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Conserved domains on  [gi|1475902778|ref|XP_026284972|]
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leukotriene A-4 hydrolase [Frankliniella occidentalis]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
leuko_A4_hydro super family cl37108
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
10-613 0e+00

leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive subset within the zinc metallopeptidase family M1 (pfam01433). The majority of the members of pfam01433 are aminopeptidases, but the sequences in this family for which the function is known are leukotriene A-4 hydrolase. A dual epoxide hydrolase and aminopeptidase activity at the same active site is indicated. The physiological substrate for aminopeptidase activity is not known.


The actual alignment was detected with superfamily member TIGR02411:

Pssm-ID: 274120 [Multi-domain]  Cd Length: 602  Bit Score: 792.82  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  10 DPTSFSRPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKVQstGQTLEYSLGSSIGTFG 89
Cdd:TIGR02411   1 DPSSLSNYKDFRTSHTDLNLSVDFTKRKLSGSVTFTLKSLTDNLNKLVLDTSYLDIQKVTIN--GLPADFAIGERKEPLG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  90 CSLTIQLPVEVPQG--LVLSVEYETSSSASALQWLSAEQTVGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAP 167
Cdd:TIGR02411  79 SPLTISLPIATSKNdeFVLNISFSTTPKCTALQWLNPEQTSGKKHPYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVESP 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 168 eaLVVLMSALQDEAgrslNSPRPGTKfhCFRQPVPIPTYLIAIAVGHLESRQIGPRSRVWSEKELVDRAAFEFD-QTETF 246
Cdd:TIGR02411 159 --LPVLMSGIRDGE----TSNDPGKY--LFKQKVPIPAYLIAIASGDLASAPIGPRSTVYSEPEQLEKCQYEFEnDTEKF 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 247 LQTAEQLCGPYVWGQYDLLVLPSSFPFGGMENPCITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGW 326
Cdd:TIGR02411 231 IKTAEDLIFPYEWGQYDLLVLPPSFPYGGMENPNLTFATPTLIAGDRSNVDVIAHELAHSWSGNLVTNCSWEHFWLNEGW 310
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 327 TVFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPLTCLVHDLRGVDPDDAFSSVPYEKGHTFLYYLEHQLGGP 406
Cdd:TIGR02411 311 TVYLERRIIGRLYGEKTRHFSALIGWGDLQESVKTLGETPEFTKLVVDLKDNDPDDAFSSVPYEKGFNFLFYLEQLLGGP 390
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 407 EAFEPFMKAYLDHFKFKSISTEDWKNFLYDFFP--GKHSVLNGIDWDSWLRKPGMPPHIPSYDTSYSDACTALADRWRKW 484
Cdd:TIGR02411 391 AEFDPFLRHYFKKFAYKSLDTYQFKDALYEYFKdkKKVDKLDAVDWETWLYSPGMPPVKPNFDTTLADECYALADRWVDA 470
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 485 SESP-PMPFNPADWGNLSSEQHVEVLAQLL---AGPALTPSKVATLGVTYNLASSQNAEIRFRWIRLGLKARWQPAIAPA 560
Cdd:TIGR02411 471 AKADdLSSFNAKDIKDFSSHQLVLFLETLTergGDWALPEGHIKRLGDIYNFAASKNAEVRFRWFRLAIQAKLEDEYPLL 550
                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1475902778 561 LQFVTEQGRMKYVRPIYRDLYDWeEARPHAISTYKQNRSSMMYVSAHTVAKDL 613
Cdd:TIGR02411 551 ADWLGTVGRMKFVRPGYRLLNAF-VDRDLAIRTFEKFKDSYHPICAMLVKKDL 602
 
Name Accession Description Interval E-value
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
10-613 0e+00

leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive subset within the zinc metallopeptidase family M1 (pfam01433). The majority of the members of pfam01433 are aminopeptidases, but the sequences in this family for which the function is known are leukotriene A-4 hydrolase. A dual epoxide hydrolase and aminopeptidase activity at the same active site is indicated. The physiological substrate for aminopeptidase activity is not known.


Pssm-ID: 274120 [Multi-domain]  Cd Length: 602  Bit Score: 792.82  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  10 DPTSFSRPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKVQstGQTLEYSLGSSIGTFG 89
Cdd:TIGR02411   1 DPSSLSNYKDFRTSHTDLNLSVDFTKRKLSGSVTFTLKSLTDNLNKLVLDTSYLDIQKVTIN--GLPADFAIGERKEPLG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  90 CSLTIQLPVEVPQG--LVLSVEYETSSSASALQWLSAEQTVGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAP 167
Cdd:TIGR02411  79 SPLTISLPIATSKNdeFVLNISFSTTPKCTALQWLNPEQTSGKKHPYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVESP 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 168 eaLVVLMSALQDEAgrslNSPRPGTKfhCFRQPVPIPTYLIAIAVGHLESRQIGPRSRVWSEKELVDRAAFEFD-QTETF 246
Cdd:TIGR02411 159 --LPVLMSGIRDGE----TSNDPGKY--LFKQKVPIPAYLIAIASGDLASAPIGPRSTVYSEPEQLEKCQYEFEnDTEKF 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 247 LQTAEQLCGPYVWGQYDLLVLPSSFPFGGMENPCITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGW 326
Cdd:TIGR02411 231 IKTAEDLIFPYEWGQYDLLVLPPSFPYGGMENPNLTFATPTLIAGDRSNVDVIAHELAHSWSGNLVTNCSWEHFWLNEGW 310
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 327 TVFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPLTCLVHDLRGVDPDDAFSSVPYEKGHTFLYYLEHQLGGP 406
Cdd:TIGR02411 311 TVYLERRIIGRLYGEKTRHFSALIGWGDLQESVKTLGETPEFTKLVVDLKDNDPDDAFSSVPYEKGFNFLFYLEQLLGGP 390
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 407 EAFEPFMKAYLDHFKFKSISTEDWKNFLYDFFP--GKHSVLNGIDWDSWLRKPGMPPHIPSYDTSYSDACTALADRWRKW 484
Cdd:TIGR02411 391 AEFDPFLRHYFKKFAYKSLDTYQFKDALYEYFKdkKKVDKLDAVDWETWLYSPGMPPVKPNFDTTLADECYALADRWVDA 470
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 485 SESP-PMPFNPADWGNLSSEQHVEVLAQLL---AGPALTPSKVATLGVTYNLASSQNAEIRFRWIRLGLKARWQPAIAPA 560
Cdd:TIGR02411 471 AKADdLSSFNAKDIKDFSSHQLVLFLETLTergGDWALPEGHIKRLGDIYNFAASKNAEVRFRWFRLAIQAKLEDEYPLL 550
                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1475902778 561 LQFVTEQGRMKYVRPIYRDLYDWeEARPHAISTYKQNRSSMMYVSAHTVAKDL 613
Cdd:TIGR02411 551 ADWLGTVGRMKFVRPGYRLLNAF-VDRDLAIRTFEKFKDSYHPICAMLVKKDL 602
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
10-454 0e+00

Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents the N-terminal catalytic domain of leukotriene A4 hydrolase (LTA4H; E.C. 3.3.2.6) and the close homolog cold-active aminopeptidase (Colwellia psychrerythraea-type peptidase; ColAP), both members of the aminopeptidase M1 family. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase is poorly understood while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals. It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives. The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase. Thermodynamic characterization using different biophysical methods shows that structurally distinct inhibitors of the LTA4H occupy different regions of the binding site; while some (RB202, ARM1 and SC57461A) bind to the hydrophobic hydrolase side, both bestatin and captopril are located at the hydrophilic peptidase side. LTB4H overexpression is associated with different pathological conditions and diseases such as cystic fibrosis, coronary heart disease, sepsis, shock, connective tissue disease, and chronic obstructive pulmonary disease. It is also overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well-known red wine polyphenolic compound with cancer chemopreventive activity.


Pssm-ID: 341062 [Multi-domain]  Cd Length: 442  Bit Score: 751.21  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  10 DPTSFSRPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKVQStGQTLEYSLGSSIGTFG 89
Cdd:cd09599     1 DPSSFSNYDEVRTTHLDLDLTVDFDKKTISGSATLTLEVLQDGADELVLDTRDLDISSVTVNG-GKELKFELGPRDPVLG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  90 CSLTIQLPVEVPQG--LVLSVEYETSSSASALQWLSAEQTVGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAP 167
Cdd:cd09599    80 SALTITLPSPLAKGdtFKVKIEYSTTPQATALQWLTPEQTAGKKHPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVP 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 168 EALVVLMSALQDEagrslNSPRPGTKFHCFRQPVPIPTYLIAIAVGHLESRQIGPRSRVWSEKELVDRAAFEFDQTETFL 247
Cdd:cd09599   160 KGLTALMSALRTG-----EKEEAGTGTYTFEQPVPIPSYLIAIAVGDLESREIGPRSGVWAEPSVVDAAAEEFADTEKFL 234
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 248 QTAEQLCGPYVWGQYDLLVLPSSFPFGGMENPCITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGWT 327
Cdd:cd09599   235 KAAEKLYGPYVWGRYDLLVLPPSFPYGGMENPCLTFATPTLIAGDRSLVDVIAHEIAHSWSGNLVTNANWEHFWLNEGFT 314
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 328 VFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPLTCLVHDLRGVDPDDAFSSVPYEKGHTFLYYLEhQLGGPE 407
Cdd:cd09599   315 VYLERRILERLYGEEYRQFEAILGWKDLQESIKEFGEDPPYTLLVPDLKGVDPDDAFSSVPYEKGFQFLYYLE-QLGGRE 393
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*...
gi 1475902778 408 AFEPFMKAYLDHFKFKSISTEDWKNFLYDFFP-GKHSVLNGIDWDSWL 454
Cdd:cd09599   394 VFDPFLRAYFKKFAFQSIDTEDFKDFLLEYFAeDKPEILDKIDWDAWL 441
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
16-460 4.27e-103

Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 325.06  E-value: 4.27e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  16 RPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKVQstGQTLEYSLGSSigtfgcSLTIQ 95
Cdd:COG0308    11 RPPGYDVTHYDLDLDLDPATTRLSGTATITFTATEAPLDSLVLDLKGLEVTSVTVD--GKPLDFTRDGE------RLTIT 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  96 LPVEVPQG--LVLSVEYET--SSSASALQWLSAEqtvGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEALV 171
Cdd:COG0308    83 LPKPLAPGetFTLEIEYSGkpSNGGEGLYRSGDP---PDGPPYLYTQCEPEGARRWFPCFDHPDDKATFTLTVTVPAGWV 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 172 VLMSALQDEAGRSLNsprpGTKFHCFRQPVPIPTYLIAIAVGHLESRQIGPRS----RVWSEKELVDRAAFEFDQTETFL 247
Cdd:COG0308   160 AVSNGNLVSETELGD----GRTTWHWADTQPIPTYLFALAAGDYAVVEDTFASgvplRVYVRPGLADKAKEAFESTKRML 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 248 QTAEQLCG-PYVWGQYDLLVLPSsFPFGGMENPCITFVTPTLLAGD-------KSLANVVAHEIAHSWTGNLVTNRTFED 319
Cdd:COG0308   236 DFFEELFGvPYPFDKYDQVAVPD-FNFGAMENQGLVTFGEKVLADEtatdadyERRESVIAHELAHQWFGNLVTCADWDD 314
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 320 FWLNEGWTVFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPltclVHDLRGVDPDDAFSSVPYEKGHTFLYYL 399
Cdd:COG0308   315 LWLNEGFATYMEQLFSEDLYGKDAADRIFVGALRSYAFAEDAGPNAHP----IRPDDYPEIENFFDGIVYEKGALVLHML 390
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1475902778 400 EHQLgGPEAFEPFMKAYLDHFKFKSISTEDWKNFLydffpGKHSvlnGID----WDSWLRKPGMP 460
Cdd:COG0308   391 RTLL-GDEAFRAGLRLYFARHAGGNATTEDFLAAL-----EEAS---GRDlsafFDQWLYQAGLP 446
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
237-453 1.57e-56

Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ widely in specificity, hydrolysing acidic, basic or neutral N-terminal residues. This family includes leukotriene-A4 hydrolase, this enzyme also has an aminopeptidase activity.


Pssm-ID: 426262 [Multi-domain]  Cd Length: 219  Bit Score: 190.19  E-value: 1.57e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 237 AFEFDQtETFLQTAEQLCGPYVWGQYDLLVLPSsFPFGGMENPCITFVTPTLLAGD---------KSLANVVAHEIAHSW 307
Cdd:pfam01433   2 ALEITV-KLLEFYEDYFNIPYPLPKYDLVALPD-FSAGAMENWGLITYRETLLLYDpgnsstsdkQRVASVIAHELAHQW 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 308 TGNLVTNRTFEDFWLNEGWTVFVERKIKGRVQGEAA--RQFCaiggLKELHETVERR--GSTDPLTCLVHDlrGVDPDDA 383
Cdd:pfam01433  80 FGNLVTMKWWDDLWLNEGFATYMEYLGTDALFPEWNiwEQFL----LDEVQNAMARDalDSSHPITQNVND--PSEIDDI 153
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 384 FSSVPYEKGHTFLYYLEHQLgGPEAFEPFMKAYLDHFKFKSISTEDWKNFLYDfFPGKHSVLNGidWDSW 453
Cdd:pfam01433 154 FDAIPYEKGASVLRMLETLL-GEEVFQKGLRSYLKKFQYGNATTEDLWDALSE-ASGPLDVDSF--MDTW 219
pepN PRK14015
aminopeptidase N; Provisional
22-329 9.81e-06

aminopeptidase N; Provisional


Pssm-ID: 237585 [Multi-domain]  Cd Length: 875  Bit Score: 48.59  E-value: 9.81e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  22 VTHIHLslDVDFKEKKLKGKADLTIDRR--SQETTQLVLDSRDLSISNVKVQstGQTL---EYSLGSSigtfgcSLTIQl 96
Cdd:PRK14015   21 IDTVDL--DFDLDPDKTRVTARLQVRRNpdAAHSAPLVLDGEDLELLSLALD--GQPLapsAYELDEE------GLTIE- 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  97 pvEVPQGLVLSVEYETSSSA-SALQWLsaeqtvgkqhpY-----LFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEAL 170
Cdd:PRK14015   90 --NLPDRFTLEIETEIDPEAnTALEGL-----------YrsggmFCTQCEAEGFRRITYFLDRPDVLARYTVRIEADKAK 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 171 V-VLMS--------ALQDeagrslnsprpGTKFHCFRQPVPIPTYLIAIAVGHLESRQ--IGPRS------RVWSEKELV 233
Cdd:PRK14015  157 YpVLLSngnlvesgELPD-----------GRHWATWEDPFPKPSYLFALVAGDLDVLEdtFTTRSgrevalEIYVEPGNL 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 234 DRAAFEFDQtetfLQTA----EQlcgpyVWG-QYDL----LVLPSSFPFGGMENpciT----FVTPTLLAG-----DKSL 295
Cdd:PRK14015  226 DKCDHAMDS----LKKSmkwdEE-----RFGlEYDLdifmIVAVDDFNMGAMEN---KglniFNSKYVLADpetatDADY 293
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|.
gi 1475902778 296 AN---VVAHEIAHSWTGNLVTNRtfeDfW----LNEGWTVF 329
Cdd:PRK14015  294 ERiesVIAHEYFHNWTGNRVTCR---D-WfqlsLKEGLTVF 330
 
Name Accession Description Interval E-value
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
10-613 0e+00

leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive subset within the zinc metallopeptidase family M1 (pfam01433). The majority of the members of pfam01433 are aminopeptidases, but the sequences in this family for which the function is known are leukotriene A-4 hydrolase. A dual epoxide hydrolase and aminopeptidase activity at the same active site is indicated. The physiological substrate for aminopeptidase activity is not known.


Pssm-ID: 274120 [Multi-domain]  Cd Length: 602  Bit Score: 792.82  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  10 DPTSFSRPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKVQstGQTLEYSLGSSIGTFG 89
Cdd:TIGR02411   1 DPSSLSNYKDFRTSHTDLNLSVDFTKRKLSGSVTFTLKSLTDNLNKLVLDTSYLDIQKVTIN--GLPADFAIGERKEPLG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  90 CSLTIQLPVEVPQG--LVLSVEYETSSSASALQWLSAEQTVGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAP 167
Cdd:TIGR02411  79 SPLTISLPIATSKNdeFVLNISFSTTPKCTALQWLNPEQTSGKKHPYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVESP 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 168 eaLVVLMSALQDEAgrslNSPRPGTKfhCFRQPVPIPTYLIAIAVGHLESRQIGPRSRVWSEKELVDRAAFEFD-QTETF 246
Cdd:TIGR02411 159 --LPVLMSGIRDGE----TSNDPGKY--LFKQKVPIPAYLIAIASGDLASAPIGPRSTVYSEPEQLEKCQYEFEnDTEKF 230
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 247 LQTAEQLCGPYVWGQYDLLVLPSSFPFGGMENPCITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGW 326
Cdd:TIGR02411 231 IKTAEDLIFPYEWGQYDLLVLPPSFPYGGMENPNLTFATPTLIAGDRSNVDVIAHELAHSWSGNLVTNCSWEHFWLNEGW 310
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 327 TVFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPLTCLVHDLRGVDPDDAFSSVPYEKGHTFLYYLEHQLGGP 406
Cdd:TIGR02411 311 TVYLERRIIGRLYGEKTRHFSALIGWGDLQESVKTLGETPEFTKLVVDLKDNDPDDAFSSVPYEKGFNFLFYLEQLLGGP 390
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 407 EAFEPFMKAYLDHFKFKSISTEDWKNFLYDFFP--GKHSVLNGIDWDSWLRKPGMPPHIPSYDTSYSDACTALADRWRKW 484
Cdd:TIGR02411 391 AEFDPFLRHYFKKFAYKSLDTYQFKDALYEYFKdkKKVDKLDAVDWETWLYSPGMPPVKPNFDTTLADECYALADRWVDA 470
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 485 SESP-PMPFNPADWGNLSSEQHVEVLAQLL---AGPALTPSKVATLGVTYNLASSQNAEIRFRWIRLGLKARWQPAIAPA 560
Cdd:TIGR02411 471 AKADdLSSFNAKDIKDFSSHQLVLFLETLTergGDWALPEGHIKRLGDIYNFAASKNAEVRFRWFRLAIQAKLEDEYPLL 550
                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1475902778 561 LQFVTEQGRMKYVRPIYRDLYDWeEARPHAISTYKQNRSSMMYVSAHTVAKDL 613
Cdd:TIGR02411 551 ADWLGTVGRMKFVRPGYRLLNAF-VDRDLAIRTFEKFKDSYHPICAMLVKKDL 602
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
10-454 0e+00

Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents the N-terminal catalytic domain of leukotriene A4 hydrolase (LTA4H; E.C. 3.3.2.6) and the close homolog cold-active aminopeptidase (Colwellia psychrerythraea-type peptidase; ColAP), both members of the aminopeptidase M1 family. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase is poorly understood while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals. It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives. The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase. Thermodynamic characterization using different biophysical methods shows that structurally distinct inhibitors of the LTA4H occupy different regions of the binding site; while some (RB202, ARM1 and SC57461A) bind to the hydrophobic hydrolase side, both bestatin and captopril are located at the hydrophilic peptidase side. LTB4H overexpression is associated with different pathological conditions and diseases such as cystic fibrosis, coronary heart disease, sepsis, shock, connective tissue disease, and chronic obstructive pulmonary disease. It is also overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well-known red wine polyphenolic compound with cancer chemopreventive activity.


Pssm-ID: 341062 [Multi-domain]  Cd Length: 442  Bit Score: 751.21  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  10 DPTSFSRPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKVQStGQTLEYSLGSSIGTFG 89
Cdd:cd09599     1 DPSSFSNYDEVRTTHLDLDLTVDFDKKTISGSATLTLEVLQDGADELVLDTRDLDISSVTVNG-GKELKFELGPRDPVLG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  90 CSLTIQLPVEVPQG--LVLSVEYETSSSASALQWLSAEQTVGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAP 167
Cdd:cd09599    80 SALTITLPSPLAKGdtFKVKIEYSTTPQATALQWLTPEQTAGKKHPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVP 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 168 EALVVLMSALQDEagrslNSPRPGTKFHCFRQPVPIPTYLIAIAVGHLESRQIGPRSRVWSEKELVDRAAFEFDQTETFL 247
Cdd:cd09599   160 KGLTALMSALRTG-----EKEEAGTGTYTFEQPVPIPSYLIAIAVGDLESREIGPRSGVWAEPSVVDAAAEEFADTEKFL 234
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 248 QTAEQLCGPYVWGQYDLLVLPSSFPFGGMENPCITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGWT 327
Cdd:cd09599   235 KAAEKLYGPYVWGRYDLLVLPPSFPYGGMENPCLTFATPTLIAGDRSLVDVIAHEIAHSWSGNLVTNANWEHFWLNEGFT 314
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 328 VFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPLTCLVHDLRGVDPDDAFSSVPYEKGHTFLYYLEhQLGGPE 407
Cdd:cd09599   315 VYLERRILERLYGEEYRQFEAILGWKDLQESIKEFGEDPPYTLLVPDLKGVDPDDAFSSVPYEKGFQFLYYLE-QLGGRE 393
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*...
gi 1475902778 408 AFEPFMKAYLDHFKFKSISTEDWKNFLYDFFP-GKHSVLNGIDWDSWL 454
Cdd:cd09599   394 VFDPFLRAYFKKFAFQSIDTEDFKDFLLEYFAeDKPEILDKIDWDAWL 441
M1 cd09595
Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 ...
23-436 1.08e-118

Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 hydrolase; The model represents the catalytic domains of M1 peptidase family members including aminopeptidase N (APN) and leukotriene A4 hydrolase (LTA4H). All peptidases in this family bind a single catalytic zinc ion which is tetrahedrally co-ordinated by three amino acid ligands and a water molecule that forms the nucleophile upon activation during catalysis. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and is present in a variety of human tissues and cell types. APN expression is dysregulated in many inflammatory diseases and is enhanced in numerous tumor cells, making it a lead target in the development of anti-cancer and anti-inflammatory drugs. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase in LTA4H is as yet unknown, while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals.


Pssm-ID: 341058 [Multi-domain]  Cd Length: 413  Bit Score: 359.07  E-value: 1.08e-118
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  23 THIHLSLDVDFKEKKLKGKADLTIDRrSQETTQLVLDSRDLSISNVKVQstGQTLEYSLGSSigTFGCSLTIQLPVEVPQ 102
Cdd:cd09595     1 YHYDLDLDVDFTTKTLNGTETLTVDA-SQVGRELVLDLVGLTIHSVSVN--GAAVDFGEREH--YDGEKLTIPGPKPPGQ 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 103 GLVLSVEYETSSSASALQWLSaEQTVGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEALVVL-MSALQDEa 181
Cdd:cd09595    76 TFTVRISFEAKPSKNLLGWLW-EQTAGKEKPYLFTQFEATHARRIFPCIDHPAVKATFTVTITTPKKDLLAsNGALVGE- 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 182 grslNSPRPGTKFHCFRQPVPIPTYLIAIAVGHLESRQIGPRSR------VWSEKELVDRAAFEFDQTETFLQTAEQ-LC 254
Cdd:cd09595   154 ----ETGANGRKTYRFEDTPPIPTYLVAVVVGDLEFKYVTVKSQprvglsVYSEPLQVDQAQYAFDATRAALAWFEDyFG 229
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 255 GPYVWGQYDLLVLPSsFPFGGMENPCITFVTPTLLA-------GDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGWT 327
Cdd:cd09595   230 GPYPLPKYDLLAVPD-FNSGAMENPGLITFRTTYLLrskvtdtGARSIENVIAHELAHQWFGNLVTMRWWNDLWLNEGFA 308
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 328 VFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPLTCLVHDlrgVDPDDAFSSVPYEKGHTFLYYLEhQLGGPE 407
Cdd:cd09595   309 VYYENRIMDATFGTSSRHLDQLSGSSDLNTEQLLEDSSPTSTPVRSP---ADPDVAYDGVTYAKGALVLRMLE-ELVGEE 384
                         410       420
                  ....*....|....*....|....*....
gi 1475902778 408 AFEPFMKAYLDHFKFKSISTEDWKNFLYD 436
Cdd:cd09595   385 AFDKGVQAYFNRHKFKNATTDDFIDALEE 413
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
16-460 4.27e-103

Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 325.06  E-value: 4.27e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  16 RPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKVQstGQTLEYSLGSSigtfgcSLTIQ 95
Cdd:COG0308    11 RPPGYDVTHYDLDLDLDPATTRLSGTATITFTATEAPLDSLVLDLKGLEVTSVTVD--GKPLDFTRDGE------RLTIT 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  96 LPVEVPQG--LVLSVEYET--SSSASALQWLSAEqtvGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEALV 171
Cdd:COG0308    83 LPKPLAPGetFTLEIEYSGkpSNGGEGLYRSGDP---PDGPPYLYTQCEPEGARRWFPCFDHPDDKATFTLTVTVPAGWV 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 172 VLMSALQDEAGRSLNsprpGTKFHCFRQPVPIPTYLIAIAVGHLESRQIGPRS----RVWSEKELVDRAAFEFDQTETFL 247
Cdd:COG0308   160 AVSNGNLVSETELGD----GRTTWHWADTQPIPTYLFALAAGDYAVVEDTFASgvplRVYVRPGLADKAKEAFESTKRML 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 248 QTAEQLCG-PYVWGQYDLLVLPSsFPFGGMENPCITFVTPTLLAGD-------KSLANVVAHEIAHSWTGNLVTNRTFED 319
Cdd:COG0308   236 DFFEELFGvPYPFDKYDQVAVPD-FNFGAMENQGLVTFGEKVLADEtatdadyERRESVIAHELAHQWFGNLVTCADWDD 314
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 320 FWLNEGWTVFVERKIKGRVQGEAARQFCAIGGLKELHETVERRGSTDPltclVHDLRGVDPDDAFSSVPYEKGHTFLYYL 399
Cdd:COG0308   315 LWLNEGFATYMEQLFSEDLYGKDAADRIFVGALRSYAFAEDAGPNAHP----IRPDDYPEIENFFDGIVYEKGALVLHML 390
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1475902778 400 EHQLgGPEAFEPFMKAYLDHFKFKSISTEDWKNFLydffpGKHSvlnGID----WDSWLRKPGMP 460
Cdd:COG0308   391 RTLL-GDEAFRAGLRLYFARHAGGNATTEDFLAAL-----EEAS---GRDlsafFDQWLYQAGLP 446
M1_APN_like cd09603
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly ...
22-434 2.05e-63

Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly bacterial and some archaeal M1 peptidases with smilarity to the catalytic domain of aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341066 [Multi-domain]  Cd Length: 410  Bit Score: 214.76  E-value: 2.05e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  22 VTHIHLSLDVDFKEKKLKGKADLTIdRRSQETTQLVLDSRDLSISNVKVQSTGQTLEYSLGSSigtfgcsLTIQLPVEVP 101
Cdd:cd09603     3 VLHYDLDLDYDPATKSLSGTATITF-RATQDLDSLQLDLVGLTVSSVTVDGVPAAFFTHDGDK-------LVITLPRPLA 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 102 QG--LVLSVEYETSSSASALQWLSAEQTVGKqHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEALVV-----LM 174
Cdd:cd09603    75 AGetFTVTVRYSGKPRPAGYPPGDGGGWEEG-DDGVWTAGQPEGASTWFPCNDHPDDKATYDITVTVPAGLTVvsngrLV 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 175 SALQDEAGRslnsprpgTKFHcFRQPVPIPTYLIAIAVGHLESRQIGPRSRV----WSEKELVDRAAFEFDQTETFLQTA 250
Cdd:cd09603   154 STTTNGGGT--------TTWH-WKMDYPIATYLVTLAVGRYAVVEDGSGGGIplryYVPPGDAAKAKASFARTPEMLDFF 224
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 251 EQLCGPYVWGQYDLLVLPSSFpfGGMENPCITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGWTVFV 330
Cdd:cd09603   225 EELFGPYPFEKYGQVVVPDLG--GGMEHQTATTYGNNFLNGDRGSERLIAHELAHQWFGDSVTCADWADIWLNEGFATYA 302
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 331 E----RKIKGRvqgEAARQFcaiggLKELHETVERRGSTDPltclvhdlRGVDPDDAFSSVPYEKGHTFLYYLEHQLgGP 406
Cdd:cd09603   303 EwlwsEHKGGA---DAYRAY-----LAGQRQDYLNADPGPG--------RPPDPDDLFDRDVYQKGALVLHMLRNLL-GD 365
                         410       420
                  ....*....|....*....|....*...
gi 1475902778 407 EAFEPFMKAYLDHFKFKSISTEDWKNFL 434
Cdd:cd09603   366 EAFFAALRAYLARYAHGNVTTEDFIAAA 393
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
237-453 1.57e-56

Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ widely in specificity, hydrolysing acidic, basic or neutral N-terminal residues. This family includes leukotriene-A4 hydrolase, this enzyme also has an aminopeptidase activity.


Pssm-ID: 426262 [Multi-domain]  Cd Length: 219  Bit Score: 190.19  E-value: 1.57e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 237 AFEFDQtETFLQTAEQLCGPYVWGQYDLLVLPSsFPFGGMENPCITFVTPTLLAGD---------KSLANVVAHEIAHSW 307
Cdd:pfam01433   2 ALEITV-KLLEFYEDYFNIPYPLPKYDLVALPD-FSAGAMENWGLITYRETLLLYDpgnsstsdkQRVASVIAHELAHQW 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 308 TGNLVTNRTFEDFWLNEGWTVFVERKIKGRVQGEAA--RQFCaiggLKELHETVERR--GSTDPLTCLVHDlrGVDPDDA 383
Cdd:pfam01433  80 FGNLVTMKWWDDLWLNEGFATYMEYLGTDALFPEWNiwEQFL----LDEVQNAMARDalDSSHPITQNVND--PSEIDDI 153
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 384 FSSVPYEKGHTFLYYLEHQLgGPEAFEPFMKAYLDHFKFKSISTEDWKNFLYDfFPGKHSVLNGidWDSW 453
Cdd:pfam01433 154 FDAIPYEKGASVLRMLETLL-GEEVFQKGLRSYLKKFQYGNATTEDLWDALSE-ASGPLDVDSF--MDTW 219
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
23-455 4.35e-56

Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), aminopeptidase Q (APQ), tricorn interacting factor F3, and endoplasmic reticulum aminopeptidase 1 (ERAP1); This M1 peptidase family includes eukaryotic and bacterial members: the catalytic domains of aminopeptidase N (APN), aminopeptidase Q (APQ, laeverin), endoplasmic reticulum aminopeptidase 1 (ERAP1) as well as tricorn interacting factor F3. Aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease, preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is considered a marker of differentiation since it is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. ERAP1, also known as endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP), adipocyte derived leucine aminopeptidase (A-LAP), or aminopeptidase regulating tumor necrosis factor receptor I (THFRI) shedding (ARTS-1), associates with the closely related ER aminopeptidase ERAP2, for the final trimming of peptides within the ER for presentation by MHC class I molecules. ERAP1 is associated with ankylosing spondylitis (AS), an inflammatory arthritis that predominantly affects the spine. ERAP1 also aids in the shedding of membrane-bound cytokine receptors. The tricorn interacting factor F3, together with factors F1 and F2, degrades the tricorn protease products, producing free amino acids, thus completing the proteasomal degradation pathway. F3 is homologous to F2, but not F1, and shows a strong preference for glutamate in the P1' position. APQ, also known as laeverin, is specifically expressed in human embryo-derived extravillous trophoblasts (EVTs) that invade the uterus during early placentation. It cleaves the N-terminal amino acid of various peptides such as angiotensin III, endokinin C, and kisspeptin-10, all expressed in the placenta in large quantities. APN is a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs are also putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341064 [Multi-domain]  Cd Length: 442  Bit Score: 195.88  E-value: 4.35e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  23 THIHLSLDVDFKEKKLKGKADLTIDRRsQETTQLVLDSRDLSISNVKVQSTGQTLEYSLGSSIGTFGCSLTIQLPVEVPQ 102
Cdd:cd09601     1 LHYDLTLTPDLENFTFSGSVTITLEVL-EPTDTIVLHAKDLTITSASLTLKGGSGIIEVTVVTDEETEFLTITLDETLPP 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 103 G--LVLSVEY--ETSSSASALQWLSAEQTVGKQHPYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEALVVL--MSA 176
Cdd:cd09601    80 GenYTLSIEFtgKLNDDLRGFYRSSYTDEDGETRYLAATQFEPTDARRAFPCFDEPAFKATFDITITHPKGYTALsnMPP 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 177 LQDEagrslnSPRPGTKFHCFRQPVPIPTYLIAIAVGHLESRQI----GPRSRVWSEKELVDRAAFEFDQTETFLQTAEQ 252
Cdd:cd09601   160 VEST------ELEDGWKTTTFETTPPMSTYLVAFVVGDFEYIESttksGVPVRVYARPGKIEQGDFALEVAPKILDFYED 233
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 253 LCG-PYVWGQYDLLVLPSsFPFGGMENP-CITFVTPTLLAGDKS--------LANVVAHEIAHSWTGNLVTNRTFEDFWL 322
Cdd:cd09601   234 YFGiPYPLPKLDLVAIPD-FAAGAMENWgLITYRETALLYDPKTssasdkqrVAEVIAHELAHQWFGNLVTMKWWDDLWL 312
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 323 NEGWTVFVERKIKGRVQGE--AARQFcaigglkeLHETVER------RGSTDPLTCLVHDLRgvDPDDAFSSVPYEKGHT 394
Cdd:cd09601   313 NEGFATYMEYLAVDKLFPEwnMWDQF--------VVDELQSaleldsLASSHPIEVPVESPS--EISEIFDAISYSKGAS 382
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1475902778 395 FLYYLEHqLGGPEAFEPFMKAYLDHFKFKSISTEDwknfLYDFFPGKHSVLNGID----WDSWLR 455
Cdd:cd09601   383 VLRMLEN-FLGEEVFRKGLRKYLKKHAYGNATTDD----LWEALQEASGESKPLDvkeiMDSWTL 442
M1_APN cd09602
Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the ...
16-453 1.59e-44

Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the catalytic domain of bacterial and eukaryotic aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341065 [Multi-domain]  Cd Length: 440  Bit Score: 164.22  E-value: 1.59e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  16 RPELVAVTHIHLSLDVDFKEKKLKGKADLTIDRRSQeTTQLVLDSRDLSISNVKVQstGQTLEYSLGSsiGTFgcsltIQ 95
Cdd:cd09602     9 RAALISVVSYDLDLDLTEGAETFRGTVTIRFTLREP-GASLFLDFRGGEVKSVTLN--GRPLDPSAFD--GER-----IT 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  96 LPVEVPQGL-VLSVEYET--SSSASALQWlSAEQTVGKQhpYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEALVV 172
Cdd:cd09602    79 LPGLLKAGEnTVVVEFTApySSDGEGLHR-FVDPADGET--YLYTLFEPDDARRVFPCFDQPDLKATFTLTVTAPADWTV 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 173 LMSALQDEAgrslnSPRPGTKFHCFRQPVPIPTYLIAIAVG--HLESRQIGPRS-RVWSEKELvdrAAFEFDQTETFLQT 249
Cdd:cd09602   156 ISNGPETST-----EEAGGRKRWRFAETPPLSTYLFAFVAGpyHRVEDEHDGIPlGLYCRESL---AEYERDADEIFEVT 227
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 250 A------EQLCG-PYVWGQYDLLVLPSsFPFGGMENP-CITF---------VTPTLLAGdksLANVVAHEIAHSWTGNLV 312
Cdd:cd09602   228 KqgldfyEDYFGiPYPFGKYDQVFVPE-FNFGAMENPgAVTFresylfreePTRAQRLR---RANTILHEMAHMWFGDLV 303
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 313 TNRTFEDFWLNEGWTVFVERKIKGRVQG--EAARQFCAigGLKELHETVERRGSTDPLTCLVHDLrgvdpDDAFS---SV 387
Cdd:cd09602   304 TMKWWDDLWLNESFADFMAAKALAEATPftDAWLTFLL--RRKPWAYRADQLPTTHPIAQDVPDL-----EAAGSnfdGI 376
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1475902778 388 PYEKGHTFLYYLEHQLgGPEAFEPFMKAYLDHFKFksiSTEDWKNFLydffpgkhSVLN---GIDWDSW 453
Cdd:cd09602   377 TYAKGASVLKQLVALV-GEEAFRAGLREYFKKHAY---GNATLDDLI--------AALDeasGRDLSAW 433
Leuk-A4-hydro_C pfam09127
Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of ...
500-613 1.90e-44

Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of two layers of parallel alpha-helices, five in the inner layer and four in the outer, arranged in an antiparallel manner, with perpendicular loops containing short helical segments on top. They are required for the formation of a deep cleft harbouring the catalytic Zn2+ site in Leukotriene A4 hydrolase.


Pssm-ID: 462686  Cd Length: 112  Bit Score: 153.80  E-value: 1.90e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 500 LSSEQHVEVLAQLLAGPALTPSKVATLGVTYNLASSQNAEIRFRWIRLGLKARWQPAIAPALQFVTEQGRMKYVRPIYRD 579
Cdd:pfam09127   1 WSSNQKVVFLERLLEFSPLSPEQLKALDEVYKLSESKNAEIRFRWLRLALKAKYEPAYPEVAEFLGEVGRMKFVRPLYRA 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1475902778 580 LYDWEeaRPHAISTYKQNRSSMMYVSAHTVAKDL 613
Cdd:pfam09127  81 LNKVD--RDLAVETFEKNKDFYHPICRAMVEKDL 112
M1_APN_like cd09604
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains ...
255-434 9.17e-27

Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains bacterial M1 peptidases with smilarity to the catalytic domain of aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341067 [Multi-domain]  Cd Length: 440  Bit Score: 113.52  E-value: 9.17e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 255 GPYVWGQYDllVLPSSFPFGGMENPCITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTNRTFEDFWLNEGWTVFVERKI 334
Cdd:cd09604   255 GPYPYPELD--VVQGPFGGGGMEYPGLVFIGSRLYDPKRSLEGVVVHEIAHQWFYGIVGNDERREPWLDEGLATYAESLY 332
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 335 KGRVQGEAARQFcaigGLKELHETVERRGSTDPLTCLVHDLRgvDPDDAFSSVpYEKGHTFLYYLEHQLgGPEAFEPFMK 414
Cdd:cd09604   333 LEEKYGKEAADE----LLGRRYYRAYARGPGGPINLPLDTFP--DGSYYSNAV-YSKGALFLEELREEL-GDEAFDKALR 404
                         170       180
                  ....*....|....*....|
gi 1475902778 415 AYLDHFKFKSISTEDWKNFL 434
Cdd:cd09604   405 EYYRRYKFKHPTPEDFFRTA 424
Peptidase_M1_N pfam17900
Peptidase M1 N-terminal domain; This domain is found at the N-terminus of aminopeptidases from ...
23-207 3.72e-20

Peptidase M1 N-terminal domain; This domain is found at the N-terminus of aminopeptidases from the M1 family.


Pssm-ID: 465557 [Multi-domain]  Cd Length: 186  Bit Score: 88.56  E-value: 3.72e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  23 THIHLSLDVDFKEKKLKGKADLTIdRRSQETTQLVLDSRDLSISNVKVQSTGQTLEYSLGSSIGTF-GCSLTIQLP--VE 99
Cdd:pfam17900   3 EHYDLDLKIDLKNFTFSGSVTITL-QLNNATNVIVLHASDLTIRSISLSDEVTSDGVPADFTEDQKdGEKLTIVLPetLN 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 100 VPQGLVLSVEYET--SSSASALQWLSAEQTVGKQHpYLFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEALVVL--MS 175
Cdd:pfam17900  82 QTGPYTLEIEYSGelNDSMTGFYRSTYTDNGEKKV-LVTTQFEPTDARSAFPCFDEPSVKATFTISIIHPKDYTALsnMP 160
                         170       180       190
                  ....*....|....*....|....*....|..
gi 1475902778 176 ALQDEAGrslnspRPGTKFHCFRQPVPIPTYL 207
Cdd:pfam17900 161 VIASEPL------ENGWVITTFEQTPKMSTYL 186
M1_APN cd09600
Peptidase M1 family, including aminopeptidase N catalytic domain; This model represents the ...
22-430 5.63e-20

Peptidase M1 family, including aminopeptidase N catalytic domain; This model represents the catalytic domain of aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. It includes bacterial-type alanyl aminopeptidases as well as PfA-M1 aminopeptidase (Plasmodium falciparum-type). APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.


Pssm-ID: 341063 [Multi-domain]  Cd Length: 434  Bit Score: 92.96  E-value: 5.63e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  22 VTHIHLSLDVDFKEKKLKgkADLTIDRR--SQETTQLVLDSRDLSISNVKVQstGQTL---EYSLGSSigtfgcSLTIql 96
Cdd:cd09600     9 IDHVDLDFDLDDDETIVT--SRLRVRRNpdSGEGAPLVLDGEDLELLSVKID--GKPLspsDYTLDEE------GLTI-- 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  97 pVEVPQGLVLSVEYETSSSA-SALQWLsaeqtvgkqhpY-----LFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEAL 170
Cdd:cd09600    77 -KNVPDRFVLEIEVRINPAAnTSLEGL-----------YksggiLCTQCEAEGFRRITYFPDRPDVMSKFTVTIEADKEK 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 171 V-VLMS-----ALQDEAGrslnsprpGTKFHCFRQPVPIPTYLIAIAVGHLESR--QIGPRS------RVWSEKELVDRA 236
Cdd:cd09600   145 YpVLLSngnliEEGELPN--------GRHFAVWEDPFPKPSYLFALVAGDLGSVedTFTTKSgrkvklRIYVEPGNEDKC 216
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 237 AFEFDqtetFLQTA----EQlcgpyVWG-QYDL----LVLPSSFPFGGMENP-CITFVTPTLLAG-----DKSLAN---V 298
Cdd:cd09600   217 HHAME----SLKKAmkwdEE-----RFGlEYDLdlfnIVAVDDFNMGAMENKgLNIFNSKYVLADpetatDADYERiesV 287
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 299 VAHEIAHSWTGNLVTNRTFEDFWLNEGWTVFverkikgRVQgeaarQFCAigglkELHE-TVERRGStdpltclVHDLRG 377
Cdd:cd09600   288 IAHEYFHNWTGNRVTCRDWFQLSLKEGLTVF-------RDQ-----EFSA-----DMNSrAVKRIED-------VRRLRS 343
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 378 VD-PDDA-------------------FSSVpYEKG-------HTFLyylehqlgGPEAFEPFMKAYLDHFKFKSISTEDW 430
Cdd:cd09600   344 AQfPEDAgpmahpirpdsyieinnfyTVTV-YEKGaevirmlHTLL--------GEEGFRKGMDLYFERHDGQAVTCEDF 414
GluZincin cd09594
Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, ...
256-334 2.51e-18

Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, M2, M3, M4, M13, M32 and M36 (fungalysins); The Gluzincin family (thermolysin-like peptidases or TLPs) includes several zinc-dependent metallopeptidases such as M1, M2, M3, M4, M13, M32, M36 peptidases (MEROPS classification), which contain the HEXXH motif as part of their active site. Peptidases in this family bind a single catalytic zinc ion which is tetrahedrally co-ordinated by three amino acid ligands and a water molecule that forms the nucleophile on activation during catalysis. The M1 family includes aminopeptidase N (APN) and leukotriene A4 hydrolase (LTA4H). APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and is present in a variety of human tissues and cell types. LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity such that the two activities occupy different, but overlapping sites. The M3_like peptidases include the M2_ACE, M3 or neurolysin-like family (subfamilies M3B_PepF and M3A) and M32_Taq peptidases. The M2 peptidase angiotensin converting enzyme (ACE, EC 3.4.15.1) catalyzes the conversion of decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II. ACE is a key component of the renin-angiotensin system that regulates blood pressure, thus ACE inhibitors are important for the treatment of hypertension. M3A includes thimet oligopeptidase (TOP; endopeptidase 3.4.24.15), neurolysin (3.4.24.16), and the mitochondrial intermediate peptidase; and M3B includes oligopeptidase F. The M32 family includes eukaryotic enzymes from protozoa Trypanosoma cruzi, a causative agent of Chagas' disease, and from Leishmania major, a parasite that causes leishmaniasis, making these enzymes attractive targets for drug development. The M4 family includes secreted protease thermolysin (EC 3.4.24.27), pseudolysin, aureolysin, and neutral protease as well as bacillolysin (EC 3.4.24.28) that degrade extracellular proteins and peptides for bacterial nutrition, especially prior to sporulation. Thermolysin is widely used as a nonspecific protease to obtain fragments for peptide sequencing as well as in production of the artificial sweetener aspartame. The M13 family includes neprilysin (EC 3.4.24.11) and endothelin-converting enzyme I (ECE-1, EC 3.4.24.71), which fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity and are prime therapeutic targets for selective inhibition. The peptidase M36 fungalysin family includes endopeptidases from pathogenic fungi. Fungalysin hydrolyzes extracellular matrix proteins such as elastin and keratin. Aspergillus fumigatus causes the pulmonary disease aspergillosis by invading the lungs of immuno-compromised animals and secreting fungalysin that possibly breaks down proteinaceous structural barriers.


Pssm-ID: 341057 [Multi-domain]  Cd Length: 105  Bit Score: 80.61  E-value: 2.51e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 256 PYVWGQYDLLVLPS---SFPFGGMENP-CITFVTPTLLAGDKSLANVVAHEIAHSWTGNLVTN-RTFEDFWLNEGWTVFV 330
Cdd:cd09594    22 YPVSPIYSLLVYPAyveVNAYNAMWIPsTNIFYGAGILDTLSGTIDVLAHELTHAFTGQFSNLmYSWSSGWLNEGISDYF 101

                  ....
gi 1475902778 331 ERKI 334
Cdd:cd09594   102 GGLV 105
M1_like_TAF2 cd09839
TATA binding protein (TBP) associated factor 2; This family includes TATA binding protein (TBP) ...
22-322 1.37e-11

TATA binding protein (TBP) associated factor 2; This family includes TATA binding protein (TBP) associated factor 2 (TAF2, TBP-associated factor TAFII150, transcription initiation factor TFIID subunit 2, RNA polymerase II TBP-associated factor subunit B), and has homology to the M1 gluzincin family. TAF2 is part of the TFIID multidomain subunit complex essential for transcription of most protein-encoded genes by RNA polymerase II. TAF2 is known to interact with the initiator element (Inr) found at the transcription start site of many genes, thus possibly playing a key role in promoter binding as well as start-site selection. Image analysis has shown TAF2 to form a complex with TAF1 and TBP, inferring its role in promoter recognition. Peptidases in the M1 family bind a single catalytic zinc ion which is tetrahedrally co-ordinated by three amino acid ligands and a water molecule that forms the nucleophile on activation during catalysis. TAF2, however, lacks these active site residues.


Pssm-ID: 341074 [Multi-domain]  Cd Length: 531  Bit Score: 67.25  E-value: 1.37e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  22 VTHIHLSLDVDFKEKKLKGKADLTIDRRSQETTQLVLDSRDLSISNVKV-------------------QSTGQTLEYSLG 82
Cdd:cd09839     1 VAHQKVELDVDFANRSIIGYTEITIVPTSPDLRTIRLNCRQCKIKSVTVngveaeftyndplqnldlsDNTDVNAHHELK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  83 SSIGTFGCS-------LTIQLPVEV---PQG----------------------LVLSVEYETSSSASALQWLSAEQTVGK 130
Cdd:cd09839    81 RKLAAALAEpdegneeLVISLPPSVkieLQDpnsastqattsspdtsedeftpLTIRIEYSLKNPRDGLHFVGPDEGGDK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 131 QHPYLFSQCQAIH--ARSMVPCQDTPSSKITYSAEISAPEAL-----VVLMSALQDEAGRSLNSPRP------------- 190
Cdd:cd09839   161 RYPHVYTTNSPLPgsARCWFPCVDSLWERCTWELEITVPRTLgdagrPPLAGSKEDEDDDDLTEEDKelemvvvcsgdlv 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 191 GTKFH---------CFRQPVPIPTYLIAIAVGHLESRQIGPRSRVWSEKELVDRA----AFEFDQTET-------FLQTA 250
Cdd:cd09839   241 EQVVHpedpskktfSFSLSNPTSAQHIGFAVGPFEIVPLPEFRESEEDDKLGSSAvevtGFCLPGRLEelrntcsFLHKA 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 251 ----EQLCGPYVWGQYDLLVLPS----SFPFGGMenpciTFVTPTLLAGDKSL------ANVVAHEIAHSWTGNLVTNRT 316
Cdd:cd09839   321 mdffEEEYGSYPFSSYKQVFVDDlpedVSSFASL-----SICSSRLLYPPDIIdqayetRRKLAHALASQWFGINIIPKT 395

                  ....*.
gi 1475902778 317 FEDFWL 322
Cdd:cd09839   396 WSDTWL 401
pepN PRK14015
aminopeptidase N; Provisional
22-329 9.81e-06

aminopeptidase N; Provisional


Pssm-ID: 237585 [Multi-domain]  Cd Length: 875  Bit Score: 48.59  E-value: 9.81e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  22 VTHIHLslDVDFKEKKLKGKADLTIDRR--SQETTQLVLDSRDLSISNVKVQstGQTL---EYSLGSSigtfgcSLTIQl 96
Cdd:PRK14015   21 IDTVDL--DFDLDPDKTRVTARLQVRRNpdAAHSAPLVLDGEDLELLSLALD--GQPLapsAYELDEE------GLTIE- 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778  97 pvEVPQGLVLSVEYETSSSA-SALQWLsaeqtvgkqhpY-----LFSQCQAIHARSMVPCQDTPSSKITYSAEISAPEAL 170
Cdd:PRK14015   90 --NLPDRFTLEIETEIDPEAnTALEGL-----------YrsggmFCTQCEAEGFRRITYFLDRPDVLARYTVRIEADKAK 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 171 V-VLMS--------ALQDeagrslnsprpGTKFHCFRQPVPIPTYLIAIAVGHLESRQ--IGPRS------RVWSEKELV 233
Cdd:PRK14015  157 YpVLLSngnlvesgELPD-----------GRHWATWEDPFPKPSYLFALVAGDLDVLEdtFTTRSgrevalEIYVEPGNL 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475902778 234 DRAAFEFDQtetfLQTA----EQlcgpyVWG-QYDL----LVLPSSFPFGGMENpciT----FVTPTLLAG-----DKSL 295
Cdd:PRK14015  226 DKCDHAMDS----LKKSmkwdEE-----RFGlEYDLdifmIVAVDDFNMGAMEN---KglniFNSKYVLADpetatDADY 293
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|.
gi 1475902778 296 AN---VVAHEIAHSWTGNLVTNRtfeDfW----LNEGWTVF 329
Cdd:PRK14015  294 ERiesVIAHEYFHNWTGNRVTCR---D-WfqlsLKEGLTVF 330
 
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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