P03420 (FUS_HRSVA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fusion glycoprotein F0
Short name=Protein F

Cleaved into the following 2 chains:

1. Fusion glycoprotein F2
2. Fusion glycoprotein F1

Gene names

Name:

F

Organism

Human respiratory syncytial virus A (strain A2) [Complete proteome]

Taxonomic identifier

11259 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Mononegavirales › Paramyxoviridae › Pneumovirinae › Pneumovirus › Human respiratory syncytial virus › Human respiratory syncytial virus A

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	574 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	Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions 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 plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis. Ref.10 Ref.11
Subunit structure	Homotrimer of disulfide-linked F1-F2 By similarity. Interacts with glycoprotein G. Interacts with host RHOA; this interaction facilitates virus-induced syncytium formation. Ref.7 Ref.8 Ref.12
Subcellular location	Virion membrane; Single-pass type I membrane protein. Host cell membrane; Single-pass membrane protein.
Post-translational modification	The F glycoprotein is synthesized as a inactive precursor that is heavily N-glycosylated and processed by host cell furin in the Golgi to yield the mature F1 and F2 proteins. The cleavage site between F1 and F2 requires the minimal sequence [KR]-X-[KR]-R.
Sequence similarities	Belongs to the paramyxoviruses fusion glycoprotein family.

Ontologies

Keywords
Biological process	Fusion of virus membrane with host cell membrane Fusion of virus membrane with host membrane Syncytium formation induced by viral infection Viral penetration into host cytoplasm Virus entry into host cell
Cellular component	Host cell membrane Host membrane Membrane Viral envelope protein Virion
Domain	Coiled coil Signal Transmembrane Transmembrane helix
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	positive regulation of syncytium formation by virus Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via membrane fusion with the plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 574

553

Fusion glycoprotein F0

PRO_0000039234

Chain

22 – 136

115

Fusion glycoprotein F2

PRO_0000039235

Chain

137 – 574

438

Fusion glycoprotein F1

PRO_0000039236

Regions

Topological domain

27 – 529

503

Extracellular By similarity

Transmembrane

530 – 550

21

Helical; Potential

Topological domain

551 – 574

24

Cytoplasmic By similarity

Region

137 – 157

21

Fusion peptide By similarity

Coiled coil

155 – 183

29

Potential

Coiled coil

491 – 516

26

Potential

Sites

Site

136 – 137

2

Cleavage; by host By similarity

Amino acid modifications

Lipidation

550

1

S-palmitoyl cysteine; by host Ref.6

Glycosylation

27

1

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

Glycosylation

70

1

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

Glycosylation

116

1

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

Glycosylation

126

1

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

Glycosylation

500

1

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

Disulfide bond

69 ↔ 212

Interchain (between F2 and F1 chains) By similarity

Disulfide bond

358 ↔ 367

By similarity

Disulfide bond

382 ↔ 393

By similarity

Natural variations

Natural variant

102

1

P → A in strain: Cold-passage attenuated.

Natural variant

218

1

E → A in strain: Cold-passage attenuated.

Natural variant

379

1

I → V in strain: Cold-passage attenuated.

Natural variant

447

1

M → V in strain: Cold-passage attenuated.

Natural variant

523

1

T → I in strain: Cold-passage attenuated.

Secondary structure

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574

Helix Strand Turn

Details...

Beta strand

29 – 33

5

Helix

34 – 36

3

Beta strand

38 – 60

23

Beta strand

72 – 75

4

Helix

78 – 94

17

Helix

95 – 97

3

Beta strand

150 – 153

4

Helix

154 – 201

48

Helix

203 – 226

24

Helix

228 – 240

13

Beta strand

243 – 246

4

Turn

249 – 251

3

Helix

254 – 263

10

Beta strand

264 – 266

3

Helix

268 – 275

8

Helix

278 – 284

7

Beta strand

286 – 293

8

Beta strand

296 – 318

23

Beta strand

333 – 336

4

Beta strand

340 – 344

5

Beta strand

346 – 352

7

Helix

355 – 357

3

Beta strand

358 – 361

4

Beta strand

364 – 368

5

Helix

369 – 371

3

Beta strand

373 – 375

3

Helix

377 – 383

7

Beta strand

386 – 388

3

Beta strand

395 – 400

6

Beta strand

404 – 407

4

Beta strand

409 – 415

7

Beta strand

422 – 425

4

Beta strand

431 – 434

4

Beta strand

437 – 443

7

Turn

444 – 446

3

Beta strand

448 – 452

5

Beta strand

455 – 460

6

Beta strand

467 – 469

3

Helix

485 – 513

29

Sequences

	Sequence		Length	Mass (Da)
	P03420 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: A4066D9DC98933AA	FASTA	574	63,453
	10 20 30 40 50 60 MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT GWYTSVITIE 70 80 90 100 110 120 LSNIKENKCN GTDAKVKLIK QELDKYKNAV TELQLLMQST PPTNNRARRE LPRFMNYTLN 130 140 150 160 170 180 NAKKTNVTLS KKRKRRFLGF LLGVGSAIAS GVAVSKVLHL EGEVNKIKSA LLSTNKAVVS 190 200 210 220 230 240 LSNGVSVLTS KVLDLKNYID KQLLPIVNKQ SCSISNIETV IEFQQKNNRL LEITREFSVN 250 260 270 280 290 300 AGVTTPVSTY MLTNSELLSL INDMPITNDQ KKLMSNNVQI VRQQSYSIMS IIKEEVLAYV 310 320 330 340 350 360 VQLPLYGVID TPCWKLHTSP LCTTNTKEGS NICLTRTDRG WYCDNAGSVS FFPQAETCKV 370 380 390 400 410 420 QSNRVFCDTM NSLTLPSEIN LCNVDIFNPK YDCKIMTSKT DVSSSVITSL GAIVSCYGKT 430 440 450 460 470 480 KCTASNKNRG IIKTFSNGCD YVSNKGMDTV SVGNTLYYVN KQEGKSLYVK GEPIINFYDP 490 500 510 520 530 540 LVFPSDEFDA SISQVNEKIN QSLAFIRKSD ELLHNVNAGK STTNIMITTI IIVIIVILLS 550 560 570 LIAVGLLLYC KARSTPVTLS KDQLSGINNI AFSN

References

[1]	"Nucleotide sequence of the gene encoding the fusion (F) glycoprotein of human respiratory syncytial virus." Collins P.L., Huang Y.T., Wertz G.W. Proc. Natl. Acad. Sci. U.S.A. 81:7683-7687(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Nucleotide sequence analysis of the respiratory syncytial virus subgroup A cold-passaged (cp) temperature sensitive (ts) cpts-248/404 live attenuated virus vaccine candidate." Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R., Crowe J.E. Jr. Virology 225:419-422(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[3]	"Acquisition of the ts phenotype by a chemically mutagenized cold-passaged human respiratory syncytial virus vaccine candidate results from the acquisition of a single mutation in the polymerase (L) gene." Crowe J.E. Jr., Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R. Virus Genes 13:269-273(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[4]	"A cold-passaged, attenuated strain of human respiratory syncytial virus contains mutations in the F and L genes." Connors M., Crowe J.E. Jr., Firestone C.Y., Murphy B.R., Collins P.L. Virology 208:478-484(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[5]	"Recombinant respiratory syncytial virus (RSV) bearing a set of mutations from cold-passaged RSV is attenuated in chimpanzees." Whitehead S.S., Juhasz K., Firestone C.Y., Collins P.L., Murphy B.R. J. Virol. 72:4467-4471(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[6]	"Fatty acid acylation of the fusion glycoprotein of human respiratory syncytial virus." Arumugham R.G., Seid R.C. Jr., Doyle S., Hildreth S.W., Paradisio P.R. J. Biol. Chem. 264:10339-10342(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-550.
[7]	"RhoA interacts with the fusion glycoprotein of respiratory syncytial virus and facilitates virus-induced syncytium formation." Pastey M.K., Crowe J.E. Jr., Graham B.S. J. Virol. 73:7262-7270(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST RHOA.
[8]	"The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate." Feldman S.A., Audet S., Beeler J.A. J. Virol. 74:6442-6447(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HEPARAN SULFATE.
[9]	"Furin cleavage of the respiratory syncytial virus fusion protein is not a requirement for its transport to the surface of virus-infected cells." Sugrue R.J., Brown C., Brown G., Aitken J., McL Rixon H.W. J. Gen. Virol. 82:1375-1386(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE BY HOST FURIN.
[10]	"Respiratory syncytial virus (RSV) fusion protein subunit F2, not attachment protein G, determines the specificity of RSV infection." Schlender J., Zimmer G., Herrler G., Conzelmann K.K. J. Virol. 77:4609-4616(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HOST CELL SPECIFICITY.
[11]	"The fusion protein of respiratory syncytial virus triggers p53-dependent apoptosis." Eckardt-Michel J., Lorek M., Baxmann D., Grunwald T., Keil G.M., Zimmer G. J. Virol. 82:3236-3249(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[12]	"The RSV F and G glycoproteins interact to form a complex on the surface of infected cells." Low K.W., Tan T., Ng K., Tan B.H., Sugrue R.J. Biochem. Biophys. Res. Commun. 366:308-313(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GLYCOPROTEIN G.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M11486 Genomic RNA. Translation: AAB59858.1.
U50362 Genomic RNA. Translation: AAB86664.1.
U50363 Genomic RNA. Translation: AAB86676.1.
AF035006 Genomic RNA. Translation: AAC14902.1.
U63644 Genomic RNA. Translation: AAC55970.1.

PIR

VGNZA2. A04035.
B28929.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IXT	X-ray	2.75	C/P	254-277	[»]
3KPE	X-ray	1.47	A	159-209	[»]
			B	482-520	[»]
3RKI	X-ray	3.20	A/B/C	1-524	[»]
3RRR	X-ray	2.82	A/C/E/G/I/M	26-109	[»]
			B/D/F/H/L/N	147-513	[»]
3RRT	X-ray	3.20	A/C/E	26-109	[»]
			B/D/F	147-513	[»]

ProteinModelPortal

P03420.

SMR

P03420. Positions 158-207, 477-516.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48772N.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR000776. Fusion_F0_Paramyxovir.
[Graphical view]

Pfam

PF00523. Fusion_gly. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P03420.

Entry information

Entry name

FUS_HRSVA

Accession

Primary (citable) accession number: P03420
Secondary accession number(s): P88811

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	April 3, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program