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P03420 (FUS_HRSVA) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHuman respiratory syncytial virus A (strain A2) [Complete proteome]
Taxonomic identifier11259 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesMononegaviralesParamyxoviridaePneumovirinaePneumovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length574 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 574553Fusion glycoprotein F0
PRO_0000039234
Chain22 – 136115Fusion glycoprotein F2
PRO_0000039235
Chain137 – 574438Fusion glycoprotein F1
PRO_0000039236

Regions

Topological domain27 – 529503Extracellular By similarity
Transmembrane530 – 55021Helical; Potential
Topological domain551 – 57424Cytoplasmic By similarity
Region137 – 15721Fusion peptide By similarity
Coiled coil155 – 18329 Potential
Coiled coil491 – 51626 Potential

Sites

Site136 – 1372Cleavage; by host By similarity

Amino acid modifications

Lipidation5501S-palmitoyl cysteine; by host Ref.6
Glycosylation271N-linked (GlcNAc...); by host Potential
Glycosylation701N-linked (GlcNAc...); by host Potential
Glycosylation1161N-linked (GlcNAc...); by host Potential
Glycosylation1261N-linked (GlcNAc...); by host Potential
Glycosylation5001N-linked (GlcNAc...); by host Potential
Disulfide bond69 ↔ 212Interchain (between F2 and F1 chains) By similarity
Disulfide bond358 ↔ 367 By similarity
Disulfide bond382 ↔ 393 By similarity

Natural variations

Natural variant1021P → A in strain: Cold-passage attenuated.
Natural variant2181E → A in strain: Cold-passage attenuated.
Natural variant3791I → V in strain: Cold-passage attenuated.
Natural variant4471M → V in strain: Cold-passage attenuated.
Natural variant5231T → I in strain: Cold-passage attenuated.

Secondary structure

.................................................................................... 574
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03420 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: A4066D9DC98933AA

FASTA57463,453
        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 

« Hide

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.
PIRVGNZA2. A04035.
B28929.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3IXTX-ray2.75C/P254-277[»]
3KPEX-ray1.47A159-209[»]
B482-520[»]
3RKIX-ray3.20A/B/C1-524[»]
3RRRX-ray2.82A/C/E/G/I/M26-109[»]
B/D/F/H/L/N147-513[»]
3RRTX-ray3.20A/C/E26-109[»]
B/D/F147-513[»]
4CCFX-ray2.65A/B/C/D/E/F1-574[»]
4JHWX-ray3.60F26-513[»]
4MMQX-ray3.25A26-107[»]
B137-513[»]
4MMRX-ray3.10A26-107[»]
B137-513[»]
4MMSX-ray2.40A/C/E26-107[»]
B/D/F137-513[»]
4MMTX-ray3.05A26-107[»]
B137-513[»]
4MMUX-ray3.00A26-107[»]
B137-513[»]
4MMVX-ray2.81A26-107[»]
B137-513[»]
ProteinModelPortalP03420.
SMRP03420. Positions 158-207, 477-516.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-48772N.

Protein family/group databases

TCDB1.G.2.1.3. the viral pore-forming membrane fusion protein-2 (vmfp2) family.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR000776. Fusion_F0_Paramyxovir.
[Graphical view]
PfamPF00523. Fusion_gly. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP03420.

Entry information

Entry nameFUS_HRSVA
AccessionPrimary (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: February 19, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references