SPARQL | HTML5 RDFa and Microdata document
http://rdf.wikipathways.org/Pathway/WP4861_r140454/Complex/d477c http://rdf.wikipathways.org/Pathway/WP4861_r140454/Complex/df8e0 http://rdf.wikipathways.org/Pathway/WP4861_r140454/Complex/f8553 http://rdf.wikipathways.org/Pathway/WP4861_r140454/Complex/fbd45 http://rdf.wikipathways.org/Pathway/WP4861_r140454/ComplexBinding/d477c http://rdf.wikipathways.org/Pathway/WP4861_r140454/ComplexBinding/df8e0 http://rdf.wikipathways.org/Pathway/WP4861_r140454/ComplexBinding/f8553 http://rdf.wikipathways.org/Pathway/WP4861_r140454/ComplexBinding/fbd45 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/fc5c1 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id315b7e46 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id334c961f http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id36593f74 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id3b399cfb http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id5555a7cf http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id74bb08d8 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id7f19c7ea http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id7f4a3b95 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/id8122cdf4 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/ida575a860 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/idad3f9625 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/idb174dd6a http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/idc828ca15 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/idda829af2 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/iddbc481e4 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/iddcd631b5 http://rdf.wikipathways.org/Pathway/WP4861_r140454/WP/Interaction/ided8176a0 https://identifiers.org/wikipathways/WP4861_r140454
http://www.w3.org/1999/02/22-rdf-syntax-ns#type
http://www.w3.org/2004/02/skos/core#Collection
http://vocabularies.wikipathways.org/wp#Pathway
http://xmlns.com/foaf/0.1/page
http://www.wikipathways.org/instance/WP4861_r140454
http://purl.org/dc/elements/1.1/identifier
https://identifiers.org/wikipathways/WP4861
http://purl.org/dc/elements/1.1/source http://purl.org/dc/elements/1.1/title
Endoplasmic reticulum stress response in coronavirus infection
http://purl.org/dc/terms/description
This pathway model describes how the three branches of the Unfolded Protein Response (UPR) signaling pathway are activated and regulated during human coronavirus infection [DOI: 10.1146/annurev-micro-020518-115759]. During coronavirus infection, viral proteins are produced in large amounts in the ER, exceeding the ER’s protein folding capacity and leading to large amounts of unfolded proteins. This results in ER stress and activation of the UPR through transmembrane sensors PERK, IRE1 and ATF6. Pathways activation occurs when the protein chaperone GRP78 (HSPA5) dissociates from the PERK/IRE1/ATF6 to bind unfolded proteins, which leads to oligomerization, autophosphorylation and activation [DOI: 10.1107/S0907444911006445].
Activated PERK inactivates eIF2α by phosphorylation, leading to a decrease in overall protein synthesis. eIF2α can also be phosphorylated by several other kinases (HRI, GCN2, PKR). PKR activation is shown to be suppressed by coronavirus nsp15 and dsRNA-binding activity of MERS-CoV protein 4a. Activated IRE1 (ERN1) has multiple downstream effects. The IRE1 RNase domain is involved in unconventional splicing of XBP1, creating XBP1S which induces expression of protein folding genes. The RNase domain can also break down mRNAs (IRE1-dependent mRNA decay, RIDD), helping to establish ER homeostasis. Finally, the kinase activity of IRE1 also activates a signaling cascade that leads to the JNK pathway, triggering apoptosis. It is thought that the SARS-CoV E protein suppresses activation of the IRE1 pathway and SARS-CoV-induced apoptosis [10.1371/journal.ppat.1002315].
Activated ATF6 is translocated to Golgi and cleaved [DOI: 10.1016/s1097-2765(00)00133-7] to release ATF6-p50, a transcription factor that induces the expression of protein chaperone genes as well as CHOP and XBP1. There is evidence that SARS-CoV infection inhibits ATF6 cleavage [10.1016/j.virol.2009.02.021].
Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.
http://purl.org/dc/terms/identifier http://purl.org/dc/terms/references
https://identifiers.org/pubmed/31226023
https://identifiers.org/pubmed/32353859
https://identifiers.org/pubmed/19304306
https://identifiers.org/pubmed/22028656
http://purl.org/spar/cito/cites
https://identifiers.org/pubmed/31226023
https://identifiers.org/pubmed/21543844
https://identifiers.org/pubmed/32353859
https://identifiers.org/pubmed/19304306
https://identifiers.org/pubmed/22028656
http://vocabularies.wikipathways.org/wp#diseaseOntologyTag
http://purl.obolibrary.org/obo/DOID_934
http://purl.obolibrary.org/obo/DOID_2945
http://vocabularies.wikipathways.org/wp#isAbout
http://rdf.wikipathways.org/Pathway/WP4861_r140454
http://vocabularies.wikipathways.org/wp#ontologyTag
http://purl.obolibrary.org/obo/DOID_934
http://purl.obolibrary.org/obo/PW_0000237
http://purl.obolibrary.org/obo/DOID_2945
http://purl.obolibrary.org/obo/PW_0000013
http://vocabularies.wikipathways.org/wp#Curation:AnalysisCollection
http://vocabularies.wikipathways.org/wp#Curation:COVID19
http://vocabularies.wikipathways.org/wp#organism
http://purl.obolibrary.org/obo/NCBITaxon_9606
http://vocabularies.wikipathways.org/wp#organismName http://vocabularies.wikipathways.org/wp#pathwayOntologyTag
http://purl.obolibrary.org/obo/PW_0000237
http://purl.obolibrary.org/obo/PW_0000013
http://xmlns.com/foaf/0.1/img
https://www.wikipathways.org//wpi/wpi.php?action=downloadFile&type=png&pwTitle=Pathway:WP4861&oldid=140454
https://www.wikipathways.org//wpi/wpi.php?action=downloadFile&type=svg&pwTitle=Pathway:WP4861&oldid=140454
https://identifiers.org/pubmed/32353859 https://identifiers.org/uniprot/P19525 https://identifiers.org/uniprot/Q9BQI3 https://identifiers.org/uniprot/Q9NZJ5 https://identifiers.org/wikipathways/WP354 https://identifiers.org/pubmed/31226023 https://identifiers.org/pubmed/19304306 https://identifiers.org/pubmed/22028656 https://identifiers.org/uniprot/Q86XI6 https://identifiers.org/uniprot/Q9UD71 https://identifiers.org/ensembl/ENSG00000171791 https://identifiers.org/uniprot/P10415 https://identifiers.org/uniprot/P45983 https://identifiers.org/uniprot/Q9H492 https://identifiers.org/uniprot/Q96A00 https://identifiers.org/ensembl/ENSG00000100219 https://identifiers.org/ensembl/ENSG00000175197 https://identifiers.org/uniprot/O14974 https://identifiers.org/uniprot/O75460 https://identifiers.org/uniprot/P0DTC2 https://identifiers.org/uniprot/P0DTC4 https://identifiers.org/uniprot/P17861 https://identifiers.org/uniprot/P18850 https://identifiers.org/uniprot/P35638 https://identifiers.org/uniprot/Q53XC0 https://identifiers.org/uniprot/Q6GQY8 https://identifiers.org/uniprot/Q9BZL4 https://identifiers.org/wikidata/Q87917579 https://identifiers.org/wikipathways/WP4861 https://identifiers.org/uniprot/Q9ULJ8 https://identifiers.org/uniprot/Q9UQK1 https://identifiers.org/uniprot/O43462 https://identifiers.org/uniprot/O75807 https://identifiers.org/uniprot/P11021 https://identifiers.org/uniprot/P18848 https://identifiers.org/uniprot/P36873 https://identifiers.org/uniprot/P62136 https://identifiers.org/uniprot/P62140 https://identifiers.org/uniprot/Q14703 https://identifiers.org/uniprot/Q8TAE6 https://identifiers.org/uniprot/Q16821 https://identifiers.org/uniprot/Q96KQ4 https://identifiers.org/uniprot/B7ZBB8 https://identifiers.org/uniprot/D3DTX6 https://identifiers.org/uniprot/O95685 https://identifiers.org/uniprot/P41236 https://identifiers.org/uniprot/Q12972 https://identifiers.org/uniprot/Q13522 https://identifiers.org/uniprot/Q15435 https://identifiers.org/uniprot/Q5SRK2 https://identifiers.org/uniprot/Q5SWA1 https://identifiers.org/uniprot/Q6ZSY5 https://identifiers.org/uniprot/Q8WVI7 https://identifiers.org/uniprot/Q96C90 https://identifiers.org/uniprot/Q96I34 https://identifiers.org/uniprot/Q96QC0 https://identifiers.org/uniprot/Q96T49 https://identifiers.org/uniprot/Q9H7J1 https://identifiers.org/uniprot/Q9NXH3 https://identifiers.org/wikidata/Q2819370 https://identifiers.org/wikidata/Q7251492