| Gene Name | KHDRBS1 |
| HF Protein Name | KH domain-containing, RNA-binding, signal transduction-associated protein 1 |
| HF Function | Positively regulates viral protein translation |
| Uniprot ID | Q07666 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 10657 |
| Host Factor (HF) Name in Paper | SAM68 |
| Gene synonyms | SAM68 |
| Ensemble Gene ID | ENSG00000121774 |
| Ensemble Transcript | ENST00000327300 [Q07666-1];ENST00000492989 [Q07666-3] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000086, GO:0003677, GO:0003723, GO:0005070, GO:0005634, GO:0005654, GO:0005829, GO:0006351, GO:0006397, GO:0007050, GO:0007165, GO:0007166, GO:0007283, GO:0008143, GO:0008266, GO:0008283, GO:0016020, GO:0017124, GO:0019904, GO:0042802, GO:0045892, GO:0045948, GO:0046831, GO:0046833, GO:0048024, GO:0051259, GO:0070618, |
| MINT ID | Q07666 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 602489 |
| PANTHER ID | N.A. |
| PDB ID(s) | 2XA6, 3QHE, |
| pfam ID | PF00013, PF16274, PF16568, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Enterovirus 71 |
| Virus Short Name | EV-71 |
| Order | Picornavirales |
| Virus Family | Picornaviridae |
| Virus Subfamily | N.A. |
| Genus | Enterovirus |
| Species | Enterovirus A |
| Host | Human, mammals |
| Cell Tropism | The gastrointestinal trac |
| Associated Disease | Hand, foot and mouth disease, meningitis |
| Mode of Transmission | Either fecal-oral or respiratory |
| VIPR DB link | https://www.viprbrc.org/brc/home.spg?decorator=picorna |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/234/picornaviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Picornaviridae |
| Paper Title | Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation |
| Author's Name | Hua Zhang, Lei Song, Haolong Cong, Po Tien |
| Journal Name | JOURNAL OF VIROLOGY |
| Pubmed ID | 26202240 |
| Abstract | Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5 untranslated region (5UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. IMPORTANCE: The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially enhance the translation of virus protein. To our knowledge, this is the first report that describes Sam68 actively participating in the life cycle of EV71 at a molecular level. These studies will not only improve our understanding of the replication of EV71 but also have the potential for aiding in developing a therapeutic strategy against EV71 infection. |
| Used Model | HeLa, U251, RD cells |
| DOI | 10.1128/JVI.01677-15 |
