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Conserved domains on  [gi|564329006|ref|XP_006229471|]
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aminopeptidase N isoform X1 [Rattus norvegicus]

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
PubMed:  7674922|37216842|21258033|10493853

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), ...
 84-545 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: 618.06  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  84 SYQVTLRPYLTPneqglYIFKGSSTVRFTCNETTNVIIIHSKKLNYTNkgnhrVALRaLGDTPAPNIDTTELVERTEYLV 163
Cdd:cd09601    2 HYDLTLTPDLEN-----FTFSGSVTITLEVLEPTDTIVLHAKDLTITS-----ASLT-LKGGSGIIEVTVVTDEETEFLT 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 164 VHLQGSLVKGHQYEMDSEFQGELADDLAGFYRSEYM-EGGNKKVVATTQMQAADARKSFPCFDEPAMKASFNITLIHPNN 242
Cdd:cd09601   71 ITLDETLPPGENYTLSIEFTGKLNDDLRGFYRSSYTdEDGETRYLAATQFEPTDARRAFPCFDEPAFKATFDITITHPKG 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 243 LTALSNMLPKDSRTLQEDpsWNVTEFHPTPKMSTYLLAYIVSEFKYVEAVSPNRVQIRIWARPSAIDegHGDYALQVTGP 322
Cdd:cd09601  151 YTALSNMPPVESTELEDG--WKTTTFETTPPMSTYLVAFVVGDFEYIESTTKSGVPVRVYARPGKIE--QGDFALEVAPK 226

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 323 ILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESALVFDPQSSSISNKERVVTVIAHELAHQWFGNLVTVDW 402
Cdd:cd09601  227 ILDFYEDYFGIPYPLPKLDLVAIPDFAAGAMENWGLITYRETALLYDPKTSSASDKQRVAEVIAHELAHQWFGNLVTMKW 306

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 403 WNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSSPaneVNTPAQISELFDSITYSKGASV 482
Cdd:cd09601  307 WDDLWLNEGFATYMEYLAVDKLFPEWNMWDQFVVDELQSALELDSLASSHPIEVP---VESPSEISEIFDAISYSKGASV 383

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564329006 483 LRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQAVDSQtaikLPASVSTIMDRWIL 545
Cdd:cd09601  384 LRMLENFLGEEVFRKGLRKYLKKHAYGNATTDDLWEALQEASGES----KPLDVKEIMDSWTL 442
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
 618-945 2.46e-109

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: 340.79  E-value: 2.46e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  618 WLLLNINVTGYYQVNYDENNWRKIQNQLQTDlsVIPVINRAQIIHDSFNLASAGKLSITLPLSNTLFLASETEYMPWEAA 697
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSK--VLSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWSAA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  698 LSSLNYFKLMFDRSEVYGPMKRYLKKQVTPLFAYFkiktnNWLDRPP-TLMEQYNEINAISTACSSGLEECRDLVVGLYS 776
Cdd:pfam11838  79 LSQLSTLRSLLSADPEYEALKAFLRKLLSPLAEKL-----GWEAPPGeSHLDRQLRALLLSAACSAGDPECVAEAKKLFD 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  777 QWMNNSDNnpIHPNLRSTVYCNAIAFGGEEEWNFAWEQFRKATVVNEADKLRSALACSNEVWILNRYLSYTLNPDYIRKQ 856
Cdd:pfam11838 154 AWLDGDDA--IPPDLRWAVYCAAVANGGEAEWDALLERYRDTTSPSEKERALRALAATPDPELLQRALELALDSDEVRNQ 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  857 DATSTIVSIANNVVGQTLVWDFVRSNWKKLFEDYGGGsFSFANLIQGVTRRFSSEFELQQLEQFKEDNSATGFGsgtRAL 936
Cdd:pfam11838 232 DLRAVIAGLASNPAGRDLAWDFVKENWDALVKRLGGG-SSLGRLVKGLTPSFSTEEELDEVEAFFADKDTPGLR---RAL 307


                  ....*....
gi 564329006  937 EQALEKTKA 945
Cdd:pfam11838 308 AQALETIRR 316
 
Name Accession Description Interval E-value
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
 84-545 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: 618.06  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  84 SYQVTLRPYLTPneqglYIFKGSSTVRFTCNETTNVIIIHSKKLNYTNkgnhrVALRaLGDTPAPNIDTTELVERTEYLV 163
Cdd:cd09601    2 HYDLTLTPDLEN-----FTFSGSVTITLEVLEPTDTIVLHAKDLTITS-----ASLT-LKGGSGIIEVTVVTDEETEFLT 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 164 VHLQGSLVKGHQYEMDSEFQGELADDLAGFYRSEYM-EGGNKKVVATTQMQAADARKSFPCFDEPAMKASFNITLIHPNN 242
Cdd:cd09601   71 ITLDETLPPGENYTLSIEFTGKLNDDLRGFYRSSYTdEDGETRYLAATQFEPTDARRAFPCFDEPAFKATFDITITHPKG 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 243 LTALSNMLPKDSRTLQEDpsWNVTEFHPTPKMSTYLLAYIVSEFKYVEAVSPNRVQIRIWARPSAIDegHGDYALQVTGP 322
Cdd:cd09601  151 YTALSNMPPVESTELEDG--WKTTTFETTPPMSTYLVAFVVGDFEYIESTTKSGVPVRVYARPGKIE--QGDFALEVAPK 226

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 323 ILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESALVFDPQSSSISNKERVVTVIAHELAHQWFGNLVTVDW 402
Cdd:cd09601  227 ILDFYEDYFGIPYPLPKLDLVAIPDFAAGAMENWGLITYRETALLYDPKTSSASDKQRVAEVIAHELAHQWFGNLVTMKW 306

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 403 WNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSSPaneVNTPAQISELFDSITYSKGASV 482
Cdd:cd09601  307 WDDLWLNEGFATYMEYLAVDKLFPEWNMWDQFVVDELQSALELDSLASSHPIEVP---VESPSEISEIFDAISYSKGASV 383

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564329006 483 LRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQAVDSQtaikLPASVSTIMDRWIL 545
Cdd:cd09601  384 LRMLENFLGEEVFRKGLRKYLKKHAYGNATTDDLWEALQEASGES----KPLDVKEIMDSWTL 442
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
75-608 2.00e-114

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 364.73  E-value: 2.00e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  75 RLPKTLIPDSYQVTLRpyLTPNEQglyIFKGSSTVRFTCNE-TTNVIIIH------------SKKLNYTNKGNHrvalra 141
Cdd:COG0308   10 YRPPGYDVTHYDLDLD--LDPATT---RLSGTATITFTATEaPLDSLVLDlkglevtsvtvdGKPLDFTRDGER------ 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 142 lgdtpapnidttelverteyLVVHLQGSLVKGHQYEMDSEFQGELADDLAGFYRSEYMEGGnkKVVATTQMQAADARKSF 221
Cdd:COG0308   79 --------------------LTITLPKPLAPGETFTLEIEYSGKPSNGGEGLYRSGDPPDG--PPYLYTQCEPEGARRWF 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 222 PCFDEPAMKASFNITLIHPNNLTALSNMLPKDSRTLqeDPSWNVTEFHPTPKMSTYLLAYIVSEFKYVEAVSPNRVQIRI 301
Cdd:COG0308  137 PCFDHPDDKATFTLTVTVPAGWVAVSNGNLVSETEL--GDGRTTWHWADTQPIPTYLFALAAGDYAVVEDTFASGVPLRV 214

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 302 WARPSaiDEGHGDYALQVTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESalVFDPQSSSISNKERV 381
Cdd:COG0308  215 YVRPG--LADKAKEAFESTKRMLDFFEELFGVPYPFDKYDQVAVPDFNFGAMENQGLVTFGEK--VLADETATDADYERR 290

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 382 VTVIAHELAHQWFGNLVTVDWWNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSspaneV 461
Cdd:COG0308  291 ESVIAHELAHQWFGNLVTCADWDDLWLNEGFATYMEQLFSEDLYGKDAADRIFVGALRSYAFAEDAGPNAHPIR-----P 365

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 462 NTPAQISELFDSITYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQAvdsqtaikLPASVSTIMD 541
Cdd:COG0308  366 DDYPEIENFFDGIVYEKGALVLHMLRTLLGDEAFRAGLRLYFARHAGGNATTEDFLAALEEA--------SGRDLSAFFD 437

                        490       500       510       520       530       540
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564329006 542 RWILQMGFPVITVNTSTGEIYQEHFLLdptskpTRPSDFNYLWIVPIPY-LKNGKEDHYWLETEKNQS 608
Cdd:COG0308  438 QWLYQAGLPTLEVEYEYDADGKVTLTL------RQTPPRPHPFHIPLEVgLLGGKLTARTVLLDGEQT 499
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
 618-945 2.46e-109

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: 340.79  E-value: 2.46e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  618 WLLLNINVTGYYQVNYDENNWRKIQNQLQTDlsVIPVINRAQIIHDSFNLASAGKLSITLPLSNTLFLASETEYMPWEAA 697
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSK--VLSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWSAA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  698 LSSLNYFKLMFDRSEVYGPMKRYLKKQVTPLFAYFkiktnNWLDRPP-TLMEQYNEINAISTACSSGLEECRDLVVGLYS 776
Cdd:pfam11838  79 LSQLSTLRSLLSADPEYEALKAFLRKLLSPLAEKL-----GWEAPPGeSHLDRQLRALLLSAACSAGDPECVAEAKKLFD 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  777 QWMNNSDNnpIHPNLRSTVYCNAIAFGGEEEWNFAWEQFRKATVVNEADKLRSALACSNEVWILNRYLSYTLNPDYIRKQ 856
Cdd:pfam11838 154 AWLDGDDA--IPPDLRWAVYCAAVANGGEAEWDALLERYRDTTSPSEKERALRALAATPDPELLQRALELALDSDEVRNQ 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  857 DATSTIVSIANNVVGQTLVWDFVRSNWKKLFEDYGGGsFSFANLIQGVTRRFSSEFELQQLEQFKEDNSATGFGsgtRAL 936
Cdd:pfam11838 232 DLRAVIAGLASNPAGRDLAWDFVKENWDALVKRLGGG-SSLGRLVKGLTPSFSTEEELDEVEAFFADKDTPGLR---RAL 307


                  ....*....
gi 564329006  937 EQALEKTKA 945
Cdd:pfam11838 308 AQALETIRR 316
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
 315-543 1.10e-108

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: 335.03  E-value: 1.10e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  315 YALQVTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESALVFDPQSSSISNKERVVTVIAHELAHQWF 394
Cdd:pfam01433   1 YALEITVKLLEFYEDYFNIPYPLPKYDLVALPDFSAGAMENWGLITYRETLLLYDPGNSSTSDKQRVASVIAHELAHQWF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  395 GNLVTVDWWNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSSpanEVNTPAQISELFDSI 474
Cdd:pfam01433  81 GNLVTMKWWDDLWLNEGFATYMEYLGTDALFPEWNIWEQFLLDEVQNAMARDALDSSHPITQ---NVNDPSEIDDIFDAI 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564329006  475 TYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQAVDSQTaiklpasVSTIMDRW 543
Cdd:pfam01433 158 PYEKGASVLRMLETLLGEEVFQKGLRSYLKKFQYGNATTEDLWDALSEASGPLD-------VDSFMDTW 219
pepN_strep_liv TIGR02412
aminopeptidase N, Streptomyces lividans type; This family is a subset of the members of the ...
 205-523 2.71e-72

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: 255.87  E-value: 2.71e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  205 KVVATTQMQAADARKSFPCFDEPAMKASFNITLIHPNNLTALSNMLPKDSRTlqeDPSWNVTEFHPTPKMSTYLLAYIVS 284
Cdd:TIGR02412 117 EVYLYTQFEPADARRVFAVFDQPDLKANFKFSVKAPEDWTVISNSRETDVTP---EPADRRWEFPETPKLSTYLTAVAAG 193

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  285 EFKYVEAVSpNRVQIRIWARPSAIDEGHGDYALQVTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRES 364
Cdd:TIGR02412 194 PYHSVQDES-RSYPLGIYARRSLAQYLDADAIFTITRQGLAFFHRKFGYPYPFKKYDQIFVPEFNAGAMENAGCVTFAEN 272

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  365 ALVFDPQSSSisNKERVVTVIAHELAHQWFGNLVTVDWWNDLWLNEGFASYVEflgadyaepTWNLKDLIVLNDVYRVMA 444
Cdd:TIGR02412 273 FLHRAEATRA--EKENRAGVILHEMAHMWFGDLVTMRWWNDLWLNESFAEYMG---------TLASAEATEYTDAWTTFA 341

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  445 V---------DALASSHPLSSPANEVNTPAQIselFDSITYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLD 515
Cdd:TIGR02412 342 AqgkqwayeaDQLPTTHPIVADVADLADALSN---FDGITYAKGASVLKQLVAWVGEEAFFAGVNAYFKRHAFGNATLDD 418


                  ....*...
gi 564329006  516 LWEHLQQA 523
Cdd:TIGR02412 419 LIDSLAKA 426
pepN PRK14015
aminopeptidase N; Provisional
 246-506 5.94e-11

aminopeptidase N; Provisional


Pssm-ID: 237585 [Multi-domain]  Cd Length: 875  Bit Score: 66.69  E-value: 5.94e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 246 LSNMLPKDSRTLQEDPSWnVTEFHPTPKMStYL-------LAYIVSEFKyveAVSPNRVQIRIWARPSaiDEGHGDYALQ 318
Cdd:PRK14015 161 LSNGNLVESGELPDGRHW-ATWEDPFPKPS-YLfalvagdLDVLEDTFT---TRSGREVALEIYVEPG--NLDKCDHAMD 233

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 319 vtgpilnffA---------QHYNTAYPLeksDQ---IALPDFNAGAMENWGLVTYrESALVF-DPQSSSISNKERVVTVI 385
Cdd:PRK14015 234 ---------SlkksmkwdeERFGLEYDL---DIfmiVAVDDFNMGAMENKGLNIF-NSKYVLaDPETATDADYERIESVI 300

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 386 AHELAHQWFGNLVTV-DWWNdLWLNEGFAsyV----EFlGADYaeptwNLKDLIVLNDVyRVM-----AVDALASSHPLS 455
Cdd:PRK14015 301 AHEYFHNWTGNRVTCrDWFQ-LSLKEGLT--VfrdqEF-SADL-----GSRAVKRIEDV-RVLraaqfAEDAGPMAHPVR 370

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564329006 456 spanevntPAQISEL--FDSIT-YSKGASVLRMLSSFLTEDLFKKGLSSYLHTF 506
Cdd:PRK14015 371 --------PDSYIEInnFYTATvYEKGAEVIRMLHTLLGEEGFRKGMDLYFERH 416
 
Name Accession Description Interval E-value
M1_APN-Q_like cd09601
Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), ...
 84-545 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: 618.06  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  84 SYQVTLRPYLTPneqglYIFKGSSTVRFTCNETTNVIIIHSKKLNYTNkgnhrVALRaLGDTPAPNIDTTELVERTEYLV 163
Cdd:cd09601    2 HYDLTLTPDLEN-----FTFSGSVTITLEVLEPTDTIVLHAKDLTITS-----ASLT-LKGGSGIIEVTVVTDEETEFLT 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 164 VHLQGSLVKGHQYEMDSEFQGELADDLAGFYRSEYM-EGGNKKVVATTQMQAADARKSFPCFDEPAMKASFNITLIHPNN 242
Cdd:cd09601   71 ITLDETLPPGENYTLSIEFTGKLNDDLRGFYRSSYTdEDGETRYLAATQFEPTDARRAFPCFDEPAFKATFDITITHPKG 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 243 LTALSNMLPKDSRTLQEDpsWNVTEFHPTPKMSTYLLAYIVSEFKYVEAVSPNRVQIRIWARPSAIDegHGDYALQVTGP 322
Cdd:cd09601  151 YTALSNMPPVESTELEDG--WKTTTFETTPPMSTYLVAFVVGDFEYIESTTKSGVPVRVYARPGKIE--QGDFALEVAPK 226

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 323 ILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESALVFDPQSSSISNKERVVTVIAHELAHQWFGNLVTVDW 402
Cdd:cd09601  227 ILDFYEDYFGIPYPLPKLDLVAIPDFAAGAMENWGLITYRETALLYDPKTSSASDKQRVAEVIAHELAHQWFGNLVTMKW 306

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 403 WNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSSPaneVNTPAQISELFDSITYSKGASV 482
Cdd:cd09601  307 WDDLWLNEGFATYMEYLAVDKLFPEWNMWDQFVVDELQSALELDSLASSHPIEVP---VESPSEISEIFDAISYSKGASV 383

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564329006 483 LRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQAVDSQtaikLPASVSTIMDRWIL 545
Cdd:cd09601  384 LRMLENFLGEEVFRKGLRKYLKKHAYGNATTDDLWEALQEASGES----KPLDVKEIMDSWTL 442
PepN COG0308
Aminopeptidase N, contains DUF3458 domain [Amino acid transport and metabolism];
75-608 2.00e-114

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


Pssm-ID: 440077 [Multi-domain]  Cd Length: 609  Bit Score: 364.73  E-value: 2.00e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  75 RLPKTLIPDSYQVTLRpyLTPNEQglyIFKGSSTVRFTCNE-TTNVIIIH------------SKKLNYTNKGNHrvalra 141
Cdd:COG0308   10 YRPPGYDVTHYDLDLD--LDPATT---RLSGTATITFTATEaPLDSLVLDlkglevtsvtvdGKPLDFTRDGER------ 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 142 lgdtpapnidttelverteyLVVHLQGSLVKGHQYEMDSEFQGELADDLAGFYRSEYMEGGnkKVVATTQMQAADARKSF 221
Cdd:COG0308   79 --------------------LTITLPKPLAPGETFTLEIEYSGKPSNGGEGLYRSGDPPDG--PPYLYTQCEPEGARRWF 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 222 PCFDEPAMKASFNITLIHPNNLTALSNMLPKDSRTLqeDPSWNVTEFHPTPKMSTYLLAYIVSEFKYVEAVSPNRVQIRI 301
Cdd:COG0308  137 PCFDHPDDKATFTLTVTVPAGWVAVSNGNLVSETEL--GDGRTTWHWADTQPIPTYLFALAAGDYAVVEDTFASGVPLRV 214

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 302 WARPSaiDEGHGDYALQVTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESalVFDPQSSSISNKERV 381
Cdd:COG0308  215 YVRPG--LADKAKEAFESTKRMLDFFEELFGVPYPFDKYDQVAVPDFNFGAMENQGLVTFGEK--VLADETATDADYERR 290

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 382 VTVIAHELAHQWFGNLVTVDWWNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSspaneV 461
Cdd:COG0308  291 ESVIAHELAHQWFGNLVTCADWDDLWLNEGFATYMEQLFSEDLYGKDAADRIFVGALRSYAFAEDAGPNAHPIR-----P 365

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 462 NTPAQISELFDSITYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQAvdsqtaikLPASVSTIMD 541
Cdd:COG0308  366 DDYPEIENFFDGIVYEKGALVLHMLRTLLGDEAFRAGLRLYFARHAGGNATTEDFLAALEEA--------SGRDLSAFFD 437

                        490       500       510       520       530       540
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564329006 542 RWILQMGFPVITVNTSTGEIYQEHFLLdptskpTRPSDFNYLWIVPIPY-LKNGKEDHYWLETEKNQS 608
Cdd:COG0308  438 QWLYQAGLPTLEVEYEYDADGKVTLTL------RQTPPRPHPFHIPLEVgLLGGKLTARTVLLDGEQT 499
ERAP1_C pfam11838
ERAP1-like C-terminal domain; This large domain is composed of 16 alpha helices organized as 8 ...
 618-945 2.46e-109

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: 340.79  E-value: 2.46e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  618 WLLLNINVTGYYQVNYDENNWRKIQNQLQTDlsVIPVINRAQIIHDSFNLASAGKLSITLPLSNTLFLASETEYMPWEAA 697
Cdd:pfam11838   1 WVKLNADDTGYYRVNYDPESLAALLEQLLSK--VLSPLDRAGLIDDAFALARAGELSTSDALDLVLAYLNETDYVVWSAA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  698 LSSLNYFKLMFDRSEVYGPMKRYLKKQVTPLFAYFkiktnNWLDRPP-TLMEQYNEINAISTACSSGLEECRDLVVGLYS 776
Cdd:pfam11838  79 LSQLSTLRSLLSADPEYEALKAFLRKLLSPLAEKL-----GWEAPPGeSHLDRQLRALLLSAACSAGDPECVAEAKKLFD 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  777 QWMNNSDNnpIHPNLRSTVYCNAIAFGGEEEWNFAWEQFRKATVVNEADKLRSALACSNEVWILNRYLSYTLNPDYIRKQ 856
Cdd:pfam11838 154 AWLDGDDA--IPPDLRWAVYCAAVANGGEAEWDALLERYRDTTSPSEKERALRALAATPDPELLQRALELALDSDEVRNQ 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  857 DATSTIVSIANNVVGQTLVWDFVRSNWKKLFEDYGGGsFSFANLIQGVTRRFSSEFELQQLEQFKEDNSATGFGsgtRAL 936
Cdd:pfam11838 232 DLRAVIAGLASNPAGRDLAWDFVKENWDALVKRLGGG-SSLGRLVKGLTPSFSTEEELDEVEAFFADKDTPGLR---RAL 307


                  ....*....
gi 564329006  937 EQALEKTKA 945
Cdd:pfam11838 308 AQALETIRR 316
Peptidase_M1 pfam01433
Peptidase family M1 domain; Members of this family are aminopeptidases. The members differ ...
 315-543 1.10e-108

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: 335.03  E-value: 1.10e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  315 YALQVTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESALVFDPQSSSISNKERVVTVIAHELAHQWF 394
Cdd:pfam01433   1 YALEITVKLLEFYEDYFNIPYPLPKYDLVALPDFSAGAMENWGLITYRETLLLYDPGNSSTSDKQRVASVIAHELAHQWF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  395 GNLVTVDWWNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSSpanEVNTPAQISELFDSI 474
Cdd:pfam01433  81 GNLVTMKWWDDLWLNEGFATYMEYLGTDALFPEWNIWEQFLLDEVQNAMARDALDSSHPITQ---NVNDPSEIDDIFDAI 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564329006  475 TYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQAVDSQTaiklpasVSTIMDRW 543
Cdd:pfam01433 158 PYEKGASVLRMLETLLGEEVFQKGLRSYLKKFQYGNATTEDLWDALSEASGPLD-------VDSFMDTW 219
M1 cd09595
Peptidase M1 family includes the catalytic domains of aminopeptidase N and leukotriene A4 ...
 83-522 1.06e-89

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: 292.04  E-value: 1.06e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  83 DSYQVTLRPYLTPneqglYIFKGSSTVRFTCNETTNVIIIHSKKLNYtnkgnHRVALralgdtpapNIDTTELVERTEYL 162
Cdd:cd09595    1 YHYDLDLDVDFTT-----KTLNGTETLTVDASQVGRELVLDLVGLTI-----HSVSV---------NGAAVDFGEREHYD 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 163 --VVHLQGSLVKGHQYEMDSEFQGELADDLAGFYRSEYMegGNKKVVATTQMQAADARKSFPCFDEPAMKASFNITLIHP 240
Cdd:cd09595   62 geKLTIPGPKPPGQTFTVRISFEAKPSKNLLGWLWEQTA--GKEKPYLFTQFEATHARRIFPCIDHPAVKATFTVTITTP 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 241 NNLTALSNMLPKDSRTLQEDPswNVTEFHPTPKMSTYLLAYIVS--EFKYVEAVSPNRVQIRIWARPSAIDEGhgDYALQ 318
Cdd:cd09595  140 KKDLLASNGALVGEETGANGR--KTYRFEDTPPIPTYLVAVVVGdlEFKYVTVKSQPRVGLSVYSEPLQVDQA--QYAFD 215

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 319 VTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESALVFDpqSSSISNKERVVTVIAHELAHQWFGNLV 398
Cdd:cd09595  216 ATRAALAWFEDYFGGPYPLPKYDLLAVPDFNSGAMENPGLITFRTTYLLRS--KVTDTGARSIENVIAHELAHQWFGNLV 293

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 399 TVDWWNDLWLNEGFASYVE--FLGADYAEPTWNLKDLIVLNDvyrVMAVDALASSHPLSSPaneVNTPAQISELFDSITY 476
Cdd:cd09595  294 TMRWWNDLWLNEGFAVYYEnrIMDATFGTSSRHLDQLSGSSD---LNTEQLLEDSSPTSTP---VRSPADPDVAYDGVTY 367

                        410       420       430       440
                 ....*....|....*....|....*....|....*....|....*.
gi 564329006 477 SKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQ 522
Cdd:cd09595  368 AKGALVLRMLEELVGEEAFDKGVQAYFNRHKFKNATTDDFIDALEE 413
M1_APN cd09602
Peptidase M1 family including aminopeptidase N catalytic domain; This model represents the ...
 84-523 1.35e-89

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: 292.88  E-value: 1.35e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  84 SYQVTLRpyLTPNEQglyIFKGSSTVRFTCNETTN------------VIIIHSKKLNYTNKGNHRVALRALgDTPAPNId 151
Cdd:cd09602   17 SYDLDLD--LTEGAE---TFRGTVTIRFTLREPGAslfldfrggevkSVTLNGRPLDPSAFDGERITLPGL-LKAGENT- 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 152 ttelverteyLVVhlqgslvkghqyemdsEFQGELADDLAGFYRseYMEGGNKKVVATTQMQAADARKSFPCFDEPAMKA 231
Cdd:cd09602   90 ----------VVV----------------EFTAPYSSDGEGLHR--FVDPADGETYLYTLFEPDDARRVFPCFDQPDLKA 141

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 232 SFNITLIHPNNLTALSNMLPKDSRTLQEdpsWNVTEFHPTPKMSTYLLAYIVSEFKYVEAvSPNRVQIRIWARPS-AIDE 310
Cdd:cd09602  142 TFTLTVTAPADWTVISNGPETSTEEAGG---RKRWRFAETPPLSTYLFAFVAGPYHRVED-EHDGIPLGLYCRESlAEYE 217

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 311 GHGDYALQVTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRESALVFDPqsSSISNKERVVTVIAHELA 390
Cdd:cd09602  218 RDADEIFEVTKQGLDFYEDYFGIPYPFGKYDQVFVPEFNFGAMENPGAVTFRESYLFREE--PTRAQRLRRANTILHEMA 295

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 391 HQWFGNLVTVDWWNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDALASSHPLSSPANEVNTPAQIsel 470
Cdd:cd09602  296 HMWFGDLVTMKWWDDLWLNESFADFMAAKALAEATPFTDAWLTFLLRRKPWAYRADQLPTTHPIAQDVPDLEAAGSN--- 372

                        410       420       430       440       450
                 ....*....|....*....|....*....|....*....|....*....|...
gi 564329006 471 FDSITYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQA 523
Cdd:cd09602  373 FDGITYAKGASVLKQLVALVGEEAFRAGLREYFKKHAYGNATLDDLIAALDEA 425
pepN_strep_liv TIGR02412
aminopeptidase N, Streptomyces lividans type; This family is a subset of the members of the ...
 205-523 2.71e-72

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: 255.87  E-value: 2.71e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  205 KVVATTQMQAADARKSFPCFDEPAMKASFNITLIHPNNLTALSNMLPKDSRTlqeDPSWNVTEFHPTPKMSTYLLAYIVS 284
Cdd:TIGR02412 117 EVYLYTQFEPADARRVFAVFDQPDLKANFKFSVKAPEDWTVISNSRETDVTP---EPADRRWEFPETPKLSTYLTAVAAG 193

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  285 EFKYVEAVSpNRVQIRIWARPSAIDEGHGDYALQVTGPILNFFAQHYNTAYPLEKSDQIALPDFNAGAMENWGLVTYRES 364
Cdd:TIGR02412 194 PYHSVQDES-RSYPLGIYARRSLAQYLDADAIFTITRQGLAFFHRKFGYPYPFKKYDQIFVPEFNAGAMENAGCVTFAEN 272

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  365 ALVFDPQSSSisNKERVVTVIAHELAHQWFGNLVTVDWWNDLWLNEGFASYVEflgadyaepTWNLKDLIVLNDVYRVMA 444
Cdd:TIGR02412 273 FLHRAEATRA--EKENRAGVILHEMAHMWFGDLVTMRWWNDLWLNESFAEYMG---------TLASAEATEYTDAWTTFA 341

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  445 V---------DALASSHPLSSPANEVNTPAQIselFDSITYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLD 515
Cdd:TIGR02412 342 AqgkqwayeaDQLPTTHPIVADVADLADALSN---FDGITYAKGASVLKQLVAWVGEEAFFAGVNAYFKRHAFGNATLDD 418


                  ....*...
gi 564329006  516 LWEHLQQA 523
Cdd:TIGR02412 419 LIDSLAKA 426
Peptidase_M1_N pfam17900
Peptidase M1 N-terminal domain; This domain is found at the N-terminus of aminopeptidases from ...
 82-278 6.09e-66

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: 219.14  E-value: 6.09e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006   82 PDSYQVTLRPYLTPneqglYIFKGSSTVRFTCNETTNVIIIHSKKLNYtnkgnHRVALRALGDTPAPNIDTTELVERTEY 161
Cdd:pfam17900   2 PEHYDLDLKIDLKN-----FTFSGSVTITLQLNNATNVIVLHASDLTI-----RSISLSDEVTSDGVPADFTEDQKDGEK 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  162 LVVHLQGSLVKGHQYEMDSEFQGELADDLAGFYRSEYMEGGNKKVVATTQMQAADARKSFPCFDEPAMKASFNITLIHPN 241
Cdd:pfam17900  72 LTIVLPETLNQTGPYTLEIEYSGELNDSMTGFYRSTYTDNGEKKVLVTTQFEPTDARSAFPCFDEPSVKATFTISIIHPK 151

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 564329006  242 NLTALSNMlPKDSRTlQEDPSWNVTEFHPTPKMSTYL 278
Cdd:pfam17900 152 DYTALSNM-PVIASE-PLENGWVITTFEQTPKMSTYL 186
M1_APN_like cd09603
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains mostly ...
 85-523 9.72e-56

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: 198.58  E-value: 9.72e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  85 YQVTLRPYLTPNEqglyiFKGSSTVRFTCNETTNVIIIHSKKLNYTnkgnhRVALralGDTPAPNIDTTElvertEYLVV 164
Cdd:cd09603    6 YDLDLDYDPATKS-----LSGTATITFRATQDLDSLQLDLVGLTVS-----SVTV---DGVPAAFFTHDG-----DKLVI 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 165 HLQGSLVKGHQYEMDSEFQGelADDLAGFYRSEYMEGGNKKVVATTQMQAADARKSFPCFDEPAMKASFNITLIHPNNLT 244
Cdd:cd09603   68 TLPRPLAAGETFTVTVRYSG--KPRPAGYPPGDGGGWEEGDDGVWTAGQPEGASTWFPCNDHPDDKATYDITVTVPAGLT 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 245 ALSNMLPKDSRTLqeDPSWNVTEF-HPTPkMSTYLLAYIVSEFKYVEAVSPNRVQIRIWARPSaiDEGHGDYALQVTGPI 323
Cdd:cd09603  146 VVSNGRLVSTTTN--GGGTTTWHWkMDYP-IATYLVTLAVGRYAVVEDGSGGGIPLRYYVPPG--DAAKAKASFARTPEM 220

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 324 LNFFAQHYnTAYPLEKSDQIALPDFNaGAMENWGLVTYRESALVFDPQSssisnkervVTVIAHELAHQWFGNLVTVDWW 403
Cdd:cd09603  221 LDFFEELF-GPYPFEKYGQVVVPDLG-GGMEHQTATTYGNNFLNGDRGS---------ERLIAHELAHQWFGDSVTCADW 289

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 404 NDLWLNEGFASYVEFLgadYAEptwnlkdlivlnDVYRVMAVDALASSHP--LSSPANEVNTPAQISELFDSITYSKGAS 481
Cdd:cd09603  290 ADIWLNEGFATYAEWL---WSE------------HKGGADAYRAYLAGQRqdYLNADPGPGRPPDPDDLFDRDVYQKGAL 354

                        410       420       430       440
                 ....*....|....*....|....*....|....*....|..
gi 564329006 482 VLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQA 523
Cdd:cd09603  355 VLHMLRNLLGDEAFFAALRAYLARYAHGNVTTEDFIAAAEEV 396
M1_LTA4H cd09599
Peptidase M1 family including Leukotriene A4 hydrolase catalytic domain; This model represents ...
 210-508 1.21e-31

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: 129.11  E-value: 1.21e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 210 TQMQAADARKSFPCFDEPAMKASFNITLIHPNNLTAL-SNMLPKDSrtlqEDPSWNVTEFH-PTPkMSTYLLAYIVSEFK 287
Cdd:cd09599  129 TQCQAIHARSLFPCQDTPSVKSTYSATVTVPKGLTALmSALRTGEK----EEAGTGTYTFEqPVP-IPSYLIAIAVGDLE 203

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 288 YVEaVSPNrvqIRIWARPSAIDEGHgdYALQVTGPILNFfAQHYNTAYPLEKSDQIALPD-FNAGAMENWGLVTYRESAL 366
Cdd:cd09599  204 SRE-IGPR---SGVWAEPSVVDAAA--EEFADTEKFLKA-AEKLYGPYVWGRYDLLVLPPsFPYGGMENPCLTFATPTLI 276

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 367 VFDpqsssISNkervVTVIAHELAHQWFGNLVTVDWWNDLWLNEGFASYVE--FLGADYAEPTWNLKDLIVLNDVyrVMA 444
Cdd:cd09599  277 AGD-----RSL----VDVIAHEIAHSWSGNLVTNANWEHFWLNEGFTVYLErrILERLYGEEYRQFEAILGWKDL--QES 345

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564329006 445 VDALASSHPLSS---PANEVNtPaqiSELFDSITYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQY 508
Cdd:cd09599  346 IKEFGEDPPYTLlvpDLKGVD-P---DDAFSSVPYEKGFQFLYYLEQLGGREVFDPFLRAYFKKFAF 408
leuko_A4_hydro TIGR02411
leukotriene A-4 hydrolase/aminopeptidase; Members of this family represent a distinctive ...
 105-581 1.67e-27

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: 118.73  E-value: 1.67e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  105 GSSTVRFTC-NETTNVIIIHSKKLNYTNkgnhrVALRALgdtPAPnidtTELVERTEY----LVVHLQGSLVKGHQYEMD 179
Cdd:TIGR02411  31 GSVTFTLKSlTDNLNKLVLDTSYLDIQK-----VTINGL---PAD----FAIGERKEPlgspLTISLPIATSKNDEFVLN 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  180 SEFqgELADDLAG--FYRSEYMEGGNKKVVaTTQMQAADARKSFPCFDEPAMKASFNITLIHPnnLTALSNMLPKDSRTl 257
Cdd:TIGR02411  99 ISF--STTPKCTAlqWLNPEQTSGKKHPYL-FSQCQAIHARSLFPCQDTPSVKSTYTAEVESP--LPVLMSGIRDGETS- 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  258 qEDPswNVTEFHPTPKMSTYLLAYIVSEFkyveAVSPNRVQIRIWARPSAIDeghgDYALQVTGPILNFF--AQHYNTAY 335
Cdd:TIGR02411 173 -NDP--GKYLFKQKVPIPAYLIAIASGDL----ASAPIGPRSTVYSEPEQLE----KCQYEFENDTEKFIktAEDLIFPY 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  336 PLEKSDQIALPD-FNAGAMENWGLvTYRESALvfdpqsssISNKERVVTVIAHELAHQWFGNLVTVDWWNDLWLNEGFAS 414
Cdd:TIGR02411 242 EWGQYDLLVLPPsFPYGGMENPNL-TFATPTL--------IAGDRSNVDVIAHELAHSWSGNLVTNCSWEHFWLNEGWTV 312

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  415 YVE--FLGADYAEPTWNLKDLIVLNDVyrVMAVDALASSHPLSSPANEVNtPAQISELFDSITYSKGASVLRMLSSFL-- 490
Cdd:TIGR02411 313 YLErrIIGRLYGEKTRHFSALIGWGDL--QESVKTLGETPEFTKLVVDLK-DNDPDDAFSSVPYEKGFNFLFYLEQLLgg 389

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  491 -------TEDLFKKGLSSYLHTFQYSNTIYlDLWEHLQQaVDSQTAIKlpasvstiMDRWILQMGFPVITVN---TSTGE 560
Cdd:TIGR02411 390 paefdpfLRHYFKKFAYKSLDTYQFKDALY-EYFKDKKK-VDKLDAVD--------WETWLYSPGMPPVKPNfdtTLADE 459

                         490       500
                  ....*....|....*....|.
gi 564329006  561 IYQEHFLLDPTSKPTRPSDFN 581
Cdd:TIGR02411 460 CYALADRWVDAAKADDLSSFN 480
pepN_proteo TIGR02414
aminopeptidase N, Escherichia coli type; The M1 family of zinc metallopeptidases contains a ...
 190-557 1.20e-26

aminopeptidase N, Escherichia coli type; The M1 family of zinc metallopeptidases contains a number of distinct, well-separated clades of proteins with aminopeptidase activity. Several are designated aminopeptidase N, EC 3.4.11.2, after the Escherichia coli enzyme, suggesting a similar activity profile (see SP|P04825 for a description of catalytic activity). This family consists of all aminopeptidases closely related to E. coli PepN and presumed to have similar (not identical) function. Nearly all are found in Proteobacteria, but members are found also in Cyanobacteria, plants, and apicomplexan parasites. This family differs greatly in sequence from the family of aminopeptidases typified by Streptomyces lividans PepN (TIGR02412), from the membrane bound aminopeptidase N family in animals, etc. [Protein fate, Degradation of proteins, peptides, and glycopeptides]


Pssm-ID: 274122 [Multi-domain]  Cd Length: 863  Bit Score: 117.42  E-value: 1.20e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  190 LAGFYRSeymeGGNkkvvATTQMQAADARKSFPCFDEPAMKASFNITLI-----HPnnlTALSNMLPKDSRTLQEDPSWn 264
Cdd:TIGR02414  98 LEGLYKS----GGN----FCTQCEAEGFRRITYFPDRPDVMSRYTVTITadkkkYP---VLLSNGNKIASGELPDGRHW- 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  265 vTEFH-PTPKMStYLLAYIVSEFKYVEAV----SPNRVQIRIWARPSaiDEGHGDYALQVTGPILNFFAQHYNTAYPLEK 339
Cdd:TIGR02414 166 -AEWEdPFPKPS-YLFALVAGDLDVLEDTfttkSGREVALRVYVEEG--NKDKCDHAMESLKKAMKWDEEVFGLEYDLDI 241

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  340 SDQIALPDFNAGAMENWGLVTYRESALVFDPQSSSISNKERVVTVIAHELAHQWFGNLVTVDWWNDLWLNEGFASY--VE 417
Cdd:TIGR02414 242 FMIVAVDDFNMGAMENKGLNIFNSKYVLADPETATDADYERIESVIAHEYFHNWTGNRVTCRDWFQLSLKEGLTVFrdQE 321

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006  418 FLGADYAEPTWNLKDLIVLNDVYrvMAVDALASSHPLsSPANEVntpaQISELFDSITYSKGASVLRMLSSFLTEDLFKK 497
Cdd:TIGR02414 322 FSADMTSRAVKRIEDVRLLRAHQ--FPEDAGPMAHPV-RPESYV----EINNFYTATVYEKGAEVIRMLHTLLGEEGFRK 394

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564329006  498 GLSSYlhtFQysntiyldlwEHLQQAVDSQTAIKLPASVS----TIMDRWILQMGFPVITVNTS 557
Cdd:TIGR02414 395 GMDLY---FS----------RHDGQAVTCEDFVAAMEDASgrdlNQFRRWYSQAGTPVLEVKEN 445
M1_APN cd09600
Peptidase M1 family, including aminopeptidase N catalytic domain; This model represents the ...
 190-506 2.53e-26

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: 112.99  E-value: 2.53e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 190 LAGFYRSeymeGGNkkvvATTQMQAADARKSFPCFDEPAMKASFNITLIHPNNL--TALSNMLPKDSRTLqeDPSWNVTE 267
Cdd:cd09600   99 LEGLYKS----GGI----LCTQCEAEGFRRITYFPDRPDVMSKFTVTIEADKEKypVLLSNGNLIEEGEL--PNGRHFAV 168

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 268 FH-PTPKMStYLLAYIVSEFKYVEAV----SPNRVQIRIWARPsaIDEGHGDYALQVTGPILNFFAQHYNTAYPLEKSDQ 342
Cdd:cd09600  169 WEdPFPKPS-YLFALVAGDLGSVEDTfttkSGRKVKLRIYVEP--GNEDKCHHAMESLKKAMKWDEERFGLEYDLDLFNI 245

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 343 IALPDFNAGAMENWGLVTYRESALVFDPQSSSISNKERVVTVIAHELAHQWFGNLVTV-DWWNdLWLNEGFASY--VEFL 419
Cdd:cd09600  246 VAVDDFNMGAMENKGLNIFNSKYVLADPETATDADYERIESVIAHEYFHNWTGNRVTCrDWFQ-LSLKEGLTVFrdQEFS 324

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 420 gADYAEPTwnlkdlivlndVYRVMAVDALAS----------SHPLsSPANEVntpaQISELFDSITYSKGASVLRMLSSF 489
Cdd:cd09600  325 -ADMNSRA-----------VKRIEDVRRLRSaqfpedagpmAHPI-RPDSYI----EINNFYTVTVYEKGAEVIRMLHTL 387

                        330
                 ....*....|....*..
gi 564329006 490 LTEDLFKKGLSSYLHTF 506
Cdd:cd09600  388 LGEEGFRKGMDLYFERH 404
M1_APN_like cd09604
Peptidase M1 family similar to aminopeptidase N catalytic domain; This family contains ...
 289-523 1.03e-21

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: 99.27  E-value: 1.03e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 289 VEAVSPNRVQIRIWARPSaiDEGHGDYALQVTGPILNFFAQHYnTAYPLEKSDqIALPDFNAGAMEnwglvtYreSALVF 368
Cdd:cd09604  214 VDAATVDGVTVNVYYLPE--NAEAAERALEYAKDALEFFSEKF-GPYPYPELD-VVQGPFGGGGME------Y--PGLVF 281

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 369 DPQSSSiSNKERVVTVIAHELAHQWFGNLVTVDWWNDLWLNEGFASYVEFLGADYAEPTWNLKDLIVLNDVYRVMAVDAL 448
Cdd:cd09604  282 IGSRLY-DPKRSLEGVVVHEIAHQWFYGIVGNDERREPWLDEGLATYAESLYLEEKYGKEAADELLGRRYYRAYARGPGG 360

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564329006 449 ASSHPLSSPANEVNTPAqiselfdsITYSKGASVLRMLSSFLTEDLFKKGLSSYLHTFQYSNTIYLDLWEHLQQA 523
Cdd:cd09604  361 PINLPLDTFPDGSYYSN--------AVYSKGALFLEELREELGDEAFDKALREYYRRYKFKHPTPEDFFRTAEEV 427
pepN PRK14015
aminopeptidase N; Provisional
 246-506 5.94e-11

aminopeptidase N; Provisional


Pssm-ID: 237585 [Multi-domain]  Cd Length: 875  Bit Score: 66.69  E-value: 5.94e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 246 LSNMLPKDSRTLQEDPSWnVTEFHPTPKMStYL-------LAYIVSEFKyveAVSPNRVQIRIWARPSaiDEGHGDYALQ 318
Cdd:PRK14015 161 LSNGNLVESGELPDGRHW-ATWEDPFPKPS-YLfalvagdLDVLEDTFT---TRSGREVALEIYVEPG--NLDKCDHAMD 233

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 319 vtgpilnffA---------QHYNTAYPLeksDQ---IALPDFNAGAMENWGLVTYrESALVF-DPQSSSISNKERVVTVI 385
Cdd:PRK14015 234 ---------SlkksmkwdeERFGLEYDL---DIfmiVAVDDFNMGAMENKGLNIF-NSKYVLaDPETATDADYERIESVI 300

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564329006 386 AHELAHQWFGNLVTV-DWWNdLWLNEGFAsyV----EFlGADYaeptwNLKDLIVLNDVyRVM-----AVDALASSHPLS 455
Cdd:PRK14015 301 AHEYFHNWTGNRVTCrDWFQ-LSLKEGLT--VfrdqEF-SADL-----GSRAVKRIEDV-RVLraaqfAEDAGPMAHPVR 370

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564329006 456 spanevntPAQISEL--FDSIT-YSKGASVLRMLSSFLTEDLFKKGLSSYLHTF 506
Cdd:PRK14015 371 --------PDSYIEInnFYTATvYEKGAEVIRMLHTLLGEEGFRKGMDLYFERH 416
GluZincin cd09594
Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, ...
 384-419 1.20e-06

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: 47.86  E-value: 1.20e-06
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 564329006 384 VIAHELAHQWFGNLVTVDW-WNDLWLNEGFASYVEFL 419
Cdd:cd09594   68 VLAHELTHAFTGQFSNLMYsWSSGWLNEGISDYFGGL 104
M1_like_TAF2 cd09839
TATA binding protein (TBP) associated factor 2; This family includes TATA binding protein (TBP) ...
 384-415 2.79e-04

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: 44.53  E-value: 2.79e-04
                         10        20        30
                 ....*....|....*....|....*....|..
gi 564329006 384 VIAHELAHQWFGNLVTVDWWNDLWLNEGFASY 415
Cdd:cd09839  377 KLAHALASQWFGINIIPKTWSDTWLVIGIAGY 408
 
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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