BioPAX pathway converted from "SMAC, XIAP-regulated apoptotic response" in the Reactome database.SMAC, 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>LEFT-TO-RIGHTXIAP 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>xiapXIAPQ5BKL8Reactome DB_ID: 10314969cytosolGENE ONTOLOGYGO:0005829UniProt:Q5BKL8xiapXenopus tropicalisNCBI Taxonomy8364UniProtQ5BKL81EQUAL497EQUALReactome Database ID Release 7510314969Database 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=10314969ReactomeR-XTR-508491Reactome 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-XTR-50849.1Reactomehttp://www.reactome.org2Caspase-3Reactome DB_ID: 10314887CASP3(29-175):CASP3(176-277)Reactome DB_ID: 10314885F6RF24casp3.2CASP3(29-175)Reactome DB_ID: 10314883UniProt:F6RF24casp3.2UniProtF6RF2429EQUAL175EQUALReactome Database ID Release 7510314883Database 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=10314883ReactomeR-XTR-1416441Reactome 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-XTR-141644.11F6RF24casp3.2CASP3(176-277)Reactome DB_ID: 10314881176EQUAL277EQUALReactome Database ID Release 7510314881Database 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=10314881ReactomeR-XTR-1416461Reactome 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-XTR-141646.11Reactome Database ID Release 7510314885Database 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=10314885ReactomeR-XTR-3508881Reactome 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-XTR-350888.12Reactome Database ID Release 7510314887Database 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=10314887ReactomeR-XTR-3508701Reactome 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-XTR-350870.1XIAP:Caspase-3Reactome DB_ID: 1040820821Reactome Database ID Release 7510408208Database 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=10408208ReactomeR-XTR-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-XTR-114304.1Reactome Database ID Release 7510408212Database 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=10408212ReactomeR-XTR-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-XTR-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 from electronic annotationEVIDENCE CODEECO:0000203INHIBITIONReactome Database ID Release 7510408213Database 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=10408213DIABLO:XIAP:Caspase-3Reactome DB_ID: 104082101DIABLO dimerReactome DB_ID: 10314973diabloDIABLOQ0IJ31Reactome DB_ID: 10314950UniProt:Q0IJ31diabloUniProtQ0IJ3156EQUAL239EQUALReactome Database ID Release 7510314950Database 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=10314950ReactomeR-XTR-1142981Reactome 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-XTR-114298.12Reactome Database ID Release 7510314973Database 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=10314973ReactomeR-XTR-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-XTR-9627054.11Reactome Database ID Release 7510408210Database 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=10408210ReactomeR-XTR-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-XTR-114305.1LEFT-TO-RIGHTXIAP 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>Caspase-7Reactome DB_ID: 10314923CASP7(24-198):CASP7(207-303)Reactome DB_ID: 10314921sema4cCASP7(207-303)F7E6A3Reactome DB_ID: 10314919UniProt:F7E6A3sema4cUniProtF7E6A3207EQUAL303EQUALReactome Database ID Release 7510314919Database 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=10314919ReactomeR-XTR-1416421Reactome 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-XTR-141642.11sema4cCASP7(24-198)F7E6A3Reactome DB_ID: 1031491724EQUAL198EQUALReactome Database ID Release 7510314917Database 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=10314917ReactomeR-XTR-1416411Reactome 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-XTR-141641.11Reactome Database ID Release 7510314921Database 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=10314921ReactomeR-XTR-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-XTR-6804359.12Reactome Database ID Release 7510314923Database 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=10314923ReactomeR-XTR-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-XTR-141643.12XIAP:Caspase-7Reactome DB_ID: 1031497112Reactome Database ID Release 7510314971Database 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=10314971ReactomeR-XTR-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-XTR-114308.1Reactome Database ID Release 7510408217Database 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=10408217ReactomeR-XTR-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-XTR-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. 38:1979-87INHIBITIONReactome Database ID Release 7510408218Database 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=10408218SMAC (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>LEFT-TO-RIGHTSMAC (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>2DIABLO dimer:XIAPReactome DB_ID: 1031497921Reactome Database ID Release 7510314979Database 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=10314979ReactomeR-XTR-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-XTR-9627391.1Reactome Database ID Release 7510408220Database 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=10408220ReactomeR-XTR-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-XTR-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 47:3832-41LEFT-TO-RIGHTSMAC 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>DIABLO:XIAP:Caspase-7Reactome DB_ID: 1031497511Reactome Database ID Release 7510314975Database 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=10314975ReactomeR-XTR-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-XTR-114353.1Reactome Database ID Release 7510314977Database 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=10314977ReactomeR-XTR-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-XTR-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 388:300-4Reactome Database ID Release 7510410004Database 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=10410004ReactomeR-XTR-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-XTR-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 3:401-10SMAC(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>LEFT-TO-RIGHTDissociation 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 Database ID Release 7510314981Database 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=10314981ReactomeR-XTR-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-XTR-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).Reactome Database ID Release 7510410008Database 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=10410008ReactomeR-XTR-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-XTR-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. 278:49517-22LEFT-TO-RIGHTSEPT4 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>SEPT4 dimerReactome DB_ID: 10408222SEPT4F7ECL8Reactome DB_ID: 10394174UniProt:F7ECL8UniProtF7ECL81EQUAL274EQUALReactome Database ID Release 7510394174Database 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=10394174ReactomeR-XTR-68058251Reactome 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-XTR-6805825.12Reactome Database ID Release 7510408222Database 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=10408222ReactomeR-XTR-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-XTR-9627347.1SEPT4 dimer:XIAPReactome DB_ID: 1040822421Reactome Database ID Release 7510408224Database 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=10408224ReactomeR-XTR-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-XTR-9627441.1Reactome Database ID Release 7510408226Database 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=10408226ReactomeR-XTR-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-XTR-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:e24655Reactome Database ID Release 7510410006Database 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=10410006ReactomeR-XTR-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-XTR-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 23:2861-74