| Gene Name | AKR1C2 |
| HF Protein Name | Aldo-keto reductase family 1 member C2 |
| HF Function | Involved in Rotavirus cell entry |
| Uniprot ID | P52895 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 1646 |
| Host Factor (HF) Name in Paper | AKR1C2 |
| Gene synonyms | DDH2 |
| Ensemble Gene ID | ENSG00000151632 |
| Ensemble Transcript | ENST00000380753 [P52895-1];ENST00000455190 [P52895-2] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0004032, GO:0005737, GO:0006693, GO:0007186, GO:0007586, GO:0008202, GO:0008284, GO:0016655, GO:0018636, GO:0030855, GO:0031406, GO:0032052, GO:0042448, GO:0044597, GO:0044598, GO:0047086, GO:0047115, GO:0051897, GO:0055114, GO:0071395, GO:0071799, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 600450 |
| PANTHER ID | PTHR11732 |
| PDB ID(s) | 1IHI, 1J96, 1XJB, 2HDJ, 2IPJ, 4JQ1, 4JQ2, 4JQ3, 4JQ4, 4JQA, 4JTQ, 4JTR, 4L1W, 4L1X, 4XO6, 4XO7, |
| pfam ID | PF00248, |
| Drug Bank ID | DB03461, DB00157, DB01586, |
| ChEMBL ID | CHEMBL5847 |
| Organism | Homo sapiens (Human) |
| Virus Name | Rotavirus A |
| Virus Short Name | RVA |
| Order | Unassigned |
| Virus Family | Reoviridae |
| Virus Subfamily | Spinareovirinae |
| Genus | Rotavirus |
| Species | Rotavirus A |
| Host | Human, vertebrates |
| Cell Tropism | N.A. |
| Associated Disease | Gastroenteritis symptoms are principally induced by the viral enterotoxin nsp4 |
| Mode of Transmission | Fecal-oral |
| VIPR DB link | https://www.viprbrc.org/brc/home.spg?decorator=reo |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsrna-viruses-2011/w/dsrna_viruses/188/reoviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Reoviridae |
| Paper Title | Genome-wide RNAi screen reveals a role for the ESCRT complex in rotavirus cell entry |
| Author's Name | Daniela Silva-Ayala, Tomas Lopez, Michelle Gutierrez, Norbert Perrimon, Susana Lopez, and Carlos F. Arias |
| Journal Name | PNAS |
| Pubmed ID | 23733942 |
| Abstract | Rotavirus (RV) is the major cause of childhood gastroenteritis worldwide. This study presents a functional genome-scale analysis of cellular proteins and pathways relevant for RV infection using RNAi. Among the 522 proteins selected in the screen for their ability to affect viral infectivity, an enriched group that participates in endocytic processes was identified. Within these proteins, subunits of the vacuolar ATPase, small GTPases, actinin 4, and, of special interest, components of the endosomal sorting complex required for transport (ESCRT) machinery were found. Here we provide evidence for a role of the ESCRT complex in the entry of simian and human RV strains in both monkey and human epithelial cells. In addition, the ESCRT-associated ATPase VPS4A and phospholipid lysobisphosphatidic acid, both crucial for the formation of intralumenal vesicles in multivesicular bodies, were also found to be required for cell entry. Interestingly, it seems that regardless of the molecules that rhesus RV and human RV strains use for cell-surface attachment and the distinct endocytic pathway used, all these viruses converge in early endosomes and use multivesicular bodies for cell entry. Furthermore, the small GTPases RHOA and CDC42, which regulate different types of clathrin-independent endocytosis, as well as early endosomal antigen 1 (EEA1), were found to be involved in this process. This work reports the direct involvement of the ESCRT machinery in the life cycle of a nonenveloped virus and highlights the complex mechanism that these viruses use to enter cells. It also illustrates the efficiency of high-throughput RNAi screenings as genetic tools for comprehensively studying the interaction between viruses and their host cells. |
| Used Model | MA104 cells |
| DOI | 10.1073/pnas.1304932110 |
