BioPAX pathway converted from "SMAC, XIAP-regulated apoptotic response" in the Reactome database.SMAC, XIAP-regulated apoptotic responseSMAC, XIAP-regulated apoptotic responseThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>XIAP binds CASP3XIAP binds CASP3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 97155152cytosolGO0005829UniProt:Q60989XiapReactomehttp://www.reactome.orgMus musculusNCBI Taxonomy10090UniProtQ60989Chain Coordinates1EQUAL497EQUALReactome DB_ID: 25341531Caspase-3 tetramer [cytosol]Caspase-3 tetramerReactome DB_ID: 25341422Caspase-3 dimer [cytosol]Caspase-3 dimerReactome DB_ID: 25341401UniProt:P70677 Casp3Casp3Casp3Cpp32FUNCTION Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Triggers cell adhesion in sympathetic neurons through RET cleavage (By similarity). Cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes.SUBUNIT Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce.TISSUE SPECIFICITY Highest expression in spleen, lung, liver, kidney and heart. Lower expression in brain, skeletal muscle and testis.PTM Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa (By similarity).PTM S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol (By similarity).SIMILARITY Belongs to the peptidase C14A family.UniProtP7067729EQUAL175EQUALReactome DB_ID: 25341411176EQUAL277EQUALReactome Database ID Release 752534142Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2534142ReactomeR-MMU-25341421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2534142.1Reactome Database ID Release 752534153Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2534153ReactomeR-MMU-25341531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2534153.1Reactome DB_ID: 98157991XIAP:Caspase-3 [cytosol]XIAP:Caspase-3Reactome DB_ID: 971551521EQUAL497EQUALReactome DB_ID: 25341531Reactome Database ID Release 759815799Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815799ReactomeR-MMU-1143041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-114304.1Reactome Database ID Release 759815803Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815803ReactomeR-MMU-96271041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627104.1X‑linked inhibitor of apoptosis protein (XIAP) suppresses cell death by inhibiting the catalytic activity of caspases (Deveraux QL et al. 1997; Paulsen M et al. 2008). XIAP consists of three bacculoviral inhibitory repeat (BIR) domains and a C‑terminal ring finger. Biochemical and structural analyses revealed that the linker connecting BIR1 to BIR2 inhibits executioner caspase‑3 and ‑7 by positioning itself at the active site (Sun C et al. 1999; Riedl SJ et al. 2001; Huang Y et al. 2001; Chai J et al. 2001). Formation of a complex between caspase‑3 or caspase‑7 and the XIAP BIR2‑linker region appears to be driven by interactions between XIAP's Leu141 and Val146 and a hydrophobic site present on both caspases. This hydrophobic site is not found in caspase‑8 or caspase‑9, perhaps explaining the binding specificity of XIAP (Riedl SJ et al. 2001). BIR2 domain of XIAP may also contribute to inhibition of executioner caspases by interacting with additional sites on the enzymes (Scott FL et al. 2005; Abhari BA & Davoodi J 2008).11257231Pubmed2001Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domainHuang, YPark, YCRich, RLSegal, DMyszka, DGWu, HCell 104:781-9015650747Pubmed2005XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPsScott, Fiona LDenault, JBRiedl, Stefan JShin, HwainRenatus, MartinSalvesen, Guy SEMBO J. 24:645-5511230124Pubmed2001Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexesBratton, S BWalker, GSrinivasula, S MSun, X MButterworth, MAlnemri, E SCohen, G MEMBO J. 20:998-1009inferred by electronic annotationIEAGOIEAINHIBITIONReactome Database ID Release 759815804Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815804Reactome DB_ID: 9815801DIABLO:XIAP:Caspase-3 [cytosol]DIABLO:XIAP:Caspase-3Reactome DB_ID: 97156171DIABLO dimer [cytosol]DIABLO dimerReactome DB_ID: 97155982UniProt:Q9JIQ3DiabloUniProtQ9JIQ356EQUAL239EQUALReactome Database ID Release 759715617Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715617ReactomeR-MMU-96270541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627054.1Reactome DB_ID: 98157991Reactome Database ID Release 759815801Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815801ReactomeR-MMU-1143051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-114305.1XIAP binds CASP7XIAP binds CASP7This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 971551521EQUAL497EQUALReactome DB_ID: 97155631Caspase-7 [cytosol]Caspase-7Reactome DB_ID: 97155612CASP7(24-198):CASP7(207-303) [cytosol]CASP7(24-198):CASP7(207-303)Reactome DB_ID: 97155571UniProt:P97864Casp7UniProtP9786424EQUAL198EQUALReactome DB_ID: 97155591207EQUAL303EQUALReactome Database ID Release 759715561Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715561ReactomeR-MMU-68043591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-6804359.1Reactome Database ID Release 759715563Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715563ReactomeR-MMU-1416431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-141643.1Reactome DB_ID: 97156151XIAP:Caspase-7 [cytosol]XIAP:Caspase-7Reactome DB_ID: 971551521EQUAL497EQUALReactome DB_ID: 97155631Reactome Database ID Release 759715615Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715615ReactomeR-MMU-1143081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-114308.1Reactome Database ID Release 759815808Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815808ReactomeR-MMU-96271071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627107.1The inhibitor‑of‑apoptosis (IAP) family of proteins such as X‑linked IAP (XIAP) suppress cell death by inhibiting the catalytic activity of caspases (Deveraux QL et al. 1997; Paulsen M et al. 2008). XIAP consists of three bacculoviral inhibitory repeat (BIR) domains and a C‑terminal ring finger. Biochemical and structural analyses revealed that the linker connecting BIR1 to BIR2 inhibits executioner caspase‑3 and ‑7 by positioning itself at the active site (Sun C et al. 1999; Riedl SJ et al. 2001; Huang Y et al. 2001; Chai J et al. 2001). Formation of a complex between caspase‑3 or caspase‑7 and the XIAP BIR2‑linker region appears to be driven by interactions between XIAP's Leu141 and Val146 and a hydrophobic site present on both caspases. This hydrophobic site is not found in caspase‑8 or caspase‑9, perhaps explaining the binding specificity of XIAP (Riedl SJ et al. 2001). BIR2 domain of XIAP may also contribute to inhibition of executioner caspases by interacting with additional sites on the enzymes (Scott FL et al. 2005; Abhari BA & Davoodi J 2008).11257230Pubmed2001Structural basis of caspase-7 inhibition by XIAPChai, JShiozaki, ESrinivasula, S MWu, QDatta, PAlnemri, E SShi, YDataa, PCell 104:769-8018521960Pubmed2008Interaction with XIAP prevents full caspase-3/-7 activation in proliferating human T lymphocytesPaulsen, MarenUssat, SandraJakob, MartenScherer, GudrunLepenies, IngaSchütze, StefanKabelitz, DieterAdam-Klages, SabineEur. J. Immunol. 38:1979-87inferred by electronic annotationIEAGOIEAINHIBITIONReactome Database ID Release 759815790Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815790Reactome DB_ID: 9715617SMAC (DIABLO) binds to IAPs SMAC (DIABLO) binds to IAPs This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>SMAC (DIABLO) binds XIAPSMAC (DIABLO) binds XIAPThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 971551521EQUAL497EQUALReactome DB_ID: 97156171Reactome DB_ID: 97156231DIABLO dimer:XIAP [cytosol]DIABLO dimer:XIAPReactome DB_ID: 971551521EQUAL497EQUALReactome DB_ID: 97156171Reactome Database ID Release 759715623Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715623ReactomeR-MMU-96273911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627391.1Reactome Database ID Release 759815810Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815810ReactomeR-MMU-96273501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627350.1Second mitochondria derived activator of caspase/direct inhibitor of apoptosis binding protein with low pI (SMAC, also known as DIABLO) is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis (Du C et al. 2000). Mitochondrial import and cleavage of its signal peptide are required for SMAC to gain its apoptotic activity (Du C et al. 2000). In vitro studies revealed that dimerization was required for its function, while monomerization of cytosolic mature SMAC attenuated interaction with XIAP (Chai J et al. 2000; Burke SP & Smith JB 2010). Moreover, SMAC dimer showed high stability in vitro as measured by high hydrostatic pressure, low and high temperatures, and chemical denaturation (Goncalves RB et al. 2008). Binding of SMAC (DIABLO) to the BIR3 region of X linked inhibitor of apoptosis protein (XIAP) competitively inhibits binding of XIAP to caspase 9, while binding to the BIR2 region sterically hinders the interaction of XIAP with CASP3 and CASP7 (Srinivasula SM et al. 2001; Abhari BA & Davoodi J 2008).10929711Pubmed2000Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibitionDu, CFang, MLi, YLi, LWang, XCell 102:33-4210972280Pubmed2000Structural and biochemical basis of apoptotic activation by Smac/DIABLOChai, JDu, CWu, J WKyin, SWang, XShi, YNature 406:855-6211242052Pubmed2001A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosisSrinivasula, S MHegde, RSaleh, ADatta, PShiozaki, EChai, JLee, R ARobbins, P DFernandes-Alnemri, TShi, YAlnemri, E SNature 410:112-618619610Pubmed2008A mechanistic insight into SMAC peptide interference with XIAP-Bir2 inhibition of executioner caspasesAbhari, Behnaz AhangarianDavoodi, JamshidJ. Mol. Biol. 381:645-5420957035Pubmed2010Monomerization of cytosolic mature smac attenuates interaction with IAPs and potentiation of caspase activationBurke, Stephen PSmith, Jeffrey BPLoS ONE 5:11140638Pubmed2000Structural basis of IAP recognition by Smac/DIABLOWu, GChai, JSuber, T LWu, J WDu, CWang, XShi, YNature 408:1008-1218307314Pubmed2008The proapoptotic protein Smac/DIABLO dimer has the highest stability as measured by pressure and urea denaturationGonçalves, Rafael BSanches, DanielSouza, Theo L FSilva, Jerson LOliveira, Andréa CBiochemistry 47:3832-41inferred by electronic annotationIEAGOIEASMAC binds XIAP:Caspase-7SMAC binds XIAP:Caspase-7This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 97156171Reactome DB_ID: 97156151Reactome DB_ID: 97156191DIABLO:XIAP:Caspase-7 [cytosol]DIABLO:XIAP:Caspase-7Reactome DB_ID: 97156171Reactome DB_ID: 97156151Reactome Database ID Release 759715619Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715619ReactomeR-MMU-1143531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-114353.1Reactome Database ID Release 759715621Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715621ReactomeR-MMU-1143541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-114354.1The linker region preceding BIR2 of XIAP is responsible for the inhibition of caspase‑3 and ‑7, which is further stabilized by interaction with the BIR2 domain itself (Scott et al. 2005). Binding of a dimeric SMAC (DIABLO) N‑terminal peptide with the BIR2 domain of XIAP effectively antagonized inhibition of caspase‑7 by XIAP (Wu G et al. 2000; Chai J et al. 2000). 14960576Pubmed2004Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells.Yang, QHDu, CJ Biol Chem 279:16963-709230442Pubmed1997X-linked IAP is a direct inhibitor of cell-death proteases.Deveraux, QLTakahashi, RSalvesen, Guy S.Reed, JCNature 388:300-4inferred by electronic annotationIEAGOIEAReactome Database ID Release 759817924Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9817924ReactomeR-MMU-1114631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-111463.1Second mitochondria‑derived activator of caspases protein (SMAC, also known as direct IAP binding protein with low pI or DIABLO) in its dimeric form interacts and antagonizes X‑linked inhibitor of apoptosis protein (XIAP) by concurrently targeting both BIR2 and BIR3 domains of XIAP (Chai J et al. 2000; Liu Z et sl. 2000; Burke SP & Smith JB 2010). XIAP inhibits apoptosis by binding to and inhibiting the effectors caspase‑3 and ‑7 and an initiator caspase‑9 (Deveraux QL et al. 1997; Paulsen M et al. 2008). During apoptosis, SMAC (DIABLO) is released from the mitochondria (Du C et al. 2000). In the cytosol, SMAC binds to XIAP displacing it from caspase:XIAP complexes liberating the active caspases (Wu G et al. 2000; Abhari BA & Davoodi J 2008).11140637Pubmed2000Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domainLiu, ZSun, COlejniczak, E TMeadows, R PBetz, S FOost, THerrmann, JWu, J CFesik, S WNature 408:1004-812042762Pubmed2002IAP proteins: blocking the road to death's doorSalvesen, Guy S.Duckett, CSNat Rev Mol Cell Biol 3:401-10inferred by electronic annotationIEAGOIEASMAC(DIABLO)-mediated dissociation of IAP:caspase complexes SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Dissociation of Caspase-7 from DIABLO:XIAP:Caspase-7Dissociation of Caspase-7 from DIABLO:XIAP:Caspase-7This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 97156191Reactome DB_ID: 97156231Reactome DB_ID: 97155631Reactome Database ID Release 759715625Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9715625ReactomeR-MMU-1143921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-114392.1The linker region preceding BIR2 of XIAP is responsible for the inhibition of caspase-3 and -7, which is further stabilized by interaction with the BIR2 domain itself (Scott et al. 2005). Binding of a dimeric SMAC (DIABLO) N-terminal peptide with the BIR2 domain of XIAP effectively antagonized inhibition of caspase-7 by XIAP (Wu G et al. 2000; Chai J et al. 2000). As DIABLO has a higher affinity for the BIR2 domain than caspase-7, DIABLO (SMAC) binding to XIAP results in the liberation of caspase-7 (Huang et al. 2001).inferred by electronic annotationIEAGOIEAReactome Database ID Release 759817928Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9817928ReactomeR-MMU-1114641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-111464.1Second mitochondria derived activator of caspase/direct inhibitor of apoptosis binding protein with low pI (SMAC, also known as DIABLO) regulates XIAP function and potentiates caspase-3, -7 and -9 activity by disrupting the interaction of caspases with XIAP. Residues 56-59 of SMAC (DIABLO) are homologous to the amino-terminal motif that is used by caspase-9 (CASP9) to bind to the BIR3 domain of XIAP. SMAC (DIABLO) competes with CASP9 for binding to BIR3 domain of XIAP promoting the release of XIAP from the CASP9:apoptosome complex (Srinivasula SM et al. 2001; Salvesen et al. 2002). The binding of SMAC to the BIR2 and BIR3 regions of XIAP creates a steric hindrance that is essential for preventing binding of XIAP linker region with effector caspases CASP3 and CASP7 thus achieving neutralization of XIAP inhibition. The strong affinity for XIAP allows SMAC (DIABLO) to displace caspase-3, -7 from the XIAP:caspase complexes (Wu G et al. 2000; Chai J et al. 2001; Huang Y et al. 2003; Abhari BA & Davoodi J 2008).14512414Pubmed2003Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein (XIAP)-mediated caspase inhibition by SmacHuang, YihuaRich, RLMyszka, David GWu, HJ. Biol. Chem. 278:49517-22inferred by electronic annotationIEAGOIEASEPT4 binds XIAPSEPT4 binds XIAPThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 971551511EQUAL497EQUALReactome DB_ID: 98158121SEPT4 dimer [cytosol]SEPT4 dimerReactome DB_ID: 97994692UniProt:P28661Septin4UniProtP286611EQUAL274EQUALReactome Database ID Release 759815812Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815812ReactomeR-MMU-96273471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627347.1Reactome DB_ID: 98158141SEPT4 dimer:XIAP [cytosol]SEPT4 dimer:XIAPReactome DB_ID: 971551511EQUAL497EQUALReactome DB_ID: 979946921EQUAL274EQUALReactome Database ID Release 759815814Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815814ReactomeR-MMU-96274411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627441.1Reactome Database ID Release 759815816Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9815816ReactomeR-MMU-96273691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9627369.1SEPT4 (known also as ARTS, an apoptosis-related protein in the TGF-beta signaling pathway) is a pro-apoptotic mitochondrial protein (Gottfried Y et al. 2004). SEPT4 is an unique member of the septin family which functions as a tumor suppressor. SEPT4 promotes apoptosis through binding and antagonizing inhibitor of apoptosis (IAP) proteins and specifically X linked IAP (XIAP) (Gottfried Y et al. 2004). NMR and fluorescence spectroscopy showed that the C-terminal domain (CTD) of SEPT4 directly binds BIR3 domain of XIAP. The BIR3 interacting region in SEPT4 CTD was mapped to SEPT4 residues 266 - 274, which are the nine C-terminal residues in the protein (Bornstein B et al. 2011; Reingewertz TH et al. 2011).15029247Pubmed2004The mitochondrial ARTS protein promotes apoptosis through targeting XIAPGottfried, YossiRotem, AsafLotan, RonaSteller, HermannLarisch, SaritEMBO J. 23:1627-3521695558Pubmed2011ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a mechanism that is different from other IAP-antagonistsBornstein, BavatGottfried, YossiEdison, NataliaShekhtman, AnnaLev, TaliGlaser, FabianLarisch, SaritApoptosis 16:869-8121949740Pubmed2011Mechanism of the interaction between the intrinsically disordered C-terminus of the pro-apoptotic ARTS protein and the Bir3 domain of XIAPReingewertz, Tali HShalev, Deborah ESukenik, ShaharBlatt, OfrahRotem-Bamberger, ShaharLebendiker, MarioLarisch, SaritFriedler, AssafPLoS ONE 6:e24655inferred by electronic annotationIEAGOIEAReactome Database ID Release 759817926Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9817926ReactomeR-MMU-1114691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-111469.1Once released from the mitochondria, SMAC binds to IAP family proteins displacing them from Caspase:IAP complexes liberating the active caspases.15077149Pubmed2004Toxic proteins released from mitochondria in cell deathSaelens, XFestjens, NVande Walle, Lvan Gurp, Mvan Loo, GVandenabeele, POncogene 23:2861-74inferred by electronic annotationIEAGOIEA