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Conserved domains on  [gi|71989076|ref|NP_001023210|]
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Puromycin-sensitive aminopeptidase [Caenorhabditis elegans]

Protein Classification

M1 family metallopeptidase( domain architecture ID 10176184)

M1 family metallopeptidase containing an ERAP1-like C-terminal domain with HEAT-like repeats is a zinc-dependent metallopeptidase with an HEXXH motif as part of its active site, similar to aminopeptidase N, a broad specificity aminopeptidase, and glutamyl aminopeptidase, which releases N-terminal glutamate from a peptide

EC:  3.4.11.-
Gene Ontology:  GO:0008237|GO:0008270|GO:0006508
MEROPS:  M1

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
87-524 0e+00

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: 678.92  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  87 THYNVRLSPCLNQFSFDGHATIDVTIKEATDVLKVHAQSLLIQSVSLITQPGDASKSLETSYDDKLNILTIKLPTTMQP- 165
Cdd:cd09601   1 LHYDLTLTPDLENFTFSGSVTITLEVLEPTDTIVLHAKDLTITSASLTLKGGSGIIEVTVVTDEETEFLTITLDETLPPg 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 166 QKVQLDFKFVGELNDKMRGFYRSQYKDKNGTEKFLASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMNVI 245
Cdd:cd09601  81 ENYTLSIEFTGKLNDDLRGFYRSSYTDEDGETRYLAATQFEPTDARRAFPCFDEPAFKATFDITITHPKGYTALSNMPPV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 246 SETPTADGkRKAVTFATSPKMSSYLVAFAVGELEYISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDIKY 325
Cdd:cd09601 161 ESTELEDG-WKTTTFETTPPMSTYLVAFVVGDFEYIESTTKSGVPVRVYARPGKIEQGDFALEVAPKILDFYEDYFGIPY 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 326 PLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPGVTSTRQKSRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFASF 405
Cdd:cd09601 240 PLPKLDLVAIPDFAAGAMENWGLITYRETALLYDPKTSSASDKQRVAEVIAHELAHQWFGNLVTMKWWDDLWLNEGFATY 319
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 406 MEYMFVGANCPEFKIWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVFQKG 485
Cdd:cd09601 320 MEYLAVDKLFPEWNMWDQFVVDELQSALELDSLASSHPIEVPVESPSEISEIFDAISYSKGASVLRMLENFLGEEVFRKG 399
                       410       420       430       440
                ....*....|....*....|....*....|....*....|...
gi 71989076 486 LRLYLKRFQYSNAVTQDLWTALSEASGQ----NVNELMSGWTQ 524
Cdd:cd09601 400 LRKYLKKHAYGNATTDDLWEALQEASGEskplDVKEIMDSWTL 442
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
602-927 2.56e-72

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: 241.41  E-value: 2.56e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   602 WVKLNSGTTGFYRVEYSDEMLTAMLPDIASRRMPVLDRFGLINDLSALLNTGRVSIAQFVQVAASSAKEDEYVVWGAIDE 681
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSKVLSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWSAALS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   682 GMSKLLACAREMSEdtLKSAKQLVVKMFEQTGAELGFAEQAGEDSQKMMLRSLVQARLARAGHQPTIDKFTQMFNDFLEK 761
Cdd:pfam11838  81 QLSTLRSLLSADPE--YEALKAFLRKLLSPLAEKLGWEAPPGESHLDRQLRALLLSAACSAGDPECVAEAKKLFDAWLDG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   762 GTPIHPDIRLATFGVVARYGGKEGFDKLMNLRETTTFQEIERQTMVAMSQTPEESLLAQLFEYGFEKNKVRPQDQLYLFL 841
Cdd:pfam11838 159 DDAIPPDLRWAVYCAAVANGGEAEWDALLERYRDTTSPSEKERALRALAATPDPELLQRALELALDSDEVRNQDLRAVIA 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   842 GTGATHMGQQYAWKYFCEHIKEFLDKYGGanSSLFQRCLKFAGESFGNEKRAVEFQDFFcncnvlSDTDRQTLARPIGQT 921
Cdd:pfam11838 239 GLASNPAGRDLAWDFVKENWDALVKRLGG--GSSLGRLVKGLTPSFSTEEELDEVEAFF------ADKDTPGLRRALAQA 310

                  ....*.
gi 71989076   922 VEAIRL 927
Cdd:pfam11838 311 LETIRR 316
 
Name Accession Description Interval E-value
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
87-524 0e+00

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: 678.92  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  87 THYNVRLSPCLNQFSFDGHATIDVTIKEATDVLKVHAQSLLIQSVSLITQPGDASKSLETSYDDKLNILTIKLPTTMQP- 165
Cdd:cd09601   1 LHYDLTLTPDLENFTFSGSVTITLEVLEPTDTIVLHAKDLTITSASLTLKGGSGIIEVTVVTDEETEFLTITLDETLPPg 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 166 QKVQLDFKFVGELNDKMRGFYRSQYKDKNGTEKFLASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMNVI 245
Cdd:cd09601  81 ENYTLSIEFTGKLNDDLRGFYRSSYTDEDGETRYLAATQFEPTDARRAFPCFDEPAFKATFDITITHPKGYTALSNMPPV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 246 SETPTADGkRKAVTFATSPKMSSYLVAFAVGELEYISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDIKY 325
Cdd:cd09601 161 ESTELEDG-WKTTTFETTPPMSTYLVAFVVGDFEYIESTTKSGVPVRVYARPGKIEQGDFALEVAPKILDFYEDYFGIPY 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 326 PLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPGVTSTRQKSRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFASF 405
Cdd:cd09601 240 PLPKLDLVAIPDFAAGAMENWGLITYRETALLYDPKTSSASDKQRVAEVIAHELAHQWFGNLVTMKWWDDLWLNEGFATY 319
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 406 MEYMFVGANCPEFKIWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVFQKG 485
Cdd:cd09601 320 MEYLAVDKLFPEWNMWDQFVVDELQSALELDSLASSHPIEVPVESPSEISEIFDAISYSKGASVLRMLENFLGEEVFRKG 399
                       410       420       430       440
                ....*....|....*....|....*....|....*....|...
gi 71989076 486 LRLYLKRFQYSNAVTQDLWTALSEASGQ----NVNELMSGWTQ 524
Cdd:cd09601 400 LRKYLKKHAYGNATTDDLWEALQEASGEskplDVKEIMDSWTL 442
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
86-705 1.00e-149

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 456.41  E-value: 1.00e-149
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  86 PTHYNVRLSPCLNQFSFDGHATIDVTIKEA-TDVLKVHAQSLLIQSVSLitqpgdASKSLETSYDDklNILTIKLPTTMQ 164
Cdd:COG0308  17 VTHYDLDLDLDPATTRLSGTATITFTATEApLDSLVLDLKGLEVTSVTV------DGKPLDFTRDG--ERLTITLPKPLA 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 165 P-QKVQLDFKFVGELNDKMRGFYRSQYKDKNGTEkflASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMN 243
Cdd:COG0308  89 PgETFTLEIEYSGKPSNGGEGLYRSGDPPDGPPY---LYTQCEPEGARRWFPCFDHPDDKATFTLTVTVPAGWVAVSNGN 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 244 VISETPTADGkRKAVTFATSPKMSSYLVAFAVGELEYISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDI 323
Cdd:COG0308 166 LVSETELGDG-RTTWHWADTQPIPTYLFALAAGDYAVVEDTFASGVPLRVYVRPGLADKAKEAFESTKRMLDFFEELFGV 244
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 324 KYPLPKCDLIAIPDFSMGAMENWGLVTYREiALLVDPGVTSTRQKSRVAlVVAHELAHLWFGNLVTMKWWTDLWLKEGFA 403
Cdd:COG0308 245 PYPFDKYDQVAVPDFNFGAMENQGLVTFGE-KVLADETATDADYERRES-VIAHELAHQWFGNLVTCADWDDLWLNEGFA 322
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 404 SFMEYMFVGANCPEfKIWLHFLNDELAS-GMGLDALRNSHPIevEIDNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVF 482
Cdd:COG0308 323 TYMEQLFSEDLYGK-DAADRIFVGALRSyAFAEDAGPNAHPI--RPDDYPEIENFFDGIVYEKGALVLHMLRTLLGDEAF 399
                       410       420       430       440       450       460       470       480
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 483 QKGLRLYLKRFQYSNAVTQDLWTALSEASGQNVNELMSGWTQQMGFPVLKVSQRQDGNNRI-LTVEQRRfisdggedPKN 561
Cdd:COG0308 400 RAGLRLYFARHAGGNATTEDFLAALEEASGRDLSAFFDQWLYQAGLPTLEVEYEYDADGKVtLTLRQTP--------PRP 471
                       490       500       510       520       530       540       550       560
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 562 SQWQVPITVAVGsSPSDVKARFLLKEKQQEFtiegVAPGEWVKLnsgttgfyrVEYSDEMLTAMLPDiasrrMPVLDRFG 641
Cdd:COG0308 472 HPFHIPLEVGLL-GGKLTARTVLLDGEQTEL----VAKPDPVLL---------LRLDDELAFLLAHD-----SDPFNRWE 532
                       570       580       590       600       610       620
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71989076 642 LINDLSallntgRVSIAQFVQvAASSAKEDEYVVWGAIdegmskllacAREMSEDTLKSAKQLV 705
Cdd:COG0308 533 ALQALW------RDGEADYLD-ALRALADTDPAVRAEA----------LALLGSDQLALARAAL 579
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
305-522 2.44e-119

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: 362.76  E-value: 2.44e-119
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   305 YSLDLSVKCIDWYNEWFDIKYPLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPGVTSTRQKSRVALVVAHELAHLWF 384
Cdd:pfam01433   1 YALEITVKLLEFYEDYFNIPYPLPKYDLVALPDFSAGAMENWGLITYRETLLLYDPGNSSTSDKQRVASVIAHELAHQWF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   385 GNLVTMKWWTDLWLKEGFASFMEYMFVGANCPEFKIWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYA 464
Cdd:pfam01433  81 GNLVTMKWWDDLWLNEGFATYMEYLGTDALFPEWNIWEQFLLDEVQNAMARDALDSSHPITQNVNDPSEIDDIFDAIPYE 160
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 71989076   465 KSNSVNRMLCYYLSEPVFQKGLRLYLKRFQYSNAVTQDLWTALSEASG-QNVNELMSGW 522
Cdd:pfam01433 161 KGASVLRMLETLLGEEVFQKGLRSYLKKFQYGNATTEDLWDALSEASGpLDVDSFMDTW 219
pepN_strep_liv TIGR02412
aminopeptidase N, Streptomyces lividans type; This family is a subset of the members of the ...
88-815 7.87e-85

aminopeptidase N, Streptomyces lividans type; This family is a subset of the members of the zinc metallopeptidase family M1 (pfam01433), with a single member characterized in Streptomyces lividans 66 and designated aminopeptidase N. The spectrum of activity may differ somewhat from the aminopeptidase N clade of E. coli and most other Proteobacteria, well separated phylogenetically within the M1 family. The M1 family also includes leukotriene A-4 hydrolase/aminopeptidase (with a bifunctional active site).


Pssm-ID: 274121 [Multi-domain]  Cd Length: 831  Bit Score: 290.92  E-value: 7.87e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076    88 HYNVRLSPCLNQFSFDGHATIDVTIKEATDVlkvhAQSLL------IQSVSLitqpgDASKSLETSYDDKlnilTIKLPT 161
Cdd:TIGR02412  18 HYEIALDLTGADEFFATRCVSTNTVRLSEPG----ADTFLdllaaqIESVTL-----NGILDVAPVYDGS----RIPLPG 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   162 TMQPQK-VQLDFKF----VGElndkmrGFYRSQykDKNGTEKFLaSTQFESTYARYAFPCFDEPIYKATFDVTLEVENHL 236
Cdd:TIGR02412  85 LLTGENtLRVEATRaytnTGE------GLHRFV--DPVDGEVYL-YTQFEPADARRVFAVFDQPDLKANFKFSVKAPEDW 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   237 TALSNMNVISETPTADGKRKavTFATSPKMSSYLVAFAVGEleYISAQTKS-GVEMRVYTVPGKKEQ--GQYSLDLSVKC 313
Cdd:TIGR02412 156 TVISNSRETDVTPEPADRRW--EFPETPKLSTYLTAVAAGP--YHSVQDESrSYPLGIYARRSLAQYldADAIFTITRQG 231
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   314 IDWYNEWFDIKYPLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPgVTSTrQKSRVALVVAHELAHLWFGNLVTMKWW 393
Cdd:TIGR02412 232 LAFFHRKFGYPYPFKKYDQIFVPEFNAGAMENAGCVTFAENFLHRAE-ATRA-EKENRAGVILHEMAHMWFGDLVTMRWW 309
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   394 TDLWLKEGFASFMEYMfVGANCPEFK-IWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYAKSNSVNRM 472
Cdd:TIGR02412 310 NDLWLNESFAEYMGTL-ASAEATEYTdAWTTFAAQGKQWAYEADQLPTTHPIVADVADLADALSNFDGITYAKGASVLKQ 388
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   473 LCYYLSEPVFQKGLRLYLKRFQYSNAVTQDLWTALSEASGQNVNELMSGWTQQMGFPVLKVSQRQDGNnriltveqrRFI 552
Cdd:TIGR02412 389 LVAWVGEEAFFAGVNAYFKRHAFGNATLDDLIDSLAKASGRDLSAWSDAWLETAGVNTLTPEITTDGG---------VVS 459
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   553 SdggEDPKNSQWQVPITVAVG--SSPSDVkarfLLKEKQQEFTIEG---VAP---GEW----VKLNSGTTGFYRVEYSDE 620
Cdd:TIGR02412 460 A---LYPESSGPPRPHRIAIGlyDLDRDD----LRRTTLVPLTISGertAVPqlvGKRapalVLLNDDDLTYAKVRLDPT 532
                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   621 MLTAMLPDIASRRMPvLDRFGLINDLSALLNTGRVSIAQFVQ-VAASSAKEDEYVVWGAIdegmsklLACAREMSEDTLK 699
Cdd:TIGR02412 533 SFDTVLAALSKLPDP-LSRAVVWASLWDSVRDGELSPDDYLStVFAHVPSETDYAVVQQV-------LSQLLRAVAAQYA 604
                         650       660       670       680       690       700       710       720
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   700 SAKQLVVKMFEQTGAELGFAE--QAGEDSQKMMLRSLVQArlarAGHQPTIDKFTQMFnDFLEKGTPIHPDIRLATFGVV 777
Cdd:TIGR02412 605 PIADRPALLAVAALACRSLRRamESGPDFQLRWLRALALT----ATDPDSLRRLLSLL-DGKIKGLALDPDLRWRIIARL 679
                         730       740       750
                  ....*....|....*....|....*....|....*...
gi 71989076   778 ARYGGKEGfDKLMNLRETTTFQEIERQTMVAMSQTPEE 815
Cdd:TIGR02412 680 AALGFIDA-DDIAAELERDNTASGEEHAAAARAARPDA 716
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
602-927 2.56e-72

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: 241.41  E-value: 2.56e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   602 WVKLNSGTTGFYRVEYSDEMLTAMLPDIASRRMPVLDRFGLINDLSALLNTGRVSIAQFVQVAASSAKEDEYVVWGAIDE 681
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSKVLSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWSAALS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   682 GMSKLLACAREMSEdtLKSAKQLVVKMFEQTGAELGFAEQAGEDSQKMMLRSLVQARLARAGHQPTIDKFTQMFNDFLEK 761
Cdd:pfam11838  81 QLSTLRSLLSADPE--YEALKAFLRKLLSPLAEKLGWEAPPGESHLDRQLRALLLSAACSAGDPECVAEAKKLFDAWLDG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   762 GTPIHPDIRLATFGVVARYGGKEGFDKLMNLRETTTFQEIERQTMVAMSQTPEESLLAQLFEYGFEKNKVRPQDQLYLFL 841
Cdd:pfam11838 159 DDAIPPDLRWAVYCAAVANGGEAEWDALLERYRDTTSPSEKERALRALAATPDPELLQRALELALDSDEVRNQDLRAVIA 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   842 GTGATHMGQQYAWKYFCEHIKEFLDKYGGanSSLFQRCLKFAGESFGNEKRAVEFQDFFcncnvlSDTDRQTLARPIGQT 921
Cdd:pfam11838 239 GLASNPAGRDLAWDFVKENWDALVKRLGG--GSSLGRLVKGLTPSFSTEEELDEVEAFF------ADKDTPGLRRALAQA 310

                  ....*.
gi 71989076   922 VEAIRL 927
Cdd:pfam11838 311 LETIRR 316
pepN PRK14015
aminopeptidase N; Provisional
224-623 6.41e-25

aminopeptidase N; Provisional


Pssm-ID: 237585 [Multi-domain]  Cd Length: 875  Bit Score: 111.76  E-value: 6.41e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  224 ATFDVTLEVEN----HLtaLSNMNVISETPTADGKRKAVTFATSPKmSSYLVAFAVGELEYISA--QTKSG--VEMRVYT 295
Cdd:PRK14015 144 ARYTVRIEADKakypVL--LSNGNLVESGELPDGRHWATWEDPFPK-PSYLFALVAGDLDVLEDtfTTRSGreVALEIYV 220
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  296 VPGKKEQGQYSLDLSVKCIDWYNEWFDIKYplpkcDL-----IAIPDFSMGAMENWGL-------VtyreialLVDPgVT 363
Cdd:PRK14015 221 EPGNLDKCDHAMDSLKKSMKWDEERFGLEY-----DLdifmiVAVDDFNMGAMENKGLnifnskyV-------LADP-ET 287
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  364 STRQK-SRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFASFMEYMFvgancpefkiwlhflndelASGMGLDA----- 437
Cdd:PRK14015 288 ATDADyERIESVIAHEYFHNWTGNRVTCRDWFQLSLKEGLTVFRDQEF-------------------SADLGSRAvkrie 348
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  438 ----LRN----------SHPIE----VEIDNpneldeIYDSITYAKSNSVNRMLCYYLSEPVFQKGLRLYLKRF--Qysn 497
Cdd:PRK14015 349 dvrvLRAaqfaedagpmAHPVRpdsyIEINN------FYTATVYEKGAEVIRMLHTLLGEEGFRKGMDLYFERHdgQ--- 419
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  498 AVT-QDLWTALSEASGQNVNELMSgWTQQMGFPVLKVSQRQDGNNRI--LTVEQRRFISDGGEDPKNsqwqVPITVAVG- 573
Cdd:PRK14015 420 AVTcEDFVAAMEDASGRDLSQFRR-WYSQAGTPRVTVSDEYDAAAGTytLTLSQSTPPTPGQPEKQP----LHIPVAIGl 494
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71989076  574 --------------SSPSDVkarFLLKEKQQEFTIEGV-------------APgewVKLNSgttgfyrvEYSDEMLT 623
Cdd:PRK14015 495 ldpdgkelplqlegEPVERV---LELTEAEQTFTFENVaerpvpsllrgfsAP---VKLEY--------DYSDEDLL 557
 
Name Accession Description Interval E-value
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
87-524 0e+00

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: 678.92  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  87 THYNVRLSPCLNQFSFDGHATIDVTIKEATDVLKVHAQSLLIQSVSLITQPGDASKSLETSYDDKLNILTIKLPTTMQP- 165
Cdd:cd09601   1 LHYDLTLTPDLENFTFSGSVTITLEVLEPTDTIVLHAKDLTITSASLTLKGGSGIIEVTVVTDEETEFLTITLDETLPPg 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 166 QKVQLDFKFVGELNDKMRGFYRSQYKDKNGTEKFLASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMNVI 245
Cdd:cd09601  81 ENYTLSIEFTGKLNDDLRGFYRSSYTDEDGETRYLAATQFEPTDARRAFPCFDEPAFKATFDITITHPKGYTALSNMPPV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 246 SETPTADGkRKAVTFATSPKMSSYLVAFAVGELEYISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDIKY 325
Cdd:cd09601 161 ESTELEDG-WKTTTFETTPPMSTYLVAFVVGDFEYIESTTKSGVPVRVYARPGKIEQGDFALEVAPKILDFYEDYFGIPY 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 326 PLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPGVTSTRQKSRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFASF 405
Cdd:cd09601 240 PLPKLDLVAIPDFAAGAMENWGLITYRETALLYDPKTSSASDKQRVAEVIAHELAHQWFGNLVTMKWWDDLWLNEGFATY 319
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 406 MEYMFVGANCPEFKIWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVFQKG 485
Cdd:cd09601 320 MEYLAVDKLFPEWNMWDQFVVDELQSALELDSLASSHPIEVPVESPSEISEIFDAISYSKGASVLRMLENFLGEEVFRKG 399
                       410       420       430       440
                ....*....|....*....|....*....|....*....|...
gi 71989076 486 LRLYLKRFQYSNAVTQDLWTALSEASGQ----NVNELMSGWTQ 524
Cdd:cd09601 400 LRKYLKKHAYGNATTDDLWEALQEASGEskplDVKEIMDSWTL 442
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
86-705 1.00e-149

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 456.41  E-value: 1.00e-149
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  86 PTHYNVRLSPCLNQFSFDGHATIDVTIKEA-TDVLKVHAQSLLIQSVSLitqpgdASKSLETSYDDklNILTIKLPTTMQ 164
Cdd:COG0308  17 VTHYDLDLDLDPATTRLSGTATITFTATEApLDSLVLDLKGLEVTSVTV------DGKPLDFTRDG--ERLTITLPKPLA 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 165 P-QKVQLDFKFVGELNDKMRGFYRSQYKDKNGTEkflASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMN 243
Cdd:COG0308  89 PgETFTLEIEYSGKPSNGGEGLYRSGDPPDGPPY---LYTQCEPEGARRWFPCFDHPDDKATFTLTVTVPAGWVAVSNGN 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 244 VISETPTADGkRKAVTFATSPKMSSYLVAFAVGELEYISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDI 323
Cdd:COG0308 166 LVSETELGDG-RTTWHWADTQPIPTYLFALAAGDYAVVEDTFASGVPLRVYVRPGLADKAKEAFESTKRMLDFFEELFGV 244
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 324 KYPLPKCDLIAIPDFSMGAMENWGLVTYREiALLVDPGVTSTRQKSRVAlVVAHELAHLWFGNLVTMKWWTDLWLKEGFA 403
Cdd:COG0308 245 PYPFDKYDQVAVPDFNFGAMENQGLVTFGE-KVLADETATDADYERRES-VIAHELAHQWFGNLVTCADWDDLWLNEGFA 322
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 404 SFMEYMFVGANCPEfKIWLHFLNDELAS-GMGLDALRNSHPIevEIDNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVF 482
Cdd:COG0308 323 TYMEQLFSEDLYGK-DAADRIFVGALRSyAFAEDAGPNAHPI--RPDDYPEIENFFDGIVYEKGALVLHMLRTLLGDEAF 399
                       410       420       430       440       450       460       470       480
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 483 QKGLRLYLKRFQYSNAVTQDLWTALSEASGQNVNELMSGWTQQMGFPVLKVSQRQDGNNRI-LTVEQRRfisdggedPKN 561
Cdd:COG0308 400 RAGLRLYFARHAGGNATTEDFLAALEEASGRDLSAFFDQWLYQAGLPTLEVEYEYDADGKVtLTLRQTP--------PRP 471
                       490       500       510       520       530       540       550       560
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 562 SQWQVPITVAVGsSPSDVKARFLLKEKQQEFtiegVAPGEWVKLnsgttgfyrVEYSDEMLTAMLPDiasrrMPVLDRFG 641
Cdd:COG0308 472 HPFHIPLEVGLL-GGKLTARTVLLDGEQTEL----VAKPDPVLL---------LRLDDELAFLLAHD-----SDPFNRWE 532
                       570       580       590       600       610       620
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71989076 642 LINDLSallntgRVSIAQFVQvAASSAKEDEYVVWGAIdegmskllacAREMSEDTLKSAKQLV 705
Cdd:COG0308 533 ALQALW------RDGEADYLD-ALRALADTDPAVRAEA----------LALLGSDQLALARAAL 579
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
305-522 2.44e-119

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: 362.76  E-value: 2.44e-119
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   305 YSLDLSVKCIDWYNEWFDIKYPLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPGVTSTRQKSRVALVVAHELAHLWF 384
Cdd:pfam01433   1 YALEITVKLLEFYEDYFNIPYPLPKYDLVALPDFSAGAMENWGLITYRETLLLYDPGNSSTSDKQRVASVIAHELAHQWF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   385 GNLVTMKWWTDLWLKEGFASFMEYMFVGANCPEFKIWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYA 464
Cdd:pfam01433  81 GNLVTMKWWDDLWLNEGFATYMEYLGTDALFPEWNIWEQFLLDEVQNAMARDALDSSHPITQNVNDPSEIDDIFDAIPYE 160
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 71989076   465 KSNSVNRMLCYYLSEPVFQKGLRLYLKRFQYSNAVTQDLWTALSEASG-QNVNELMSGW 522
Cdd:pfam01433 161 KGASVLRMLETLLGEEVFQKGLRSYLKKFQYGNATTEDLWDALSEASGpLDVDSFMDTW 219
M1_APN cd09602
Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the ...
88-525 1.11e-114

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: 358.75  E-value: 1.11e-114
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  88 HYNVRLSPCLNQFSFDGHATIDVTIKEATDVLKVHAQSLLIQSVSLitqpgdASKSLETSYDDKLNIltiKLPTTMQPQK 167
Cdd:cd09602  17 SYDLDLDLTEGAETFRGTVTIRFTLREPGASLFLDFRGGEVKSVTL------NGRPLDPSAFDGERI---TLPGLLKAGE 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 168 VQLDFKFVGELNDKMRGFYRsqYKDKNGTEKFLaSTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMNVISE 247
Cdd:cd09602  88 NTVVVEFTAPYSSDGEGLHR--FVDPADGETYL-YTLFEPDDARRVFPCFDQPDLKATFTLTVTAPADWTVISNGPETST 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 248 TPTADGKRkaVTFATSPKMSSYLVAFAVGELEYISAQTKsGVEMRVY---TVPGKKEQGQYSLDLSVKCIDWYNEWFDIK 324
Cdd:cd09602 165 EEAGGRKR--WRFAETPPLSTYLFAFVAGPYHRVEDEHD-GIPLGLYcreSLAEYERDADEIFEVTKQGLDFYEDYFGIP 241
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 325 YPLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPgVTSTrQKSRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFAS 404
Cdd:cd09602 242 YPFGKYDQVFVPEFNFGAMENPGAVTFRESYLFREE-PTRA-QRLRRANTILHEMAHMWFGDLVTMKWWDDLWLNESFAD 319
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 405 FMEYMFVGANCPEFKIWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVFQK 484
Cdd:cd09602 320 FMAAKALAEATPFTDAWLTFLLRRKPWAYRADQLPTTHPIAQDVPDLEAAGSNFDGITYAKGASVLKQLVALVGEEAFRA 399
                       410       420       430       440
                ....*....|....*....|....*....|....*....|.
gi 71989076 485 GLRLYLKRFQYSNAVTQDLWTALSEASGQNvnelMSGWTQQ 525
Cdd:cd09602 400 GLREYFKKHAYGNATLDDLIAALDEASGRD----LSAWADA 436
M1 cd09595
Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 ...
87-509 8.22e-105

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: 332.10  E-value: 8.22e-105
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  87 THYNVRLSPCLNQFSFDGHATIDVTIKEATDVLKVHAQSLLIQSVSLitQPGDASKSLETSYDD-KLNILTIKLPTtmQP 165
Cdd:cd09595   1 YHYDLDLDVDFTTKTLNGTETLTVDASQVGRELVLDLVGLTIHSVSV--NGAAVDFGEREHYDGeKLTIPGPKPPG--QT 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 166 QKVQLDFKfvGELNDKMRGFYRSQYKdknGTEKFLASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMNVI 245
Cdd:cd09595  77 FTVRISFE--AKPSKNLLGWLWEQTA---GKEKPYLFTQFEATHARRIFPCIDHPAVKATFTVTITTPKKDLLASNGALV 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 246 SETPTADGkRKAVTFATSPKMSSYLVAFAVGELE--YISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDI 323
Cdd:cd09595 152 GEETGANG-RKTYRFEDTPPIPTYLVAVVVGDLEfkYVTVKSQPRVGLSVYSEPLQVDQAQYAFDATRAALAWFEDYFGG 230
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 324 KYPLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPGVTSTrqKSRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFA 403
Cdd:cd09595 231 PYPLPKYDLLAVPDFNSGAMENPGLITFRTTYLLRSKVTDTG--ARSIENVIAHELAHQWFGNLVTMRWWNDLWLNEGFA 308
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 404 SFMEYMFVGANCPEFKIwlHFLNDELAS-GMGLDALRNSHPIEVEIDNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVF 482
Cdd:cd09595 309 VYYENRIMDATFGTSSR--HLDQLSGSSdLNTEQLLEDSSPTSTPVRSPADPDVAYDGVTYAKGALVLRMLEELVGEEAF 386
                       410       420
                ....*....|....*....|....*..
gi 71989076 483 QKGLRLYLKRFQYSNAVTQDLWTALSE 509
Cdd:cd09595 387 DKGVQAYFNRHKFKNATTDDFIDALEE 413
pepN_strep_liv TIGR02412
aminopeptidase N, Streptomyces lividans type; This family is a subset of the members of the ...
88-815 7.87e-85

aminopeptidase N, Streptomyces lividans type; This family is a subset of the members of the zinc metallopeptidase family M1 (pfam01433), with a single member characterized in Streptomyces lividans 66 and designated aminopeptidase N. The spectrum of activity may differ somewhat from the aminopeptidase N clade of E. coli and most other Proteobacteria, well separated phylogenetically within the M1 family. The M1 family also includes leukotriene A-4 hydrolase/aminopeptidase (with a bifunctional active site).


Pssm-ID: 274121 [Multi-domain]  Cd Length: 831  Bit Score: 290.92  E-value: 7.87e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076    88 HYNVRLSPCLNQFSFDGHATIDVTIKEATDVlkvhAQSLL------IQSVSLitqpgDASKSLETSYDDKlnilTIKLPT 161
Cdd:TIGR02412  18 HYEIALDLTGADEFFATRCVSTNTVRLSEPG----ADTFLdllaaqIESVTL-----NGILDVAPVYDGS----RIPLPG 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   162 TMQPQK-VQLDFKF----VGElndkmrGFYRSQykDKNGTEKFLaSTQFESTYARYAFPCFDEPIYKATFDVTLEVENHL 236
Cdd:TIGR02412  85 LLTGENtLRVEATRaytnTGE------GLHRFV--DPVDGEVYL-YTQFEPADARRVFAVFDQPDLKANFKFSVKAPEDW 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   237 TALSNMNVISETPTADGKRKavTFATSPKMSSYLVAFAVGEleYISAQTKS-GVEMRVYTVPGKKEQ--GQYSLDLSVKC 313
Cdd:TIGR02412 156 TVISNSRETDVTPEPADRRW--EFPETPKLSTYLTAVAAGP--YHSVQDESrSYPLGIYARRSLAQYldADAIFTITRQG 231
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   314 IDWYNEWFDIKYPLPKCDLIAIPDFSMGAMENWGLVTYREIALLVDPgVTSTrQKSRVALVVAHELAHLWFGNLVTMKWW 393
Cdd:TIGR02412 232 LAFFHRKFGYPYPFKKYDQIFVPEFNAGAMENAGCVTFAENFLHRAE-ATRA-EKENRAGVILHEMAHMWFGDLVTMRWW 309
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   394 TDLWLKEGFASFMEYMfVGANCPEFK-IWLHFLNDELASGMGLDALRNSHPIEVEIDNPNELDEIYDSITYAKSNSVNRM 472
Cdd:TIGR02412 310 NDLWLNESFAEYMGTL-ASAEATEYTdAWTTFAAQGKQWAYEADQLPTTHPIVADVADLADALSNFDGITYAKGASVLKQ 388
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   473 LCYYLSEPVFQKGLRLYLKRFQYSNAVTQDLWTALSEASGQNVNELMSGWTQQMGFPVLKVSQRQDGNnriltveqrRFI 552
Cdd:TIGR02412 389 LVAWVGEEAFFAGVNAYFKRHAFGNATLDDLIDSLAKASGRDLSAWSDAWLETAGVNTLTPEITTDGG---------VVS 459
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   553 SdggEDPKNSQWQVPITVAVG--SSPSDVkarfLLKEKQQEFTIEG---VAP---GEW----VKLNSGTTGFYRVEYSDE 620
Cdd:TIGR02412 460 A---LYPESSGPPRPHRIAIGlyDLDRDD----LRRTTLVPLTISGertAVPqlvGKRapalVLLNDDDLTYAKVRLDPT 532
                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   621 MLTAMLPDIASRRMPvLDRFGLINDLSALLNTGRVSIAQFVQ-VAASSAKEDEYVVWGAIdegmsklLACAREMSEDTLK 699
Cdd:TIGR02412 533 SFDTVLAALSKLPDP-LSRAVVWASLWDSVRDGELSPDDYLStVFAHVPSETDYAVVQQV-------LSQLLRAVAAQYA 604
                         650       660       670       680       690       700       710       720
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   700 SAKQLVVKMFEQTGAELGFAE--QAGEDSQKMMLRSLVQArlarAGHQPTIDKFTQMFnDFLEKGTPIHPDIRLATFGVV 777
Cdd:TIGR02412 605 PIADRPALLAVAALACRSLRRamESGPDFQLRWLRALALT----ATDPDSLRRLLSLL-DGKIKGLALDPDLRWRIIARL 679
                         730       740       750
                  ....*....|....*....|....*....|....*...
gi 71989076   778 ARYGGKEGfDKLMNLRETTTFQEIERQTMVAMSQTPEE 815
Cdd:TIGR02412 680 AALGFIDA-DDIAAELERDNTASGEEHAAAARAARPDA 716
Peptidase_M1_N pfam17900
Peptidase M1 N-terminal domain; This domain is found at the N-terminus of aminopeptidases from ...
86-270 3.25e-73

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: 239.17  E-value: 3.25e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076    86 PTHYNVRLSPCLNQFSFDGHATIDVTIKEATDVLKVHAQSLLIQSVSLITQPGDASKSLETSYDDKLNI-LTIKLPTTM- 163
Cdd:pfam17900   2 PEHYDLDLKIDLKNFTFSGSVTITLQLNNATNVIVLHASDLTIRSISLSDEVTSDGVPADFTEDQKDGEkLTIVLPETLn 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   164 QPQKVQLDFKFVGELNDKMRGFYRSQYKDkNGTEKFLASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMN 243
Cdd:pfam17900  82 QTGPYTLEIEYSGELNDSMTGFYRSTYTD-NGEKKVLVTTQFEPTDARSAFPCFDEPSVKATFTISIIHPKDYTALSNMP 160
                         170       180
                  ....*....|....*....|....*..
gi 71989076   244 VISETPTADGKRKaVTFATSPKMSSYL 270
Cdd:pfam17900 161 VIASEPLENGWVI-TTFEQTPKMSTYL 186
M1_APN_like cd09603
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly ...
87-522 1.02e-72

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: 245.96  E-value: 1.02e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  87 THYNVRLSPCLNQFSFDGHATIDVTIKEATDVLKVHAQSLLIQSVSLitqpgDASKSLETSYDDklNILTIKLPTTMQP- 165
Cdd:cd09603   4 LHYDLDLDYDPATKSLSGTATITFRATQDLDSLQLDLVGLTVSSVTV-----DGVPAAFFTHDG--DKLVITLPRPLAAg 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 166 QKVQLDFKFVGElNDKMRGFYRSQYKDKNGTEkfLASTQFESTYARYAFPCFDEPIYKATFDVTLEVENHLTALSNMNVI 245
Cdd:cd09603  77 ETFTVTVRYSGK-PRPAGYPPGDGGGWEEGDD--GVWTAGQPEGASTWFPCNDHPDDKATYDITVTVPAGLTVVSNGRLV 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 246 SETPTADGkRKAVTFATSPKMSSYLVAFAVGELEYISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFdIKY 325
Cdd:cd09603 154 STTTNGGG-TTTWHWKMDYPIATYLVTLAVGRYAVVEDGSGGGIPLRYYVPPGDAAKAKASFARTPEMLDFFEELF-GPY 231
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 326 PLPKCDLIAIPDFSmGAMENWGLVTYREIALLVDPGVTStrqksrvalVVAHELAHLWFGNLVTMKWWTDLWLKEGFASF 405
Cdd:cd09603 232 PFEKYGQVVVPDLG-GGMEHQTATTYGNNFLNGDRGSER---------LIAHELAHQWFGDSVTCADWADIWLNEGFATY 301
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 406 MEYMFVGAncpefkiwlHFLNDELASGMglDALRNSHPIEVEI-DNPNELDEIYDSITYAKSNSVNRMLCYYLSEPVFQK 484
Cdd:cd09603 302 AEWLWSEH---------KGGADAYRAYL--AGQRQDYLNADPGpGRPPDPDDLFDRDVYQKGALVLHMLRNLLGDEAFFA 370
                       410       420       430
                ....*....|....*....|....*....|....*...
gi 71989076 485 GLRLYLKRFQYSNAVTQDLWTALSEASGQNVNELMSGW 522
Cdd:cd09603 371 ALRAYLARYAHGNVTTEDFIAAAEEVSGRDLTWFFDQW 408
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
602-927 2.56e-72

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: 241.41  E-value: 2.56e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   602 WVKLNSGTTGFYRVEYSDEMLTAMLPDIASRRMPVLDRFGLINDLSALLNTGRVSIAQFVQVAASSAKEDEYVVWGAIDE 681
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSKVLSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWSAALS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   682 GMSKLLACAREMSEdtLKSAKQLVVKMFEQTGAELGFAEQAGEDSQKMMLRSLVQARLARAGHQPTIDKFTQMFNDFLEK 761
Cdd:pfam11838  81 QLSTLRSLLSADPE--YEALKAFLRKLLSPLAEKLGWEAPPGESHLDRQLRALLLSAACSAGDPECVAEAKKLFDAWLDG 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   762 GTPIHPDIRLATFGVVARYGGKEGFDKLMNLRETTTFQEIERQTMVAMSQTPEESLLAQLFEYGFEKNKVRPQDQLYLFL 841
Cdd:pfam11838 159 DDAIPPDLRWAVYCAAVANGGEAEWDALLERYRDTTSPSEKERALRALAATPDPELLQRALELALDSDEVRNQDLRAVIA 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   842 GTGATHMGQQYAWKYFCEHIKEFLDKYGGanSSLFQRCLKFAGESFGNEKRAVEFQDFFcncnvlSDTDRQTLARPIGQT 921
Cdd:pfam11838 239 GLASNPAGRDLAWDFVKENWDALVKRLGG--GSSLGRLVKGLTPSFSTEEELDEVEAFF------ADKDTPGLRRALAQA 310

                  ....*.
gi 71989076   922 VEAIRL 927
Cdd:pfam11838 311 LETIRR 316
M1_APN cd09600
Peptidase M1 family, including aminopeptidase N catalytic domain; This model represents the ...
119-523 3.23e-39

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: 151.51  E-value: 3.23e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 119 LKVHAQSLLIQSVSLITQPGDASKSLETsyDDKLNIL------TIKLPTTMQPQKvqldfkfvgelNDKMRGFYRSqykd 192
Cdd:cd09600  43 LVLDGEDLELLSVKIDGKPLSPSDYTLD--EEGLTIKnvpdrfVLEIEVRINPAA-----------NTSLEGLYKS---- 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 193 kNGtekfLASTQFES------TYaryaFPcfDEPIYKATFDVTLEVENHL--TALSNMNVISETPTADGKRKAVTFATSP 264
Cdd:cd09600 106 -GG----ILCTQCEAegfrriTY----FP--DRPDVMSKFTVTIEADKEKypVLLSNGNLIEEGELPNGRHFAVWEDPFP 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 265 KmSSYLVAFAVGELEYISAQ--TKSG--VEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDIKYPLPKCDLIAIPDFSM 340
Cdd:cd09600 175 K-PSYLFALVAGDLGSVEDTftTKSGrkVKLRIYVEPGNEDKCHHAMESLKKAMKWDEERFGLEYDLDLFNIVAVDDFNM 253
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 341 GAMENWGLVTYREIALLVDPGVTSTRQKSRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFA-----SFMEYMFVGA-- 413
Cdd:cd09600 254 GAMENKGLNIFNSKYVLADPETATDADYERIESVIAHEYFHNWTGNRVTCRDWFQLSLKEGLTvfrdqEFSADMNSRAvk 333
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 414 --NCPEFKIWLHFLNDelASGMgldalrnSHPIE----VEIDNpneldeIYDSITYAKSNSVNRMLCYYLSEPVFQKGLR 487
Cdd:cd09600 334 riEDVRRLRSAQFPED--AGPM-------AHPIRpdsyIEINN------FYTVTVYEKGAEVIRMLHTLLGEEGFRKGMD 398
                       410       420       430
                ....*....|....*....|....*....|....*..
gi 71989076 488 LYLKRFQySNAVT-QDLWTALSEASGQNVNELMSGWT 523
Cdd:cd09600 399 LYFERHD-GQAVTcEDFVAAMEDASGRDLSQFKRWYS 434
M1_APN_like cd09604
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains ...
128-522 7.30e-36

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: 141.64  E-value: 7.30e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 128 IQSVSLITQPGDASksletsYDDKLNILTIKLPTTMQP-QKVQLDFKFVGELNDKMR--GFYRSQY-----------KDK 193
Cdd:cd09604  68 IDSVKVNGKGLKLE------VTLTITRLKLALPLPLKPgESVTVEIDFTVKLPEQGGrfGYDGDEYnlaqwypklavYDD 141
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 194 NGTEKFLASTQFESTYARYAfpcfdepiykaTFDVTLevenhlTALSNMNVIS-----ETPTADGKRKAVTFATSPkmss 268
Cdd:cd09604 142 GGWNTDPYYGRGEFFYSDFG-----------DYDVTI------TVPKNYVVAAtgelqNPEEVLDGTKTWHFKAEN---- 200
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 269 ylV---AFAVGElEYI-SAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFdIKYPLPKCDLIAiPDFSMGAME 344
Cdd:cd09604 201 --VrdfAWAASP-DFVvDAATVDGVTVNVYYLPENAEAAERALEYAKDALEFFSEKF-GPYPYPELDVVQ-GPFGGGGME 275
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 345 NWGLVTyreiallVDPGVTSTRQKsrVALVVAHELAHLWF----GNLVTmkwwTDLWLKEGFASFMEYMFVGANCPEFKI 420
Cdd:cd09604 276 YPGLVF-------IGSRLYDPKRS--LEGVVVHEIAHQWFygivGNDER----REPWLDEGLATYAESLYLEEKYGKEAA 342
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 421 WLHFLNdelaSGMGLDALRNSHPIEVEIDNPNELDEiYDSITYAKSNSVNRMLCYYLSEPVFQKGLRLYLKRFQYSNAVT 500
Cdd:cd09604 343 DELLGR----RYYRAYARGPGGPINLPLDTFPDGSY-YSNAVYSKGALFLEELREELGDEAFDKALREYYRRYKFKHPTP 417
                       410       420
                ....*....|....*....|..
gi 71989076 501 QDLWTALSEASGQNVNELMSGW 522
Cdd:cd09604 418 EDFFRTAEEVSGKDLDWFFRGW 439
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
82-502 2.66e-33

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: 134.12  E-value: 2.66e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  82 TFAEP-----THYNVRLSPCLNQFSFDGHATIDVT-IKEATDVLKVHAQSLLIQSVSLitqpgDASKSLETSYDDKLNI- 154
Cdd:cd09599   4 SFSNYdevrtTHLDLDLTVDFDKKTISGSATLTLEvLQDGADELVLDTRDLDISSVTV-----NGGKELKFELGPRDPVl 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 155 ---LTIKLPTTM-QPQKVQLDFKFvgELNDKMRGFyrsQYKDKNGTE-K---FLAsTQFESTYARYAFPCFDEPIYKATF 226
Cdd:cd09599  79 gsaLTITLPSPLaKGDTFKVKIEY--STTPQATAL---QWLTPEQTAgKkhpYLF-TQCQAIHARSLFPCQDTPSVKSTY 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 227 DVTLEVENHLTALsnMNVISETPTADGKRKAVTFATSPKMSSYLVAFAVGELEY--ISAQTksgvemRVYTVPGKKEQGQ 304
Cdd:cd09599 153 SATVTVPKGLTAL--MSALRTGEKEEAGTGTYTFEQPVPIPSYLIAIAVGDLESreIGPRS------GVWAEPSVVDAAA 224
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 305 YSLD-----LSV--KCIDWYnEW--FDIkyplpkcdLIAIPDFSMGAMENwGLVTYreiallvdpgVTST---RQKSRVA 372
Cdd:cd09599 225 EEFAdtekfLKAaeKLYGPY-VWgrYDL--------LVLPPSFPYGGMEN-PCLTF----------ATPTliaGDRSLVD 284
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 373 lVVAHELAHLWFGNLVTMKWWTDLWLKEGFASFMEYMFVGA-NCPEFKiwlhflndELASGMGLDALRNS---------- 441
Cdd:cd09599 285 -VIAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLERRILERlYGEEYR--------QFEAILGWKDLQESikefgedppy 355
                       410       420       430       440       450       460
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71989076 442 ---HPIEVEIDnPnelDEIYDSITYAK-SNsvnrmLCYYLS----EPVFQKGLRLYLKRFQYSNAVTQD 502
Cdd:cd09599 356 tllVPDLKGVD-P---DDAFSSVPYEKgFQ-----FLYYLEqlggREVFDPFLRAYFKKFAFQSIDTED 415
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
86-509 2.71e-28

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: 121.42  E-value: 2.71e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076    86 PTHYNVRLSPCLNQFSFDGHATIDVTIKEA-TDVLKVHAQSLLIQSVSLITQPGDASksLETSYDDKLNILTIKLPT-TM 163
Cdd:TIGR02411  13 TSHTDLNLSVDFTKRKLSGSVTFTLKSLTDnLNKLVLDTSYLDIQKVTINGLPADFA--IGERKEPLGSPLTISLPIaTS 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   164 QPQKVQLDFKFvgELNDKMRGFYRSQYKDKNGTEKFLASTQFESTYARYAFPCFDEPIYKATFDVtlEVENHLTALSNMN 243
Cdd:TIGR02411  91 KNDEFVLNISF--STTPKCTALQWLNPEQTSGKKHPYLFSQCQAIHARSLFPCQDTPSVKSTYTA--EVESPLPVLMSGI 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   244 VISETPTADGKRkavTFATSPKMSSYLVAFAVGELEyiSAQTksGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFDI 323
Cdd:TIGR02411 167 RDGETSNDPGKY---LFKQKVPIPAYLIAIASGDLA--SAPI--GPRSTVYSEPEQLEKCQYEFENDTEKFIKTAEDLIF 239
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   324 KYPLPKCDLIAIPD-FSMGAMENWGLvTYREIALLvdpgvtsTRQKSRVAlVVAHELAHLWFGNLVTMKWWTDLWLKEGF 402
Cdd:TIGR02411 240 PYEWGQYDLLVLPPsFPYGGMENPNL-TFATPTLI-------AGDRSNVD-VIAHELAHSWSGNLVTNCSWEHFWLNEGW 310
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076   403 ASFMEYMFVGANCPEFKiwLHFlndelASGMGLDALRNS-------HPIEVEIDN--PNELDEIYDSITYAKSNSVNRML 473
Cdd:TIGR02411 311 TVYLERRIIGRLYGEKT--RHF-----SALIGWGDLQESvktlgetPEFTKLVVDlkDNDPDDAFSSVPYEKGFNFLFYL 383
                         410       420       430
                  ....*....|....*....|....*....|....*..
gi 71989076   474 CYYLSEP-VFQKGLRLYLKRFQYSNAVTQDLWTALSE 509
Cdd:TIGR02411 384 EQLLGGPaEFDPFLRHYFKKFAYKSLDTYQFKDALYE 420
pepN PRK14015
aminopeptidase N; Provisional
224-623 6.41e-25

aminopeptidase N; Provisional


Pssm-ID: 237585 [Multi-domain]  Cd Length: 875  Bit Score: 111.76  E-value: 6.41e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  224 ATFDVTLEVEN----HLtaLSNMNVISETPTADGKRKAVTFATSPKmSSYLVAFAVGELEYISA--QTKSG--VEMRVYT 295
Cdd:PRK14015 144 ARYTVRIEADKakypVL--LSNGNLVESGELPDGRHWATWEDPFPK-PSYLFALVAGDLDVLEDtfTTRSGreVALEIYV 220
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  296 VPGKKEQGQYSLDLSVKCIDWYNEWFDIKYplpkcDL-----IAIPDFSMGAMENWGL-------VtyreialLVDPgVT 363
Cdd:PRK14015 221 EPGNLDKCDHAMDSLKKSMKWDEERFGLEY-----DLdifmiVAVDDFNMGAMENKGLnifnskyV-------LADP-ET 287
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  364 STRQK-SRVALVVAHELAHLWFGNLVTMKWWTDLWLKEGFASFMEYMFvgancpefkiwlhflndelASGMGLDA----- 437
Cdd:PRK14015 288 ATDADyERIESVIAHEYFHNWTGNRVTCRDWFQLSLKEGLTVFRDQEF-------------------SADLGSRAvkrie 348
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  438 ----LRN----------SHPIE----VEIDNpneldeIYDSITYAKSNSVNRMLCYYLSEPVFQKGLRLYLKRF--Qysn 497
Cdd:PRK14015 349 dvrvLRAaqfaedagpmAHPVRpdsyIEINN------FYTATVYEKGAEVIRMLHTLLGEEGFRKGMDLYFERHdgQ--- 419
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076  498 AVT-QDLWTALSEASGQNVNELMSgWTQQMGFPVLKVSQRQDGNNRI--LTVEQRRFISDGGEDPKNsqwqVPITVAVG- 573
Cdd:PRK14015 420 AVTcEDFVAAMEDASGRDLSQFRR-WYSQAGTPRVTVSDEYDAAAGTytLTLSQSTPPTPGQPEKQP----LHIPVAIGl 494
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71989076  574 --------------SSPSDVkarFLLKEKQQEFTIEGV-------------APgewVKLNSgttgfyrvEYSDEMLT 623
Cdd:PRK14015 495 ldpdgkelplqlegEPVERV---LELTEAEQTFTFENVaerpvpsllrgfsAP---VKLEY--------DYSDEDLL 557
M1_like_TAF2 cd09839
TATA binding protein (TBP) associated factor 2; This family includes TATA binding protein (TBP) ...
210-429 3.90e-11

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


Pssm-ID: 341074 [Multi-domain]  Cd Length: 531  Bit Score: 66.48  E-value: 3.90e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 210 ARYAFPCFDEPIYKATFDVTLEV-----------------------ENHLTALSNMNVIS-------ETPTADGKRKAVT 259
Cdd:cd09839 176 ARCWFPCVDSLWERCTWELEITVprtlgdagrpplagskededdddLTEEDKELEMVVVCsgdlveqVVHPEDPSKKTFS 255
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 260 FATSPKMSSYLVAFAVG-----------ELEYISAQTKSGVEMRVYTVPGKKEQGQYSLDLSVKCIDWYNEWFdIKYPLP 328
Cdd:cd09839 256 FSLSNPTSAQHIGFAVGpfeivplpefrESEEDDKLGSSAVEVTGFCLPGRLEELRNTCSFLHKAMDFFEEEY-GSYPFS 334
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71989076 329 KCDLI----AIPDFSMGAmenwGLVtyreIA---LLVDPGVT----STRQKsrvalvVAHELAHLWFGNLVTMKWWTDLW 397
Cdd:cd09839 335 SYKQVfvddLPEDVSSFA----SLS----ICssrLLYPPDIIdqayETRRK------LAHALASQWFGINIIPKTWSDTW 400
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 71989076 398 LKEGFASFMEYMFV----GANcpEFKIWLHFLNDEL 429
Cdd:cd09839 401 LVIGIAGYMTGLFLkklfGNN--EYRFRIKKDADRV 434
GluZincin cd09594
Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, ...
374-408 2.21e-04

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: 41.32  E-value: 2.21e-04
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 71989076 374 VVAHELAHLWFGNLVTMKW-WTDLWLKEGFASFMEY 408
Cdd:cd09594  68 VLAHELTHAFTGQFSNLMYsWSSGWLNEGISDYFGG 103
 
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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