| Gene Name | PINK1 |
| HF Protein Name | PTEN-induced kinase 1 |
| HF Function | |
| Uniprot ID | P00995 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 6690 |
| Host Factor (HF) Name in Paper | PINK1 |
| Gene synonyms | PSTI |
| Ensemble Gene ID | ENSG00000164266 |
| Ensemble Transcript | ENST00000296695.10 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0004866, GO:0004867, GO:0007204, GO:0007263, GO:0010751, GO:0031667, GO:0045471, GO:0048240, GO:0050679, GO:0060046, GO:0070062, GO:0071375, GO:0090187, GO:0090277, GO:0090281, GO:2001256, |
| MINT ID | P00995 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 167790;167800;608189 |
| PANTHER ID | PTHR21312;PTHR21312:SF27 |
| PDB ID(s) | 1CGI, 1CGJ, 1HPT, 7QE8, 7QE9, |
| pfam ID | PF00050, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Japanese encephalitis virus |
| Virus Short Name | JEV |
| Order | Amarillovirales |
| Virus Family | Flaviviridae |
| Virus Subfamily | N.A. |
| Genus | Flavivirus |
| Species | Japanese encephalitis virus |
| Host | Vertebrates |
| Cell Tropism | |
| Associated Disease | Encephalitis |
| Mode of Transmission | Sexual contact, blood, breast feeding |
| VIPR DB link | https://www.viprbrc.org/brc/vipr_search.do?species=Japanese_encephalitis_virus |
| ICTV DB link | https://ictv.global/report/183/flaviviridae |
| Virus Host DB link |
| Paper Title | Japanese Encephalitis Virus NS4A Protein Interacts with PTEN-Induced Kinase 1 (PINK1) and Promotes Mitophagy in Infected Cells |
| Author's Name | Anshu Agarwal # 1, Mohd Faraz Alam # 2 3, Brohmomoy Basu 3, Sabyasachi Pattanayak 2, Shailendra Asthana 1, Gulam Hussain Syed 2, Manjula Kalia 1 3, Sudhanshu Vrati 1 3 |
| Journal Name | |
| Pubmed ID | 35604158 |
| Abstract | The nonstructural protein 4A (NS4A) of flaviviruses has been implicated as a "central organizer" of the membrane-bound replication complex during virus replication. However, its role in the host responses to virus infection is not understood. Using the yeast-two-hybrid library screen, we identified a multitude of host proteins interacting with the Japanese encephalitis virus (JEV) NS4A protein. Several of these interacting proteins are known to localize to the mitochondria. One of these proteins was PTEN-induced kinase 1 (PINK1), a serine/threonine-protein kinase known for its role in mitophagy. Here, we demonstrate the JEV-NS4A localization to the mitochondria and its interaction with PINK1 in Huh7 cells during JEV infection. The JEV-infected cells showed an enhanced mitophagy flux with a concomitant decline in the mitochondrial mass. We present data showing that JEV-NS4A alone was sufficient to induce mitophagy. Interference with mitochondrial fragmentation and mitophagy resulted in reduced virus propagation. Overall, our study provides the first evidence of mitochondrial quality control dysregulation during JEV infection, largely mediated by its NS4A protein. IMPORTANCE The JEV-infected mammalian cells show an enhanced mitophagy flux with a concomitant decline in the mitochondrial mass. We show that the NS4A protein of JEV localized to the mitochondria and interacted with PINK1 in Huh7 cells during infection with the virus and demonstrate that JEV-NS4A alone is sufficient to induce mitophagy. The study provides the first evidence of mitochondrial quality control dysregulation during JEV infection, largely mediated by its NS4A protein. |
| Used Model | NMY51,Y2H |
| DOI | 10.1128/spectrum.00830-22 |
