| Gene Name | MKRN3 |
| HF Protein Name | Probable E3 ubiquitin-protein ligase makorin-3 |
| HF Function | Essential for viral replication |
| Uniprot ID | Q13064 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 7681 |
| Host Factor (HF) Name in Paper | MKRN3 |
| Gene synonyms | D15S9 RNF63 ZNF127 |
| Ensemble Gene ID | ENSG00000179455 |
| Ensemble Transcript | ENST00000314520 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0016567, GO:0016740, GO:0030529, GO:0042802, GO:0046872, |
| MINT ID | Q13064 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 603856 |
| PANTHER ID | PTHR11224:SF38 |
| PDB ID(s) | N.A., |
| pfam ID | PF15815, PF00097, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Human SARS coronavirus |
| Virus Short Name | SARS-CoV |
| Order | Nidovirales |
| Virus Family | Coronaviridae |
| Virus Subfamily | Coronavirinae |
| Genus | Betacoronavirus |
| Species | Betacoronavirus 1 |
| Host | Bats, human |
| Cell Tropism | Epithelial cells of respiratory or enteric tracts, neurological tissues are also frequently infected |
| Associated Disease | Mainly respiratory diseases |
| 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 | The SARS-coronavirus-host Interactome: Identification of cyclophilins as Target for Pan Coronavirus Inhibitors |
| Author's Name | Susanne Pfefferle, Julia Schopf, Manfred Kogl, Caroline C. Friedel, Marcel A. Muller, Javier Carbajo-Lozoya, Thorsten Stellberger, Ekatarina von DallArmi, Petra Herzog, Stefan Kallies, Daniela Niemeyer, Vanessa Ditt, Thomas Kuri, Roland Zust, Ksenia Pumpor, Rolf Hilgenfeld, Frank Schwarz, Ralf Zimmer, Imke Steffen, Friedemann Weber, Volker Thiel, Georg Herrler, Heinz-Jurgen Thiel,Christel Schwegmann-WeÃels, Stefan Pohlmann, Jurgen Haas, Christian Drosten, and Albrecht von Brunn |
| Journal Name | PLoS PATHOGENS |
| Pubmed ID | 22046132 |
| Abstract | Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock. |
| Used Model | HEK293, HEK293lp (low passage), Vero E6, CaCo-2, HRT 18, Huh 7, FCWF- and St-cells |
| DOI | 10.1371/journal.ppat.1002331 |
