ID   FUS_HRSVB               Reviewed;         574 AA.
AC   O36634;
DT   15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 89.
DE   RecName: Full=Fusion glycoprotein F0;
DE            Short=Protein F;
DE   Contains:
DE     RecName: Full=Fusion glycoprotein F2 {ECO:0000250|UniProtKB:P03420};
DE              Short=F2;
DE   Contains:
DE     RecName: Full=p27 {ECO:0000250|UniProtKB:P03420};
DE     AltName: Full=Intervening segment;
DE     AltName: Full=Pep27;
DE     AltName: Full=Peptide 27;
DE   Contains:
DE     RecName: Full=Fusion glycoprotein F1 {ECO:0000250|UniProtKB:P03420};
DE              Short=F1;
DE   Flags: Precursor;
GN   Name=F;
OS   Human respiratory syncytial virus B (strain B1).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus;
OC   Orthopneumovirus hominis.
OX   NCBI_TaxID=79692;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9391135; DOI=10.1073/pnas.94.25.13961;
RA   Karron R.A., Buonagurio D.A., Georgiu A.F., Whitehead S.S., Adamus J.E.,
RA   Clements-Mann M.L., Harris D.O., Randolph V.B., Udem S.A., Murphy B.R.,
RA   Sidhu M.S.;
RT   "Respiratory syncytial virus (RSV) SH and G proteins are not essential for
RT   viral replication in vitro: clinical evaluation and molecular
RT   characterization of a cold-passaged, attenuated RSV subgroup B mutant.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:13961-13966(1997).
RN   [2]
RP   PALMITOYLATION AT CYS-550.
RX   PubMed=2732224; DOI=10.1016/s0021-9258(18)81623-4;
RA   Arumugham R.G., Seid R.C. Jr., Doyle S., Hildreth S.W., Paradisio P.R.;
RT   "Fatty acid acylation of the fusion glycoprotein of human respiratory
RT   syncytial virus.";
RL   J. Biol. Chem. 264:10339-10342(1989).
CC   -!- FUNCTION: [Fusion glycoprotein F0]: Inactive precursor that is cleaved
CC       at two sites by a furin-like protease to give rise to the mature F1 and
CC       F2 fusion glycoproteins. {ECO:0000250|UniProtKB:P03420}.
CC   -!- FUNCTION: [Fusion glycoprotein F1]: Class I viral fusion protein. Under
CC       the current model, the protein has at least 3 conformational states:
CC       pre-fusion native state, pre-hairpin intermediate state, and post-
CC       fusion hairpin state. During viral and plasma cell membrane fusion, the
CC       coiled coil regions assume a trimer-of-hairpins structure, positioning
CC       the fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and cellular membranes leading to
CC       delivery of the nucleocapsid into the cytoplasm. This fusion is pH
CC       independent and occurs at the plasma or endosomal membrane. The trimer
CC       of F1-F2 (F protein) also facilitates the attachment to host cell by
CC       binding to host heparan sulfate. F protein is involved in the entry
CC       into the host cell through the interaction with host IGF1R. This
CC       interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to
CC       the apical cell surface where it can bind fusion glycoprotein F1. Later
CC       in infection, F protein expressed at the plasma membrane of infected
CC       cells can mediate fusion with adjacent cells to form syncytia, a
CC       cytopathic effect that could lead to tissue necrosis. F protein may
CC       trigger p53-dependent apoptosis. {ECO:0000250|UniProtKB:P03420}.
CC   -!- FUNCTION: [Fusion glycoprotein F2]: Major determinant of the species
CC       specificity of RSV infection. The trimer of F1-F2 (F protein) also
CC       facilitates the attachment to host cell by binding to host heparan
CC       sulfate. F protein is involved in the entry into the host cell through
CC       the interaction with host IGF1R. This interaction activates
CC       PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell
CC       surface where it can bind fusion glycoprotein F1. Later in infection, F
CC       protein expressed at the plasma membrane of infected cells can mediate
CC       fusion with adjacent cells to form syncytia, a cytopathic effect that
CC       could lead to tissue necrosis. F protein seems to trigger p53-dependent
CC       apoptosis. {ECO:0000250|UniProtKB:P03420}.
CC   -!- SUBUNIT: [Fusion glycoprotein F1]: Homotrimer. Heterodimer with fusion
CC       protein F2; disulfide-linked. Interacts with host NCL; this interaction
CC       plays a role in viral entry into the host cell. As a heterodimer with
CC       F2, interacts with host heparan sulfate. As a heterodimer with F2,
CC       interacts with host IGF1R; this interaction activates PRKCZ/PKCzeta
CC       that recruits NCL/nucleolin from the host nucleus to the plasma
CC       membrane. Part of a complex composed of F1, F2 and G glycoproteins. As
CC       a heterodimer with F2, interacts with host RHOA; this interaction
CC       facilitates virus-induced syncytium formation.
CC       {ECO:0000250|UniProtKB:P03420}.
CC   -!- SUBUNIT: [Fusion glycoprotein F2]: Homotrimer. Heterodimer with fusion
CC       protein F1; disulfide-linked. As a heterodimer with F1, interacts with
CC       host heparan sulfate. As a heterodimer with F1, interacts with host
CC       IGF1R; this interaction activates PRKCZ/PKCzeta that recruits
CC       NCL/nucleolin from the host nucleus to the plasma membrane. Part of a
CC       complex composed of F1, F2 and G glycoproteins. As a heterodimer with
CC       F1, interacts with host RHOA; this interaction facilitates virus-
CC       induced syncytium formation. {ECO:0000250|UniProtKB:P03420}.
CC   -!- SUBCELLULAR LOCATION: [Fusion glycoprotein F0]: Host Golgi apparatus
CC       membrane {ECO:0000250|UniProtKB:P03420}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:P03420}.
CC   -!- SUBCELLULAR LOCATION: [Fusion glycoprotein F1]: Virion membrane
CC       {ECO:0000250|UniProtKB:P03420}; Single-pass type I membrane protein
CC       {ECO:0000250|UniProtKB:P03420}. Host cell membrane
CC       {ECO:0000250|UniProtKB:P03420}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:P03420}. Note=Localized at the host apical
CC       membrane. {ECO:0000250|UniProtKB:P03420}.
CC   -!- SUBCELLULAR LOCATION: [Fusion glycoprotein F2]: Virion membrane
CC       {ECO:0000250|UniProtKB:P03420}. Host cell membrane
CC       {ECO:0000250|UniProtKB:P03420}. Note=Localized at the host apical
CC       membrane. {ECO:0000250|UniProtKB:P03420}.
CC   -!- DOMAIN: [Fusion glycoprotein F0]: The N-terminus is a hydrophobic
CC       fusion peptide that inserts into the target host membrane (By
CC       similarity). It is buried in the center of the trimer cavity before
CC       cleavage by host furin. The coiled coil (heptad repeat) regions are
CC       probably involved in homotrimerization, heterodimerization and in the
CC       formation of a fusion-active hairpin structure (By similarity).
CC       {ECO:0000250|UniProtKB:P03420, ECO:0000250|UniProtKB:P11209}.
CC   -!- DOMAIN: [Fusion glycoprotein F1]: The N-terminus is a hydrophobic
CC       fusion peptide that inserts into the target host membrane (By
CC       similarity). It is buried in the center of the trimer cavity before
CC       cleavage by host furin. The coiled coil (heptad repeat) regions are
CC       probably involved in homotrimerization, heterodimerization and in the
CC       formation of a fusion-active hairpin structure (By similarity).
CC       {ECO:0000250|UniProtKB:P03420, ECO:0000250|UniProtKB:P11209}.
CC   -!- PTM: [Fusion glycoprotein F0]: The F glycoprotein is synthesized as a
CC       F0 inactive precursor that is heavily N-glycosylated and processed at
CC       two sites by a host furin-like protease probably in the Golgi. The
CC       cleavage site between p27 and F1 may occur after endocytosis to yield
CC       the mature F1 and F2 proteins. Both cleavages are required for membrane
CC       fusion and p27 is released from the processed protein.
CC       {ECO:0000250|UniProtKB:P03420}.
CC   -!- SIMILARITY: Belongs to the paramyxoviruses fusion glycoprotein family.
CC       {ECO:0000305}.
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DR   EMBL; AF013254; AAB82436.1; -; Genomic_RNA.
DR   RefSeq; NP_056863.1; NC_001781.1.
DR   SMR; O36634; -.
DR   GlyCosmos; O36634; 6 sites, No reported glycans.
DR   ABCD; O36634; 3 sequenced antibodies.
DR   GeneID; 1489825; -.
DR   KEGG; vg:1489825; -.
DR   Proteomes; UP000002472; Segment.
DR   GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C: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:0098670; P:entry receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-KW.
DR   GO; GO:0060141; P:positive regulation of syncytium formation by virus; IEA:UniProtKB-KW.
DR   GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.287.2480; -; 2.
DR   Gene3D; 6.10.250.1160; -; 1.
DR   Gene3D; 6.20.370.50; -; 1.
DR   InterPro; IPR000776; Fusion_F0_Paramyxovir.
DR   Pfam; PF00523; Fusion_gly; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 2.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host cell membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host Golgi apparatus; Host membrane;
KW   Host-virus interaction; Lipoprotein; Membrane; Palmitate;
KW   Reference proteome; Signal; Syncytium formation induced by viral infection;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral attachment to host entry receptor; Viral envelope protein;
KW   Viral penetration into host cytoplasm; Virion; Virus entry into host cell.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..574
FT                   /note="Fusion glycoprotein F0"
FT                   /id="PRO_0000390376"
FT   CHAIN           26..109
FT                   /note="Fusion glycoprotein F2"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT                   /id="PRO_0000390377"
FT   PEPTIDE         110..136
FT                   /note="p27"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT                   /id="PRO_0000432668"
FT   CHAIN           137..574
FT                   /note="Fusion glycoprotein F1"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT                   /id="PRO_0000390378"
FT   TOPO_DOM        26..524
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   TRANSMEM        525..550
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   TOPO_DOM        551..574
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   REGION          137..157
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000250|UniProtKB:P11209"
FT   COILED          76..96
FT                   /evidence="ECO:0000250|UniProtKB:P11209"
FT   COILED          158..209
FT                   /evidence="ECO:0000250|UniProtKB:P11209"
FT   COILED          481..516
FT                   /evidence="ECO:0000250|UniProtKB:P11209"
FT   SITE            109..110
FT                   /note="Cleavage; by host furin-like protease"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   SITE            136..137
FT                   /note="Cleavage; by host furin-like protease"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   LIPID           550
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000269|PubMed:2732224"
FT   CARBOHYD        27
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   CARBOHYD        70
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   CARBOHYD        116
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        126
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        500
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   DISULFID        37..439
FT                   /note="Interchain (between F2 and F1 chains)"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   DISULFID        69..212
FT                   /note="Interchain (between F2 and F1 chains)"
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   DISULFID        313..343
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   DISULFID        322..333
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   DISULFID        358..367
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   DISULFID        382..393
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
FT   DISULFID        416..422
FT                   /evidence="ECO:0000250|UniProtKB:P03420"
SQ   SEQUENCE   574 AA;  63710 MW;  29A127B128BF5E92 CRC64;
     MELLIHRLSA IFLTLAINAL YLTSSQNITE EFYQSTCSAV SRGYFSALRT GWYTSVITIE
     LSNIKETKCN GTDTKVKLIK QELDKYKNAV TELQLLMQNT PAANNRARRE APQYMNYTIN
     TTKNLNVSIS KKRKRRFLGF LLGVGSAIAS GIAVSKVLHL EGEVNKIKNA LLSTNKAVVS
     LSNGVSVLTS KVLDLKNYIN NQLLPIVNQQ SCRISNIETV IEFQQKNSRL LEINREFSVN
     AGVTTPLSTY MLTNSELLSL INDMPITNDQ KKLMSSNVQI VRQQSYSIMS IIKEEVLAYV
     VQLPIYGVID TPCWKLHTSP LCTTNIKEGS NICLTRTDRG WYCDNAGSVS FFPQADTCKV
     QSNRVFCDTM NSLTLPSEVS LCNTDIFNSK YDCKIMTSKT DISSSVITSL GAIVSCYGKT
     KCTASNKNRG IIKTFSNGCD YVSNKGVDTV SVGNTLYYVN KLEGKNLYVK GEPIINYYDP
     LVFPSDEFDA SISQVNEKIN QSLAFIRRSD ELLHNVNTGK STTNIMITTI IIVIIVVLLS
     LIAIGLLLYC KAKNTPVTLS KDQLSGINNI AFSK
//