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Conserved domains on  [gi|22203763|ref|NP_038522|]
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Protein Classification

M14 family carboxypeptidase N/E (domain architecture ID 10133695)

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

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List of domain hits

Name Accession Description Interval E-value
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
53-371 0e+00

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  Cd Length: 319  Bit Score: 729.86  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03865   1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 212
Cdd:cd03865  81 NEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 KNLKKIVDQNSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAHEYSSCPDDAIFQSLARAYSSFNPVM 292
Cdd:cd03865 161 KNMKKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDAIFQSLARAYSSLNPAM 240
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763 293 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLEQ 371
Cdd:cd03865 241 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
375-449 1.32e-39

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: 137.27  E-value: 1.32e-39
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22203763 375 GVKGFVRDLQGNPIANATISVDGIDHDVTSAKDGDYWRLLAPGNYKLTASAPGYLAITKKVAVPFSP-AVGVDFEL 449
Cdd:cd11308   1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFsATVVNFTL 76
 
Name Accession Description Interval E-value
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
53-371 0e+00

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  Cd Length: 319  Bit Score: 729.86  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03865   1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 212
Cdd:cd03865  81 NEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 KNLKKIVDQNSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAHEYSSCPDDAIFQSLARAYSSFNPVM 292
Cdd:cd03865 161 KNMKKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDAIFQSLARAYSSLNPAM 240
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763 293 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLEQ 371
Cdd:cd03865 241 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
67-364 7.99e-95

Zinc carboxypeptidase;


Pssm-ID: 395189 [Multi-domain]  Cd Length: 287  Bit Score: 288.04  E-value: 7.99e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763    67 WLQCTA-----ISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKgNET 141
Cdd:pfam00246   4 WLDALAarypdLVRLVSIGKSVEGRPIKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLINQLLTNYGR-DPE 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763   142 IVNLIHSTRIHIMPSLNPDGFEKAASQpgeLKDWFVGRSNAQ-----GIDLNRNFPDLDRIVY-----VNEKEGGPNNHl 211
Cdd:pfam00246  83 VTELLDDTDIYILPVVNPDGYEYTHTT---DRLWRKNRSNANgssciGVDLNRNFPDHWNEVGastnpCSETYRGPAPF- 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763   212 lknlkkivdqnskLAPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSgtaheySSCPDDAIFQSLARAYSSFNP 290
Cdd:pfam00246 159 -------------SEPETRAVIDFIRSkKPFVLYIDLHSYSQVLLYPYGYTRS------EPPPDDEELKSLARAAAKALQ 219
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763   291 VMSdpnrppcrkndDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNC-FEITVELSCEK----FPPEETLKSYWEDNKNS 364
Cdd:pfam00246 220 KMV-----------RGTSYTYGISNGDTIYPASGGSDDWAYGRLGIkYSFTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
53-354 7.46e-72

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 228.76  E-value: 7.46e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763     53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGvhePGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:smart00631   1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763    133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEKAASQPgelKDWFVGRS---NAQGIDLNRNFPDLdrivyvNEKEGGPNN 209
Cdd:smart00631  78 ENYGR-DPRVTNLLDKTDIYIVPVLNPDGYEYTHTGD---RLWRKNRSpnsNCRGVDLNRNFPFH------WGETGNPCS 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763    210 HLLKNLKKIVDqnsklaPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSGTAHEYSScpDDAIFQSLARAYSSF 288
Cdd:smart00631 148 ETYAGPSPFSE------PETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD--LDAVAKALAKALASV 219
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22203763    289 NPvmsdpnrppcrkndddSSFVDGTTNGGAWYsVPGGMQDFNYLSSN-CFEITVELSCE-----KFPPEETL 354
Cdd:smart00631 220 HG----------------TRYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQII 274
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
375-449 1.32e-39

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: 137.27  E-value: 1.32e-39
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22203763 375 GVKGFVRDLQGNPIANATISVDGIDHDVTSAKDGDYWRLLAPGNYKLTASAPGYLAITKKVAVPFSP-AVGVDFEL 449
Cdd:cd11308   1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFsATVVNFTL 76
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
375-449 1.11e-16

Carboxypeptidase regulatory-like domain;


Pssm-ID: 404503 [Multi-domain]  Cd Length: 81  Bit Score: 74.63  E-value: 1.11e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763   375 GVKGFVRDLQGNPIANATISV----DGIDHDVTSAKDGDYW-RLLAPGNYKLTASAPGYLAITKK-VAVPFSPAVGVDFE 448
Cdd:pfam13620   1 TISGTVTDPSGAPVPGATVTVtnadTGTVRTTTTDADGRFRfPGLPPGTYTVTVSAPGFASATRTgVTVTAGQTTTLDVT 80

                  .
gi 22203763   449 L 449
Cdd:pfam13620  81 L 81
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
72-195 1.08e-07

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


Pssm-ID: 225421 [Multi-domain]  Cd Length: 374  Bit Score: 53.64  E-value: 1.08e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  72 AISRIYTVGRSFEGRELLVIelsdNPGVHEPGEPEFKYIGNMHGNeavGRELLIFLAQYLCNEYQKGNETIVNLIHSTRI 151
Cdd:COG2866 119 LLVELELIGRSVEGRDDPLI----TFPESNPEHKTILITAGQHAR---GEKMVEWFLYNLILRYLDPDVQVRKLLDRADL 191
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 22203763 152 HIMPSLNPDGfekaaSQPGELkdwfvgRSNAQGIDLNRNFPDLD 195
Cdd:COG2866 192 HVVPNVNPDG-----SDLGNL------RTNANGVDLNRNFIAPN 224
PRK10602 PRK10602
murein tripeptide amidase MpaA;
150-192 2.14e-04

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 42.71  E-value: 2.14e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 22203763  150 RIHIMPSLNPDGfekaaSQPGElkdwfvgRSNAQGIDLNRNFP 192
Cdd:PRK10602  72 RHHVVLAVNPDG-----CQLGL-------RANANGVDLNRNFP 102
 
Name Accession Description Interval E-value
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
53-371 0e+00

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  Cd Length: 319  Bit Score: 729.86  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03865   1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 212
Cdd:cd03865  81 NEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 KNLKKIVDQNSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAHEYSSCPDDAIFQSLARAYSSFNPVM 292
Cdd:cd03865 161 KNMKKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDAIFQSLARAYSSLNPAM 240
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763 293 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLEQ 371
Cdd:cd03865 241 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
53-371 0e+00

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


Pssm-ID: 349431  Cd Length: 292  Bit Score: 519.90  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03858   1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYqKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPgelKDWFVGRSNAQGIDLNRNFPDLDRIVYvnekeggpnnhll 212
Cdd:cd03858  81 ENY-GKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGD---CGGLIGRNNANGVDLNRNFPDQFFQVY------------- 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 knlkkivDQNSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAHEYSSCPDDAIFQSLARAYSSFNPVM 292
Cdd:cd03858 144 -------SDNNPRQPETKAVMNWLESIPFVLSANLHGGALVANYPYDDTRSGKSTEYSPSPDDAVFRMLARSYSDAHPTM 216
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763 293 SDPNRPPCrknDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLEQ 371
Cdd:cd03858 217 SMGKPCCC---DDDENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
53-371 1.24e-141

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  Cd Length: 313  Bit Score: 408.55  E-value: 1.24e-141
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03864   1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNH-- 210
Cdd:cd03864  81 EEYRNGNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNGYLVGRNNANGVDLNRNFPDLNTLMYYNEKYGGPNHHlp 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 211 LLKNLKkivdqnSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDET-----RSGTAHEYSSCPDDAIFQSLARAY 285
Cdd:cd03864 161 LPDNWK------SQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSreprvRGFRRTAYSPTPDDKLFQKLAKTY 234
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 286 SSFNPVMSdpnrppcRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSL 365
Cdd:cd03864 235 SYAHGWMH-------KGWNCGDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREAL 307

                ....*.
gi 22203763 366 ISYLEQ 371
Cdd:cd03864 308 ISYMEQ 313
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
53-371 9.79e-139

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: 400.47  E-value: 9.79e-139
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03868   1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEKaaSQPGEL--KDWFVGRSNAQGIDLNRNFPDLDRivyvnekeggpnnh 210
Cdd:cd03868  81 ENYGK-DERVTRLVNSTDIHLMPSMNPDGFEN--SKEGDCsgDPGYGGRENANNVDLNRNFPDQFE-------------- 143
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 211 llknlKKIVDQNSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAH-EYSSCPDDAIFQSLARAYSSFN 289
Cdd:cd03868 144 -----DSDDRLLEGRQPETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECgVYSKSPDDAVFRHLAHTYADNH 218
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 290 PVMSdpNRPPCrkndDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYL 369
Cdd:cd03868 219 PTMH--KGNNC----CEDSFKDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYM 292

                ..
gi 22203763 370 EQ 371
Cdd:cd03868 293 EQ 294
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
53-371 4.40e-130

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: 379.56  E-value: 4.40e-130
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03869   1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGG-----P 207
Cdd:cd03869  81 QEYLAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGGWSLGRWTSDGIDINHNFPDLNSLLWEAEDRKWvprkvP 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 208 NNHLlknlkKIVD----QNSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRS-GTAHEYSSCPDDAIFQSLA 282
Cdd:cd03869 161 NHHI-----PIPEwylsENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTpWKTQEYTPTPDDHVFRWLA 235
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 283 RAYSSFNPVMSDPNRPPCrkNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNK 362
Cdd:cd03869 236 YSYASTHRLMTDASRRPC--HTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNR 313

                ....*....
gi 22203763 363 NSLISYLEQ 371
Cdd:cd03869 314 ESLLVFMEQ 322
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
53-370 1.55e-128

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: 375.38  E-value: 1.55e-128
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03867   1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVY-VNEKEGGPNNHL 211
Cdd:cd03867  81 SEYLLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAGYNGWTSGRQNAQNLDLNRNFPDLTSEAYrLARTRGARLDHI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 212 lknlkKIVDQ--NSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAH-EYSSCPDDAIFQSLARAYSSF 288
Cdd:cd03867 161 -----PIPQSywWGKVAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEkMFSPTPDEKMFKLLAKAYADA 235
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 289 NPVMSDPNRPPCRKNDDDSSfvdGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISY 368
Cdd:cd03867 236 HPMMSDRSENRCGGNFLKRG---GIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNF 312

                ..
gi 22203763 369 LE 370
Cdd:cd03867 313 ME 314
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
51-371 4.63e-120

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  Cd Length: 296  Bit Score: 353.10  E-value: 4.63e-120
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  51 FEYHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQY 130
Cdd:cd03863   6 FRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIEY 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 131 LCNEYQKGNEtIVNLIHSTRIHIMPSLNPDGFEKaaSQPGElKDWFVGRSNAQGIDLNRNFPDldrivyvnekeggpnnh 210
Cdd:cd03863  86 LCKNFGTDPE-VTDLVQNTRIHIMPSMNPDGYEK--SQEGD-RGGTVGRNNSNNYDLNRNFPD----------------- 144
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 211 llkNLKKIVDqnsKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAhEYSSCPDDAIFQSLARAYSSFNP 290
Cdd:cd03863 145 ---QFFQITD---PPQPETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLA-TYSKSPDDAVFQQLALSYSKENS 217
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 291 VMSDPNrpPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLE 370
Cdd:cd03863 218 KMYQGS--PCKELYPNEYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRRSLLQFIK 295

                .
gi 22203763 371 Q 371
Cdd:cd03863 296 Q 296
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
53-371 7.04e-106

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: 316.74  E-value: 7.04e-106
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03866   1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEkAASQPGELkdWFVGRSNAQGIDLNRNFPDldrivyvnekeggpnnhll 212
Cdd:cd03866  81 TSYGS-DPVITRLINSTRIHIMPSMNPDGFE-ATKKPDCY--YTKGRYNKNGYDLNRNFPD------------------- 137
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 knlkkIVDQNS-KLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTA--HEYSSCPDDAIFQSLARAYSSFN 289
Cdd:cd03866 138 -----AFEENNvQRQPETRAVMDWIKNETFVLSANLHGGALVASYPFDNGNSGTGqlGYYSVSPDDDVFIYLAKTYSYNH 212
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 290 PVMSDPNRppCrknDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYL 369
Cdd:cd03866 213 TNMYKGIE--C---SNSQSFPGGITNGYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYI 287

                ..
gi 22203763 370 EQ 371
Cdd:cd03866 288 KQ 289
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
53-370 4.60e-98

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


Pssm-ID: 349482  Cd Length: 276  Bit Score: 296.25  E-value: 4.60e-98
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPgEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd18172   1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDET-EPAFKFVGNMHGDEPVGRELLLRLADWLC 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKGNETIVNLIHSTRIHIMPSLNPDGFEKAAsqpgelkdwfvgRSNAQGIDLNRNFPDldrivyvNEKEGGPNNHLl 212
Cdd:cd18172  80 ANYKAKDPLAAKIVENAHLHLVPTMNPDGFARRR------------RNNANNVDLNRDFPD-------QFFPKNLRNDL- 139
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 knlkkivdqnSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAHeYSSCPDDAIFQSLARAYSSFNPVM 292
Cdd:cd18172 140 ----------AARQPETLAVMNWSRSVRFTASANLHEGALVANYPWDGNADGRTK-YSASPDDATFRRLASVYAQAHPNM 208
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22203763 293 SDPnrppcrkndddSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLE 370
Cdd:cd18172 209 AKS-----------KEFPGGITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALAA 275
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
67-364 7.99e-95

Zinc carboxypeptidase;


Pssm-ID: 395189 [Multi-domain]  Cd Length: 287  Bit Score: 288.04  E-value: 7.99e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763    67 WLQCTA-----ISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKgNET 141
Cdd:pfam00246   4 WLDALAarypdLVRLVSIGKSVEGRPIKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLINQLLTNYGR-DPE 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763   142 IVNLIHSTRIHIMPSLNPDGFEKAASQpgeLKDWFVGRSNAQ-----GIDLNRNFPDLDRIVY-----VNEKEGGPNNHl 211
Cdd:pfam00246  83 VTELLDDTDIYILPVVNPDGYEYTHTT---DRLWRKNRSNANgssciGVDLNRNFPDHWNEVGastnpCSETYRGPAPF- 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763   212 lknlkkivdqnskLAPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSgtaheySSCPDDAIFQSLARAYSSFNP 290
Cdd:pfam00246 159 -------------SEPETRAVIDFIRSkKPFVLYIDLHSYSQVLLYPYGYTRS------EPPPDDEELKSLARAAAKALQ 219
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763   291 VMSdpnrppcrkndDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNC-FEITVELSCEK----FPPEETLKSYWEDNKNS 364
Cdd:pfam00246 220 KMV-----------RGTSYTYGISNGDTIYPASGGSDDWAYGRLGIkYSFTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
53-371 6.61e-93

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  Cd Length: 281  Bit Score: 282.93  E-value: 6.61e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPgEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd18173   4 YPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA-EPEFKYTSTMHGDETTGYELMLRLIDYLL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELkdwfVGRSNAQGIDLNRNFPDldrivyvneKEGGPNNhll 212
Cdd:cd18173  83 TNYGT-DPRITNLVDNTEIWINPLANPDGTYAGGNNTVSG----ATRYNANGVDLNRNFPD---------PVDGDHP--- 145
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 knlkkivDQNSkLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDetrsgtaHEYSSCPDDAIFQSLARAYSSFNPVM 292
Cdd:cd18173 146 -------DGNG-WQPETQAMMNFADEHNFVLSANFHGGAEVVNYPWD-------TWYSRHPDDDWFQDISREYADTNQAN 210
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763 293 SDPNRppcrknddDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLEQ 371
Cdd:cd18173 211 SPPMY--------MSEFNNGITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
53-371 9.20e-75

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  Cd Length: 283  Bit Score: 236.57  E-value: 9.20e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd06245   1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDwfvGRSNAQGIDLNRNFPdldrivyvnEKEGGPnnhll 212
Cdd:cd06245  81 HNYKK-DSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKI---GEKNANGVDLDTDFE---------SNANNR----- 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 213 knlkkivdqNSKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGTAHEysscpddAIFQSLARAYSSFNPVM 292
Cdd:cd06245 143 ---------SGAAQPETKAIMDWLKEKDFTLSVALDGGSLVVTYPYDKPVQTVENK-------ETLKHLAKVYANNHPTM 206
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 293 --SDPNRPpcrkNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKSYWEDNKNSLISYLE 370
Cdd:cd06245 207 haGDPGCC----SNSDENFTNGVIRASEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIV 282

                .
gi 22203763 371 Q 371
Cdd:cd06245 283 E 283
Zn_pept smart00631
Zn_pept domain;
53-354 7.46e-72

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 228.76  E-value: 7.46e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763     53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGvhePGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:smart00631   1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763    133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEKAASQPgelKDWFVGRS---NAQGIDLNRNFPDLdrivyvNEKEGGPNN 209
Cdd:smart00631  78 ENYGR-DPRVTNLLDKTDIYIVPVLNPDGYEYTHTGD---RLWRKNRSpnsNCRGVDLNRNFPFH------WGETGNPCS 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763    210 HLLKNLKKIVDqnsklaPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSGTAHEYSScpDDAIFQSLARAYSSF 288
Cdd:smart00631 148 ETYAGPSPFSE------PETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD--LDAVAKALAKALASV 219
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22203763    289 NPvmsdpnrppcrkndddSSFVDGTTNGGAWYsVPGGMQDFNYLSSN-CFEITVELSCE-----KFPPEETL 354
Cdd:smart00631 220 HG----------------TRYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQII 274
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
375-449 1.32e-39

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: 137.27  E-value: 1.32e-39
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22203763 375 GVKGFVRDLQGNPIANATISVDGIDHDVTSAKDGDYWRLLAPGNYKLTASAPGYLAITKKVAVPFSP-AVGVDFEL 449
Cdd:cd11308   1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFsATVVNFTL 76
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
109-365 9.68e-35

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


Pssm-ID: 349427 [Multi-domain]  Cd Length: 216  Bit Score: 129.12  E-value: 9.68e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 109 YIGNMHGNEAVGRELLIFLAQYLCNEYqkGNETIVNLIHSTRIHIMPSLNPDGFEKAASqpgelkdwFVGRSNAQGIDLN 188
Cdd:cd00596   3 ITGGIHGNEVIGVELALALIEYLLENY--GNDPLKRLLDNVELWIVPLVNPDGFARVID--------SGGRKNANGVDLN 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 189 RNFPdldrivYVNEKEGGPNNHLLKNlkkivdQNSKLA--PETKAVIHWIMDIPFVLSANLHGGDLVANYPYdetrsgtA 266
Cdd:cd00596  73 RNFP------YNWGKDGTSGPSSPTY------RGPAPFsePETQALRDLAKSHRFDLAVSYHSSSEAILYPY-------G 133
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 267 HEYSSCPDDAIFQSLARAYSSFNPVmsdpnrppcrkndddssFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVEL-SC 345
Cdd:cd00596 134 YTNEPPPDFSEFQELAAGLARALGA-----------------GEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELgTA 196
                       250       260
                ....*....|....*....|
gi 22203763 346 EKFPPEETLKSYWEDNKNSL 365
Cdd:cd00596 197 DYPLPGTLLDRRLERNLAAL 216
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
53-361 2.81e-34

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


Pssm-ID: 349432 [Multi-domain]  Cd Length: 292  Bit Score: 130.07  E-value: 2.81e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVhEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03859   4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGE------LKDWFVGRSNAQGIDLNRNFPdldrivYV--NEKE 204
Cdd:cd03859  83 ENYGT-DPRITNLVDNREIWIIPVVNPDGYEYNRETGGGrlwrknRRPNNGNNPGSDGVDLNRNYG------YHwgGDNG 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 205 GGPNNHllknlkkiVDQN-------SklAPETKAVIHWIMDIPFVLSANLHG-GDLVaNYPYDETRSGTAheysscPDDA 276
Cdd:cd03859 156 GSSPDP--------SSETyrgpapfS--EPETQAIRDLVESHDFKVAISYHSyGELV-LYPWGYTSDAPT------PDED 218
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 277 IFQSLARAYSSFNPVMSDPNrppcrkndddSSFVDGTTNGGAwysvpggmQDFNYLSSNCFEITVEL---SCEKFPPEET 353
Cdd:cd03859 219 VFEELAEEMASYNGGGYTPQ----------QSSDLYPTNGDT--------DDWMYGEKGIIAFTPELgpeFYPFYPPPSQ 280

                ....*...
gi 22203763 354 LKSYWEDN 361
Cdd:cd03859 281 IDPLAEEN 288
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
375-449 1.11e-16

Carboxypeptidase regulatory-like domain;


Pssm-ID: 404503 [Multi-domain]  Cd Length: 81  Bit Score: 74.63  E-value: 1.11e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763   375 GVKGFVRDLQGNPIANATISV----DGIDHDVTSAKDGDYW-RLLAPGNYKLTASAPGYLAITKK-VAVPFSPAVGVDFE 448
Cdd:pfam13620   1 TISGTVTDPSGAPVPGATVTVtnadTGTVRTTTTDADGRFRfPGLPPGTYTVTVSAPGFASATRTgVTVTAGQTTTLDVT 80

                  .
gi 22203763   449 L 449
Cdd:pfam13620  81 L 81
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
53-164 1.32e-16

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  Cd Length: 359  Bit Score: 81.12  E-value: 1.32e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd06905   6 YYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYLL 85
                        90       100       110
                ....*....|....*....|....*....|..
gi 22203763 133 NEYQKgNETIVNLIHSTRIHIMPSLNPDGFEK 164
Cdd:cd06905  86 TNYGK-DPEITRLLDTRTFYILPRLNPDGAEA 116
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
78-369 4.86e-13

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


Pssm-ID: 349475 [Multi-domain]  Cd Length: 214  Bit Score: 68.07  E-value: 4.86e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  78 TVGRSFEGRELLVIELSDNPG--VHepgepefkYIGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIVnlihstrihIMP 155
Cdd:cd06904   3 VYGTSVKGRPILAYKFGPGSRarIL--------IIGGIHGDEPEGVSLVEHLLRWLKNHPASGDFHIV---------VVP 65
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 156 SLNPDGFEKAAsqpgelkdwfvgRSNAQGIDLNRNFPdldrivyvnekegGPNNHLLKNLKKIVDQNSKLA----PETKA 231
Cdd:cd06904  66 CLNPDGLAAGT------------RTNANGVDLNRNFP-------------TKNWEPDARKPKDPRYYPGPKpasePETRA 120
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 232 VIHWIMDIP--FVLSanLHgGDLVANYpydetrsgtaheysscpDDAIFQSLARAYSSFN--PVMSDPnrppcrknddds 307
Cdd:cd06904 121 LVELIERFKpdRIIS--LH-APYLVNY-----------------DGPAKSLLAEKLAQATgyPVVGDV------------ 168
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22203763 308 sfvdGTTNG--GAWysvpGGMQdfnylsSNCFEITVELscekfPPEETLKSYWEDNKNSLISYL 369
Cdd:cd06904 169 ----GYTPGslGTY----AGIE------RNIPVITLEL-----PEAVSIDELWQDLKRALIEAI 213
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
109-365 1.01e-12

Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like domain of Gamma-D-glutamyl-L-diamino acid endopeptidase 1 (also known as Gamma-D-glutamyl-meso-diaminopimelate peptidase I, and Endopeptidase I (ENP1); EC 3.4.19.11). ENP1 is a member of the M14 family of metallocarboxypeptidases (MCPs), and is classified as belonging to subfamily C. However it has an exceptional type of activity of hydrolyzing the gamma-D-Glu-(L)meso-diaminopimelic acid (gamma-D-Glu-Dap) bond of L-Ala-gamma-D-Glu-(L)meso-diaminopimelic acid and L-Ala-gamma-D-Glu-(L)meso-diaminopimelic acid(L)-D-Ala peptides. ENP1 has a different substrate specificity and cellular role than MpaA (MpaA does not belong to this group). ENP1 hydrolyzes the gamma-D-Glu-Dap bond of MurNAc-tripeptide and MurNAc-tetrapeptide, as well as the amide bond of free tripeptide and tetrapeptide. ENP1 is active on spore cortex peptidoglycan, and is produced at stage IV of sporulation in forespore and spore integuments.


Pssm-ID: 349448 [Multi-domain]  Cd Length: 238  Bit Score: 67.75  E-value: 1.01e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 109 YIGNMHGNEAVGRELLI-FLAQYLCNEYQKGNET---IVNLIHSTRIHIMPSLNPDGFE------KAASQPGELKDWFVG 178
Cdd:cd06229   3 YNASFHAREYITTLLLMkFIEDYAKAYVNKSYIRgkdVGELLNKVTLHIVPMVNPDGVEisqngsNAINPYYLRLVAWNK 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 179 --------RSNAQGIDLNRNFPdldrIVYVNEKEGGPNNHLLKNL--KKIVDQnsklaPETKAVIHWIMDIPFVLSANLH 248
Cdd:cd06229  83 kgtdftgwKANIRGVDLNRNFP----AGWEKEKRLGPKAPGPRDYpgKEPLSE-----PETKAMAALTRQNDFDLVLAYH 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 249 GGDLVANYPYDetrsGTAHEYSscpdDAIFQSLARAySSFNPVmsdpnrpPCRKNDDDSSFVDgttnggaWYSvpggmQD 328
Cdd:cd06229 154 SQGEEIYWGYN----GLEPEES----KAMAEKFASV-SGYEPV-------EAEAIDSYGGFKD-------WFI-----YE 205
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 22203763 329 FNYLSsncfeITVELSCEKFP-PEETLKSYWEDNKNSL 365
Cdd:cd06229 206 FKKPS-----FTIETGKGNNPlPISQFDEIYEKNKGVL 238
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
53-192 1.21e-12

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


Pssm-ID: 349433  Cd Length: 300  Bit Score: 68.32  E-value: 1.21e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  53 YHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELSDNPGvhEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 132
Cdd:cd03860   1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGG--KGGKPAIVIHGGQHAREWISTSTVEYLAHQLL 78
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22203763 133 NEYQKGNeTIVNLIHSTRIHIMPSLNPDGFEKAAS---------QPgelkdwfVGRSNAQGIDLNRNFP 192
Cdd:cd03860  79 SGYGSDA-TITALLDKFDFYIIPVVNPDGYVYTWTtdrlwrknrQP-------TGGSSCVGIDLNRNWG 139
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
109-195 7.70e-10

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  Cd Length: 203  Bit Score: 58.63  E-value: 7.70e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 109 YIGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIVNLIhstrIHIMPSLNPDGFEK-AASQPGELKDWFVGRSNAQGIDL 187
Cdd:cd03857   4 LAAQIHGNETTGTEALMELIRDLASESDEAAKLLDNIV----ILLVPQLNPDGAELfVNFYLDSMNGLPGTRYNANGIDL 79

                ....*...
gi 22203763 188 NRNFPDLD 195
Cdd:cd03857  80 NRDHVKLT 87
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
109-191 2.85e-08

Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a functionally uncharacterized subgroup of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. Two major subfamilies of the M14 family, defined based on sequence and structural homology, are the A/B and N/E subfamilies. Enzymes belonging to the A/B subfamily are normally synthesized as inactive precursors containing preceding signal peptide, followed by an N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The A/B enzymes can be further divided based on their substrate specificity; Carboxypeptidase A-like (CPA-like) enzymes favor hydrophobic residues while carboxypeptidase B-like (CPB-like) enzymes only cleave the basic residues lysine or arginine. The A forms have slightly different specificities, with Carboxypeptidase A1 (CPA1) preferring aliphatic and small aromatic residues, and CPA2 preferring the bulky aromatic side chains. Enzymes belonging to the N/E subfamily enzymes are not produced as inactive precursors and instead rely on their substrate specificity and subcellular compartmentalization to prevent inappropriate 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  Cd Length: 220  Bit Score: 54.23  E-value: 2.85e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 109 YIGNMHGNEAVGRELLIFLAQYLCNEYQKGnetivNLIHSTRIHIMPSLNPDGFEkaasqpgelKDWfvgRSNAQGIDLN 188
Cdd:cd06242   6 LVGQQHGNEPAGREAALALARDLAFGDDAR-----ELLEKVNVLVVPRANPDGRA---------ANT---RGNANGVDLN 68

                ...
gi 22203763 189 RNF 191
Cdd:cd06242  69 RDH 71
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
72-195 1.08e-07

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


Pssm-ID: 225421 [Multi-domain]  Cd Length: 374  Bit Score: 53.64  E-value: 1.08e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  72 AISRIYTVGRSFEGRELLVIelsdNPGVHEPGEPEFKYIGNMHGNeavGRELLIFLAQYLCNEYQKGNETIVNLIHSTRI 151
Cdd:COG2866 119 LLVELELIGRSVEGRDDPLI----TFPESNPEHKTILITAGQHAR---GEKMVEWFLYNLILRYLDPDVQVRKLLDRADL 191
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 22203763 152 HIMPSLNPDGfekaaSQPGELkdwfvgRSNAQGIDLNRNFPDLD 195
Cdd:COG2866 192 HVVPNVNPDG-----SDLGNL------RTNANGVDLNRNFIAPN 224
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
87-366 2.74e-07

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  Cd Length: 267  Bit Score: 51.69  E-value: 2.74e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  87 ELLVIELSdNPGVHEPGE-PEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIVNLIHsTRIHIMPSLNPDGFEKA 165
Cdd:cd06226   1 DIRALKLT-NKQATPPGEkPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDY-TELHLVPQVNPDGRKIA 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 166 ASqpGELKdwfvgRSNA-----------QGIDLNRNFPdldrivyvnEKEGGPNNHllKNLKKIVDQNSKLA--PETKAV 232
Cdd:cd06226  79 ET--GLLW-----RKNTnttpcpassptYGVDLNRNSS---------FKWGGAGAG--GSACSETYRGPSAAsePETQAI 140
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 233 IHWIMDipfvLSANLHGGDLVANYPydETRSG---TAHEYS------------SCPDDAIFQSLARAYSSFNPVmsDPNR 297
Cdd:cd06226 141 ENYVKQ----LFPDQRGPGLTDPAP--DDTSGiyiDIHSYGnlvlypwgwtgtPAPNAAGLRTLGRKFAYFNGY--TPQQ 212
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 298 PPCRKNdddssfVDGTTNggawysvpggmqDFNYLSSNCFEITVELSCEKFPPEETLKS-YWEDNKNSLI 366
Cdd:cd06226 213 AVALYP------TDGTTD------------DFAYGTLGVAAYTFELGTAFFESCSYFENtILPDNLPALY 264
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
111-236 1.08e-06

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


Pssm-ID: 349457  Cd Length: 217  Bit Score: 49.28  E-value: 1.08e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 111 GNMHGNEAVGRELLIFLAQYLCneyQKGNETIVNLIHSTRIHIMPSLNPDGFEKAASQPGELKDwFVGRSNAQGIDLNRN 190
Cdd:cd06238   8 YSIHGNELSGSEAAMQVAYHLA---AGQDEATRALLENTVIVIDPNQNPDGRERFVNWFNQNRG-AVGDPDPQSMEHNEP 83
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 22203763 191 FPdldrivyvnekeGGPNNHLLKNLKKivDQNSKLAPETKAVIHWI 236
Cdd:cd06238  84 WP------------GGRTNHYLFDLNR--DWLAQTQPESRARAAAI 115
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
112-192 2.75e-06

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  Cd Length: 224  Bit Score: 48.42  E-value: 2.75e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 112 NMHGNEAVGRELLIFLAQYLCNEYQKGNETIV-----NLIHSTRIHIMPSLNPDGFEKAASqpGELKdWfvgRSNAQGID 186
Cdd:cd06227   9 GEHARELISVESALRLLRQLCGGLQEPAASALrelarEILDNVELKIIPNANPDGRRLVES--GDYC-W---RGNENGVD 82

                ....*.
gi 22203763 187 LNRNFP 192
Cdd:cd06227  83 LNRNWG 88
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
113-194 3.76e-06

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


Pssm-ID: 349458  Cd Length: 194  Bit Score: 47.41  E-value: 3.76e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 113 MHGNEAVGRELLIFLAQYLcneYQKGNETIVNLIHSTrIHIMPSLNPDGFEKAAsqpgelkdwfvgRSNAQGIDLNRNFP 192
Cdd:cd06239   8 MHGNEPTGTEALLDLISYL---RRERQEFEKILERLT-LVAIPMLNPDGAELFT------------RHNAEGIDLNRDAR 71

                ..
gi 22203763 193 DL 194
Cdd:cd06239  72 AL 73
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
109-191 1.86e-05

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


Pssm-ID: 349447  Cd Length: 294  Bit Score: 46.22  E-value: 1.86e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 109 YIGNMHGNEAVGRELLIFLAQYLCNEYQKGN-----------ETIVNLIHSTRIHIMPSLNPDGfeKAASQPgELKDWFV 177
Cdd:cd06228   5 FIGGVHAREWGSPDILIYFAADLLEAYTNNTgltyggktftaAQVKSILENVDLVVFPLVNPDG--RWYSQT-SESMWRK 81
                        90       100
                ....*....|....*....|..
gi 22203763 178 GRSNAQ--------GIDLNRNF 191
Cdd:cd06228  82 NRNPASagdggsciGVDINRNF 103
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
73-191 7.49e-05

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


Pssm-ID: 349442 [Multi-domain]  Cd Length: 301  Bit Score: 44.35  E-value: 7.49e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  73 ISRIyTVGRSFEGRELLVIELSDNPgvhePGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKgNETIVNLIHSTRIH 152
Cdd:cd03870  27 VSKL-QIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIVSDYGK-DPSITSILDTMDIF 100
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 22203763 153 IMPSLNPDGF-----------EKAASQPGelkdwfvgrSNAQGIDLNRNF 191
Cdd:cd03870 101 LEIVTNPDGYvfthssnrlwrKTRSVNPG---------SLCIGVDPNRNW 141
M14-like cd03862
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
105-192 1.28e-04

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


Pssm-ID: 349434  Cd Length: 245  Bit Score: 43.57  E-value: 1.28e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 105 PEFKYIGNMHGNEAVG-RELLIFLAQYLcnEYQKGNETIVNLIHSTRIHIMPSLNPDGFekaasqpgelkdWFVGRSNAQ 183
Cdd:cd03862   1 PVVGLVGGVHGLERIGtQVILAFLRSLL--ARLKWDKLLQELLEEVRLVVIPIVNPGGM------------ALKTRSNPN 66

                ....*....
gi 22203763 184 GIDLNRNFP 192
Cdd:cd03862  67 GVDLMRNAP 75
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
61-196 1.45e-04

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  Cd Length: 256  Bit Score: 43.32  E-value: 1.45e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  61 EALVSvWLQCTAISRIYTVGRSFEGRELLVIELSDNPG----------VHePGEP--EF-------KYIGNmhgNEAVGR 121
Cdd:cd06234   7 LDLVA-RAQASPGVRLEVLGQTLDGRDIDLLTIGDPGTgkkkvwiiarQH-PGETmaEWfmeglldRLLDE---DDPVSR 81
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22203763 122 ELLiflaqylcneyQKgnetivnlihsTRIHIMPSLNPDGfekaaSQPGELkdwfvgRSNAQGIDLNRNF--PDLDR 196
Cdd:cd06234  82 ALL-----------EK-----------AVFYVVPNMNPDG-----SVRGNL------RTNAAGVNLNREWanPSLER 125
PRK10602 PRK10602
murein tripeptide amidase MpaA;
150-192 2.14e-04

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 42.71  E-value: 2.14e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 22203763  150 RIHIMPSLNPDGfekaaSQPGElkdwfvgRSNAQGIDLNRNFP 192
Cdd:PRK10602  72 RHHVVLAVNPDG-----CQLGL-------RANANGVDLNRNFP 102
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
52-191 4.61e-04

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  Cd Length: 300  Bit Score: 41.89  E-value: 4.61e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  52 EYHRYPELREALVSVWLQCTAISRIYTVGRSFEGRELLVIELsdnpGVHEPGEPEFKYIG-NMHGNEAVGRELLIFLAQY 130
Cdd:cd03872   1 VYHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIDcGIHAREWIGPAFCQWFVKE 76
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 22203763 131 LCNEYQKgNETIVNLIHSTRIHIMPSLNPDGFEKAASQPgelKDWFVGRSN-----AQGIDLNRNF 191
Cdd:cd03872  77 AINSYQT-DPAMKKMLNQLYFYVMPVFNVDGYHYSWTND---RFWRKTRSKnsrfqCRGVDANRNW 138
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
109-191 4.83e-04

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  Cd Length: 239  Bit Score: 41.52  E-value: 4.83e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 109 YI-GNMHGNEAVGRE-LLIFLAQYLCNEYQKgnetiVNLihstriHIMPSLNPDGFEKaasqpgelkdwfVGRSNAQGID 186
Cdd:cd06231  46 LIsAGIHGDEPAGVEaLLRFLESLAEKYLRR-----VNL------LVLPCVNPWGFER------------NTRENADGID 102

                ....*
gi 22203763 187 LNRNF 191
Cdd:cd06231 103 LNRSF 107
M14-like cd06241
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
110-342 5.07e-04

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


Pssm-ID: 349460  Cd Length: 215  Bit Score: 41.47  E-value: 5.07e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 110 IGNMHGNEAVGRE-LLIF---LAQYlcneyqKGNETIVNLIhstrIHIMPSLNPDGFEKA-----ASQPGELKdwfVG-R 179
Cdd:cd06241   7 QAGIHPGEVEGKEaSLMLlrdIAQG------GKKHLLDNLI----LLFVPIFNADGNDRRskgnrPNQNGPLE---VGwR 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 180 SNAQGIDLNRNFPDLDrivyvnekeggpnnhllknlkkivdqnsklAPETKAVI----HWIMDIpFVlsaNLHGGDlVAN 255
Cdd:cd06241  74 TNAQGLDLNRDFMKLE------------------------------APETRALAklfnQWDPDL-FI---DTHTTD-GSD 118
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 256 YPYDETRSGTAHE-YSSCP----DDAIFQSLARAYSSFNpvmSDPNRPPCRKNDDDSSFVDGTTNGGAWYSvpggmqdFN 330
Cdd:cd06241 119 HQYDLTYAFSQNPaGDPGLsayvRDVFLPAVSAALERKG---HLPLPGIDGNDGGDPSKGWYTYTHHPRYS-------TG 188
                       250
                ....*....|...
gi 22203763 331 YLS-SNCFEITVE 342
Cdd:cd06241 189 YGGlRNRMSILVE 201
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
80-263 2.64e-03

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


Pssm-ID: 349467  Cd Length: 297  Bit Score: 39.75  E-value: 2.64e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  80 GRSFEGRELLVIELSDNPGVHEPgEPEFKYIGNMHGNEAVGrellIFLAQYLCNEYQKGNETIVNLIHSTRIHIMPSLNP 159
Cdd:cd06248  28 GYTFEGRPIKYVRIRSTNSEDTS-KPTIMIEGGINPREWIS----PPAALYAIHKLVEDVETQSDLLNNFDWIILPVANP 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763 160 DGFEKAASQPGELKDWFVGRSNAQ-----GIDLNRNFpdldRIVYVNE-KEGGPNNHLLKNLKKIVDqnsklaPETKAVI 233
Cdd:cd06248 103 DGYVFTHTNDREWTKNRSTNSNPLgqicfGVNINRNF----DYQWNPVlSSESPCSELYAGPSAFSE------AESRAIR 172
                       170       180       190
                ....*....|....*....|....*....|..
gi 22203763 234 HWIMD--IPFVLSANLHGGDLVANYPYDETRS 263
Cdd:cd06248 173 DILHEhgNRIHLYISFHSGGSFILYPWGYDGS 204
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
52-191 5.95e-03

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


Pssm-ID: 349465  Cd Length: 300  Bit Score: 38.64  E-value: 5.95e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  52 EYHRYPELREalVSVWLQCTA-----ISRIYTVGRSFEGRELLVIELSDNpgvhepgEPEFKYI----GNMHGNEAVGRE 122
Cdd:cd06246   1 YYEQYHSLNE--IYSWIEFITerhpdMLTKIHIGSSFEKYPLYVLKVSGK-------EQTAKNAiwidCGIHAREWISPA 71
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 22203763 123 LLIFLAQYLCNEYQKgNETIVNLIHSTRIHIMPSLNPDG--FEKAASQPGELKDWFVGRSNAQGIDLNRNF 191
Cdd:cd06246  72 FCLWFIGHASYFYGI-IGQHTNLLNLVDFYVMPVVNVDGydYSWKKNRMWRKNRSKHANNRCIGTDLNRNF 141
M14_Nna1-like cd18429
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
76-224 8.30e-03

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


Pssm-ID: 349485  Cd Length: 253  Bit Score: 37.82  E-value: 8.30e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22203763  76 IYTVGRSFEGRELLVIELSDNPGVHEpgepefKYI-GNMHGNEAVGRelliFLAQYLCNEYQKGNETIVNLIHSTRIHIM 154
Cdd:cd18429  17 ITTIGKTVEGRPLEIIRIGNESAPHR------VFLrARAHPWEAGGN----WVVEGLVERLLQNDEEAKRFLKRYCVYIL 86
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 22203763 155 PSLNPDGFEKAASqpgelkdwfvgRSNAQGIDLNRN--FPDLDRIVyvnekeggPNNHLLKN-LKKIVDQNSK 224
Cdd:cd18429  87 PMANKDGVARGRT-----------RFNANGKDLNREwdKPADPVLA--------PENFALEKwLEEMIKAGKK 140
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.19
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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