtgtpAPNAAGLRTLGRKFAYFNG--YTPQQAVALYPTD-------- 220

                        250       260
                 ....*....|....*....|....*....
gi 2789654   743 gaqwynvpGGMQDWNYLNTNCFEVTIELG 771
Cdd:cd06226  221 --------GTTDDFAYGTLGVAAYTFELG 241

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: 78.54 E-value: 7.86e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   566 YIGNMHGNEVVGRELLLNLIEYLCKN-------FGTDPEvtDLVQSTRIHIMPSMNPDGYEKSQEG--------DR---- 626
Cdd:cd06229    3 YNASFHAREYITTLLLMKFIEDYAKAyvnksyiRGKDVG--ELLNKVTLHIVPMVNPDGVEISQNGsnainpyyLRlvaw 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   627 --GGTVGRN---NSNNYDLNRNFPDQF-------FQV---TDPP------QPETLAVMSWLKTYPFVLSANLHggslvvn 685
Cdd:cd06229   81 nkKGTDFTGwkaNIRGVDLNRNFPAGWekekrlgPKApgpRDYPgkeplsEPETKAMAALTRQNDFDLVLAYH------- 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   686 ypfdddEQGIAIYSKspddavFQQLALSYSKENKKMYQGSpckdlypTEYFPHGITNGAQWynvpGGMQDWNYLNTNCFE 765
Cdd:cd06229  154 ------SQGEEIYWG------YNGLEPEESKAMAEKFASV-------SGYEPVEAEAIDSY----GGFKDWFIYEFKKPS 210

                        250       260
                 ....*....|....*....|....*...
gi 2789654   766 VTIELGCVKYPKA-EELPKYWEQNRRSL 792
Cdd:cd06229  211 FTIETGKGNNPLPiSQFDEIYEKNKGVL 238

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: 79.20 E-value: 2.97e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    47 RYLHAAELGQALRDLvAEAPPGLARLFSIGRSVEGRPLWVLRLTAGLPELPEARqdgekkkkeeeeeeeeegeeggggal 126
Cdd:cd06905    5 RYYTYAELTARLKAL-AEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEK-------------------------- 57

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2789654   127 pgrPQVKLVGNMHGDEPLARPLLLRLAQELVRGwAGGDERLGRLLNTTDLYLLPSLNPDGFE 188
Cdd:cd06905   58 ---PALWVDGNIHGNEVTGSEVALYLAEYLLTN-YGKDPEITRLLDTRTFYILPRLNPDGAE 115

Carboxypeptidase regulatory-like domain;

Pssm-ID: 433354 [Multi-domain] Cd Length: 81 Bit Score: 71.93 E-value: 3.04e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     384 GVKGYVRDAiTGAGLENATIVVA----GIAHNITAGKFGDYH-RLLVPGTYNVTAVVMGYAPVTKENIEVKEGDATVVDF 458
Cdd:pfam13620    1 TISGTVTDP-SGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTGVTVTAGQTTTLDV 79


                   ..
gi 2789654     459 SL 460
Cdd:pfam13620   80 TL 81

Carboxypeptidase regulatory-like domain;

Pssm-ID: 433354 [Multi-domain] Cd Length: 81 Bit Score: 68.46 E-value: 4.65e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     802 GIWGFVLDATdGRGILNATISVAD----INHPVTTYKDGDYW-RLLVQGTYKVTASARGYDPVTKT-VEVDSKGGVQVNF 875
Cdd:pfam13620    1 TISGTVTDPS-GAPVPGATVTVTNtdtgTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTgVTVTAGQTTTLDV 79


                   ..
gi 2789654     876 TL 877
Cdd:pfam13620   80 TL 81

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

Pssm-ID: 349450 [Multi-domain] Cd Length: 239 Bit Score: 66.95 E-value: 7.36e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   566 YI-GNMHGNEVVGRELLLNLIEylcknfgTDPEvtDLVQSTRIHIMPSMNPDGYEKSQegdrggtvgRNNSNNYDLNRNF 644
Cdd:cd06231   46 LIsAGIHGDEPAGVEALLRFLE-------SLAE--KYLRRVNLLVLPCVNPWGFERNT---------RENADGIDLNRSF 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   645 pdqffqVTDPPQPETLAVMSWLKTYP-FVLSANLHGgslvvnypfDDDEQGIAIYSKSPDDAVFQQlALSYSKENKKMYQ 723
Cdd:cd06231  108 ------LKDSPSPEVRALMEFLASLGrFDLHLDLHE---------DWDSDGFYLYELGPALKAGRD-GLQAVDAVIPPDP 171

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 2789654   724 GSPCKDLYPTeyfPHG-ITNGAQWYNVPGG-MQDWNYLNTNCFEVTIE 769
Cdd:cd06231  172 ISLTIDGSPA---PDGvILRPDDPAERPGWpFAIYLVANGAVRTYTTE 216

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

Pssm-ID: 349433 [Multi-domain] Cd Length: 300 Bit Score: 67.94 E-value: 8.26e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    48 YLHAAELGQALRDLvAEAPPGLARLFSIGRSVEGRPLWVLRLTAGLPElpearqdgekkkkeeeeeeeeegeeggggalP 127
Cdd:cd03860    1 YHPLDDIVQWLDDL-AAAFPDNVEIFTIGKSYEGRDITGIHIWGSGGK-------------------------------G 48

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   128 GRPQVKLVGNMHGDEPLARPLLLRLAQELVRGwAGGDERLGRLLNTTDLYLLPSLNPDGFE------------RARegdc 195
Cdd:cd03860   49 GKPAIVIHGGQHAREWISTSTVEYLAHQLLSG-YGSDATITALLDKFDFYIIPVVNPDGYVytwttdrlwrknRQP---- 123

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2789654   196 ggggggegggepggRENS--RGRDLNRSFPDQFGSAQPDLEP------------VPEVRALIAWMRRNK 250
Cdd:cd03860  124 --------------TGGSscVGIDLNRNWGYKWGGPGASTNPcsetyrgpsafsAPETKALADFINALA 178

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: 66.01 E-value: 3.17e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPNHSEPeePKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd03860    1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGGKGGK--PAIVIHGGQHAREWISTSTVEYLAHQLL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQE-----RGCTSKLGHANAHGRDLDTDFTSNYSR-----------YSG 1077
Cdd:cd03860   79 SGYGSDATITALLDKFDFYIIPVVNPDGYVYTWTtdrlwRKNRQPTGGSSCVGIDLNRNWGYKWGGpgastnpcsetYRG 158

                        170
                 ....*....|..
gi 2789654  1078 TR---EPETKAI 1086
Cdd:cd03860  159 PSafsAPETKAL 170

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: 63.45 E-value: 6.22e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   958 TSLGQSVEFRQIWSLEISNKPNhsepeePKIRFVAGIHGNAPVGTELLLALaeflcMNYKKNSAVTKLIdrtRIVIVPSL 1037
Cdd:cd06904    2 KVYGTSVKGRPILAYKFGPGSR------ARILIIGGIHGDEPEGVSLVEHL-----LRWLKNHPASGDF---HIVVVPCL 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1038 NPDGREiAQERGctsklghaNAHGRDLDTDF-TSNYS----------RYSGTR---EPETKAIIeNLILKQDFSLSVALD 1103
Cdd:cd06904   68 NPDGLA-AGTRT--------NANGVDLNRNFpTKNWEpdarkpkdprYYPGPKpasEPETRALV-ELIERFKPDRIISLH 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1104 GGSLLVtypFDKPAQTVenkdTLKHLASvyANNHPlmHLGQPGcpnksdeNIPG------GVIRGsewhshlgsmkdfsv 1177
Cdd:cd06904  138 APYLVN---YDGPAKSL----LAEKLAQ--ATGYP--VVGDVG-------YTPGslgtyaGIERN--------------- 184

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 2789654  1178 tfghCPEITVytsccYFPSAGQLPGLWADHRKSLLSML 1215
Cdd:cd06904  185 ----IPVITL-----ELPEAVSIDELWQDLKRALIEAI 213

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: 63.44 E-value: 7.88e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   569 NMHGNEVVGRELLLNLIEYLC--KNFGTDPEVTDLVQSTR----IHIMPSMNPDGYEKSQEGD---RGgtvgrnNSNNYD 639
Cdd:cd06227    9 GEHARELISVESALRLLRQLCggLQEPAASALRELAREILdnveLKIIPNANPDGRRLVESGDycwRG------NENGVD 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2789654   640 LNRNFPDQFFQVTDPPQ------------PETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDD 690
Cdd:cd06227   83 LNRNWGVDWGKGEKGAPseeypgpkpfsePETRALRDLALSFKPHAFVSVHSGMLAIYTPYAY 145

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

Pssm-ID: 349465 [Multi-domain] Cd Length: 300 Bit Score: 64.44 E-value: 1.06e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   509 RHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNpgvheagEPEFKYI----GNMHGNEVVGRELLLNL 584
Cdd:cd06246    4 QYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGK-------EQTAKNAiwidCGIHAREWISPAFCLWF 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   585 IEYLCKNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDR-----GGTVGRNNSNNYDLNRNFP-------------D 646
Cdd:cd06246   77 IGHASYFYGIIGQHTNLLNLVDFYVMPVVNVDGYDYSWKKNRmwrknRSKHANNRCIGTDLNRNFDagwcgkgassdscS 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   647 QFFQVTDP-PQPETLAVMSWLKTYPFVLSA--NLHGGSLVVNYPFDddeqgiAIYSKSPDDAVFQQLALSYSKENKKMYQ 723
Cdd:cd06246  157 ETYCGPYPeSEPEVKAVASFLRRHKDTIKAyiSMHSYSQMVLFPYS------YTRNKSKDHDELSLLAKEAVTAIRKTSR 230

                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 2789654   724 gspckdlypTEYfPHGitNGAQ-WYNVPGGMQDWNY 758
Cdd:cd06246  231 ---------NRY-TYG--PGAEtIYLAPGGSDDWAY 254

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: 62.09 E-value: 5.42e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   511 HHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDnPGVHEAGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 590
Cdd:cd06248    2 HSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRS-TNSEDTSKPTIMIEGGINPREWISPPAALYAIHKLVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   591 NfgtDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNY--------DLNRNFPDQFFQV--TDPP----- 655
Cdd:cd06248   81 D---VETQSDLLNNFDWIILPVANPDGYVFTHTNDREWTKNRSTNSNPlgqicfgvNINRNFDYQWNPVlsSESPcsely 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 2789654   656 -------QPETLAVMSWLKTY--PFVLSANLHGGSLVVNYPF 688
Cdd:cd06248  158 agpsafsEAESRAIRDILHEHgnRIHLYISFHSGGSFILYPW 199

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

Pssm-ID: 349430 [Multi-domain] Cd Length: 203 Bit Score: 60.55 E-value: 6.17e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   566 YIGNMHGNEVVGRELLLNLIeylcKNFGTDP-EVTDLVQSTRIHIMPSMNPDGYE----KSQEGDRGGTVGRNNSNNYDL 640
Cdd:cd03857    4 LAAQIHGNETTGTEALMELI----RDLASESdEAAKLLDNIVILLVPQLNPDGAElfvnFYLDSMNGLPGTRYNANGIDL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   641 NRNFPDQffqvtdpPQPETLAVMS-WLKTYPFVLsANLHggslvvnypfdDDEQGIAIYSKSPDDAVFQQLALSYSKENK 719
Cdd:cd03857   80 NRDHVKL-------TQPETQAVAEnFIHWWPDIF-IDLH-----------EQVGASIPYPTPPDAPNYNLVDLRSDAENG 140

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 2789654   720 KMYQgSPCKDLYPTE---YFPHGITNGAQWYNVPGGMQDWNYLN 760
Cdd:cd03857  141 QEHI-RLIAGEGSGElgkYFSPMRGGFDDSTGGNGIGRTSGFHG 183

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: 59.39 E-value: 1.69e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   569 NMHGNEVVGRELLLNLIEYLCKN--------------FGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQegdrggtvgRNN 634
Cdd:cd06244    7 NIHGNEVEGVDALLEFLEMLATEpnvtyntlvkyykvENVDLEVKDLLDDVFFIVVPTENPDGRVANT---------RTN 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 2789654   635 SNNYDLNRnfpDQFFQVtdppQPETLAVMSWLKTYPFVLSANLHG 679
Cdd:cd06244   78 ANGFDLNR---DNAYQT----QPETRAMQELISKWNPVTFLDMHG 115

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: 60.48 E-value: 2.21e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   566 YIGNMHGNEVVGRELLLNLIE-------------YLCKNFGTDpEVTDLVQSTRIHIMPSMNPDGYEKSQE--------- 623
Cdd:cd06228    5 FIGGVHAREWGSPDILIYFAAdlleaytnntgltYGGKTFTAA-QVKSILENVDLVVFPLVNPDGRWYSQTsesmwrknr 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   624 -----GDRGGTVGRNNSNNYDLNRNFPDQF----FQVTDPPQ------------PETLAVMSWLKTYP----FVlsaNLH 678
Cdd:cd06228   84 npasaGDGGSCIGVDINRNFDFLWDFPRYFdpgrVPASTSPCsetyhgpsafsePETRNVVWLFDAYPnirwFV---DVH 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   679 GGSLVVNYPFDDDE------------------QGIAI------YSKSPDDAVFQQLA----LSYSKENKKMYQGSPCKDL 730
Cdd:cd06228  161 SASELILYSWGDDEnqstdpamnflnpaydgkRGIAGdtryreFIPSDDRTIAVNLAnrmaLAIAAVRGRVYTVQQAFGL 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2789654   731 YPT-----EY-FPHGITNGAqwynvpggmqdwnylNTNCFEVTIELGCVKYPKAEELPkyweqnrrsllQFIKQVHRGI 803
Cdd:cd06228  241 YPTsgasdDYaYSRHFVNPA---------------KRKVYGFTIEWGTEFQPAYSEME-----------NIIRDVSAGL 293

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: 59.24 E-value: 2.31e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2789654   566 YIGNMHGNEVVGRELLLNLIEYLCKnfgtDPEVTDLVQSTRIHIMPSMNPDGYEKSQegdrggtvgRNNSNNYDLNRNF 644
Cdd:cd06242    6 LVGQQHGNEPAGREAALALARDLAF----GDDARELLEKVNVLVVPRANPDGRAANT---------RGNANGVDLNRDH 71

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

Pssm-ID: 349467 [Multi-domain] Cd Length: 297 Bit Score: 60.16 E-value: 2.49e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   934 YRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNkPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLC 1013
Cdd:cd06248    1 YHSLDEIDEYLDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRS-TNSEDTSKPTIMIEGGINPREWISPPAALYAIHKLV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1014 MNykkNSAVTKLIDRTRIVIVPSLNPDG--------REIAQERGCTSKLGHANAHGRDLDTDFTSNYSR----------- 1074
Cdd:cd06248   80 ED---VETQSDLLNNFDWIILPVANPDGyvfthtndREWTKNRSTNSNPLGQICFGVNINRNFDYQWNPvlssespcsel 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1075 YSGTR---EPETKAiIENLILKQD--FSLSVALDGGSLLVTYPFDKPAQTVENKDTLkHLASVYA------NNHPLMHLG 1143
Cdd:cd06248  157 YAGPSafsEAESRA-IRDILHEHGnrIHLYISFHSGGSFILYPWGYDGSTSSNARQL-HLAGVAAaaaissNNGRPYVVG 234

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 2789654  1144 QPGcpnKSDENIPGGVirgSEW-HSHLGSMKDFSVTFGHCP 1183
Cdd:cd06248  235 QSS---VLLYRAAGTS---SDYaMGIAGIDYTYELPGYSSG 269

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: 58.20 E-value: 3.34e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   570 MHGNEVVGRELLLNLIEYLCKnfgTDPEVTDLVQSTRIHIMPSMNPDGYEKSQegdrggtvgRNNSNNYDLNRNfpdqff 649
Cdd:cd06239    8 MHGNEPTGTEALLDLISYLRR---ERQEFEKILERLTLVAIPMLNPDGAELFT---------RHNAEGIDLNRD------ 69

                         90       100       110
                 ....*....|....*....|....*....|
gi 2789654   650 qVTDPPQPETLAVMSWLKTYPFVLSANLHG 679
Cdd:cd06239   70 -ARALQTPESRALKAVLDSFSPKFAFNLHD 98

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: 56.58 E-value: 1.97e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   988 IRFVAGIHGNAPVGTELLLALAEFLCMNYKKNSA-----VTKLIDRTRIVIVPSLNPDGREIAQE--------------- 1047
Cdd:cd06229    1 VLYNASFHAREYITTLLLMKFIEDYAKAYVNKSYirgkdVGELLNKVTLHIVPMVNPDGVEISQNgsnainpyylrlvaw 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2789654  1048 -RGCTSKLG-HANAHGRDLDTDFTSN-------------YSRYSGTR---EPETKAIIeNLILKQDFSLSVALD 1103
Cdd:cd06229   81 nKKGTDFTGwKANIRGVDLNRNFPAGwekekrlgpkapgPRDYPGKEplsEPETKAMA-ALTRQNDFDLVLAYH 153

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: 55.83 E-value: 3.11e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   568 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVQSTRIHIMPSMNPDGYEK------------------SQEGDRGGT 629
Cdd:cd06238    8 YSIHGNELSGSEAAMQVAYHLAA--GQDEATRALLENTVIVIDPNQNPDGRERfvnwfnqnrgavgdpdpqSMEHNEPWP 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 2789654   630 VGRNNSNNYDLNRnfpDQFFQVtdppQPETLAVMSWLKTY-PFVL 673
Cdd:cd06238   86 GGRTNHYLFDLNR---DWLAQT----QPESRARAAAIHRWrPQVV 123

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: 55.39 E-value: 3.85e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   986 PKIRFVAGIHGNAPVGTELllalaeflCMNYKKNSAVTK----LIDRTRIVIVPSLNPDGREiAQERGctsklghaNAHG 1061
Cdd:cd06242    2 PTVLLVGQQHGNEPAGREA--------ALALARDLAFGDdareLLEKVNVLVVPRANPDGRA-ANTRG--------NANG 64

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 2789654  1062 RDLDTDFTSnysrysgTREPETKAIIENLilkQDFSLSVALDG 1104
Cdd:cd06242   65 VDLNRDHLL-------LSTPETRALARVL---RDYRPEVVIDA 97

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

Pssm-ID: 349430 [Multi-domain] Cd Length: 203 Bit Score: 54.39 E-value: 7.73e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   134 LVGNMHGDEPLARPLLLrlaqELVRGWAGGDERLGRLLNTTDLYLLPSLNPDGFERaregdCGGGGGGEGGGEPGGRENS 213
Cdd:cd03857    4 LAAQIHGNETTGTEALM----ELIRDLASESDEAAKLLDNIVILLVPQLNPDGAEL-----FVNFYLDSMNGLPGTRYNA 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2789654   214 RGRDLNRsfpDQFGSAQpdlepvPEVRALIAWMRRNKFLLSGNLHgGSVVASYPYDDSPTHRPTGVYSKSADDEV 288
Cdd:cd03857   75 NGIDLNR---DHVKLTQ------PETQAVAENFIHWWPDIFIDLH-EQVGASIPYPTPPDAPNYNLVDLRSDAEN 139

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: 55.15 E-value: 1.20e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   522 RYANEYPSITRLYSVGKSVELRELYVMEISdNPGVHEAGEpeFKYIGnMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDL 601
Cdd:cd03871   18 QVASKNPDLVSRSQIGTTFEGRPIYLLKVG-KPGSNKKAI--FMDCG-FHAREWISPAFCQWFVREAVRTYGKEKIMTKL 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   602 VQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNN-----YDLNRNFPDQFFQV---TDP-----------PQPETLAV 662
Cdd:cd03871   94 LDRLDFYILPVLNIDGYVYTWTKNRMWRKTRSPNAGsscigTDPNRNFNAGWCTVgasSNPcsetycgsapeSEKETKAL 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   663 MSWLKTYPFVLSANL--HGGSLVVNYPFDDDeqgiaiYSKSPDDAVFQQLALSYSKEnkkmyqgspCKDLYPTEYfPHGi 740
Cdd:cd03871  174 ANFIRNNLSSIKAYLtiHSYSQMLLYPYSYT------YKLAPNHEELNSIAKGAVKE---------LSSLYGTKY-TYG- 236

                        250
                 ....*....|....*...
gi 2789654   741 TNGAQWYNVPGGMQDWNY 758
Cdd:cd03871  237 PGATTIYPAAGGSDDWAY 254

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: 52.57 E-value: 4.55e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   514 SDMEIFLRRYANEYPsiTRLYSVGKSVELRELYVMEIsdnpgvheaGEPEFK----YIGNMHGNEVVGRELLLNLIEYLC 589
Cdd:cd06237    1 ADYDAWIDSLAKKPF--VKRSTIGKSVEGRPIEALTI---------GNPDSKelvvLLGRQHPPEVTGALAMQAFVETLL 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   590 knfGTDPEVTDLVQSTRIHIMPSMNPDGYeksqegDRGGTvgRNNSNNYDLNRNFpdQFFQvtdppQPETLAVMSWLKTY 669
Cdd:cd06237   70 ---ADTELAKAFRARFRVLVVPLLNPDGV------DLGHW--RHNAGGVDLNRDW--GPFT-----QPETRAVRDFLLEL 131

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 2789654   670 pfvlsANLHGGSLV-----------VNYPFDDDEQG 694
Cdd:cd06237  132 -----VEEPGGKVVfgldfhstwedVFYTQPDDEKT 162

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: 52.07 E-value: 7.01e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   515 DMEIFLRRYA-NEYPSITRlysVGKSVELRELYVMEISDNPGVHEAgepefkYI-GNMHGNEVVGRELLLNLIEYLCKNf 592
Cdd:cd18429    1 DLDRLLAKIRkNPLVEITT---IGKTVEGRPLEIIRIGNESAPHRV------FLrARAHPWEAGGNWVVEGLVERLLQN- 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   593 gtDPEVTDLVQSTRIHIMPSMNPDGYEksqegdRGGTvgRNNSNNYDLNRN--FPdqffqvTDPP-QPETLAVMSWL--- 666
Cdd:cd18429   71 --DEEAKRFLKRYCVYILPMANKDGVA------RGRT--RFNANGKDLNREwdKP------ADPVlAPENFALEKWLeem 134

                        170       180       190
                 ....*....|....*....|....*....|.
gi 2789654   667 ---KTYPFvLSANLH---GGSLVVNYPFDDD 691
Cdd:cd18429  135 ikaGKKPD-LAIELHndgGGNLHVSRPPVDG 164

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: 50.80 E-value: 1.65e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   166 RLGRLLNTTDLYLLPSLNPDGFERAREGDCGGGGGGEGGGEPGGRE--------NSRGRDLNRSFPDQFGSAQ------- 230
Cdd:cd06229   39 DVGELLNKVTLHIVPMVNPDGVEISQNGSNAINPYYLRLVAWNKKGtdftgwkaNIRGVDLNRNFPAGWEKEKrlgpkap 118

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 2789654   231 -----PDLEPV--PEVRALIAWMRRNKFLLSGNLH 258
Cdd:cd06229  119 gprdyPGKEPLsePETKAMAALTRQNDFDLVLAYH 153

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

Pssm-ID: 349466 [Multi-domain] Cd Length: 298 Bit Score: 51.39 E-value: 1.76e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   509 RHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEI---SDNPgvheagepefKYIGNM----HGNEVVGRELL 581
Cdd:cd06247    3 KYHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKP----------KKIIWMdcgiHAREWIAPAFC 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   582 LNLIEYLCKNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNN-----YDLNRNF------------ 644
Cdd:cd06247   73 QWFVKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTTDRLWRKSRSPHNNgtcygTDLNRNFnsqwcsigasrn 152

                        170       180
                 ....*....|....*....|....
gi 2789654   645 -PDQFFQVTDP-PQPETLAVMSWL 666
Cdd:cd06247  153 cCSIIFCGTGPeSEPETKAVADLI 176

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

Pssm-ID: 433425 [Multi-domain] Cd Length: 88 Bit Score: 46.43 E-value: 3.29e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     803 IWGFVLDATDGRGILNATISVADINHPVTTYKDGDY-WRLLVQGTYKVTASARGYDPVTKTVEVDSKGGVQVNFTLSRTD 881
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTDADGNFeLKNLPAGTYTLVVSFVGYKTQEKKVTVSNDNTLDVNFLLKEDA 80


                   ....*
gi 2789654     882 AKVEE 886
Cdd:pfam13715   81 LLLDE 85

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: 50.36 E-value: 3.56e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   510 HHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEIsdnpGVHEAGEPEFKYIG-NMHGNEVVGRELLLNLIEYL 588
Cdd:cd03872    2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIDcGIHAREWIGPAFCQWFVKEA 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2789654   589 CKNFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRNNSNNY-----DLNRNF 644
Cdd:cd03872   78 INSYQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDRFWRKTRSKNSRFqcrgvDANRNW 138

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: 48.99 E-value: 7.73e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   969 IWSLEISNKPNHSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCMNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQE- 1047
Cdd:cd06226    2 IRALKLTNKQATPPGEKPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDYTELHLVPQVNPDGRKIAETg 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2789654  1048 -----------RGCTSklghaNAHGRDLDTDFTSNY-----------SRYSGT---REPETKAI 1086
Cdd:cd06226   82 llwrkntnttpCPASS-----PTYGVDLNRNSSFKWggagaggsacsETYRGPsaaSEPETQAI 140

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: 47.84 E-value: 1.01e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   992 AGIHGNAPVGTELLLALAEFlcMNYKKnSAVTKLIDRTRIVIVPSLNPDGRE----IAQERGCTSKLGHANAHGRDLDTD 1067
Cdd:cd03857    6 AQIHGNETTGTEALMELIRD--LASES-DEAAKLLDNIVILLVPQLNPDGAElfvnFYLDSMNGLPGTRYNANGIDLNRD 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 2789654  1068 FTSnysrysgTREPETKAIIENLIlkqDFSLSVALDG---GSLLVTYPF 1113
Cdd:cd03857   83 HVK-------LTQPETQAVAENFI---HWWPDIFIDLheqVGASIPYPT 121

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: 48.07 E-value: 1.23e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   127 PGRPQVKLVGNMHGDEPlarplllrlaqelvrgwAG--G-----DERLGRLLNTTDLYLLPSLNPDGFER-AREgdcggg 198
Cdd:cd06231   40 GDKPRVLISAGIHGDEP-----------------AGveAllrflESLAEKYLRRVNLLVLPCVNPWGFERnTRE------ 96

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2789654   199 gggegggepggreNSRGRDLNRSFpdQFGSaqpdlePVPEVRALIAWMR-RNKFLLSGNLH 258
Cdd:cd06231   97 -------------NADGIDLNRSF--LKDS------PSPEVRALMEFLAsLGRFDLHLDLH 136

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: 48.20 E-value: 1.73e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   511 HHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPgvheAGEPEFKYIGNMHGNEVVGRELLLNLIEYLCK 590
Cdd:cd03870    7 HTLEEIYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIVS 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2789654   591 NFGTDPEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVGRN-NSNNY----DLNRNFPDQF 648
Cdd:cd03870   83 DYGKDPSITSILDTMDIFLEIVTNPDGYVFTHSSNRLWRKTRSvNPGSLcigvDPNRNWDAGF 145

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: 47.92 E-value: 2.23e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   933 RYRPYKDLSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEI---SNKPNhsepeepKIRFV-AGIHGNAPVGTELLLAL 1008
Cdd:cd06247    3 KYHPMDEIYQWMDQMQEKNSEVVSQHYLGQTYEKRPMYYLKIgwpSDKPK-------KIIWMdCGIHAREWIAPAFCQWF 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1009 AEFLCMNYKKNSAVTKLIDRTRIVIVPSLNPDGREIAQE-----RGCTSKLGHANAHGRDLDTDFTSNY-----SR---- 1074
Cdd:cd06247   76 VKEILQNYKTDSRLNKLLKNLDFYVLPVLNIDGYIYSWTtdrlwRKSRSPHNNGTCYGTDLNRNFNSQWcsigaSRnccs 155

                        170       180
                 ....*....|....*....|....*.
gi 2789654  1075 --YSGT---REPETKAIIENLILKQD 1095
Cdd:cd06247  156 iiFCGTgpeSEPETKAVADLIEKKKS 181

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

Pssm-ID: 349460 [Multi-domain] Cd Length: 215 Bit Score: 46.87 E-value: 2.96e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   567 IGNMHGNEVVGRELLLNLIEYLCknFGtdpEVTDLVQSTRIHIMPSMNPDGYEKSQEGDRGGTVG------RNNSNNYDL 640
Cdd:cd06241    7 QAGIHPGEVEGKEASLMLLRDIA--QG---GKKHLLDNLILLFVPIFNADGNDRRSKGNRPNQNGplevgwRTNAQGLDL 81


                 ....
gi 2789654   641 NRNF 644
Cdd:cd06241   82 NRDF 85

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: 45.73 E-value: 5.58e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   129 RPQVKLVGNMHGDEPLARplllrlaqELVRGWAggderlgRLLNTTD------LYLLPSLNPDGFERA-REgdcgggggg 201
Cdd:cd06904   23 RARILIIGGIHGDEPEGV--------SLVEHLL-------RWLKNHPasgdfhIVVVPCLNPDGLAAGtRT--------- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   202 egggepggreNSRGRDLNRSFPDQ--------------FGSAQPDLEpvPEVRALIAWMRRNK--FLLSgnLHGGSVVAS 265
Cdd:cd06904   79 ----------NANGVDLNRNFPTKnwepdarkpkdpryYPGPKPASE--PETRALVELIERFKpdRIIS--LHAPYLVNY 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   266 YPYDDSPthrptgvysksaddevfkyLAKAYASHHPIMRTGKPncpgeegetfqdGITNGAqwydveGGMqdynyvWA-- 343
Cdd:cd06904  145 DGPAKSL-------------------LAEKLAQATGYPVVGDV------------GYTPGS------LGT------YAgi 181

                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 2789654   344 --NCFEITLELscckyPPTSELQQEWENNRESLLTFI 378
Cdd:cd06904  182 erNIPVITLEL-----PEAVSIDELWQDLKRALIEAI 213

Carboxypeptidase regulatory-like domain;

Pssm-ID: 433354 [Multi-domain] Cd Length: 81 Bit Score: 42.27 E-value: 8.02e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2789654    1221 GVHGFVQDKSGKAISKATIVL-----NEGLRVYTKEGGYFHV-LLAPGLHNINAIADGYQQ 1275
Cdd:pfam13620    1 TISGTVTDPSGAPVPGATVTVtntdtGTVRTTTTDADGRYRFpGLPPGTYTVTVSAPGFKT 61

murein tripeptide amidase MpaA;

Pssm-ID: 182582 Cd Length: 237 Bit Score: 45.02 E-value: 1.41e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2789654    606 RIHIMPSMNPDGyekSQEGDRGgtvgrnNSNNYDLNRNFPDQFFQ 650
Cdd:PRK10602   72 RHHVVLAVNPDG---CQLGLRA------NANGVDLNRNFPAANWK 107

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

Pssm-ID: 349429 Cd Length: 252 Bit Score: 44.88 E-value: 1.83e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   163 GDERLGRLLNTTDLYLLPSLNPDGFERARegdcggggggegggepgGRENSRGRDLNRSFpdqfgsAQPDLEPVPEVRAL 242
Cdd:cd03856   73 DDDPAQQLRAEYNFYIIPMVNPDGVARGH-----------------WRTNSRGMDLNRDW------HAPDALLSPETYAV 129

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   243 IAWmrrnkfLLSGNLHGGSVVasYPYDDSPTHRPTGVYSKSADDEVFKYLAKAYASHHPIMRTGKPNCPGEEGETFQDGI 322
Cdd:cd03856  130 AAA------LAERVQSPEGVV--LALDLHGDNRNVFLTGPDNKDESTNHNPDKLNSLLTETDRRLPDYNTEASPGDNPGG 201

                        170
                 ....*....|....*....
gi 2789654   323 TNGAQW-YDVEGGMQDYNY 340
Cdd:cd03856  202 TVGKQWiADVYQITHSVTL 220

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: 43.57 E-value: 4.21e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   562 PEFKYIGNMHGNEVVGRELLLNLIEYLCKNFGTDPEVTDLVQSTRIHIMPSMNPDGYeksqegdRGGTvgRNNSNNYDLN 641
Cdd:cd03862    1 PVVGLVGGVHGLERIGTQVILAFLRSLLARLKWDKLLQELLEEVRLVVIPIVNPGGM-------ALKT--RSNPNGVDLM 71


                 ....
gi 2789654   642 RNFP 645
Cdd:cd03862   72 RNAP 75

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

Pssm-ID: 433425 [Multi-domain] Cd Length: 88 Bit Score: 40.27 E-value: 4.67e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654     385 VKGYVRDAITGAGLENATIVVAGI-AHNITAGKfGDYH-RLLVPGTYNVTAVVMGYAPVTKEnIEVKEGDATVVDFSLQP 462
Cdd:pfam13715    1 ISGTVVDENTGEPLPGATVYVKGTtKGTVTDAD-GNFElKNLPAGTYTLVVSFVGYKTQEKK-VTVSNDNTLDVNFLLKE 78


                   ...
gi 2789654     463 TVV 465
Cdd:pfam13715   79 DAL 81

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: 42.79 E-value: 4.86e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   138 MHGDEPLARPLLLRLAQELVRGWAGGDerlgRLLNTTDLYLLPSLNPDGFERaregdcggggggegggepGGRENSRGRD 217
Cdd:cd06239    8 MHGNEPTGTEALLDLISYLRRERQEFE----KILERLTLVAIPMLNPDGAEL------------------FTRHNAEGID 65

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 2789654   218 LNRsfpdqfgSAQpDLEPvPEVRALIAWMRRNKFLLSGNLHG 259
Cdd:cd06239   66 LNR-------DAR-ALQT-PESRALKAVLDSFSPKFAFNLHD 98

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: 43.96 E-value: 4.96e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   940 LSEFLRGLYLNYPHITNLTSLGQSVEFRQIWSLEISNKPnhsePEEPKIRFVAGIHGNAPVGTELLLALAEFLCMNYKKN 1019
Cdd:cd03870   12 IYFWMDNLVAEHPNLVSKLQIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIVSDYGKD 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1020 SAVTKLIDRTRIVIVPSLNPDGREIAQE-----RGCTSKLGHANAHGRDL----DTDFTSNYSR-------YSGT---RE 1080
Cdd:cd03870   88 PSITSILDTMDIFLEIVTNPDGYVFTHSsnrlwRKTRSVNPGSLCIGVDPnrnwDAGFGGPGASsnpcsetYHGPhanSE 167

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2789654  1081 PETKAIIENLILKQDFSLSVALDGGSLLVTYPFDKPAQTVENKDTL--------KHLASVY 1133
Cdd:cd03870  168 VEVKSIVDFIQSHGNFKAFISIHSYSQLLMYPYGYTVEKAPDQEELdevakkavKALASLH 228

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: 41.90 E-value: 1.29e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   129 RPQVKLVGNMHGDEPLARPLLLRLAQELvrgwAGGDERLgRLLNTTDLYLLPSLNPDGFERARegdcggggggegggepg 208
Cdd:cd06242    1 KPTVLLVGQQHGNEPAGREAALALARDL----AFGDDAR-ELLEKVNVLVVPRANPDGRAANT----------------- 58

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 2789654   209 gRENSRGRDLNRsfpDQFGSAQpdlepvPEVRALIAWMRR 248
Cdd:cd06242   59 -RGNANGVDLNR---DHLLLST------PETRALARVLRD 88

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: 41.52 E-value: 1.73e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   957 LTSLGQSVEFRQIWSLEISNKPNhsePEEPKIRFVAGIHGNAPVGTELLLALAeflcmnykkNSAVTKLIDRTRIVIVPS 1036
Cdd:cd06231   17 VRELGEVGYQGYPLFALKSPNPR---GDKPRVLISAGIHGDEPAGVEALLRFL---------ESLAEKYLRRVNLLVLPC 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2789654  1037 LNPDGREiAQERgctsklghANAHGRDLDTDFTsnysrySGTREPETKAIIENLILKQDFSLSVAL 1102
Cdd:cd06231   85 VNPWGFE-RNTR--------ENADGIDLNRSFL------KDSPSPEVRALMEFLASLGRFDLHLDL 135

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: 41.01 E-value: 2.74e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654    59 RDLVAEAP-PGLARLFSIGRSVEGRPLWVLRLTAGLPELPE----ARQDgekkkkeeeeeeeeegeeggggalPGRPQVK 133
Cdd:cd06234    7 LDLVARAQaSPGVRLEVLGQTLDGRDIDLLTIGDPGTGKKKvwiiARQH------------------------PGETMAE 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654   134 LVgnMHGdeplarplllrlaqeLVRGWAGGDERLGR-LLNTTDLYLLPSLNPDGFER--ARegdcggggggegggepggr 210
Cdd:cd06234   63 WF--MEG---------------LLDRLLDEDDPVSRaLLEKAVFYVVPNMNPDGSVRgnLR------------------- 106

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 2789654   211 ENSRGRDLNRSFpdqfgsAQPDLEPVPEVRALIAWMRRNKFLLSGNLHG 259
Cdd:cd06234  107 TNAAGVNLNREW------ANPSLERSPEVFAVRQAMDATGVDFFLDVHG 149

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: 40.63 E-value: 3.60e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1027 DRTRIVIVPSLNPDGREiaqergctskLGH--ANAHGRDLDTD---FTsnysrysgtrEPETKAI---IENLILKQDFSL 1098
Cdd:cd06237   80 ARFRVLVVPLLNPDGVD----------LGHwrHNAGGVDLNRDwgpFT----------QPETRAVrdfLLELVEEPGGKV 139


                 ....*
gi 2789654  1099 SVALD 1103
Cdd:cd06237  140 VFGLD 144

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: 40.33 E-value: 3.69e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 2789654   568 GNMHGNEVVGRELLLNLIEYLCKnfGTDPEVTDLVQSTRIHIMPSMNPDGYEK 620
Cdd:cd06240    8 GGLHATEVAGSQMLPELAYRLAT--SDDEEVRRILDNVILLLVPSANPDGQDL 58

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: 39.95 E-value: 6.01e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2789654  1022 VTKLIDRTRIVIVPSLNPDGREIAQ-----ERGctsklghaNAHGRDLDTDFTSNYSR---------YSGTR---EPETK 1084
Cdd:cd06227   44 AREILDNVELKIIPNANPDGRRLVEsgdycWRG--------NENGVDLNRNWGVDWGKgekgapseeYPGPKpfsEPETR 115

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 2789654  1085 AIIEnLILKQDFSLSVALDGGSLLVTYPFD----KPAQTVENK 1123
Cdd:cd06227  116 ALRD-LALSFKPHAFVSVHSGMLAIYTPYAysasVPRPNRAAD 157