BioPAX pathway converted from "Caspase mediated cleavage of BAP31" in the Reactome database.LEFT-TO-RIGHT3.4.22Caspase mediated cleavage of BAP31Caspase-8 mediated cleavage of BAP31 at the ER produces a pro-apoptotic p20 fragment that remains at the ER (Breckenridgeet al., 2003). Cleavage stimulates Ca2+-dependent mitochondrial fission, enhancing the release of cytochrome C (Breckenridgeet al., 2003).Authored: Schulze-Osthoff, K, 2008-05-18 10:00:05Reviewed: Ranganathan, S, 2008-06-11 19:13:33Edited: Matthews, L, 2008-06-02 07:41:19BAP31BCAP31(2-245)Reactome DB_ID: 201587endoplasmic reticulum membraneGENE ONTOLOGYGO:0005789UniProt:P51572 BCAP31BCAP31BAP31DXS1357EFUNCTION Functions as a chaperone protein. Is one of the most abundant endoplasmic reticulum (ER) proteins. Plays a role in the export of secreted proteins in the ER, the recognition of abnormally folded protein and their targeting to the ER associated-degradation (ERAD). Also serves as a cargo receptor for the export of transmembrane proteins. May be involved in CASP8-mediated apoptosis.SUBUNIT Homodimer and heterodimer with BCAP29. Binds CASP8 (isoform 9) as a complex containing BCAP31, BCAP29, BCL2 and/or BCL2L1. Interacts with VAMP3, VAMP1 and membrane IgD immunoglobulins. May interact with ACTG1 and non-muscle myosin II. Interacts with HACD2 (PubMed:15024066).SUBUNIT (Microbial infection) Interacts (via C-terminus) with HRSV membrane protein SH; this interaction is direct.TISSUE SPECIFICITY Ubiquitous. Highly expressed in neurons and discrete endocrine cells.PTM Cleaved by CASP8 and other caspases.DISEASE BCAP31 is deleted in the chromosome Xq28 deletion syndrome which involves BCAP31 and the and the promoter region of ABCD1.SIMILARITY Belongs to the BCAP29/BCAP31 family.Homo sapiensNCBI Taxonomy9606UniProtP515722EQUAL245EQUALReactome Database ID Release 75201587Database 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=201587ReactomeR-HSA-2015871Reactome 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-HSA-201587.1Reactomehttp://www.reactome.orgBCAP31(165-237)BAP31 fragment (165-237)Reactome DB_ID: 351909165EQUAL237EQUALReactome Database ID Release 75351909Database 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=351909ReactomeR-HSA-3519091Reactome 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-HSA-351909.1p20BCAP31(2-164)BAP31 fragment (2-164)BAP31-p20Reactome DB_ID: 3518262EQUAL164EQUALReactome Database ID Release 75351826Database 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=351826ReactomeR-HSA-3518261Reactome 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-HSA-351826.1BCAP31(238-246)BAP31 fragment (238-246)Reactome DB_ID: 351912cytosolGENE ONTOLOGYGO:0005829238EQUAL246EQUALReactome Database ID Release 75351912Database 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=351912ReactomeR-HSA-3519121Reactome 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-HSA-351912.1ACTIVATIONactive caspase-8 Reactome DB_ID: 2671818mitochondrial outer membraneGENE ONTOLOGYGO:0005741Caspase-8 dimerReactome DB_ID: 351836CASP8(385-479)p10 subunit of Caspase 8Reactome DB_ID: 351828UniProt:Q14790 CASP8CASP8MCH5FUNCTION Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death (PubMed:23516580, PubMed:8681376, PubMed:8681377, PubMed:9006941, PubMed:9184224). Binding to the adapter molecule FADD recruits it to either receptor (PubMed:8681376, PubMed:8681377). The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:9006941). May participate in the Granzyme B (GZMB) apoptotic pathways (PubMed:8755496). Cleaves PARP1 (PubMed:8681376). Cleaves RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281).ACTIVITY REGULATION CASP8 activity is restricted by RIPK1 (By similarity). Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis (PubMed:23516580).SUBUNIT Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit (PubMed:10508784). Interacts with FADD, CFLAR and PEA15 (PubMed:10442631). Interacts with TNFAIP8L2 (By similarity). Interacts with CASP8AP2 (PubMed:16378960). Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation (PubMed:15069192). Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium (PubMed:15509781). Interacts with UBR2ca (PubMed:28602583). Interacts with RIPK1 (By similarity). Interacts with stimulated TNFRSF10B; this interaction is followed by CASP8 proteolytic cleavage and activation (PubMed:18846110).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation.SUBUNIT (Microbial infection) Interacts with NleF from pathogenic E.coli.SUBUNIT (Microbial infection) Interacts with molluscum contagiosum virus protein MC160.TISSUE SPECIFICITY Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle.PTM (Microbial infection) Proteolytically cleaved by the cowpox virus CRMA death inhibitory protein.PTM Generation of the subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease. GZMB and CASP10 can be involved in these processing events.PTM Phosphorylation on Ser-387 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes.POLYMORPHISM Genetic variations in CASP8 are associated with reduced risk of lung cancer [MIM:211980] in a population of Han Chinese subjects. Genetic variations are also associated with decreased risk of cancer of various other forms including esophageal, gastric, colorectal, cervical, and breast, acting in an allele dose-dependent manner.SIMILARITY Belongs to the peptidase C14A family.UniProtQ14790385EQUAL479EQUALReactome Database ID Release 75351828Database 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=351828ReactomeR-HSA-3518281Reactome 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-HSA-351828.11CASP8CASP8(217-374)p18 subunit of Caspase 8Reactome DB_ID: 351869217EQUAL374EQUALReactome Database ID Release 75351869Database 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=351869ReactomeR-HSA-3518691Reactome 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-HSA-351869.11Reactome Database ID Release 75351836Database 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=351836ReactomeR-HSA-3518361Reactome 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-HSA-351836.12Reactome Database ID Release 752671818Database 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=2671818ReactomeR-HSA-26718181Reactome 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-HSA-2671818.1GENE ONTOLOGYGO:0004197gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 75351848Database 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=351848Reactome Database ID Release 75351894Database 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=351894ReactomeR-HSA-3518941Reactome 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-HSA-351894.112668660Pubmed2003Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosolBreckenridge, DGStojanovic, MMarcellus, RCShore, GCJ Cell Biol 160:1115-27