| Gene Name | PTPA |
| HF Protein Name | Serine/threonine-protein phosphatase 2A activator |
| HF Function | Essential for virus replication |
| Uniprot ID | Q15257 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 5524 |
| Host Factor (HF) Name in Paper | PP1 |
| Gene synonyms | PPP2R4 |
| Ensemble Gene ID | ENSG00000119383 |
| Ensemble Transcript | ENST00000337738 [Q15257-1];ENST00000355007 [Q15257-4];ENST00000357197 [Q15257-3];ENST00000358994 [Q15257-2];ENST00000393370 [Q15257-2] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0000159, GO:0003755, GO:0005102, GO:0005524, GO:0005634, GO:0005654, GO:0005737, GO:0008160, GO:0019888, GO:0030472, GO:0032515, GO:0032516, GO:0034704, GO:0035307, GO:0035308, GO:0042803, GO:0043065, GO:0043666, GO:0046982, GO:0051721, GO:0070062, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 600756 |
| PANTHER ID | PTHR10012 |
| PDB ID(s) | 2G62, 2HV6, 2HV7, 2IXM, 4LAC, 4NY3, |
| pfam ID | PF03095, |
| Drug Bank ID | N.A., |
| ChEMBL ID | CHEMBL2505 |
| Organism | Homo sapiens (Human) |
| Virus Name | Human herpesvirus 1 |
| Virus Short Name | HSV1 |
| Order | Herpesvirales |
| Virus Family | Herpesviridae |
| Virus Subfamily | Alphaherpesvirinae |
| Genus | Simplexvirus |
| Species | Herpes simplex virus 1 |
| Host | Human, mammals |
| Cell Tropism | Primary site of infection: epithelial mucosal cells , latency: remains latent in sensory neurons (ganglions) |
| Associated Disease | Skin vesicles or mucosal ulcers, rarely encephalitis and meningitis |
| Mode of Transmission | Contact, saliva |
| VIPR DB link | http://www.viprbrc.org/brc/vipr_allSpecies_search.do?method=SubmitForm&decorator=herpes |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/91/herpesviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Herpesviridae |
| Paper Title | ICP345 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2 (eIF2 ) and protein phosphatase 2 |
| Author's Name | Yapeng Li, Cuizhu Zhang, Xiangdong Chen, Jia Yu, Yu Wang, Yin Yang , Mingjuan Du, Huali Jin , Yijie Ma, Bin He, and Youjia Cao |
| Journal Name | The Journal Of Biological Chemistry |
| Pubmed ID | 21622569 |
| Abstract | The ICP34.5 protein of herpes simplex virus type 1 is a neurovirulence factor that plays critical roles in viral replication and anti-host responses. One of its functions is to recruit protein phosphatase 1 (PP1) that leads to the dephosphorylation of the alpha subunit of translation initiation factor eIF2 (eIF2alpha), which is inactivated by infection-induced phosphorylation. As PP1 is a protein phosphatase with a wide range of substrates, the question remains to be answered how ICP34.5 directs PP1 to specifically dephosphorylate eIF2alpha. Here we report that ICP34.5 not only binds PP1 but also associates with eIF2alpha by in vitro and in vivo assays. The binding site of eIF2alpha is identified at amino acids 233-248 of ICP34.5, which falls in the highly homologous region with human gene growth arrest and DNA damage 34. The interaction between ICP34.5 and eIF2alpha is independent of the phosphorylation status of eIF2alpha at serine 51. Deletion mutation of this region results in the failure of dephosphorylation of eIF2alpha by PP1 and, consequently, interrupts viral protein synthesis and replication. Our data illustrated that the binding between viral protein ICP34.5 and the host eIF2alpha is crucial for the specific dephosphorylation of eIF2alpha by PP1. We propose that herpes simplex virus protein ICP34.5 bridges PP1 and eIF2alpha via their binding motifs and thereby facilitates the protein synthesis and viral replication. |
| Used Model | Vero, HeLa, and HEK293T cells |
| DOI | 10.1074/jbc.M111.232439 |
