</head> <body> Authors: Luis Cristobal Monraz Gomez, Inna Kuperstein, Institut Curie Barbara Brauner, Andreas Ruepp, Helmholtz Zentrum München / Institute of Experimental Genetics, Germany <br/> <br/> DESCRIPTION: This diagram depicts the activity of the Unfolded Protein Response (UPR) that leads to endoplasmic reticulum stress and further apoptosis. During the Sars-CoV-2 infection, this mechanism is activated in the infected cells of the host. 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<body> BiP(= GRP78 = HSPA5) has a dual function, in addition to its chaperone role it is a bona fide ER lumenal Ca2+ storage protein contributing, under resting cell conditions, to around 25% of the store, with a stoichiometry of 1-2 moles of calcium/mole of BiP. 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<celldesigner:name>GTP</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:annotation> </celldesigner:species> <celldesigner:species id="s_id_path_0_sa608" name="Met_minus_tRNA"> <celldesigner:notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> <rdf:RDF xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#"> <rdf:Description rdf:about="#s_id_path_0_sa608"> <dcterms:modified rdf:parseType="Resource"/> </rdf:Description> </rdf:RDF> </body> </html> </celldesigner:notes> <celldesigner:annotation> <celldesigner:complexSpecies>s_id_path_0_csa8</celldesigner:complexSpecies> <celldesigner:speciesIdentity> <celldesigner:class>RNA</celldesigner:class> <celldesigner:rnaReference>r_s_id_path_0_sa608</celldesigner:rnaReference> </celldesigner:speciesIdentity> </celldesigner:annotation> </celldesigner:species> <celldesigner:species id="s_id_path_1_sa176" name="PACS2"> <celldesigner:notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> PACS-2 co-localizes with ADAM17 on early endosomes (PMID:26108729). 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 also controls formation of ER lipid-synthesizing centers found on mitochondria-associated membranes and ER homeostasis.In response to apoptotic inducers, PACS-2 translocates Bid to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated Bid, the release of cytochrome c, and the activation of caspase-3, thereby causing cell death (PMID:15692567). The cytosolic sorting protein PACS-2 regulates the distribution and activity of calnexin. Under control conditions, over 80% of calnexin localizes to the ER, mainly at the MAM. However, through a protein-protein interaction, PACS-2 causes calnexin to distribute between the ER and the plasma membrane. PACS-2 thus affects the homeostasis of ER Ca2+ (PMID:19144519.) <rdf:RDF xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#"> <rdf:Description rdf:about="#s_id_path_1_sa176"> <dcterms:modified rdf:parseType="Resource"/></rdf:Description> </rdf:RDF> </body> </html> </celldesigner:notes> <celldesigner:annotation> <celldesigner:complexSpecies>s_id_path_1_csa18</celldesigner:complexSpecies> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa176</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:annotation> </celldesigner:species> <celldesigner:species id="s_id_path_1_sa177" name="ADAM17"> <celldesigner:notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> PACS-2 interacts with ADAM17 under basal conditions. 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 loss did not affect constitutive ADAM17 internalization, but rather decreased the cell-surface recycling and stability of internalized ADAM17. PACS-2 co-localizes with ADAM17 on early endosomes and PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. 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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). <rdf:RDF xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#"> <rdf:Description rdf:about="#s_id_path_1_sa7"> <dcterms:modified rdf:parseType="Resource"/></rdf:Description> </rdf:RDF> </body> </html> </celldesigner:notes> <celldesigner:annotation> <celldesigner:complexSpecies>s_id_path_1_csa4</celldesigner:complexSpecies> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> 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<celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="0.38999999999993407" id="rs1" name="K63" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_1_sa153" name="MFN2" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa597" name="cleaved~CASP3" type="TRUNCATED"/> <celldesigner:protein id="p_s_id_path_0_sa87" name="EIF2S1" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.170000000000002" id="rs1" name="Ser51" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa435" name="BID" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1780972450961835" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa239" name="MAP1LC3A" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa244" name="CASP8" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="0.3899999999999885" id="rs1" name="K63" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa261" name="AP_minus_1" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="0.39269908169872414" id="rs1" side="none"/> <celldesigner:modificationResidue angle="5.890486225480862" id="rs2" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa61" name="MBTPS2" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa180" name="BAK1" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa157" name="BCAP31" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa3" name="PACS2" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa166" name="p20" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa152" name="BCL2" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1780972450961367" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa104" name="ATF4" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa39" name="MAP3K5" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.178097245096169" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_1_sa99" name="MFN1" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa317" name="EIF2B5" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa596" name="CASP3" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa95" name="MCU" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa629" name="DDIT3" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1780972450962035" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa93" name="EIF2S3" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa98" name="MFN2" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa171" name="ADAM17" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa92" name="EIF2S2" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa146" name="RMDN3" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa260" name="AP_minus_1" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="0.39269908169869727" id="rs1" side="none"/> <celldesigner:modificationResidue angle="5.890486225480853" id="rs2" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa89" name="EIF2S3" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa174" name="ADAM17" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa180" name="ACE2,_space_soluble" type="TRUNCATED"/> <celldesigner:protein id="p_s_id_path_0_sa69" name="DDIT3" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1780972450961635" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa487" name="TMBIM6" type="RECEPTOR"/> <celldesigner:protein id="p_s_id_path_1_sa175" name="PACS2" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa254" name="TRIM13" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa93" name="MCU1" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa473" name="ERN1" type="RECEPTOR"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1780972450961735" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_1_sa28" name="MCUb" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa156" name="BCAP31" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa9" name="RMDN3" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa40" name="MAPK8" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="2.74889357189106" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa600" name="CAPN1" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa170" name="ITPR3" type="RECEPTOR"/> <celldesigner:protein id="p_s_id_path_0_sa65" name="ATF6" type="RECEPTOR"/> <celldesigner:protein id="p_s_id_path_0_sa145" name="MAP3K4" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1780972450961826" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa246" name="FADD" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa474" name="ERN1" type="RECEPTOR"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.178097245096172" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa615" name="EIF2AK4" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa434" name="BCL2L11" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1780972450961993" id="rs1" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_0_sa290" name="EIF2AK1" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa32" name="MCU1" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa94" name="MCU2" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_0_sa97" name="EIF2S1" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1700000000000643" id="rs1" name="Ser51" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="p_s_id_path_1_sa145" name="ACE2" type="RECEPTOR"/> <celldesigner:protein id="p_s_id_path_0_sa494" name="RYR1" type="RECEPTOR"/> <celldesigner:protein id="p_s_id_path_0_sa295" name="EIF2S1" type="GENERIC"> <celldesigner:listOfModificationResidues> <celldesigner:modificationResidue angle="1.1699999999999573" id="rs1" name="Ser51" side="none"/> </celldesigner:listOfModificationResidues> </celldesigner:protein> <celldesigner:protein id="pr155" name="S" type="GENERIC"/> <celldesigner:protein id="p_s_id_path_1_sa178" name="ACE2,_space_membrane_minus_bound" type="RECEPTOR"/> </celldesigner:listOfProteins> <celldesigner:listOfGenes> <celldesigner:gene id="g_s_id_path_1_sa122" name="MFN2" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa122" name="ERO1A" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa70" name="DDIT3" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa28" name="XBP1" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa516" name="DNAJC3" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa484" name="TRIB3" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa55" name="BCL2" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa105" name="ATF4" type="GENE"/> <celldesigner:gene id="g_s_id_path_0_sa605" name="HYOU1" type="GENE"> <celldesigner:notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> Charge: 0 </body> </html> </celldesigner:notes> </celldesigner:gene> <celldesigner:gene id="g_s_id_path_0_sa109" name="PPP1R15A" type="GENE"/> <celldesigner:gene id="g_s_id_path_1_sa125" name="HSPA5" type="GENE"/> <celldesigner:gene id="gn12" name="ACE2" type="GENE"/> </celldesigner:listOfGenes> <celldesigner:listOfRNAs> <celldesigner:RNA id="r_s_id_path_0_sa108" name="PPP1R15A" type="RNA"/> <celldesigner:RNA id="r_s_id_path_1_sa149" name="HSPA5" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa71" name="DDIT3" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa106" name="ATF4" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa485" name="TRIB3" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa607" name="Met_minus_tRNA" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa206" name="XBP1" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa54" name="BCL2" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa293" name="Met_minus_tRNA" type="RNA"> <celldesigner:notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> HGNC_ID: 34779 </body> </html> </celldesigner:notes> </celldesigner:RNA> <celldesigner:RNA id="r_s_id_path_0_sa517" name="DNAJC3" type="RNA"/> <celldesigner:RNA id="r_s_id_path_1_sa148" name="MFN2" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa608" name="Met_minus_tRNA" type="RNA"/> <celldesigner:RNA id="r_s_id_path_0_sa604" name="HYOU1" type="RNA"> <celldesigner:notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> Charge: 0 </body> </html> </celldesigner:notes> </celldesigner:RNA> <celldesigner:RNA id="r_s_id_path_0_sa123" name="ERO1A" type="RNA"/> <celldesigner:RNA id="rn15" name="ACE2" type="RNA"/> </celldesigner:listOfRNAs> <celldesigner:listOfAntisenseRNAs/> <celldesigner:listOfLayers/> <celldesigner:listOfBlockDiagrams/> </celldesigner:extension> </annotation> <listOfUnitDefinitions> <unitDefinition metaid="substance" id="substance" name="substance"> <listOfUnits> <unit metaid="CDMT00322" kind="mole"/> </listOfUnits> </unitDefinition> <unitDefinition metaid="volume" id="volume" name="volume"> <listOfUnits> <unit metaid="CDMT00323" kind="litre"/> </listOfUnits> </unitDefinition> <unitDefinition metaid="area" id="area" name="area"> <listOfUnits> <unit metaid="CDMT00324" kind="metre" exponent="2"/> </listOfUnits> </unitDefinition> <unitDefinition metaid="length" id="length" name="length"> <listOfUnits> <unit metaid="CDMT00326" kind="metre"/> </listOfUnits> </unitDefinition> <unitDefinition metaid="time" id="time" name="time"> <listOfUnits> <unit metaid="CDMT00332" kind="second"/> </listOfUnits> </unitDefinition> </listOfUnitDefinitions> <listOfCompartments> <compartment metaid="s_id_path_1_ca8" id="s_id_path_1_ca8" name="early_space_endosome" size="1" units="volume" outside="s_id_path_0_ca6"> <annotation> <celldesigner:extension> <celldesigner:name>early_space_endosome</celldesigner:name> </celldesigner:extension> </annotation> </compartment> <compartment metaid="default" id="default" size="1" units="volume"/> <compartment metaid="s_id_path_0_ca2" id="s_id_path_0_ca2" name="nucleus" size="1" units="volume" outside="s_id_path_0_ca6"> <annotation> <celldesigner:extension> <celldesigner:name>nucleus</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_ca2"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0005634"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> <compartment metaid="s_id_path_1_ca3" id="s_id_path_1_ca3" name="mitochondrial matrix" size="1" units="volume" outside="s_id_path_1_ca1"> <annotation> <celldesigner:extension> <celldesigner:name>mitochondrial matrix</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_ca3"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0005759"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> <compartment metaid="s_id_path_1_ca1" id="s_id_path_1_ca1" name="mitochondrion" size="1" units="volume" outside="s_id_path_0_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 21689 MAM (mitochondria-associated endoplasmic reticulum membrane) </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:name>mitochondrion</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_ca1"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0005739"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> <compartment metaid="s_id_path_0_ca1" id="s_id_path_0_ca1" name="endoplasmic reticulum" size="1" units="volume" outside="s_id_path_0_ca6"> <annotation> <celldesigner:extension> <celldesigner:name>endoplasmic reticulum</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_ca1"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0005783"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> <compartment metaid="s_id_path_1_ca9" id="s_id_path_1_ca9" name="mitochondria-associated endoplasmic reticulum membrane" size="1" units="volume" outside="s_id_path_0_ca6"> <annotation> <celldesigner:extension> <celldesigner:name>mitochondria-associated endoplasmic reticulum membrane</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_ca9"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0044233"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> <compartment metaid="s_id_path_0_ca3" id="s_id_path_0_ca3" name="Golgi apparatus" size="1" units="volume" outside="s_id_path_0_ca6"> <annotation> <celldesigner:extension> <celldesigner:name>Golgi apparatus</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_ca3"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0005794"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> <compartment metaid="s_id_path_0_ca7" id="s_id_path_0_ca7" name="autophagosome" size="1" units="volume" outside="s_id_path_0_ca6"> <annotation> <celldesigner:extension> <celldesigner:name>autophagosome</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_ca7"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0005776"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> <compartment metaid="s_id_path_0_ca6" id="s_id_path_0_ca6" name="cell" size="1" units="volume" outside="default"> <annotation> <celldesigner:extension> <celldesigner:name>cell</celldesigner:name> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_ca6"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0005737"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </compartment> </listOfCompartments> <listOfSpecies> <species metaid="s_id_path_0_csa20" id="s_id_path_0_csa20" name="BAX:ERN1" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>BAX:ERN1</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re17"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa6" id="s_id_path_0_csa6" name="TRAF2:ERN1" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>TRAF2:ERN1</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re18"/> <celldesigner:catalyzed reaction="path_0_re75"/> <celldesigner:catalyzed reaction="path_0_re28"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_1_csa14" id="s_id_path_1_csa14" name="SIGMAR1:ITPR3" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 30590907 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 (17981125). SigR1(=SIGMAR1) interacts with BiP (=HSPA5=GRP78) in normal condition. 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>SIGMAR1:ITPR3</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re19"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa14"> <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> </species> <species metaid="s_id_path_0_csa21" id="s_id_path_0_csa21" name="EIF2AK3:EIF2AK3" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>EIF2AK3:EIF2AK3</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re61"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa35" id="s_id_path_0_csa35" name="GCN2:ATP" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>GCN2:ATP</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re61"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_1_csa2" id="s_id_path_1_csa2" name="ITPR3:HSPA9:VDAC1" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 30590033, 29491369 GRP75 (=HSPA9) localizes in mitochondria-associated membranes (MAMs) and acts as a bridging molecule between the two organelles by assembling the IP3R-GRP75-VDAC complex, which is involved in the transport of Ca2+ from the endoplasmic reticulum (ER) to mitochondria (PMID:30590033). In mammalian cells, four types of connectors between ER and mitochondria have been identified. One of these connectors comprises IP3R3(= ITPR3) that forms a complex with the 75 kDa glucose-regulated protein GRP75 (= HSPA9) and the mitochondrial voltage-dependent anion channel 1 (VDAC1), which serves as a calcium exchange platform between ER and mitochondria. These three proteins are referred to as tethering and calcium signaling proteins at MAMs (PMID:29491369). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>ITPR3:HSPA9:VDAC1</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re19"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa2"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30590033"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29491369"/> </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> </species> <species metaid="s_id_path_0_csa30" id="s_id_path_0_csa30" name="EIF2:GDP" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>EIF2:GDP</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa2" id="s_id_path_0_csa2" name="ERN1:Unfolded_space_protein" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>ERN1:Unfolded_space_protein</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa31" id="s_id_path_0_csa31" name="EIF2S3:GDP" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>EIF2S3:GDP</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_1_csa13" id="s_id_path_1_csa13" name="SIGMAR1:HSPA5" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 30590907, 25704011 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). BiP(= GRP78 = HSPA5) 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 (PMID:25704011). 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>SIGMAR1:HSPA5</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa13"> <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> </species> <species metaid="s_id_path_1_csa17" id="s_id_path_1_csa17" name="MFN2:MFN2" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> In mammalian cells, four types of connectors between ER and mitochondria have been identified. One of them comprises 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>MFN2:MFN2</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa17"> <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> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_csa34" id="s_id_path_0_csa34" name="EIF2B" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>EIF2B</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re63"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa8" id="s_id_path_0_csa8" name="Ternary_space_Complex" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>Ternary_space_Complex</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_1_csa18" id="s_id_path_1_csa18" name="PACS2_minus_ADAM17_space_interaction" compartment="s_id_path_1_ca8" initialAmount="0"> <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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>PACS2_minus_ADAM17_space_interaction</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa18"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26108729"/> </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> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_csa19" id="s_id_path_0_csa19" name="BAK1:ERN1" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>innerSurface</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>BAK1:ERN1</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re17"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_1_csa1" id="s_id_path_1_csa1" name="FIS1:BCAP31" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Fis1 and Bap31 interact. 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>FIS1:BCAP31</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa1"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15692567"/> </rdf:Bag> </bqbiol:isDescribedBy> <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> </species> <species metaid="s_id_path_1_csa5" id="s_id_path_1_csa5" name="VAPB:RMDN3" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 29491369 In mammalian cells, four types of connectors between ER and mitochondria have been identified. One of these connectors relies on vesicle-associated membrane protein-associated protein B (VAPB), an ER protein binding the mitochondrial protein tyrosine phosphatase-interacting protein 51 (PTPIP51 = RMDN3).(PMID:29491369) It is shown that the VAPB-PTPIP51 tethers regulate autophagy and that expression of a synthetic linker protein that artificially tethers ER and mitochondria also reduces autophagosome formation, and that this artificial tether rescues the effects of siRNA loss of VAPB or PTPIP51 on autophagy.Overexpression of VAPB or PTPIP51 to tighten ER-mitochondria contacts impairs, whereas small interfering RNA (siRNA)-mediated loss of VAPB or PTPIP51 to loosen contacts stimulates, autophagosome formation (PMID:28132811). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>VAPB:RMDN3</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa5"> <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: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> </species> <species metaid="s_id_path_0_csa33" id="s_id_path_0_csa33" name="EIF2_minus_P:GDP" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>EIF2_minus_P:GDP</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re65"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa50" id="s_id_path_0_csa50" name="ERN1:BCL2L11" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>ERN1:BCL2L11</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re18"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa25" id="s_id_path_0_csa25" name="CASP8:CASP8_minus_ubq:FADD" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>CASP8:CASP8_minus_ubq:FADD</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa26" id="s_id_path_0_csa26" name="CASP8:FADD:MAP1LC3A:SQSTM1:ATG5" compartment="s_id_path_0_ca7" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>CASP8:FADD:MAP1LC3A:SQSTM1:ATG5</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_1_csa4" id="s_id_path_1_csa4" name="MFN1:MFN2" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 29491369 In mammalian cells, four types of connectors between ER and mitochondria have been identified. One of them comprises 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>MFN1:MFN2</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa4"> <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> </species> <species metaid="s_id_path_1_csa16" id="s_id_path_1_csa16" name="MCU:MICU1:MICU2:SMDT1" compartment="s_id_path_1_ca3" initialAmount="0"> <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. EMRE was required for the interaction of MCU with MICU1 and MICU2. EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium conducting role of MCU. It is proposed that EMRE interacts with MICU1 and MICU2 in the IMS and with MCU oligomers in the inner membrane, thus linking the calcium sensing activity of MICU1 and MICU2 to the channel activity of MCU, as in cells lacking EMRE, the interaction between MCU-FLAG and MICU1 and MICU2 was completely lost. Similarly, MCU was not associated with immunoprecipitated MICU1-FLAG in cells lacking EMRE. In the absence of EMRE, MCU still oligomerized and interacted with MCUb. Moreover, in the absence of EMRE, the interaction between MICU1 and MICU2 was intact. These data indicate that loss of EMRE specifically interrupted the association of MCU with MICU1 and MICU2. Furthermore, MCUb, MICU1 and MICU2 appear to be dispensable for MCU-EMRE interaction because in cells lacking MCUb or MICU1, EMRE was still associated with immunoprecipitated MCU-FLAG (PMID:24231807). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>MCU:MICU1:MICU2:SMDT1</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa16"> <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> </species> <species metaid="s_id_path_0_csa51" id="s_id_path_0_csa51" name="ERN1:BBC3" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>ERN1:BBC3</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re18"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa1" id="s_id_path_0_csa1" name="ATF6:HSPA5" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>ATF6:HSPA5</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa56" id="s_id_path_0_csa56" name="CAPN1:Ca2_plus_" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>CAPN1:Ca2_plus_</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re321"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_csa7" id="s_id_path_0_csa7" name="EIF2:GDP:Met_minus_tRNA" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>EIF2:GDP:Met_minus_tRNA</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_1_csa6" id="s_id_path_1_csa6" name="Mitochondrial_space_calcium_space_uniporter_space_complex" compartment="s_id_path_1_ca3" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 26968367 MICU1, MICU2, MCUb and EMRE were detected by protein immunoblotting after immunoprecipitation of MCU-FLAG from HEK-293T and HeLa cells. EMRE was required for the interaction of MCU with MICU1 and MICU2. EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium conducting role of MCU. It is proposed that EMRE interacts with MICU1 and MICU2 in the IMS and with MCU oligomers in the inner membrane, thus linking the calcium sensing activity of MICU1 and MICU2 to the channel activity of MCU, as in cells lacking EMRE, the interaction between MCU-FLAG and MICU1 and MICU2 was completely lost. Similarly, MCU was not associated with immunoprecipitated MICU1-FLAG in cells lacking EMRE. In the absence of EMRE, MCU still oligomerized and interacted with MCUb. Moreover, in the absence of EMRE, the interaction between MICU1 and MICU2 was intact. These data indicate that loss of EMRE specifically interrupted the association of MCU with MICU1 and MICU2. Furthermore, MCUb, MICU1 and MICU2 appear to be dispensable for MCU-EMRE interaction because in cells lacking MCUb or MICU1, EMRE was still associated with immunoprecipitated MCU-FLAG (PMID:24231807). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>Mitochondrial_space_calcium_space_uniporter_space_complex</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re25"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_csa6"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26968367"/> </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> </species> <species metaid="s264" id="s264" name="ACE2:Spike" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>ACE2:Spike</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s269" id="s269" name="HSPA5-Spike interaction" compartment="default" initialAmount="0"> <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). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>HSPA5-Spike interaction</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s269"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32340551"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s281" id="s281" name="ACE2-SARS-CoV interaction" compartment="s_id_path_0_ca6" initialAmount="0"> <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(PMID:19411314). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>COMPLEX</celldesigner:class> <celldesigner:name>ACE2-SARS-CoV interaction</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description 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<head> <title/> </head> <body> 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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xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa135"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0043066"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa120" id="s_id_path_1_sa120" name="unfolded_space_protein_space_response_space_(UPR)" compartment="s_id_path_0_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>It is shown that Mfn2 is essential for an appropriate elaboration of the UPR and ER homeostasis (PMID:22511781). 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). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>unfolded_space_protein_space_response_space_(UPR)</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa120"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0030968"/> </rdf:Bag> </bqbiol:is> <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> </species> <species metaid="s_id_path_0_sa15" id="s_id_path_0_sa15" name="retrograde_space_transport_space_from_space_ER_space_to_space_cytosol" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>retrograde_space_transport_space_from_space_ER_space_to_space_cytosol</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re42"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa15"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0030970"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa628" id="s_id_path_0_sa628" name="Apoptosis" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>Apoptosis</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa628"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0006921"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa96" id="s_id_path_0_sa96" name="Translation_space_initiation" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>Translation_space_initiation</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa96"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0006412"/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa69" id="s_id_path_1_sa69" name="ER_space_stress" compartment="s_id_path_0_ca1" initialAmount="0"> <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). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>ER_space_stress</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re40"/> <celldesigner:catalyzed reaction="path_1_re137"/> <celldesigner:catalyzed reaction="path_1_re108"/> <celldesigner:catalyzed reaction="path_1_re42"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa69"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0034976"/> </rdf:Bag> </bqbiol:is> <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> </species> <species metaid="s_id_path_1_sa97" id="s_id_path_1_sa97" name="mitochondrion_minus_endoplasmic_space_reticulum_space_membrane_space_tethering_space_" compartment="s_id_path_0_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>It is shown that the VAPB-PTPIP51 tethers regulate autophagy and that expression of a synthetic linker protein that artificially tethers ER and mitochondria also reduces autophagosome formation, and that this artificial tether rescues the effects of siRNA loss of VAPB or PTPIP51 on autophagy.Overexpression of VAPB or PTPIP51 to tighten ER-mitochondria contacts impairs, whereas small interfering RNA (siRNA)-mediated loss of VAPB or PTPIP51 to loosen contacts stimulates, autophagosome formation (PMID:28132811). 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name="high_space_Ca2_plus__space_cytosolic_space_concentration" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>high_space_Ca2_plus__space_cytosolic_space_concentration</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re324"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa259"> <bqbiol:is> <rdf:Bag> <rdf:li 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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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>Ca2_plus__space_cytosolic_space_concentration</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa151"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28132811"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0007204"/> </rdf:Bag> </bqbiol:is> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s274" id="s274" name="pulmonary fibrosis" compartment="default" initialAmount="0"> <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> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>pulmonary fibrosis</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s274"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:mesh:D011658"/> </rdf:Bag> </bqbiol:is> <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> </species> <species metaid="s280" id="s280" name="viral entry into host cell" compartment="s_id_path_0_ca6" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Soluble ACE2 was enzymatically active and partially inhibited virus entry into target cells via sACE2 competition for S protein binding (PMID:19411314). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>viral entry into host cell</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="re144"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s280"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0046718"/> </rdf:Bag> </bqbiol:is> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19411314"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa110" id="s_id_path_1_sa110" name="Apoptosis" compartment="s_id_path_0_ca1" initialAmount="0" hasOnlySubstanceUnits="true" charge="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Overexpression of MFN2 induces apoptosis, perhaps by excessive ER–mitochondria tethering and Ca2+ transfer (PMID:19052620). Depletion of PACS-2 induced cleavage of BAP31 to p20, similar to the process observed during apoptosis (PMDI:15692567). 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). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>Apoptosis</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re133"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa110"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0006915"/> </rdf:Bag> </bqbiol:is> <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:15692567"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22511781"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s289" id="s289" name="SARS-CoV infection" compartment="default" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>SARS-CoV infection</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> </annotation> </species> <species metaid="s290" id="s290" name="viral RNA genome replication" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>viral RNA genome replication</celldesigner:name> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s290"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0039694"/> </rdf:Bag> </bqbiol:is> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:14647384"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa60" id="s_id_path_1_sa60" name="Ca2_plus__space_ER_space_depletion" compartment="s_id_path_0_ca1" initialAmount="0"> <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> <celldesigner:extension> <celldesigner:positionToCompartment>innerSurface</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PHENOTYPE</celldesigner:class> <celldesigner:name>Ca2_plus__space_ER_space_depletion</celldesigner:name> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re40"/> <celldesigner:catalyzed reaction="path_1_re42"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa60"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:obo.go:GO%3A0032471"/> </rdf:Bag> </bqbiol:is> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17981125"/> </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:10029"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa57" id="s_id_path_0_sa57" name="ATF6" compartment="s_id_path_0_ca3" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa57</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa57"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:ATF6"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa630" id="s_id_path_0_sa630" name="DDIT3" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa630</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re38"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa630"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:DDIT3"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa459" id="s_id_path_0_sa459" name="BAK1" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa459</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re17"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa459"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BAK1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa598" id="s_id_path_0_sa598" name="CASP9" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa598</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa598"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:CSAP9"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa204" id="s_id_path_0_sa204" name="TRAF2" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa204</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re75"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa204"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:TRAF2"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa158" id="s_id_path_1_sa158" name="FIS1" compartment="s_id_path_1_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa158</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa158"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:21689"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa4" id="s_id_path_0_sa4" name="HSPA5" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa4</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa4"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:5238"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa238" id="s_id_path_0_sa238" name="SQSTM1_space_" compartment="s_id_path_0_ca7" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa238</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa238"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:SQSTM1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa88" id="s_id_path_1_sa88" name="ITPR3" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Sig-1R stabilizes IP3R3 at MAM (PMID:17981125). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa88</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa88"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:6182"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17981125"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa3" id="s_id_path_0_sa3" name="ATF6" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa3</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF 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<celldesigner:catalyzed reaction="path_0_re61"/> <celldesigner:catalyzed reaction="path_0_re162"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa624"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:DNAJC3"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa433" id="s_id_path_0_sa433" name="BCL2L11" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa433</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa433"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BCL2L11"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa153" id="s_id_path_0_sa153" name="BCL2L1" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa153</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re17"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa153"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BCL2L1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa625" id="s_id_path_0_sa625" name="ERO1A" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa625</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re317"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa625"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:ERO1A"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa475" id="s_id_path_0_sa475" name="BCL2L11" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa475</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa475"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BCL2L11"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa90" id="s_id_path_0_sa90" name="EIF2S1" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa90</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa90"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:EIF2S1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa458" id="s_id_path_0_sa458" name="BAX" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa458</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re17"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa458"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BAX"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa603" id="s_id_path_0_sa603" name="PPP2CA" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa603</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re249"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa603"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:PPP2CA"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa88" id="s_id_path_0_sa88" name="EIF2S2" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa88</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa88"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:EIF2S2"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa599" id="s_id_path_0_sa599" name="cleaved~CASP9" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa599</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa599"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:CASP9"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa34" id="s_id_path_1_sa34" name="MCU" compartment="s_id_path_1_ca3" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 23526 Pubmed_ID: 24231807 It is proposed that EMRE interacts with MICU1 and MICU2 in the IMS and with MCU oligomers in the inner membrane, thus linking the calcium sensing activity of MICU1 and MICU2 to the channel activity of MCU, as in cells lacking EMRE, the interaction between MCU-FLAG and MICU1 and MICU2 was completely lost. Similarly, MCU was not associated with immunoprecipitated MICU1-FLAG in cells lacking EMRE. In the absence of EMRE, MCU still oligomerized and interacted with MCUb. Moreover, in the absence of EMRE, the interaction between MICU1 and MICU2 was intact. These data indicate that loss of EMRE specifically interrupted the association of MCU with MICU1 and MICU2. Furthermore, MCUb, MICU1 and MICU2 appear to be dispensable for MCU-EMRE interaction because in cells lacking MCUb or MICU1, EMRE was still associated with immunoprecipitated MCU-FLAG (PMID:24231807). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>innerSurface</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa34</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa34"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:23526"/> </rdf:Bag> </bqbiol:isEncodedBy> <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> </species> <species metaid="s_id_path_0_sa107" id="s_id_path_0_sa107" name="PPP1R15A" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa107</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re80"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa107"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:PPP1R15A"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa602" id="s_id_path_0_sa602" name="CAPN1" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa602</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa602"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:CAPN1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa203" id="s_id_path_0_sa203" name="Unfolded_space_protein" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa203</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re129"/> <celldesigner:catalyzed reaction="path_0_re1"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> </annotation> </species> <species metaid="s_id_path_0_sa144" id="s_id_path_0_sa144" name="MAP3K4" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa144</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa144"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MAP3K4"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa147" id="s_id_path_1_sa147" name="VAPB" compartment="s_id_path_0_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 12649 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) to form at least some of the MAM tethers (PMID: 28132811). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa147</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa147"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:12649"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa147" id="s_id_path_0_sa147" name="CDK5" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa147</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re93"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa147"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:CDK5"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa43" id="s_id_path_0_sa43" name="MAPK14" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa43</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re374"/> <celldesigner:catalyzed reaction="path_0_re81"/> <celldesigner:catalyzed reaction="path_0_re32"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa43"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MAPK14"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa121" id="s_id_path_0_sa121" name="ERO1A" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa121</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa121"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:ERO1A"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa210" id="s_id_path_0_sa210" name="EIF2AK2" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa210</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re61"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa210"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:EIF2AK2"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa241" id="s_id_path_0_sa241" name="ATG5" compartment="s_id_path_0_ca7" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa241</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa241"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:ATG5"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa60" id="s_id_path_0_sa60" name="MBTPS1" compartment="s_id_path_0_ca3" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa60</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re44"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa60"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MBTPS1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa2" id="s_id_path_0_sa2" name="EIF2AK3" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa2</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa2"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:EIF2AK3"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa127" id="s_id_path_0_sa127" name="BAX" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa127</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa127"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BAX"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa35" id="s_id_path_1_sa35" name="SMDT1" compartment="s_id_path_1_ca3" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 25055 Pubmed_ID: 24231807 It is proposed that EMRE interacts with MICU1 and MICU2 in the IMS and with MCU oligomers in the inner membrane, thus linking the calcium sensing activity of MICU1 and MICU2 to the channel activity of MCU, as in cells lacking EMRE, the interaction between MCU-FLAG and MICU1 and MICU2 was completely lost. Similarly, MCU was not associated with immunoprecipitated MICU1-FLAG in cells lacking EMRE. In the absence of EMRE, MCU still oligomerized and interacted with MCUb. Moreover, in the absence of EMRE, the interaction between MICU1 and MICU2 was intact. These data indicate that loss of EMRE specifically interrupted the association of MCU with MICU1 and MICU2. Furthermore, MCUb, MICU1 and MICU2 appear to be dispensable for MCU-EMRE interaction because in cells lacking MCUb or MICU1, EMRE was still associated with immunoprecipitated MCU-FLAG (PMID:24231807). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>outerSurface</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa35</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa35"> <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:hgnc:25055"/> </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> </species> <species metaid="s_id_path_0_sa41" id="s_id_path_0_sa41" name="MAPK8" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa41</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re221"/> <celldesigner:catalyzed reaction="path_0_re154"/> <celldesigner:catalyzed reaction="path_0_re81"/> <celldesigner:catalyzed reaction="path_0_re222"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa41"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MAPK8"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa626" id="s_id_path_0_sa626" name="XBP1" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa626</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re50"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa626"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:XBP1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa33" id="s_id_path_1_sa33" name="MCU2" compartment="s_id_path_1_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 31830 Pubmed_ID: 24231807 It is proposed that EMRE interacts with MICU1 and MICU2 in the IMS and with MCU oligomers in the inner membrane, thus linking the calcium sensing activity of MICU1 and MICU2 to the channel activity of MCU, as in cells lacking EMRE, the interaction between MCU-FLAG and MICU1 and MICU2 was completely lost. Similarly, MCU was not associated with immunoprecipitated MICU1-FLAG in cells lacking EMRE. In the absence of EMRE, MCU still oligomerized and interacted with MCUb. Moreover, in the absence of EMRE, the interaction between MICU1 and MICU2 was intact. These data indicate that loss of EMRE specifically interrupted the association of MCU with MICU1 and MICU2. Furthermore, MCUb, MICU1 and MICU2 appear to be dispensable for MCU-EMRE interaction because in cells lacking MCUb or MICU1, EMRE was still associated with immunoprecipitated MCU-FLAG (PMID:24231807). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa33</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa33"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:31830"/> </rdf:Bag> </bqbiol:isEncodedBy> <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> </species> <species metaid="s_id_path_0_sa436" id="s_id_path_0_sa436" name="BID" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa436</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> </celldesigner:extension> 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xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> 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). 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). In mammalian cells, four types of connectors between ER and mitochondria have been identified. One of them comprises 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa153</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa153"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:16877"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa597" id="s_id_path_0_sa597" name="cleaved~CASP3" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa597</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa597"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:CASP3"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa87" id="s_id_path_0_sa87" name="EIF2S1" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa87</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa87"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:EIF2S1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa435" id="s_id_path_0_sa435" name="BID" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa435</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa435"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BID"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa239" id="s_id_path_0_sa239" name="MAP1LC3A" compartment="s_id_path_0_ca7" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa239</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa239"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MAP1LC3A"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa261" id="s_id_path_0_sa261" name="AP_minus_1" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa261</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> <celldesigner:modification residue="rs2" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa261"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:JUNB"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOSL1"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOSL2"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:JUND"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:JUN"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOSB"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOS"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa61" id="s_id_path_0_sa61" name="MBTPS2" compartment="s_id_path_0_ca3" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa61</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re45"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa61"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MBTPS2"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa166" id="s_id_path_1_sa166" name="p20" compartment="s_id_path_0_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body> Depletion of PACS-2 induced cleavage of BAP31 to p20, similar to the process observed during apoptosis. Mitochondria fragmentation and BiP induction in PACS-2-depleted cells resulted directly from the cleavage of BAP31 to p20 (PMID:15692567). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa166</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa166"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BCAP31"/> </rdf:Bag> </bqbiol:isEncodedBy> 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xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa104"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:ATF4"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa39" id="s_id_path_0_sa39" name="MAP3K5" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa39</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re30"/> <celldesigner:catalyzed reaction="path_0_re29"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa39"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MAP3K5"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa99" id="s_id_path_1_sa99" name="MFN1" compartment="s_id_path_1_ca1" initialAmount="0"> <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 (PMID:1905620). In mammalian cells, four types of connectors between ER and mitochondria have been identified. One of these connectors comprises 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa99</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa99"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:1826"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa596" id="s_id_path_0_sa596" name="CASP3" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa596</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa596"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:CASP3"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa629" id="s_id_path_0_sa629" name="DDIT3" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa629</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re154"/> <celldesigner:catalyzed reaction="path_0_re76"/> <celldesigner:catalyzed reaction="path_0_re252"/> <celldesigner:catalyzed reaction="path_0_re67"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa629"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:DDIT3"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa98" id="s_id_path_1_sa98" name="MFN2" compartment="s_id_path_0_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 16877 Pubmed_ID: 29491369, 22511781, 19052620 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). 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). In mammalian cells, four types of connectors between ER and mitochondria have been identified. One of them comprises 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa98</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa98"> <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:22511781"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:16877"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19052620"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa171" id="s_id_path_1_sa171" name="ADAM17" compartment="s_id_path_0_ca6" initialAmount="0"> <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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa171</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="re138"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa171"> <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:hgnc:HGNC%3A195"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa146" id="s_id_path_1_sa146" name="RMDN3" compartment="s_id_path_1_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 25550 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) to form at least some of the MAM tethers (PMID: 28132811). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa146</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa146"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:25550"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa260" id="s_id_path_0_sa260" name="AP_minus_1" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa260</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa260"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:JUNB"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOSL1"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOSL2"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:JUND"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:JUN"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOSB"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:FOS"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa174" id="s_id_path_1_sa174" name="ADAM17" compartment="s_id_path_1_ca8" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 195 Pubmed_ID: 32264791, 26108729 PACS-2 interacts with ADAM17 under basal conditions. 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 loss did not affect constitutive ADAM17 internalization, but rather decreased the cell-surface recycling and stability of internalized ADAM17. PACS-2 co-localizes with ADAM17 on early endosomes and 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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa174</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa174"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:195"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32264791"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26108729"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa180" id="s_id_path_1_sa180" name="ACE2,_space_soluble" compartment="default" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 19411314, 32264791 ACE2 must be cell attached to function as a SARS-CoV receptor. Soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface (PMID:19411314). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa180</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="re140"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa180"> <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:hgnc.symbol:ACE2"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa487" id="s_id_path_0_sa487" name="TMBIM6" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>innerSurface</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa487</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re107"/> <celldesigner:catalyzed reaction="path_0_re317"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa487"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:TMBIM6"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa175" id="s_id_path_1_sa175" name="PACS2" compartment="s_id_path_1_ca8" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 23794 Pubmed_ID: 15692567, 26108729 PACS-2 co-localizes with ADAM17 on early endosomes (PMID:26108729). 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 also controls formation of ER lipid-synthesizing centers found on mitochondria-associated membranes and ER homeostasis.In response to apoptotic inducers, PACS-2 translocates Bid to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated Bid, the release of cytochrome c, and the activation of caspase-3, thereby causing cell death (PMID:15692567). The cytosolic sorting protein PACS-2 regulates the distribution and activity of calnexin. Under control conditions, over 80% of calnexin localizes to the ER, mainly at the MAM. However, through a protein-protein interaction, PACS-2 causes calnexin to distribute between the ER and the plasma membrane. PACS-2 thus affects the homeostasis of ER Ca2+ (PMID:19144519.) The knockdown of PACS-2 uncouples mitochondria from the ER. PACS-2 downregulation induces BAP31 cleavage-dependent cell death, which suggests an antiapoptotic role of this factor (PMID:29491369). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa175</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa175"> <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:hgnc:23794"/> </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> </species> <species metaid="s_id_path_0_sa254" id="s_id_path_0_sa254" name="TRIM13" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa254</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re373"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" 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xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa156"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:16695"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa40" id="s_id_path_0_sa40" name="MAPK8" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa40</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa40"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MAPK8"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa65" id="s_id_path_0_sa65" name="ATF6" compartment="s_id_path_0_ca2" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa65</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re18"/> <celldesigner:catalyzed reaction="path_0_re76"/> <celldesigner:catalyzed reaction="path_0_re50"/> <celldesigner:catalyzed reaction="path_0_re273"/> <celldesigner:catalyzed reaction="path_0_re327"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa65"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:ATF6"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa145" id="s_id_path_0_sa145" name="MAP3K4" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa145</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re29"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa145"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:MAP3K4"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa434" id="s_id_path_0_sa434" name="BCL2L11" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa434</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfModifications> <celldesigner:modification residue="rs1" state="phosphorylated"/> </celldesigner:listOfModifications> </celldesigner:state> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa434"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:BCL2L11"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa290" id="s_id_path_0_sa290" name="EIF2AK1" compartment="s_id_path_0_ca6" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa290</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re80"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa290"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:EIF2AK1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa32" id="s_id_path_1_sa32" name="MCU1" compartment="s_id_path_1_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 1530 Pubmed_ID: 24231807 It is proposed that EMRE interacts with MICU1 and MICU2 in the IMS and with MCU oligomers in the inner membrane, thus linking the calcium sensing activity of MICU1 and MICU2 to the channel activity of MCU, as in cells lacking EMRE, the interaction between MCU-FLAG and MICU1 and MICU2 was completely lost. Similarly, MCU was not associated with immunoprecipitated MICU1-FLAG in cells lacking EMRE. In the absence of EMRE, MCU still oligomerized and interacted with MCUb. Moreover, in the absence of EMRE, the interaction between MICU1 and MICU2 was intact. These data indicate that loss of EMRE specifically interrupted the association of MCU with MICU1 and MICU2. Furthermore, MCUb, MICU1 and MICU2 appear to be dispensable for MCU-EMRE interaction because in cells lacking MCUb or MICU1, EMRE was still associated with immunoprecipitated MCU-FLAG (PMID:24231807). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa32</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa32"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:1530"/> </rdf:Bag> </bqbiol:isEncodedBy> <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> </species> <species metaid="s_id_path_1_sa145" id="s_id_path_1_sa145" name="ACE2" compartment="s_id_path_0_ca6" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 19411314, 32264791 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). ACE2 must be cell attached to function as a SARS-CoV receptor. Soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface (PMID:19411314). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa145</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re110"/> <celldesigner:catalyzed reaction="path_1_re137"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa145"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:HGNC%3A13557"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15692567"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32264791"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19411314"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa494" id="s_id_path_0_sa494" name="RYR1" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>innerSurface</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa494</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_0_re107"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa494"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:RYR1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s260" id="s260" name="SIGMAR1" compartment="s_id_path_0_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 8157 BiP(= GRP78 = HSPA5) 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 (PMID:25704011). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa82</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s260"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:8157"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s261" id="s261" name="ERN1" compartment="s_id_path_0_ca1" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa1</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s261"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:ERN1"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s262" id="s262" name="PACS2" compartment="s_id_path_0_ca1" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 23794 Pubmed_ID: 15692567 PACS-2 co-localizes with ADAM17 on early endosomes (PMID:26108729). 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 also controls formation of ER lipid-synthesizing centers found on mitochondria-associated membranes and ER homeostasis.In response to apoptotic inducers, PACS-2 translocates Bid to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated Bid, the release of cytochrome c, and the activation of caspase-3, thereby causing cell death (PMID:15692567). The cytosolic sorting protein PACS-2 regulates the distribution and activity of calnexin. Under control conditions, over 80% of calnexin localizes to the ER, mainly at the MAM. However, through a protein-protein interaction, PACS-2 causes calnexin to distribute between the ER and the plasma membrane. PACS-2 thus affects the homeostasis of ER Ca2+ (PMID:19144519.) The knockdown of PACS-2 uncouples mitochondria from the ER. PACS-2 downregulation induces BAP31 cleavage-dependent cell death, which suggests an antiapoptotic role of this factor (PMID:29491369). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa3</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re133"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s262"> <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:hgnc:23794"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s263" id="s263" name="S" compartment="default" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>pr155</celldesigner:proteinReference> </celldesigner:speciesIdentity> <celldesigner:listOfCatalyzedReactions> <celldesigner:catalyzed reaction="path_1_re110"/> </celldesigner:listOfCatalyzedReactions> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s263"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P59594"/> </rdf:Bag> </bqbiol:isEncodedBy> <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:uniprot:W6A028"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s267" id="s267" name="HSPA5" compartment="default" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_0_sa4</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s267"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32340551"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:HGNC%3A5238"/> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32169481"/> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30978349"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s272" id="s272" name="SIGMAR1" compartment="s_id_path_1_ca9" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>HGNC_ID: 8157 BiP(= GRP78 = HSPA5) 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 (PMID:25704011). ER stress such as TG (Thapsigargin) caused a dramatic redistribution of Sig-1Rs only when the stress lasted longer than 30 min. The significant decrease of Sig-1R immunoreactivity in MAM and the increase of Sig-1Rs in ER reticular network and nuclear envelope indicate that the redistribution may involve translocation of Sig-1Rs from MAM to the periphery of the ER. Sig-1R stabilizes IP3R3 at MAM (PMID:17981125). </body> </html> </notes> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa82</celldesigner:proteinReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s272"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc:8157"/> </rdf:Bag> </bqbiol:isEncodedBy> <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> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25704011"/> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa178" id="s_id_path_1_sa178" name="ACE2,_space_membrane_minus_bound" compartment="s_id_path_0_ca6" initialAmount="0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <title/> </head> <body>Pubmed_ID: 19411314, 32264791 ACE2 must be cell attached to function as a SARS-CoV receptor. Soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface (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> <celldesigner:extension> <celldesigner:positionToCompartment>transmembrane</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>PROTEIN</celldesigner:class> <celldesigner:proteinReference>p_s_id_path_1_sa178</celldesigner:proteinReference> <celldesigner:state> <celldesigner:listOfStructuralStates> <celldesigner:structuralState structuralState="active"/> </celldesigner:listOfStructuralStates> </celldesigner:state> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" 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initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>RNA</celldesigner:class> <celldesigner:rnaReference>r_s_id_path_0_sa108</celldesigner:rnaReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_0_sa108"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:PPP1R15A"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_1_sa149" id="s_id_path_1_sa149" name="HSPA5" compartment="s_id_path_0_ca2" initialAmount="0"> <annotation> <celldesigner:extension> <celldesigner:positionToCompartment>inside</celldesigner:positionToCompartment> <celldesigner:speciesIdentity> <celldesigner:class>RNA</celldesigner:class> <celldesigner:rnaReference>r_s_id_path_1_sa149</celldesigner:rnaReference> </celldesigner:speciesIdentity> </celldesigner:extension> <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/"> <rdf:Description rdf:about="#s_id_path_1_sa149"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:hgnc.symbol:HSPA5"/> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF> </annotation> </species> <species metaid="s_id_path_0_sa71" id="s_id_path_0_sa71" name="DDIT3" compartment="s_id_path_0_ca2" 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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. 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