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P03420

- FUS_HRSVA

UniProt

P03420 - FUS_HRSVA

Protein

Fusion glycoprotein F0

Gene

F

Organism
Human respiratory syncytial virus A (strain A2)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 1 (21 Jul 1986)
      Previous versions | rss
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    Functioni

    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.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei136 – 1372Cleavage; by hostBy similarity

    GO - Biological processi

    1. fusion of virus membrane with host plasma membrane Source: UniProtKB-KW
    2. positive regulation of syncytium formation by virus Source: UniProtKB-KW

    Keywords - Biological processi

    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

    Protein family/group databases

    TCDBi1.G.2.1.3. the viral pore-forming membrane fusion protein-2 (vmfp2) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fusion glycoprotein F0
    Short name:
    Protein F
    Cleaved into the following 2 chains:
    Gene namesi
    Name:F
    OrganismiHuman respiratory syncytial virus A (strain A2)
    Taxonomic identifieri11259 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesMononegaviralesParamyxoviridaePneumovirinaePneumovirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000007678: Genome

    Subcellular locationi

    GO - Cellular componenti

    1. host cell plasma membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. viral envelope Source: UniProtKB-KW
    4. virion membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cell membrane, Host membrane, Membrane, Viral envelope protein, Virion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2121Sequence AnalysisAdd
    BLAST
    Chaini22 – 574553Fusion glycoprotein F0PRO_0000039234Add
    BLAST
    Chaini22 – 136115Fusion glycoprotein F2PRO_0000039235Add
    BLAST
    Chaini137 – 574438Fusion glycoprotein F1PRO_0000039236Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi27 – 271N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi69 ↔ 212Interchain (between F2 and F1 chains)By similarity
    Glycosylationi70 – 701N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi116 – 1161N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi126 – 1261N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi358 ↔ 367By similarity
    Disulfide bondi382 ↔ 393By similarity
    Glycosylationi500 – 5001N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi550 – 5501S-palmitoyl cysteine; by host1 Publication

    Post-translational modificationi

    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.1 Publication

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

    Interactioni

    Subunit structurei

    Homotrimer of disulfide-linked F1-F2 By similarity. Interacts with glycoprotein G. Interacts with host RHOA; this interaction facilitates virus-induced syncytium formation.By similarity3 Publications

    Protein-protein interaction databases

    DIPiDIP-48772N.

    Structurei

    Secondary structure

    1
    574
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi29 – 335
    Turni34 – 374
    Beta strandi38 – 4912
    Beta strandi51 – 6010
    Helixi74 – 9825
    Helixi139 – 1413
    Helixi149 – 15810
    Helixi160 – 20142
    Helixi204 – 2063
    Beta strandi208 – 2114
    Helixi217 – 23923
    Turni240 – 2423
    Beta strandi243 – 2464
    Turni249 – 2513
    Helixi254 – 26310
    Beta strandi264 – 2663
    Helixi268 – 2769
    Helixi278 – 2836
    Beta strandi286 – 2927
    Beta strandi294 – 30512
    Beta strandi307 – 31812
    Beta strandi326 – 3294
    Beta strandi333 – 3364
    Beta strandi340 – 3456
    Beta strandi348 – 3536
    Helixi355 – 3573
    Beta strandi358 – 3614
    Beta strandi364 – 3685
    Helixi369 – 3713
    Beta strandi373 – 3753
    Helixi377 – 3804
    Helixi381 – 3844
    Beta strandi386 – 3883
    Beta strandi389 – 3913
    Beta strandi394 – 3985
    Beta strandi404 – 4074
    Beta strandi409 – 4168
    Beta strandi422 – 4265
    Turni427 – 4293
    Beta strandi430 – 4345
    Beta strandi437 – 4448
    Beta strandi449 – 4524
    Beta strandi455 – 4584
    Beta strandi466 – 4694
    Helixi474 – 4774
    Turni480 – 4823
    Helixi487 – 51428

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP03420.
    SMRiP03420. Positions 158-207, 477-516.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03420.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini27 – 529503ExtracellularBy similarityAdd
    BLAST
    Topological domaini551 – 57424CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei530 – 55021HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni137 – 15721Fusion peptideBy similarityAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili155 – 18329Sequence AnalysisAdd
    BLAST
    Coiled coili491 – 51626Sequence AnalysisAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Coiled coil, Signal, Transmembrane, Transmembrane helix

    Family and domain databases

    InterProiIPR000776. Fusion_F0_Paramyxovir.
    [Graphical view]
    PfamiPF00523. Fusion_gly. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P03420-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT    50
    GWYTSVITIE LSNIKENKCN GTDAKVKLIK QELDKYKNAV TELQLLMQST 100
    PPTNNRARRE LPRFMNYTLN NAKKTNVTLS KKRKRRFLGF LLGVGSAIAS 150
    GVAVSKVLHL EGEVNKIKSA LLSTNKAVVS LSNGVSVLTS KVLDLKNYID 200
    KQLLPIVNKQ SCSISNIETV IEFQQKNNRL LEITREFSVN AGVTTPVSTY 250
    MLTNSELLSL INDMPITNDQ KKLMSNNVQI VRQQSYSIMS IIKEEVLAYV 300
    VQLPLYGVID TPCWKLHTSP LCTTNTKEGS NICLTRTDRG WYCDNAGSVS 350
    FFPQAETCKV QSNRVFCDTM NSLTLPSEIN LCNVDIFNPK YDCKIMTSKT 400
    DVSSSVITSL GAIVSCYGKT KCTASNKNRG IIKTFSNGCD YVSNKGMDTV 450
    SVGNTLYYVN KQEGKSLYVK GEPIINFYDP LVFPSDEFDA SISQVNEKIN 500
    QSLAFIRKSD ELLHNVNAGK STTNIMITTI IIVIIVILLS LIAVGLLLYC 550
    KARSTPVTLS KDQLSGINNI AFSN 574
    Length:574
    Mass (Da):63,453
    Last modified:July 21, 1986 - v1
    Checksum:iA4066D9DC98933AA
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti102 – 1021P → A in strain: Cold-passage attenuated.
    Natural varianti218 – 2181E → A in strain: Cold-passage attenuated.
    Natural varianti379 – 3791I → V in strain: Cold-passage attenuated.
    Natural varianti447 – 4471M → V in strain: Cold-passage attenuated.
    Natural varianti523 – 5231T → I in strain: Cold-passage attenuated.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    PIRiA04035. VGNZA2.
    B28929.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    PIRi A04035. VGNZA2.
    B28929.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    4CCF X-ray 2.65 A/B/C/D/E/F 1-574 [» ]
    4JHW X-ray 3.60 F 26-513 [» ]
    4MMQ X-ray 3.25 A 26-107 [» ]
    B 137-513 [» ]
    4MMR X-ray 3.10 A 26-107 [» ]
    B 137-513 [» ]
    4MMS X-ray 2.40 A/C/E 26-107 [» ]
    B/D/F 137-513 [» ]
    4MMT X-ray 3.05 A 26-107 [» ]
    B 137-513 [» ]
    4MMU X-ray 3.00 A 26-107 [» ]
    B 137-513 [» ]
    4MMV X-ray 2.81 A 26-107 [» ]
    B 137-513 [» ]
    ProteinModelPortali P03420.
    SMRi P03420. Positions 158-207, 477-516.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-48772N.

    Protein family/group databases

    TCDBi 1.G.2.1.3. the viral pore-forming membrane fusion protein-2 (vmfp2) family.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P03420.

    Family and domain databases

    InterProi IPR000776. Fusion_F0_Paramyxovir.
    [Graphical view ]
    Pfami PF00523. Fusion_gly. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiFUS_HRSVA
    AccessioniPrimary (citable) accession number: P03420
    Secondary accession number(s): P88811
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: October 1, 2014
    This is version 92 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3