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Conserved domains on  [gi|209364521|ref|NP_776328|]
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carboxypeptidase E precursor [Bos taurus]

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

Graphical summary

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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 ...
52-370 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: 719.07  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDWFVGRSNAQGIDLNRNFPDLDRIVYINEKEGGPNNHLL 211
Cdd:cd03865   81 NEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 KNLKKIVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDDIFQSLARAYSSFNPPM 291
Cdd:cd03865  161 KNMKKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDAIFQSLARAYSSLNPAM 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 292 SDPDRPPCRKNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQQ 370
Cdd:cd03865  241 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
374-448 4.85e-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: 135.73  E-value: 4.85e-39
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209364521 374 GVKGFVRDLQGNPIANATLSVEGIDHDVTSAKDGDYWRLLVPGNYKLTASAPGYLAIAKKVAVPYSP-AVRVDFEL 448
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 ...
52-370 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: 719.07  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDWFVGRSNAQGIDLNRNFPDLDRIVYINEKEGGPNNHLL 211
Cdd:cd03865   81 NEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 KNLKKIVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDDIFQSLARAYSSFNPPM 291
Cdd:cd03865  161 KNMKKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDAIFQSLARAYSSLNPAM 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 292 SDPDRPPCRKNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQQ 370
Cdd:cd03865  241 SDPNRPPCRKNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLINYIEQ 319
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
58-363 1.77e-97

Zinc carboxypeptidase;


Pssm-ID: 425553 [Multi-domain]  Cd Length: 287  Bit Score: 294.98  E-value: 1.77e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521   58 LREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKg 137
Cdd:pfam00246   1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGR- 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  138 NETIVQLIHNTRIHIMPSLNPDGFEKAASQlgeLKDWFVGRSNAQ-----GIDLNRNFPDL-----DRIVYINEKEGGPN 207
Cdd:pfam00246  80 DPEITELLDDTDIYILPVVNPDGYEYTHTT---DRLWRKNRSNANgssciGVDLNRNFPDHwnevgASSNPCSETYRGPA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  208 NHllknlkkivdqntkLAPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSgsaheySSCPDDDIFQSLARAYSS 286
Cdd:pfam00246 157 PF--------------SEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD------EPPPDDEELKSLARAAAK 216
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  287 FNPPMSdpdrppcrkndDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNC-FEITVELSCEK----FPPEETLKNYWEDNK 361
Cdd:pfam00246 217 ALQKMV-----------RGTSYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETW 285

                  ..
gi 209364521  362 NS 363
Cdd:pfam00246 286 EA 287
Zn_pept smart00631
Zn_pept domain;
52-356 2.69e-71

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 227.22  E-value: 2.69e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521    52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGvhePGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:smart00631   1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521   132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEKAASQlgeLKDWFVGRS---NAQGIDLNRNFPDLdrivyiNEKEGGPNN 208
Cdd:smart00631  78 ENYGR-DPRVTNLLDKTDIYIVPVLNPDGYEYTHTG---DRLWRKNRSpnsNCRGVDLNRNFPFH------WGETGNPCS 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521   209 HLLKNLKKIVDqntklaPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSGSAHEYSScpDDDIFQSLARAYSSF 287
Cdd:smart00631 148 ETYAGPSPFSE------PETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD--LDAVAKALAKALASV 219
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 209364521   288 NPpmsdpdrppcrkndddSSFVEGTTNGAAWYsVPGGMQDFNYLSSN-CFEITVELSCE-----KFPPEETLKNY 356
Cdd:smart00631 220 HG----------------TRYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
374-448 4.85e-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: 135.73  E-value: 4.85e-39
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209364521 374 GVKGFVRDLQGNPIANATLSVEGIDHDVTSAKDGDYWRLLVPGNYKLTASAPGYLAIAKKVAVPYSP-AVRVDFEL 448
Cdd:cd11308    1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFsATVVNFTL 76
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
374-448 5.52e-16

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 72.70  E-value: 5.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  374 GVKGFVRDLQGNPIANATLSVE----GIDHDVTSAKDGDYW-RLLVPGNYKLTASAPGYLAIAKK-VAVPYSPAVRVDFE 447
Cdd:pfam13620   1 TISGTVTDPSGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTgVTVTAGQTTTLDVT 80

                  .
gi 209364521  448 L 448
Cdd:pfam13620  81 L 81
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
71-194 3.19e-08

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


Pssm-ID: 225421 [Multi-domain]  Cd Length: 374  Bit Score: 55.57  E-value: 3.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  71 AVSRIYTVGRSFEGRELLVLelsdNPGVHEPGEPEFKYIGNMHGNeavGRELLIFLAQYLCNEYQKGNETIVQLIHNTRI 150
Cdd:COG2866  119 LLVELELIGRSVEGRDDPLI----TFPESNPEHKTILITAGQHAR---GEKMVEWFLYNLILRYLDPDVQVRKLLDRADL 191
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 209364521 151 HIMPSLNPDGfekaaSQLGELkdwfvgRSNAQGIDLNRNFPDLD 194
Cdd:COG2866  192 HVVPNVNPDG-----SDLGNL------RTNANGVDLNRNFIAPN 224
PRK10602 PRK10602
murein tripeptide amidase MpaA;
149-191 1.02e-05

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 46.56  E-value: 1.02e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 209364521 149 RIHIMPSLNPDGfekaaSQLGElkdwfvgRSNAQGIDLNRNFP 191
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 ...
52-370 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: 719.07  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDWFVGRSNAQGIDLNRNFPDLDRIVYINEKEGGPNNHLL 211
Cdd:cd03865   81 NEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEGGPNNHLL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 KNLKKIVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDDIFQSLARAYSSFNPPM 291
Cdd:cd03865  161 KNMKKAVDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDAIFQSLARAYSSLNPAM 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 292 SDPDRPPCRKNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQQ 370
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 ...
52-370 0e+00

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


Pssm-ID: 349431 [Multi-domain]  Cd Length: 292  Bit Score: 516.43  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03858    1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYqKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQlgeLKDWFVGRSNAQGIDLNRNFPDLDRIVYinekeggpnnhll 211
Cdd:cd03858   81 ENY-GKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEG---DCGGLIGRNNANGVDLNRNFPDQFFQVY------------- 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 knlkkivDQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEYSSCPDDDIFQSLARAYSSFNPPM 291
Cdd:cd03858  144 -------SDNNPRQPETKAVMNWLESIPFVLSANLHGGALVANYPYDDTRSGKSTEYSPSPDDAVFRMLARSYSDAHPTM 216
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 292 SDPDRPPCrknDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQQ 370
Cdd:cd03858  217 SMGKPCCC---DDDENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFLEQ 292
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
52-370 1.44e-142

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


Pssm-ID: 349436 [Multi-domain]  Cd Length: 313  Bit Score: 410.86  E-value: 1.44e-142
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03864    1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDWFVGRSNAQGIDLNRNFPDLDRIVYINEKEGGPNNH-- 209
Cdd:cd03864   81 EEYRNGNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNGYLVGRNNANGVDLNRNFPDLNTLMYYNEKYGGPNHHlp 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 210 LLKNLKKIVDqntklaPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDET-----RSGSAHEYSSCPDDDIFQSLARAY 284
Cdd:cd03864  161 LPDNWKSQVE------PETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSreprvRGFRRTAYSPTPDDKLFQKLAKTY 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 285 SSFNPPMSdpdrppcRKNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSL 364
Cdd:cd03864  235 SYAHGWMH-------KGWNCGDYFDEGITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREAL 307

                 ....*.
gi 209364521 365 ISYIQQ 370
Cdd:cd03864  308 ISYMEQ 313
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
52-370 4.60e-138

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: 398.54  E-value: 4.60e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03868    1 YHNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDWFVGRSNAQGIDLNRNFPDLdrivyinekeggpnnhlL 211
Cdd:cd03868   81 ENYGK-DERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDPGYGGRENANNVDLNRNFPDQ-----------------F 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 KNLKKIVDQNtkLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAH-EYSSCPDDDIFQSLARAYSSFNPP 290
Cdd:cd03868  143 EDSDDRLLEG--RQPETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECgVYSKSPDDAVFRHLAHTYADNHPT 220
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 291 MSDpdRPPCrkndDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQQ 370
Cdd:cd03868  221 MHK--GNNC----CEDSFKDGITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYMEQ 294
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
52-370 3.27e-128

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: 374.94  E-value: 3.27e-128
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03869    1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDWFVGRSNAQGIDLNRNFPDLDRIVYINEKEGG-----P 206
Cdd:cd03869   81 QEYLAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGGWSLGRWTSDGIDINHNFPDLNSLLWEAEDRKWvprkvP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 207 NNHLlknlkKIVD----QNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRS-GSAHEYSSCPDDDIFQSLA 281
Cdd:cd03869  161 NHHI-----PIPEwylsENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTpWKTQEYTPTPDDHVFRWLA 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 282 RAYSSFNPPMSDPDRPPCrkNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNK 361
Cdd:cd03869  236 YSYASTHRLMTDASRRPC--HTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNR 313

                 ....*....
gi 209364521 362 NSLISYIQQ 370
Cdd:cd03869  314 ESLLVFMEQ 322
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
52-369 1.08e-127

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: 373.07  E-value: 1.08e-127
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03867    1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDWFVGRSNAQGIDLNRNFPDLDRIVY-INEKEGGPNNHL 210
Cdd:cd03867   81 SEYLLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAGYNGWTSGRQNAQNLDLNRNFPDLTSEAYrLARTRGARLDHI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 211 lknlkKIVDQ--NTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSG-SAHEYSSCPDDDIFQSLARAYSSF 287
Cdd:cd03867  161 -----PIPQSywWGKVAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPlEEKMFSPTPDEKMFKLLAKAYADA 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 288 NPPMSDPDRPPCRKNDDDSSfveGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISY 367
Cdd:cd03867  236 HPMMSDRSENRCGGNFLKRG---GIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNF 312

                 ..
gi 209364521 368 IQ 369
Cdd:cd03867  313 ME 314
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
42-370 1.11e-121

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


Pssm-ID: 349435 [Multi-domain]  Cd Length: 296  Bit Score: 357.33  E-value: 1.11e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  42 RPQEdgisFEYHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRE 121
Cdd:cd03863    2 QPVD----FRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRE 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 122 LLIFLAQYLCNEYQKGNEtIVQLIHNTRIHIMPSLNPDGFEKaaSQLGElKDWFVGRSNAQGIDLNRNFPDldrivyine 201
Cdd:cd03863   78 LLLNLIEYLCKNFGTDPE-VTDLVQNTRIHIMPSMNPDGYEK--SQEGD-RGGTVGRNNSNNYDLNRNFPD--------- 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 202 keggpnnhllkNLKKIVDqntKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAhEYSSCPDDDIFQSLA 281
Cdd:cd03863  145 -----------QFFQITD---PPQPETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLA-TYSKSPDDAVFQQLA 209
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 282 RAYSSFNPPMSDPDrpPCRKNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNK 361
Cdd:cd03863  210 LSYSKENSKMYQGS--PCKELYPNEYFPHGITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNR 287

                 ....*....
gi 209364521 362 NSLISYIQQ 370
Cdd:cd03863  288 RSLLQFIKQ 296
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
52-370 4.69e-108

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: 322.13  E-value: 4.69e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03866    1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEkaASQLGELKdWFVGRSNAQGIDLNRNFPDldrivyinekeggpnnhll 211
Cdd:cd03866   81 TSYGS-DPVITRLINSTRIHIMPSMNPDGFE--ATKKPDCY-YTKGRYNKNGYDLNRNFPD------------------- 137
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 knlkkIVDQNT-KLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSA--HEYSSCPDDDIFQSLARAYSSFN 288
Cdd:cd03866  138 -----AFEENNvQRQPETRAVMDWIKNETFVLSANLHGGALVASYPFDNGNSGTGqlGYYSVSPDDDVFIYLAKTYSYNH 212
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 289 PPMSDPDRppCrknDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYI 368
Cdd:cd03866  213 TNMYKGIE--C---SNSQSFPGGITNGYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEYI 287

                 ..
gi 209364521 369 QQ 370
Cdd:cd03866  288 KQ 289
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
52-369 4.35e-101

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


Pssm-ID: 349482 [Multi-domain]  Cd Length: 276  Bit Score: 303.95  E-value: 4.35e-101
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPgEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd18172    1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDET-EPAFKFVGNMHGDEPVGRELLLRLADWLC 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKGNETIVQLIHNTRIHIMPSLNPDGFEKAAsqlgelkdwfvgRSNAQGIDLNRNFPDldrivyiNEKEGGPNNHLl 211
Cdd:cd18172   80 ANYKAKDPLAAKIVENAHLHLVPTMNPDGFARRR------------RNNANNVDLNRDFPD-------QFFPKNLRNDL- 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 knlkkivdqnTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHeYSSCPDDDIFQSLARAYSSFNPPM 291
Cdd:cd18172  140 ----------AARQPETLAVMNWSRSVRFTASANLHEGALVANYPWDGNADGRTK-YSASPDDATFRRLASVYAQAHPNM 208
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209364521 292 SDPdrppcrkndddSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQ 369
Cdd:cd18172  209 AKS-----------KEFPGGITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAMLALAA 275
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
58-363 1.77e-97

Zinc carboxypeptidase;


Pssm-ID: 425553 [Multi-domain]  Cd Length: 287  Bit Score: 294.98  E-value: 1.77e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521   58 LREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKg 137
Cdd:pfam00246   1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGR- 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  138 NETIVQLIHNTRIHIMPSLNPDGFEKAASQlgeLKDWFVGRSNAQ-----GIDLNRNFPDL-----DRIVYINEKEGGPN 207
Cdd:pfam00246  80 DPEITELLDDTDIYILPVVNPDGYEYTHTT---DRLWRKNRSNANgssciGVDLNRNFPDHwnevgASSNPCSETYRGPA 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  208 NHllknlkkivdqntkLAPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSgsaheySSCPDDDIFQSLARAYSS 286
Cdd:pfam00246 157 PF--------------SEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD------EPPPDDEELKSLARAAAK 216
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  287 FNPPMSdpdrppcrkndDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNC-FEITVELSCEK----FPPEETLKNYWEDNK 361
Cdd:pfam00246 217 ALQKMV-----------RGTSYTYGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETW 285

                  ..
gi 209364521  362 NS 363
Cdd:pfam00246 286 EA 287
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
52-370 1.59e-91

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


Pssm-ID: 349483 [Multi-domain]  Cd Length: 281  Bit Score: 279.46  E-value: 1.59e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPgEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd18173    4 YPTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEEA-EPEFKYTSTMHGDETTGYELMLRLIDYLL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELkdwfVGRSNAQGIDLNRNFPDldrivyineKEGGPNNhll 211
Cdd:cd18173   83 TNYGT-DPRITNLVDNTEIWINPLANPDGTYAGGNNTVSG----ATRYNANGVDLNRNFPD---------PVDGDHP--- 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 knlkkivDQNTkLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDetrsgsaHEYSSCPDDDIFQSLARAYSSFNPPM 291
Cdd:cd18173  146 -------DGNG-WQPETQAMMNFADEHNFVLSANFHGGAEVVNYPWD-------TWYSRHPDDDWFQDISREYADTNQAN 210
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 292 SDPDRppcrknddDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQQ 370
Cdd:cd18173  211 SPPMY--------MSEFNNGITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLNYIEQ 281
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
52-370 9.46e-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 [Multi-domain]  Cd Length: 283  Bit Score: 236.57  E-value: 9.46e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDwfvGRSNAQGIDLNRNFPdldrivyinEKEGGPNNHll 211
Cdd:cd06245   81 HNYKK-DSAITKLLNRTRIHIVPSLNPDGAEKAEEKKCTSKI---GEKNANGVDLDTDFE---------SNANNRSGA-- 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 212 knlkkivdqntkLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSGSAHEysscpddDIFQSLARAYSSFNPPM 291
Cdd:cd06245  146 ------------AQPETKAIMDWLKEKDFTLSVALDGGSLVVTYPYDKPVQTVENK-------ETLKHLAKVYANNHPTM 206
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 292 SDPDrPPCrKNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKNYWEDNKNSLISYIQQ 370
Cdd:cd06245  207 HAGD-PGC-CSNSDENFTNGVIRASEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSMIVE 283
Zn_pept smart00631
Zn_pept domain;
52-356 2.69e-71

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 227.22  E-value: 2.69e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521    52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGvhePGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:smart00631   1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGS---HDKPAIFIDAGIHAREWIGPATALYLINQLL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521   132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEKAASQlgeLKDWFVGRS---NAQGIDLNRNFPDLdrivyiNEKEGGPNN 208
Cdd:smart00631  78 ENYGR-DPRVTNLLDKTDIYIVPVLNPDGYEYTHTG---DRLWRKNRSpnsNCRGVDLNRNFPFH------WGETGNPCS 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521   209 HLLKNLKKIVDqntklaPETKAVIHWIMD-IPFVLSANLHGGDLVANYPYDETRSGSAHEYSScpDDDIFQSLARAYSSF 287
Cdd:smart00631 148 ETYAGPSPFSE------PETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLPPNVDD--LDAVAKALAKALASV 219
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 209364521   288 NPpmsdpdrppcrkndddSSFVEGTTNGAAWYsVPGGMQDFNYLSSN-CFEITVELSCE-----KFPPEETLKNY 356
Cdd:smart00631 220 HG----------------TRYTYGISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQIIPTG 277
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
374-448 4.85e-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: 135.73  E-value: 4.85e-39
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209364521 374 GVKGFVRDLQGNPIANATLSVEGIDHDVTSAKDGDYWRLLVPGNYKLTASAPGYLAIAKKVAVPYSP-AVRVDFEL 448
Cdd:cd11308    1 GIKGFVTDATGNPIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFsATVVNFTL 76
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
108-364 1.38e-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: 131.43  E-value: 1.38e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 108 YIGNMHGNEAVGRELLIFLAQYLCNEYqkGNETIVQLIHNTRIHIMPSLNPDGFEKAASqlgelkdwFVGRSNAQGIDLN 187
Cdd:cd00596    3 ITGGIHGNEVIGVELALALIEYLLENY--GNDPLKRLLDNVELWIVPLVNPDGFARVID--------SGGRKNANGVDLN 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 188 RNFPdldrivYINEKEGGPNNHLLKNlkkivdQNTKLA--PETKAVIHWIMDIPFVLSANLHGGDLVANYPYdetrsgsA 265
Cdd:cd00596   73 RNFP------YNWGKDGTSGPSSPTY------RGPAPFsePETQALRDLAKSHRFDLAVSYHSSSEAILYPY-------G 133
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 266 HEYSSCPDDDIFQSLARAYSSFNPPmsdpdrppcrkndddssFVEGTTNGAAWYSVPGGMQDFNYLSSNCFEITVELSCE 345
Cdd:cd00596  134 YTNEPPPDFSEFQELAAGLARALGA-----------------GEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELGTA 196
                        250       260
                 ....*....|....*....|
gi 209364521 346 KFPPEETLKN-YWEDNKNSL 364
Cdd:cd00596  197 DYPLPGTLLDrRLERNLAAL 216
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
52-360 6.88e-32

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: 123.52  E-value: 6.88e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVhEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03859    4 YHTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDE-DEDEPEVLFMGLHHAREWISLEVALYFADYLL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGE------LKDWFVGRSNAQGIDLNRNFPdldrIVYINEKEGG 205
Cdd:cd03859   83 ENYGT-DPRITNLVDNREIWIIPVVNPDGYEYNRETGGGrlwrknRRPNNGNNPGSDGVDLNRNYG----YHWGGDNGGS 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 206 PNNHllknlkkiVDQNTK-----LAPETKAVIHWIMDIPFVLSANLHG-GDLVaNYPYDETRSGSAheysscPDDDIFQS 279
Cdd:cd03859  158 SPDP--------SSETYRgpapfSEPETQAIRDLVESHDFKVAISYHSyGELV-LYPWGYTSDAPT------PDEDVFEE 222
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 280 LARAYSSFNPPmsdpdrppcrkndddssfveGTTNGAAW--YSVPGGMQDFNYLSSNCFEITVEL---SCEKFPPEETLK 354
Cdd:cd03859  223 LAEEMASYNGG--------------------GYTPQQSSdlYPTNGDTDDWMYGEKGIIAFTPELgpeFYPFYPPPSQID 282

                 ....*.
gi 209364521 355 NYWEDN 360
Cdd:cd03859  283 PLAEEN 288
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
52-163 2.13e-17

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


Pssm-ID: 349476 [Multi-domain]  Cd Length: 359  Bit Score: 83.44  E-value: 2.13e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGVHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd06905    6 YYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYLAEYLL 85
                         90       100       110
                 ....*....|....*....|....*....|..
gi 209364521 132 NEYQKgNETIVQLIHNTRIHIMPSLNPDGFEK 163
Cdd:cd06905   86 TNYGK-DPEITRLLDTRTFYILPRLNPDGAEA 116
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
374-448 5.52e-16

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 72.70  E-value: 5.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  374 GVKGFVRDLQGNPIANATLSVE----GIDHDVTSAKDGDYW-RLLVPGNYKLTASAPGYLAIAKK-VAVPYSPAVRVDFE 447
Cdd:pfam13620   1 TISGTVTDPSGAPVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRTgVTVTAGQTTTLDVT 80

                  .
gi 209364521  448 L 448
Cdd:pfam13620  81 L 81
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
77-369 1.02e-13

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


Pssm-ID: 349475 [Multi-domain]  Cd Length: 214  Bit Score: 70.00  E-value: 1.02e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  77 TVGRSFEGRELLVLELSDNPG--VHepgepefkYIGNMHGNEAVGRELLIFLAQYLCNEyqkgnetivQLIHNTRIHIMP 154
Cdd:cd06904    3 VYGTSVKGRPILAYKFGPGSRarIL--------IIGGIHGDEPEGVSLVEHLLRWLKNH---------PASGDFHIVVVP 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 155 SLNPDGFEKAAsqlgelkdwfvgRSNAQGIDLNRNFPdldrivyinekegGPNNHLLKNLKKIVDQNTKLA----PETKA 230
Cdd:cd06904   66 CLNPDGLAAGT------------RTNANGVDLNRNFP-------------TKNWEPDARKPKDPRYYPGPKpasePETRA 120
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 231 VIHWIMDIP--FVLSanLHgGDLVANYpydetrsgsaheysscpDDDIFQSLARAYSSFN--PPMSDPDRPPcrkndddS 306
Cdd:cd06904  121 LVELIERFKpdRIIS--LH-APYLVNY-----------------DGPAKSLLAEKLAQATgyPVVGDVGYTP-------G 173
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 209364521 307 SFveGTtngaaWysvpGGMQdfnylsSNCFEITVELscekfPPEETLKNYWEDNKNSLISYIQ 369
Cdd:cd06904  174 SL--GT-----Y----AGIE------RNIPVITLEL-----PEAVSIDELWQDLKRALIEAIK 214
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
108-247 1.21e-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: 67.36  E-value: 1.21e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 108 YIGNMHGNEAVGRELLI-FLAQYLCNEYQKGNET---IVQLIHNTRIHIMPSLNPDGFEkaASQLG---------ELKDW 174
Cdd:cd06229    3 YNASFHAREYITTLLLMkFIEDYAKAYVNKSYIRgkdVGELLNKVTLHIVPMVNPDGVE--ISQNGsnainpyylRLVAW 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 175 FVGR-------SNAQGIDLNRNFPdldrIVYINEKEGGPNNHLLKNL--KKIVDQntklaPETKAVIHWIMDIPFVLSAN 245
Cdd:cd06229   81 NKKGtdftgwkANIRGVDLNRNFP----AGWEKEKRLGPKAPGPRDYpgKEPLSE-----PETKAMAALTRQNDFDLVLA 151

                 ..
gi 209364521 246 LH 247
Cdd:cd06229  152 YH 153
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
52-191 2.68e-12

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


Pssm-ID: 349433 [Multi-domain]  Cd Length: 300  Bit Score: 67.17  E-value: 2.68e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  52 YHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELSDNPGvhEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLC 131
Cdd:cd03860    1 YHPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGG--KGGKPAIVIHGGQHAREWISTSTVEYLAHQLL 78
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 209364521 132 NEYQKGNeTIVQLIHNTRIHIMPSLNPDGFEKAASqlgelKD--W-----FVGRSNAQGIDLNRNFP 191
Cdd:cd03860   79 SGYGSDA-TITALLDKFDFYIIPVVNPDGYVYTWT-----TDrlWrknrqPTGGSSCVGIDLNRNWG 139
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
108-341 2.24e-11

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


Pssm-ID: 349430 [Multi-domain]  Cd Length: 203  Bit Score: 62.86  E-value: 2.24e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 108 YIGNMHGNEAVGRELLIFLAQYLCNEYQKGNEtivqLIHNTRIHIMPSLNPDGFEK-AASQLGELKDWFVGRSNAQGIDL 186
Cdd:cd03857    4 LAAQIHGNETTGTEALMELIRDLASESDEAAK----LLDNIVILLVPQLNPDGAELfVNFYLDSMNGLPGTRYNANGIDL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 187 NRNFPDLDRivyinekeggpnnhllknlkkivdqntklaPETKA----VIHWIMDIPFvlsaNLHGGDlvanypydetrs 262
Cdd:cd03857   80 NRDHVKLTQ------------------------------PETQAvaenFIHWWPDIFI----DLHEQV------------ 113
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 263 GSAHEYSSCPDDDIFQSLARAYSSFNPPMSDPDRPPCRKNDDDSSFVEGTTNGAAWYSVPGGMQDFNYLssNCFEITVE 341
Cdd:cd03857  114 GASIPYPTPPDAPNYNLVDLRSDAENGQEHIRLIAGEGSGELGKYFSPMRGGFDDSTGGNGIGRTSGFH--GAISILFE 190
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
86-191 2.16e-08

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


Pssm-ID: 349445 [Multi-domain]  Cd Length: 267  Bit Score: 55.15  E-value: 2.16e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  86 ELLVLELSdNPGVHEPGE-PEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKGNETIVQLIHnTRIHIMPSLNPDGFEKA 164
Cdd:cd06226    1 DIRALKLT-NKQATPPGEkPKFFMMAAIHAREYTTAELVARFAEDLVAGYGTDADATWLLDY-TELHLVPQVNPDGRKIA 78
                         90       100       110
                 ....*....|....*....|....*....|.
gi 209364521 165 ASQLGELKDWFVG----RSNAQGIDLNRNFP 191
Cdd:cd06226   79 ETGLLWRKNTNTTpcpaSSPTYGVDLNRNSS 109
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
108-190 2.65e-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 [Multi-domain]  Cd Length: 220  Bit Score: 54.23  E-value: 2.65e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 108 YIGNMHGNEAVGRELLIFLAQYLCNEYQKGNetivqLIHNTRIHIMPSLNPDGFEkaasqlgelKDWfvgRSNAQGIDLN 187
Cdd:cd06242    6 LVGQQHGNEPAGREAALALARDLAFGDDARE-----LLEKVNVLVVPRANPDGRA---------ANT---RGNANGVDLN 68

                 ...
gi 209364521 188 RNF 190
Cdd:cd06242   69 RDH 71
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
71-194 3.19e-08

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


Pssm-ID: 225421 [Multi-domain]  Cd Length: 374  Bit Score: 55.57  E-value: 3.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  71 AVSRIYTVGRSFEGRELLVLelsdNPGVHEPGEPEFKYIGNMHGNeavGRELLIFLAQYLCNEYQKGNETIVQLIHNTRI 150
Cdd:COG2866  119 LLVELELIGRSVEGRDDPLI----TFPESNPEHKTILITAGQHAR---GEKMVEWFLYNLILRYLDPDVQVRKLLDRADL 191
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 209364521 151 HIMPSLNPDGfekaaSQLGELkdwfvgRSNAQGIDLNRNFPDLD 194
Cdd:COG2866  192 HVVPNVNPDG-----SDLGNL------RTNANGVDLNRNFIAPN 224
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
110-235 4.51e-08

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


Pssm-ID: 349457  Cd Length: 217  Bit Score: 53.52  E-value: 4.51e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 110 GNMHGNEAVGRELLIFLAQYLCneyQKGNETIVQLIHNTRIHIMPSLNPDGFEKAASQLGELKDwFVGRSNAQGIDLNRN 189
Cdd:cd06238    8 YSIHGNELSGSEAAMQVAYHLA---AGQDEATRALLENTVIVIDPNQNPDGRERFVNWFNQNRG-AVGDPDPQSMEHNEP 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 209364521 190 FPdldrivyinekeGGPNNHLLKNLKKivDQNTKLAPETKAVIHWI 235
Cdd:cd06238   84 WP------------GGRTNHYLFDLNR--DWLAQTQPESRARAAAI 115
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
111-274 6.69e-08

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


Pssm-ID: 349446 [Multi-domain]  Cd Length: 224  Bit Score: 53.04  E-value: 6.69e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 111 NMHGNEAVGRELLIFLAQYLCNEYQKGNETIVQ-----LIHNTRIHIMPSLNPDGFEKAASqlGELKdWfvgRSNAQGID 185
Cdd:cd06227    9 GEHARELISVESALRLLRQLCGGLQEPAASALRelareILDNVELKIIPNANPDGRRLVES--GDYC-W---RGNENGVD 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 186 LNRNFPdldriVYINEKEGGPNNHllknlkkiVDQNTKL--APETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSG 263
Cdd:cd06227   83 LNRNWG-----VDWGKGEKGAPSE--------EYPGPKPfsEPETRALRDLALSFKPHAFVSVHSGMLAIYTPYAYSASV 149
                        170
                 ....*....|.
gi 209364521 264 SAHEYSSCPDD 274
Cdd:cd06227  150 PRPNRAADMDD 160
M14_PaCCP-like cd06234
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases similar ...
60-195 1.45e-06

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


Pssm-ID: 349453 [Multi-domain]  Cd Length: 256  Bit Score: 49.49  E-value: 1.45e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  60 EALVSvWLQCAAVSRIYTVGRSFEGRELLVLELSDnpgvHEPGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYqkgNE 139
Cdd:cd06234    7 LDLVA-RAQASPGVRLEVLGQTLDGRDIDLLTIGD----PGTGKKKVWIIARQHPGETMAEWFMEGLLDRLLDED---DP 78
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 209364521 140 TIVQLIHNTRIHIMPSLNPDGfekaaSQLGELkdwfvgRSNAQGIDLNRNF--PDLDR 195
Cdd:cd06234   79 VSRALLEKAVFYVVPNMNPDG-----SVRGNL------RTNAAGVNLNREWanPSLER 125
M14-like cd06228
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
108-190 1.69e-06

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


Pssm-ID: 349447  Cd Length: 294  Bit Score: 49.69  E-value: 1.69e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 108 YIGNMHGNEAVGRELLIFLAQYLCNEYQKGN-----------ETIVQLIHNTRIHIMPSLNPDGfeKAASQLgELKDWFV 176
Cdd:cd06228    5 FIGGVHAREWGSPDILIYFAADLLEAYTNNTgltyggktftaAQVKSILENVDLVVFPLVNPDG--RWYSQT-SESMWRK 81
                         90       100
                 ....*....|....*....|..
gi 209364521 177 GRSNAQ--------GIDLNRNF 190
Cdd:cd06228   82 NRNPASagdggsciGVDINRNF 103
M14-like cd06239
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
112-193 4.50e-06

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


Pssm-ID: 349458 [Multi-domain]  Cd Length: 194  Bit Score: 47.02  E-value: 4.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 112 MHGNEAVGRELLIFLAQYLcneYQKGNETIVQLIHNTrIHIMPSLNPDGFEKAAsqlgelkdwfvgRSNAQGIDLNRNFP 191
Cdd:cd06239    8 MHGNEPTGTEALLDLISYL---RRERQEFEKILERLT-LVAIPMLNPDGAELFT------------RHNAEGIDLNRDAR 71

                 ..
gi 209364521 192 DL 193
Cdd:cd06239   72 AL 73
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
72-190 9.88e-06

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


Pssm-ID: 349442 [Multi-domain]  Cd Length: 301  Bit Score: 47.43  E-value: 9.88e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  72 VSRIyTVGRSFEGRELLVLELSDNPgvhePGEPEFKYIGNMHGNEAVGRELLIFLAQYLCNEYQKgNETIVQLIHNTRIH 151
Cdd:cd03870   27 VSKL-QIGSSFENRPMYVLKFSTGG----EERPAIWIDAGIHSREWVTQASAIWTAEKIVSDYGK-DPSITSILDTMDIF 100
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 209364521 152 IMPSLNPDGFekAASQLGElKDWFVGRS-----NAQGIDLNRNF 190
Cdd:cd03870  101 LEIVTNPDGY--VFTHSSN-RLWRKTRSvnpgsLCIGVDPNRNW 141
PRK10602 PRK10602
murein tripeptide amidase MpaA;
149-191 1.02e-05

murein tripeptide amidase MpaA;


Pssm-ID: 182582  Cd Length: 237  Bit Score: 46.56  E-value: 1.02e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 209364521 149 RIHIMPSLNPDGfekaaSQLGElkdwfvgRSNAQGIDLNRNFP 191
Cdd:PRK10602  72 RHHVVLAVNPDG-----CQLGL-------RANANGVDLNRNFP 102
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
375-450 7.54e-05

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


Pssm-ID: 433425 [Multi-domain]  Cd Length: 88  Bit Score: 41.42  E-value: 7.54e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 209364521  375 VKGFVRDL-QGNPIANATLSVEGIDHDVTSAKDGDY-WRLLVPGNYKLTASAPGYLAIAKKVAVPYSPAVRVDFELES 450
Cdd:pfam13715   1 ISGTVVDEnTGEPLPGATVYVKGTTKGTVTDADGNFeLKNLPAGTYTLVVSFVGYKTQEKKVTVSNDNTLDVNFLLKE 78
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
79-264 1.71e-04

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


Pssm-ID: 349467 [Multi-domain]  Cd Length: 297  Bit Score: 43.22  E-value: 1.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  79 GRSFEGRELLVLELSDNPGVHEPgEPEFKYIGNMHGNEAVGrellIFLAQYLCNEYQKGNETIVQLIHNTRIHIMPSLNP 158
Cdd:cd06248   28 GYTFEGRPIKYVRIRSTNSEDTS-KPTIMIEGGINPREWIS----PPAALYAIHKLVEDVETQSDLLNNFDWIILPVANP 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 159 DGFEKAASQLGELKDWFVGRSNAQ-----GIDLNRNFpdldRIVYINE-KEGGPNNHLLKNLKKIVDqntklaPETKAVI 232
Cdd:cd06248  103 DGYVFTHTNDREWTKNRSTNSNPLgqicfGVNINRNF----DYQWNPVlSSESPCSELYAGPSAFSE------AESRAIR 172
                        170       180       190
                 ....*....|....*....|....*....|....
gi 209364521 233 HWIMD--IPFVLSANLHGGDLVANYPYDETRSGS 264
Cdd:cd06248  173 DILHEhgNRIHLYISFHSGGSFILYPWGYDGSTS 206
M14-like cd03862
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
104-191 2.32e-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: 42.80  E-value: 2.32e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 104 PEFKYIGNMHGNEAVG-RELLIFLAQYLcnEYQKGNETIVQLIHNTRIHIMPSLNPDGFekaasqlgelkdWFVGRSNAQ 182
Cdd:cd03862    1 PVVGLVGGVHGLERIGtQVILAFLRSLL--ARLKWDKLLQELLEEVRLVVIPIVNPGGM------------ALKTRSNPN 66

                 ....*....
gi 209364521 183 GIDLNRNFP 191
Cdd:cd03862   67 GVDLMRNAP 75
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
51-190 2.78e-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 [Multi-domain]  Cd Length: 300  Bit Score: 42.66  E-value: 2.78e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  51 EYHRYPELREALVSVWLQCAAVSRIYTVGRSFEGRELLVLELsdnpGVHEPGEPEFKYIG-NMHGNEAVGRELLIFLAQY 129
Cdd:cd03872    1 VYHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIDcGIHAREWIGPAFCQWFVKE 76
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 209364521 130 LCNEYQKgNETIVQLIHNTRIHIMPSLNPDGFEKAASQlgeLKDWFVGRSN-----AQGIDLNRNF 190
Cdd:cd03872   77 AINSYQT-DPAMKKMLNQLYFYVMPVFNVDGYHYSWTN---DRFWRKTRSKnsrfqCRGVDANRNW 138
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
108-190 6.52e-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 [Multi-domain]  Cd Length: 239  Bit Score: 41.14  E-value: 6.52e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521 108 YI-GNMHGNEAVGRE-LLIFLAQYLCNEYQKGNetivqlihntrIHIMPSLNPDGFEKaasqlgelkdwfVGRSNAQGID 185
Cdd:cd06231   46 LIsAGIHGDEPAGVEaLLRFLESLAEKYLRRVN-----------LLVLPCVNPWGFER------------NTRENADGID 102

                 ....*
gi 209364521 186 LNRNF 190
Cdd:cd06231  103 LNRSF 107
M14_Nna1-like cd03856
Peptidase M14-like domain of ATP/GTP binding proteins, cytosolic carboxypeptidases and related ...
66-195 1.88e-03

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


Pssm-ID: 349429  Cd Length: 252  Bit Score: 39.88  E-value: 1.88e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  66 WLQ-CAAVSRI--YTVGRSFEGRELLVLElsdnpgVHEPGEPEFKY----IGNMHGNEAVGRelliFLAQYLCNEYQKGN 138
Cdd:cd03856    5 WLNlIATQPLVqlLEIGVTEQGREIQALQ------SLRTERSDDKSwlflIARQHPGETTGA----WVFFGFLDQLLSDD 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 209364521 139 ETIVQLIHNTRIHIMPSLNPDGfekaaSQLGELkdwfvgRSNAQGIDLNRNF--PDLDR 195
Cdd:cd03856   75 DPAQQLRAEYNFYIIPMVNPDG-----VARGHW------RTNSRGMDLNRDWhaPDALL 122
M14_CPB2 cd06246
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B2 subgroup; Peptidase M14 ...
51-190 2.19e-03

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


Pssm-ID: 349465 [Multi-domain]  Cd Length: 300  Bit Score: 39.79  E-value: 2.19e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209364521  51 EYHRYPELREalVSVWLQCAAVS-----RIYTVGRSFEGRELLVLELSDNpgvhepgEPEFKYI----GNMHGNEAVGRE 121
Cdd:cd06246    1 YYEQYHSLNE--IYSWIEFITERhpdmlTKIHIGSSFEKYPLYVLKVSGK-------EQTAKNAiwidCGIHAREWISPA 71
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 209364521 122 LLIFLAQYLCNEYQKgNETIVQLIHNTRIHIMPSLNPDG--FEKAASQLGELKDWFVGRSNAQGIDLNRNF 190
Cdd:cd06246   72 FCLWFIGHASYFYGI-IGQHTNLLNLVDFYVMPVVNVDGydYSWKKNRMWRKNRSKHANNRCIGTDLNRNF 141
M14-like cd06240
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
110-175 7.64e-03

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


Pssm-ID: 349459  Cd Length: 212  Bit Score: 37.64  E-value: 7.64e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 209364521 110 GNMHGNEAVGRELLIFLAQYLCNEyqkgNETIVQLI-HNTRIHIMPSLNPDGFEKaasqlgeLKDWF 175
Cdd:cd06240    8 GGLHATEVAGSQMLPELAYRLATS----DDEEVRRIlDNVILLLVPSANPDGQDL-------VVDWY 63
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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