ID SPIKE_SARS2 Reviewed; 1273 AA. AC P0DTC2; DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot. DT 22-APR-2020, sequence version 1. DT 22-APR-2020, entry version 1. DE RecName: Full=Spike glycoprotein {ECO:0000255|HAMAP-Rule:MF_04099}; DE Short=S glycoprotein {ECO:0000255|HAMAP-Rule:MF_04099}; DE AltName: Full=E2 {ECO:0000255|HAMAP-Rule:MF_04099}; DE AltName: Full=Peplomer protein {ECO:0000255|HAMAP-Rule:MF_04099}; DE Contains: DE RecName: Full=Spike protein S1 {ECO:0000255|HAMAP-Rule:MF_04099}; DE Contains: DE RecName: Full=Spike protein S2 {ECO:0000255|HAMAP-Rule:MF_04099}; DE Contains: DE RecName: Full=Spike protein S2' {ECO:0000255|HAMAP-Rule:MF_04099}; DE Flags: Precursor; GN Name=S {ECO:0000255|HAMAP-Rule:MF_04099}; ORFNames=2; OS Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2). OC Viruses; Riboviria; Nidovirales; Cornidovirineae; Coronaviridae; OC Orthocoronavirinae; Betacoronavirus; unclassified Betacoronavirus. OX NCBI_TaxID=2697049; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=32015508; DOI=10.1038/s41586-020-2008-3; RA Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., RA Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y., RA Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z.; RT "A new coronavirus associated with human respiratory disease in China."; RL Nature 579:265-269(2020). RN [2] RP FUNCTION (SPIKE PROTEIN S1). RX PubMed=32142651; DOI=10.1016/j.cell.2020.02.052; RA Hoffmann M., Kleine-Weber H., Schroeder S., Krueger N., Herrler T., RA Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., RA Mueller M.A., Drosten C., Poehlmann S.; RT "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a RT clinically proven protease inhibitor."; RL Cell 181:1-10(2020). RN [3] {ECO:0000244|PDB:6M17} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS), FUNCTION (SPIKE PROTEIN RP S1), DOMAIN, AND INTERACTION WITH HUMAN ACE2 (SPIKE PROTEIN S1). RX PubMed=32132184; DOI=10.1126/science.abb2762; RA Yan R., Zhang Y., Li Y., Xia L., Guo Y., Zhou Q.; RT "Structural basis for the recognition of the SARS-CoV-2 by full-length RT human ACE2."; RL Science 0:0-0(2020). RN [4] {ECO:0000244|PDB:6VSB} RP STRUCTURE BY ELECTRON MICROSCOPY (3.46 ANGSTROMS), FUNCTION (SPIKE PROTEIN RP S1), INTERACTION WITH HUMAN ACE2 (SPIKE PROTEIN S1), SUBUNIT, AND RP GLYCOSYLATION. RX PubMed=32075877; DOI=10.1126/science.abb2507; RA Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L., Abiona O., RA Graham B.S., McLellan J.S.; RT "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation."; RL Science 367:1260-1263(2020). RN [5] {ECO:0000244|PDB:6VXX, ECO:0000244|PDB:6VYB} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS), FUNCTION (SPIKE PROTEIN RP S1), SUBUNIT (SPIKE PROTEIN S1), INTERACTION WITH HUMAN ACE2 (SPIKE PROTEIN RP S1), MUTAGENESIS OF 679-GLN--ALA-684, GLYCOSYLATION AT ASN-61; ASN-122; RP ASN-61; ASN-165; ASN-234; ASN-282; ASN-331; ASN-343; ASN-603; ASN-616; RP ASN-657; ASN-709; ASN-717; ASN-801; ASN-1074; ASN-1098 AND ASN-1134, AND RP DISULFIDE BOND. RX PubMed=32155444; DOI=10.1016/j.cell.2020.02.058; RA Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D.; RT "Structure, function, and antigenicity of the SARS-CoV-2 spike RT glycoprotein."; RL Cell 180:1-12(2020). CC -!- FUNCTION: [Spike protein S1]: attaches the virion to the cell membrane CC by interacting with host receptor, initiating the infection (By CC similarity). Binding to human ACE2 receptor and internalization of the CC virus into the endosomes of the host cell induces conformational CC changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, CC PubMed:32155444). Uses also human TMPRSS2 for priming in human lung CC cells which is an essential step for viral entry (PubMed:32142651). CC Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and CC activate membranes fusion within endosomes. {ECO:0000255|HAMAP- CC Rule:MF_04099, ECO:0000269|PubMed:32075877, CC ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32155444}. CC -!- FUNCTION: [Spike protein S2]: mediates fusion of the virion and CC cellular membranes by acting as a class I viral fusion protein. Under CC the current model, the protein has at least three conformational CC states: pre-fusion native state, pre-hairpin intermediate state, and CC post-fusion hairpin state. During viral and target cell membrane CC fusion, the coiled coil regions (heptad repeats) assume a trimer-of- CC hairpins structure, positioning the fusion peptide in close proximity CC to the C-terminal region of the ectodomain. The formation of this CC structure appears to drive apposition and subsequent fusion of viral CC and target cell membranes. {ECO:0000255|HAMAP-Rule:MF_04099}. CC -!- FUNCTION: [Spike protein S2']: Acts as a viral fusion peptide which is CC unmasked following S2 cleavage occurring upon virus endocytosis. CC {ECO:0000255|HAMAP-Rule:MF_04099}. CC -!- SUBUNIT: [Spike glycoprotein]: Homotrimer; each monomer consists of a CC S1 and a S2 subunit (PubMed:32155444, PubMed:32075877). The resulting CC peplomers protrude from the virus surface as spikes (By similarity). CC Interacts with the accessory proteins 3a and 7a. {ECO:0000255|HAMAP- CC Rule:MF_04099, ECO:0000269|PubMed:32075877, CC ECO:0000269|PubMed:32155444}. CC -!- SUBUNIT: [Spike protein S1]: Binds to human ACE2. CC {ECO:0000269|PubMed:32075877, ECO:0000269|PubMed:32132184, CC ECO:0000269|PubMed:32155444, ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP- CC Rule:MF_04099}; Single-pass type I membrane protein {ECO:0000255|HAMAP- CC Rule:MF_04099}. Host endoplasmic reticulum-Golgi intermediate CC compartment membrane {ECO:0000255|HAMAP-Rule:MF_04099}; Single-pass CC type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04099}. Host cell CC membrane {ECO:0000255|HAMAP-Rule:MF_04099}; Single-pass type I membrane CC protein {ECO:0000255|HAMAP-Rule:MF_04099}. Note=Accumulates in the CC endoplasmic reticulum-Golgi intermediate compartment, where it CC participates in virus particle assembly. Colocalizes with S in the host CC endoplasmic reticulum-Golgi intermediate compartment. Some S oligomers CC are transported to the host plasma membrane, where they may mediate CC cell-cell fusion. {ECO:0000255|HAMAP-Rule:MF_04099}. CC -!- DOMAIN: The KxHxx motif seems to function as an ER retrieval and binds CC COPI in vitro. {ECO:0000250|UniProtKB:P59594}. CC -!- PTM: The cytoplasmic Cys-rich domain is palmitoylated. Spike CC glycoprotein is digested within host endosomes. {ECO:0000255|HAMAP- CC Rule:MF_04099}. CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The CC precurssor is processed into S1 and S2 by host cell furin or another CC cellular protease to yield the mature S1 and S2 proteins CC (PubMed:32155444). Additionally, a second cleavage leads to the release CC of a fusion peptide after viral attachment to host cell receptor (By CC similarity). The presence of a furin polybasic cleavage site sets SARS- CC CoV-2 S apart from SARS-CoV S that possesses a monobasic S1/S2 cleavage CC site processed upon entry of target cells (PubMed:32155444). CC {ECO:0000255|HAMAP-Rule:MF_04099, ECO:0000269|PubMed:32155444}. CC -!- PTM: Highly decorated by heterogeneous N-linked glycans protruding from CC the trimer surface. {ECO:0000269|PubMed:32075877, CC ECO:0000269|PubMed:32155444}. CC -!- SIMILARITY: Belongs to the betacoronaviruses spike protein family. CC {ECO:0000255|HAMAP-Rule:MF_04099}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; MN908947; QHD43416.1; -; Genomic_RNA. DR PDB; 6M17; EM; 2.90 A; E/F=319-541. DR PDB; 6VSB; EM; 3.46 A; A/B/C=1-1209. DR PDB; 6VXX; EM; 2.80 A; A/B/C=14-1211. DR PDB; 6VYB; EM; 3.20 A; A/B/C=14-1211. DR PDBsum; 6M17; -. DR PDBsum; 6VSB; -. DR PDBsum; 6VXX; -. DR PDBsum; 6VYB; -. DR Proteomes; UP000464024; Genome. DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro. DR GO; GO:0019031; C:viral envelope; IEA:InterPro. DR GO; GO:0061025; P:membrane fusion; IEA:InterPro. DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IEA:InterPro. DR Gene3D; 1.20.5.300; -; 1. DR Gene3D; 1.20.5.790; -; 1. DR Gene3D; 3.30.70.1840; -; 1. DR HAMAP; MF_04099; BETA_CORONA_SPIKE; 1. DR InterPro; IPR002552; Corona_S2. DR InterPro; IPR027400; S_HR2. DR InterPro; IPR018548; Spike_rcpt-bd. DR InterPro; IPR036326; Spike_rcpt-bd_sf. DR Pfam; PF01601; Corona_S2; 1. DR Pfam; PF09408; Spike_rec_bind; 1. DR SUPFAM; SSF111474; SSF111474; 1. DR SUPFAM; SSF143587; SSF143587; 1. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Disulfide bond; KW Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; KW Host cell membrane; Host membrane; Host-virus interaction; Lipoprotein; KW Membrane; Palmitate; Reference proteome; Signal; Transmembrane; KW Transmembrane helix; Viral attachment to host cell; Viral envelope protein; KW Viral penetration into host cytoplasm; Virion; Virulence; KW Virus entry into host cell. FT SIGNAL 1..12 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT CHAIN 13..1273 FT /note="Spike glycoprotein" FT /id="PRO_0000449646" FT CHAIN 13..685 FT /note="Spike protein S1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT /id="PRO_0000449647" FT CHAIN 686..1273 FT /note="Spike protein S2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT /id="PRO_0000449648" FT CHAIN 816..1273 FT /note="Spike protein S2'" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT /id="PRO_0000449649" FT TOPO_DOM 13..1213 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT TRANSMEM 1214..1234 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT TOPO_DOM 1235..1273 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT REGION 319..541 FT /note="Receptor-binding domain (RBD)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32132184" FT REGION 437..508 FT /note="Receptor-binding motif; binding to human ACE2" FT /evidence="ECO:0000250|UniProtKB:P59594" FT REGION 788..806 FT /note="Fusion peptide" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT REGION 920..970 FT /note="Heptad repeat 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT REGION 1163..1202 FT /note="Heptad repeat 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT COILED 949..993 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT COILED 1176..1203 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT MOTIF 1269..1273 FT /note="KxHxx" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT SITE 685..686 FT /note="Cleavage" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT SITE 815..816 FT /note="Cleavage" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT CARBOHYD 17 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT CARBOHYD 61 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 74 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT CARBOHYD 122 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 149 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT CARBOHYD 165 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 234 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 282 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 331 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 343 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 603 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 616 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 657 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 709 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 717 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 801 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 1074 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 1098 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 1134 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099, FT ECO:0000269|PubMed:32155444" FT CARBOHYD 1158 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT CARBOHYD 1173 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT CARBOHYD 1194 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099" FT DISULFID 131..166 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 291..301 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 336..361 FT /evidence="ECO:0000244|PDB:6VXX, ECO:0000255|HAMAP- FT Rule:MF_04099, ECO:0000269|PubMed:32155444" FT DISULFID 379..432 FT /evidence="ECO:0000244|PDB:6VXX, ECO:0000255|HAMAP- FT Rule:MF_04099, ECO:0000269|PubMed:32155444" FT DISULFID 391..525 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 538..590 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 617..649 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 662..671 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 738..760 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 743..749 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 1032..1043 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT DISULFID 1082..1126 FT /evidence="ECO:0000244|PDB:6VXX, FT ECO:0000269|PubMed:32155444" FT MUTAGEN 679..684 FT /note="NSPRRA->IL: About 50% stronger entry efficiency in FT Vero E6 cells while 30% weaker entry efficiency in hACE2- FT expressing BHK cells." FT /evidence="ECO:0000269|PubMed:32155444" SQ SEQUENCE 1273 AA; 141178 MW; B17BE6D9F1C4EA34 CRC64; MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMESEFRVY SSANNCTFEY VSQPFLMDLE GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NLVRDLPQGF SALEPLVDLP IGINITRFQT LLALHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YLYRLFRKSN LKPFERDIST EIYQAGSTPC NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILDITPC SFGGVSVITP GTNTSNQVAV LYQDVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEHVNNSY ECDIPIGAGI CASYQTQTNS PRRARSVASQ SIIAYTMSLG AENSVAYSNN SIAIPTNFTI SVTTEILPVS MTKTSVDCTM YICGDSTECS NLLLQYGSFC TQLNRALTGI AVEQDKNTQE VFAQVKQIYK TPPIKDFGGF NFSQILPDPS KPSKRSFIED LLFNKVTLAD AGFIKQYGDC LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFGA GAALQIPFAM QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TASALGKLQD VVNQNAQALN TLVKQLSSNF GAISSVLNDI LSRLDKVEAE VQIDRLITGR LQSLQTYVTQ QLIRAAEIRA SANLAATKMS ECVLGQSKRV DFCGKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDVVI GIVNNTVYDP LQPELDSFKE ELDKYFKNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL QELGKYEQYI KWPWYIWLGF IAGLIAIVMV TIMLCCMTSC CSCLKGCCSC GSCCKFDEDD SEPVLKGVKL HYT //