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Conserved domains on  [gi|289803028|gb|ADD20764|]
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FI02158p [Drosophila melanogaster]

Protein Classification

M1 family metallopeptidase( domain architecture ID 10329674)

M1 family metallopeptidase similar to aminopeptidase N (APN; EC 3.4.11.2) that preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and to Caenorhabditis elegans aminopeptidase-like protein AC3.5 that is likely inactive

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
GluZincin super family cl14813
Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, ...
60-502 1.05e-69

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.


The actual alignment was detected with superfamily member cd09601:

Pssm-ID: 472708 [Multi-domain]  Cd Length: 442  Bit Score: 238.63  E-value: 1.05e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  60 LSYEVLIEPHMDNQNFEGSIRMHLRWIGDSKKVYFHAHDtllIDVSQINLTTLNmgdgtlDKNVIILRGVRLPRKPVFVL 139
Cdd:cd09601    1 LHYDLTLTPDLENFTFSGSVTITLEVLEPTDTIVLHAKD---LTITSASLTLKG------GSGIIEVTVVTDEETEFLTI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 140 YLKDKIKKGSECLLDIYFQGNISETEEGLFRSYYTNsgNDGEEIYLA-TNLKPNNARRLFPCFDEPGIKVPFNVSIARPK 218
Cdd:cd09601   72 TLDETLPPGENYTLSIEFTGKLNDDLRGFYRSSYTD--EDGETRYLAaTQFEPTDARRAFPCFDEPAFKATFDITITHPK 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 219 GYITLFNTPLhnTINHPKLRSYSLDFFHTTAPMSTHAFGFVILKLhmwnEHKIVKSSDIPAINIWS--NNLSSTnlldiQ 296
Cdd:cd09601  150 GYTALSNMPP--VESTELEDGWKTTTFETTPPMSTYLVAFVVGDF----EYIESTTKSGVPVRVYArpGKIEQG-----D 218
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 297 NKLNVAHTTIQHF---FNIPLPLTKLDVIAIPSLAT-------LPFISASGILI--ARESEILKKDVFE-ISRELIYQWI 363
Cdd:cd09601  219 FALEVAPKILDFYedyFGIPYPLPKLDLVAIPDFAAgamenwgLITYRETALLYdpKTSSASDKQRVAEvIAHELAHQWF 298
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 364 GIWITPEWWTDANVNKALISFIASEIVFEINGGIEFNGKYpmtILYSLYYELSK---------RYPNSHITGIKHEFASI 434
Cdd:cd09601  299 GNLVTMKWWDDLWLNEGFATYMEYLAVDKLFPEWNMWDQF---VVDELQSALELdslasshpiEVPVESPSEISEIFDAI 375
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 289803028 435 ---KVQLIIRMLSLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAITTQAKADNSLDsdlsILSIAESWLE 502
Cdd:cd09601  376 sysKGASVLRMLENFLGEEVFRKGLRKYLKKHAYGNATTDDLWEALQEASGESKPLD----VKEIMDSWTL 442
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
583-910 4.53e-58

ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 HEAT-like repeats. This domain forms a concave face that faces towards the active site of the peptidase.


:

Pssm-ID: 463368 [Multi-domain]  Cd Length: 316  Bit Score: 202.12  E-value: 4.53e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  583 FIIVNEEEIGPFPVNYDDNNWNMLSKYLRTEEkresIPVYTRAKLLHDAWNLAYAGELNFSTALNVTLFLKYERNHIVWS 662
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSKV----LSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWS 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  663 PVFTFLDQVGKRLEKSSINKKFELYIIELLAPLYEYLG-TAHFNEDINITELRKLTTSFLCKAGYFPCFKEARRAFNIWI 741
Cdd:pfam11838  77 AALSQLSTLRSLLSADPEYEALKAFLRKLLSPLAEKLGwEAPPGESHLDRQLRALLLSAACSAGDPECVAEAKKLFDAWL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  742 NSSF---PNFETPVpneyICSIFKWGSMKEWMFGLDRlceFPKSRIQSDRTHLLKMLAgCPAQRDKIFILLELAIlkNIS 818
Cdd:pfam11838 157 DGDDaipPDLRWAV----YCAAVANGGEAEWDALLER---YRDTTSPSEKERALRALA-ATPDPELLQRALELAL--DSD 226
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  819 IFSDTDKMLIISTVTSRSIGYTTLLDFLSNNWDDIHHKFYNNtNIWTKLISSATGMFSTQEGYDLVKKFYDEHYGH-FGR 897
Cdd:pfam11838 227 EVRNQDLRAVIAGLASNPAGRDLAWDFVKENWDALVKRLGGG-SSLGRLVKGLTPSFSTEEELDEVEAFFADKDTPgLRR 305
                         330
                  ....*....|...
gi 289803028  898 AqhiIEKSLRNIK 910
Cdd:pfam11838 306 A---LAQALETIR 315
 
Name Accession Description Interval E-value
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
60-502 1.05e-69

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: 238.63  E-value: 1.05e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  60 LSYEVLIEPHMDNQNFEGSIRMHLRWIGDSKKVYFHAHDtllIDVSQINLTTLNmgdgtlDKNVIILRGVRLPRKPVFVL 139
Cdd:cd09601    1 LHYDLTLTPDLENFTFSGSVTITLEVLEPTDTIVLHAKD---LTITSASLTLKG------GSGIIEVTVVTDEETEFLTI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 140 YLKDKIKKGSECLLDIYFQGNISETEEGLFRSYYTNsgNDGEEIYLA-TNLKPNNARRLFPCFDEPGIKVPFNVSIARPK 218
Cdd:cd09601   72 TLDETLPPGENYTLSIEFTGKLNDDLRGFYRSSYTD--EDGETRYLAaTQFEPTDARRAFPCFDEPAFKATFDITITHPK 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 219 GYITLFNTPLhnTINHPKLRSYSLDFFHTTAPMSTHAFGFVILKLhmwnEHKIVKSSDIPAINIWS--NNLSSTnlldiQ 296
Cdd:cd09601  150 GYTALSNMPP--VESTELEDGWKTTTFETTPPMSTYLVAFVVGDF----EYIESTTKSGVPVRVYArpGKIEQG-----D 218
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 297 NKLNVAHTTIQHF---FNIPLPLTKLDVIAIPSLAT-------LPFISASGILI--ARESEILKKDVFE-ISRELIYQWI 363
Cdd:cd09601  219 FALEVAPKILDFYedyFGIPYPLPKLDLVAIPDFAAgamenwgLITYRETALLYdpKTSSASDKQRVAEvIAHELAHQWF 298
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 364 GIWITPEWWTDANVNKALISFIASEIVFEINGGIEFNGKYpmtILYSLYYELSK---------RYPNSHITGIKHEFASI 434
Cdd:cd09601  299 GNLVTMKWWDDLWLNEGFATYMEYLAVDKLFPEWNMWDQF---VVDELQSALELdslasshpiEVPVESPSEISEIFDAI 375
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 289803028 435 ---KVQLIIRMLSLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAITTQAKADNSLDsdlsILSIAESWLE 502
Cdd:cd09601  376 sysKGASVLRMLENFLGEEVFRKGLRKYLKKHAYGNATTDDLWEALQEASGESKPLD----VKEIMDSWTL 442
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
583-910 4.53e-58

ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 HEAT-like repeats. This domain forms a concave face that faces towards the active site of the peptidase.


Pssm-ID: 463368 [Multi-domain]  Cd Length: 316  Bit Score: 202.12  E-value: 4.53e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  583 FIIVNEEEIGPFPVNYDDNNWNMLSKYLRTEEkresIPVYTRAKLLHDAWNLAYAGELNFSTALNVTLFLKYERNHIVWS 662
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSKV----LSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWS 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  663 PVFTFLDQVGKRLEKSSINKKFELYIIELLAPLYEYLG-TAHFNEDINITELRKLTTSFLCKAGYFPCFKEARRAFNIWI 741
Cdd:pfam11838  77 AALSQLSTLRSLLSADPEYEALKAFLRKLLSPLAEKLGwEAPPGESHLDRQLRALLLSAACSAGDPECVAEAKKLFDAWL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  742 NSSF---PNFETPVpneyICSIFKWGSMKEWMFGLDRlceFPKSRIQSDRTHLLKMLAgCPAQRDKIFILLELAIlkNIS 818
Cdd:pfam11838 157 DGDDaipPDLRWAV----YCAAVANGGEAEWDALLER---YRDTTSPSEKERALRALA-ATPDPELLQRALELAL--DSD 226
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  819 IFSDTDKMLIISTVTSRSIGYTTLLDFLSNNWDDIHHKFYNNtNIWTKLISSATGMFSTQEGYDLVKKFYDEHYGH-FGR 897
Cdd:pfam11838 227 EVRNQDLRAVIAGLASNPAGRDLAWDFVKENWDALVKRLGGG-SSLGRLVKGLTPSFSTEEELDEVEAFFADKDTPgLRR 305
                         330
                  ....*....|...
gi 289803028  898 AqhiIEKSLRNIK 910
Cdd:pfam11838 306 A---LAQALETIR 315
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
50-533 3.66e-33

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 136.31  E-value: 3.66e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  50 EVRLPKEVLPLSYEVLIEPHMDNQNFEGSIRMHLRWIGDskkvyfhAHDTLLIDVSQINLTTLNMGDGTLDknvIILRGV 129
Cdd:COG0308    8 EAYRPPGYDVTHYDLDLDLDPATTRLSGTATITFTATEA-------PLDSLVLDLKGLEVTSVTVDGKPLD---FTRDGE 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 130 RLprkpvfVLYLKDKIKKGSECLLDIYFQGNISETEEGLFRSYYTNSGNDgeeiYLATNLKPNNARRLFPCFDEPGIKVP 209
Cdd:COG0308   78 RL------TITLPKPLAPGETFTLEIEYSGKPSNGGEGLYRSGDPPDGPP----YLYTQCEPEGARRWFPCFDHPDDKAT 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 210 FNVSIARPKGYITLFNTPLHNTINHPKLRSYslDFFHTTAPMSTHAFGFVILKLHmwnEHKIVKSSDIPaINIW---SNN 286
Cdd:COG0308  148 FTLTVTVPAGWVAVSNGNLVSETELGDGRTT--WHWADTQPIPTYLFALAAGDYA---VVEDTFASGVP-LRVYvrpGLA 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 287 LSSTNLLDIQNK-LNVAHttiqHFFNIPLPLTKLDVIAIPSL-------ATLPFISASGILIARESEILKKDVFE-ISRE 357
Cdd:COG0308  222 DKAKEAFESTKRmLDFFE----ELFGVPYPFDKYDQVAVPDFnfgamenQGLVTFGEKVLADETATDADYERRESvIAHE 297
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 358 LIYQWIGIWITPEWWTDANVNKALISFIASEIVFEinggiefngKYPMTILYSLYYELSKRY-------PNSH------I 424
Cdd:COG0308  298 LAHQWFGNLVTCADWDDLWLNEGFATYMEQLFSED---------LYGKDAADRIFVGALRSYafaedagPNAHpirpddY 368
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 425 TGIKHEFASI---KVQLIIRMLSLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAITTQAKAdnsldsDLSilSIAESWL 501
Cdd:COG0308  369 PEIENFFDGIvyeKGALVLHMLRTLLGDEAFRAGLRLYFARHAGGNATTEDFLAALEEASGR------DLS--AFFDQWL 440
                        490       500       510
                 ....*....|....*....|....*....|....*
gi 289803028 502 EHSRLPLVTIIRDYDSETAI---VQQKVYLRERLH 533
Cdd:COG0308  441 YQAGLPTLEVEYEYDADGKVtltLRQTPPRPHPFH 475
Peptidase_M1_N pfam17900
Peptidase M1 N-terminal domain; This domain is found at the N-terminus of aminopeptidases from ...
59-253 6.66e-26

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: 105.50  E-value: 6.66e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028   59 PLSYEVLIEPHMDNQNFEGSIRMHLRWIGDSKKVYFHAHDTLLIDVSQinlttlnMGDGTLDkNVIILRGVRLPRKPVFV 138
Cdd:pfam17900   2 PEHYDLDLKIDLKNFTFSGSVTITLQLNNATNVIVLHASDLTIRSISL-------SDEVTSD-GVPADFTEDQKDGEKLT 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  139 LYLKDKIKKGSECLLDIYFQGNISETEEGLFRSYYTNSGndGEEIYLATNLKPNNARRLFPCFDEPGIKVPFNVSIARPK 218
Cdd:pfam17900  74 IVLPETLNQTGPYTLEIEYSGELNDSMTGFYRSTYTDNG--EKKVLVTTQFEPTDARSAFPCFDEPSVKATFTISIIHPK 151
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 289803028  219 GYITLFNTPLHNTinHPKLRSYSLDFFHTTAPMST 253
Cdd:pfam17900 152 DYTALSNMPVIAS--EPLENGWVITTFEQTPKMST 184
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
82-217 1.03e-03

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: 42.84  E-value: 1.03e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028   82 HLRWIGDSKKVYFHAHDTLLIDVSQINLTTLNMGDGTLDKNVIILRGVRLP-----RKPVF----VLYLKDKIKKGSECL 152
Cdd:TIGR02411  17 DLNLSVDFTKRKLSGSVTFTLKSLTDNLNKLVLDTSYLDIQKVTINGLPADfaigeRKEPLgsplTISLPIATSKNDEFV 96
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 289803028  153 LDIYFQGNISETeeGLfrSYYTNSGNDGEEI-YLATNLKPNNARRLFPCFDEPGIKVPFNVSIARP 217
Cdd:TIGR02411  97 LNISFSTTPKCT--AL--QWLNPEQTSGKKHpYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVESP 158
 
Name Accession Description Interval E-value
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
60-502 1.05e-69

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: 238.63  E-value: 1.05e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  60 LSYEVLIEPHMDNQNFEGSIRMHLRWIGDSKKVYFHAHDtllIDVSQINLTTLNmgdgtlDKNVIILRGVRLPRKPVFVL 139
Cdd:cd09601    1 LHYDLTLTPDLENFTFSGSVTITLEVLEPTDTIVLHAKD---LTITSASLTLKG------GSGIIEVTVVTDEETEFLTI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 140 YLKDKIKKGSECLLDIYFQGNISETEEGLFRSYYTNsgNDGEEIYLA-TNLKPNNARRLFPCFDEPGIKVPFNVSIARPK 218
Cdd:cd09601   72 TLDETLPPGENYTLSIEFTGKLNDDLRGFYRSSYTD--EDGETRYLAaTQFEPTDARRAFPCFDEPAFKATFDITITHPK 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 219 GYITLFNTPLhnTINHPKLRSYSLDFFHTTAPMSTHAFGFVILKLhmwnEHKIVKSSDIPAINIWS--NNLSSTnlldiQ 296
Cdd:cd09601  150 GYTALSNMPP--VESTELEDGWKTTTFETTPPMSTYLVAFVVGDF----EYIESTTKSGVPVRVYArpGKIEQG-----D 218
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 297 NKLNVAHTTIQHF---FNIPLPLTKLDVIAIPSLAT-------LPFISASGILI--ARESEILKKDVFE-ISRELIYQWI 363
Cdd:cd09601  219 FALEVAPKILDFYedyFGIPYPLPKLDLVAIPDFAAgamenwgLITYRETALLYdpKTSSASDKQRVAEvIAHELAHQWF 298
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 364 GIWITPEWWTDANVNKALISFIASEIVFEINGGIEFNGKYpmtILYSLYYELSK---------RYPNSHITGIKHEFASI 434
Cdd:cd09601  299 GNLVTMKWWDDLWLNEGFATYMEYLAVDKLFPEWNMWDQF---VVDELQSALELdslasshpiEVPVESPSEISEIFDAI 375
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 289803028 435 ---KVQLIIRMLSLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAITTQAKADNSLDsdlsILSIAESWLE 502
Cdd:cd09601  376 sysKGASVLRMLENFLGEEVFRKGLRKYLKKHAYGNATTDDLWEALQEASGESKPLD----VKEIMDSWTL 442
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
583-910 4.53e-58

ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 HEAT-like repeats. This domain forms a concave face that faces towards the active site of the peptidase.


Pssm-ID: 463368 [Multi-domain]  Cd Length: 316  Bit Score: 202.12  E-value: 4.53e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  583 FIIVNEEEIGPFPVNYDDNNWNMLSKYLRTEEkresIPVYTRAKLLHDAWNLAYAGELNFSTALNVTLFLKYERNHIVWS 662
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSKV----LSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWS 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  663 PVFTFLDQVGKRLEKSSINKKFELYIIELLAPLYEYLG-TAHFNEDINITELRKLTTSFLCKAGYFPCFKEARRAFNIWI 741
Cdd:pfam11838  77 AALSQLSTLRSLLSADPEYEALKAFLRKLLSPLAEKLGwEAPPGESHLDRQLRALLLSAACSAGDPECVAEAKKLFDAWL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  742 NSSF---PNFETPVpneyICSIFKWGSMKEWMFGLDRlceFPKSRIQSDRTHLLKMLAgCPAQRDKIFILLELAIlkNIS 818
Cdd:pfam11838 157 DGDDaipPDLRWAV----YCAAVANGGEAEWDALLER---YRDTTSPSEKERALRALA-ATPDPELLQRALELAL--DSD 226
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  819 IFSDTDKMLIISTVTSRSIGYTTLLDFLSNNWDDIHHKFYNNtNIWTKLISSATGMFSTQEGYDLVKKFYDEHYGH-FGR 897
Cdd:pfam11838 227 EVRNQDLRAVIAGLASNPAGRDLAWDFVKENWDALVKRLGGG-SSLGRLVKGLTPSFSTEEELDEVEAFFADKDTPgLRR 305
                         330
                  ....*....|...
gi 289803028  898 AqhiIEKSLRNIK 910
Cdd:pfam11838 306 A---LAQALETIR 315
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
50-533 3.66e-33

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 136.31  E-value: 3.66e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  50 EVRLPKEVLPLSYEVLIEPHMDNQNFEGSIRMHLRWIGDskkvyfhAHDTLLIDVSQINLTTLNMGDGTLDknvIILRGV 129
Cdd:COG0308    8 EAYRPPGYDVTHYDLDLDLDPATTRLSGTATITFTATEA-------PLDSLVLDLKGLEVTSVTVDGKPLD---FTRDGE 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 130 RLprkpvfVLYLKDKIKKGSECLLDIYFQGNISETEEGLFRSYYTNSGNDgeeiYLATNLKPNNARRLFPCFDEPGIKVP 209
Cdd:COG0308   78 RL------TITLPKPLAPGETFTLEIEYSGKPSNGGEGLYRSGDPPDGPP----YLYTQCEPEGARRWFPCFDHPDDKAT 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 210 FNVSIARPKGYITLFNTPLHNTINHPKLRSYslDFFHTTAPMSTHAFGFVILKLHmwnEHKIVKSSDIPaINIW---SNN 286
Cdd:COG0308  148 FTLTVTVPAGWVAVSNGNLVSETELGDGRTT--WHWADTQPIPTYLFALAAGDYA---VVEDTFASGVP-LRVYvrpGLA 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 287 LSSTNLLDIQNK-LNVAHttiqHFFNIPLPLTKLDVIAIPSL-------ATLPFISASGILIARESEILKKDVFE-ISRE 357
Cdd:COG0308  222 DKAKEAFESTKRmLDFFE----ELFGVPYPFDKYDQVAVPDFnfgamenQGLVTFGEKVLADETATDADYERRESvIAHE 297
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 358 LIYQWIGIWITPEWWTDANVNKALISFIASEIVFEinggiefngKYPMTILYSLYYELSKRY-------PNSH------I 424
Cdd:COG0308  298 LAHQWFGNLVTCADWDDLWLNEGFATYMEQLFSED---------LYGKDAADRIFVGALRSYafaedagPNAHpirpddY 368
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 425 TGIKHEFASI---KVQLIIRMLSLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAITTQAKAdnsldsDLSilSIAESWL 501
Cdd:COG0308  369 PEIENFFDGIvyeKGALVLHMLRTLLGDEAFRAGLRLYFARHAGGNATTEDFLAALEEASGR------DLS--AFFDQWL 440
                        490       500       510
                 ....*....|....*....|....*....|....*
gi 289803028 502 EHSRLPLVTIIRDYDSETAI---VQQKVYLRERLH 533
Cdd:COG0308  441 YQAGLPTLEVEYEYDADGKVtltLRQTPPRPHPFH 475
M1 cd09595
Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 ...
61-477 1.07e-32

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: 131.80  E-value: 1.07e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  61 SYEVLIEPHMDNQNFEGSIRMHLRWIGDSKKVYFHAHDTllidvsQINLTTLNMGDG-TLDKNVIILRGVRLPRKPVfvl 139
Cdd:cd09595    2 HYDLDLDVDFTTKTLNGTETLTVDASQVGRELVLDLVGL------TIHSVSVNGAAVdFGEREHYDGEKLTIPGPKP--- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 140 ylkdkikKGSECLLDIYFQGNISETEEGLFRSYYTNSgndgEEIYLATNLKPNNARRLFPCFDEPGIKVPFNVSIARPKG 219
Cdd:cd09595   73 -------PGQTFTVRISFEAKPSKNLLGWLWEQTAGK----EKPYLFTQFEATHARRIFPCIDHPAVKATFTVTITTPKK 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 220 YITLFNTPLHNTINHPKLRsySLDFFHTTAPMSTHAFGFVILKL-HMWNEHKIVKSSDIPainIWSnnlSSTNLLDIQNK 298
Cdd:cd09595  142 DLLASNGALVGEETGANGR--KTYRFEDTPPIPTYLVAVVVGDLeFKYVTVKSQPRVGLS---VYS---EPLQVDQAQYA 213
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 299 LNVAHTTIQHF---FNIPLPLTKLDVIAIPSL-------ATLPFISASGILIARESEILKKDVFE-ISRELIYQWIGIWI 367
Cdd:cd09595  214 FDATRAALAWFedyFGGPYPLPKYDLLAVPDFnsgamenPGLITFRTTYLLRSKVTDTGARSIENvIAHELAHQWFGNLV 293
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 368 TPEWWTDANVNKALISFIASEIVFEING----GIEFNGKYP--MTI------LYSLYYELSKRYPNSHITGIKHEfasiK 435
Cdd:cd09595  294 TMRWWNDLWLNEGFAVYYENRIMDATFGtssrHLDQLSGSSdlNTEqlledsSPTSTPVRSPADPDVAYDGVTYA----K 369
                        410       420       430       440
                 ....*....|....*....|....*....|....*....|..
gi 289803028 436 VQLIIRMLSLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAI 477
Cdd:cd09595  370 GALVLRMLEELVGEEAFDKGVQAYFNRHKFKNATTDDFIDAL 411
Peptidase_M1_N pfam17900
Peptidase M1 N-terminal domain; This domain is found at the N-terminus of aminopeptidases from ...
59-253 6.66e-26

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: 105.50  E-value: 6.66e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028   59 PLSYEVLIEPHMDNQNFEGSIRMHLRWIGDSKKVYFHAHDTLLIDVSQinlttlnMGDGTLDkNVIILRGVRLPRKPVFV 138
Cdd:pfam17900   2 PEHYDLDLKIDLKNFTFSGSVTITLQLNNATNVIVLHASDLTIRSISL-------SDEVTSD-GVPADFTEDQKDGEKLT 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  139 LYLKDKIKKGSECLLDIYFQGNISETEEGLFRSYYTNSGndGEEIYLATNLKPNNARRLFPCFDEPGIKVPFNVSIARPK 218
Cdd:pfam17900  74 IVLPETLNQTGPYTLEIEYSGELNDSMTGFYRSTYTDNG--EKKVLVTTQFEPTDARSAFPCFDEPSVKATFTISIIHPK 151
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 289803028  219 GYITLFNTPLHNTinHPKLRSYSLDFFHTTAPMST 253
Cdd:pfam17900 152 DYTALSNMPVIAS--EPLENGWVITTFEQTPKMST 184
M1_APN cd09602
Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the ...
139-502 3.00e-17

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: 85.26  E-value: 3.00e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 139 LYLKDKIKKGsECLLDIYFQGNISETEEGLFRsyYTNSgNDGEEiYLATNLKPNNARRLFPCFDEPGIKVPFNVSIARPK 218
Cdd:cd09602   77 ITLPGLLKAG-ENTVVVEFTAPYSSDGEGLHR--FVDP-ADGET-YLYTLFEPDDARRVFPCFDQPDLKATFTLTVTAPA 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 219 GYITLFNTPLHNTINHPKLRSYSldfFHTTAPMSTHAFGFVILKLHMW-NEHKivkssDIPaINIWSNNLSSTNLLDIQN 297
Cdd:cd09602  152 DWTVISNGPETSTEEAGGRKRWR---FAETPPLSTYLFAFVAGPYHRVeDEHD-----GIP-LGLYCRESLAEYERDADE 222
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 298 KLNVAHTTIQHF---FNIPLPLTKLDVIAIPSLAtlpfISA---SGILIARESEILKKDVFE---------ISRELIYQW 362
Cdd:cd09602  223 IFEVTKQGLDFYedyFGIPYPFGKYDQVFVPEFN----FGAmenPGAVTFRESYLFREEPTRaqrlrrantILHEMAHMW 298
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 363 IGIWITPEWWTDANVNKALISFIASEIVFEINGGIE----FN-GKYPMTilyslYYElsKRYPNSH-ITG-IKH------ 429
Cdd:cd09602  299 FGDLVTMKWWDDLWLNESFADFMAAKALAEATPFTDawltFLlRRKPWA-----YRA--DQLPTTHpIAQdVPDleaags 371
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 289803028 430 EFASI---KVQLIIRMLSLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAIttqakaDNSLDSDLSilSIAESWLE 502
Cdd:cd09602  372 NFDGItyaKGASVLKQLVALVGEEAFRAGLREYFKKHAYGNATLDDLIAAL------DEASGRDLS--AWADAWLR 439
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
309-500 7.94e-17

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: 80.41  E-value: 7.94e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  309 FFNIPLPLTKLDVIAIPSLatlpfiSAS-----GILIARESEIL----------KKDVFE-ISRELIYQWIGIWITPEWW 372
Cdd:pfam01433  16 YFNIPYPLPKYDLVALPDF------SAGamenwGLITYRETLLLydpgnsstsdKQRVASvIAHELAHQWFGNLVTMKWW 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  373 TDANVNKALISFIASEIVFEINGGIEFNGKYPMTILYSLYYELSKRYPNS------HITGIKHEFASI---KVQLIIRML 443
Cdd:pfam01433  90 DDLWLNEGFATYMEYLGTDALFPEWNIWEQFLLDEVQNAMARDALDSSHPitqnvnDPSEIDDIFDAIpyeKGASVLRML 169
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 289803028  444 SLTVGKYTFRLGIQSFICDYKFKTYKSSDFWNAITtqaKADNSLDsdlsILSIAESW 500
Cdd:pfam01433 170 ETLLGEEVFQKGLRSYLKKFQYGNATTEDLWDALS---EASGPLD----VDSFMDTW 219
M1_APN_like cd09603
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly ...
60-374 9.23e-09

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: 58.75  E-value: 9.23e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028  60 LSYEVLIEPHMDNQNFEGSIRMHLRWIGDSKKVYFHAHDTlliDVSQINLTTLNMGDGTLDKNVIIlrgVRLPRKpvfvl 139
Cdd:cd09603    4 LHYDLDLDYDPATKSLSGTATITFRATQDLDSLQLDLVGL---TVSSVTVDGVPAAFFTHDGDKLV---ITLPRP----- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 140 ylkdkIKKGSECLLDIYFQGNISETEEGLFRSYYTNSGNDGeeiyLATNLKPNNARRLFPCFDEPGIKVPFNVSIARPKG 219
Cdd:cd09603   73 -----LAAGETFTVTVRYSGKPRPAGYPPGDGGGWEEGDDG----VWTAGQPEGASTWFPCNDHPDDKATYDITVTVPAG 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 220 YITLFNTPLHNTINHPKlrSYSLDFFHTTAPMSTHAFGFVILKlhmWNEHKIVKSSDIPaINIWsnnLSSTNLLDIQNKL 299
Cdd:cd09603  144 LTVVSNGRLVSTTTNGG--GTTTWHWKMDYPIATYLVTLAVGR---YAVVEDGSGGGIP-LRYY---VPPGDAAKAKASF 214
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028 300 NVAHTTIQHF--FNIPLPLTKLDVIAIPSL------ATLPFISASGILIARESEILkkdvfeISRELIYQWIGIWITPEW 371
Cdd:cd09603  215 ARTPEMLDFFeeLFGPYPFEKYGQVVVPDLgggmehQTATTYGNNFLNGDRGSERL------IAHELAHQWFGDSVTCAD 288

                 ...
gi 289803028 372 WTD 374
Cdd:cd09603  289 WAD 291
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
82-217 1.03e-03

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: 42.84  E-value: 1.03e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 289803028   82 HLRWIGDSKKVYFHAHDTLLIDVSQINLTTLNMGDGTLDKNVIILRGVRLP-----RKPVF----VLYLKDKIKKGSECL 152
Cdd:TIGR02411  17 DLNLSVDFTKRKLSGSVTFTLKSLTDNLNKLVLDTSYLDIQKVTINGLPADfaigeRKEPLgsplTISLPIATSKNDEFV 96
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 289803028  153 LDIYFQGNISETeeGLfrSYYTNSGNDGEEI-YLATNLKPNNARRLFPCFDEPGIKVPFNVSIARP 217
Cdd:TIGR02411  97 LNISFSTTPKCT--AL--QWLNPEQTSGKKHpYLFSQCQAIHARSLFPCQDTPSVKSTYTAEVESP 158
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
184-224 7.10e-03

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: 39.75  E-value: 7.10e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 289803028 184 YLATNLKPNNARRLFPCFDEPGIKVPFNVSIARPKGYITLF 224
Cdd:cd09599  126 YLFTQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALM 166
 
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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