6U7K,6U7K,6U7K


Conserved Protein Domain Family
PDEV-like_Spike_SD1-2_S1-2_S2

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cd22376: PDEV-like_Spike_SD1-2_S1-2_S2 
SD-1 and SD-2 subdomains, the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from Porcine epidemic diarrhea virus and related alphacoronavirus
This group contains the SD-1 and SD-2 subdomains of the S1 subunit C-terminal domain (C-domain), the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from alphacoronaviruses, including porcine epidemic diarrhea virus (PEDV), Scotophilus bat coronavirus, and swine enteric coronavirus, among others. The CoV S protein is an envelope glycoprotein that plays a very important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains the coronavirus fusion machinery and is primarily alpha-helical. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-domain. The S1 C-domain also contains two subdomains (SD-1 and SD-2), which connect the S1 and S2 subunits. Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including SARS-CoV-2, SARS-CoV and MERS-CoV use the C-domain to bind their receptors. The S2 subunit comprises the fusion peptide (FP), a second proteolytic site (S2'), followed by an internal fusion peptide (IFP) and two heptad-repeat domains (HR1 and HR2) preceding the transmembrane domain (TM). After binding of the S1 subunit RBD on the virion to its receptor on the target cell, the HR1 and HR2 domains interact with each other to form a six-helix bundle (6-HB) fusion core, bringing viral and cellular membranes into close proximity for fusion and infection. In order to catalyze the membrane fusion reaction, CoV S needs to be primed through cleavage at the S1/S2 and S2' sites. In the case of human-infecting coronaviruses such as SARS-CoV-2, HCoV-OC43, MERS-CoV, and HKU1 the spike protein contains an insertion of (R/K)-(2X)n-(R/K) (furin cleavage motif) at the S1/S2 site, which is absent in SARS-CoV and other SARS-related coronaviruses, as well as Rousettus bat coronavirus HKU9. The region modeled in this cd (SD-1 and SD-2, the S1/S2 cleavage region, and the S2 fusion subunit) plays an essential role in viral entry by initiating fusion of the viral and cellular membranes.
Statistics
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PSSM-Id: 411963
Aligned: 25 rows
Threshold Bit Score: 1222.69
Created: 20-May-2020
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 20 residues -Click on image for an interactive view with Cn3D
Feature 1:S1/S2 cleavage region
Evidence:
  • Comment:the S glycoprotein needs to be primed through cleavage at the S1/S2 site located within the S1/S2 cleavage region, and the S2' site (R/S) in order to mediate membrane fusion
  • Comment:the S1/S2 site may contain a variant furin cleavage motif or other protease cleavage motif

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                      
6U7K_A     637 DVSFMTLDVCTKYTIYGFKGEGIITl-tNSSILAGVYYTSDSGQLLAFKNVTSGaVYSVTPCSFSEQAAYVNdDIVGVIS 715  Porcine epidemic...
AYR18455   637 DVSFVHLNVCTSYTIYGHKGEGIIRp-tNTSYLAGLYYTSTSGQLLAFKNVTSGvVYSVTPCSYAQQAAFIQnKIVGVMS 715  Alphacoronavirus...
AYR18499   639 DISELHLDTCTTYTIYGFRGDGVIRl-tNQTLLSGVYYTSESGQLLAFKNVTTGqIYSVTPCQLVQQVAFVEdKIVGVIS 717  Alphacoronavirus...
Q0Q466     639 DISELHLDTCTTYTIYGFRGDGVIRltnQTFLSGVYYTSESGQLLAFKNVTTGQ-IYSVTPCQLVQQVAFVEdRIVGVIS 717  Scotophilus bat ...
QER90704   629 DVSFYQEGVCSQYTIYGHKGEGIISksnLAYLSGLYYTSPSGQILAFKNITTGD-IYSVLPCSYSQQAVFIGgVIVGVMN 707  Bat alphacoronav...
ABG11964   639 DISELHLDTCTTYTIYGFRGDGVIRltnQTLLSGVYYTSESGQLLAFKNVTTGQ-IYSVTPCQLVQQVAFVEdRIVGVIS 717  Bat coronavirus ...
QDE55565   636 DVSFFTEGVCSQYTIYGHKGEGIISksnTEYIAGLYYTSPSGQILAFKNITTGD-IYSVLPCSFSQQAAFIDgAIVGVMS 714  Bat alphacoronav...
ABG11965   625 DVSFFEEGVCSQYTIYGHKGQGKIVksdVEYLAGLYYTAPSGQILAFKNITTGD-IYSVLPCSFSQQAVFIEgRIVGVMS 703  Bat coronavirus ...
ANA96048   630 DVSFMSLNVCTQYTIYGFKGEGVIQqtnQTLLAGVYYASASGQLLAFKNVTTGV-IYSVTPCVFAQQAALIAdDIVGIMS 708  Bat coronavirus
ASL24654   631 DVSTVVLDVCCTYSIYGHTGDGVIRltnDTYLGGLYYTSPGGALLGFKNVSTGE-IYSVTPCSLTQQVAVVSdDIVGVVS 709  Myotis lucifugus...
Feature 1                                                      ####################            
6U7K_A     716 SLs----nSTFNNTRELPGFFYHSNDGSNCTEPVLVYSNIGVCKSGSIGYVPSQYGQVKIAPTVTGNISIPTNFSMSIRT 791  Porcine epidemic...
AYR18455   716 SVs----sSNFTHTMDLPGFYYHTNNASNCTSPALVYSNLGVCSTGAIGYLPPKQEEPKVQPMFTGNVSIPTNFTMSIRT 791  Alphacoronavirus...
AYR18499   718 SVan--ntVFFNSTRTFPGFYYHSNDTNNCTSPRLVYSNIGVCTSGAIGLLSPKAARPQIQPMFQGNISIPTNFTLSVRT 795  Alphacoronavirus...
Q0Q466     718 SAnn---tGFFNSTRTFPGFYYHSNDTTNCTSPRLVYSNIGVCTSGAIGLLSPKAAQPQVQPMFQGNISIPTNFTMSVRT 794  Scotophilus bat ...
QER90704   708 GFnn---tLPYSFTRELPGFFYHSNDSSNCTEPALVYSNIGVCKSGSLGVVGVRNTQPKIQPMSEGVISVPTNLTMQIRT 784  Bat alphacoronav...
ABG11964   718 SAnn---tGFFNSTRTFPGFYYHSNDTTNCTSPRLVYSNIGVCTSGAIGLLSPKAAQPQIQPMFQGNISIPTNFTMSVRT 794  Bat coronavirus ...
QDE55565   715 SInn---tLNYNHTRELPGFYYHSNDSANCTEPALVYSNIGVCKSGAIGLVAARTVQPKIQPMSEGIVSIPTNLTMQIRT 791  Bat alphacoronav...
ABG11965   704 SIns---tYAYNYTKELPGFFYHSNDDSNCTEPALVYSNIGVCKNGAIGLVGIRNTQPKIQPMSEGVISIPTNLTMQIRT 780  Bat coronavirus ...
ANA96048   709 SQpe---sEQFNDTKELPGFYYHSNSPENCTEPILVYSNIGVCASGSIGIVPLAEKPPSIQPMIVGNVSIPTNFTMGLRA 785  Bat coronavirus
ASL24654   710 SSaklsdqFSFAYTTVTDQFYYMTDGNSTCAEPVLTYSSLGVCQDGALRIMQPRQDTTQPTPIVSGVISIATNFTLSVVT 789  Myotis lucifugus...
Feature 1                                                                                      
6U7K_A     792 EYLQLYNTPVSVDCATYVCNGNSRCKQLLTQYTAACKTIESALQlSARLESVEVNSMLTISEEALQLATISSFNGDGYNF 871  Porcine epidemic...
AYR18455   792 EYLQLFNNPVSIDCAMYVCNGNLRCKTLLAQYTSSCKTIESALQlSARLESLEVNSMLTVSEEALKLGTIDTFVGGGYNF 871  Alphacoronavirus...
AYR18499   796 EYVQLFNKPVSVDCAMYVCNGNERCKQLLTQYTSACKNIESALQlSARLESMEVNSMLTVSDEALKLATISQFPGGGYNF 875  Alphacoronavirus...
Q0Q466     795 EYIQLFNKPVSVDCAMYVCNGNDRCKQLLSQYTSACKNIESALQlSARLESMEVNSMLTVSDEALKLATISQFPGGGYNF 874  Scotophilus bat ...
QER90704   785 EYIQLFNRPVSIDCAMYVCNGNPRCNALLSQYASACQTIESSLQlGARLESIEVNDMLTVSDEALRLSTIDTFGGGNYNF 864  Bat alphacoronav...
ABG11964   795 EYVQLFNKPVSVDCAMYVCNGNERCXQLLXQYTSACKNIESALQlSARLESMEVNSMLTVSDEALKLATIXXFPGGGYNF 874  Bat coronavirus ...
QDE55565   792 EYIQLFNKPVSIDCAMYVCNGNPRCNLLLSQYASACQTIESSLQmGARLESAEVSDMLTISEKALSLGTIEQFKGGDYNF 871  Bat alphacoronav...
ABG11965   781 EYIQLFSKPVSIDCAMYVCNGNERCNRLLGQYASACRTIESSLQlSARLESVEVNDMLTISEKALELGTIQKFGGGDYNF 860  Bat coronavirus ...
ANA96048   786 EYVQLFNTPVSIDCAMYVCGGNVRCKQLLAQYTSACKTIESALQlSARLESLEVNSMLAVSDEALALATIDTFPGGGYNF 865  Bat coronavirus
ASL24654   790 EYIQLANTPISVDCAMYVCNGNPRCNMLLSQYSSACQTIESALQlSAKLESIEVTNLLTVSEDNLQIANITTFNGGGYNF 869  Myotis lucifugus...
Feature 1                                                                                      
6U7K_A     872 TNVLGasvydpasgrvvqkRSVIEDLLFNKVVTNGLGTVDEDYKRCSNGRSVADLVCAQYYSGVMVLPGVVDAEKLHMYS 951  Porcine epidemic...
AYR18455   872 TNVLGasv---------ysRSFIEDLLFNKVVTNGLGTVDQDYKSCSKGLSVADLACAQYFNGIMVLPGVADWDKIHMYS 942  Alphacoronavirus...
AYR18499   876 TNILPanp---------gaRSVIEDILFDKVVTSGLGTVDEDYKRCSNGLSIADLACAQHYNGIMVLPGVADWEKVHMYS 946  Alphacoronavirus...
Q0Q466     875 TNILPanp---------gaRSVIEDILFDKVVTSGLGTVDEDYKRCSNGLSIADLACAQHYNGIMVLPGVADWEKVHMYS 945  Scotophilus bat ...
QER90704   865 SNVLGasp---------gqRSFIEDILFDKVVTNGLGTVDEDYKKCTNGLSIADLACAQYYSGVMVLPGVADAEKVHMYS 935  Bat alphacoronav...
ABG11964   875 XNILPanp---------gaRSVIEDILFDKVVTSGLGTVDEDYKRCSNGLSIADLACAQHYNGIMVLPGVADWEKVHMYS 945  Bat coronavirus ...
QDE55565   872 SNVLGasa---------gqKSFIEDLLFDKVVTNGLGTVDEDYKKCTNGVSLSDLTCAQYYNGIMVLPGVADAEKVHMYS 942  Bat alphacoronav...
ABG11965   861 TNVLGtst---------gqKSVIEDILFDKVVTNGLGTVDEDYKKCTNGLSISDLVCAQYYNGIMVLPGVADAEKVHMYS 931  Bat coronavirus ...
ANA96048   866 TNFLApas---------sgRSAIEELLFDKVVTTGLGTVDQDYKSCTNGLEIKDLVCAQYYNGIMVLPGVVSPNMLHTYS 936  Bat coronavirus
ASL24654   870 TNLMGsty---------stKSVIEDVLFDKVVTSGLGTVDADYKACSNGLSVADLVCAQYYQGVMVLPGVVDAEKLHMYS 940  Myotis lucifugus...
Feature 1                                                                                      
6U7K_A     952 ASLIGGMALGGITAAAALPFSYAVQARLNYLALQTDVLQRNQQLLAESFNSAIGNITSAFESVKEAISQTSKGLNTVAHA 1031 Porcine epidemic...
AYR18455   943 ASLVGGMTLGGITSSAALPFSYAVQARLNYVALQTDVLQRNQQMLAESFNSAIGNITLAFESVNDAIYQTSQGLSTVAEA 1022 Alphacoronavirus...
AYR18499   947 ASLVGGMTLGGITSAAALPFSYAVQARLNYVALQTDVLQRNQQMLANSFNSAISNITLAFESVNNAIYQTSAGLNTVAEA 1026 Alphacoronavirus...
Q0Q466     946 ASLVGGMTLGGITSAAALPFSYAVQARLNYVALQTDVLQRNQQMLANSFNSAISNITLAFESVNNAIYQTSAGLNTVAEA 1025 Scotophilus bat ...
QER90704   936 ASLMGGMALGGVTSVAALPFSYAVQARLNYVALQTDVLQRNQQLLAQSFNNAISNITMAFEGVNDAIQQTSQGLSTVAQA 1015 Bat alphacoronav...
ABG11964   946 ASLVGGMTLGGITXXAALPFSYAVQARLNYVALQTDVLQRNQQMLANSFNSAISNITLAFESVNNAIYQTSAGLNTVAEA 1025 Bat coronavirus ...
QDE55565   943 ASLMGGMVLGGVTAAAALPFSYAVQARLNYVALQTDVLQRNQQMLAQSFNSAISNITMAFENVNDAIQQTSQGLSTVAQA 1022 Bat alphacoronav...
ABG11965   932 ASLMGGMALGGITAAAALPFSYAVQARLNYVALQTDVLQRNQQLLAQSFNNAIGNITMAFESVNDAIEQTSQGLSTVAQA 1011 Bat coronavirus ...
ANA96048   937 AALTGGMVMGGLTAAAALPFSYSVQARLNYVALQTDVLQRNQQMLAQSFNNAIGNITSAFDRINDAISQTSMGLSTVAQA 1016 Bat coronavirus
ASL24654   941 ASLMGGMALGGITAAAALPFSYAVQARLNYVALQTDVLQRNQQMLAESFNNAIGNITNAFSSVNDAISQTADGLHTVAEA 1020 Myotis lucifugus...
Feature 1                                                                                      
6U7K_A    1032 LTKVQEVVNSQGSALNQLTVQLQHNFQAISSSIDDIYSRLDILSADVQVDRLITGRLSALNAFVAQTLTKYTEVQASRKL 1111 Porcine epidemic...
AYR18455  1023 LSKVQDVVNNQGSALNQLTVQLQNNFQAISSSINDIYSRLDQITADAQVDRLITGRLSALNAFVAQSLTKYSEVQASRQL 1102 Alphacoronavirus...
AYR18499  1027 LSKVQDVVNSQGNALNQLTVQLQNNFQAISNSIGDIYSRLDQITADAQVDRLITGRLAALNAFVAQSLTKYAEVQASRTL 1106 Alphacoronavirus...
Q0Q466    1026 LSKVQDVVNGQGNALSQLTVQLQNNFQAISNSIGDIYSRLDQITADAQVDRLITGRLAALNAFVAQSLTKYAEVQASRTL 1105 Scotophilus bat ...
QER90704  1016 LTKVQDVVNTQGLALSHLTKQLQNNFQAISSSISDIYARLDQLTADAQVDRLITGRLAALNAFVSQTMTKYVEVQASRRL 1095 Bat alphacoronav...
ABG11964  1026 LSKVQDVVNGQGNALSQLTVQLQNNFQAISNSIGDIYSRLDQITADAQVDRLITGRLAALNAFVAQSLTKYAEVQASRTL 1105 Bat coronavirus ...
QDE55565  1023 LTKVQDVVNTQGLALSHLTNQLQNNFQAISSSISDIYARLDQLTADAQVDRLITGRLAALNAFVSQTMTKYVEVQASRRL 1102 Bat alphacoronav...
ABG11965  1012 LTKVQDVVNGQGLALSHLTNQLQNNFQAISSSISDIYARLDQLTADAQVDRLITGRLSALNAFVSQTMTRYVEVQASRRL 1091 Bat coronavirus ...
ANA96048  1017 LSKVQDVVNLQGNALSHLTSQLQNNFQAISASINDIYSRLDQLSADAQVDRLITGRLAALNSFVAQSLTKYAETQASRQL 1096 Bat coronavirus
ASL24654  1021 LSKVQDVVNTQGMALNHLTLQLQHNFQAISSSIADIYRRLDQLTADAQVDRLINGRLAALNAFVSQTLTKYSQVQASRAL 1100 Myotis lucifugus...
Feature 1                                                                                      
6U7K_A    1112 AQQKVNECVKSQSQRYGFCGGDgeHIFSLVQAAPQGLLFLHTVLVPGDFVNVLAIAGLCVNGEIaltlrepg-lvlfthe 1190 Porcine epidemic...
AYR18455  1103 ALQKVNECVKSQSNRYGFCGGDgeHIFSLTQAAPQGLMFLHTVLVPSGFVNVTAVAGLCVSGNMamtlr-------qggf 1175 Alphacoronavirus...
AYR18499  1107 AKQKVNECVKSQSPRYGFCGDEgeHIFSITQAAPQGLMFLHTVLVPTGFINVTAVTGLCVDDNIamtlr-------qsgf 1179 Alphacoronavirus...
Q0Q466    1106 AKQKVNECVKSQSPRYGFCGDEgeHIFSLTQAAPQGLMFLHTVLVPNGFINVTAVTGLCVDETIamtlr-------qsgf 1178 Scotophilus bat ...
QER90704  1096 AQQKVNECVKSQSTRYGFCGDDgeHIFSIVQGAPQGLMFLHTVLVPSSYVNVTAVAGLCVDDTKafvlret----glvmf 1171 Bat alphacoronav...
ABG11964  1106 AKQKVNECVKSQSPRYGFCGDDgeHIFSITQAAPQGLLFLHTVLVPTGFINVTAVTGLCVDDNLamtlr-------qsgl 1178 Bat coronavirus ...
QDE55565  1103 AQQKVNECVKSQSTRYGFCGDDgeHIFSIVQGAPQGLMFLHTVLVPSSYINVTAVSGLCVDDTKafvlke-----pglvm 1177 Bat alphacoronav...
ABG11965  1092 AQQKVNECVKSQSTRYGFCGDDgeHIFSMVQGAPQGLMFLHTVLVPSGYVNVTAVSGLCVDDTRafvlrep----glvmf 1167 Bat coronavirus ...
ANA96048  1097 ATQKINECVKSQSTRYGFCGGDgdHIFSVTQAAPQGLMFFHAVLQPSGFVNVSAIAGLCVDQTAafalkafglilfstea 1176 Bat coronavirus
ASL24654  1101 AKQKINECVLSQSPRFGFCGDGgrHVFTVTQAAPQGLLFLHTVLRPTSSINVTAAAGICVDGSGyalse--------pgl 1172 Myotis lucifugus...
Feature 1                                                                                      
6U7K_A    1191 lQTYTATEYFVSSRRMFEPRKPTVSDfVQIESCVVTYVNLTSDQLPDVIPDYIDVNKTLDEILASLPNRTGPSLPLDVFN 1270 Porcine epidemic...
AYR18455  1176 iLFVQGDEYFVSPRKMFEPRKPQVTDfVQIATCIISYVNITNEQLPDIIPDYIDVNKTLDDILASLPNNTAPELPLEIFN 1255 Alphacoronavirus...
AYR18499  1180 vLFVQNDKYLVSPRKMFEPRRPEVADfVRIKTCQISYVNITNEQLPDIIPDYVDVNKTIDEILANLPNNTVPDLPLDVFN 1259 Alphacoronavirus...
Q0Q466    1179 vLFVQNGNYLVSPRKMFEPRRPEVADfVQVKTCTISYVNITNNQLPDIIPDYVDVNKTIDEILANLPNNTVPDLPLDVFN 1258 Scotophilus bat ...
QER90704  1172 kSSDSDETYFLTPRKMFEPRSISVTDlVQVETCLVSYFNLTSNELPDVVPDYVDVNKTLEDILASLPNRSEPTFPLDVFN 1251 Bat alphacoronav...
ABG11964  1179 vLFVQGGNYLVSPRKMFEPRKPEVADfVRIKTCEISYVNITNDRLPDIIPDYVDVNKTIDDILANLPNNTVPDLLLDVFN 1258 Bat coronavirus ...
QDE55565  1178 fKYSGNTSYFLTPRKMFEPRTISVSDlVQVESCVVTYFNLSSSELPDVVPDYIDVNKTLEEILNSLPNRTEPEFPLDVFN 1257 Bat alphacoronav...
ABG11965  1168 kQDSSTNSYFLTPRKMFEPRAISVTDlVQVETCLVAYFNLSSDQLPDVVPDYIDVNKTLEDILASLPNRTEPNFPLDVFN 1247 Bat coronavirus ...
ANA96048  1177 pLSGFSTRYYVTPRKMFEPRVPQISDfVRLESCQINATNITQDMLPDIIPEYVDVNKTLDDIISSLPNTTGPGLSLDVFN 1256 Bat coronavirus
ASL24654  1173 vLVYEQNQYVITPRVMFEPRQPQISDfVRIDGCDVEYFNVTSDLLPDIFPDFIDVNKTLEDILSQLQNNTGPKFDIDIFN 1252 Myotis lucifugus...
Feature 1                                                       
6U7K_A    1271 ATYLNLTGEIADLEQRSESLRNTTEELRSLINNINNTLVDLEWLNRVET 1319 Porcine epidemic diarrhea virus CV777
AYR18455  1256 QTYLNLTGEIADLEARSESLKNTTEELKQLIQNINNTLVDLQWLNRVET 1304 Alphacoronavirus sp.
AYR18499  1260 QTFLNLTGEIADLEARSESLKNTSEELRQLIQNINNTLVDLQWLNRVET 1308 Alphacoronavirus sp.
Q0Q466    1259 QTFLNLTGEIADLEARSESLKNTSEELRQLIQNINNTLVDLQWLNRVET 1307 Scotophilus bat coronavirus 512
QER90704  1252 ATYLNLTGEIADLEQRADALHNTSEELRRLIDNINNTLVDLEWLNRVET 1300 Bat alphacoronavirus
ABG11964  1259 QTFLNLTGEIADLDARSESLKNTSEELRQLIQNINNTLVDLQWLNRVET 1307 Bat coronavirus A527/2005
QDE55565  1258 ATYLNLTGEIADLEKRADALHNTSEELRRLIDNINSTLVDLEWLNRVET 1306 Bat alphacoronavirus
ABG11965  1248 ATYLNLTGEXADLEMRSEYLKNTTEELRLLINSINSTLVDLEWLNRVET 1296 Bat coronavirus A701/2005
ANA96048  1257 ATYLNLTGEIADLEVRADALHNVTEDLRHLINNINSTLVDLEWLNRVEN 1305 Bat coronavirus
ASL24654  1253 ATYLNLSSEIADLELRSESLHNTTEELKRLIDNINSTLVDLEWLNRVET 1301 Myotis lucifugus coronavirus

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