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   12-AUG-2020, entry version 3.
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; Sarbecovirus.
OX   NCBI_TaxID=2697049;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
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), AND CLEAVAGE BETWEEN S1 AND S2 BY HOST
RP   TMPRSS2.
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]
RP   CLEAVAGE BETWEEN S1 AND S2 BY HOST FURIN, FUNCTION, AND MUTAGENESIS OF
RP   681-PRO--ALA-684.
RX   PubMed=32362314; DOI=10.1016/j.molcel.2020.04.022;
RA   Hoffmann M., Kleine-Weber H., Poehlmann S.;
RT   "A multibasic cleavage site in the Spike protein of SARS-CoV-2 is essential
RT   for infection of human lung cells.";
RL   Mol. Cell 0:0-0(2020).
RN   [4]
RP   GLYCOSYLATION AT ASN-17; ASN-61; ASN-74; ASN-122; ASN-149; ASN-165;
RP   ASN-234; ASN-282; ASN-331; ASN-343; ASN-603; ASN-616; ASN-657; ASN-709;
RP   ASN-717; ASN-801; ASN-1074; ASN-1098; ASN-1134; ASN-1158; ASN-1173 AND
RP   ASN-1194, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=32366695; DOI=10.1126/science.abb9983;
RA   Watanabe Y., Allen J.D., Wrapp D., McLellan J.S., Crispin M.;
RT   "Site-specific glycan analysis of the SARS-CoV-2 spike.";
RL   Science 0:0-0(2020).
RN   [5]
RP   GLYCOSYLATION AT ASN-61; ASN-74; ASN-122; ASN-149; ASN-165; ASN-234;
RP   ASN-282; THR-323; SER-325; ASN-331; ASN-343; ASN-616; ASN-657; ASN-709;
RP   ASN-717; ASN-801; ASN-1074; ASN-1098 AND ASN-1194, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=32363391; DOI=10.1093/glycob/cwaa042;
RA   Shajahan A., Supekar N.T., Gleinich A.S., Azadi P.;
RT   "Deducing the N- and O- glycosylation profile of the spike protein of novel
RT   coronavirus SARS-CoV-2.";
RL   Glycobiology 0:0-0(2020).
RN   [6] {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   [7] {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   [8] {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).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF SPIKE PROTEIN S1 AND IN COMPLEX
RP   WITH HOST ACE2.
RX   PubMed=32225176; DOI=10.1038/s41586-020-2180-5;
RA   Lan J., Ge J., Yu J., Shan S., Zhou H., Fan S., Zhang Q., Shi X., Wang Q.,
RA   Zhang L., Wang X.;
RT   "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the
RT   ACE2 receptor.";
RL   Nature 0:0-0(2020).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF SPIKE PROTEIN S1 AND IN COMPLEX
RP   WITH HOST ACE2, INTERACTION WITH HOST ACE2, AND MUTAGENESIS OF GLN-493 AND
RP   ASN-501.
RX   PubMed=32225175; DOI=10.1038/s41586-020-2179-y;
RA   Shang J., Ye G., Shi K., Wan Y., Luo C., Aihara H., Geng Q., Auerbach A.,
RA   Li F.;
RT   "Structural basis of receptor recognition by SARS-CoV-2.";
RL   Nature 0:0-0(2020).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (3.08 ANGSTROMS) OF SPIKE PROTEIN S1 AND IN COMPLEX
RP   WITH HUMAN ANTIBODY CR3022, AND DISULFIDE BOND.
RX   PubMed=32245784; DOI=10.1126/science.abb7269;
RA   Yuan M., Wu N.C., Zhu X., Lee C.D., So R.T.Y., Lv H., Mok C.K.P.,
RA   Wilson I.A.;
RT   "A highly conserved cryptic epitope in the receptor-binding domains of
RT   SARS-CoV-2 and SARS-CoV.";
RL   Science 0:0-0(2020).
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 receptor and internalization of the virus into the endosomes
CC       of the host cell induces conformational changes in the Spike
CC       glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses
CC       also human TMPRSS2 for priming in human lung cells which is an
CC       essential step for viral entry (PubMed:32142651). Can be alternatively
CC       processed by host furin (PubMed:32362314). Proteolysis by cathepsin
CC       CTSL may unmask the fusion peptide of S2 and activate membranes fusion
CC       within endosomes. {ECO:0000255|HAMAP-Rule:MF_04099,
CC       ECO:0000269|PubMed:32075877, ECO:0000269|PubMed:32142651,
CC       ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32362314}.
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   -!- FUNCTION: [Spike glycoprotein]: May down-regulate host tetherin (BST2)
CC       by lysosomal degradation, thereby counteracting its antiviral activity.
CC       {ECO:0000250|UniProtKB:P59594}.
CC   -!- SUBUNIT: [Spike glycoprotein]: Homotrimer; each monomer consists of a
CC       S1 and a S2 subunit (PubMed:32075877, PubMed:32155444,
CC       PubMed:32245784). The resulting peplomers protrude from the virus
CC       surface as spikes (By similarity). Interacts with ORF3a protein and
CC       ORF7a protein. {ECO:0000255|HAMAP-Rule:MF_04099,
CC       ECO:0000269|PubMed:32075877, ECO:0000269|PubMed:32155444,
CC       ECO:0000269|PubMed:32245784}.
CC   -!- SUBUNIT: [Spike protein S1]: Binds to host ACE2.
CC       {ECO:0000269|PubMed:32075877, ECO:0000269|PubMed:32132184,
CC       ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32225175,
CC       ECO:0000269|PubMed:32225176}.
CC   -!- INTERACTION:
CC       P0DTC2; P0DTC2: S; NbExp=4; IntAct=EBI-25474821, EBI-25474821;
CC       P0DTC2; Q9BYF1: ACE2; Xeno; NbExp=23; IntAct=EBI-25474821, EBI-7730807;
CC       P0DTC2; P35613: BSG; Xeno; NbExp=5; IntAct=EBI-25474821, EBI-750709;
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   -!- DOMAIN: Fusion peptide 1 (FP1) and fusion peptide 2 (FP2) function
CC       cooperatively and have a membrane-ordering effect on lipid headgroups
CC       and shallow hydrophobic regions of target bilayers. They are considered
CC       as two domains of an extended, bipartite FP. The membrane-ordering
CC       activity is calcium-dependent and also dependent on correct folding,
CC       which is maintained by an internal disulfide bond in FP2.
CC       {ECO:0000255|HAMAP-Rule:MF_04099}.
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       precursor 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       PubMed:32362314). {ECO:0000255|HAMAP-Rule:MF_04099,
CC       ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32362314}.
CC   -!- PTM: Highly decorated by heterogeneous N-linked glycans protruding from
CC       the trimer surface (PubMed:32075877, PubMed:32155444). Highly
CC       glycosylated by host both on S1 and S2 subunits, occluding many regions
CC       across the surface of the protein. This may shield viral epitopes from
CC       acquired immune response (PubMed:32366695, PubMed:32363391).
CC       {ECO:0000269|PubMed:32075877, ECO:0000269|PubMed:32155444,
CC       ECO:0000269|PubMed:32363391, ECO:0000269|PubMed:32366695}.
CC   -!- SIMILARITY: Belongs to the betacoronaviruses spike protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04099}.
CC   -!- CAUTION: Asn-17, Asn-603, Asn-1134, Asn-1158, and Asn-1173 are non
CC       glycosylated when S1 or S2 are expressed individually in HEK293 cells.
CC       {ECO:0000269|PubMed:32363391}.
DR   EMBL; MN908947; QHD43416.1; -; Genomic_RNA.
DR   RefSeq; YP_009724390.1; NC_045512.2.
DR   PDB; 6LVN; X-ray; 2.47 A; A/B/C/D=1168-1203.
DR   PDB; 6LXT; X-ray; 2.90 A; A/B/C/D/E/F=910-988, A/B/C/D/E/F=1162-1206.
DR   PDB; 6LZG; X-ray; 2.50 A; B=319-527.
DR   PDB; 6M0J; X-ray; 2.45 A; E=319-541.
DR   PDB; 6M17; EM; 2.90 A; E/F=319-541.
DR   PDB; 6VSB; EM; 3.46 A; A/B/C=1-1208.
DR   PDB; 6VW1; X-ray; 2.68 A; E/F=455-518.
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   PDB; 6W41; X-ray; 3.08 A; C=319-541.
DR   PDB; 6YLA; X-ray; 2.42 A; A/E=330-532.
DR   PDB; 6YM0; X-ray; 4.36 A; E=330-532.
DR   PDB; 6YOR; EM; 3.30 A; A/E=330-532.
DR   PDB; 7BZ5; X-ray; 1.84 A; A=319-541.
DR   PDBsum; 6LVN; -.
DR   PDBsum; 6LXT; -.
DR   PDBsum; 6LZG; -.
DR   PDBsum; 6M0J; -.
DR   PDBsum; 6M17; -.
DR   PDBsum; 6VSB; -.
DR   PDBsum; 6VW1; -.
DR   PDBsum; 6VXX; -.
DR   PDBsum; 6VYB; -.
DR   PDBsum; 6W41; -.
DR   PDBsum; 6YLA; -.
DR   PDBsum; 6YM0; -.
DR   PDBsum; 6YOR; -.
DR   PDBsum; 7BZ5; -.
DR   SMR; P0DTC2; -.
DR   BioGRID; 4383848; 7.
DR   ComplexPortal; CPX-5682; SARS-CoV-2 Spike protein complex.
DR   IntAct; P0DTC2; 20.
DR   GlyConnect; 2838; 256 N-Linked glycans (24 sites), 5 O-Linked glycans (3 sites).
DR   GlyConnect; 2839; 38 N-Linked glycans (20 sites).
DR   GlyConnect; 2840; 109 N-Linked glycans (22 sites).
DR   GlyGen; P0DTC2; 24 sites, 172 N-linked glycans (22 sites), 4 O-linked glycans (2 sites).
DR   ABCD; P0DTC2; 65 sequenced antibodies.
DR   GeneID; 43740568; -.
DR   SIGNOR; P0DTC2; -.
DR   Proteomes; UP000464024; Genome.
DR   GO; GO:0044173; C:host cell endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0046789; F:host cell surface receptor binding; IDA:UniProtKB.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR   GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IEA:InterPro.
DR   GO; GO:0046718; P:viral entry into host cell; IDA:UniProtKB.
DR   Gene3D; 1.20.5.790; -; 1.
DR   HAMAP; MF_04099; BETA_CORONA_SPIKE; 1.
DR   InterPro; IPR043473; S2_sf_CoV.
DR   InterPro; IPR027400; S_HR2_CoV.
DR   InterPro; IPR018548; Spike_rcpt-bd_bCoV.
DR   InterPro; IPR036326; Spike_rcpt-bd_sf_CoV.
DR   InterPro; IPR002552; Spike_S2_CoV.
DR   Pfam; PF01601; Corona_S2; 1.
DR   Pfam; PF09408; Spike_rec_bind; 1.
DR   SUPFAM; SSF111474; SSF111474; 2.
DR   SUPFAM; SSF143587; SSF143587; 1.
DR   PROSITE; PS51921; BCOV_S1_CTD; 1.
DR   PROSITE; PS51922; BCOV_S1_NTD; 1.
DR   PROSITE; PS51923; COV_S2_HR1; 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;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host tetherin by virus; Lipoprotein; Membrane; Palmitate;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW   Viral attachment to host cell; Viral envelope protein; Viral immunoevasion;
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   DOMAIN          13..303
FT                   /note="BetaCoV S1-NTD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01270"
FT   DOMAIN          334..527
FT                   /note="BetaCoV S1-CTD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01269,
FT                   ECO:0000269|PubMed:32132184"
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          816..837
FT                   /note="Fusion peptide 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT   REGION          835..855
FT                   /note="Fusion peptide 2"
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; by TMPRSS2 or furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32362314"
FT   SITE            815..816
FT                   /note="Cleavage; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT   CARBOHYD        17
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        61
FT                   /note="N-linked (GlcNAc...) (hybrid) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        74
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32363391, ECO:0000269|PubMed:32366695"
FT   CARBOHYD        122
FT                   /note="N-linked (GlcNAc...) (hybrid) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        149
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32363391, ECO:0000269|PubMed:32366695"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        282
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        323
FT                   /note="O-linked (GalNAc) threonine; by host"
FT                   /evidence="ECO:0000269|PubMed:32363391"
FT   CARBOHYD        325
FT                   /note="O-linked (HexNAc...) serine; by host"
FT                   /evidence="ECO:0000269|PubMed:32363391"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        603
FT                   /note="N-linked (GlcNAc...) (hybrid) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32366695"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        657
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        709
FT                   /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT                   host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        717
FT                   /note="N-linked (GlcNAc...) (hybrid) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        801
FT                   /note="N-linked (GlcNAc...) (hybrid) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        1074
FT                   /note="N-linked (GlcNAc...) (hybrid) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        1098
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32363391,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        1134
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32366695"
FT   CARBOHYD        1158
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        1173
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32366695"
FT   CARBOHYD        1194
FT                   /note="N-linked (GlcNAc...) (complex) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099,
FT                   ECO:0000269|PubMed:32363391, ECO:0000269|PubMed:32366695"
FT   DISULFID        15..136
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01270"
FT   DISULFID        131..166
FT                   /evidence="ECO:0000244|PDB:6VXX, ECO:0000255|PROSITE-
FT                   ProRule:PRU01270, ECO:0000269|PubMed:32155444"
FT   DISULFID        291..301
FT                   /evidence="ECO:0000244|PDB:6VXX, ECO:0000255|PROSITE-
FT                   ProRule:PRU01270, ECO:0000269|PubMed:32155444"
FT   DISULFID        336..361
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01269,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32245784"
FT   DISULFID        379..432
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01269,
FT                   ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32245784"
FT   DISULFID        391..525
FT                   /evidence="ECO:0000244|PDB:6VXX, ECO:0000255|PROSITE-
FT                   ProRule:PRU01269, ECO:0000269|PubMed:32155444,
FT                   ECO:0000269|PubMed:32225175, ECO:0000269|PubMed:32225176,
FT                   ECO:0000269|PubMed:32245784"
FT   DISULFID        480..488
FT                   /evidence="ECO:0000269|PubMed:32245784"
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        840..851
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
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         493
FT                   /note="Q->N: Reduced host ACE2-binding affinity in vitro."
FT                   /evidence="ECO:0000269|PubMed:32225175"
FT   MUTAGEN         493
FT                   /note="Q->Y: Reduced host ACE2-binding affinity in vitro."
FT                   /evidence="ECO:0000269|PubMed:32225175"
FT   MUTAGEN         501
FT                   /note="N->T: Reduced host ACE2-binding affinity in vitro."
FT                   /evidence="ECO:0000269|PubMed:32225175"
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"
FT   MUTAGEN         681..684
FT                   /note="PRRA->RRRK: Optimized cleavage by host furin."
FT                   /evidence="ECO:0000269|PubMed:32362314"
FT   MUTAGEN         682..684
FT                   /note="Missing: Complete loss of cleavage by host furin."
FT                   /evidence="ECO:0000269|PubMed:32362314"
FT   STRAND          28..30
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          39..43
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          46..55
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          61..65
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          83..85
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          90..98
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          101..109
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          111..114
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          117..122
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          125..129
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          169..171
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          188..197
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          200..209
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          213..215
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          223..229
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          237..244
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          265..269
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          271..279
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          285..290
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           295..302
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          310..319
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          324..328
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           339..342
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   HELIX           350..352
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          354..358
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          360..362
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   HELIX           365..369
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          375..382
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   HELIX           384..387
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          388..390
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          392..403
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   HELIX           404..409
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          411..413
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   HELIX           417..421
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          431..437
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   HELIX           439..442
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   TURN            445..447
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          452..454
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          476..478
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          491..494
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   HELIX           503..505
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          506..516
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          518..520
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          536..543
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          546..554
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          565..567
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          573..577
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          579..581
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          584..588
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          592..599
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   TURN            602..604
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          609..613
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   TURN            617..619
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          642..645
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          648..652
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          663..667
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          670..675
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          691..696
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          700..702
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          711..728
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          733..736
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           738..742
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           747..753
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           754..759
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           761..782
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          786..788
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   TURN            803..805
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          811..813
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           817..823
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          856..861
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           867..884
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           887..890
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           898..907
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   TURN            908..910
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           914..918
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           920..940
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           942..945
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           946..964
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           965..967
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           977..981
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           986..1032
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   TURN            1040..1043
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          1044..1056
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          1059..1079
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          1081..1100
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          1102..1105
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   TURN            1117..1119
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   STRAND          1120..1125
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   TURN            1126..1128
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           1142..1146
FT                   /evidence="ECO:0000244|PDB:6VXX"
FT   HELIX           1170..1201
FT                   /evidence="ECO:0000244|PDB:6LVN"
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
//