</head><body>Under continuous ER Ca2+ depletion, Sig-1R was triggered to dissociate from BiP to bind IP3R3 (=ITPR3) and redistribute from MAM to the entire ER network (PMID:17981125). When ER is under stress or when ER Ca2+ is depleted, SigR1 switches its interacting partner from BiP (=HSPA5=GRP78) to IP3R (=ITPR3). This process protects IP3R from degradation, resulting in restoration of Ca2+ transfer from the ER to mitochondria.(PMID:30590907) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re42"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590907" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17981125" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10029" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_0_csa7"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_0_sa293" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa7_in_0" /><qual:input qual:qualitativeSpecies="path_0_csa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa7_in_1" /><qual:input 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<rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26587781" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23430059" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_csa13"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa87" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa13_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa82" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa13_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_csa13" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_csa13_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa87</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa82</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>IP were performed in wild-type CHO cells. Endogenous Sig-1Rs co-immunoprecipitated BiP (=HSPA5=GRP78), and conversely BiP co-immunoprecipitated endogenous Sig-1Rs. Importantly, efficient coIP of these endogenous proteins requires using lysates from MAM in which both Sig-1Rs and BiP are enriched. No other ER chaperones, including GRP94, calnexin, calreticulin, PDI, ERp57, and cyclophilin B could be detected in immunoprecipitants of endogenous Sig-1Rs, indicating a highly specific interaction between Sig-1Rs and BiP (PMID:17981125).The C-terminus of the sigma-1 receptor possesses a molecular chaperone activity that stabilizes ER proteins, thus being able to regulate their degradation. The association of another ER chaperone BiP regulates the chaperone activity of the sigma-1 receptor. The sigma-1 receptor forming a complex with BiP is in a dormant state, whereas the free sigma-1 receptor that dissociates from BiP exerts maximum chaperone activity. The association between sigma-1 receptors and BiP is Ca2+-dependent, and thus the depletion of ER Ca2+ activates the sigma-1 receptor chaperone. Importantly, even in the presence of ER Ca2+, sigma-1 receptor agonists cause the dissociation of BiP from sigma-1 receptors, leading to activation of sigma-1 receptor chaperone (25704011). When ER is under stress or when ER Ca2+ is depleted, SigR1 switches its interacting partner from BiP to IP3R. This process protects IP3R from degradation, resulting in restoration of Ca2+ transfer from the ER to mitochondria.(PMID:30590907) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re147"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25704011" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590907" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17981125" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10029" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_csa5"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa147" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa5_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa146" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa5_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_csa5" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_csa5_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa147</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa146</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The integral ER protein vesicle-associated membrane protein-associated protein B (VAPB) was shown to bind to the outer mitochondrial membrane protein, protein tyrosine phosphatase interacting protein 51 (PTPIP51=RMDN3) (PMID: 28132811). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re103"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_0_csa8"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_0_csa7" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa8_in_0" /><qual:input qual:qualitativeSpecies="path_0_sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa8_in_1" /><qual:input qual:qualitativeSpecies="path_0_csa34" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa8_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_0_csa8" qual:transitionEffect="assignmentLevel" qual:id="tr_path_0_csa8_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_0_csa7</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_0_sa102</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_0_csa34</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><annotation><rdf:RDF><rdf:Description rdf:about="#path_0_re63"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23850759" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_csa18"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa175" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa18_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa174" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa18_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_csa18" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_csa18_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa175</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa174</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>PACS-2 co-localizes with ADAM17 on early endosomes (PMID:26108729). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re152"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26108729" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_csa1"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa156" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa1_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa158" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa1_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_csa1" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_csa1_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa156</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa158</ci><cn 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The Fis1-Bap31 complex (ARCosome) that spans the mitochondria-ER interface serves as a platform to activate the initiator procaspase-8, and thereby bridges two critical organelles for apoptosis signalling (PMID:21183955) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re126"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21183955" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_csa17"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa98" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa17_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa153" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa17_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_csa17" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_csa17_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa98</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa153</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>MFN2 regulates shape of the ER and tethers it to mitochondria, by engaging in homo- and hetero-complexes comprising MFN2 at the ER and MFN2 or MFN1 on mitochondria. Ablation or silencing of mitofusin 2 in mouse embryonic fibroblasts and HeLa cells disrupts ER morphology and loosens ER–mitochondria interactions, thereby reducing the efficiency of mitochondrial Ca2+ uptake in response to stimuli that generate inositol-1,4,5-trisphosphate(PMID:19052620). MFN2, a dynamin-related GTPase identified at the ER surface, contributes to ER and mitochondria tethering either by homologous interaction between ER-associated MFN2 and mitochondrial MFN2 or by heterologous interaction with mitofusin 1 (MFN1), a homolog protein only located at the outer mitochondrial membrane.(PMID:29491369) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re120"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29491369" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19052620" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_0_csa51"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_0_sa617" qual:transitionEffect="none" qual:sign="positive" 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<bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17991856" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23430059" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_0_csa30"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_0_sa88" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa30_in_0" /><qual:input qual:qualitativeSpecies="path_0_csa31" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa30_in_1" /><qual:input qual:qualitativeSpecies="path_0_sa90" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_csa30_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_0_csa30" qual:transitionEffect="assignmentLevel" qual:id="tr_path_0_csa30_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm 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</rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_csa4"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa98" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa4_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa99" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_csa4_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_csa4" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_csa4_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa98</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa99</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>MFN2, a dynamin-related GTPase identified at the ER surface, contributes to ER and mitochondria tethering either by homologous interaction between ER-associated MFN2 and mitochondrial MFN2 or by heterologous interaction with mitofusin 1 (MFN1), a homolog protein only located at the outer mitochondrial membrane.(PMID:29491369) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re53"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19052620" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29491369" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590907" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition 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type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>MICU1, MICU2, MCUb and EMRE were detected by protein immunoblotting after immunoprecipitation of MCU-FLAG from HEK-293T and HeLa cells.(PMID:24231807). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re58"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:24231807" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa29"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa145" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa29_in_0" /><qual:input qual:qualitativeSpecies="sa258" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa29_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa29" qual:transitionEffect="assignmentLevel" qual:id="tr_csa29_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa145</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa258</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 in complex with ACE2 was determined (PMID:32225175). Biophysical and structural evidence are provided that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S (PMID:32075877). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re134"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32075877" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32225175" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P0DTC2" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:2697049" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa30"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa258" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa30_in_0" /><qual:input qual:qualitativeSpecies="sa262" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa30_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa30" qual:transitionEffect="assignmentLevel" qual:id="tr_csa30_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa258</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa262</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>More than one host-cell receptor is reported to be recognized by the viral spike protein, among them is the cell-surface Heat Shock Protein A5 (HSPA5), also termed GRP78 or BiP. Upon viral infection, HSPA5 is upregulated, then translocating to the cell membrane where it is subjected to be recognized by the SARS-CoV-2 spike (PMID: 32340551). The present in silico perspective suggests the existence of a COVID-19 spike protein-GRP78 binding site. The binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues can be used to develop therapeutics specific against COVID-19 (PMID:32169481). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re135"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32340551" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32169481" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P0DTC2" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa31"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa178" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa31_in_0" /><qual:input qual:qualitativeSpecies="sa275" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa31_in_1" /><qual:input qual:qualitativeSpecies="path_1_sa180" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_csa31_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa31" qual:transitionEffect="assignmentLevel" qual:id="tr_csa31_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa178</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa275</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa180</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ACE2 must be cell attached to function as a SARS-CoV receptor. Soluble ACE2 was enzymatically active and partially inhibited virus entry into target cells via sACE2 competition for S protein binding. The SARS CoV spike receptor-binding domain is bound to ACE2 (PMID:19411314). 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rdf:resource="urn:miriam:pubmed:23850759" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23430059" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa87"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_csa13" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa87_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa69" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa87_in_1" /><qual:input qual:qualitativeSpecies="path_1_sa60" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa87_in_2" /><qual:input qual:qualitativeSpecies="path_1_sa149" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa87_in_3" /><qual:input qual:qualitativeSpecies="path_1_sa145" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_path_1_sa87_in_4" 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was triggered to dissociate from BiP to bind IP3R3 (=ITPR3) and redistribute from MAM to the entire ER network (PMID:17981125). When ER is under stress or when ER Ca2+ is depleted, SigR1 switches its interacting partner from BiP (=HSPA5=GRP78) to IP3R (=ITPR3). This process protects IP3R from degradation, resulting in restoration of Ca2+ transfer from the ER to mitochondria.(PMID:30590907) The protein levels of GRP78 (=HSPA5), eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice (PMID:31775868). Time course studies analyzing the expression of Mfn2 and known ER stress proteins were performed in MEFs (mouse embryonic fibroblasts) treated with TG (thapsigargin). Mfn2 up-regulation occurred in the late phase of ER stress (8 h) and was accompanied by increases in CHOP (=DDIT3), Grp94 (=HSP90B1), Grp78 (=HSPA5), GADD34 (=PPP1R15A), and p58IPK (=DNAJC3) expression. (PMID:22511781). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re40"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590907" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25704011" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17981125" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10029" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re137"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:31775868" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22511781" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa149"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa125" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa149_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa145" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_path_1_sa149_in_1" /><qual:input qual:qualitativeSpecies="sa275" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa149_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa149" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa149_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa125</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa275</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa145</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice (PMID:31775868).SARS-CoV S, E, M, and NSP6 proteins were expressed in 293FT cells. All four proteins have at least one transmembrane domain and are abundantly expressed in infected cells. It was observed that among the four, only S activated transcription from GRP94/78 promoters to approximately fivefold. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein (PMID:16940539). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re110"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22511781" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:31775868" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:16940539" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P59594" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li 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Transfection of VAPB or PTPIP51 both induced significant increases in mitochondrial and corresponding decreases in cytosolic Ca2+ levels in these experiments. These results complement previous studies that show that siRNA knockdown of VAPB or PTPIP51 reduce mitochondrial and increase cytosolic Ca2+ levels following IP3-receptor-mediated Ca2+ release (PMID:28132811) Transfection of VAPB or PTPIP51 both induced significant increases in mitochondrial and corresponding decreases in cytosolic Ca2+ levels in these experiments. These results complement previous studies that show that siRNA knockdown of VAPB or PTPIP51 reduce mitochondrial and increase cytosolic Ca2+ levels following IP3-receptor-mediated Ca2+ release (PMID:28132811) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re128"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21183955" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re129"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqmodel:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0051561" /> </rdf:Bag> </bqmodel:is> </rdf:Description> <rdf:Description rdf:about="#path_1_re111"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa169"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa3" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_path_1_sa169_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa169" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa169_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_1_sa3</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>PACS-2 controls the apposition of mitochondria with the ER, as depletion of PACS-2 causes BAP31-dependent mitochondria fragmentation and uncoupling from the ER. 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VAPB or PTPIP51 (= RMDN3) overexpression inhibits basal autophagy and autophagic flux (PMID: 28132811). Disruption of Ca2+ transfer from MAM-located IP3 receptors to mitochondria stimulates autophagy (PMID: 28132811). Loosening ER-mitochondria contacts via loss of VAPB or PTPIP51 induces whereas tightening contacts by overexpression of VAPB or PTPIP51 impairs basal autophagy (PMID:28132811). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re113"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re114"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re119"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re118"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_0_sa107"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_0_sa108" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_sa107_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_0_sa107" qual:transitionEffect="assignmentLevel" qual:id="tr_path_0_sa107_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_0_sa108</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><annotation><rdf:RDF><rdf:Description rdf:about="#path_0_re68"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23850759" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa154"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa169" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa154_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa154" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa154_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_1_sa169</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>PACS-2 controls the apposition of mitochondria with the ER, as depletion of PACS-2 causes BAP31-dependent mitochondria fragmentation and uncoupling from the ER. PACS-2 depletion induced mitochondria fragmentation by promoting mitochondria fission rather than by inhibiting fusion (PMID:15692567). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re142"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15692567" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa159"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa158" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa159_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa159" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa159_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_1_sa158</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Fis1 expression leads to increased mitochondrial calcium accumulation and to outer mitochondrial membrane depolarization (PMID:21183955). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re127"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21183955" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa86"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_csa13" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa86_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa69" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa86_in_1" /><qual:input qual:qualitativeSpecies="path_1_sa60" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa86_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa86" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa86_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>path_1_sa69</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa60</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>path_1_csa13</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Under continuous ER Ca2+ depletion, Sig-1R was triggered to dissociate from BiP to bind IP3R3 (=ITPR3) and redistribute from MAM to the entire ER network (PMID:17981125). When ER is under stress or when ER Ca2+ is depleted, SigR1 switches its interacting partner from BiP (=HSPA5=GRP78) to IP3R (=ITPR3). This process protects IP3R from degradation, resulting in restoration of Ca2+ transfer from the ER to mitochondria.(PMID:30590907) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re40"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590907" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25704011" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17981125" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10029" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_0_sa206"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_0_sa28" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_sa206_in_0" /><qual:input qual:qualitativeSpecies="path_0_sa65" 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xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_0_sa44</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><annotation><rdf:RDF><rdf:Description rdf:about="#path_0_re367"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23850759" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa120"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa69" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa120_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa98" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa120_in_1" /><qual:input qual:qualitativeSpecies="path_1_sa166" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa120_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa120" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa120_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>path_1_sa69</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa98</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa166</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ER stress activates complex cytoplasmic and nuclear signaling pathways, collectively called the unfolded protein response (UPR). Initially, the UPR seeks to reestablish ER homoeostasis via translational attenuation to decrease ER load, transcriptional activation of chaperone genes to increase the folding capacity of the ER, and activation of the ER-associated degradation machinery to clear misfolded proteins. If ER stress is unresolved, apoptosis is triggered (PMID: 22511781). Mfn2 is a regulator of the ER stress response. It is shown that it is selectively up-regulated in response to ER stress, whereas other mitochondrial shaping proteins are not. Furthermore, it is shown that Mfn2 is essential for an appropriate elaboration of the UPR and ER homeostasis (PMID:22511781). The finding that the UPR induced by PACS-2 depletion could be prevented by expression of a caspase-resistant crBAP31 demonstrates that this UPR is a direct result of the p20-mediated uncoupling of the fragmented mitochondria from the ER (PMID:15692567) </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re73"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22511781" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re71"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22511781" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re144"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li 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The ER-resident protein BAP31 (B-cell receptor-associated protein 31), the mitochondrial fission protein FIS1 (fission 1 homolog) and the phosphofurin acidic cluster sorting protein-2 (PACS-2) are MAM connectors involved in the induction of apoptosis (PMID:29491369). MFN2 regulates shape of the ER and tethers it to mitochondria, by engaging in homo- and hetero-complexes comprising MFN2 at the ER and MFN2 or MFN1 on mitochondria (PMID:19052620). PACS-2 controls the apposition of mitochondria with the ER, as depletion of PACS-2 causes BAP31-dependent mitochondria fragmentation and uncoupling from the ER (PMID:15692567). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re50"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590907" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#path_1_re49"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19052620" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590907" 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</rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa166"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa156" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa166_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa3" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_path_1_sa166_in_1" /><qual:input qual:qualitativeSpecies="path_1_sa110" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa166_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa166" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa166_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa156</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa110</ci><cn 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qual:qualitativeSpecies="path_0_csa6" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_sa39_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_0_sa39" qual:transitionEffect="assignmentLevel" qual:id="tr_path_0_sa39_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>path_0_sa118</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_0_csa6</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>path_0_sa38</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><annotation><rdf:RDF><rdf:Description rdf:about="#path_0_re75"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23850759" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa110"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa98" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa110_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa69" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa110_in_1" /><qual:input qual:qualitativeSpecies="path_1_sa86" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_path_1_sa110_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa110" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa110_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>path_1_sa98</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa69</ci><cn type="integer">1</cn></apply><apply><eq 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Genetic ablation of Mfn2 in mouse embryonic fibroblasts amplified ER stress and exacerbated ER stress-induced apoptosis. If ER stress is unresolved, apoptosis is triggered (PMID:22511781). 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Mfn2 but not Mfn1 is an ER stress-inducible protein that is required for the proper temporal sequence of the ER stress response (PMID:22511781). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re108"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22511781" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa171"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_csa18" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa171_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa171" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa171_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_1_csa18</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The sorting protein PACS-2 was identified as a regulator of ADAM17 trafficking and ErbB signalling. PACS-2 regulates cell-surface availability of mature ADAM17. It was found that PACS-2 interacted with mature ADAM17, and that PACS-2/ADAM17 co-localization overlapped substantially with transferrin-positive early endosomes. PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. Hence, PACS-2 sustains ADAM17 cell-surface activity by diverting ADAM17 away from degradative pathways (PMID:26108729). The metalloproteinase ADAM17 is responsible for mediating ACE2 shedding from the cell membrane-bound domain, which can be promoted by Ang II, and release of ACE2 as a soluble form in plasma impairing brain ACE2 compensatory activity and thus contributing to the development of neurogenic hypertension. ADAM17 (a disintegrin and metalloproteinase 17)-mediated proteolytic cleavage of ACE2 is upregulated by endocytosed SARS-CoV-2 spike proteins (PMID:32264791). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#path_1_re153"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26108729" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_0_sa37"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_0_sa627" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_0_sa37_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_0_sa37" qual:transitionEffect="assignmentLevel" qual:id="tr_path_0_sa37_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" 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These results complement previous studies that show that siRNA knockdown of VAPB or PTPIP51 reduce mitochondrial and increase cytosolic Ca2+ levels following IP3-receptor-mediated Ca2+ release (PMID:28132811) Transfection of VAPB or PTPIP51 both induced significant increases in mitochondrial and corresponding decreases in cytosolic Ca2+ levels in these experiments. 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/></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>path_0_sa69</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_0_sa65</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>path_0_sa122</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><annotation><rdf:RDF><rdf:Description rdf:about="#path_0_re76"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23850759" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25387528" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_path_1_sa178"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa145" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa178_in_0" /><qual:input qual:qualitativeSpecies="path_1_sa171" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_path_1_sa178_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="path_1_sa178" qual:transitionEffect="assignmentLevel" qual:id="tr_path_1_sa178_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>path_1_sa145</ci><cn type="integer">1</cn></apply><apply><eq /><ci>path_1_sa171</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ADAM17 is responsible for constitutive ACE2 shedding in primary human airway epithelial cells (PMID:19411314). The metalloproteinase ADAM17 is responsible for mediating ACE2 shedding from the cell membrane-bound domain, which can be promoted by Ang II, and release of ACE2 as a soluble form in plasma impairing brain ACE2 compensatory activity and thus contributing to the development of neurogenic hypertension. ADAM17 (a disintegrin and metalloproteinase 17)-mediated proteolytic cleavage of ACE2 is upregulated by endocytosed SARS-CoV-2 spike proteins (PMID:32264791). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re138"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19411314" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32264791" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15983030" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa266"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa145" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa266_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa266" qual:transitionEffect="assignmentLevel" qual:id="tr_sa266_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_1_sa145</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Angiotensin converting enzyme-2 (ACE2) is protective but mRNA and activity are severely downregulated in both human and experimental lung fibrosis, suggesting that ACE-2 protects against lung fibrogenesis by limiting the local accumulation of the profibrotic peptide ANG II (PMID:18441099). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re139"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:18441099" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa271"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa31" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_0" /><qual:input qual:qualitativeSpecies="sa279" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_1" /><qual:input qual:qualitativeSpecies="path_1_sa180" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa271_in_2" /><qual:input qual:qualitativeSpecies="csa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa271" qual:transitionEffect="assignmentLevel" qual:id="tr_sa271_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>csa31</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa279</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>path_1_sa180</ci><cn type="integer">0</cn></apply><apply><eq /><ci>csa30</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ACE2 is expressed predominantly at the apical surface of human airway epithelia, facilitating SARS-CoV entry. (PMID:19411314). Soluble ACE2 was enzymatically active and partially inhibited virus entry into target cells via sACE2 competition for S protein binding(PMID:19411314). Human bronchus epithelial cells, BEAS2B, were transfected with the MERS-CoV spike and the membrane proteins evaluated. In this study GRP78 was identified as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment (PMID:29887526). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re141"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19411314" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re142"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19411314" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P59594" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re143"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29887526" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:W6A028" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:1335626" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa278"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa271" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa278_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa278" qual:transitionEffect="assignmentLevel" qual:id="tr_sa278_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa271</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ACE2 is a functional receptor for SARS-CoV. Consistent with the basal replication observed in both infection assays, minor expression of ACE2 on 293T cells was subsequently detected by an anti-ACE2 antibody (PMID:14647384). Additional data indicate that SARS-CoV S protein or SARS virus infection directly downregulates pulmonary ACE2 expression (PMID:19411314). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re144"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:14647384" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19411314" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P59594" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa280"><qual:listOfInputs><qual:input qual:qualitativeSpecies="path_1_sa145" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa280_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa280" qual:transitionEffect="assignmentLevel" qual:id="tr_sa280_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>path_1_sa145</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ACE2-transfected 293T cells supported efficient replication of SARS-CoV (PMID:14647384). </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re145"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:14647384" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition></qual:listOfTransitions></model></sbml>

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