Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person MAGUK p55 subfamily member 5 (MPP5, also known as PALS1), a ...
| Class:Id | Summation:9689614 |
|---|---|
| _displayName | MAGUK p55 subfamily member 5 (MPP5, also known as PALS1), a ... |
| _timestamp | 2022-03-01 03:07:58 |
| created | [InstanceEdit:9689615] Shamovsky, Veronica, 2020-05-21 |
| literatureReference | [LiteratureReference:9696717] The SARS coronavirus E protein interacts with PALS1 and alters tight junction formation and epithelial morphogenesis [LiteratureReference:9696713] The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis [LiteratureReference:9704960] Coronavirus envelope (E) protein remains at the site of assembly [LiteratureReference:9704980] Comparing the binding properties of peptides mimicking the Envelope protein of SARS-CoV and SARS-CoV-2 to the PDZ domain of the tight junction-associated PALS1 protein [LiteratureReference:9704985] A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2 [LiteratureReference:9704956] Molecular phylogeny and missense mutations of envelope proteins across coronaviruses [LiteratureReference:9704966] Is There a Link Between the Pathogenic Human Coronavirus Envelope Protein and Immunopathology? A Review of the Literature [LiteratureReference:9704978] Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis |
| modified | [InstanceEdit:9696721] Shamovsky, Veronica, 2020-07-28 [InstanceEdit:9704965] Shamovsky, Veronica, 2020-10-15 [InstanceEdit:9710586] Shamovsky, Veronica, 2021-01-05 [InstanceEdit:9713608] Shamovsky, Veronica, 2021-01-27 [InstanceEdit:9767623] Shamovsky, Veronica, 2022-03-01 |
| text | MAGUK p55 subfamily member 5 (MPP5, also known as PALS1), a tight junction‑associated protein, is a member of the CRUMBS3:MPP5:PATJ polarity complex, which is crucial for the establishment and maintenance of epithelial polarity in mammals. MPP5 has multiple protein‑protein interaction domains including a PSD‑95/Dlg/ZO‑1 (PDZ) domain. A functional PDZ domain‑binding motif has been identified at the carboxy‑terminus of severe acute respiratory syndrome coronavirus type 1 (SARS‑CoV‑1) envelope (E) protein (Teoh KT et al. 2010; Jimenez‑Guardeño JM et al. 2014). SARS‑CoV‑1 E is abundantly expressed inside the infected cell and is involved in pathogenic viral mechanisms (Venkatagopalan P et al. 2015). Infection of mice with recombinant viruses lacking an E protein PDZ domain‑binding motif was associated with decreased expression of inflammatory cytokines and increased survival (Jimenez‑Guardeño JM et al. 2014). SARS‑CoV‑1 E was found to interfere with host PDZ‐dependent interactions of MPP5, thus favoring viral replication (Teoh KT et al. 2010). Coimmunoprecipitation and pull‑down assays showed that the viral E protein interacted with MPP5 in human embryonic kidney 293T (HEK293T) and African green monkey kidney Vero E6 cells (Teoh KT et al. 2010). The last four carboxy‑terminal amino acids (DLLV) of E interacted with the PDZ domain of MPP5 (Teoh KT et al. 2010). Immunofluorescence assay showed that MPP5 was mainly localized at cell‑cell junctions in monolayers of non infected Vero E6 cells, while the binding of SARS‑CoV‑1 E to MPP5 (PALS1) redistributed MPP5 from the tight junctions of the lung epithelium to the ER‑Golgi intermediate compartment (ERGIC) where E assembles in SARS‑CoV‑1‑infected cells (Teoh KT et al. 2010). Ectopic expression of E in Madin‑Darby canine kidney II (MDCKII) epithelial cells altered cyst morphogenesis, delayed formation of tight junctions, affected cell polarity, and modified the subcellular distribution of PALS1, in a PDZ‑binding motif‑dependent manner (Teoh KT et al. 2010). These findings suggest that SARS‑CoV‑1 E interacts with MPP5 (PALS1) and most likely retains MPP5 at the virus assembly site in mammalian cells. However, the relevance of this interaction during virus infection and its impact on virulence in vivo was not tested. A sequence comparison of the E proteins of the pathogenic human CoVs, SARS‑CoV‑1, MERS‑CoV, and SARS‑CoV‑2, demonstrated a very high sequence similarity between SARS‑CoV‑1 E and SARS‑CoV‑2 E (Grifoni A et al. 2020; Schoeman D & Fielding BC 2020; Hassan SS et al. 2020). This similarity is not shared with the MERS‑CoV E protein (Schoeman D & Fielding BC 2020). In silico modelling analyses of E proteins conformation and docking suggested a strengthened binding of SARS‑CoV‑2 E protein with the tight junction‑associated MPP5 protein (De Maio F et al. 2020). Equilibrium and kinetic binding experiments between peptides mimicking the E protein of SARS‑CoV‑1 and SARS‑CoV‑2 and the PDZ domain of MPP5 further support that the binding affinity of SARS‑CoV‑2 E protein for MPP5 is increased compared to SARS-CoV-1 E protein (Toto A et al. 2020). |
| (summation) | [Reaction:9689608] MPP5 binds SARS-CoV-1 E pentamer [Homo sapiens] |
| [Change default viewing format] | |
