Conserved Protein Domain Family
M1_APN_3

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cd09602: M1_APN_3 
Peptidase M1 family containing Aminopeptidase N
This family contains 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 consists of a small N-terminal cytoplasmic domain, a single transmembrane domain and a large extracellular ectodomain that contains the active site. It 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.
Statistics
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PSSM-Id: 189009
View PSSM: cd09602
Aligned: 36 rows
Threshold Bit Score: 447.444
Threshold Setting Gi: 118370736
Created: 15-Sep-2010
Updated: 17-Jan-2013
Structure
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Aligned Rows:
Hierarchy
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Display:
 
Zn binding site
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:The zinc ion is tetrahedrally co-ordinated by three amino acid ligands and a water molecule

cd09602 is part of a hierarchy of related CD models.
Use the graphical representation to navigate this hierarchy.
cd09602 is a member of the superfamily cl14813.
cd02699:M4cd06258:M3_likecd06455:M3A_TOPcd06456:M3A_DCPcd06457:M3A_MIPcd06459:M3B_PepFcd06460:M32_Taqcd06461:M2_ACEcd08662:M13cd09594:GluZincincd09595:M1cd09596:M36cd09597:M4_neutral_proteasecd09598:M4_uncharacterizedcd09599:M1_LTA4Hcd09600:M1_APN_1cd09601:M1_APN_2cd09602:M1_APN_3cd09603:M1_APN_4cd09604:M1_APN_5cd09605:M3Acd09606:M3B_PepF_1cd09607:M3B_PepF_2cd09608:M3B_PepF_3cd09609:M3B_PepF_4cd09610:M3B_PepF_5cd09839:M1_TAF21183779191183779171183707361454983391461821492840355098870470725503573315449211630438308030072975718322275990020407243726442547869081183798751461815431461840301455358781183996211455189382421378016245060317032871584199128572524227496111256826179298303121197151552983275415903774129130292325682592928403142511971692211837791911837791711837073614549833914618214928403550988704707255035733154492116304383080300729757183222759900204072437264425478690811837987514618154314618403014553587811839962114551893824213780162450603170328715841991285725242274961112568261792983031211971515529832754159037741291302923256825929284031425119716922
cd09602 Sequence Cluster
cd09602 Sequence Cluster
Sub-family Hierarchy
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 cd09602 Branch
 Whole Hierarchy
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CD Hierarchy
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 1703287     14 RATLLt-vDSYEIDLDLTgaqeggtYRSVTTVRFDva-------egGGESFIDLvap--tvHEVTLNgdaldta------ 77
gi 146182149   20 RSQLVk-nVSYNLHFIFFenq--rtFDGLIKINFDfdlsk-nqtkiDENSQIDYill--dyAGKSISqivingkeiimqq 93
gi 118377919  506 RNSILksvDNYEVTLNLLkg---tdYNGTVVIDFKfkql----lqqGQHLQLDYdgq-evdYVALVDqqrqeikq---le 574
gi 118377917 1046 NASQSq-kLNSSNYSNLTlqk-gtdYYGTVEIHLHlqdn----rntDNHVQIDFagq--kvDFVKIRnidqsdsqfrnik 1117
gi 118370736   26 REQYIysiNQYEIYLNLNidl-yqdYCGEKVISVSild------knDQEEQIHFq-----yVPNKLSipl---------- 83
gi 284035509   49 RKQAIs-qLAYALKFDIPaqk-nqpILSTETITFDwaasrwtkdasARQLPLDFkeerthlQTVSVNgtrvpv------- 119
gi 88704707    69 RAERIs-rLSYELQFSVPgdr-trpLAGRAILRFNla-------gnDSPLAIDFaqgadsvLSVSSSgapvay------- 132
gi 255035733   40 RKQHId-sIRYAIELDIPagk-agkIVGKETISFHld-------alDSALVLDFnadaghlLDVRVGdeqvgh------- 103
gi 154492116   43 RKEHFk-eVRYNLFFSIPesr-eeaVTGKADITLAir--------eRLPVIIDFrgeseqvASVLLNgrkvpy------- 105
gi 304383080   43 REQTIs-qPAYHLNFTIPke---gvVKGEAIISFVs---------kTRRVVLDFqadanqlHTIMVNgqkana------- 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 1703287     78 evfqdsRIALPgll-------pgRNILRVVADCaytntgeglh----rfvdpvddqaYLYTQFEvpDARRVFASFEQPDL 146
gi 146182149   94 dmwhdnFIKINidql-----kmqQNVVEIIFQGnfhndglgirqvthpvknnyqnntLIYTLFPtnNAHRVFPCFDQPDI 168
gi 118377919  575 yvfenqRILIGseqfs---gvtiDSVVSIKLKFknqyynlddgl---nstitdqnnqYIYAQGEvaNTYKIFPCIEQINF 648
gi 118377917 1118 ftfernRVMIDseeimqdlkqnnKISIMIQFKNqynntvqdrg----lfstitgenqYLYSQGEvaSMHYIFPCVEQINF 1193
gi 118370736   84 ---kdiQKHLNkk--------dhNLTFLIAFQNeyskvraegiv---kyseesqnkfYFYCQGEvgCTQMIFPCIDMVNF 149
gi 284035509  120 -vfeseHLLIStall-----kpkNNVISIGFTAgnlsl--------------nrnddYLYTLLVpdRTRTVFPCFDQPDL 179
gi 88704707   133 -dfdkeHLIIPtaal-----regDNVLTLDFIApqdav--------------nrnpdYLFTLFVpdRARTVFPLFDQPDL 192
gi 255035733  104 -qfvneHIVIDpkhl-----rkgRNEVVIDFVAgdqsl--------------nrsedYLYTLFVpdRASTCFPLFDQPNL 163
gi 154492116  106 -tvkdeHIVIDtrev-----angENRVTIEFTAndqsl--------------nrrdeFLYTLLVpdRARTLFPCFDQPDM 165
gi 304383080  103 -tvvneHIVLPrsli-----rkgKNTVALQFTAgdkal--------------nrhtdFLYTLLVpdKARMLFPCFDQPNL 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 1703287    147 KATFQFTVKAPegWTVISNSp---------------tPEPKdnVWEFEPTp-rISSYVTALIVGPYHsvhsvy---ekdg 207
gi 146182149  169 KAKFSLLIDAPqtWTVISIQmenfqgyvdayskqsmdSKVVlsRWYFEQTp-lISTYLFSFVMGDLSkverdiqygqnka 247
gi 118377919  649 RATFDLTVTHPasWKVVSNEpils----------qlnISFDtqKTVFKKSqiaLPNYLFTLCAGDYEqykn------iyn 712
gi 118377917 1194 RAPFQLSLVHPadWVVISNSsiay----------qqnINNLtvLSKFETTq-pFPCYLYGIFAGNYVvynq------kyk 1256
gi 118370736  150 RSHYTLTVQHPqnWMVSSHTewyk----------qekIIDEivVTYFPQTkiaFPTYLFGFYAGDYFkysd------kyr 213
gi 284035509  180 KATFQVSLTVPanWEAMTNSple-----------rstLTGDrkTVRFQTSn-lIPTYLFSFVAGKFTavtr-------tl 240
gi 88704707   193 KARYSLTLEVPksWTALGNGrla-----------gveERNGrrMFRFRETr-aIPSYLFAFVAGEFEvvsq-------sv 253
gi 255035733  164 KASYQLTLKMPveWEAVSNGkln-----------aqtTSNGkrIYAFEATk-pVSSYLFAFAAGKFFketr-------tq 224
gi 154492116  166 KSLFTLSLEVPssWQAVANGaveq---------vdstSVAGckRISFRETe-pLSTYLFSFVAGKLTrety-------sr 228
gi 304383080  163 KAQFTLTLTVPngWCAVSNTaiv-----------dsvSISEgmRYTFGTTr-lLPTYLFSFVVGRFQktst-------vc 223
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 1703287    208 qSVPLGIYCRpsl--aehLDADAIFEVTRQGFDWFqEKFDYAYPF--KKYDQLFVPeFNAGAMENAGAVTIRDQYVFrsk 283
gi 146182149  248 qNIKLRLFSRaqvgqileNQMEEISFIIQHGLTFFeNFFQTPYPFsnQKYDQVFCPqFHYAGMENPGLVCFTENYLIteq 327
gi 118377919  713 dKIGMDTYYRkekaqfvaTQIQDFNDITKFGINYMeEYTKINYYM--DKYDSVYCIdYTYYGMENPGCTTLEERRYVfeq 790
gi 118377917 1257 eKVDLNIYCRkekakvieNQIDELFQITKFGLNLMeEYTEIDFYM--KKLDLVFCDnYNFYGMENPGCISLEEKRYIfee 1334
gi 118370736  214 dNIDINIYCRqnliqfldEQVNEYFKQIKFALDFMeSYTGVKYFF--QKFDLFFCPyYKDIGMETFGCISLDENYYLcni 291
gi 284035509  241 kGRSMTLLHRetdstklrLSTDLLFSLHADALTFLeDYTQIKYPF--QKFDFVAVPdFQYGGMEHVGAIDYRSSALFldn 318
gi 88704707   254 rGREMTLLHRetdgeklaRNLDSIFETHADALDWLeEYTAIDYPF--DKFAFALIPdFPYGGMEHVGAIAYRASSLLlee 331
gi 255035733  225 dGREMTMYYRetdttkvnRNRDEVFRLHAQSLTWLeDYTSIEYPF--GKFDFVLLPsFQYGGMEHPGAVFYNESALFlde 302
gi 154492116  229 dGRNISIYHRetdp-kkvAQCPDIASEVFDALEWQeEYTQIPYPF--AKYDLIILPeFQFGGMEHTGATLYTDGRMFlne 305
gi 304383080  224 dGLPMTAYYRetdt-akvSQLPEVFRQIAYSKRWLeDYTGIKMPF--EKYDFIMIPgFQFGGMEHPGAVLYKHNSIFlgp 300
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                      #   #                  #                           
gi 1703287    284 vtd---------------aayevRAATILHELAHMWFGDLVTMEWWnDLWLNESFATYAEAACQaaapg--skwphSWTT 346
gi 146182149  328 kst---------------nihttRASSILHELSHMWFGNLVTMKWWnDIWLNESFATYISYLCLsevdef-rtkymNPWI 391
gi 118377919  791 ere--------------pikialRSDILFHEISHMWFGDCISLDWWnNLFLKEGFANFFGYKINkeyfk---gkelEWYY 853
gi 118377917 1335 ere--------------plkimrRAYIMFHEIAHMWFGDFVSLEWWnNLFLKEGFATFFGYKAVskyf-----sqlEYGI 1395
gi 118370736  292 iteaieakdiqnaivkryvfdldRVETLFHEIAHQWFGNYVSIKWWnDLFFKEGFANLFSQKMIyqyfknengielRSQL 371
gi 284035509  319 gat--------------rdqrlsRAHVIAHETAHMWFGDLVTMRWFdDVWLKEVFANFIADKIMevst----pdanYDLQ 380
gi 88704707   332 sps--------------enqllnRAQLIAHETAHMWFGNLVTMRWFnDVWTKEVFANFMADKVVnpqf----pdtdHALN 393
gi 255035733  303 nas--------------vnrkmaRASVIAHESAHMWFGDLVTMDWFnDVWLKEVFANFMAAKIVhpsf----peinHDLR 364
gi 154492116  306 npt--------------lnerlaRSSLIAHETSHMWFGDFVTMEWFnDVWTKEVFANYYASQIIkplf----pevnHSLN 367
gi 304383080  301 tpt--------------pdellrRAELLAHETTHYWFGDLVTMRWFnDVWTKEVFANYLAAKIMqply----pdidHPLN 362
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 1703287    347 FANQMKTWaYRQDQLPSTHPIMADisdld--dvlvnFDGITYAKGASVLKQLVAy-vGEEAFFKGVQAYFKRHafgNTRL 423
gi 146182149  392 KFCEYKSNgFNQDSKLSTHSIAQEiestd--vsmeiYDSITYSKGAGIIKQLVFl-iGLPSFQSFLHLYFQRYqwqNASM 468
gi 118377919  854 EMGKVKAV-YDESNPETVFPLSHErglyqdyesmnyHSDISYQKGGSVFQMMEQkiyGEQDFQNRIIKYFKNNqftVAGI 932
gi 118377917 1396 HIELQKIMiLIDENKANMITLSHEklpyydysmfkaHNCISYNKGGMFFQFLEQkvyGEQQFKELLRQYLRENsfsKVDE 1475
gi 118370736  372 DQFDFLQDdLKIDYTLMHTPLKYDmyle-----lntHNDITYMKSQNIFDLLEYkiyGQEKFNKILQKLLQDFqnqSISS 446
gi 284035509  381 FVVDHYPAaYGVDRTEGANPIGQPlsnlq--eagslYGGIIYHKAPIMMRQLEQl-mGKDALRDGLREYLKKYssgNASW 457
gi 88704707   394 FLVSHYPQaYGVDRSEGANPIRQQldnln--lagqmYGPIIYHKAPIMMRQLELl-lGKTAFRDGLRTYLTRFsygNATW 470
gi 255035733  365 FLLAHYPNaYDVDRTAGTNPILQQlgnlk--nagtlYGAIIYMKAPIVMRQLERk-iGEKMMQESLREYLKTYsfgNARW 441
gi 154492116  368 FMLDYIPAaYSEDRTAGANPVKQQlenmr--daglmYGNIIYDKSPVILEMLIKk-mGKESFRKGIQEYLKTYaygNATW 444
gi 304383080  363 FLRSYQTRaLTEDRTQGTHPIQQPldnln--nagllYGNIIYCKAPVMMRKLEEt-iGEKNFRDGLSEYLKTYsygNATW 439
                         490       500       510
                  ....*....|....*....|....*....|
Feature 1                                       
gi 1703287    424 SDLLGALEEt---sGRDLKTWSKAWLETAG 450
gi 146182149  469 HDFFSMIQLvl-kqDKKFENFNIEMWIDQY 497
gi 118377919  933 QEFLAELKEddsisRKYIFNKGISYYDQGV 962
gi 118377917 1476 KSFLKYFKDiy--sQKYLFKNHLSYFCESQ 1503
gi 118370736  447 KDFLTYFDDqv--tKKLLTTQGYVYFKGQN 474
gi 284035509  458 HDLITILDTh---tPADLQAWNRVWVTETG 484
gi 88704707   471 PALIEILDEk---tPIDLGSWSEVWVNTPG 497
gi 255035733  442 DDLIGIIDKr---tPQDIAAWSNVWVKTPG 468
gi 154492116  445 EGLIGILDKy---tDDDLTAWSRVWVNEKG 471
gi 304383080  440 DNLVNIFAKk----DPRVLQFNDVWVKSKG 465

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