ID   SPIKE_WCPV              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;
DE            Short=S glycoprotein;
DE   AltName: Full=E2;
DE   AltName: Full=Peplomer protein;
DE   Contains:
DE     RecName: Full=Spike protein S1;
DE   Contains:
DE     RecName: Full=Spike protein S2;
DE   Contains:
DE     RecName: Full=Spike protein S2';
DE   Flags: Precursor;
GN   Name=S; ORFNames=2;
OS   Wuhan seafood market pneumonia virus.
OC   Viruses; Riboviria; Nidovirales; Cornidovirineae; Coronaviridae;
OC   Orthocoronavirinae; Betacoronavirus; unclassified Betacoronavirus.
OX   NCBI_TaxID=2697049;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Hu Y., Song Z.-G., 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 novel coronavirus associated with a respiratory disease in Wuhan of
RT   Hubei province, China.";
RL   Submitted (JAN-2020) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: [Spike protein S1]: attaches the virion to the cell membrane
CC       by interacting with host receptor, initiating the infection. Binding to
CC       human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the
CC       virus into the endosomes of the host cell induces conformational
CC       changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask
CC       the fusion peptide of S2 and activate membranes fusion within
CC       endosomes. {ECO:0000250|UniProtKB:P59594}.
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:0000250|UniProtKB:P59594}.
CC   -!- FUNCTION: [Spike protein S2']: Acts as a viral fusion peptide which is
CC       unmasked following S2 cleavage occurring upon virus endocytosis.
CC       {ECO:0000250|UniProtKB:P59594}.
CC   -!- SUBUNIT: [Spike glycoprotein]: Homotrimer; each monomer consists of a
CC       S1 and a S2 subunit. The resulting peplomers protrude from the virus
CC       surface as spikes. Interacts with the accessory proteins 3a and 7a.
CC       {ECO:0000250|UniProtKB:P59594}.
CC   -!- SUBUNIT: [Spike protein S1]: Binds to human ACE2. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane
CC       protein. Host endoplasmic reticulum-Golgi intermediate compartment
CC       membrane; Single-pass type I membrane protein. Host cell membrane;
CC       Single-pass type I membrane protein. 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:0000250|UniProtKB:P59594}.
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.
CC       {ECO:0000250|UniProtKB:P59594}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The
CC       precursor is processed into S1 and S2 by host cell furin or another
CC       cellular protease to yield the mature S1 and S2 proteins. Additionally,
CC       a second cleavage leads to the release of a fusion peptide after viral
CC       attachment to host cell receptor. {ECO:0000250|UniProtKB:P59594}.
CC   -!- MISCELLANEOUS: nCoV is the prototype of the virus isolated during the
CC       severe coronavirus outbreak in originated in Wuhan in 2020.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the betacoronaviruses spike protein family.
CC       {ECO:0000305}.
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DR   EMBL; MN908947; QHD43416.1; -; Genomic_RNA.
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   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   3: Inferred from homology;
KW   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; Signal; Transmembrane; Transmembrane helix;
KW   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..13
FT                   /evidence="ECO:0000255"
FT   CHAIN           14..1273
FT                   /note="Spike glycoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT                   /id="PRO_0000449646"
FT   CHAIN           14..685
FT                   /note="Spike protein S1"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT                   /id="PRO_0000449647"
FT   CHAIN           686..1273
FT                   /note="Spike protein S2"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT                   /id="PRO_0000449648"
FT   CHAIN           816..1273
FT                   /note="Spike protein S2'"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT                   /id="PRO_0000449649"
FT   TRANSMEM        1214..1234
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          319..541
FT                   /note="Receptor-binding domain"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
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:0000250|UniProtKB:P59594"
FT   REGION          920..970
FT                   /note="Heptad repeat 1"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT   REGION          1163..1202
FT                   /note="Heptad repeat 2"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT   COILED          1176..1203
FT                   /evidence="ECO:0000255"
FT   MOTIF           1269..1273
FT                   /note="KxHxx"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT   SITE            685..686
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT   SITE            815..816
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT   DISULFID        336..361
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT   DISULFID        379..432
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
FT   DISULFID        480..488
FT                   /evidence="ECO:0000250|UniProtKB:P59594"
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
//