| Gene Name | POLK |
| HF Protein Name | DNA polymerase kappa |
| HF Function | Makes covalently close circular DNA of Hepatitis B Virus |
| Uniprot ID | Q9UBT6 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 51426 |
| Host Factor (HF) Name in Paper | POLK |
| Gene synonyms | DINB1 |
| Ensemble Gene ID | ENSG00000122008 |
| Ensemble Transcript | ENST00000241436 [Q9UBT6-1];ENST00000504026 [Q9UBT6-6];ENST00000508526 [Q9UBT6-3];ENST00000509126 [Q9UBT6-5];ENST00000510815 [Q9UBT6-4];ENST00000515295 [Q9UBT6-2] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0003684, GO:0003887, GO:0005654, GO:0006260, GO:0006281, GO:0006283, GO:0006296, GO:0006297, GO:0006974, GO:0016604, GO:0019985, GO:0033683, GO:0034644, GO:0042276, GO:0046872, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 605650 |
| PANTHER ID | N.A. |
| PDB ID(s) | 1T94, 2LSI, 2OH2, 2W7O, 2W7P, 3IN5, 3PZP, 4BA9, 4GK5, 4U6P, 4U7C, 5T14, 5W2A, 5W2C, |
| pfam ID | PF00817, PF11799, PF11798, |
| Drug Bank ID | DB08237, |
| ChEMBL ID | CHEMBL5365 |
| Organism | Homo sapiens (Human) |
| Virus Name | Hepatitis B virus |
| Virus Short Name | HBV |
| Order | Unassigned |
| Virus Family | Hepadnaviridae |
| Virus Subfamily | N.A. |
| Genus | Orthohepadnavirus |
| Species | Hepatitis B virus |
| Host | Human, mammals |
| Cell Tropism | Hepatocytes |
| Associated Disease | Hepatitis, hepatocellular carcinoma(chronic infections), cirrhosis |
| Mode of Transmission | Sexual contact, blood, maternal-neonatal |
| VIPR DB link | N.A. |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/reverse-transcribing-dna-and-rna-viruses-2011/w/rt_viruses/155/hepadnaviridae |
| Virus Host DB link | N.A. |
| Paper Title | DNA Polymerase ? Is a Key Cellular Factor for the Formation of Covalently Closed Circular DNA of Hepatitis B Virus |
| Author's Name | Yonghe Qi, Zhenchao Gao, Guangwei Xu, Bo Peng, Chenxuan Liu, Huan Yan, Qiyan Yao, Guoliang Sun, Yang Liu, Dingbin Tang, Zilin Song, Wenhui He, Yinyan Sun, Ju-Tao Guo, Wenhui Li |
| Journal Name | PLOS Pathogens |
| Pubmed ID | 27783675 |
| Abstract | Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined. Here we conducted targeted genetic screening in combination with chemical inhibition to identify the cellular DNA polymerase(s) responsible for cccDNA formation, and exploited recombinant HBV with capsid coding deficiency which infects HepG2-NTCP cells with similar efficiency of wild-type HBV to assure cccDNA synthesis is exclusively from de novo HBV infection. We found that DNA polymerase κ (POLK), a Y-family DNA polymerase with maximum activity in non-dividing cells, substantially contributes to cccDNA formation during de novo HBV infection. Depleting gene expression of POLK in HepG2-NTCP cells by either siRNA knockdown or CRISPR/Cas9 knockout inhibited the conversion of rcDNA into cccDNA, while the diminished cccDNA formation in, and hence the viral infection of, the knockout cells could be effectively rescued by ectopic expression of POLK. These studies revealed that POLK is a crucial host factor required for cccDNA formation during a de novo HBV infection and suggest that POLK may be a potential target for developing antivirals against HBV. |
| Used Model | HepG2 and 293T cells |
| DOI | 10.1371/journal.ppat.1005893 |
