| Gene Name | TMPRSS2 |
| HF Protein Name | Transmembrane protease serine 2 |
| HF Function | Activates Coronavirus for Cathepsin independent host cell entry |
| Uniprot ID | O15393 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 7113 |
| Host Factor (HF) Name in Paper | TMPRSS2 |
| Gene synonyms | PRSS10 |
| Ensemble Gene ID | ENSG00000184012 |
| Ensemble Transcript | ENST00000332149 [O15393-1];ENST00000398585 [O15393-2];ENST00000458356 [O15393-1] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0004252, GO:0005044, GO:0005886, GO:0005887, GO:0006508, GO:0008236, GO:0016540, GO:0046598, GO:0070062, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 602060 |
| PANTHER ID | N.A. |
| PDB ID(s) | N.A., |
| pfam ID | PF15494, PF00089, |
| Drug Bank ID | N.A., |
| ChEMBL ID | CHEMBL1795140 |
| Organism | Homo sapiens (Human) |
| Virus Name | Human coronavirus 229E |
| Virus Short Name | HCoV-229E |
| Order | Nidovirales |
| Virus Family | Coronaviridae |
| Virus Subfamily | Coronavirinae |
| Genus | Alphacoronavirus |
| Species | Alphacoronavirus 1 |
| Host | Human, pig, cat, dog and bat |
| Cell Tropism | Epithelial cells of respiratory or enteric tracts, neurological tissues are also frequently infected |
| Associated Disease | Mainly respiratory diseases, and gastroenteritis |
| Mode of Transmission | Respiratory or fecal-oral in humans |
| VIPR DB link | https://www.viprbrc.org/brc/vipr_allSpecies_search.spg?method=SubmitForm&decorator=corona |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/222/coronaviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Coronaviridae |
| Paper Title | TMPRSS2 Activates the Human coronavirus 229E for cathepsin Independent Host cell entry and Is Expressed in viral target cells in the respiratory epithelium |
| Author's Name | Stephanie Bertram, Ronald Dijkman, Matthias Habjan, Adeline Heurich, Stefanie Gierer, Ilona Glowacka, Kathrin Welsch, Michael Winkler, Heike Schneider, Heike Hofmann-Winkler, Volker Thiel, and Stefan Pohlmann |
| Journal Name | JOURNAL OF VIROLOGY |
| Pubmed ID | 23536651 |
| Abstract | Infection with human coronavirus 229E (HCoV-229E) is associated with the common cold and may result in pneumonia in immunocompromised patients. The viral spike (S) protein is incorporated into the viral envelope and mediates infectious entry of HCoV-229E into host cells, a process that depends on the activation of the S-protein by host cell proteases. However, the proteases responsible for HCoV-229E activation are incompletely defined. Here we show that the type II transmembrane serine proteases TMPRSS2 and HAT cleave the HCoV-229E S-protein (229E-S) and augment 229E-S-driven cell-cell fusion, suggesting that TMPRSS2 and HAT can activate 229E-S. Indeed, engineered expression of TMPRSS2 and HAT rendered 229E-S-driven virus-cell fusion insensitive to an inhibitor of cathepsin L, a protease previously shown to facilitate HCoV-229E infection. Inhibition of endogenous cathepsin L or TMPRSS2 demonstrated that both proteases can activate 229E-S for entry into cells that are naturally susceptible to infection. In addition, evidence was obtained that activation by TMPRSS2 rescues 229E-S-dependent cell entry from inhibition by IFITM proteins. Finally, immunohistochemistry revealed that TMPRSS2 is coexpressed with CD13, the HCoV-229E receptor, in human airway epithelial (HAE) cells, and that CD13+Â TMPRSS2+Â cells are preferentially targeted by HCoV-229E, suggesting that TMPRSS2 can activate HCoV-229E in infected humans. In sum, our results indicate that HCoV-229E can employ redundant proteolytic pathways to ensure its activation in host cells. In addition, our observations and previous work suggest that diverse human respiratory viruses are activated by TMPRSS2, which may constitute a target for antiviral intervention. |
| Used Model | Caco-2 cells and 293T cells |
| DOI | 10.1128/JVI.03372-12 |
