| IED ID | IndEnz0002003198 |
| Enzyme Type ID | protease003198 |
| Protein Name |
Fusion glycoprotein F0 Cleaved into: Fusion glycoprotein F2 F2 ; p27 Intervening segment Pep27 Peptide 27 ; Fusion glycoprotein F1 F1 |
| Gene Name | F |
| Organism | Human respiratory syncytial virus A (strain A2) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Negarnaviricota Haploviricotina Monjiviricetes Mononegavirales Pneumoviridae Orthopneumovirus Human respiratory syncytial virus Human respiratory syncytial virus A Human respiratory syncytial virus A (strain A2) |
| Enzyme Sequence | MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPPTNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEINLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGMDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN |
| Enzyme Length | 574 |
| Uniprot Accession Number | P03420 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: [Fusion glycoprotein F0]: Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins. {ECO:0000269|PubMed:23593008}.; FUNCTION: [Fusion glycoprotein F1]: Class I viral fusion protein (PubMed:23618766). 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 (PubMed:23618766). During viral and plasma cell membrane fusion, the coiled coil regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain (PubMed:23618766, PubMed:19966279). The formation of this structure appears to drive apposition and subsequent fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm (PubMed:23593008, PubMed:23618766). This fusion is pH independent and occurs at the plasma or endosomal membrane (Probable). The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate (PubMed:10864656). F protein is involved in the entry into the host cell through the interaction with host IGFR1 (PubMed:32494007). This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1 (PubMed:32494007, PubMed:21841784). Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (PubMed:10438814). F protein may trigger p53-dependent apoptosis (PubMed:18216092). {ECO:0000269|PubMed:10438814, ECO:0000269|PubMed:10864656, ECO:0000269|PubMed:18216092, ECO:0000269|PubMed:19966279, ECO:0000269|PubMed:21841784, ECO:0000269|PubMed:23593008, ECO:0000269|PubMed:23618766, ECO:0000269|PubMed:32494007, ECO:0000305|PubMed:23593008, ECO:0000305|PubMed:30723301}.; FUNCTION: [Fusion glycoprotein F2]: Major determinant of the species specificity of RSV infection (PubMed:12663767). The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate (PubMed:10864656). F protein is involved in the entry into the host cell through the interaction with host IGFR1 (PubMed:32494007). This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1 (PubMed:32494007). Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (PubMed:10438814). F protein seems to trigger p53-dependent apoptosis (PubMed:18216092). {ECO:0000269|PubMed:10438814, ECO:0000269|PubMed:10864656, ECO:0000269|PubMed:12663767, ECO:0000269|PubMed:18216092, ECO:0000269|PubMed:32494007}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (27); Chain (3); Coiled coil (3); Disulfide bond (7); Glycosylation (6); Helix (17); Lipidation (1); Mutagenesis (18); Natural variant (5); Peptide (1); Region (1); Signal peptide (1); Site (2); Topological domain (2); Transmembrane (1); Turn (6) |
| Keywords | 3D-structure;Cleavage on pair of basic residues;Coiled coil;Direct protein sequencing;Disulfide bond;Fusion of virus membrane with host cell membrane;Fusion of virus membrane with host membrane;Glycoprotein;Host Golgi apparatus;Host cell membrane;Host membrane;Host-virus interaction;Lipoprotein;Membrane;Palmitate;Reference proteome;Signal;Syncytium formation induced by viral infection;Transmembrane;Transmembrane helix;Viral attachment to host cell;Viral attachment to host entry receptor;Viral envelope protein;Viral penetration into host cytoplasm;Virion;Virus entry into host cell |
| Interact With | Itself |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Fusion glycoprotein F0]: Host Golgi apparatus membrane {ECO:0000305|PubMed:16160180}; Single-pass membrane protein {ECO:0000269|PubMed:16160180}.; SUBCELLULAR LOCATION: [Fusion glycoprotein F1]: Virion membrane {ECO:0000269|PubMed:23776214}; Single-pass type I membrane protein {ECO:0000269|PubMed:16160180}. Host cell membrane {ECO:0000269|PubMed:16160180}; Single-pass membrane protein {ECO:0000269|PubMed:16160180}. Note=Localized at the host apical membrane. {ECO:0000269|PubMed:16160180}.; SUBCELLULAR LOCATION: [Fusion glycoprotein F2]: Virion membrane {ECO:0000269|PubMed:23776214}. Host cell membrane {ECO:0000305}. Note=Localized at the host apical membrane. {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Fusion glycoprotein F0]: The F glycoprotein is synthesized as a F0 inactive precursor that is heavily N-glycosylated and processed at two sites by a host furin-like protease probably in the Golgi (PubMed:11493675, PubMed:11369882, PubMed:23593008, PubMed:11418598). The cleavage site between p27 and F1 may occur after endocytosis to yield the mature F1 and F2 proteins (Probable). Both cleavages are required for membrane fusion and p27 is released from the processed protein (PubMed:11493675, PubMed:23593008, PubMed:12127793). {ECO:0000269|PubMed:11369882, ECO:0000269|PubMed:11418598, ECO:0000269|PubMed:11493675, ECO:0000269|PubMed:12127793, ECO:0000269|PubMed:23593008, ECO:0000305|PubMed:23593008}. |
| Signal Peptide | SIGNAL 1..25; /evidence=ECO:0000255 |
| Structure 3D | NMR spectroscopy (1); Electron microscopy (2); X-ray crystallography (63) |
| Cross Reference PDB | 2MDP; 3IXT; 3KPE; 3O41; 3O45; 3RKI; 3RRR; 3RRT; 4CCF; 4JHW; 4MMQ; 4MMR; 4MMS; 4MMT; 4MMU; 4MMV; 4ZYP; 5C69; 5C6B; 5EA3; 5EA4; 5EA5; 5EA6; 5EA7; 5EA8; 5J3D; 5K6B; 5K6C; 5K6F; 5K6G; 5K6H; 5K6I; 5KWW; 5TOJ; 5TOK; 5TPN; 5U68; 5UDC; 5W23; 6APB; 6APD; 6CXC; 6DC3; 6DC5; 6EAD; 6EAE; 6EAF; 6EAG; 6EAH; 6EAI; 6EAJ; 6EAK; 6EAL; 6EAM; 6EAN; 6NTX; 6OE4; 6OE5; 6OJ7; 6OUS; 6VKC; 6VKD; 6VKE; 6W52; 7LUE; 7MMN; |
| Mapped Pubmed ID | 20881049; 24760890; 26161532; 27791117; 31951396; 32407115; 33137810; 33823129; 34420474; |
| Motif | |
| Gene Encoded By | |
| Mass | 63,453 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |