{"metadata":{"accession":"PF11289","entry_id":null,"type":"family","go_terms":null,"source_database":"pfam","member_databases":null,"integrated":"IPR024407","hierarchy":null,"name":{"name":"Betacoronavirus viroporin","short":"bCoV_viroporin"},"description":[{"text":"<p>This entry represents protein 3a encoded by Orf3/3a, also known as X1, which forms homotetrameric potassium, sodium or calcium sensitive ion channels (viroporin) that causes ER-stress in host cells and may modulate virus release. This is a pro-apoptosis-inducing protein that localises to the endoplasmic reticulum (ER)-Golgi compartment. SARS-CoV causes apoptosis of infected cells through NLRP3 inflammasome activation [[cite:PUB00075660],[cite:PUB00075661],[cite:PUB00056032],[cite:PUB00075662]]. Protein 3a also promotes the ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mediated by its interaction with TNF receptor-associated factor 3 (TRAF3). This protein induces NF-kappa B activation and upregulates fibrinogen secretion with high cytokine production [[cite:PUB00094124]]. Through the activation of the PERK pathway of unfolded protein response (UPR), this protein causes phosphorylation of eIF2-alpha leading to reduced translation of cellular proteins and as the activation of pro-apoptotic downstream  effectors (i.e ATF4, CHOP).</p>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00075662":{"PMID":20020050,"ISBN":null,"volume":"4","issue":"12","year":2009,"title":"The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor.","URL":null,"raw_pages":"e8342","medline_journal":"PLoS One","ISO_journal":"PLoS ONE","authors":["Minakshi R","Padhan K","Rani M","Khan N","Ahmad F","Jameel S."],"DOI_URL":"http://dx.doi.org/10.1371/journal.pone.0008342"},"PUB00075661":{"PMID":15781262,"ISBN":null,"volume":"330","issue":"1","year":2005,"title":"The severe acute respiratory syndrome coronavirus 3a is a novel structural protein.","URL":null,"raw_pages":"286-92","medline_journal":"Biochem Biophys Res Commun","ISO_journal":"Biochem. Biophys. Res. Commun.","authors":["Shen S","Lin PS","Chao YC","Zhang A","Yang X","Lim SG","Hong W","Tan YJ."],"DOI_URL":"http://dx.doi.org/10.1016/j.bbrc.2005.02.153"},"PUB00056032":{"PMID":16894145,"ISBN":null,"volume":"103","issue":"33","year":2006,"title":"Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.","URL":null,"raw_pages":"12540-5","medline_journal":"Proc Natl Acad Sci U S A","ISO_journal":"Proc. Natl. Acad. Sci. U.S.A.","authors":["Lu W","Zheng BJ","Xu K","Schwarz W","Du L","Wong CK","Chen J","Duan S","Deubel V","Sun B."],"DOI_URL":"http://dx.doi.org/10.1073/pnas.0605402103"},"PUB00094124":{"PMID":31034780,"ISBN":null,"volume":"33","issue":"8","year":2019,"title":"Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.","URL":null,"raw_pages":"8865-8877","medline_journal":"FASEB J","ISO_journal":"FASEB J.","authors":["Siu KL","Yuen KS","Castano-Rodriguez C","Ye ZW","Yeung ML","Fung SY","Yuan S","Chan CP","Yuen KY","Enjuanes L","Jin DY."],"DOI_URL":null},"PUB00075660":{"PMID":15135062,"ISBN":null,"volume":"565","issue":"1-3","year":2004,"title":"Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus.","URL":null,"raw_pages":"111-6","medline_journal":"FEBS Lett","ISO_journal":"FEBS Lett.","authors":["Yu CJ","Chen YC","Hsiao CH","Kuo TC","Chang SC","Lu CY","Wei WC","Lee CH","Huang LM","Chang MF","Ho HN","Lee FJ."],"DOI_URL":"http://dx.doi.org/10.1016/j.febslet.2004.03.086"}},"set_info":null,"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":1,"interactions":0,"matches":78,"pathways":0,"proteins":78,"proteomes":3,"sets":0,"structural_models":{"alphafold":2},"structures":6,"taxa":58},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":1,"alignment:full":5},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":null}}