| Gene Name | GRK2 |
| HF Protein Name | Beta-adrenergic receptor kinase 1 |
| HF Function | Promotes YFV entry and replication |
| Uniprot ID | P25098 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 156 |
| Host Factor (HF) Name in Paper | GRK2 |
| Gene synonyms | ADRBK1 BARK BARK1 |
| Ensemble Gene ID | ENSG00000173020 |
| Ensemble Transcript | ENST00000308595 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0002029, GO:0003108, GO:0004672, GO:0004703, GO:0005524, GO:0005737, GO:0005829, GO:0005886, GO:0005929, GO:0007186, GO:0007213, GO:0007217, GO:0007507, GO:0016020, GO:0018105, GO:0018107, GO:0019079, GO:0031623, GO:0031694, GO:0031755, GO:0033605, GO:0045988, GO:0046718, GO:0047696, GO:0060048, |
| MINT ID | P25098 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 109635 |
| PANTHER ID | N.A. |
| PDB ID(s) | 1BAK, 3CIK, 3KRW, 3KRX, 3V5W, 4MK0, 4PNK, 5HE1, 5UKK, 5UKL, 5UUU, 5UVC, 5WG3, 5WG4, 5WG5, |
| pfam ID | PF00169, PF00069, PF00615, |
| Drug Bank ID | DB00171, |
| ChEMBL ID | CHEMBL4079 |
| Organism | Homo sapiens (Human) |
| Virus Name | Yellow fever virus |
| Virus Short Name | YFV |
| Order | Unassigned |
| Virus Family | Flaviviridae |
| Virus Subfamily | N.A. |
| Genus | Flavivirus |
| Species | Yellow fever virus |
| Host | Human, mammals, mosquitoes and ticks |
| Cell Tropism | N.A. |
| Associated Disease | Hemorrhagic fever, encephalitis |
| Mode of Transmission | Arthropod bite, mainly mosquitoes |
| VIPR DB link | http://www.viprbrc.org/brc/home.spg?decorator=flavi |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/flaviviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Flaviviridae |
| Paper Title | G protein-coupled receptor kinase 2 promotes flaviviridae entry and replication |
| Author's Name | Caroline Le Sommer, Nicholas J. Barrows, Shelton S. Bradrick, James L. Pearson, Mariano A. Garcia-Blanco |
| Journal Name | PLOS Neglected Tropical Diseases |
| Pubmed ID | 23029581 |
| Abstract | Flaviviruses cause a wide range of severe diseases ranging from encephalitis to hemorrhagic fever. Discovery of host factors that regulate the fate of flaviviruses in infected cells could provide insight into the molecular mechanisms of infection and therefore facilitate the development of anti-flaviviral drugs. We performed genome-scale siRNA screens to discover human host factors required for yellow fever virus (YFV) propagation. Using a 2 × 2 siRNA pool screening format and a duplicate of the screen, we identified a high confidence list of YFV host factors. To find commonalities between flaviviruses, these candidates were compared to host factors previously identified for West Nile virus (WNV) and dengue virus (DENV). This comparison highlighted a potential requirement for the G protein-coupled receptor kinase family, GRKs, for flaviviral infection. The YFV host candidate GRK2 (also known as ADRBK1) was validated both in siRNA-mediated knockdown HuH-7 cells and in GRK(-/-) mouse embryonic fibroblasts. Additionally, we showed that GRK2 was required for efficient propagation of DENV and Hepatitis C virus (HCV) indicating that GRK2 requirement is conserved throughout the Flaviviridae. Finally, we found that GRK2 participates in multiple distinct steps of the flavivirus life cycle by promoting both entry and RNA synthesis. Together, our findings identified GRK2 as a novel regulator of flavivirus infection and suggest that inhibition of GRK2 function may constitute a new approach for treatment of flavivirus associated diseases. |
| Used Model | HuH-7 cells and Vero cells |
| DOI | 10.1371/journal.pntd.0001820 |
