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Conserved domains on  [gi|228008326|ref|NP_062670|]
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probable carboxypeptidase X1 precursor [Mus musculus]

Protein Classification

carboxypeptidase X family protein( domain architecture ID 10044218)

carboxypeptidase X (CPX) family protein is an M14 family zinc carboxypeptidase that 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

CATH:  3.40.630.10
EC:  3.4.17.-
Gene Ontology:  GO:0006508|GO:0004181|GO:0008270
MEROPS:  M14
PubMed:  7674922|10493853

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
288-609 0e+00

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: 644.58  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03869    1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVGWAEGRWTHQGIDLNHNFADLNTQLWYAEDDGLVPDTVP 447
Cdd:cd03869   81 QEYLAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGGWSLGRWTSDGIDINHNFPDLNSLLWEAEDRKWVPRKVP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 NHHLPLPTYYTLPNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAARELTPTPDDAVFRWLSTVYAG 527
Cdd:cd03869  161 NHHIPIPEWYLSENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYAS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 528 TNRAMQDTDRRPCHSQDFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTYL 607
Cdd:cd03869  241 THRLMTDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFM 320

                 ..
gi 228008326 608 EQ 609
Cdd:cd03869  321 EQ 322
FA58C cd00057
Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached ...
106-262 1.07e-44

Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.


:

Pssm-ID: 238014 [Multi-domain]  Cd Length: 143  Bit Score: 156.74  E-value: 1.07e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 106 PPLGLESLRvSDSQLEASSSQSFGLGAHRGRLNiqsgledgdlYDGAWCAEQQDTEPWLQVDAKNPVRFAGIVTQGRNSV 185
Cdd:cd00057    1 EPLGMESGL-ADDQITASSSYSSGWEASRARLN----------SDNAWTPAVNDPPQWLQVDLGKTRRVTGIQTQGRKGG 69
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 228008326 186 WRYDWVTSFKVQFSNDSQTW--WKSRnstGMDIVFPANSDAETPVLNLLPEPQVARFIRLLPQTWFqgGAPCLRAEILA 262
Cdd:cd00057   70 GSSEWVTSYKVQYSLDGETWttYKDK---GEEKVFTGNSDGSTPVTNDFPPPIVARYIRILPTTWN--GNISLRLELYG 143
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
613-689 2.72e-33

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: 122.25  E-value: 2.72e-33
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 228008326 613 GITGVVRDKDTElGIADAVIAVEGINHDVTTAWGGDYWRLLTPGDYVVTASAEGYHTVRQHCQVTFEEGPVPCNFLL 689
Cdd:cd11308    1 GIKGFVTDATGN-PIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
 
Name Accession Description Interval E-value
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
288-609 0e+00

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: 644.58  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03869    1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVGWAEGRWTHQGIDLNHNFADLNTQLWYAEDDGLVPDTVP 447
Cdd:cd03869   81 QEYLAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGGWSLGRWTSDGIDINHNFPDLNSLLWEAEDRKWVPRKVP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 NHHLPLPTYYTLPNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAARELTPTPDDAVFRWLSTVYAG 527
Cdd:cd03869  161 NHHIPIPEWYLSENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYAS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 528 TNRAMQDTDRRPCHSQDFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTYL 607
Cdd:cd03869  241 THRLMTDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFM 320

                 ..
gi 228008326 608 EQ 609
Cdd:cd03869  321 EQ 322
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
294-602 2.34e-80

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 258.00  E-value: 2.34e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  294 MRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLCHEFLRg 373
Cdd:pfam00246   1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGR- 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  374 DPRVTRLLTETRIHLLPSMNPDGYEtAYHRGSELvgWAEGRWTHQ-----GIDLNHNFADlntqLWyaeddglvpDTVPN 448
Cdd:pfam00246  80 DPEITELLDDTDIYILPVVNPDGYE-YTHTTDRL--WRKNRSNANgssciGVDLNRNFPD----HW---------NEVGA 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  449 HHLPLPTYYTLPNATVAPETWAVIKWMKR-IPFVLSANLHGGELVVSYPFDMTRTpwaarelTPTPDDAVFRWLSTVYAG 527
Cdd:pfam00246 144 SSNPCSETYRGPAPFSEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAK 216
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  528 TNRAMqdtdrrpCHSQDFSlhGNVINGADWHTVPGSMNDFSYLHTNC-FEVTVELSCDK----FPHEKELPQEWENNKDA 602
Cdd:pfam00246 217 ALQKM-------VRGTSYT--YGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
Zn_pept smart00631
Zn_pept domain;
288-595 3.59e-67

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 222.60  E-value: 3.59e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEhelGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:smart00631   1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGSH---DKPAIFIDAGIHAREWIGPATALYLINQLL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   368 HEFLRgDPRVTRLLTETRIHLLPSMNPDGYEtaYHRGSElVGWAEGRWTHQ---GIDLNHNFADlntqLWYAEDDglvpd 444
Cdd:smart00631  78 ENYGR-DPRVTNLLDKTDIYIVPVLNPDGYE--YTHTGD-RLWRKNRSPNSncrGVDLNRNFPF----HWGETGN----- 144
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   445 tvpnhhlPLPTYYTLPNATVAPETWAVIKWMKR-IPFVLSANLHGGELVVSYPFDMTRTPWAAREltpTPDDAVFRWLST 523
Cdd:smart00631 145 -------PCSETYAGPSPFSEPETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVAKALAK 214
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   524 VYAgtnramqdtdrrpchsqdfSLHGN-----VINGADWHtVPGSMNDFSYLHTN-CFEVTVELSCD-----KFPHEKEL 592
Cdd:smart00631 215 ALA-------------------SVHGTrytygISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQII 274

                   ...
gi 228008326   593 PQE 595
Cdd:smart00631 275 PTG 277
FA58C cd00057
Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached ...
106-262 1.07e-44

Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.


Pssm-ID: 238014 [Multi-domain]  Cd Length: 143  Bit Score: 156.74  E-value: 1.07e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 106 PPLGLESLRvSDSQLEASSSQSFGLGAHRGRLNiqsgledgdlYDGAWCAEQQDTEPWLQVDAKNPVRFAGIVTQGRNSV 185
Cdd:cd00057    1 EPLGMESGL-ADDQITASSSYSSGWEASRARLN----------SDNAWTPAVNDPPQWLQVDLGKTRRVTGIQTQGRKGG 69
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 228008326 186 WRYDWVTSFKVQFSNDSQTW--WKSRnstGMDIVFPANSDAETPVLNLLPEPQVARFIRLLPQTWFqgGAPCLRAEILA 262
Cdd:cd00057   70 GSSEWVTSYKVQYSLDGETWttYKDK---GEEKVFTGNSDGSTPVTNDFPPPIVARYIRILPTTWN--GNISLRLELYG 143
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
613-689 2.72e-33

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: 122.25  E-value: 2.72e-33
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 228008326 613 GITGVVRDKDTElGIADAVIAVEGINHDVTTAWGGDYWRLLTPGDYVVTASAEGYHTVRQHCQVTFEEGPVPCNFLL 689
Cdd:cd11308    1 GIKGFVTDATGN-PIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
FA58C smart00231
Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached ...
107-263 5.17e-31

Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.


Pssm-ID: 214572  Cd Length: 139  Bit Score: 118.38  E-value: 5.17e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   107 PLGLESlrvsDSQLEASSSqsfGLGAHRGRLNIQSgledgdlyDGAWCAEQQDTEPWLQVDAKNPVRFAGIVTQGRNSVW 186
Cdd:smart00231   5 PLGLES----DSQITASSS---YWAAKIARLNGGS--------DGGWCPAKNDLPPWIQVDLGRLRTVTGVITGRRHGNG 69
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 228008326   187 ryDWVTSFKVqFSNDSQTW--WKSRNstgmDIVFPANSDAETPVLNLLPEPQVARFIRLLPQTWfqGGAPCLRAEILAC 263
Cdd:smart00231  70 --DWVTYKLE-YSDDGVNWttYKDGN----SKVFPGNSDAGTVVLNDFPPPIVARYVRILPTGW--NGNIILRVELLGC 139
F5_F8_type_C pfam00754
F5/8 type C domain; This domain is also known as the discoidin (DS) domain family.
123-260 2.57e-30

F5/8 type C domain; This domain is also known as the discoidin (DS) domain family.


Pssm-ID: 459925 [Multi-domain]  Cd Length: 127  Bit Score: 115.62  E-value: 2.57e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  123 SSSQSFGLGAHRGRLniqsgleDGDlYDGAWCAEQQDTEPWLQVDAKNPVRFAGIVTQGRNSVWRYdWVTSFKVQFSNDS 202
Cdd:pfam00754   4 ASSSYSGEGPAAAAL-------DGD-PNTAWSAWSGDDPQWIQVDLGKPKKITGVVTQGRQDGSNG-YVTSYKIEYSLDG 74
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 228008326  203 QTWwksrnSTGMDIVFPANSDAETPVLNLLPEPQVARFIRLLPQTWFQGGAPCLRAEI 260
Cdd:pfam00754  75 ENW-----TTVKDEKIPGNNDNNTPVTNTFDPPIKARYVRIVPTSWNGGNGIALRAEL 127
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
287-520 1.27e-26

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 111.70  E-value: 1.27e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 287 RHHNYKAMRKLMKQVnEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGehelGEPEVRYVAGMHGNEALGRELllllMQFL 366
Cdd:COG2866   18 RYYTYEELLALLAKL-AAASPLVELESIGKSVEGRPIYLLKIGDPAE----GKPKVLLNAQQHGNEWTGTEA----LLGL 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 367 CHEFLRG-DPRVTRLLTETRIHLLPSMNPDGYEtayhrgselVGWaegRWTHQGIDLNHNFADlntqLWYAEddglvpdt 445
Cdd:COG2866   89 LEDLLDNyDPLIRALLDNVTLYIVPMLNPDGAE---------RNT---RTNANGVDLNRDWPA----PWLSE-------- 144
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 228008326 446 vpnhhlplptyytlpnatvaPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAarELTPTPDDAVFRW 520
Cdd:COG2866  145 --------------------PETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGS--FLAPSYDEEREAF 197
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
613-689 4.10e-10

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 56.52  E-value: 4.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  613 GITGVVRDKDTElGIADAVIAVE----GINHDVTTAWGGDYW-RLLTPGDYVVTASAEGYHTVRQHcQVTFEEG-PVPCN 686
Cdd:pfam13620   1 TISGTVTDPSGA-PVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRT-GVTVTAGqTTTLD 78

                  ...
gi 228008326  687 FLL 689
Cdd:pfam13620  79 VTL 81
 
Name Accession Description Interval E-value
M14_CPX_like cd03869
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase X subgroup; Peptidase ...
288-609 0e+00

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: 644.58  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03869    1 HHNYKDMRQLMKVVNEMCPNITRIYNIGKSYQGLKLYAMEISDNPGEHEVGEPEFRYVAGAHGNEVLGRELLLLLMQFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVGWAEGRWTHQGIDLNHNFADLNTQLWYAEDDGLVPDTVP 447
Cdd:cd03869   81 QEYLAGNPRIRHLVEETRIHLLPSVNPDGYEKAYEAGSELGGWSLGRWTSDGIDINHNFPDLNSLLWEAEDRKWVPRKVP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 NHHLPLPTYYTLPNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAARELTPTPDDAVFRWLSTVYAG 527
Cdd:cd03869  161 NHHIPIPEWYLSENATVAPETRAVIAWMEKIPFVLGGNLQGGELVVSYPYDMTRTPWKTQEYTPTPDDHVFRWLAYSYAS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 528 TNRAMQDTDRRPCHSQDFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTYL 607
Cdd:cd03869  241 THRLMTDASRRPCHTEDFQKEDGTVNGASWHTVAGSMNDFSYLHTNCFELSIYLGCDKFPHESELPEEWENNRESLLVFM 320

                 ..
gi 228008326 608 EQ 609
Cdd:cd03869  321 EQ 322
M14_CP_N-E_like cd03858
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase (CP) N/E-like subfamily of ...
288-609 5.25e-154

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: 448.25  E-value: 5.25e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03858    1 HHNYEELEEFLKQVAKRYPNITRLYSIGKSVEGRELWVLEISDNPGVHEPGEPEFKYVANMHGNEVVGRELLLLLAEYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFlRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSelvGWAEGRWTHQGIDLNHNFADLNTQLWYaeddglvpdtvp 447
Cdd:cd03858   81 ENY-GKDPRVTQLVNSTRIHIMPSMNPDGYEKAQEGDC---GGLIGRNNANGVDLNRNFPDQFFQVYS------------ 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 nhhlplptyytlPNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPwAARELTPTPDDAVFRWLSTVYAG 527
Cdd:cd03858  145 ------------DNNPRQPETKAVMNWLESIPFVLSANLHGGALVANYPYDDTRSG-KSTEYSPSPDDAVFRMLARSYSD 211
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 528 TNRAMQDTDRRPCHSqDFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTYL 607
Cdd:cd03858  212 AHPTMSMGKPCCCDD-DENFPNGITNGAAWYSVSGGMQDFNYLHTNCFEITLELGCCKYPPASELPKYWEDNKRSLLNFL 290

                 ..
gi 228008326 608 EQ 609
Cdd:cd03858  291 EQ 292
M14_CPZ cd03867
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase Z subgroup; Peptidase ...
288-608 8.19e-126

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: 376.92  E-value: 8.19e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03867    1 HHSYSQMVRVLKKTAARCAHIARTYSIGRSFEGKDLLVIEFSSNPGQHELLEPEVKYIGNMHGNEVVGREMLIYLAQYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVGWAEGRWTHQGIDLNHNFADLNTQLW-YAEDDGLVPDtv 446
Cdd:cd03867   81 SEYLLGNPRIQTLINTTRIHLLPSMNPDGYEVAAEEGAGYNGWTSGRQNAQNLDLNRNFPDLTSEAYrLARTRGARLD-- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 447 pnhHLPLPTYYTLpnATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAARELTPTPDDAVFRWLSTVYA 526
Cdd:cd03867  159 ---HIPIPQSYWW--GKVAPETKAVMKWMRSIPFVLSASLHGGDLVVSYPYDFSKHPLEEKMFSPTPDEKMFKLLAKAYA 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 527 GTNRAMQDTDRRPChSQDFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTY 606
Cdd:cd03867  234 DAHPMMSDRSENRC-GGNFLKRGGIINGAEWYSFTGGMADFNYLHTNCFEVTVELGCEKFPPEEELYTIWQENKEALLNF 312

                 ..
gi 228008326 607 LE 608
Cdd:cd03867  313 ME 314
M14_CPN cd03864
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase N subgroup; Peptidase M14 ...
288-609 1.64e-122

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: 368.49  E-value: 1.64e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03864    1 HHRYDDLVRALYAVQNECPYITRIYSIGRSVEGRHLYVLEFSDNPGIHEPLEPEFKYVGNMHGNEVLGRELLIQLSEFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVGWAEGRWTHQGIDLNHNFADLNTQLWYAEDDGlvpdtVP 447
Cdd:cd03864   81 EEYRNGNERITRLIQDTRIHILPSMNPDGYEVAARQGPEFNGYLVGRNNANGVDLNRNFPDLNTLMYYNEKYG-----GP 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 NHHLPLPTYYtlpNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTP----WAARELTPTPDDAVFRWLST 523
Cdd:cd03864  156 NHHLPLPDNW---KSQVEPETLAVIQWMQNYNFVLSANLHGGAVVANYPYDKSREPrvrgFRRTAYSPTPDDKLFQKLAK 232
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 524 VYAGTNRAMQdtdrRPCHSQDFSLHGnVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDAL 603
Cdd:cd03864  233 TYSYAHGWMH----KGWNCGDYFDEG-ITNGASWYSLSKGMQDFNYLHTNCFEITLELSCDKFPPEEELEREWLGNREAL 307

                 ....*.
gi 228008326 604 LTYLEQ 609
Cdd:cd03864  308 ISYMEQ 313
M14_CPE cd03865
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase E subgroup; Peptidase M14 ...
288-609 9.67e-121

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


Pssm-ID: 349437 [Multi-domain]  Cd Length: 319  Bit Score: 363.92  E-value: 9.67e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03865    1 YHRYPELREALVSVWLQCPAISRIYTVGRSFEGRELLVIEVSDNPGEHEPGEPEFKYVGNMHGNEAVGRELLIFLAQYLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVGWAEGRWTHQGIDLNHNFADLNTQLWYAEDDGlvpdtVP 447
Cdd:cd03865   81 NEYQKGNETIINLIHSTRIHIMPSLNPDGFEKAASQPGELKDWFVGRSNAQGIDLNRNFPDLDRIVYVNEKEG-----GP 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 NHHLPLPTYYTL-PNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPwAARELTPTPDDAVFRWLSTVYA 526
Cdd:cd03865  156 NNHLLKNMKKAVdQNTKLAPETKAVIHWIMDIPFVLSANLHGGDLVANYPYDETRSG-SAHEYSSCPDDAIFQSLARAYS 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 527 GTNRAMQDTDRRPC--HSQDFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALL 604
Cdd:cd03865  235 SLNPAMSDPNRPPCrkNDDDSSFVDGTTNGGAWYSVPGGMQDFNYLSSNCFEITVELSCEKFPPEETLKGYWEDNKNSLI 314

                 ....*
gi 228008326 605 TYLEQ 609
Cdd:cd03865  315 NYIEQ 319
M14_CPD_I cd03868
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain I subgroup; The ...
289-609 6.61e-112

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: 340.38  E-value: 6.61e-112
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 289 HNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLCH 368
Cdd:cd03868    2 HNYDELTDLLHKLAETYPNIAKLHSIGKSVQGRELWVLEISDNVNRREPGKPMFKYVANMHGDETVGRQLLIYLAQYLLE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 369 EFLRgDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVGWAEGRWTHQGIDLNHNFADlntqlwyaEDDGLVPDTVPN 448
Cdd:cd03868   82 NYGK-DERVTRLVNSTDIHLMPSMNPDGFENSKEGDCSGDPGYGGRENANNVDLNRNFPD--------QFEDSDDRLLEG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 449 HhlplptyytlpnatvAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAARELTPTPDDAVFRWLSTVYAGT 528
Cdd:cd03868  153 R---------------QPETLAMMKWIVENPFVLSANLHGGSVVASYPFDDSPSHIECGVYSKSPDDAVFRHLAHTYADN 217
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 529 NRAMQdtDRRPCHSQDFSlHGnVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTYLE 608
Cdd:cd03868  218 HPTMH--KGNNCCEDSFK-DG-ITNGAEWYDVPGGMQDFNYVHSNCFEITLELSCCKYPPASELPKEWDNNKEALLSYME 293

                 .
gi 228008326 609 Q 609
Cdd:cd03868  294 Q 294
M14_CPD_II cd03863
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain II subgroup; The ...
285-609 3.53e-98

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: 304.95  E-value: 3.53e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 285 DFRHHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQ 364
Cdd:cd03863    5 DFRHHHFSDMEIFLRRYANEYPSITRLYSVGKSVELRELYVMEISDNPGVHEPGEPEFKYIGNMHGNEVVGRELLLNLIE 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 365 FLCHEFlRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSELVgwaEGRWTHQGIDLNHNFADLNTQLwyaeddglvpd 444
Cdd:cd03863   85 YLCKNF-GTDPEVTDLVQNTRIHIMPSMNPDGYEKSQEGDRGGT---VGRNNSNNYDLNRNFPDQFFQI----------- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 445 TVPnhhlplptyytlpnatVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAAreLTPTPDDAVFRWLSTV 524
Cdd:cd03863  150 TDP----------------PQPETLAVMSWLKTYPFVLSANLHGGSLVVNYPFDDDEQGLAT--YSKSPDDAVFQQLALS 211
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 525 YAGTNRAMQDTdrRPC---HSQDFSLHGnVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKD 601
Cdd:cd03863  212 YSKENSKMYQG--SPCkelYPNEYFPHG-ITNGAQWYNVPGGMQDWNYLNTNCFEVTIELGCVKYPKAEELPKYWEQNRR 288

                 ....*...
gi 228008326 602 ALLTYLEQ 609
Cdd:cd03863  289 SLLQFIKQ 296
M14_CPM cd03866
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup; Peptidase M14 ...
288-609 5.81e-81

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: 259.73  E-value: 5.81e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd03866    1 YHNQEQMETYLKDVNKNYPSITHLHSIGKSVEGRDLWVLVLGRFPTKHRIGIPEFKYVANMHGDEVVGRELLLHLIEFLV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFlRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSElvgWAEGRWTHQGIDLNHNFADLntqlwyaeddglvpdtvp 447
Cdd:cd03866   81 TSY-GSDPVITRLINSTRIHIMPSMNPDGFEATKKPDCY---YTKGRYNKNGYDLNRNFPDA------------------ 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 nhhlplptyYTLPNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRT-PWAARELTPTPDDAVFRWLSTVYA 526
Cdd:cd03866  139 ---------FEENNVQRQPETRAVMDWIKNETFVLSANLHGGALVASYPFDNGNSgTGQLGYYSVSPDDDVFIYLAKTYS 209
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 527 GTNRAMQDTDRRPcHSQDFSlhGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTY 606
Cdd:cd03866  210 YNHTNMYKGIECS-NSQSFP--GGITNGYQWYPLQGGMQDYNYVWGQCFEITLELSCCKYPPEETLPQFWNDNRVALIEY 286

                 ...
gi 228008326 607 LEQ 609
Cdd:cd03866  287 IKQ 289
Peptidase_M14 pfam00246
Zinc carboxypeptidase;
294-602 2.34e-80

Zinc carboxypeptidase;


Pssm-ID: 459730 [Multi-domain]  Cd Length: 287  Bit Score: 258.00  E-value: 2.34e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  294 MRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLCHEFLRg 373
Cdd:pfam00246   1 IEAWLDALAARYPDLVRLVSIGKSVEGRPLKVLKISSGPGEHNPGKPAVFIDGGIHAREWIGPATALYLIHQLLTNYGR- 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  374 DPRVTRLLTETRIHLLPSMNPDGYEtAYHRGSELvgWAEGRWTHQ-----GIDLNHNFADlntqLWyaeddglvpDTVPN 448
Cdd:pfam00246  80 DPEITELLDDTDIYILPVVNPDGYE-YTHTTDRL--WRKNRSNANgssciGVDLNRNFPD----HW---------NEVGA 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  449 HHLPLPTYYTLPNATVAPETWAVIKWMKR-IPFVLSANLHGGELVVSYPFDMTRTpwaarelTPTPDDAVFRWLSTVYAG 527
Cdd:pfam00246 144 SSNPCSETYRGPAPFSEPETRAVADFIRSkKPFVLYISLHSYSQVLLYPYGYTRD-------EPPPDDEELKSLARAAAK 216
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  528 TNRAMqdtdrrpCHSQDFSlhGNVINGADWHTVPGSMNDFSYLHTNC-FEVTVELSCDK----FPHEKELPQEWENNKDA 602
Cdd:pfam00246 217 ALQKM-------VRGTSYT--YGITNGATIYPASGGSDDWAYGRLGIkYSYTIELRDTGrygfLLPASQIIPTAEETWEA 287
M14_CP_bacteria cd18173
bacterial peptidase M14 carboxypeptidase, uncharacterized; This family contains only bacterial ...
289-609 3.68e-74

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: 241.33  E-value: 3.68e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 289 HNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHElGEPEVRYVAGMHGNEALGRELllllMQFLCH 368
Cdd:cd18173    5 PTYEEYEAMMQSFAANYPNICRLVSIGTSVQGRKLLALKISDNVNTEE-AEPEFKYTSTMHGDETTGYEL----MLRLID 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 369 EFLRG---DPRVTRLLTETRIHLLPSMNPDGYetaYHRGSELVGWAEgRWTHQGIDLNHNFADlntqlwyaeddglvPDT 445
Cdd:cd18173   80 YLLTNygtDPRITNLVDNTEIWINPLANPDGT---YAGGNNTVSGAT-RYNANGVDLNRNFPD--------------PVD 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 446 VPNhhlplPTYYTLPnatvaPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPwaareltpTPDDAVFRWLSTVY 525
Cdd:cd18173  142 GDH-----PDGNGWQ-----PETQAMMNFADEHNFVLSANFHGGAEVVNYPWDTWYSR--------HPDDDWFQDISREY 203
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 526 AGTNRAMQDTDRrpcHSqdfSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLT 605
Cdd:cd18173  204 ADTNQANSPPMY---MS---EFNNGITNGYDWYEVYGGRQDYMYYWHGCREVTIELSNTKWPPASQLPTYWNYNRESLLN 277

                 ....
gi 228008326 606 YLEQ 609
Cdd:cd18173  278 YIEQ 281
M14_CP_plant cd18172
Zinc carboxypeptidase, including SOL1, a carboxypeptidase D in plant; This family includes ...
288-608 1.10e-67

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: 223.83  E-value: 1.10e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHElGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd18172    1 YHSNAELEDALKAFTRRCGAISRLIVIGSSVNGFPLWALEISDGPGEDE-TEPAFKFVGNMHGDEPVGRELLLRLADWLC 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRGDPRVTRLLTETRIHLLPSMNPDGYEtayhrgselvgwAEGRWTHQGIDLNHNFADLntqlwyaeddgLVPDTVP 447
Cdd:cd18172   80 ANYKAKDPLAAKIVENAHLHLVPTMNPDGFA------------RRRRNNANNVDLNRDFPDQ-----------FFPKNLR 136
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 448 NHhlplptyytlpNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMT---RTPWAAreltpTPDDAVFRWLSTV 524
Cdd:cd18172  137 ND-----------LAARQPETLAVMNWSRSVRFTASANLHEGALVANYPWDGNadgRTKYSA-----SPDDATFRRLASV 200
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 525 YAGTNRAMQDtdrrpchSQDFSlhGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALL 604
Cdd:cd18172  201 YAQAHPNMAK-------SKEFP--GGITNGAQWYPLYGGMQDWNYLHTGCMDLTLEVNDNKWPPEDRLVQIWAEHRKAML 271

                 ....
gi 228008326 605 TYLE 608
Cdd:cd18172  272 ALAA 275
Zn_pept smart00631
Zn_pept domain;
288-595 3.59e-67

Zn_pept domain;


Pssm-ID: 214748 [Multi-domain]  Cd Length: 277  Bit Score: 222.60  E-value: 3.59e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEhelGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:smart00631   1 YHSYEEIEAWLKELAARYPDLVRLVSIGKSVEGRPIWVLKISNGGSH---DKPAIFIDAGIHAREWIGPATALYLINQLL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   368 HEFLRgDPRVTRLLTETRIHLLPSMNPDGYEtaYHRGSElVGWAEGRWTHQ---GIDLNHNFADlntqLWYAEDDglvpd 444
Cdd:smart00631  78 ENYGR-DPRVTNLLDKTDIYIVPVLNPDGYE--YTHTGD-RLWRKNRSPNSncrGVDLNRNFPF----HWGETGN----- 144
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   445 tvpnhhlPLPTYYTLPNATVAPETWAVIKWMKR-IPFVLSANLHGGELVVSYPFDMTRTPWAAREltpTPDDAVFRWLST 523
Cdd:smart00631 145 -------PCSETYAGPSPFSEPETKAVRDFIRSnRRFKLYIDLHSYSQLILYPYGYTKNDLPPNV---DDLDAVAKALAK 214
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   524 VYAgtnramqdtdrrpchsqdfSLHGN-----VINGADWHtVPGSMNDFSYLHTN-CFEVTVELSCD-----KFPHEKEL 592
Cdd:smart00631 215 ALA-------------------SVHGTrytygISNGAIYP-ASGGSDDWAYGVLGiPFSFTLELRDDgrygfLLPPSQII 274

                   ...
gi 228008326   593 PQE 595
Cdd:smart00631 275 PTG 277
M14_CPD_III cd06245
Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase D, domain III subgroup; ...
288-609 1.32e-66

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: 221.17  E-value: 1.32e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLLMQFLC 367
Cdd:cd06245    1 YHSYKQLSKFLRGLNSNYPTITNLTSLGQSVEKRDIWVLEIGNKPNESEPSEPKILFVGGIHGNAPVGTELLLLLAHFLC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HeFLRGDPRVTRLLTETRIHLLPSMNPDGYETAYHRG-SELVGWAEGRwthqGIDLNHNFadlntqlwyaeddglvpdtv 446
Cdd:cd06245   81 H-NYKKDSAITKLLNRTRIHIVPSLNPDGAEKAEEKKcTSKIGEKNAN----GVDLDTDF-------------------- 135
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 447 pnhhlplPTYYTLPNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAARELtptpddavFRWLSTVYA 526
Cdd:cd06245  136 -------ESNANNRSGAAQPETKAIMDWLKEKDFTLSVALDGGSLVVTYPYDKPVQTVENKET--------LKHLAKVYA 200
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 527 GTNRAMQDTDRRPCHSQDFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELSCDKFPHEKELPQEWENNKDALLTY 606
Cdd:cd06245  201 NNHPTMHAGDPGCCSNSDENFTNGVIRASEWHSHKGSMLDFSYKFGSCPEITVYTSCCYFPPAEELLTLWAEHKKSLLSM 280

                 ...
gi 228008326 607 LEQ 609
Cdd:cd06245  281 IVE 283
FA58C cd00057
Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached ...
106-262 1.07e-44

Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.


Pssm-ID: 238014 [Multi-domain]  Cd Length: 143  Bit Score: 156.74  E-value: 1.07e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 106 PPLGLESLRvSDSQLEASSSQSFGLGAHRGRLNiqsgledgdlYDGAWCAEQQDTEPWLQVDAKNPVRFAGIVTQGRNSV 185
Cdd:cd00057    1 EPLGMESGL-ADDQITASSSYSSGWEASRARLN----------SDNAWTPAVNDPPQWLQVDLGKTRRVTGIQTQGRKGG 69
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 228008326 186 WRYDWVTSFKVQFSNDSQTW--WKSRnstGMDIVFPANSDAETPVLNLLPEPQVARFIRLLPQTWFqgGAPCLRAEILA 262
Cdd:cd00057   70 GSSEWVTSYKVQYSLDGETWttYKDK---GEEKVFTGNSDGSTPVTNDFPPPIVARYIRILPTTWN--GNISLRLELYG 143
M14_CPT cd03859
Peptidase M14 Carboxypeptidase T subfamily; Peptidase M14-like domain of carboxypeptidase (CP) ...
289-603 2.88e-35

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: 135.46  E-value: 2.88e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 289 HNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHElGEPEVRYVAGMHGNEALGRELLLLLMQFLCH 368
Cdd:cd03859    5 HTYAELVAELDQLAAEYPEITKLISIGKSVEGRPIWAVKISDNPDEDE-DEPEVLFMGLHHAREWISLEVALYFADYLLE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 369 EFLRgDPRVTRLLTETRIHLLPSMNPDGYEtaYHRGSELVGW--------AEGRWTHQGIDLNHNFAdlntQLWYAEDDG 440
Cdd:cd03859   84 NYGT-DPRITNLVDNREIWIIPVVNPDGYE--YNRETGGGRLwrknrrpnNGNNPGSDGVDLNRNYG----YHWGGDNGG 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 441 LVPDtvpnhhlPLPTYYTLPNATVAPETWAVIKWMKRIPFVLSANLHG-GELVVSypfdmtrtPWAARELTPTPDDAVFR 519
Cdd:cd03859  157 SSPD-------PSSETYRGPAPFSEPETQAIRDLVESHDFKVAISYHSyGELVLY--------PWGYTSDAPTPDEDVFE 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 520 WLSTVYAGTNramqdtdrrpchsqdfslHGNVINGADWH--TVPGSMNDFSYLHTNCFEVTVEL---SCDKFPHEKELPQ 594
Cdd:cd03859  222 ELAEEMASYN------------------GGGYTPQQSSDlyPTNGDTDDWMYGEKGIIAFTPELgpeFYPFYPPPSQIDP 283

                 ....*....
gi 228008326 595 EWENNKDAL 603
Cdd:cd03859  284 LAEENLPAA 292
Peptidase_M14NE-CP-C_like cd11308
Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, ...
613-689 2.72e-33

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: 122.25  E-value: 2.72e-33
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 228008326 613 GITGVVRDKDTElGIADAVIAVEGINHDVTTAWGGDYWRLLTPGDYVVTASAEGYHTVRQHCQVTFEEGPVPCNFLL 689
Cdd:cd11308    1 GIKGFVTDATGN-PIANATISVEGINHDVTTAKDGDYWRLLLPGTYNVTASAPGYQPVTKTVTVPNNFSATVVNFTL 76
FA58C smart00231
Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached ...
107-263 5.17e-31

Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.


Pssm-ID: 214572  Cd Length: 139  Bit Score: 118.38  E-value: 5.17e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326   107 PLGLESlrvsDSQLEASSSqsfGLGAHRGRLNIQSgledgdlyDGAWCAEQQDTEPWLQVDAKNPVRFAGIVTQGRNSVW 186
Cdd:smart00231   5 PLGLES----DSQITASSS---YWAAKIARLNGGS--------DGGWCPAKNDLPPWIQVDLGRLRTVTGVITGRRHGNG 69
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 228008326   187 ryDWVTSFKVqFSNDSQTW--WKSRNstgmDIVFPANSDAETPVLNLLPEPQVARFIRLLPQTWfqGGAPCLRAEILAC 263
Cdd:smart00231  70 --DWVTYKLE-YSDDGVNWttYKDGN----SKVFPGNSDAGTVVLNDFPPPIVARYVRILPTGW--NGNIILRVELLGC 139
F5_F8_type_C pfam00754
F5/8 type C domain; This domain is also known as the discoidin (DS) domain family.
123-260 2.57e-30

F5/8 type C domain; This domain is also known as the discoidin (DS) domain family.


Pssm-ID: 459925 [Multi-domain]  Cd Length: 127  Bit Score: 115.62  E-value: 2.57e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  123 SSSQSFGLGAHRGRLniqsgleDGDlYDGAWCAEQQDTEPWLQVDAKNPVRFAGIVTQGRNSVWRYdWVTSFKVQFSNDS 202
Cdd:pfam00754   4 ASSSYSGEGPAAAAL-------DGD-PNTAWSAWSGDDPQWIQVDLGKPKKITGVVTQGRQDGSNG-YVTSYKIEYSLDG 74
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 228008326  203 QTWwksrnSTGMDIVFPANSDAETPVLNLLPEPQVARFIRLLPQTWFQGGAPCLRAEI 260
Cdd:pfam00754  75 ENW-----TTVKDEKIPGNNDNNTPVTNTFDPPIKARYVRIVPTSWNGGNGIALRAEL 127
MpaA COG2866
Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis];
287-520 1.27e-26

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


Pssm-ID: 442113 [Multi-domain]  Cd Length: 337  Bit Score: 111.70  E-value: 1.27e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 287 RHHNYKAMRKLMKQVnEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGehelGEPEVRYVAGMHGNEALGRELllllMQFL 366
Cdd:COG2866   18 RYYTYEELLALLAKL-AAASPLVELESIGKSVEGRPIYLLKIGDPAE----GKPKVLLNAQQHGNEWTGTEA----LLGL 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 367 CHEFLRG-DPRVTRLLTETRIHLLPSMNPDGYEtayhrgselVGWaegRWTHQGIDLNHNFADlntqLWYAEddglvpdt 445
Cdd:COG2866   89 LEDLLDNyDPLIRALLDNVTLYIVPMLNPDGAE---------RNT---RTNANGVDLNRDWPA----PWLSE-------- 144
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 228008326 446 vpnhhlplptyytlpnatvaPETWAVIKWMKRIPFVLSANLHGGELVVSYPFDMTRTPWAarELTPTPDDAVFRW 520
Cdd:COG2866  145 --------------------PETRALRDLLDEHDPDFVLDLHGQGELFYWFVGTTEPTGS--FLAPSYDEEREAF 197
Peptidase_M14_like cd00596
M14 family of metallocarboxypeptidases and related proteins; The M14 family of ...
344-603 3.06e-26

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: 107.16  E-value: 3.06e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 344 YVAGMHGNEALGRELLLLLMQFLCHEFLRGDprVTRLLTETRIHLLPSMNPDGYETAYHRGselvgwaeGRWTHQGIDLN 423
Cdd:cd00596    3 ITGGIHGNEVIGVELALALIEYLLENYGNDP--LKRLLDNVELWIVPLVNPDGFARVIDSG--------GRKNANGVDLN 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 424 HNFaDLNtqlWYAEDDglvpdtvpnhHLPLPTYYTLPNATVAPETWAVIKWMKRIPFVLSANLHGGELVVSYPFdmtrtp 503
Cdd:cd00596   73 RNF-PYN---WGKDGT----------SGPSSPTYRGPAPFSEPETQALRDLAKSHRFDLAVSYHSSSEAILYPY------ 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 504 waARELTPTPDDAVFRWLSTVYAGTNramqdtdrrpchsqdFSLHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVEL-S 582
Cdd:cd00596  133 --GYTNEPPPDFSEFQELAAGLARAL---------------GAGEYGYGYSYTWYSTTGTADDWLYGELGILAFTVELgT 195
                        250       260
                 ....*....|....*....|.
gi 228008326 583 CDKFPHEKELPQEWENNKDAL 603
Cdd:cd00596  196 ADYPLPGTLLDRRLERNLAAL 216
M14-like cd06905
Peptidase M14-like domain; uncharacterized subfamily; A functionally uncharacterized subgroup ...
284-398 2.14e-19

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: 90.37  E-value: 2.14e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 284 LDFRH-HNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHELGEPEVRYVAGMHGNEALGRELLLLL 362
Cdd:cd06905    1 LAFDRyYTYAELTARLKALAEAYPNLVRLESIGKSYEGRDIWLLTITNGETGPADEKPALWVDGNIHGNEVTGSEVALYL 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 228008326 363 MQFLCHEFLRgDPRVTRLLTETRIHLLPSMNPDGYE 398
Cdd:cd06905   81 AEYLLTNYGK-DPEITRLLDTRTFYILPRLNPDGAE 115
M14_CP_A-B_like cd03860
Peptidase M14 carboxypeptidase subfamily A/B-like; The Peptidase M14 Carboxypeptidase (CP) A/B ...
289-427 2.92e-11

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: 64.86  E-value: 2.92e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 289 HNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHelGEPEVRYVAGMHgnealGRE-LLLLLMQFLC 367
Cdd:cd03860    2 HPLDDIVQWLDDLAAAFPDNVEIFTIGKSYEGRDITGIHIWGSGGKG--GKPAIVIHGGQH-----AREwISTSTVEYLA 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 368 HEFLRG---DPRVTRLLTETRIHLLPSMNPDGYE-TayhrgselvgwaegrWTH----------------QGIDLNHNFA 427
Cdd:cd03860   75 HQLLSGygsDATITALLDKFDFYIIPVVNPDGYVyT---------------WTTdrlwrknrqptggsscVGIDLNRNWG 139
CarboxypepD_reg pfam13620
Carboxypeptidase regulatory-like domain;
613-689 4.10e-10

Carboxypeptidase regulatory-like domain;


Pssm-ID: 433354 [Multi-domain]  Cd Length: 81  Bit Score: 56.52  E-value: 4.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326  613 GITGVVRDKDTElGIADAVIAVE----GINHDVTTAWGGDYW-RLLTPGDYVVTASAEGYHTVRQHcQVTFEEG-PVPCN 686
Cdd:pfam13620   1 TISGTVTDPSGA-PVPGATVTVTntdtGTVRTTTTDADGRYRfPGLPPGTYTVTVSAPGFKTATRT-GVTVTAGqTTTLD 78

                  ...
gi 228008326  687 FLL 689
Cdd:pfam13620  79 VTL 81
M14_MpaA-like cd06904
Peptidase M14-like domain of Escherichia coli Murein Peptide Amidase A and related proteins; ...
314-607 4.52e-10

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: 59.98  E-value: 4.52e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 314 IGKSHQGLKLYVMEMSDHPGehelgePEVRYVAGMHGNEALGrelllllmQFLCHEFLRgdprvtRLLTET-----RIHL 388
Cdd:cd06904    4 YGTSVKGRPILAYKFGPGSR------ARILIIGGIHGDEPEG--------VSLVEHLLR------WLKNHPasgdfHIVV 63
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 389 LPSMNPDGYEtAYHRGSElvgwaegrwthQGIDLNHNFadlNTQLWyaEDDGLVPDTvpnhhlplPTYYTLPNATVAPET 468
Cdd:cd06904   64 VPCLNPDGLA-AGTRTNA-----------NGVDLNRNF---PTKNW--EPDARKPKD--------PRYYPGPKPASEPET 118
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 469 WAVIKWMKRIP--FVLSanLHggelvvsypfdmtrtpwaarelTPTPDDavfrwlstvyagtnramQDTDRRPCHSQDFS 546
Cdd:cd06904  119 RALVELIERFKpdRIIS--LH----------------------APYLVN-----------------YDGPAKSLLAEKLA 157
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 228008326 547 LHGNVINGADWHTVPGSMNDFSYLHTNCFEVTVELscdkfPHEKELPQEWENNKDALLTYL 607
Cdd:cd06904  158 QATGYPVVGDVGYTPGSLGTYAGIERNIPVITLEL-----PEAVSIDELWQDLKRALIEAI 213
M14-like cd03857
Peptidase M14-like domain; uncharacterized subfamily; Peptidase M14-like domain of a ...
344-502 1.02e-09

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: 59.01  E-value: 1.02e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 344 YVAGMHGNEALGRElllLLMQFLCHEFLRGDPrVTRLLTETRIHLLPSMNPDGYE-TAYHRGSELVGWAEGRWTHQGIDL 422
Cdd:cd03857    4 LAAQIHGNETTGTE---ALMELIRDLASESDE-AAKLLDNIVILLVPQLNPDGAElFVNFYLDSMNGLPGTRYNANGIDL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 423 NHNFADLN---TQLWYAEDDGLVPDTVPNHH------LPLPTYYTLPNATVAPEtwAVIKWMKRIPFVLSANLHGGELVV 493
Cdd:cd03857   80 NRDHVKLTqpeTQAVAENFIHWWPDIFIDLHeqvgasIPYPTPPDAPNYNLVDL--RSDAENGQEHIRLIAGEGSGELGK 157

                 ....*....
gi 228008326 494 SYPFDMTRT 502
Cdd:cd03857  158 YFSPMRGGF 166
M14_Endopeptidase_I cd06229
Peptidase M14 carboxypeptidase family-like domain of Endopeptidase I; Peptidase M14-like ...
342-487 2.68e-08

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: 55.42  E-value: 2.68e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 342 VRYVAGMHGNEALgreLLLLLMQFLcHEFLRG--------DPRVTRLLTETRIHLLPSMNPDGYETAYH-------RGSE 406
Cdd:cd06229    1 VLYNASFHAREYI---TTLLLMKFI-EDYAKAyvnksyirGKDVGELLNKVTLHIVPMVNPDGVEISQNgsnainpYYLR 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 407 LVGWAEGRWTH-------QGIDLNHNFAdlntQLWYAEDDglvpdtvPNHHLPLPTYYTLPNATVAPETWAVIKWMKRIP 479
Cdd:cd06229   77 LVAWNKKGTDFtgwkaniRGVDLNRNFP----AGWEKEKR-------LGPKAPGPRDYPGKEPLSEPETKAMAALTRQND 145

                 ....*...
gi 228008326 480 FVLSANLH 487
Cdd:cd06229  146 FDLVLAYH 153
M14_CPA6 cd03872
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A6 subgroup; ...
288-503 9.26e-07

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


Pssm-ID: 349444 [Multi-domain]  Cd Length: 300  Bit Score: 51.13  E-value: 9.26e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 288 HHNYKAMRKLMKQVNEQCPNITRIYSIGKSHQGLKLYVMEMsdhpGEHELGEPEVRYV-AGMHGNEALGrellLLLMQFL 366
Cdd:cd03872    2 YHSLEEIESWMFYMNKTHSDLVHMFSIGKSYEGRSLYVLKL----GKRSRSYKKAVWIdCGIHAREWIG----PAFCQWF 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 367 CHEFL---RGDPRVTRLLTETRIHLLPSMNPDGYETAYHRGSelvGWAEGR------WTHqGIDLNHNFadlnTQLWYAE 437
Cdd:cd03872   74 VKEAInsyQTDPAMKKMLNQLYFYVMPVFNVDGYHYSWTNDR---FWRKTRsknsrfQCR-GVDANRNW----KVKWCDE 145
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 228008326 438 DDGLVP--DTvpnhhlplptyYTLPNATVAPETWAVIKWM----KRIPFVLSANLHGGELVVSYPFDMTRTP 503
Cdd:cd03872  146 GASLHPcdDT-----------YCGPFPESEPEVKAVAQFLrkhrKHVRAYLSFHAYAQMLLYPYSYKYATIP 206
M14_CP_insect cd06248
Peptidase M14 carboxypeptidase subfamily A/B-like; This family includes peptidase M14 ...
298-509 1.50e-06

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: 50.53  E-value: 1.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 298 MKQVNEQCPNITRIYSIGKSHQGLKLYVMEMSDHPGEHElGEPEVRYVAGMHGNEALgrelLLLLMQFLCHEFLRGDPRV 377
Cdd:cd06248   11 LDGLAEESPDVVTVVEGGYTFEGRPIKYVRIRSTNSEDT-SKPTIMIEGGINPREWI----SPPAALYAIHKLVEDVETQ 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 378 TRLLTETRIHLLPSMNPDGYETA-----YHRGSELVGWAEGRWTHQGIDLNHNFAdlntQLWYAEddglvpDTVPNhhlP 452
Cdd:cd06248   86 SDLLNNFDWIILPVANPDGYVFThtndrEWTKNRSTNSNPLGQICFGVNINRNFD----YQWNPV------LSSES---P 152
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 453 LPTYYTLPNATVAPETWAVIKWM--KRIPFVLSANLHGGELVVSYPFDMT-RTPWAAREL 509
Cdd:cd06248  153 CSELYAGPSAFSEAESRAIRDILheHGNRIHLYISFHSGGSFILYPWGYDgSTSSNARQL 212
M14-like cd06242
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
340-432 1.07e-05

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


Pssm-ID: 349461 [Multi-domain]  Cd Length: 220  Bit Score: 47.30  E-value: 1.07e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 340 PEVRYVAGMHGNEALGRELLLLLMQFLCheflrGDPRVTRLLTETRIHLLPSMNPDGYEtAYHRGSELvgwaegrwthqG 419
Cdd:cd06242    2 PTVLLVGQQHGNEPAGREAALALARDLA-----FGDDARELLEKVNVLVVPRANPDGRA-ANTRGNAN-----------G 64
                         90
                 ....*....|...
gi 228008326 420 IDLNHNFADLNTQ 432
Cdd:cd06242   65 VDLNRDHLLLSTP 77
M14-like cd06238
Peptidase M14-like domain; uncharacterized subgroup; Peptidase M14-like domain of a ...
349-425 7.51e-05

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


Pssm-ID: 349457  Cd Length: 217  Bit Score: 44.66  E-value: 7.51e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 349 HGNEALGRELLlllMQFLCHEFLRGDPRVTRLLTETRIHLLPSMNPDGYETA---YHRGSELVG------------WAEG 413
Cdd:cd06238   11 HGNELSGSEAA---MQVAYHLAAGQDEATRALLENTVIVIDPNQNPDGRERFvnwFNQNRGAVGdpdpqsmehnepWPGG 87
                         90
                 ....*....|..
gi 228008326 414 RWTHQGIDLNHN 425
Cdd:cd06238   88 RTNHYLFDLNRD 99
M14_Nna1-like cd06237
Peptidase M14-like domain of ATP/GTP binding proteins and cytosolic carboxypeptidases; ...
289-521 2.78e-04

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


Pssm-ID: 349456 [Multi-domain]  Cd Length: 239  Bit Score: 42.94  E-value: 2.78e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 289 HNYKAMRKLMKQvneqcPNITRIySIGKSHQGLKLYVMEMSD-------------HPgehelgePEVR-YVAGMHGNEAL 354
Cdd:cd06237    2 DYDAWIDSLAKK-----PFVKRS-TIGKSVEGRPIEALTIGNpdskelvvllgrqHP-------PEVTgALAMQAFVETL 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 355 GRELLlllmqfLCHEFLRgdprvtrlltETRIHLLPSMNPDGyetayhrgselVgwAEGRWTHQ--GIDLN---HNFadl 429
Cdd:cd06237   69 LADTE------LAKAFRA----------RFRVLVVPLLNPDG-----------V--DLGHWRHNagGVDLNrdwGPF--- 116
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 430 nTQlwyaeddglvpdtvpnhhlplptyytlpnatvaPETWAVIKWMKRIpfvlsANLHGGELV-----------VSYPFD 498
Cdd:cd06237  117 -TQ---------------------------------PETRAVRDFLLEL-----VEEPGGKVVfgldfhstwedVFYTQP 157
                        250       260
                 ....*....|....*....|...
gi 228008326 499 mtrtpwaaRELTPTPDDAVFRWL 521
Cdd:cd06237  158 --------DDEKTNPPGFTPDWL 172
M14_CPA cd03870
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup; Peptidase M14 ...
306-426 4.64e-04

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: 42.81  E-value: 4.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 306 PNITRIYSIGKSHQGLKLYVMEMSDHPGEhelgEPEVRYVAGMHGNEALGRELLLLLMQFLCHEFLRgDPRVTRLLTETR 385
Cdd:cd03870   24 PNLVSKLQIGSSFENRPMYVLKFSTGGEE----RPAIWIDAGIHSREWVTQASAIWTAEKIVSDYGK-DPSITSILDTMD 98
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 228008326 386 IHLLPSMNPDGYetAY-HRGSELvgWAEGRWTHQ-----GIDLNHNF 426
Cdd:cd03870   99 IFLEIVTNPDGY--VFtHSSNRL--WRKTRSVNPgslciGVDPNRNW 141
CarbopepD_reg_2 pfam13715
CarboxypepD_reg-like domain; This domain family is found in bacteria, archaea and eukaryotes, ...
614-689 5.13e-04

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


Pssm-ID: 433425 [Multi-domain]  Cd Length: 88  Bit Score: 39.50  E-value: 5.13e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 228008326  614 ITGVVRDKDTELGIADAVIAVEGINHDVTTAWGGDY-WRLLTPGDYVVTASAEGYHTVRQHCQVTfEEGPVPCNFLL 689
Cdd:pfam13715   1 ISGTVVDENTGEPLPGATVYVKGTTKGTVTDADGNFeLKNLPAGTYTLVVSFVGYKTQEKKVTVS-NDNTLDVNFLL 76
M14-CPA-like cd06227
Peptidase M14 carboxypeptidase A-like domain; uncharacterized subfamily; A functionally ...
345-516 5.14e-04

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: 42.26  E-value: 5.14e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 345 VAGMHGNEALGRELLLLLMQFLCHE-----FLRGDPRVTRLLTETRIHLLPSMNPDGyeTAYHRGSELVgWaegRWTHQG 419
Cdd:cd06227    7 VFGEHARELISVESALRLLRQLCGGlqepaASALRELAREILDNVELKIIPNANPDG--RRLVESGDYC-W---RGNENG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 420 IDLNHNFADlntqLWYAEDDGLVPDTVPNHHlPLPtyytlpnatvAPETWAVIKWMKRIPFVLSANLHGGELVVsYpfdm 499
Cdd:cd06227   81 VDLNRNWGV----DWGKGEKGAPSEEYPGPK-PFS----------EPETRALRDLALSFKPHAFVSVHSGMLAI-Y---- 140
                        170
                 ....*....|....*..
gi 228008326 500 trTPWAARELTPTPDDA 516
Cdd:cd06227  141 --TPYAYSASVPRPNRA 155
M14_REP34-like cd06231
Peptidase M14-like domain similar to rapid encystment phenotype 34 (REP34); This family ...
346-427 6.02e-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: 41.91  E-value: 6.02e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 346 AGMHGNEALGRELllllmqfLCHeFLRGDPRvtRLLTETRIHLLPSMNPDGYEtayhRGSelvgwaegRWTHQGIDLNHN 425
Cdd:cd06231   49 AGIHGDEPAGVEA-------LLR-FLESLAE--KYLRRVNLLVLPCVNPWGFE----RNT--------RENADGIDLNRS 106

                 ..
gi 228008326 426 FA 427
Cdd:cd06231  107 FL 108
M14_CPT_like cd06226
Peptidase M14-like domain of an uncharacterized group of Peptidase M14 Carboxypeptidase T (CPT) ...
374-478 1.04e-03

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: 41.67  E-value: 1.04e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 374 DPRVTRLLTETRIHLLPSMNPDGY---ETAY-HRGSELVGWAEGRWTHQGIDLNHNFadlnTQLWyaeddglvpDTVPNH 449
Cdd:cd06226   52 DADATWLLDYTELHLVPQVNPDGRkiaETGLlWRKNTNTTPCPASSPTYGVDLNRNS----SFKW---------GGAGAG 118
                         90       100
                 ....*....|....*....|....*....
gi 228008326 450 HLPLPTYYTLPNATVAPETWAVIKWMKRI 478
Cdd:cd06226  119 GSACSETYRGPSAASEPETQAIENYVKQL 147
M14_CPB cd03871
Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase B subgroup; Peptidase M14 ...
299-426 1.58e-03

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


Pssm-ID: 349443 [Multi-domain]  Cd Length: 300  Bit Score: 41.28  E-value: 1.58e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 299 KQVNEQCPNITRIYSIGKSHQGLKLYVMEMsdhpGEHELGEPEVRYVAGMHGNEALGrelllllmQFLCHEFLRG----- 373
Cdd:cd03871   17 EQVASKNPDLVSRSQIGTTFEGRPIYLLKV----GKPGSNKKAIFMDCGFHAREWIS--------PAFCQWFVREavrty 84
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 228008326 374 --DPRVTRLLTETRIHLLPSMNPDGYETAYHRGSElvgWAEGRWTHQ-----GIDLNHNF 426
Cdd:cd03871   85 gkEKIMTKLLDRLDFYILPVLNIDGYVYTWTKNRM---WRKTRSPNAgssciGTDPNRNF 141
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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