6VSB,5X59,5I08


Conserved Protein Domain Family
betaCoV_Spike_SD1-2_S1-S2_S2

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cd22370: betaCoV_Spike_SD1-2_S1-S2_S2 
SD-1 and SD-2 subdomains, the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from betacoronaviruses
This family 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 betacoronaviruses, including three highly pathogenic human coronaviruses (CoVs), Middle East respiratory syndrome coronavirus (MERS-CoV), Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and SARS coronavirus 2 (SARS-CoV-2), also known as a 2019 novel coronavirus (2019-nCoV). 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: 411957
Aligned: 8 rows
Threshold Bit Score: 1035.51
Created: 20-May-2020
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 10 residues -Click on image for an interactive view with Cn3D
Feature 1:S1/S2 cleavage region
Evidence:
  • Comment:the S1/S2 cleavage region spans the sequence between highlighted residues
  • 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
  • Comment:SARS-CoV-2 contains an insertion of RRAR (furin cleavage site) at the S1/S2 site of the Spike protein, which is absent in SARS-CoV and other SARS-related coronaviruses

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                         
6VSB_A        543 FNGLTGTGVLTESNKkfl-pfqQFGRDiaDTTDAVRdpqtLEILDITPCSFGGVSVITPGtntsnqvAVLYQDVNCTEVP 621  Severe acute ...
5X59_A        591 LYGVSGRGVFQNCTAvgv-rqqRFVYDayQNLVGYYsd-dGNYYCLRACVSVPVSVIYDKetk--thATLFGSVACEHIS 666  Middle East r...
ADY17911      569 VYGYNGQGILVETNEtfp-sfqNVQLWpnGQLKAFKdpqsNQVIAVLPCAEADVSVATAGnht-nevATLFTGAPCSGVQ 646  Zaria bat cor...
YP_009072440  589 IYGYKGTGVIVSANYtfq-sfqTVQLTstGSLHSFKy--nNTIYGILPCAQAQVSIVTAGsnh-dnvAVVYNGLGCNAFQ 664  Bat Hp-betaco...
AVP25406      531 LYGYTGTGVLNATTAisi-psdKVFSAsdTGDIVAVrv-nGTVYTIRPCVSVPISVGYHAgy---erALLFNGLSCADRT 605  Rousettus bat...
5I08_A        611 LYGITGQGIFKEVSAayynnwqNLLYDsnGNIIGFKdfltNKTYTILPCYSGRVSAAFYQnss--spALLYRNLKCSYVL 688  Human coronav...
QJX68370      543 FNGLTGTGVLTESNKkfl-pfqQFGRDiaDTTDAVRdpqtLEILDITPCSFGGVSVITPGtntsnqvAVLYQGVNCTEVP 621  Severe acute ...
QIQ54048      543 FNGLTGTGVLTTSKKqfl-pfqQFGRDisDTTDAVRdpqtLEILDITPCSFGGVSVITPGtntsnqvAVLYQDVNCTEVP 621  Pangolin coro...
Feature 1                                                               ###                   ####
6VSB_A        622 Vaihadqltptw--rvystgsnvfQTRAGCLIGAe--hVNNSYECDIPIGAGICASYqtqtnspgsassvasqsiiAYTM 697  Severe acute ...
5X59_A        667 StmsqysrstrsmlkrrdstygplQTPVGCVLGLvn-sSLFVEDCKLPLGQSLCALPdtpstltprsvssvpgemrLASI 745  Middle East r...
ADY17911      647 Akllgvsttsmw-rrisenttkgiDTPVGCLFGAvl-sTSNSTECQFSLGLDTCLNItrgrvgsr---saghlkesSTYN 721  Zaria bat cor...
YP_009072440  665 Skmqgvdntew---svytnfsspiDTPVGCLTGAiq-aQENSTECQFALGLDSCVNYtadtrlrta--raadraltFNYM 738  Bat Hp-betaco...
AVP25406      606 Saitmpastyws-taraqsasnyyDTISGCVYNVdynnATTVNQCVMPLGNSLCLVPntqrv----------agsrLTLV 674  Rousettus bat...
5I08_A        689 Nnisfis------------qpfyfDSYLGCVLNAvnltSYSVSSCDLRMGSGFCIDYalpssggsg--sgisspyrFVTF 754  Human coronav...
QJX68370      622 Vaihadqltptw--rvystgsnvfQTRAGCLIGAe--hVNNSYECDIPIGAGICASYqtqtnsprrarsvasqsiiAYTM 697  Severe acute ...
QIQ54048      622 Maihaeqltpaw--rvysaganvfQTRAGCLVGAe--hVNNSYECDIPVGAGICASYhsmssfrs----vnqrsiiAYTM 693  Pangolin coro...
Feature 1         ##               #                                                              
6VSB_A        698 SLgaens------vaysNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTgIA 771  Severe acute ...
5X59_A        746 AFnhpiqv---dqlnssYFKLSIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCSKINQALHgAN 822  Middle East r...
ADY17911      722 YFfqdmpke--seipfsNFTVEIPDNFTIAIEYETLPIRMSKISVDCSRYVCGTDVVCANQLVQYGKFCDNINEALRgVS 799  Zaria bat cor...
YP_009072440  739 YFaqelpsqseqsvafdNSTLQIPINFTIGIEYETIPVTMPKVTVDCAQYVCGDNSECRTLLVQYGTFCETINDALRgVA 818  Bat Hp-betaco...
AVP25406      675 NFdpmyvsd-svtsltpIYWVNIPTNFTLAATEEFIQTTAPKMNIDCARYLCGDSSRCLTVSLQYGTFCDDINKALLrVS 753  Rousettus bat...
5I08_A        755 EPfnvsfvndsvetvggLFEIQIPTNFTIAGHEEFIQTSSPKVTIDCSAFVCSNYAACHDLLSEYGTFCDNINSILNeVN 834  Human coronav...
QJX68370      698 SLgaens------vaysNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTgIA 771  Severe acute ...
QIQ54048      694 SLgaens------vaysNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSIECSNLLLQYGSFCTQLNRALTgIA 767  Pangolin coro...
Feature 1                                                                                         
6VSB_A        772 VEQDKNTQEVFAQVKqiyktp------pikdfGGFNFSQILpdps----kpskRSFIEDLLFNKVTLADAGFIKQygDCL 841  Severe acute ...
5X59_A        823 LRQDDSVRNLFASVKssqssp-----iipgfgGDFNLTLLEpvsist-gsrsaRSAIEDLLFDKVTIADPGYMQGydDCM 896  Middle East r...
ADY17911      800 LQQDSNVAELLSDIKqltrvsd----ldlkdiNGFNFSSLYntdyldatssgrRSAIEDLLFNKVVTADVGFMKKyeECT 875  Zaria bat cor...
YP_009072440  819 LQQDVNQKDVFSSVRrlakvss---pmnlgnlNGFNFSSILnqeaingnnfqaRSAIEDLFFDKIETADVGFQKKydECT 895  Bat Hp-betaco...
AVP25406      754 QLLDTSLLALFKEFStnvrpe-----aelsldGAYNFTGLMgclgsncggkshRSALSELLYNKVKVADPGFMSSyqKCI 828  Rousettus bat...
5I08_A        835 DLLDITQLQVANALMqgvtlssnlntnlhsdvDNIDFKSLLgclgsq-cgsssRSLLEDLLFNKVKLSDVGFVEAynNCT 913  Human coronav...
QJX68370      772 VEQDKNTQEVFAQVKqiyktp------pikdfGGFNFSQILpdps----kpskRSFIEDLLFNKVTLADAGFIKQygDCL 841  Severe acute ...
QIQ54048      768 VEQDKNTQEVFAQVKqiyktp------pikdfGGFNFLQILpdps----kpskRSFIEDLLFNKVTLADAGFIKQygDCL 837  Pangolin coro...
Feature 1                                                                                         
6VSB_A        842 GDia---arDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGtitsgwtfgagAALQIPFAMQMAYRFNGIGVTQNVLYE 918  Severe acute ...
5X59_A        897 QQgpa-sarDLICAQYVAGYKVLPPLMDVNMEAAYTSSLLGSiagvgwtaglsSFAAIPFAQSIFYRLNGVGITQQVLSE 975  Middle East r...
ADY17911      876 GGsv---fkDLDCAQSFNGLKVLPPQMSDAHVGVYTTAAAMG-----------SFFSIPNTMQMAYRFNGIAVTQSVLVD 941  Zaria bat cor...
YP_009072440  896 GGsv---vkDLGCAQSFNGLMVLPPQMTDAHVAAYTTSAALG-----------SFFSIPNTMQMAYRFNGIAVTQKVLVD 961  Bat Hp-betaco...
AVP25406      829 DSqwggevrDLICTQTYNGISVLPPIVAPGMQALYTSLLVGAvassgytfgitSVGVIPFATQLQFRLNGIGVTTQVLVE 908  Rousettus bat...
5I08_A        914 GGse---irDLLCVQSFNGIKVLPPILSETQISGYTTAATVAamfp----pwsAAAGVPFSLNVQYRINGLGVTMDVLNK 986  Human coronav...
QJX68370      842 GDia---arDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGtitsgwtfgagAALQIPFAMQMAYRFNGIGVTQNVLYE 918  Severe acute ...
QIQ54048      838 GDia---arDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGtitsgwtfgagAALQIPFAMQMAYRFNGIGVTQNVLYE 914  Pangolin coro...
Feature 1                                                                                         
6VSB_A        919 NQKLIANQFNSAIGKIQDSLSSTAsALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLIT 998  Severe acute ...
5X59_A        976 NQKLIANKFNQALGAMQTGFTTTNeAFQKVQDAVNNNAQALSKLASELSNTFGAISASIGDIIQRLDVLEQDAQIDRLIN 1055 Middle East r...
ADY17911      942 NQKEIANKFNQALTSIQQGFTATNsAVQKLQDVVNANAAALNTLVTQLGNNFGAISSAINDITQRLDKLEAAVQIDRLIN 1021 Zaria bat cor...
YP_009072440  962 NQKQIANKFNQAMMSVQTGFKATSsALEKLQKVVNDNAQALNNLVAQLTNNFGAISSAINDITQRLDKLEADAQIDRLIN 1041 Bat Hp-betaco...
AVP25406      909 NQKLIASSFNKALTSIQEGFTATNqALAKMQAVINQHASQLQTLVIQLGNSFGAISSSLNEIFSRLEGLAADAEVDRLIN 988  Rousettus bat...
5I08_A        987 NQKLIANAFNKALLSIQNGFTATNsALAKIQSVVNANAQALNSLLQQLFNKFGAISSSLQEILSRLDNLEAQVQIDRLIN 1066 Human coronav...
QJX68370      919 NQKLIANQFNSAIGKIQDSLSSTAsALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLIT 998  Severe acute ...
QIQ54048      915 NQKLIANQFNSAIGKIQDSLSSTAsALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLIT 994  Pangolin coro...
Feature 1                                                                                         
6VSB_A        999 GRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGyHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTA 1078 Severe acute ...
5X59_A       1056 GRLTTLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGtHIVSFVVNAPNGLYFMHVGYYPSNHIEVVSA 1135 Middle East r...
ADY17911     1022 GRLQVLQTFVTQQLIMASEIRASAQLAKQKMSECVLSQSKRQDFCGRGlHLMSFPQSAPQGMVFLHVLYRPTSYINVTST 1101 Zaria bat cor...
YP_009072440 1042 GRLQVLQTFVTQQLIRASEIRASAKLAAQKMSECVQGQSQRLDFCGRGmHLMSFPQAAPYGMVFLHVLYKPTDYINVTTV 1121 Bat Hp-betaco...
AVP25406      989 GRMVVLNTYVTQLLIQASELRAQNQLAVQKISECVKAQSSRNDFCGNGtHVLSIPQLAPNGVLFIHYTYRPTEYAYVQTS 1068 Rousettus bat...
5I08_A       1067 GRLTALNAYVSQQLSDITLIKAGASRAIEKVNECVKSQSPRINFCGNGnHILSLVQNAPYGLLFIHFSYKPTSFKTVLVS 1146 Human coronav...
QJX68370      999 GRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGyHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTA 1078 Severe acute ...
QIQ54048      995 GRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGyHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTA 1074 Pangolin coro...
Feature 1                                                                                         
6VSB_A       1079 PAICHDGKahfp---regvFVSNg-----tHWFVTQRNFYEPQIITTDNtfVSGNcdvvIGIVNNtv--ydPLQPELDs- 1147 Severe acute ...
5X59_A       1136 YGLCDAANptnciapvngyFIKTnntrivdEWSYTGSSFYAPEPITSLNtkYVAPq---VTYQNIstnlppPLLGNSTgi 1212 Middle East r...
ADY17911     1102 PAICSENKayfp---tdgvFVLHd-----nQWMITKRNFYDPVNISLSNvrYAGScdviTTYANHti--fePDNSTLQd- 1170 Zaria bat cor...
YP_009072440 1122 PAICSNDVayfp---vdgvFVYYn-----nSLMFTKRNYFEPEIITIDNirSAGScnvdVTYVNHti--ynPEMPELEd- 1190 Bat Hp-betaco...
AVP25406     1069 AGLCYNKTgyap---kggmFVLPnn---tnLWHFTAMNFYNPVNITVFNtqILTScslnFTAVNYtv--lePLQYSDFd- 1139 Rousettus bat...
5I08_A       1147 PGLCLSGDrgiap--kqgyFIKQn-----dSWMFTGSSYYYPEPISDKNvvFMNScsvnFTKAPFiy--lnNSIPNLSd- 1216 Human coronav...
QJX68370     1079 PAICHDGKahfp---regvFVSNg-----tHWFVTQRNFYEPQIITTDNtfVSGNcdvvIGIVNNtv--ydPLQPELDs- 1147 Severe acute ...
QIQ54048     1075 PAICHEGKahfp---regvFVSNg-----tHWFITQRNFYEPQIITTDNtfVSGScdvvIGIVNNtv--ydPLQPELDs- 1143 Pangolin coro...
Feature 1                                                                       
6VSB_A       1148 -FKEELdky-----fknHTSPDVDLgdisGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL 1203 Severe acute respiratory syndro...
5X59_A       1213 dFQDELdef-----fknVSTSIPNFgsltQINTTLLDLTYEMLSLQQVVKALNESYIDLKEL 1269 Middle East respiratory syndrom...
ADY17911     1171 -FMHELeeirknlsmsaPNSPNFTLpglsDINASFVDLSKEMETLQNVVRQLNKSVIDLKEL 1231 Zaria bat coronavirus
YP_009072440 1191 -FKQELeeirknfstglPNRPNFTLpgleGINASMVDLSEEVKILNDVVKELNASLINLQEL 1251 Bat Hp-betacoronavirus/Zhejiang...
AVP25406     1140 -FDAQFekf-----yknISSHFNNTfdpnQFNFSTVDVKEQLDTLTNVVKQLNESVIDLKQM 1195 Rousettus bat coronavirus HKU9
5I08_A       1217 -FEAELslw-----fknHTSIAPNLtfnsHINATFLDLYYEMNVIQESIKSLNGSGYIPEAP 1272 Human coronavirus HKU1 (isolate...
QJX68370     1148 -FKEELdky-----fknHTSPDVDLgdisGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL 1203 Severe acute respiratory syndro...
QIQ54048     1144 -FKEELdky-----fknHTSPDVDLgdisGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL 1199 Pangolin coronavirus

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