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Conserved domains on  [gi|755493701|ref|XP_011246196|]
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aminopeptidase RNPEPL1 isoform X2 [Mus musculus]

Protein Classification

M1 family metallopeptidase( domain architecture ID 10176143)

M1 family metallopeptidase is a zinc-dependent metallopeptidase that functions as an aminopeptidase and contains an HEXXH motif as part of its active site; such as aminopeptidase B that selectively removes arginine and/or lysine residues from the N-terminus of peptide substrates

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
18-358 1.60e-161

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: 467.71  E-value: 1.60e-161
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  18 PPAPQIWWLDPELTYGNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQVLMSA--TQSVYVEEEGLYHFH 95
Cdd:cd09599  106 PQATALQWLTPEQTAGKKHPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALMSAlrTGEKEEAGTGTYTFE 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  96 MEHPVPAYLVALVAGDLKPADIGPRSRVWAEPCLLPtATSKLSGAVEQWLSAAERLYGPYMWGRYDIVFLPPSFPIVAME 175
Cdd:cd09599  186 QPVPIPSYLIAIAVGDLESREIGPRSGVWAEPSVVD-AAAEEFADTEKFLKAAEKLYGPYVWGRYDLLVLPPSFPYGGME 264
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 176 NPCLTFIISSILESDEFLVIDVIHEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAAFTCLETAFRLDALHR 255
Cdd:cd09599  265 NPCLTFATPTLIAGDRSLVDVIAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLERRILERLYGEEYRQFEAILGWKDLQE 344
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 256 QMRLLGEDSPvSKLQVKLEPGVNPSHLMNLFTYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSFLS 335
Cdd:cd09599  345 SIKEFGEDPP-YTLLVPDLKGVDPDDAFSSVPYEKGFQFLYYLEQL-GGREVFDPFLRAYFKKFAFQSIDTEDFKDFLLE 422
                        330       340
                 ....*....|....*....|...
gi 755493701 336 FFPELKeqsVDCRAGLEFERWLN 358
Cdd:cd09599  423 YFAEDK---PEILDKIDWDAWLY 442
Leuk-A4-hydro_C pfam09127
Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of ...
406-519 3.48e-37

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: 133.38  E-value: 3.48e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  406 WRTFQTALFLDRLLDGSPLPQEVVMSLSKCYSsLLDSMNAEIRIRWLQIVVRNDYYPDLHRVRRFLESQMSRMYTIPLYE 485
Cdd:pfam09127   1 WSSNQKVVFLERLLEFSPLSPEQLKALDEVYK-LSESKNAEIRFRWLRLALKAKYEPAYPEVAEFLGEVGRMKFVRPLYR 79
                          90       100       110
                  ....*....|....*....|....*....|....
gi 755493701  486 DLCTgALKSFALEVFYQTQGRLHPNLRRTIQQIL 519
Cdd:pfam09127  80 ALNK-VDRDLAVETFEKNKDFYHPICRAMVEKDL 112
 
Name Accession Description Interval E-value
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
18-358 1.60e-161

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: 467.71  E-value: 1.60e-161
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  18 PPAPQIWWLDPELTYGNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQVLMSA--TQSVYVEEEGLYHFH 95
Cdd:cd09599  106 PQATALQWLTPEQTAGKKHPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALMSAlrTGEKEEAGTGTYTFE 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  96 MEHPVPAYLVALVAGDLKPADIGPRSRVWAEPCLLPtATSKLSGAVEQWLSAAERLYGPYMWGRYDIVFLPPSFPIVAME 175
Cdd:cd09599  186 QPVPIPSYLIAIAVGDLESREIGPRSGVWAEPSVVD-AAAEEFADTEKFLKAAEKLYGPYVWGRYDLLVLPPSFPYGGME 264
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 176 NPCLTFIISSILESDEFLVIDVIHEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAAFTCLETAFRLDALHR 255
Cdd:cd09599  265 NPCLTFATPTLIAGDRSLVDVIAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLERRILERLYGEEYRQFEAILGWKDLQE 344
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 256 QMRLLGEDSPvSKLQVKLEPGVNPSHLMNLFTYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSFLS 335
Cdd:cd09599  345 SIKEFGEDPP-YTLLVPDLKGVDPDDAFSSVPYEKGFQFLYYLEQL-GGREVFDPFLRAYFKKFAFQSIDTEDFKDFLLE 422
                        330       340
                 ....*....|....*....|...
gi 755493701 336 FFPELKeqsVDCRAGLEFERWLN 358
Cdd:cd09599  423 YFAEDK---PEILDKIDWDAWLY 442
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
25-519 2.05e-123

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: 376.04  E-value: 2.05e-123
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701   25 WLDPELTYGNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLgvQVLMSATQ-SVYVEEEGLYHFHMEHPVPAY 103
Cdd:TIGR02411 112 WLNPEQTSGKKHPYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVESPL--PVLMSGIRdGETSNDPGKYLFKQKVPIPAY 189
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  104 LVALVAGDLKPADIGPRSRVWAEPCLLPTATSKLSGAVEQWLSAAERLYGPYMWGRYDIVFLPPSFPIVAMENPCLTFII 183
Cdd:TIGR02411 190 LIAIASGDLASAPIGPRSTVYSEPEQLEKCQYEFENDTEKFIKTAEDLIFPYEWGQYDLLVLPPSFPYGGMENPNLTFAT 269
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  184 SSILESDEFLViDVI-HEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAAFTCLETAFRLDALHRQMRLLGE 262
Cdd:TIGR02411 270 PTLIAGDRSNV-DVIaHELAHSWSGNLVTNCSWEHFWLNEGWTVYLERRIIGRLYGEKTRHFSALIGWGDLQESVKTLGE 348
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  263 DSPVSKLQVKLEPGvNPSHLMNLFTYEKGYCFVYYLSQLCGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSFLSFFPELKE 342
Cdd:TIGR02411 349 TPEFTKLVVDLKDN-DPDDAFSSVPYEKGFNFLFYLEQLLGGPAEFDPFLRHYFKKFAYKSLDTYQFKDALYEYFKDKKK 427
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  343 qsVDCRAGLEFERWLNATGPPLAEPDLSqgSSLTRPVEALFQLWTAEPLEQAAASASAIDISKWRTFQTALFLDRLL--- 419
Cdd:TIGR02411 428 --VDKLDAVDWETWLYSPGMPPVKPNFD--TTLADECYALADRWVDAAKADDLSSFNAKDIKDFSSHQLVLFLETLTerg 503
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  420 DGSPLPQEVVMSLSKCYsSLLDSMNAEIRIRWLQIVVRNDYYPDLHRVRRFLESQmSRM-YTIPLYEDLCTGALKSFALE 498
Cdd:TIGR02411 504 GDWALPEGHIKRLGDIY-NFAASKNAEVRFRWFRLAIQAKLEDEYPLLADWLGTV-GRMkFVRPGYRLLNAFVDRDLAIR 581
                         490       500
                  ....*....|....*....|.
gi 755493701  499 VFYQTQGRLHPNLRRTIQQIL 519
Cdd:TIGR02411 582 TFEKFKDSYHPICAMLVKKDL 602
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
33-370 2.97e-64

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 221.06  E-value: 2.97e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  33 GNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQVLMSAT-QSVYVEEEGL--YHFHMEHPVPAYLVALVA 109
Cdd:COG0308  117 PDGPPYLYTQCEPEGARRWFPCFDHPDDKATFTLTVTVPAGWVAVSNGNlVSETELGDGRttWHWADTQPIPTYLFALAA 196
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 110 GDL-----KPADiGPRSRVWAEPCLLPTATSKLsGAVEQWLSAAERLYG-PYMWGRYDIVFLPpSFPIVAMENPCLTFII 183
Cdd:COG0308  197 GDYavvedTFAS-GVPLRVYVRPGLADKAKEAF-ESTKRMLDFFEELFGvPYPFDKYDQVAVP-DFNFGAMENQGLVTFG 273
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 184 SSIL----------ESDEFLVIdviHEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAaftclETAFRLDAL 253
Cdd:COG0308  274 EKVLadetatdadyERRESVIA---HELAHQWFGNLVTCADWDDLWLNEGFATYMEQLFSEDLYGK-----DAADRIFVG 345
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 254 HRQMRLLGEDSPVSKLQVKLEPGVNPSHLMNLFTYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSF 333
Cdd:COG0308  346 ALRSYAFAEDAGPNAHPIRPDDYPEIENFFDGIVYEKGALVLHMLRTL-LGDEAFRAGLRLYFARHAGGNATTEDFLAAL 424
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....
gi 755493701 334 -------LSFFpelkeqsvdcragleFERWLNATGPPLAEPDLS 370
Cdd:COG0308  425 eeasgrdLSAF---------------FDQWLYQAGLPTLEVEYE 453
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
148-333 2.89e-42

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: 151.29  E-value: 2.89e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  148 AERLYGPYMWGRYDIVFLPpSFPIVAMENPCLTFIISSIL--------ESDEFLVIDVI-HEVAHSWFGNAVTNATWEEM 218
Cdd:pfam01433  14 EDYFNIPYPLPKYDLVALP-DFSAGAMENWGLITYRETLLlydpgnssTSDKQRVASVIaHELAHQWFGNLVTMKWWDDL 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  219 WLSEGLATYAQRRITTETYGAafTCLETAFRLDALHRQMRL--LGEDSPVSklqVKLEPGVNPSHLMNLFTYEKGYCFVY 296
Cdd:pfam01433  93 WLNEGFATYMEYLGTDALFPE--WNIWEQFLLDEVQNAMARdaLDSSHPIT---QNVNDPSEIDDIFDAIPYEKGASVLR 167
                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 755493701  297 YLSQLCgGPQRFDDFLRAYVEKYKFTSVVAQDLLDSF 333
Cdd:pfam01433 168 MLETLL-GEEVFQKGLRSYLKKFQYGNATTEDLWDAL 203
Leuk-A4-hydro_C pfam09127
Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of ...
406-519 3.48e-37

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: 133.38  E-value: 3.48e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  406 WRTFQTALFLDRLLDGSPLPQEVVMSLSKCYSsLLDSMNAEIRIRWLQIVVRNDYYPDLHRVRRFLESQMSRMYTIPLYE 485
Cdd:pfam09127   1 WSSNQKVVFLERLLEFSPLSPEQLKALDEVYK-LSESKNAEIRFRWLRLALKAKYEPAYPEVAEFLGEVGRMKFVRPLYR 79
                          90       100       110
                  ....*....|....*....|....*....|....
gi 755493701  486 DLCTgALKSFALEVFYQTQGRLHPNLRRTIQQIL 519
Cdd:pfam09127  80 ALNK-VDRDLAVETFEKNKDFYHPICRAMVEKDL 112
 
Name Accession Description Interval E-value
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
18-358 1.60e-161

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: 467.71  E-value: 1.60e-161
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  18 PPAPQIWWLDPELTYGNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQVLMSA--TQSVYVEEEGLYHFH 95
Cdd:cd09599  106 PQATALQWLTPEQTAGKKHPYLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALMSAlrTGEKEEAGTGTYTFE 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  96 MEHPVPAYLVALVAGDLKPADIGPRSRVWAEPCLLPtATSKLSGAVEQWLSAAERLYGPYMWGRYDIVFLPPSFPIVAME 175
Cdd:cd09599  186 QPVPIPSYLIAIAVGDLESREIGPRSGVWAEPSVVD-AAAEEFADTEKFLKAAEKLYGPYVWGRYDLLVLPPSFPYGGME 264
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 176 NPCLTFIISSILESDEFLVIDVIHEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAAFTCLETAFRLDALHR 255
Cdd:cd09599  265 NPCLTFATPTLIAGDRSLVDVIAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLERRILERLYGEEYRQFEAILGWKDLQE 344
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 256 QMRLLGEDSPvSKLQVKLEPGVNPSHLMNLFTYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSFLS 335
Cdd:cd09599  345 SIKEFGEDPP-YTLLVPDLKGVDPDDAFSSVPYEKGFQFLYYLEQL-GGREVFDPFLRAYFKKFAFQSIDTEDFKDFLLE 422
                        330       340
                 ....*....|....*....|...
gi 755493701 336 FFPELKeqsVDCRAGLEFERWLN 358
Cdd:cd09599  423 YFAEDK---PEILDKIDWDAWLY 442
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
25-519 2.05e-123

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: 376.04  E-value: 2.05e-123
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701   25 WLDPELTYGNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLgvQVLMSATQ-SVYVEEEGLYHFHMEHPVPAY 103
Cdd:TIGR02411 112 WLNPEQTSGKKHPYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVESPL--PVLMSGIRdGETSNDPGKYLFKQKVPIPAY 189
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  104 LVALVAGDLKPADIGPRSRVWAEPCLLPTATSKLSGAVEQWLSAAERLYGPYMWGRYDIVFLPPSFPIVAMENPCLTFII 183
Cdd:TIGR02411 190 LIAIASGDLASAPIGPRSTVYSEPEQLEKCQYEFENDTEKFIKTAEDLIFPYEWGQYDLLVLPPSFPYGGMENPNLTFAT 269
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  184 SSILESDEFLViDVI-HEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAAFTCLETAFRLDALHRQMRLLGE 262
Cdd:TIGR02411 270 PTLIAGDRSNV-DVIaHELAHSWSGNLVTNCSWEHFWLNEGWTVYLERRIIGRLYGEKTRHFSALIGWGDLQESVKTLGE 348
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  263 DSPVSKLQVKLEPGvNPSHLMNLFTYEKGYCFVYYLSQLCGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSFLSFFPELKE 342
Cdd:TIGR02411 349 TPEFTKLVVDLKDN-DPDDAFSSVPYEKGFNFLFYLEQLLGGPAEFDPFLRHYFKKFAYKSLDTYQFKDALYEYFKDKKK 427
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  343 qsVDCRAGLEFERWLNATGPPLAEPDLSqgSSLTRPVEALFQLWTAEPLEQAAASASAIDISKWRTFQTALFLDRLL--- 419
Cdd:TIGR02411 428 --VDKLDAVDWETWLYSPGMPPVKPNFD--TTLADECYALADRWVDAAKADDLSSFNAKDIKDFSSHQLVLFLETLTerg 503
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  420 DGSPLPQEVVMSLSKCYsSLLDSMNAEIRIRWLQIVVRNDYYPDLHRVRRFLESQmSRM-YTIPLYEDLCTGALKSFALE 498
Cdd:TIGR02411 504 GDWALPEGHIKRLGDIY-NFAASKNAEVRFRWFRLAIQAKLEDEYPLLADWLGTV-GRMkFVRPGYRLLNAFVDRDLAIR 581
                         490       500
                  ....*....|....*....|.
gi 755493701  499 VFYQTQGRLHPNLRRTIQQIL 519
Cdd:TIGR02411 582 TFEKFKDSYHPICAMLVKKDL 602
M1 cd09595
Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 ...
29-332 5.81e-65

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: 218.08  E-value: 5.81e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  29 ELTYGNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQVL-MSATQSVYVEEEGL--YHFHMEHPVPAYLV 105
Cdd:cd09595   97 EQTAGKEKPYLFTQFEATHARRIFPCIDHPAVKATFTVTITTPKKDLLAsNGALVGEETGANGRktYRFEDTPPIPTYLV 176
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 106 ALVAGDLKPADIGPRSR------VWAEPCLLPTATSKLSGAVEQWLSAAERLYGPYMWGRYDIVFLPPsFPIVAMENPCL 179
Cdd:cd09595  177 AVVVGDLEFKYVTVKSQprvglsVYSEPLQVDQAQYAFDATRAALAWFEDYFGGPYPLPKYDLLAVPD-FNSGAMENPGL 255
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 180 TFIISSIL-------ESDEFLVIDVIHEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAAFTCLETAFRLDA 252
Cdd:cd09595  256 ITFRTTYLlrskvtdTGARSIENVIAHELAHQWFGNLVTMRWWNDLWLNEGFAVYYENRIMDATFGTSSRHLDQLSGSSD 335
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 253 LHRQMRLLGEdspvSKLQVKLEPGVNPSHLMNLFTYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVAQDLLDS 332
Cdd:cd09595  336 LNTEQLLEDS----SPTSTPVRSPADPDVAYDGVTYAKGALVLRMLEEL-VGEEAFDKGVQAYFNRHKFKNATTDDFIDA 410
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
33-370 2.97e-64

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 221.06  E-value: 2.97e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  33 GNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQVLMSAT-QSVYVEEEGL--YHFHMEHPVPAYLVALVA 109
Cdd:COG0308  117 PDGPPYLYTQCEPEGARRWFPCFDHPDDKATFTLTVTVPAGWVAVSNGNlVSETELGDGRttWHWADTQPIPTYLFALAA 196
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 110 GDL-----KPADiGPRSRVWAEPCLLPTATSKLsGAVEQWLSAAERLYG-PYMWGRYDIVFLPpSFPIVAMENPCLTFII 183
Cdd:COG0308  197 GDYavvedTFAS-GVPLRVYVRPGLADKAKEAF-ESTKRMLDFFEELFGvPYPFDKYDQVAVP-DFNFGAMENQGLVTFG 273
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 184 SSIL----------ESDEFLVIdviHEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAaftclETAFRLDAL 253
Cdd:COG0308  274 EKVLadetatdadyERRESVIA---HELAHQWFGNLVTCADWDDLWLNEGFATYMEQLFSEDLYGK-----DAADRIFVG 345
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 254 HRQMRLLGEDSPVSKLQVKLEPGVNPSHLMNLFTYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSF 333
Cdd:COG0308  346 ALRSYAFAEDAGPNAHPIRPDDYPEIENFFDGIVYEKGALVLHMLRTL-LGDEAFRAGLRLYFARHAGGNATTEDFLAAL 424
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....
gi 755493701 334 -------LSFFpelkeqsvdcragleFERWLNATGPPLAEPDLS 370
Cdd:COG0308  425 eeasgrdLSAF---------------FDQWLYQAGLPTLEVEYE 453
M1_APN_like cd09603
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly ...
18-333 1.56e-44

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: 162.75  E-value: 1.56e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  18 PPAPQIWWLDPELTYGNakPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQV-----LMSATqsvyVEEEGL- 91
Cdd:cd09603   90 RPAGYPPGDGGGWEEGD--DGVWTAGQPEGASTWFPCNDHPDDKATYDITVTVPAGLTVvsngrLVSTT----TNGGGTt 163
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  92 -YHFHMEHPVPAYLVALVAGDLKPADIGPRSRV----WAEPCLLPTATSKLSGAVEQwLSAAERLYGPYMWGRYDIVFLP 166
Cdd:cd09603  164 tWHWKMDYPIATYLVTLAVGRYAVVEDGSGGGIplryYVPPGDAAKAKASFARTPEM-LDFFEELFGPYPFEKYGQVVVP 242
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 167 PSFpiVAMENPCLTFIISSILESDEFLVIDVIHEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGAAftclet 246
Cdd:cd09603  243 DLG--GGMEHQTATTYGNNFLNGDRGSERLIAHELAHQWFGDSVTCADWADIWLNEGFATYAEWLWSEHKGGAD------ 314
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 247 AFRlDALHRQMRLLGEDSPVSKlqvklePGVNPSHLMNLFTYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVA 326
Cdd:cd09603  315 AYR-AYLAGQRQDYLNADPGPG------RPPDPDDLFDRDVYQKGALVLHMLRNL-LGDEAFFAALRAYLARYAHGNVTT 386

                 ....*..
gi 755493701 327 QDLLDSF 333
Cdd:cd09603  387 EDFIAAA 393
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
148-333 2.89e-42

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: 151.29  E-value: 2.89e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  148 AERLYGPYMWGRYDIVFLPpSFPIVAMENPCLTFIISSIL--------ESDEFLVIDVI-HEVAHSWFGNAVTNATWEEM 218
Cdd:pfam01433  14 EDYFNIPYPLPKYDLVALP-DFSAGAMENWGLITYRETLLlydpgnssTSDKQRVASVIaHELAHQWFGNLVTMKWWDDL 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  219 WLSEGLATYAQRRITTETYGAafTCLETAFRLDALHRQMRL--LGEDSPVSklqVKLEPGVNPSHLMNLFTYEKGYCFVY 296
Cdd:pfam01433  93 WLNEGFATYMEYLGTDALFPE--WNIWEQFLLDEVQNAMARdaLDSSHPIT---QNVNDPSEIDDIFDAIPYEKGASVLR 167
                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 755493701  297 YLSQLCgGPQRFDDFLRAYVEKYKFTSVVAQDLLDSF 333
Cdd:pfam01433 168 MLETLL-GEEVFQKGLRSYLKKFQYGNATTEDLWDAL 203
Leuk-A4-hydro_C pfam09127
Leukotriene A4 hydrolase, C-terminal; Members of this family adopt a structure consisting of ...
406-519 3.48e-37

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: 133.38  E-value: 3.48e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  406 WRTFQTALFLDRLLDGSPLPQEVVMSLSKCYSsLLDSMNAEIRIRWLQIVVRNDYYPDLHRVRRFLESQMSRMYTIPLYE 485
Cdd:pfam09127   1 WSSNQKVVFLERLLEFSPLSPEQLKALDEVYK-LSESKNAEIRFRWLRLALKAKYEPAYPEVAEFLGEVGRMKFVRPLYR 79
                          90       100       110
                  ....*....|....*....|....*....|....
gi 755493701  486 DLCTgALKSFALEVFYQTQGRLHPNLRRTIQQIL 519
Cdd:pfam09127  80 ALNK-VDRDLAVETFEKNKDFYHPICRAMVEKDL 112
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
49-333 1.96e-35

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: 138.10  E-value: 1.96e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  49 RSFFPCFDTPAVKCTYSAVVKAPLGVQVLmSATQSVYVEEEG----LYHFHMEHPVPAYLVALVAGDLK----PADIGPR 120
Cdd:cd09601  126 RRAFPCFDEPAFKATFDITITHPKGYTAL-SNMPPVESTELEdgwkTTTFETTPPMSTYLVAFVVGDFEyiesTTKSGVP 204
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 121 SRVWAEPCLLPTATSKLSGAVEQwLSAAERLYG-PY----MwgryDIVFLPpSFPIVAMENP-CLTFIISSIL------- 187
Cdd:cd09601  205 VRVYARPGKIEQGDFALEVAPKI-LDFYEDYFGiPYplpkL----DLVAIP-DFAAGAMENWgLITYRETALLydpktss 278
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 188 ESDEFLVIDVI-HEVAHSWFGNAVTNATWEEMWLSEGLATYAqrrittETYGAAFTC----LETAFRLDALHRQMRLlge 262
Cdd:cd09601  279 ASDKQRVAEVIaHELAHQWFGNLVTMKWWDDLWLNEGFATYM------EYLAVDKLFpewnMWDQFVVDELQSALEL--- 349
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755493701 263 DS-----PVSKlqvklePGVNPSHLMNLF---TYEKGYCFVYYLSQLcGGPQRFDDFLRAYVEKYKFTSVVAQDLLDSF 333
Cdd:cd09601  350 DSlasshPIEV------PVESPSEISEIFdaiSYSKGASVLRMLENF-LGEEVFRKGLRKYLKKHAYGNATTDDLWEAL 421
M1_APN cd09602
Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the ...
49-333 3.66e-29

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: 120.31  E-value: 3.66e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  49 RSFFPCFDTPAVKCTYSAVVKAPLGVQVLmSATQSVYVEEEG---LYHFHMEHPVPAYLVALVAGDLKPAD---IGPRSR 122
Cdd:cd09602  128 RRVFPCFDQPDLKATFTLTVTAPADWTVI-SNGPETSTEEAGgrkRWRFAETPPLSTYLFAFVAGPYHRVEdehDGIPLG 206
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 123 VWAEPCLLPTATSK--LSGAVEQWLSAAERLYG-PYMWGRYDIVFLPpSFPIVAMENP-CLTFIISSIL-----ESDEFL 193
Cdd:cd09602  207 LYCRESLAEYERDAdeIFEVTKQGLDFYEDYFGiPYPFGKYDQVFVP-EFNFGAMENPgAVTFRESYLFreeptRAQRLR 285
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 194 VIDVI-HEVAHSWFGNAVTNATWEEMWLSEGLATYAQRRITTETYGaaFTCLETAFrldALHRQMRLLGEDS-----PVS 267
Cdd:cd09602  286 RANTIlHEMAHMWFGDLVTMKWWDDLWLNESFADFMAAKALAEATP--FTDAWLTF---LLRRKPWAYRADQlptthPIA 360
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755493701 268 klqvklEPGVNPSHLMNLF---TYEKGYCF----VYYLsqlcgGPQRFDDFLRAYVEKYKFTSVVAQDLLDSF 333
Cdd:cd09602  361 ------QDVPDLEAAGSNFdgiTYAKGASVlkqlVALV-----GEEAFRAGLREYFKKHAYGNATLDDLIAAL 422
M1_APN_like cd09604
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains ...
149-333 1.34e-25

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: 109.67  E-value: 1.34e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 149 ERLYGPYMWGRYDIVFLPPSFpiVAMENPCLTFIISSILESDEFLVIDVIHEVAHSWFGNAVTNATWEEMWLSEGLATYA 228
Cdd:cd09604  251 SEKFGPYPYPELDVVQGPFGG--GGMEYPGLVFIGSRLYDPKRSLEGVVVHEIAHQWFYGIVGNDERREPWLDEGLATYA 328
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 229 QRRITTETYGAAFTCLETAFRLDALHRQMRLLGEDSPVSKLQVKLEPGVNpshlmnlfTYEKGYCFVYYLSQLCgGPQRF 308
Cdd:cd09604  329 ESLYLEEKYGKEAADELLGRRYYRAYARGPGGPINLPLDTFPDGSYYSNA--------VYSKGALFLEELREEL-GDEAF 399
                        170       180
                 ....*....|....*....|....*
gi 755493701 309 DDFLRAYVEKYKFTSVVAQDLLDSF 333
Cdd:cd09604  400 DKALREYYRRYKFKHPTPEDFFRTA 424
M1_like_TAF2 cd09839
TATA binding protein (TBP) associated factor 2; This family includes TATA binding protein (TBP) ...
28-227 1.01e-08

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: 58.01  E-value: 1.01e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  28 PELTYGNAKPFVFTQGHSVCN--RSFFPCFDTPAVKCTYSAVVKAP----------LGVQVLMSATQSVYVEEEGL---- 91
Cdd:cd09839  154 PDEGGDKRYPHVYTTNSPLPGsaRCWFPCVDSLWERCTWELEITVPrtlgdagrppLAGSKEDEDDDDLTEEDKELemvv 233
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  92 --------------------YHFHMEHPVPAYLVALVAGDLKPADIGPRSRVWAEP------------CL------LPTA 133
Cdd:cd09839  234 vcsgdlveqvvhpedpskktFSFSLSNPTSAQHIGFAVGPFEIVPLPEFRESEEDDklgssavevtgfCLpgrleeLRNT 313
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 134 TSKLSGAVEQWlsaaERLYGPYMWGRYDIVFLPPsfpivaMENPCLTFIISSILeSDEFL----VIDVI--------HEV 201
Cdd:cd09839  314 CSFLHKAMDFF----EEEYGSYPFSSYKQVFVDD------LPEDVSSFASLSIC-SSRLLyppdIIDQAyetrrklaHAL 382
                        250       260
                 ....*....|....*....|....*.
gi 755493701 202 AHSWFGNAVTNATWEEMWLSEGLATY 227
Cdd:cd09839  383 ASQWFGINIIPKTWSDTWLVIGIAGY 408
M1_APN cd09600
Peptidase M1 family, including aminopeptidase N catalytic domain; This model represents the ...
94-227 2.67e-08

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: 56.37  E-value: 2.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701  94 FHMEHPVPAYLVALVAGDL------------KPADIgprsRVWAEPCLLPtatsKLSGAVEQwLSAA----ERLYG-PYM 156
Cdd:cd09600  169 WEDPFPKPSYLFALVAGDLgsvedtfttksgRKVKL----RIYVEPGNED----KCHHAMES-LKKAmkwdEERFGlEYD 239
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 157 WGRYDIVFLPpSFPIVAMENPCLT-FIISSIL-------ESDEFLVIDVI-HEVAHSWFGNAVTNATWEEMWLSEGLATY 227
Cdd:cd09600  240 LDLFNIVAVD-DFNMGAMENKGLNiFNSKYVLadpetatDADYERIESVIaHEYFHNWTGNRVTCRDWFQLSLKEGLTVF 318
Peptidase_M1_N pfam17900
Peptidase M1 N-terminal domain; This domain is found at the N-terminus of aminopeptidases from ...
33-104 1.09e-07

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: 52.35  E-value: 1.09e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755493701   33 GNAKPFVFTQGHSVCNRSFFPCFDTPAVKCTYSAVVKAPLGVQVL--MSATQSVyVEEEGL--YHFHMEHPVPAYL 104
Cdd:pfam17900 112 GEKKVLVTTQFEPTDARSAFPCFDEPSVKATFTISIIHPKDYTALsnMPVIASE-PLENGWviTTFEQTPKMSTYL 186
GluZincin cd09594
Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, ...
152-227 3.24e-07

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: 48.63  E-value: 3.24e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493701 152 YGPYMWGRYDIVFLPP---SFPIVAMENPcLTFIISSILESDEF-LVIDVI-HEVAHSWFGNAVTN-ATWEEMWLSEGLA 225
Cdd:cd09594   20 FRYPVSPIYSLLVYPAyveVNAYNAMWIP-STNIFYGAGILDTLsGTIDVLaHELTHAFTGQFSNLmYSWSSGWLNEGIS 98

                 ..
gi 755493701 226 TY 227
Cdd:cd09594   99 DY 100
 
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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