P59594 (SPIKE_CVHSA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Spike glycoprotein
Short name=S glycoprotein

Alternative name(s):
E2
Peplomer protein

Cleaved into the following 2 chains:

1. Spike protein S1
2. Spike protein S2

Gene names

Name:	S
ORF Names:	2

Organism

Human SARS coronavirus (SARS-CoV) (Severe acute respiratory syndrome coronavirus)

Taxonomic identifier

227859 [NCBI]

Taxonomic lineage

Viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Coronaviridae › Coronavirinae › Betacoronavirus

Virus host

Homo sapiens (Human) [TaxID: 9606]
Paguma larvata (Masked palm civet) [TaxID: 9675]

Protein attributes

Sequence length	1255 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.
Subunit structure	Homotrimer. Binds to human and palm civet ACE2 and human CLEC4M/DC-SIGNR. Interacts with the accessory proteins 3a and 7a. Ref.22 Ref.23 Ref.26 Ref.27 Ref.32 Ref.33
Subcellular location	Virion membrane; Single-pass type I membrane protein. Host endoplasmic reticulum-Golgi intermediate compartment membrane; Single-pass type I membrane protein By similarity. Host cell membrane; Single-pass type I membrane protein. Note: Accumulates in the endoplasmic reticulum-Golgi intermediate compartment, where it participates in virus particle assembly By similarity. Some S oligomers are transported to the plasma membrane, where they may mediate cell-cell fusion. Ref.29
Domain	The KxHxx motif seems to function as an ER retrieval and binds COPI in vitro.
Post-translational modification	The cytoplasmic Cys-rich domain is palmitoylated. Spike glycoprotein is digested by cathepsin CTSL within endosomes. Ref.35
Miscellaneous	Tor2 is the prototype of the virus isolated during the severe SARS outbreak in 2002-2003. GD03 has been isolated from the second mild SARS outbreak in winter 2003-2004. SZ3 has been isolated from palm civet, the presumed animal reservoir. The spike proteins from those three isolates display a strong affinity for palm civet ACE2 receptor, whereas only the Tor2 spike protein efficiently binds human ACE2. This may explain the high pathogenicity of Tor2 virus, whose spike is highly adapted to the human host. Therefore, the lack of severity of disease during the 2003-2004 outbreak could be due to the incomplete adaptation of GD03 virus to bind human ACE2. Mutation Asn-479 and Thr-487 in palm civet coronavirus seems necessary and sufficient for the virus to acquire the ability to efficiently infect humans.
Sequence similarities	Belongs to the coronaviruses spike protein family.
Caution	Cleavage into S1 and S2 remains controversial, since biochemical evidence for this proteolytic cleavage is largely negative.

Ontologies

Keywords
Biological process	Fusion of virus membrane with host endosomal membrane Fusion of virus membrane with host membrane Host-virus interaction Initiation of viral infection Viral attachment to host cell Viral penetration into host cytoplasm Virulence
Cellular component	Host cell membrane Host membrane Membrane Viral envelope protein Virion
Domain	Coiled coil Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular membrane fusion Inferred from electronic annotation. Source: InterPro pathogenesis Non-traceable author statement. Source: UniProtKB transmission of virus Non-traceable author statement. Source: UniProtKB virion attachment, binding of host cell surface receptor Inferred from direct assay. Source: BHF-UCL
Cellular component	host cell endoplasmic reticulum-Golgi intermediate compartment membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Non-traceable author statement. Source: UniProtKB virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	host cell surface receptor binding Inferred from physical interaction. Source: BHF-UCL structural molecule activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 13

13

Potential

Chain

14 – 1255

1242

Spike glycoprotein

PRO_0000037208

Chain

14 – 667

654

Spike protein S1 Potential

PRO_0000037209

Chain

668 – 1255

588

Spike protein S2 Potential

PRO_0000037210

Regions

Topological domain

14 – 1195

1182

Extracellular Potential

Transmembrane

1196 – 1216

21

Helical; Potential

Topological domain

1217 – 1255

39

Cytoplasmic Potential

Region

306 – 527

222

Receptor-binding domain

Region

424 – 494

71

Receptor-binding motif; binding to human ACE2

Region

770 – 788

19

Fusion peptide Potential

Region

902 – 952

51

Heptad repeat 1

Region

1145 – 1184

40

Heptad repeat 2

Coiled coil

931 – 975

45

Potential

Coiled coil

1157 – 1185

29

Potential

Motif

1251 – 1255

5

KxHxx

Compositional bias

1217 – 1236

20

Cys-rich

Sites

Site

667 – 668

2

Cleavage Potential

Amino acid modifications

Glycosylation

29

1

N-linked (GlcNAc...); by host Potential

Glycosylation

65

1

N-linked (GlcNAc...); by host Potential

Glycosylation

73

1

N-linked (GlcNAc...); by host Potential

Glycosylation

109

1

N-linked (GlcNAc...); by host Potential

Glycosylation

118

1

N-linked (GlcNAc...); by host Potential

Glycosylation

119

1

N-linked (GlcNAc...); by host Potential

Glycosylation

158

1

N-linked (GlcNAc...); by host Potential

Glycosylation

227

1

N-linked (GlcNAc...); by host Potential

Glycosylation

269

1

N-linked (GlcNAc...); by host Potential

Glycosylation

318

1

N-linked (GlcNAc...); by host Potential

Glycosylation

330

1

N-linked (GlcNAc...); by host Potential

Glycosylation

357

1

N-linked (GlcNAc...); by host Potential

Glycosylation

589

1

N-linked (GlcNAc...); by host Potential

Glycosylation

602

1

N-linked (GlcNAc...); by host Potential

Glycosylation

691

1

N-linked (GlcNAc...); by host Potential

Glycosylation

699

1

N-linked (GlcNAc...); by host Potential

Glycosylation

783

1

N-linked (GlcNAc...); by host Potential

Glycosylation

1056

1

N-linked (GlcNAc...); by host Potential

Glycosylation

1080

1

N-linked (GlcNAc...); by host Potential

Glycosylation

1116

1

N-linked (GlcNAc...); by host Potential

Glycosylation

1140

1

N-linked (GlcNAc...); by host Potential

Glycosylation

1155

1

N-linked (GlcNAc...); by host Potential

Glycosylation

1176

1

N-linked (GlcNAc...); by host Potential

Disulfide bond

323 ↔ 348

Disulfide bond

366 ↔ 419

Disulfide bond

467 ↔ 474

Natural variations

Natural variant

49

1

S → L in strain: Isolate GZ50.

Natural variant

77

1

G → D in strain: Isolate BJ01, Isolate BJ02, Isolate BJ03, Isolate GZ50, Isolate CUHK-W1, Isolate HKU-36871, Isolate GD01, Isolate GD03 and Isolate SZ3.

Natural variant

78

1

N → D in strain: Isolate GD03.

Natural variant

118

1

N → S in strain: Isolate Shanghai LY.

Natural variant

139

1

A → V in strain: Isolate GD03.

Natural variant

144

1

M → L in strain: Isolate BJ03.

Natural variant

147

1

Q → R in strain: Isolate GD03.

Natural variant

193

1

F → S in strain: Isolate Shanghai LY.

Natural variant

227

1

N → K in strain: Isolate SZ3.

Natural variant

239

1

S → L in strain: Isolate GD01 and Isolate SZ3.

Natural variant

244

1

I → T in strain: Isolate BJ01, Isolate BJ02, Isolate BJ03, Isolate BJ04, Isolate GZ50, Isolate CUHK-W1, Isolate HKU-36871, Isolate GD01, Isolate GD03 and Isolate SZ3.

Natural variant

261

1

T → K in strain: Isolate SZ3.

Natural variant

311

1

G → R in strain: Isolate GD01 and Isolate BJ02.

Natural variant

344

1

K → R in strain: Isolate GD01, Isolate GD03 and Isolate SZ3; no effect on affinity with either human or palm civet ACE2. Ref.30

Natural variant

360

1

F → S in strain: Isolate GD03 and Isolate SZ3; no effect on affinity with either human or palm civet ACE2. Ref.30

Natural variant

426

1

R → G in strain: Isolate Shanghai LY.

Natural variant

437

1

N → D in strain: Isolate Shanghai LY.

Natural variant

472

1

L → P in strain: Isolate GD03.

Natural variant

479

1

N → K in strain: Isolate SZ3; 20fold decrease of affinity with human ACE2; no effect on affinity with palm civet ACE2. Ref.30

Natural variant

480

1

D → G in strain: Isolate GD03.

Natural variant

487

1

T → S in strain: Isolate GD03 and Isolate SZ3; 20fold decrease of affinity with human ACE2; decrease of affinity with palm civet ACE2. Ref.30

Natural variant

501

1

F → Y in strain: Isolate GD01.

Natural variant

577

1

S → A in strain: Isolate Tor2 and Isolate Shanghai QXC1.

Natural variant

605

1

D → N in strain: Isolate Shanghai QXC1.

Natural variant

607

1

S → P in strain: Isolate SZ3.

Natural variant

608

1

T → A in strain: Isolate Shanghai QXC1.

Natural variant

609

1

A → L in strain: Isolate GD03.

Natural variant

613

1

D → E in strain: Isolate GD03.

Natural variant

665

1

L → S in strain: Isolate GD03 and Isolate SZ3.

Natural variant

701

1

S → L in strain: Isolate SZ3.

Natural variant

743

1

T → A in strain: Isolate SZ3.

Natural variant

743

1

T → R in strain: Isolate GD03.

Natural variant

754

1

A → V in strain: Isolate SZ3.

Natural variant

765

1

A → V in strain: Isolate GD03.

Natural variant

778

1

Y → D in strain: Isolate GD01, Isolate GZ50, Isolate GD03 and Isolate SZ3.

Natural variant

794

1

P → S in strain: Isolate GD01.

Natural variant

804

1

L → P in strain: Isolate Shanghai LY.

Natural variant

860 – 861

2

VS → LR in strain: Isolate BJ03.

Natural variant

894

1

T → A in strain: Isolate SZ3.

Natural variant

999

1

E → G in strain: Isolate Shanghai LY.

Natural variant

1001

1

R → M in strain: Isolate BJ04.

Natural variant

1132

1

E → G in strain: Isolate Shanghai QXC1.

Natural variant

1148

1

L → F in strain: Isolate Frankfurt 1 and Isolate FRA.

Natural variant

1163

1

K → E in strain: Isolate GD03 and Isolate SZ3.

Experimental info

Mutagenesis

323

1

C → A: No effect on human ACE2 binding in vitro. Ref.26

Mutagenesis

348

1

C → A: Complete loss of human ACE2 binding in vitro. Ref.26

Mutagenesis

452

1

E → A: 90% loss of human ACE2 binding in vitro. Ref.26

Mutagenesis

454

1

D → A: Complete loss of human ACE2 binding in vitro. Ref.26

Mutagenesis

463

1

D → A: Partial loss of human ACE2 binding in vitro. Ref.26

Mutagenesis

467

1

C → A: Complete loss of human ACE2 binding in vitro. Ref.26

Mutagenesis

474

1

C → A: Complete loss of human ACE2 binding in vitro. Ref.26

Mutagenesis

480

1

D → A: No effect on human ACE2 binding in vitro. Ref.26

Mutagenesis

667

1

R → S: 40% loss of cell-cell fusion. Ref.34

Mutagenesis

672

1

K → S: No effect on cell-cell fusion. Ref.34

Mutagenesis

1251

1

K → A: Decrease in Golgi localization, and complete loss of COPI binding; when associated to A-1253. Ref.36

Mutagenesis

1253

1

H → A: Decrease in Golgi localization, and complete loss of COPI binding; when associated to A-1251. Ref.36

Secondary structure

1

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1255

Helix Strand Turn

Details...

Helix

326 – 329

4

Beta strand

341 – 345

5

Beta strand

347 – 349

3

Helix

353 – 356

4

Beta strand

362 – 369

8

Helix

371 – 373

3

Beta strand

374 – 376

3

Beta strand

378 – 390

13

Helix

391 – 396

6

Helix

404 – 408

5

Beta strand

418 – 424

7

Helix

426 – 429

4

Beta strand

431 – 433

3

Beta strand

439 – 441

3

Beta strand

477 – 480

4

Beta strand

483 – 487

5

Helix

489 – 491

3

Beta strand

492 – 502

11

Beta strand

509 – 511

3

Helix

894 – 972

79

Helix

1004 – 1016

13

Helix

1017 – 1020

4

Helix

1151 – 1186

36

Sequences

	Sequence		Length	Mass (Da)
	P59594 [UniParc]. Last modified April 23, 2003. Version 1. Checksum: 1C49ACA2CFD38FC0	FASTA	1,255	139,125
	10 20 30 40 50 60 MFIFLLFLTL TSGSDLDRCT TFDDVQAPNY TQHTSSMRGV YYPDEIFRSD TLYLTQDLFL 70 80 90 100 110 120 PFYSNVTGFH TINHTFGNPV IPFKDGIYFA ATEKSNVVRG WVFGSTMNNK SQSVIIINNS 130 140 150 160 170 180 TNVVIRACNF ELCDNPFFAV SKPMGTQTHT MIFDNAFNCT FEYISDAFSL DVSEKSGNFK 190 200 210 220 230 240 HLREFVFKNK DGFLYVYKGY QPIDVVRDLP SGFNTLKPIF KLPLGINITN FRAILTAFSP 250 260 270 280 290 300 AQDIWGTSAA AYFVGYLKPT TFMLKYDENG TITDAVDCSQ NPLAELKCSV KSFEIDKGIY 310 320 330 340 350 360 QTSNFRVVPS GDVVRFPNIT NLCPFGEVFN ATKFPSVYAW ERKKISNCVA DYSVLYNSTF 370 380 390 400 410 420 FSTFKCYGVS ATKLNDLCFS NVYADSFVVK GDDVRQIAPG QTGVIADYNY KLPDDFMGCV 430 440 450 460 470 480 LAWNTRNIDA TSTGNYNYKY RYLRHGKLRP FERDISNVPF SPDGKPCTPP ALNCYWPLND 490 500 510 520 530 540 YGFYTTTGIG YQPYRVVVLS FELLNAPATV CGPKLSTDLI KNQCVNFNFN GLTGTGVLTP 550 560 570 580 590 600 SSKRFQPFQQ FGRDVSDFTD SVRDPKTSEI LDISPCSFGG VSVITPGTNA SSEVAVLYQD 610 620 630 640 650 660 VNCTDVSTAI HADQLTPAWR IYSTGNNVFQ TQAGCLIGAE HVDTSYECDI PIGAGICASY 670 680 690 700 710 720 HTVSLLRSTS QKSIVAYTMS LGADSSIAYS NNTIAIPTNF SISITTEVMP VSMAKTSVDC 730 740 750 760 770 780 NMYICGDSTE CANLLLQYGS FCTQLNRALS GIAAEQDRNT REVFAQVKQM YKTPTLKYFG 790 800 810 820 830 840 GFNFSQILPD PLKPTKRSFI EDLLFNKVTL ADAGFMKQYG ECLGDINARD LICAQKFNGL 850 860 870 880 890 900 TVLPPLLTDD MIAAYTAALV SGTATAGWTF GAGAALQIPF AMQMAYRFNG IGVTQNVLYE 910 920 930 940 950 960 NQKQIANQFN KAISQIQESL TTTSTALGKL QDVVNQNAQA LNTLVKQLSS NFGAISSVLN 970 980 990 1000 1010 1020 DILSRLDKVE AEVQIDRLIT GRLQSLQTYV TQQLIRAAEI RASANLAATK MSECVLGQSK 1030 1040 1050 1060 1070 1080 RVDFCGKGYH LMSFPQAAPH GVVFLHVTYV PSQERNFTTA PAICHEGKAY FPREGVFVFN 1090 1100 1110 1120 1130 1140 GTSWFITQRN FFSPQIITTD NTFVSGNCDV VIGIINNTVY DPLQPELDSF KEELDKYFKN 1150 1160 1170 1180 1190 1200 HTSPDVDLGD ISGINASVVN IQKEIDRLNE VAKNLNESLI DLQELGKYEQ YIKWPWYVWL 1210 1220 1230 1240 1250 GFIAGLIAIV MVTILLCCMT SCCSCLKGAC SCGSCCKFDE DDSEPVLKGV KLHYT

References

[1]	"Characterization of a novel coronavirus associated with severe acute respiratory syndrome." Rota P.A., Oberste M.S., Monroe S.S., Nix W.A., Campagnoli R., Icenogle J.P., Penaranda S., Bankamp B., Maher K., Chen M.-H., Tong S., Tamin A., Lowe L., Frace M., DeRisi J.L., Chen Q., Wang D., Erdman D.D. , Peret T.C.T., Burns C., Ksiazek T.G., Rollin P.E., Sanchez A., Liffick S., Holloway B., Limor J., McCaustland K., Olsen-Rasmussen M., Fouchier R., Guenther S., Osterhaus A.D.M.E., Drosten C., Pallansch M.A., Anderson L.J., Bellini W.J. Science 300:1394-1399(2003) [PubMed: 12730500] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Urbani.
[2]	"The genome sequence of the SARS-associated coronavirus." Marra M.A., Jones S.J.M., Astell C.R., Holt R.A., Brooks-Wilson A., Butterfield Y.S.N., Khattra J., Asano J.K., Barber S.A., Chan S.Y., Cloutier A., Coughlin S.M., Freeman D., Girn N., Griffith O.L., Leach S.R., Mayo M., McDonald H. , Montgomery S.B., Pandoh P.K., Petrescu A.S., Robertson A.G., Schein J.E., Siddiqui A., Smailus D.E., Stott J.M., Yang G.S., Plummer F., Andonov A., Artsob H., Bastien N., Bernard K., Booth T.F., Bowness D., Czub M., Drebot M., Fernando L., Flick R., Garbutt M., Gray M., Grolla A., Jones S., Feldmann H., Meyers A., Kabani A., Li Y., Normand S., Stroher U., Tipples G.A., Tyler S., Vogrig R., Ward D., Watson B., Brunham R.C., Krajden M., Petric M., Skowronski D.M., Upton C., Roper R.L. Science 300:1399-1404(2003) [PubMed: 12730501] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Tor2.
[3]	"Coronavirus genomic-sequence variations and the epidemiology of the severe acute respiratory syndrome." Tsui S.K.W., Chim S.S.C., Lo Y.M.D. N. Engl. J. Med. 349:187-188(2003) [PubMed: 12853594] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate CUHK-Su10 and Isolate CUHK-W1.
[4]	"The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39)." Zeng F.Y., Chan C.W., Chan M.N., Chen J.D., Chow K.Y.C., Hon C.C.C., Hui R.K.H., Li J., Li V.Y.Y., Wang C.Y., Wang P.Y., Guan Y., Zheng B., Poon L.L.M., Chan K.H., Yuen K.Y., Peiris J.S.M., Leung F.C. Exp. Biol. Med. 228:866-873(2003) [PubMed: 12876307] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate HKU-39849.
[5]	"Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China." Guan Y., Zheng B.J., He Y.Q., Liu X.L., Zhuang Z.X., Cheung C.L., Luo S.W., Li P.H., Zhang L.J., Guan Y.J., Butt K.M., Wong K.L., Chan K.W., Lim W., Shortridge K.F., Yuen K.Y., Peiris J.S.M., Poon L.L.M. Science 302:276-278(2003) [PubMed: 12958366] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate GZ50 and Isolate HKU-36871.
[6]	Qin E., Zhu Q., Yu M., Fan B., Chang G., Si B., Yang B., Peng W., Jiang T., Liu B., Deng Y., Liu H., Zhang Y., Wang C., Li Y., Gan Y., Li X., Lu F. , Tan G., Yang R., Cao W.S., Wang J., Chen W., Cong L., Deng Y., Dong W., Han Y., Hu W., Lei M., Li C., Li G., Li G., Li H., Li S., Li S., Li W., Li W., Lin W., Liu J., Liu Z., Lu H., Ni P., Qi Q., Sun Y., Tang L., Tong Z., Wang J., Wang X., Wu Q., Xi Y., Xu Z., Yang L., Ye C., Ye J., Zhang B., Zhang F., Zhang J., Zhang X., Zhou J., Yang H. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate BJ01, Isolate BJ02, Isolate BJ03, Isolate BJ04 and Isolate GD01.
[7]	"Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection." Ruan Y., Wei C.L., Ling A.E., Vega V.B., Thoreau H., Se Thoe S.Y., Chia J.-M., Ng P., Chiu K.P., Lim L., Zhang T., Chan K.P., Oon L.E.L., Ng M.L., Leo S.Y., Ng L.F.P., Ren E.C., Stanton L.W., Long P.M., Liu E.T. Lancet 361:1779-1785(2003) [PubMed: 12781537] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Sin2500, Isolate Sin2677, Isolate Sin2679, Isolate Sin2748 and Isolate sin2774.
[8]	Erratum Ruan Y., Wei C.L., Ling A.E., Vega V.B., Thoreau H., Se Thoe S.Y., Chia J.-M., Ng P., Chiu K.P., Lim L., Zhang T., Chan K.P., Oon L.E.L., Ng M.L., Leo S.Y., Ng L.F.P., Ren E.C., Stanton L.W., Long P.M., Liu E.T. Lancet 361:1832-1832(2003)
[9]	"The complete genome of SARS coronavirus clone TW1." Yeh S.-H., Kao C.-L., Tsai C.-Y., Liu C.-J., Chen D.-S., Chen P.-J. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate TW1.
[10]	"SARS virus is a close relative of type II coronaviruses." Eickmann M., Becker S., Klenk H.-D., Doerr H.W., Stadler K., Censini S., Guidotti S., Masignani V., Scarselli M., Mora M., Donati C., Han J., Song H.C., Abrignani S., Covacci A., Rappuoli R. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate FRA.
[11]	"Mechanisms and enzymes involved in SARS coronavirus genome expression." Thiel V., Ivanov K.A., Putics A., Hertzig T., Schelle B., Bayer S., Weissbrich B., Snijder E.J., Rabenau H., Doerr H.W., Gorbalenya A.E., Ziebuhr J. J. Gen. Virol. 84:2305-2315(2003) [PubMed: 12917450] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Frankfurt 1.
[12]	"Genomic sequence of SARS isolate from the first fatal case in Taiwan." Yang J.-Y., Lin J.-H., Chiu S.-C., Wang S.-F., Lee S.C., Lin Y.-C., Hsu C.-K., Chen H.-Y., Chang J.G., Chen P.-J., Su I.-J. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate TWC.
[13]	"SARS coronavirus ZJ01 isolate spike glycoprotein." Cong L.-M., Ding G.-Q., Lu Y.-Y., Weng J.-Q., Yan J.-Y., Hu N.-P., Wo J.-E., Chen S.-Y., Zhang Y.-J., Mei L.-L., Wang Z.-G., Yao J., Zhu H.-P., Lu Q.-Y., Li M.-H., Gong L.-M., Shi W., Li L.-J. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Isolate ZJ01.
[14]	Yuan Z., Zhang X., Hu Y., Lan S., Wang H., Zhou Z., Wen Y. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Shanghai LY.
[15]	Chang J.-G.C., Lin T.-H., Chen C.-M., Lin C.-S., Chan W.-L., Shih M.-C. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Taiwan TC1, Isolate Taiwan TC2 and Isolate Taiwan TC3.
[16]	Shu H.Y., Wu K.M., Tsai S.F. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate TWH, Isolate TWJ, Isolate TWK, Isolate TWS and Isolate TWY.
[17]	Canducci F., Clementi M., Poli G., Vicenzi E. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate HSR 1.
[18]	Yang J.-Y., Lin J.-H., Chiu S.-C., Wang S.-F., Lee H.-C., Lin Y.-C., Hsu C.-K., Chen H.-Y., Chen P.-J., Su I.-J. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate TWC2 and Isolate TWC3.
[19]	Balotta C., Corvasce S., Violin M., Galli M., Moroni M., Vigevani G.M., Ruan Y.J., Salemi M. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate AS.
[20]	"Analysis of SARS coronavirus genome in Shanghai isolates." Yuan Z., Zhang X., Hu Y., Lan S., Wang H., Zhou Z., Wen Y. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Shanghai QXC1.
[21]	"Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human." Song H.D., Tu C.C., Zhang G.W., Wang S.Y., Zheng K., Lei L.C., Chen Q.X., Gao Y.W., Zhou H.Q., Xiang H., Zheng H.J., Chern S.W., Cheng F., Pan C.M., Xuan H., Chen S.J., Luo H.M., Zhou D.H. , Liu Y.F., He J.F., Qin P.Z., Li L.H., Ren Y.Q., Liang W.J., Yu Y.D., Anderson L., Wang M., Xu R.H., Wu X.W., Zheng H.Y., Chen J.D., Liang G., Gao Y., Liao M., Fang L., Jiang L.Y., Li H., Chen F., Di B., He L.J., Lin J.Y., Tong S., Kong X., Du L., Hao P., Tang H., Bernini A., Yu X.J., Spiga O., Guo Z.M., Pan H.Y., He W.Z., Manuguerra J.C., Fontanet A., Danchin A., Niccolai N., Li Y.X., Wu C.I., Zhao G.P. Proc. Natl. Acad. Sci. U.S.A. 102:2430-2435(2005) [PubMed: 15695582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate GD03.
[22]	"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus." Li W., Moore M.J., Vasilieva N., Sui J., Wong S.-K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M. Nature 426:450-454(2003) [PubMed: 14647384] [Abstract] Cited for: INTERACTION WITH HUMAN ACE2, CHARACTERIZATION OF CELLULAR RECEPTOR.
[23]	"A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2." Wong S.K., Li W., Moore M.J., Choe H., Farzan M. J. Biol. Chem. 279:3197-3201(2004) [PubMed: 14670965] [Abstract] Cited for: INTERACTION WITH HUMAN ACE2.
[24]	"Characterization of the heptad repeat regions, HR1 and HR2, and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome (SARS) coronavirus." Xu Y., Zhu J., Liu Y., Lou Z., Yuan F., Liu Y., Cole D.K., Ni L., Su N., Qin L., Li X., Bai Z., Bell J.I., Pang H., Tien P., Gao G.F., Rao Z. Biochemistry 43:14064-14071(2004) [PubMed: 15518555] [Abstract] Cited for: CHARACTERIZATION OF HEPTAD REPEAT REGIONS.
[25]	"The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells." Wu X.D., Shang B., Yang R.F., Yu H., Ma Z.H., Shen X., Ji Y.Y., Lin Y., Wu Y.D., Lin G.M., Tian L., Gan X.Q., Yang S., Jiang W.H., Dai E.H., Wang X.Y., Jiang H.L., Xie Y.H. , Zhu X.L., Pei G., Li L., Wu J.R., Sun B. Cell Res. 14:400-406(2004) [PubMed: 15450134] [Abstract] Cited for: CLEAVAGE.
[26]	"CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus." Jeffers S.A., Tusell S.M., Gillim-Ross L., Hemmila E.M., Achenbach J.E., Babcock G.J., Thomas W.D. Jr., Thackray L.B., Young M.D., Mason R.J., Ambrosino D.M., Wentworth D.E., Demartini J.C., Holmes K.V. Proc. Natl. Acad. Sci. U.S.A. 101:15748-15753(2004) [PubMed: 15496474] [Abstract] Cited for: INTERACTION WITH HUMAN CLEC4M/DC-SIGNR, MUTAGENESIS OF CYS-323; CYS-348; GLU-452; ASP-454; ASP-463; CYS-467; CYS-474 AND ASP-480.
[27]	"Oligomerization of the SARS-CoV S glycoprotein: dimerization of the N-terminus and trimerization of the ectodomain." Xiao X., Feng Y., Chakraborti S., Dimitrov D.S. Biochem. Biophys. Res. Commun. 322:93-99(2004) [PubMed: 15313178] [Abstract] Cited for: HOMOTRIMERIZATION.
[28]	"Identification and characterization of the putative fusion peptide of the severe acute respiratory syndrome-associated coronavirus spike protein." Sainz B. Jr., Rausch J.M., Gallaher W.R., Garry R.F., Wimley W.C. J. Virol. 79:7195-7206(2005) [PubMed: 15890958] [Abstract] Cited for: CHARACTERIZATION OF FUSION PEPTIDE.
[29]	"Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and E." Nal B., Chan C., Kien F., Siu L., Tse J., Chu K., Kam J., Staropoli I., Crescenzo-Chaigne B., Escriou N., van der Werf S., Yuen K.Y., Altmeyer R. J. Gen. Virol. 86:1423-1434(2005) [PubMed: 15831954] [Abstract] Cited for: SUBCELLULAR LOCATION.
[30]	"Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2." Li W., Zhang C., Sui J., Kuhn J.H., Moore M.J., Luo S., Wong S.-K., Huang I.-C., Xu K., Vasilieva N., Murakami A., He Y., Marasco W.A., Guan Y., Choe H., Farzan M. EMBO J. 24:1634-1643(2005) [PubMed: 15791205] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ARG-344; SER-360; LYS-479 AND SER-487.
[31]	"Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry." Simmons G., Gosalia D.N., Rennekamp A.J., Reeves J.D., Diamond S.L., Bates P. Proc. Natl. Acad. Sci. U.S.A. 102:11876-11881(2005) [PubMed: 16081529] [Abstract] Cited for: PROTEOLYSIS BY HUMAN CTSL.
[32]	"A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis." Tan Y.-J., Teng E., Shen S., Tan T.H.P., Goh P.-Y., Fielding B.C., Ooi E.-E., Tan H.-C., Lim S.G., Hong W. J. Virol. 78:6723-6734(2004) [PubMed: 15194747] [Abstract] Cited for: INTERACTION WITH ACCESSORY PROTEIN 3A.
[33]	"Severe acute respiratory syndrome coronavirus 7a accessory protein is a viral structural protein." Huang C., Ito N., Tseng C.-T.K., Makino S. J. Virol. 80:7287-7294(2006) [PubMed: 16840309] [Abstract] Cited for: INTERACTION WITH ACCESSORY PROTEIN 7A.
[34]	"Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry." Follis K.E., York J., Nunberg J.H. Virology 350:358-369(2006) [PubMed: 16519916] [Abstract] Cited for: MUTAGENESIS OF ARG-667 AND LYS-672.
[35]	"Palmitoylation of the cysteine-rich endodomain of the SARS-coronavirus spike glycoprotein is important for spike-mediated cell fusion." Petit C.M., Chouljenko V.N., Iyer A., Colgrove R., Farzan M., Knipe D.M., Kousoulas K.G. Virology 360:264-274(2007) [PubMed: 17134730] [Abstract] Cited for: PALMITOYLATION.
[36]	"The cytoplasmic tail of the severe acute respiratory syndrome coronavirus spike protein contains a novel endoplasmic reticulum retrieval signal that binds COPI and promotes interaction with membrane protein." McBride C.E., Li J., Machamer C.E. J. Virol. 81:2418-2428(2007) [PubMed: 17166901] [Abstract] Cited for: ENDOPLASMIC RETICULUM RETENTION MOTIF, MUTAGENESIS OF LYS-1251 AND HIS-1253.
[37]	"Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core." Xu Y., Lou Z., Liu Y., Pang H., Tien P., Gao G.F., Rao Z. J. Biol. Chem. 279:49414-49419(2004) [PubMed: 15345712] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 900-948.
[38]	"Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein." Supekar V.M., Bruckmann C., Ingallinella P., Bianchi E., Pessi A., Carfi A. Proc. Natl. Acad. Sci. U.S.A. 101:17958-17963(2004) [PubMed: 15604146] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 895-972 AND 1142-1180.
[39]	"Molecular modelling of S1 and S2 subunits of SARS coronavirus spike glycoprotein." Spiga O., Bernini A., Ciutti A., Chiellini S., Menciassi N., Finetti F., Causarono V., Anselmi F., Prischi F., Niccolai N. Biochem. Biophys. Res. Commun. 310:78-83(2003) [PubMed: 14511651] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 17-680.
[40]	"Structure of SARS coronavirus spike receptor-binding domain complexed with receptor." Li F., Li W., Farzan M., Harrison S.C. Science 309:1864-1868(2005) [PubMed: 16166518] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 323-502 IN COMPLEX WITH HUMAN ACE2.
[41]	"Structures and polymorphic interactions of two heptad-repeat regions of the SARS virus S2 protein." Deng Y., Liu J., Zheng Q., Yong W., Lu M. Structure 14:889-899(2006) [PubMed: 16698550] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1150-1193.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY278741 Genomic RNA. Translation: AAP13441.1.
AY274119 Genomic RNA. Translation: AAP41037.1.
AY282752 Genomic RNA. Translation: AAP30713.1.
AY278554 Genomic RNA. Translation: AAP13567.1.
AY278491 Genomic RNA. No translation available.
AY304495 Genomic RNA. No translation available.
AY304492 Genomic RNA. No translation available.
AY278487 Genomic RNA. No translation available.
AY278488 Genomic RNA. Translation: AAP30030.1.
AY278490 Genomic RNA. No translation available.
AY279354 Genomic RNA. No translation available.
AY278489 Genomic RNA. Translation: AAP51227.1.
AY283794 Genomic RNA. No translation available.
AY283795 Genomic RNA. No translation available.
AY283796 Genomic RNA. No translation available.
AY283797 Genomic RNA. No translation available.
AY283798 Genomic RNA. No translation available.
AY291451 Genomic RNA. Translation: AAP37017.1.
AY310120 Genomic RNA. Translation: AAP50485.1.
AY291315 Genomic RNA. Translation: AAP33697.1.
AY304486 Genomic RNA. No translation available.
AY321118 Genomic RNA. No translation available.
AY323976 mRNA. Translation: AAP73417.1.
AY322207 Genomic RNA. Translation: AAP82968.1.
AY338174 Genomic RNA. Translation: AAQ01597.1.
AY338175 Genomic RNA. Translation: AAQ01609.1.
AY348314 Genomic RNA. Translation: AAP97882.1.
AP006557 Genomic RNA. Translation: BAC81348.1.
AP006558 Genomic RNA. Translation: BAC81362.1.
AP006559 Genomic RNA. Translation: BAC81376.1.
AP006560 Genomic RNA. Translation: BAC81390.1.
AP006561 Genomic RNA. Translation: BAC81404.1.
AY323977 Genomic RNA. Translation: AAP72986.1.
AY362698 Genomic RNA. No translation available.
AY362699 Genomic RNA. No translation available.
AY427439 Genomic RNA. Translation: AAQ94060.1.
AY463059 Genomic RNA. Translation: AAR86788.1.
AY525636 Genomic RNA. Translation: AAS10463.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q4Z	model	-	A	17-680	[»]
1T7G	model	-	A/C/E	17-680	[»]
			B/D/F	737-1026	[»]
1U4K	model	-	D	764-1089	[»]
1WNC	X-ray	2.80	A/B/C/D/E/F	900-1185	[»]
1WYY	X-ray	2.20	A/B	885-1189	[»]
1XJP	model	-	A	17-680	[»]
1ZV7	X-ray	1.70	A/B	1150-1193	[»]
1ZV8	X-ray	1.94	A/C/E/G/I/K	901-950	[»]
			B/D/F/H/J/L	1150-1185	[»]
1ZVB	X-ray	1.70	A/B/C	940-973	[»]
2AJF	X-ray	2.90	E/F	323-502	[»]
2BEQ	X-ray	1.60	A/B/C	914-949	[»]
			D/E/F	1148-1193	[»]
2BEZ	X-ray	1.60	C	896-972	[»]
			F	1142-1183	[»]
2DD8	X-ray	2.30	S	317-518	[»]
2FXP	NMR	-	A/B/C	1141-1193	[»]
2GHV	X-ray	2.20	C/E	317-510	[»]
2GHW	X-ray	2.30	A/C	317-510	[»]
3BGF	X-ray	3.00	A/S	318-510	[»]
3D0G	X-ray	2.80	E/F	324-502	[»]
3D0H	X-ray	3.10	E/F	324-502	[»]
3D0I	X-ray	2.90	E/F	324-502	[»]

ProteinModelPortal

P59594.

SMR

P59594. Positions 321-512, 896-972, 1148-1193.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29105N.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR002552. Corona_S2.
IPR018548. Spike_rcpt-bd.
[Graphical view]

Pfam

PF01601. Corona_S2. 1 hit.
PF09408. Spike_rec_bind. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

SPIKE_CVHSA

Accession

Primary (citable) accession number: P59594
Secondary accession number(s): Q6QU82 , Q7T696, Q7TA19, Q7TFA2, Q7TFB1, Q80BV6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	April 23, 2003
Last modified:	September 21, 2011
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program