{"gene":"BCAP31","run_date":"2026-04-28T17:12:38","timeline":{"discoveries":[{"year":1997,"finding":"BAP31 (p28) is an integral ER membrane protein that forms a complex with Bcl-2/Bcl-XL and procaspase-8 (pro-FLICE); caspase-8 and caspase-1, but not caspase-3, cleave BAP31 at two identical AAVD/G recognition sites; the resulting N-terminal p20 fragment induces apoptosis when expressed ectopically; Bax prevents Bcl-2 from associating with the complex.","method":"Co-immunoprecipitation in co-transfected 293T cells; in vitro cleavage assay with purified caspases; ectopic expression of p20 fragment","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (Co-IP, in vitro enzymatic assay, ectopic expression phenotype) in founding paper","pmids":["9334338"],"is_preprint":false},{"year":1997,"finding":"BAP31 controls ER export of cellubrevin; the interaction requires the transmembrane regions of both proteins; truncation of the BAP31 cytoplasmic tail prevents ER export of cellubrevin but not of the transferrin receptor, establishing a cargo-specific sorting role.","method":"Affinity pulldown with immobilized recombinant cellubrevin; co-immunoprecipitation from fibroblast detergent extracts; subcellular fractionation; immunocytochemistry; nocodazole treatment; BAP31 truncation mutants","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 — biochemical interaction confirmed by multiple methods plus domain-mapping mutagenesis","pmids":["9396746"],"is_preprint":false},{"year":1998,"finding":"The predicted death effector homology (vDED) domain in the cytosolic region of BAP31 interacts with Ced-4 and contributes to procaspase-8 recruitment; Bcl-XL associates cooperatively with the BAP31 cytosolic domain dependent on procaspase-8 and Ced-4; Bcl-XL binds directly but weakly to the transmembrane region of BAP31.","method":"Co-transfection and co-immunoprecipitation in human cells; domain-deletion mutant analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP with domain-mapping in multiple constructs; consistent with founding complex paper","pmids":["9452422"],"is_preprint":false},{"year":2000,"finding":"Caspase-resistant BAP31 (crBAP31, D→A mutations at both cleavage sites) inhibits Fas-mediated cytochrome c release from mitochondria, BAX/BAK oligomerization, membrane blebbing, and apoptotic actin redistribution, revealing that BAP31 cleavage by caspase-8 is required for ER-mitochondria cross-talk during Fas-induced apoptosis; full-length BAP31 is a direct inhibitor of caspase-8-initiated cytochrome c release.","method":"Stable expression of caspase-resistant BAP31 mutant in KB epithelial cells; Fas stimulation; cytochrome c release assay; mitochondrial membrane potential measurement; Bap31-null mouse cells reconstituted with crBAP31","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 — site-directed mutagenesis, null cells, multiple functional readouts; replicated across cell types","pmids":["10958671"],"is_preprint":false},{"year":2002,"finding":"The procaspase-8 isoform procaspase-8L, characterized by an N-terminal extension (Nex) domain, is selectively recruited to the BAP31 complex at the ER; this recruitment requires the Nex domain; BAP31 and its homologue BAP29 are required for procaspase-8L processing during E1A-induced apoptosis by a FADD-independent, Bcl-2-sensitive mechanism.","method":"Co-immunoprecipitation; gene deletion of Bap29/Bap31; dominant-negative Nex mutant; caspase activity assays (IETDase, DEVDase)","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — genetic deletion combined with dominant-negative and biochemical interaction, multiple functional readouts","pmids":["11917123"],"is_preprint":false},{"year":2003,"finding":"The p20 caspase-8 cleavage fragment of BAP31 induces Ca2+ release from the ER, mitochondrial Ca2+ uptake, Drp1 recruitment to mitochondria, and mitochondrial fission; this Ca2+-dependent fission sensitises mitochondria to caspase-8-induced cytochrome c release. Inhibition of Drp1 or ER-mitochondrial Ca2+ signalling prevents p20-induced fission.","method":"Adenoviral expression of p20 BAP31; Ca2+ imaging; cytochrome c release assay; dominant-negative Drp1 expression; mitochondrial morphology imaging","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal approaches (live imaging, dominant-negative, inhibitors, cytochrome c assay) in a single rigorous study; highly cited","pmids":["12668660"],"is_preprint":false},{"year":2003,"finding":"BAP31 specifically associates with nonmuscle myosin heavy chain B and nonmuscle gamma-actin (components of the cytoskeletal actomyosin complex); Fas-induced apoptosis releases BAP31 from these motor proteins.","method":"Capillary LC-MS/MS characterisation of BAP31 immunocomplex from HepG2 cell lysate; co-immunoprecipitation","journal":"European journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2/3 — MS identification confirmed by Co-IP, single lab","pmids":["12605685"],"is_preprint":false},{"year":2003,"finding":"High-molecular-weight BAP29/BAP31 complexes retain membrane-bound IgD (mIgD) in the ER; BAP complex binding to mIg correlates with ER retention; overexpression of BAP29/BAP31 in Drosophila S2 cells prevents aberrant surface transport of mIgD in the absence of Igα/Igβ; retention is through true ER retention, not retrieval.","method":"Blue native PAGE; co-immunoprecipitation; surface expression assays; heterologous expression in Drosophila S2 cells","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (native PAGE, Co-IP, heterologous system) demonstrating mechanistic retention function","pmids":["12886015"],"is_preprint":false},{"year":2003,"finding":"Uncleaved full-length BAP31 in association with the putative ER ion channel protein A4 acts as a direct inhibitor of Fas-initiated BAX oligomerization and cytochrome c release from mitochondria, independently of its ability to sequester p20 BAP31; A4 was identified as a constitutive binding partner of BAP31 via split-ubiquitin yeast two-hybrid screen.","method":"Split-ubiquitin yeast two-hybrid screen; co-immunoprecipitation; Bap31-null mouse cells reconstituted with crBAP31 and/or A4; cytochrome c release assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — genetic null cells, interaction screen confirmed by Co-IP, functional reconstitution","pmids":["12529377"],"is_preprint":false},{"year":2004,"finding":"Active caspase-8 localises predominantly on the outer mitochondrial membrane (OMM) as an integral protein during apoptosis; OMM-localised active caspase-8 can cleave ER-localised BAP31, generating pro-apoptotic BAP20, which mediates mitochondria-ER cross-talk through a Ca2+-dependent mechanism.","method":"Subcellular fractionation; immunofluorescence microscopy; dominant-negative mutants; siRNA; caspase-8-deficient Jurkat cells; BAP31 cleavage assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — multiple independent approaches (fractionation, imaging, genetic loss-of-function, dominant-negative) in single study","pmids":["15254227"],"is_preprint":false},{"year":2004,"finding":"BAP31 is required to maintain the stability of PTPLB (a novel ER membrane protein tyrosine phosphatase-like family member); loss of Bap31 in knockout mouse cells leads to increased PTPLB proteasomal degradation, consistent with a chaperone/quality-control function for BAP31 in the ER membrane.","method":"Yeast split-ubiquitin screen with BAP31 as bait; Bap31-null mouse ES cells; proteasomal degradation assays; reconstitution with human BAP31","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 — genetic null cells, interaction screen, reconstitution experiment","pmids":["15024066"],"is_preprint":false},{"year":2004,"finding":"BAP31 specifically binds to CD11b/CD18 integrin via its cytoplasmic tail (not the I-domain of CD11b); BAP31 co-localises with CD11b/CD18 in neutrophil secondary granules and both redistribute to the plasma membrane together following fMLP stimulation, implicating BAP31 in intracellular trafficking of CD11b/CD18.","method":"Monoclonal antibody generation; co-immunoprecipitation; GST-fusion protein binding assay; immunolocalization; subcellular fractionation of PMN","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2-3 — biochemical interaction confirmed by Co-IP and pulldown, localization data, but functional consequence inferred","pmids":["15294914"],"is_preprint":false},{"year":2005,"finding":"BAP31 is required for cell surface expression of the tetraspanins CD9 and CD81; in Bap31-null mouse cells, CD9/CD81 surface levels are reduced and integrin-mediated cell adhesion and survival under serum stress are impaired; reconstitution of BAP31 restores these functions; the p20 BAP31 caspase fragment inhibits tetraspanin/integrin-mediated cell attachment in cells protected from apoptosis by Bcl-2.","method":"Bap31-null mouse cells; wild-type BAP31 reconstitution; flow cytometry for surface expression; cell adhesion assay; serum-starvation apoptosis assay; antagonising antibodies against CD9, integrins","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — genetic null and reconstitution with multiple orthogonal functional readouts","pmids":["15946936"],"is_preprint":false},{"year":2005,"finding":"BAP31 interacts with and retains cytochrome P450 2C2 in the ER; BAP31 knockdown or Bap31-null cells cause P450 2C2 redistribution away from the ER to the nuclear envelope and cell surface; the interaction is mediated through transmembrane domains; overexpression of P450 2C2 induces formation of the pro-apoptotic p20 BAP31 fragment.","method":"Bimolecular fluorescence complementation; co-immunoprecipitation; siRNA knockdown; Bap31-null ES cells; reconstitution; immunofluorescence","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods and genetic null cell validation","pmids":["16332681"],"is_preprint":false},{"year":2006,"finding":"BAP31 overexpression increases surface MHC class I levels by accelerating the rate of ER export of newly synthesised peptide-loaded class I molecules and by stabilising them post-ER; Bap31 deficiency does not reduce surface class I, indicating redundancy; Bap29 overexpression decreases surface class I.","method":"YFP-Bap31 transfection; flow cytometry; radioimmunoprecipitation pulse-chase; Bap31 knockdown/null cells","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 — overexpression and loss-of-function with quantitative surface and trafficking assays, but redundancy complicates interpretation","pmids":["17056546"],"is_preprint":false},{"year":2008,"finding":"BAP31 associates with Sec61β and TRAM components of the Sec61 translocon, and with the Derlin-1 dislocation complex; BAP31 associates with the N-terminus of newly synthesised CFTRΔf508 and promotes its retrotranslocation from the ER for degradation by the 26S proteasome; depletion of BAP31 reduces proteasomal degradation of ΔF508 and allows a significant fraction to reach the cell surface.","method":"Co-immunoprecipitation; siRNA depletion; proteasome inhibitor treatments; surface biotinylation; pulse-chase","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1-2 — published in Cell, multiple orthogonal Co-IP and functional assays establishing a mechanistic ERAD pathway","pmids":["18555783"],"is_preprint":false},{"year":2008,"finding":"Bap31 is an itinerant ER protein that cycles between peripheral ER and a juxtanuclear ER-quality-control compartment; cycling requires the second and third transmembrane domains and depends on microtubules and dynein-dynactin; overexpression of Sar1p and Arf1 mutants affects Bap31 cycling.","method":"Live-cell fluorescence imaging; FRAP; nocodazole/dynein-dynactin inhibition; domain deletion mutants; dominant-negative Sar1/Arf1","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — direct localization experiments with functional domain mapping and pharmacological/genetic perturbations","pmids":["18287538"],"is_preprint":false},{"year":2009,"finding":"BAP31 interacts with MHC class I (HLA-A2) in the ER and traffics with it via export vesicles to the ER-Golgi intermediate compartment; peptide loading of MHC class I increases FRET between Bap31 and HLA-A2 and promotes forward traffic; overexpression of Bap29 blocks this forward traffic.","method":"FRET imaging; quantitative fluorescence microscopy; Bap29 overexpression competition assay","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 — direct imaging-based interaction and trafficking experiment with functional perturbation by Bap29","pmids":["19342655"],"is_preprint":false},{"year":2010,"finding":"Fis1 (mitochondrial fission protein) interacts with BAP31 at the ER interface to form the 'ARCosome' complex spanning mitochondria and ER; this complex recruits procaspase-8 in a vDED-dependent manner; Fis1-BAP31 interaction facilitates caspase-8 activation, which drives BAP31 cleavage into pro-apoptotic p20BAP31, releasing Ca2+ from the ER as a feedback signal to activate mitochondria.","method":"Co-immunoprecipitation; split-ubiquitin two-hybrid; dominant-negative constructs; vDED deletion mutants; Ca2+ imaging; apoptosis assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal biochemical and cell-biological methods, reciprocal Co-IP, domain mutagenesis, functional readouts; highly cited","pmids":["21183955"],"is_preprint":false},{"year":2011,"finding":"BAP31 and the ER chaperone BiP are essential for ER-to-cytosol dislocation of SV40 during viral infection; both proteins co-localise with incoming virus in discrete ER foci and promote virus crossing of the ER membrane, implicating them as ERAD factors required for SV40 retrotranslocation.","method":"siRNA screen; co-localisation by immunofluorescence; infection assays with VP2-deficient virus-like particles","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 — siRNA screen followed by co-localisation and functional rescue, published in Nature Cell Biology","pmids":["21947079"],"is_preprint":false},{"year":2013,"finding":"The proapoptotic p53 target CDIP1 interacts with BAP31 at the ER membrane upon ER stress; CDIP1 binding to BAP31 is required for BAP31 cleavage and BAP31-Bcl-2 association; the CDIP1-BAP31 complex recruits Bcl-2 and activates caspase-8/tBid, driving BAX oligomerisation and mitochondrial apoptosis; genetic knockout of CDIP1 in mice impairs ER-stress-mediated apoptosis.","method":"Co-immunoprecipitation; CDIP1 genetic knockout mouse; caspase-8/tBid activation assays; BAX oligomerisation assay; ER stress induction","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — in vivo genetic knockout combined with multiple biochemical Co-IP and functional assays","pmids":["24139803"],"is_preprint":false},{"year":2013,"finding":"Crystal structures of the BAP31 vDED (variant death effector domain) cytoplasmic region show that it forms a dimeric parallel coiled coil with no structural similarity to canonical DED domains; solution studies indicate a second α-helical coiled-coil domain in the C-terminal cytoplasmic region; no direct interaction was detected between the cytoplasmic domains of BAP29 and BAP31.","method":"X-ray crystallography (two crystal forms); biophysical solution studies (SEC, CD, DLS, analytical ultracentrifugation)","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1 — crystal structures with solution validation; directly refutes predicted DED fold","pmids":["23967155"],"is_preprint":false},{"year":2013,"finding":"Loss-of-function mutations in BCAP31 in humans cause ER morphology disruption and Golgi disorganisation in patient fibroblasts without activating the unfolded protein response or cell-death effectors, demonstrating a role for BAP31 in ER-to-Golgi crosstalk in vivo.","method":"Patient-derived primary fibroblasts; electron microscopy; UPR marker analysis; Golgi morphology by immunofluorescence","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 — human loss-of-function genetics with direct cellular phenotype characterisation","pmids":["24011989"],"is_preprint":false},{"year":2015,"finding":"BAP31 directly interacts with RSV small hydrophobic (SH) protein; co-localisation was shown in transfected cells; direct interaction of the BAP31 C-terminal endodomain with SH protein was demonstrated by NMR titration of purified proteins in detergent micelles.","method":"Membrane-based yeast two-hybrid screen; co-immunoprecipitation; NMR titration of purified proteins","journal":"Virology","confidence":"Medium","confidence_rationale":"Tier 1-3 — NMR provides direct biophysical evidence but single lab; pulldown confirmed","pmids":["25854864"],"is_preprint":false},{"year":2017,"finding":"BAP31 conditional knockout in the mouse thymus reduces T cell numbers; BAP31-deficient T cells show decreased proliferation upon TCR stimulation; BAP31 regulates phosphorylation of Zap70, Lck, and Lat (upstream TCR signal members) and Akt, GSK, JNK, and ERK (downstream members), and controls expression of CD3/TCRα/TCRβ and cytokines IL-2, IFN-γ, IL-6, and TNF-α.","method":"Cre/LoxP conditional knockdown mouse; T cell proliferation assays; Western blot for TCR pathway phosphorylation; flow cytometry; ELISA","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo conditional KO with multiple pathway readouts; single lab","pmids":["28333124"],"is_preprint":false},{"year":2017,"finding":"Hepatocyte-specific BAP31 deletion in mice increases SREBP1C expression and its target genes (ACC1, SCD1), promotes hepatic lipid accumulation and steatosis; BAP31 interacts with SREBP1C and INSIG1 by co-immunoprecipitation, and BAP31 deletion reduces INSIG1 levels, suggesting BAP31 regulates SREBP1C via INSIG1.","method":"Hepatocyte-specific conditional knockout mice; high-fat diet challenge; co-immunoprecipitation; Western blot; glucose/insulin tolerance tests","journal":"Journal of lipid research","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo KO with Co-IP interaction data; single lab","pmids":["29113994"],"is_preprint":false},{"year":2018,"finding":"BAP31 binds RTN3 and positively regulates its stability; BAP31 conditional knockout in hippocampus/cortex of APP/PS1 mice decreases RTN3 monomer levels, increases RTN3 aggregates, enhances BACE1 activity and APP processing, and increases amyloid-β plaque deposition.","method":"Co-immunoprecipitation; conditional knockout mouse crossed with AD model mice; hippocampal neuron cultures; amyloid plaque quantification","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 — genetic model with biochemical interaction, single lab","pmids":["30596517"],"is_preprint":false},{"year":2019,"finding":"BAP31 interacts with Tom40 (mitochondrial outer membrane import channel) within ER-mitochondria contact sites; this BAP31-Tom40 complex stimulates translocation of NDUFS4 (complex I subunit) from the cytosol to mitochondria; disruption of the complex reduces mitochondrial complex I activity and oxygen consumption.","method":"Co-immunoprecipitation; BAP31 knockdown; NDUFS4 mitochondrial localisation assay; oxygen consumption measurement","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 2 — Co-IP establishing interaction, loss-of-function with two functional readouts (NDUFS4 import and respiration), published in Science Advances","pmids":["31206022"],"is_preprint":false},{"year":2019,"finding":"BAP31 negatively regulates autophagy by forming a complex with STX17 (a SNARE required for autophagosome formation); loss of BAP31 stimulates autophagy, promotes adaptation to ER stress, and enhances tumour cell invasion; BAP31 thus acts as a tumour suppressor by inhibiting autophagy-mediated ER stress adaptation.","method":"Co-immunoprecipitation of BAP31-STX17 complex; BAP31 knockdown/knockout; autophagy flux assays; in vivo tumour growth assay","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP interaction and KO functional data, single lab","pmids":["31671609"],"is_preprint":false},{"year":2019,"finding":"BAP31 deficiency upregulates LPS-induced proinflammatory cytokines in microglia by increasing IRAK1 protein levels, which in turn increases NF-κB p65 and c-Jun nuclear translocation and transcriptional activity; knockdown of IRAK1 or use of an IRAK1 inhibitor reverses these effects.","method":"BAP31 conditional knockdown mice (Cre/LoxP); BV2 cell knockdown; ELISA; Western blot; immunofluorescence; IRAK1 inhibitor treatment; cognitive behavioural tests","journal":"Journal of neuroinflammation","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo and in vitro KD with pathway epistasis (IRAK1 inhibitor rescue); single lab","pmids":["31883536"],"is_preprint":false},{"year":2019,"finding":"BCAP31 interacts with EGFR and inhibits ligand-independent EGFR recycling, thereby sustaining EGFR autophosphorylation and downstream signalling activation in triple-negative breast cancer cells.","method":"Co-immunoprecipitation; BCAP31 knockdown; surface EGFR trafficking assays; EGFR phosphorylation analysis","journal":"Theranostics","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP with functional trafficking and signalling readouts; single lab","pmids":["31588230"],"is_preprint":false},{"year":2019,"finding":"BAP31 specifically interacts with and protects the cyclin kinase inhibitor p27kip1 from proteasomal degradation; an intrabody (VH-D1) targeting BAP31 blocks the BAP31-p27kip1 interaction, increases p27kip1 stability, inhibits gastric cancer cell proliferation, and activates caspase-dependent apoptosis.","method":"Co-immunoprecipitation; intrabody expression; proteasome inhibitor assay; xenograft tumour model","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP interaction with intrabody blocking and functional rescue; single lab","pmids":["30338855"],"is_preprint":false},{"year":2023,"finding":"BAP31 directly binds VDAC1 and affects VDAC1 oligomerisation and polyubiquitination, thereby regulating cell proliferation and ferroptosis (lipid peroxidation); HNF4A binds the BAP31 promoter and drives its transcription.","method":"Co-immunoprecipitation; BAP31 knockdown; VDAC1 oligomerisation assay; lipid peroxidation assay; ChIP assay for HNF4A at BAP31 promoter; xenograft model","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP and ChIP with functional knockdown data; single lab","pmids":["37296105"],"is_preprint":false},{"year":2000,"finding":"Limited caspase cleavage of BAP31 during apoptosis (by TNF, staurosporine, Fas) occurs selectively at only the more carboxy-terminal of the two caspase recognition sites, removing eight amino acids including the KKXX COPI-binding motif; this cleavage redistributes Golgi mannosidase II and blocks ER-to-Golgi transport of viral glycoproteins.","method":"In-cell apoptosis induction (multiple stimuli); Western blot with site-specific antibodies; Golgi morphology imaging; viral glycoprotein trafficking assay","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 — multiple stimuli and orthogonal functional readouts; single lab","pmids":["11078879"],"is_preprint":false},{"year":2023,"finding":"BAP31 interacts with Perilipin1 via its C-terminal cytoplasmic domain on lipid droplet surfaces; BAP31 depletion in adipocytes represses Perilipin1 proteasomal degradation, enhancing Perilipin1 levels, blocking lipid droplet degradation, and promoting super-sized lipid droplet formation, while inhibiting adipogenesis and lipolysis.","method":"Adipocyte-specific BAP31 conditional knockout mice; co-immunoprecipitation; proteasomal degradation assays; lipid droplet imaging; lipolysis assays","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo KO with biochemical interaction and multiple functional readouts; single lab","pmids":["37063427"],"is_preprint":false},{"year":2024,"finding":"BAP31 promotes PINK1 phosphorylation by directly binding to PINK1, thereby activating PINK1/Parkin-mediated mitophagy; BAP31 downregulation reduces PINK1 phosphorylation, impairs mitophagy, increases mitochondrial ROS, and activates the mROS/ROS/NF-κB pathway, leading to alveolar epithelial cell apoptosis and inflammation in ALI.","method":"BCAP31 transgenic and conditional knockout mice (Sftpc-Cre); co-immunoprecipitation of BAP31-PINK1; PINK1 phosphorylation assays; mitophagy flux assays; mitochondrial membrane permeability and ROS measurements; LPS-ALI model","journal":"Research","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo transgenic/KO mouse with Co-IP interaction and multiple functional pathway readouts; single lab","pmids":["39381793"],"is_preprint":false},{"year":1996,"finding":"The specificity of BAP31/BAP29 association with membrane IgD (but not IgM) resides in specific amino acids within the transmembrane sequence of the δm heavy chain; full-length murine and human BAP31 cDNAs encode 245/246 aa proteins with N-terminal hydrophobic region and C-terminal α-helical domain ending in a KKXX ER-retention motif; BAP31 is encoded on the X chromosome.","method":"Mutational analysis of IgD transmembrane sequence; BAP31 cDNA cloning; transfection co-immunoprecipitation; chromosomal mapping","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — mutagenesis defining transmembrane interaction specificity; foundational structural and genetic characterisation","pmids":["8612576"],"is_preprint":false}],"current_model":"BAP31 is a ubiquitously expressed polytopic ER integral membrane protein that functions as a broad-specificity cargo receptor/chaperone (controlling ER retention, export, and ERAD of client membrane proteins including IgD, cellubrevin, MHC class I, CFTR, CD9/CD81, P450 2C2, and EGFR), a mitochondria-associated membrane (MAM) tetherer (via a Fis1-BAP31 ARCosome complex and a BAP31-Tom40 bridge that supports mitochondrial complex I assembly), and a central apoptosis regulator (forming an ER complex with Bcl-2/Bcl-XL and procaspase-8/procaspase-8L; upon death-receptor signalling, caspase-8 cleaves BAP31 at AAVD/G sites to generate p20-BAP31, which releases ER Ca2+, recruits Drp1, and drives mitochondrial fission and cytochrome c release, while full-length BAP31 is itself anti-apoptotic)."},"narrative":{"teleology":[{"year":1996,"claim":"Cloning of BAP31 established it as an ER-resident integral membrane protein with a C-terminal KKXX motif whose transmembrane domain confers selective binding to membrane IgD but not IgM, defining it as a cargo-selective ER-retention factor.","evidence":"cDNA cloning, transmembrane mutagenesis, Co-IP, chromosomal mapping","pmids":["8612576"],"confidence":"High","gaps":["No trafficking assay directly showing retention versus retrieval","Interaction partners beyond Ig not explored"]},{"year":1997,"claim":"Discovery that BAP31 forms a ternary complex with Bcl-2/Bcl-XL and procaspase-8, and that caspase-8 cleaves BAP31 at two AAVD sites to generate a pro-apoptotic p20 fragment, established BAP31 as a direct molecular link between ER and apoptosis signaling.","evidence":"Co-IP in 293T cells; in vitro caspase cleavage; ectopic p20 expression","pmids":["9334338"],"confidence":"High","gaps":["Mechanism by which p20 induces death not yet resolved","Physiological stoichiometry of the complex unknown"]},{"year":1997,"claim":"BAP31 was shown to control ER export of cellubrevin in a cargo-specific manner dependent on its cytoplasmic tail, extending its role from ER retention to active forward trafficking.","evidence":"Affinity pulldown, Co-IP, BAP31 tail truncation mutants, nocodazole treatment in fibroblasts","pmids":["9396746"],"confidence":"High","gaps":["Coat machinery engaged by BAP31 tail not identified","Whether BAP31 acts catalytically or stoichiometrically unclear"]},{"year":2000,"claim":"Expression of caspase-resistant BAP31 (crBAP31) demonstrated that cleavage of BAP31 is required for Fas-induced ER-to-mitochondria apoptotic cross-talk, and that intact BAP31 is itself an inhibitor of cytochrome c release, resolving the dual pro-/anti-apoptotic roles of BAP31.","evidence":"Site-directed mutagenesis of cleavage sites; crBAP31 stable expression in KB cells and Bap31-null mouse cells; cytochrome c release, BAX oligomerization, membrane potential assays","pmids":["10958671","11078879"],"confidence":"High","gaps":["Identity of the ER-to-mitochondria signal downstream of uncleaved BAP31 unknown","Whether limited C-terminal clipping versus full cleavage have distinct outputs remained unclear"]},{"year":2003,"claim":"The p20 fragment was shown to trigger ER Ca²⁺ release, mitochondrial Ca²⁺ uptake, Drp1 recruitment, and mitochondrial fission, establishing the mechanistic pathway from BAP31 cleavage to mitochondrial fragmentation and cytochrome c release.","evidence":"Adenoviral p20 expression; Ca²⁺ imaging; dominant-negative Drp1; mitochondrial morphology analysis","pmids":["12668660"],"confidence":"High","gaps":["Channel or mechanism of p20-induced ER Ca²⁺ release not identified","Whether p20 forms a pore or activates an existing channel unknown"]},{"year":2003,"claim":"BAP29/BAP31 heteromeric complexes were shown to retain membrane IgD in the ER by a true retention rather than retrieval mechanism, and the ER partner A4 was identified as a constitutive BAP31-binding protein that contributes to anti-apoptotic function, broadening the repertoire of BAP31 quality-control complexes.","evidence":"Blue native PAGE; heterologous expression in Drosophila S2 cells; split-ubiquitin screen; Bap31-null reconstitution","pmids":["12886015","12529377"],"confidence":"High","gaps":["Identity and stoichiometry of high-MW BAP31 complexes not fully resolved","Mechanism by which A4 contributes to anti-apoptotic signaling unclear"]},{"year":2004,"claim":"Demonstration that BAP31 stabilizes the ER membrane protein PTPLB and traffics with CD11b/CD18 integrins expanded BAP31's client repertoire to include non-immunoglobulin cargo, confirming a general chaperone/quality-control function.","evidence":"Bap31-null mouse ES cells; proteasomal degradation assays for PTPLB; Co-IP and fractionation in neutrophils for CD11b/CD18","pmids":["15024066","15294914"],"confidence":"High","gaps":["Whether BAP31 directly stabilizes PTPLB via folding assistance or by shielding from ERAD unknown","Functional consequence of BAP31-CD11b interaction on immune function not tested"]},{"year":2005,"claim":"BAP31 was shown to be required for surface expression of tetraspanins CD9/CD81 and for ER retention of cytochrome P450 2C2, establishing that BAP31 can either promote or prevent ER exit depending on the cargo.","evidence":"Bap31-null cells with reconstitution; flow cytometry; BiFC and immunofluorescence for P450 2C2","pmids":["15946936","16332681"],"confidence":"High","gaps":["Determinants within cargo that dictate export versus retention by BAP31 not defined","Structural basis for bidirectional sorting unknown"]},{"year":2008,"claim":"BAP31 was found to associate with the Sec61 translocon and Derlin-1 dislocation complex and to channel misfolded CFTR∆F508 for proteasomal degradation, directly placing BAP31 within the ERAD retrotranslocation machinery.","evidence":"Co-IP of BAP31 with Sec61β, TRAM, Derlin-1; siRNA depletion; pulse-chase and surface biotinylation for CFTR∆F508","pmids":["18555783"],"confidence":"High","gaps":["Whether BAP31 serves as a receptor that hands off substrates to Derlin-1 or acts within the channel complex not resolved","ERAD substrates beyond CFTR not systematically cataloged"]},{"year":2008,"claim":"Live-cell imaging revealed BAP31 cycles between peripheral ER and a juxtanuclear quality-control compartment in a microtubule/dynein-dependent manner, providing a dynamic trafficking framework for its cargo-sorting functions.","evidence":"FRAP; nocodazole and dynein-dynactin inhibition; TM domain deletion mutants; dominant-negative Sar1/Arf1","pmids":["18287538"],"confidence":"High","gaps":["Nature and identity of the juxtanuclear QC compartment not fully characterized","How BAP31 cycling is regulated under stress conditions unknown"]},{"year":2010,"claim":"Discovery of the Fis1–BAP31 ARCosome complex at ER–mitochondria contact sites showed that BAP31 physically tethers these organelles and recruits procaspase-8 for activation, providing the structural basis for ER–mitochondria apoptotic signaling.","evidence":"Co-IP; split-ubiquitin two-hybrid; vDED deletion mutants; Ca²⁺ imaging; apoptosis assays","pmids":["21183955"],"confidence":"High","gaps":["Stoichiometry and ultrastructure of the ARCosome not determined","Whether ARCosome has non-apoptotic functions at MAMs unclear"]},{"year":2013,"claim":"Crystal structures of the BAP31 cytoplasmic region revealed a dimeric parallel coiled-coil rather than a canonical DED fold, overturning the structural model of procaspase-8 recruitment, while CDIP1 was identified as a p53-dependent activator that engages BAP31 to trigger ER-stress-to-mitochondria apoptotic signaling.","evidence":"X-ray crystallography and biophysical studies for structure; CDIP1 knockout mouse with Co-IP and caspase activation assays","pmids":["23967155","24139803"],"confidence":"High","gaps":["How a coiled-coil mediates procaspase-8 recruitment without a DED fold is structurally unresolved","Whether CDIP1 is the sole p53-dependent activator of BAP31 cleavage unknown"]},{"year":2013,"claim":"Human loss-of-function mutations in BCAP31 were shown to cause ER morphology disruption and Golgi disorganization without activating the UPR, establishing BCAP31 as a disease gene and demonstrating its in vivo requirement for ER–Golgi homeostasis.","evidence":"Patient-derived fibroblasts; electron microscopy; UPR marker analysis; Golgi immunofluorescence","pmids":["24011989"],"confidence":"High","gaps":["Full clinical phenotypic spectrum not delineated in this study","Whether Golgi disruption is secondary to ER cargo mis-sorting not tested"]},{"year":2019,"claim":"A BAP31–Tom40 bridge at ER–mitochondria contacts was shown to facilitate import of NDUFS4 into mitochondria and sustain complex I activity, revealing a non-apoptotic tethering function of BAP31 in mitochondrial bioenergetics.","evidence":"Co-IP of BAP31–Tom40; BAP31 knockdown; NDUFS4 import and oxygen consumption assays","pmids":["31206022"],"confidence":"High","gaps":["Structural interface between BAP31 and Tom40 not mapped","Whether other mitochondrial import substrates depend on this bridge unknown"]},{"year":2019,"claim":"BAP31 was found to interact with STX17, EGFR, and p27kip1, extending its regulatory reach to autophagy, receptor trafficking, and cell-cycle control beyond its canonical ER quality-control and apoptosis functions.","evidence":"Co-IP; BAP31 knockdown/KO with autophagy flux, EGFR recycling, and p27 stability assays","pmids":["31671609","31588230","30338855"],"confidence":"Medium","gaps":["Mechanisms linking ER-localized BAP31 to cytosolic p27 stability are unclear","Whether STX17 and EGFR interactions are direct or bridged not fully resolved","Findings from single labs await independent replication"]},{"year":2023,"claim":"BAP31 was shown to bind VDAC1 and Perilipin1, regulating ferroptosis and lipid-droplet dynamics, further implicating BAP31 at membrane contact sites beyond the ER–mitochondria axis.","evidence":"Co-IP; adipocyte-specific KO mice; VDAC1 oligomerization and lipid peroxidation assays; lipid droplet imaging","pmids":["37296105","37063427"],"confidence":"Medium","gaps":["Whether BAP31 localizes to lipid droplet surfaces directly or acts via ER–LD contacts not established","Mechanism of BAP31 regulation of VDAC1 oligomerization unclear","Single-lab findings"]},{"year":2024,"claim":"BAP31 was found to promote PINK1 phosphorylation and PINK1/Parkin-mediated mitophagy, linking BAP31's MAM-tethering function to mitochondrial quality control beyond the previously known apoptotic pathway.","evidence":"BAP31 transgenic and conditional KO mice; Co-IP of BAP31–PINK1; mitophagy flux and ROS assays; LPS-ALI model","pmids":["39381793"],"confidence":"Medium","gaps":["Whether BAP31 stabilizes PINK1 directly or facilitates its import/retention on the OMM is unresolved","Single lab; awaits independent confirmation","Relationship to the Tom40 bridge unknown"]},{"year":null,"claim":"How BAP31 discriminates between cargo destined for ER retention, forward transport, or ERAD remains structurally and mechanistically undefined; the atomic basis of its interactions with procaspase-8 (given the non-DED coiled-coil fold) and with Tom40/Fis1 at MAMs has not been determined.","evidence":"","pmids":[],"confidence":"High","gaps":["No full-length BAP31 structure available","Sorting code within cargo transmembrane domains not systematically defined","Coiled-coil–procaspase-8 binding mechanism unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0038024","term_label":"cargo receptor activity","supporting_discovery_ids":[1,7,12,13,14,15,17]},{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[10,13,25,26]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,3,5,8,20,28]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,1,7,13,15,16,36]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[22,33]}],"pathway":[{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[0,3,5,9,18,20]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1,7,12,14,15,16,17]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[10,15,16]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[18,27]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[28,35]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[14,17,24,29]}],"complexes":["BAP31–Bcl-2/Bcl-XL–procaspase-8 ER complex","Fis1–BAP31 ARCosome","BAP31–Tom40 MAM bridge","BAP29/BAP31 heteromeric quality-control complex"],"partners":["FIS1","TOMM40","BCL2","CASP8","DERL1","STX17","CDIP1","BAP29"],"other_free_text":[]},"mechanistic_narrative":"BAP31 is a polytopic ER integral membrane protein that functions as a broad-specificity cargo receptor and quality-control factor governing ER retention, export, and degradation of diverse transmembrane clients, while simultaneously serving as a central platform linking ER stress and death-receptor signaling to mitochondrial apoptosis. As a cargo receptor, BAP31 retains membrane IgD via transmembrane-domain interactions [PMID:8612576, PMID:12886015], promotes ER export of cellubrevin, MHC class I, and tetraspanins CD9/CD81 [PMID:9396746, PMID:15946936, PMID:17056546], and channels misfolded CFTR∆F508 through the Sec61/Derlin-1 retrotranslocation machinery for proteasomal degradation [PMID:18555783]. In apoptosis, BAP31 forms an ER-localized complex with Bcl-2/Bcl-XL and procaspase-8; caspase-8 cleaves BAP31 at AAVD sites to generate the p20 fragment, which triggers ER Ca²⁺ release, Drp1-dependent mitochondrial fission, and cytochrome c release, whereas uncleaved BAP31 is itself anti-apoptotic [PMID:9334338, PMID:12668660, PMID:10958671]. BAP31 also tethers ER to mitochondria through a Fis1–BAP31 ARCosome complex that activates caspase-8 and through a BAP31–Tom40 bridge that facilitates mitochondrial complex I subunit import [PMID:21183955, PMID:31206022]; loss-of-function mutations in humans cause ER and Golgi disorganization [PMID:24011989]."},"prefetch_data":{"uniprot":{"accession":"P51572","full_name":"B-cell receptor-associated protein 31","aliases":["6C6-AG tumor-associated antigen","Protein CDM","p28"],"length_aa":246,"mass_kda":28.0,"function":"Functions as a chaperone protein (PubMed:18287538, PubMed:9396746). Is one of the most abundant endoplasmic reticulum (ER) proteins (PubMed:18287538, PubMed:9396746). 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) (PubMed:18287538, PubMed:9396746). Also serves as a cargo receptor for the export of transmembrane proteins (By similarity). Plays a role in the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) by stimulating the translocation of NDUFS4 and NDUFB11 from the cytosol to the mitochondria via interaction with TOMM40 (PubMed:31206022). In response to ER stress, delocalizes from the ER-mitochondria contact sites and binds BCL2 (PubMed:31206022). May be involved in CASP8-mediated apoptosis (PubMed:10958671)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/P51572/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/BCAP31","classification":"Not Classified","n_dependent_lines":177,"n_total_lines":1208,"dependency_fraction":0.14652317880794702},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000185825","cell_line_id":"CID000368","localizations":[{"compartment":"er","grade":3}],"interactors":[{"gene":"COPA","stoichiometry":4.0},{"gene":"COPB2","stoichiometry":4.0},{"gene":"COPE","stoichiometry":4.0},{"gene":"ARF4","stoichiometry":0.2},{"gene":"ARHGAP15","stoichiometry":0.2},{"gene":"ARL6IP1","stoichiometry":0.2},{"gene":"BCAP29","stoichiometry":0.2},{"gene":"TMX3","stoichiometry":0.2},{"gene":"ESYT1","stoichiometry":0.2},{"gene":"ATL3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000368","total_profiled":1310},"omim":[{"mim_id":"621108","title":"DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 18; DNAJC2","url":"https://www.omim.org/entry/621108"},{"mim_id":"619516","title":"BIFUNCTIONAL APOPTOSIS REGULATOR; BFAR","url":"https://www.omim.org/entry/619516"},{"mim_id":"615939","title":"PROTEIN TYROSINE PHOSPHATASE-LIKE (PROLINE INSTEAD OF CATALYTIC ARGININE), MEMBER B; PTPLB","url":"https://www.omim.org/entry/615939"},{"mim_id":"610423","title":"PHOSPHOFURIN ACIDIC CLUSTER SORTING PROTEIN 2; PACS2","url":"https://www.omim.org/entry/610423"},{"mim_id":"300475","title":"DEAFNESS, DYSTONIA, AND CEREBRAL HYPOMYELINATION; DDCH","url":"https://www.omim.org/entry/300475"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Endoplasmic reticulum","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/BCAP31"},"hgnc":{"alias_symbol":["DXS1357E","BAP31","6C6-Ag","CDM"],"prev_symbol":[]},"alphafold":{"accession":"P51572","domains":[{"cath_id":"-","chopping":"2-150","consensus_level":"high","plddt":88.6927,"start":2,"end":150}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P51572","model_url":"https://alphafold.ebi.ac.uk/files/AF-P51572-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P51572-F1-predicted_aligned_error_v6.png","plddt_mean":84.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BCAP31","jax_strain_url":"https://www.jax.org/strain/search?query=BCAP31"},"sequence":{"accession":"P51572","fasta_url":"https://rest.uniprot.org/uniprotkb/P51572.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P51572/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P51572"}},"corpus_meta":[{"pmid":"12668660","id":"PMC_12668660","title":"Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol.","date":"2003","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12668660","citation_count":452,"is_preprint":false},{"pmid":"21183955","id":"PMC_21183955","title":"Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction.","date":"2010","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21183955","citation_count":430,"is_preprint":false},{"pmid":"11518968","id":"PMC_11518968","title":"Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration.","date":"2001","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/11518968","citation_count":359,"is_preprint":false},{"pmid":"9334338","id":"PMC_9334338","title":"p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum.","date":"1997","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9334338","citation_count":283,"is_preprint":false},{"pmid":"16183649","id":"PMC_16183649","title":"Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16183649","citation_count":191,"is_preprint":false},{"pmid":"12617685","id":"PMC_12617685","title":"First-second shell interactions in metal binding sites in proteins: a PDB survey and DFT/CDM calculations.","date":"2003","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/12617685","citation_count":159,"is_preprint":false},{"pmid":"9804161","id":"PMC_9804161","title":"Rapid cytochrome c release, activation of caspases 3, 6, 7 and 8 followed by Bap31 cleavage in HeLa cells treated with photodynamic therapy.","date":"1998","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/9804161","citation_count":145,"is_preprint":false},{"pmid":"15254227","id":"PMC_15254227","title":"Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death.","date":"2004","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15254227","citation_count":142,"is_preprint":false},{"pmid":"21947079","id":"PMC_21947079","title":"BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic reticulum to the cytosol.","date":"2011","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/21947079","citation_count":136,"is_preprint":false},{"pmid":"9396746","id":"PMC_9396746","title":"Export of cellubrevin from the endoplasmic reticulum is controlled by BAP31.","date":"1997","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9396746","citation_count":135,"is_preprint":false},{"pmid":"18555783","id":"PMC_18555783","title":"BAP31 interacts with Sec61 translocons and promotes retrotranslocation of CFTRDeltaF508 via the derlin-1 complex.","date":"2008","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/18555783","citation_count":132,"is_preprint":false},{"pmid":"31206022","id":"PMC_31206022","title":"BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites.","date":"2019","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/31206022","citation_count":117,"is_preprint":false},{"pmid":"11917123","id":"PMC_11917123","title":"The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11917123","citation_count":106,"is_preprint":false},{"pmid":"10958671","id":"PMC_10958671","title":"Caspase-resistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation and release of cytochrome c from mitochondria.","date":"2000","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10958671","citation_count":102,"is_preprint":false},{"pmid":"18287538","id":"PMC_18287538","title":"Bap31 is an itinerant protein that moves between the peripheral endoplasmic reticulum (ER) and a juxtanuclear compartment related to ER-associated Degradation.","date":"2008","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/18287538","citation_count":100,"is_preprint":false},{"pmid":"8612576","id":"PMC_8612576","title":"The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence.","date":"1996","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/8612576","citation_count":92,"is_preprint":false},{"pmid":"30770794","id":"PMC_30770794","title":"MiR-451a suppressing BAP31 can inhibit proliferation and increase apoptosis through inducing ER stress in colorectal cancer.","date":"2019","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/30770794","citation_count":84,"is_preprint":false},{"pmid":"12047197","id":"PMC_12047197","title":"Factors governing the protonation state of cysteines in proteins: an Ab initio/CDM study.","date":"2002","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/12047197","citation_count":84,"is_preprint":false},{"pmid":"24139803","id":"PMC_24139803","title":"CDIP1-BAP31 complex transduces apoptotic signals from endoplasmic reticulum to mitochondria under endoplasmic reticulum stress.","date":"2013","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/24139803","citation_count":83,"is_preprint":false},{"pmid":"9452422","id":"PMC_9452422","title":"Bcl-XL cooperatively associates with the Bap31 complex in the endoplasmic reticulum, dependent on procaspase-8 and Ced-4 adaptor.","date":"1998","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9452422","citation_count":79,"is_preprint":false},{"pmid":"12191913","id":"PMC_12191913","title":"The CDM protein DOCK2 in lymphocyte migration.","date":"2002","source":"Trends in cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12191913","citation_count":77,"is_preprint":false},{"pmid":"31535369","id":"PMC_31535369","title":"Melatonin attenuates ER stress and mitochondrial damage in septic cardiomyopathy: A new mechanism involving BAP31 upregulation and MAPK-ERK pathway.","date":"2019","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/31535369","citation_count":76,"is_preprint":false},{"pmid":"10559471","id":"PMC_10559471","title":"Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins.","date":"1999","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/10559471","citation_count":74,"is_preprint":false},{"pmid":"12886015","id":"PMC_12886015","title":"A high-molecular-weight complex of membrane proteins BAP29/BAP31 is involved in the retention of membrane-bound IgD in the endoplasmic reticulum.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12886015","citation_count":74,"is_preprint":false},{"pmid":"21151997","id":"PMC_21151997","title":"Membrane-Associated RING-CH proteins associate with Bap31 and target CD81 and CD44 to lysosomes.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21151997","citation_count":67,"is_preprint":false},{"pmid":"18684816","id":"PMC_18684816","title":"Bap31 is a novel target of the human papillomavirus E5 protein.","date":"2008","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/18684816","citation_count":67,"is_preprint":false},{"pmid":"24011989","id":"PMC_24011989","title":"Mutations in BCAP31 cause a severe X-linked phenotype with deafness, dystonia, and central hypomyelination and disorganize the Golgi apparatus.","date":"2013","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24011989","citation_count":56,"is_preprint":false},{"pmid":"12529377","id":"PMC_12529377","title":"Uncleaved BAP31 in association with A4 protein at the endoplasmic reticulum is an inhibitor of Fas-initiated release of cytochrome c from mitochondria.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12529377","citation_count":56,"is_preprint":false},{"pmid":"9988320","id":"PMC_9988320","title":"Leishmania spp: completely defined medium without serum and macromolecules (CDM/LP) for the continuous in vitro cultivation of infective promastigote forms.","date":"1999","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/9988320","citation_count":55,"is_preprint":false},{"pmid":"30022068","id":"PMC_30022068","title":"BAP31, a newly defined cancer/testis antigen, regulates proliferation, migration, and invasion to promote cervical cancer progression.","date":"2018","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/30022068","citation_count":53,"is_preprint":false},{"pmid":"17056546","id":"PMC_17056546","title":"Bap31 enhances the endoplasmic reticulum export and quality control of human class I MHC molecules.","date":"2006","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/17056546","citation_count":52,"is_preprint":false},{"pmid":"15294914","id":"PMC_15294914","title":"Association of BAP31 with CD11b/CD18. Potential role in intracellular trafficking of CD11b/CD18 in neutrophils.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15294914","citation_count":52,"is_preprint":false},{"pmid":"11274174","id":"PMC_11274174","title":"Control of cystic fibrosis transmembrane conductance regulator expression by BAP31.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11274174","citation_count":50,"is_preprint":false},{"pmid":"15024066","id":"PMC_15024066","title":"The yeast split-ubiquitin membrane protein two-hybrid screen identifies BAP31 as a regulator of the turnover of endoplasmic reticulum-associated protein tyrosine phosphatase-like B.","date":"2004","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15024066","citation_count":48,"is_preprint":false},{"pmid":"11992258","id":"PMC_11992258","title":"Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: a novel neonatal phenotype similar to peroxisomal biogenesis disorders.","date":"2002","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11992258","citation_count":47,"is_preprint":false},{"pmid":"16448126","id":"PMC_16448126","title":"A DFT/CDM Study of metal-carboxylate interactions in metalloproteins: factors governing the maximum number of metal-bound carboxylates.","date":"2006","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/16448126","citation_count":47,"is_preprint":false},{"pmid":"37296105","id":"PMC_37296105","title":"HNF4A-BAP31-VDAC1 axis synchronously regulates cell proliferation and ferroptosis in gastric cancer.","date":"2023","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/37296105","citation_count":46,"is_preprint":false},{"pmid":"33930507","id":"PMC_33930507","title":"BAP31: Physiological functions and roles in disease.","date":"2021","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/33930507","citation_count":45,"is_preprint":false},{"pmid":"15946936","id":"PMC_15946936","title":"BAP31 and its caspase cleavage product regulate cell surface expression of tetraspanins and integrin-mediated cell survival.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15946936","citation_count":44,"is_preprint":false},{"pmid":"28333124","id":"PMC_28333124","title":"BAP31 is involved in T cell activation through TCR signal pathways.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28333124","citation_count":42,"is_preprint":false},{"pmid":"21285974","id":"PMC_21285974","title":"Fis1, Bap31 and the kiss of death between mitochondria and endoplasmic reticulum.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21285974","citation_count":41,"is_preprint":false},{"pmid":"16332681","id":"PMC_16332681","title":"BAP31 is involved in the retention of cytochrome P450 2C2 in the endoplasmic reticulum.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16332681","citation_count":41,"is_preprint":false},{"pmid":"30338855","id":"PMC_30338855","title":"A BAP31 intrabody induces gastric cancer cell death by inhibiting p27kip1 proteasome degradation.","date":"2019","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30338855","citation_count":39,"is_preprint":false},{"pmid":"19342655","id":"PMC_19342655","title":"Interaction of Bap31 and MHC class I molecules and their traffic out of the endoplasmic reticulum.","date":"2009","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/19342655","citation_count":39,"is_preprint":false},{"pmid":"32381456","id":"PMC_32381456","title":"Pirfenidone alleviates lipopolysaccharide-induced lung injury by accentuating BAP31 regulation of ER stress and mitochondrial injury.","date":"2020","source":"Journal of autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/32381456","citation_count":38,"is_preprint":false},{"pmid":"31883536","id":"PMC_31883536","title":"BAP31 regulates IRAK1-dependent neuroinflammation in microglia.","date":"2019","source":"Journal of neuroinflammation","url":"https://pubmed.ncbi.nlm.nih.gov/31883536","citation_count":38,"is_preprint":false},{"pmid":"17030600","id":"PMC_17030600","title":"The CDM superfamily protein MBC directs myoblast fusion through a mechanism that requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of direct interaction with DCrk.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17030600","citation_count":35,"is_preprint":false},{"pmid":"33363167","id":"PMC_33363167","title":"BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma.","date":"2020","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/33363167","citation_count":32,"is_preprint":false},{"pmid":"33210473","id":"PMC_33210473","title":"MiR-362 suppresses cervical cancer progression via directly targeting BAP31 and activating TGFβ/Smad pathway.","date":"2020","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33210473","citation_count":32,"is_preprint":false},{"pmid":"22472424","id":"PMC_22472424","title":"Contiguous deletion of SLC6A8 and BAP31 in a patient with severe dystonia and sensorineural deafness.","date":"2012","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/22472424","citation_count":32,"is_preprint":false},{"pmid":"18303888","id":"PMC_18303888","title":"Mononuclear versus binuclear metal-binding sites: metal-binding affinity and selectivity from PDB survey and DFT/CDM calculations.","date":"2008","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/18303888","citation_count":32,"is_preprint":false},{"pmid":"30596517","id":"PMC_30596517","title":"BAP31 deficiency contributes to the formation of amyloid-β plaques in Alzheimer's disease by reducing the stability of RTN3.","date":"2018","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/30596517","citation_count":32,"is_preprint":false},{"pmid":"29113994","id":"PMC_29113994","title":"Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice.","date":"2017","source":"Journal of lipid research","url":"https://pubmed.ncbi.nlm.nih.gov/29113994","citation_count":29,"is_preprint":false},{"pmid":"10762002","id":"PMC_10762002","title":"Refining the mouse chromosomal location of Cdm, the major gene associated with susceptibility to cadmium-induced testicular necrosis.","date":"2000","source":"Pharmacogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/10762002","citation_count":29,"is_preprint":false},{"pmid":"24597975","id":"PMC_24597975","title":"Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1.","date":"2014","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24597975","citation_count":28,"is_preprint":false},{"pmid":"12605685","id":"PMC_12605685","title":"The resident endoplasmic reticulum protein, BAP31, associates with gamma-actin and myosin B heavy chain.","date":"2003","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12605685","citation_count":27,"is_preprint":false},{"pmid":"11561007","id":"PMC_11561007","title":"Endoplasmic reticulum membrane-sorting protein of lymphocytes (BAP31) is highly expressed in neurons and discrete endocrine cells.","date":"2001","source":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society","url":"https://pubmed.ncbi.nlm.nih.gov/11561007","citation_count":26,"is_preprint":false},{"pmid":"20378542","id":"PMC_20378542","title":"Yet1p and Yet3p, the yeast homologs of BAP29 and BAP31, interact with the endoplasmic reticulum translocation apparatus and are required for inositol prototrophy.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20378542","citation_count":26,"is_preprint":false},{"pmid":"7806238","id":"PMC_7806238","title":"A new human gene (DXS1357E) with ubiquitous expression, located in Xq28 adjacent to the adrenoleukodystrophy gene.","date":"1994","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/7806238","citation_count":25,"is_preprint":false},{"pmid":"31588230","id":"PMC_31588230","title":"BCAP31 drives TNBC development by modulating ligand-independent EGFR trafficking and spontaneous EGFR phosphorylation.","date":"2019","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/31588230","citation_count":24,"is_preprint":false},{"pmid":"30081561","id":"PMC_30081561","title":"Induction of Liver Steatosis in BAP31-Deficient Mice Burdened with Tunicamycin-Induced Endoplasmic Reticulum Stress.","date":"2018","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30081561","citation_count":24,"is_preprint":false},{"pmid":"22994209","id":"PMC_22994209","title":"Contiguous ABCD1 DXS1357E deletion syndrome: report of an autopsy case.","date":"2012","source":"Neuropathology : official journal of the Japanese Society of Neuropathology","url":"https://pubmed.ncbi.nlm.nih.gov/22994209","citation_count":23,"is_preprint":false},{"pmid":"31671609","id":"PMC_31671609","title":"BAP31 Inhibits Cell Adaptation to ER Stress Conditions, Negatively Regulating Autophagy Induction by Interaction with STX17.","date":"2019","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/31671609","citation_count":23,"is_preprint":false},{"pmid":"25903101","id":"PMC_25903101","title":"BAP31, a promising target for the immunotherapy of malignant melanomas.","date":"2015","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/25903101","citation_count":22,"is_preprint":false},{"pmid":"30503502","id":"PMC_30503502","title":"Inhibition of BAP31 expression inhibits cervical cancer progression by suppressing metastasis and inducing intrinsic and extrinsic apoptosis.","date":"2018","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/30503502","citation_count":21,"is_preprint":false},{"pmid":"36549351","id":"PMC_36549351","title":"BAP31 regulates the expression of ICAM-1/VCAM-1 via MyD88/NF-κB pathway in acute lung injury mice model.","date":"2022","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36549351","citation_count":20,"is_preprint":false},{"pmid":"32582765","id":"PMC_32582765","title":"MicroRNA-362-3p Inhibits Migration and Invasion via Targeting BCAP31 in Cervical Cancer.","date":"2020","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/32582765","citation_count":20,"is_preprint":false},{"pmid":"11078879","id":"PMC_11078879","title":"Limited caspase cleavage of human BAP31.","date":"2000","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/11078879","citation_count":20,"is_preprint":false},{"pmid":"32132574","id":"PMC_32132574","title":"BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32132574","citation_count":19,"is_preprint":false},{"pmid":"23967155","id":"PMC_23967155","title":"Structural and biophysical characterization of the cytoplasmic domains of human BAP29 and BAP31.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23967155","citation_count":19,"is_preprint":false},{"pmid":"31188831","id":"PMC_31188831","title":"An interferon-like small chemical compound CDM-3008 suppresses hepatitis B virus through induction of interferon-stimulated genes.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/31188831","citation_count":19,"is_preprint":false},{"pmid":"17660202","id":"PMC_17660202","title":"Consensus Data Mining (CDM) Protein Secondary Structure Prediction Server: combining GOR V and Fragment Database Mining (FDM).","date":"2007","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/17660202","citation_count":19,"is_preprint":false},{"pmid":"25044748","id":"PMC_25044748","title":"Distal Xq28 microdeletions: clarification of the spectrum of contiguous gene deletions involving ABCD1, BCAP31, and SLC6A8 with a new case and review of the literature.","date":"2014","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/25044748","citation_count":19,"is_preprint":false},{"pmid":"35292697","id":"PMC_35292697","title":"Analysis of treatment pattern of anti-dementia medications in newly diagnosed Alzheimer's dementia using OMOP CDM.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/35292697","citation_count":17,"is_preprint":false},{"pmid":"35090998","id":"PMC_35090998","title":"Lanthanum decreased VAPB-PTPP51, BAP31-FIS1, and MFN2-MFN1 expression of mitochondria-associated membranes and induced abnormal autophagy in rat hippocampus.","date":"2022","source":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","url":"https://pubmed.ncbi.nlm.nih.gov/35090998","citation_count":17,"is_preprint":false},{"pmid":"19642664","id":"PMC_19642664","title":"Metal-binding affinity and selectivity of nonstandard natural amino acid residues from DFT/CDM calculations.","date":"2009","source":"The journal of physical chemistry. B","url":"https://pubmed.ncbi.nlm.nih.gov/19642664","citation_count":17,"is_preprint":false},{"pmid":"15315443","id":"PMC_15315443","title":"Oxyanion selectivity in sulfate and molybdate transport proteins: an ab initio/CDM study.","date":"2004","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/15315443","citation_count":14,"is_preprint":false},{"pmid":"25854864","id":"PMC_25854864","title":"Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein.","date":"2015","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/25854864","citation_count":14,"is_preprint":false},{"pmid":"28332767","id":"PMC_28332767","title":"BCAP31-associated encephalopathy and complex movement disorder mimicking mitochondrial encephalopathy.","date":"2017","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/28332767","citation_count":14,"is_preprint":false},{"pmid":"36895489","id":"PMC_36895489","title":"The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation.","date":"2023","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36895489","citation_count":14,"is_preprint":false},{"pmid":"37063427","id":"PMC_37063427","title":"BAP31 depletion inhibited adipogenesis, repressed lipolysis and promoted lipid droplets abnormal growth via attenuating Perilipin1 proteasomal degradation.","date":"2023","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37063427","citation_count":12,"is_preprint":false},{"pmid":"31953925","id":"PMC_31953925","title":"Possible mitochondrial dysfunction in a patient with deafness, dystonia, and cerebral hypomyelination (DDCH) due to BCAP31 Mutation.","date":"2020","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31953925","citation_count":12,"is_preprint":false},{"pmid":"31330203","id":"PMC_31330203","title":"BCAP31-related syndrome: The first de novo report.","date":"2019","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31330203","citation_count":12,"is_preprint":false},{"pmid":"16895422","id":"PMC_16895422","title":"Competition between protein ligands and cytoplasmic inorganic anions for the metal cation: a DFT/CDM study.","date":"2006","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/16895422","citation_count":11,"is_preprint":false},{"pmid":"26102500","id":"PMC_26102500","title":"Epitope Mapping of Antibodies Suggests the Novel Membrane Topology of B-Cell Receptor Associated Protein 31 on the Cell Surface of Embryonic Stem Cells: The Novel Membrane Topology of BAP31.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26102500","citation_count":10,"is_preprint":false},{"pmid":"39381793","id":"PMC_39381793","title":"BCAP31 Alleviates Lipopolysaccharide-Mediated Acute Lung Injury via Induction of PINK1/Parkin in Alveolar Epithelial Type II Cell.","date":"2024","source":"Research (Washington, D.C.)","url":"https://pubmed.ncbi.nlm.nih.gov/39381793","citation_count":9,"is_preprint":false},{"pmid":"32652807","id":"PMC_32652807","title":"De novo mutation and skewed X-inactivation in girl with BCAP31-related syndrome.","date":"2020","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/32652807","citation_count":9,"is_preprint":false},{"pmid":"35449837","id":"PMC_35449837","title":"BAP31 Promotes Proliferation, Invasion, and Metastasis of Liver Cancer Cells via Activating PI3K/AKT Pathway.","date":"2022","source":"Journal of healthcare engineering","url":"https://pubmed.ncbi.nlm.nih.gov/35449837","citation_count":9,"is_preprint":false},{"pmid":"33603160","id":"PMC_33603160","title":"Further delineation of BCAP31-linked intellectual disability: description of 17 new families with LoF and missense variants.","date":"2021","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/33603160","citation_count":9,"is_preprint":false},{"pmid":"27714454","id":"PMC_27714454","title":"Plant-specific 4/1 polypeptide interacts with an endoplasmic reticulum protein related to human BAP31.","date":"2016","source":"Planta","url":"https://pubmed.ncbi.nlm.nih.gov/27714454","citation_count":9,"is_preprint":false},{"pmid":"35359416","id":"PMC_35359416","title":"BAP31 Regulates Wnt Signaling to Modulate Cell Migration in Lung Cancer.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35359416","citation_count":8,"is_preprint":false},{"pmid":"33777312","id":"PMC_33777312","title":"Regulation of Superoxide by BAP31 through Its Effect on p22phox and Keap1/Nrf2/HO-1 Signaling Pathway in Microglia.","date":"2021","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/33777312","citation_count":8,"is_preprint":false},{"pmid":"32681719","id":"PMC_32681719","title":"Schimke XLID syndrome results from a deletion in BCAP31.","date":"2020","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/32681719","citation_count":7,"is_preprint":false},{"pmid":"32222221","id":"PMC_32222221","title":"Cell-derived matrices (CDM)-Methods, challenges and applications.","date":"2020","source":"Methods in cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32222221","citation_count":6,"is_preprint":false},{"pmid":"38434584","id":"PMC_38434584","title":"BAP31 Promotes Adhesion Between Endothelial Cells and Macrophages Through the NF-κB Signaling Pathway in Sepsis.","date":"2024","source":"Journal of inflammation research","url":"https://pubmed.ncbi.nlm.nih.gov/38434584","citation_count":6,"is_preprint":false},{"pmid":"38069061","id":"PMC_38069061","title":"BAP31-Mediated miR-206/133b Cluster Promotes Transendothelial Migration and Metastasis of Colorectal Cancer.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38069061","citation_count":6,"is_preprint":false},{"pmid":"37762705","id":"PMC_37762705","title":"Knockdown of BAP31 Downregulates Galectin-3 to Inhibit the Wnt/β-Catenin Signaling Pathway to Modulate 5-FU Chemosensitivity and Cancer Stemness in Colorectal Cancer.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37762705","citation_count":6,"is_preprint":false},{"pmid":"38474195","id":"PMC_38474195","title":"BAP31 Promotes Angiogenesis via Galectin-3 Upregulation in Neuroblastoma.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38474195","citation_count":6,"is_preprint":false},{"pmid":"36018529","id":"PMC_36018529","title":"BAP31 affects macrophage polarization through regulating helper T cells activation.","date":"2022","source":"Journal of molecular histology","url":"https://pubmed.ncbi.nlm.nih.gov/36018529","citation_count":6,"is_preprint":false},{"pmid":"19857118","id":"PMC_19857118","title":"Novel immunohistochemical monoclonal antibody against rat B cell receptor Associated Protein 31 (BAP31).","date":"2009","source":"Hybridoma (2005)","url":"https://pubmed.ncbi.nlm.nih.gov/19857118","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":48749,"output_tokens":9086,"usd":0.141268},"stage2":{"model":"claude-opus-4-6","input_tokens":12935,"output_tokens":4577,"usd":0.26865},"total_usd":0.409918,"stage1_batch_id":"msgbatch_01TqNM6p6FsoMBT2jzQTwKBr","stage2_batch_id":"msgbatch_01Ya473eco8sTHbvRymQaU8o","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1997,\n      \"finding\": \"BAP31 (p28) is an integral ER membrane protein that forms a complex with Bcl-2/Bcl-XL and procaspase-8 (pro-FLICE); caspase-8 and caspase-1, but not caspase-3, cleave BAP31 at two identical AAVD/G recognition sites; the resulting N-terminal p20 fragment induces apoptosis when expressed ectopically; Bax prevents Bcl-2 from associating with the complex.\",\n      \"method\": \"Co-immunoprecipitation in co-transfected 293T cells; in vitro cleavage assay with purified caspases; ectopic expression of p20 fragment\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (Co-IP, in vitro enzymatic assay, ectopic expression phenotype) in founding paper\",\n      \"pmids\": [\"9334338\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"BAP31 controls ER export of cellubrevin; the interaction requires the transmembrane regions of both proteins; truncation of the BAP31 cytoplasmic tail prevents ER export of cellubrevin but not of the transferrin receptor, establishing a cargo-specific sorting role.\",\n      \"method\": \"Affinity pulldown with immobilized recombinant cellubrevin; co-immunoprecipitation from fibroblast detergent extracts; subcellular fractionation; immunocytochemistry; nocodazole treatment; BAP31 truncation mutants\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — biochemical interaction confirmed by multiple methods plus domain-mapping mutagenesis\",\n      \"pmids\": [\"9396746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"The predicted death effector homology (vDED) domain in the cytosolic region of BAP31 interacts with Ced-4 and contributes to procaspase-8 recruitment; Bcl-XL associates cooperatively with the BAP31 cytosolic domain dependent on procaspase-8 and Ced-4; Bcl-XL binds directly but weakly to the transmembrane region of BAP31.\",\n      \"method\": \"Co-transfection and co-immunoprecipitation in human cells; domain-deletion mutant analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP with domain-mapping in multiple constructs; consistent with founding complex paper\",\n      \"pmids\": [\"9452422\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Caspase-resistant BAP31 (crBAP31, D→A mutations at both cleavage sites) inhibits Fas-mediated cytochrome c release from mitochondria, BAX/BAK oligomerization, membrane blebbing, and apoptotic actin redistribution, revealing that BAP31 cleavage by caspase-8 is required for ER-mitochondria cross-talk during Fas-induced apoptosis; full-length BAP31 is a direct inhibitor of caspase-8-initiated cytochrome c release.\",\n      \"method\": \"Stable expression of caspase-resistant BAP31 mutant in KB epithelial cells; Fas stimulation; cytochrome c release assay; mitochondrial membrane potential measurement; Bap31-null mouse cells reconstituted with crBAP31\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — site-directed mutagenesis, null cells, multiple functional readouts; replicated across cell types\",\n      \"pmids\": [\"10958671\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The procaspase-8 isoform procaspase-8L, characterized by an N-terminal extension (Nex) domain, is selectively recruited to the BAP31 complex at the ER; this recruitment requires the Nex domain; BAP31 and its homologue BAP29 are required for procaspase-8L processing during E1A-induced apoptosis by a FADD-independent, Bcl-2-sensitive mechanism.\",\n      \"method\": \"Co-immunoprecipitation; gene deletion of Bap29/Bap31; dominant-negative Nex mutant; caspase activity assays (IETDase, DEVDase)\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic deletion combined with dominant-negative and biochemical interaction, multiple functional readouts\",\n      \"pmids\": [\"11917123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The p20 caspase-8 cleavage fragment of BAP31 induces Ca2+ release from the ER, mitochondrial Ca2+ uptake, Drp1 recruitment to mitochondria, and mitochondrial fission; this Ca2+-dependent fission sensitises mitochondria to caspase-8-induced cytochrome c release. Inhibition of Drp1 or ER-mitochondrial Ca2+ signalling prevents p20-induced fission.\",\n      \"method\": \"Adenoviral expression of p20 BAP31; Ca2+ imaging; cytochrome c release assay; dominant-negative Drp1 expression; mitochondrial morphology imaging\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal approaches (live imaging, dominant-negative, inhibitors, cytochrome c assay) in a single rigorous study; highly cited\",\n      \"pmids\": [\"12668660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"BAP31 specifically associates with nonmuscle myosin heavy chain B and nonmuscle gamma-actin (components of the cytoskeletal actomyosin complex); Fas-induced apoptosis releases BAP31 from these motor proteins.\",\n      \"method\": \"Capillary LC-MS/MS characterisation of BAP31 immunocomplex from HepG2 cell lysate; co-immunoprecipitation\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — MS identification confirmed by Co-IP, single lab\",\n      \"pmids\": [\"12605685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"High-molecular-weight BAP29/BAP31 complexes retain membrane-bound IgD (mIgD) in the ER; BAP complex binding to mIg correlates with ER retention; overexpression of BAP29/BAP31 in Drosophila S2 cells prevents aberrant surface transport of mIgD in the absence of Igα/Igβ; retention is through true ER retention, not retrieval.\",\n      \"method\": \"Blue native PAGE; co-immunoprecipitation; surface expression assays; heterologous expression in Drosophila S2 cells\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (native PAGE, Co-IP, heterologous system) demonstrating mechanistic retention function\",\n      \"pmids\": [\"12886015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Uncleaved full-length BAP31 in association with the putative ER ion channel protein A4 acts as a direct inhibitor of Fas-initiated BAX oligomerization and cytochrome c release from mitochondria, independently of its ability to sequester p20 BAP31; A4 was identified as a constitutive binding partner of BAP31 via split-ubiquitin yeast two-hybrid screen.\",\n      \"method\": \"Split-ubiquitin yeast two-hybrid screen; co-immunoprecipitation; Bap31-null mouse cells reconstituted with crBAP31 and/or A4; cytochrome c release assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — genetic null cells, interaction screen confirmed by Co-IP, functional reconstitution\",\n      \"pmids\": [\"12529377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Active caspase-8 localises predominantly on the outer mitochondrial membrane (OMM) as an integral protein during apoptosis; OMM-localised active caspase-8 can cleave ER-localised BAP31, generating pro-apoptotic BAP20, which mediates mitochondria-ER cross-talk through a Ca2+-dependent mechanism.\",\n      \"method\": \"Subcellular fractionation; immunofluorescence microscopy; dominant-negative mutants; siRNA; caspase-8-deficient Jurkat cells; BAP31 cleavage assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple independent approaches (fractionation, imaging, genetic loss-of-function, dominant-negative) in single study\",\n      \"pmids\": [\"15254227\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"BAP31 is required to maintain the stability of PTPLB (a novel ER membrane protein tyrosine phosphatase-like family member); loss of Bap31 in knockout mouse cells leads to increased PTPLB proteasomal degradation, consistent with a chaperone/quality-control function for BAP31 in the ER membrane.\",\n      \"method\": \"Yeast split-ubiquitin screen with BAP31 as bait; Bap31-null mouse ES cells; proteasomal degradation assays; reconstitution with human BAP31\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — genetic null cells, interaction screen, reconstitution experiment\",\n      \"pmids\": [\"15024066\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"BAP31 specifically binds to CD11b/CD18 integrin via its cytoplasmic tail (not the I-domain of CD11b); BAP31 co-localises with CD11b/CD18 in neutrophil secondary granules and both redistribute to the plasma membrane together following fMLP stimulation, implicating BAP31 in intracellular trafficking of CD11b/CD18.\",\n      \"method\": \"Monoclonal antibody generation; co-immunoprecipitation; GST-fusion protein binding assay; immunolocalization; subcellular fractionation of PMN\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — biochemical interaction confirmed by Co-IP and pulldown, localization data, but functional consequence inferred\",\n      \"pmids\": [\"15294914\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"BAP31 is required for cell surface expression of the tetraspanins CD9 and CD81; in Bap31-null mouse cells, CD9/CD81 surface levels are reduced and integrin-mediated cell adhesion and survival under serum stress are impaired; reconstitution of BAP31 restores these functions; the p20 BAP31 caspase fragment inhibits tetraspanin/integrin-mediated cell attachment in cells protected from apoptosis by Bcl-2.\",\n      \"method\": \"Bap31-null mouse cells; wild-type BAP31 reconstitution; flow cytometry for surface expression; cell adhesion assay; serum-starvation apoptosis assay; antagonising antibodies against CD9, integrins\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic null and reconstitution with multiple orthogonal functional readouts\",\n      \"pmids\": [\"15946936\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"BAP31 interacts with and retains cytochrome P450 2C2 in the ER; BAP31 knockdown or Bap31-null cells cause P450 2C2 redistribution away from the ER to the nuclear envelope and cell surface; the interaction is mediated through transmembrane domains; overexpression of P450 2C2 induces formation of the pro-apoptotic p20 BAP31 fragment.\",\n      \"method\": \"Bimolecular fluorescence complementation; co-immunoprecipitation; siRNA knockdown; Bap31-null ES cells; reconstitution; immunofluorescence\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods and genetic null cell validation\",\n      \"pmids\": [\"16332681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"BAP31 overexpression increases surface MHC class I levels by accelerating the rate of ER export of newly synthesised peptide-loaded class I molecules and by stabilising them post-ER; Bap31 deficiency does not reduce surface class I, indicating redundancy; Bap29 overexpression decreases surface class I.\",\n      \"method\": \"YFP-Bap31 transfection; flow cytometry; radioimmunoprecipitation pulse-chase; Bap31 knockdown/null cells\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — overexpression and loss-of-function with quantitative surface and trafficking assays, but redundancy complicates interpretation\",\n      \"pmids\": [\"17056546\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"BAP31 associates with Sec61β and TRAM components of the Sec61 translocon, and with the Derlin-1 dislocation complex; BAP31 associates with the N-terminus of newly synthesised CFTRΔf508 and promotes its retrotranslocation from the ER for degradation by the 26S proteasome; depletion of BAP31 reduces proteasomal degradation of ΔF508 and allows a significant fraction to reach the cell surface.\",\n      \"method\": \"Co-immunoprecipitation; siRNA depletion; proteasome inhibitor treatments; surface biotinylation; pulse-chase\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — published in Cell, multiple orthogonal Co-IP and functional assays establishing a mechanistic ERAD pathway\",\n      \"pmids\": [\"18555783\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Bap31 is an itinerant ER protein that cycles between peripheral ER and a juxtanuclear ER-quality-control compartment; cycling requires the second and third transmembrane domains and depends on microtubules and dynein-dynactin; overexpression of Sar1p and Arf1 mutants affects Bap31 cycling.\",\n      \"method\": \"Live-cell fluorescence imaging; FRAP; nocodazole/dynein-dynactin inhibition; domain deletion mutants; dominant-negative Sar1/Arf1\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiments with functional domain mapping and pharmacological/genetic perturbations\",\n      \"pmids\": [\"18287538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"BAP31 interacts with MHC class I (HLA-A2) in the ER and traffics with it via export vesicles to the ER-Golgi intermediate compartment; peptide loading of MHC class I increases FRET between Bap31 and HLA-A2 and promotes forward traffic; overexpression of Bap29 blocks this forward traffic.\",\n      \"method\": \"FRET imaging; quantitative fluorescence microscopy; Bap29 overexpression competition assay\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct imaging-based interaction and trafficking experiment with functional perturbation by Bap29\",\n      \"pmids\": [\"19342655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Fis1 (mitochondrial fission protein) interacts with BAP31 at the ER interface to form the 'ARCosome' complex spanning mitochondria and ER; this complex recruits procaspase-8 in a vDED-dependent manner; Fis1-BAP31 interaction facilitates caspase-8 activation, which drives BAP31 cleavage into pro-apoptotic p20BAP31, releasing Ca2+ from the ER as a feedback signal to activate mitochondria.\",\n      \"method\": \"Co-immunoprecipitation; split-ubiquitin two-hybrid; dominant-negative constructs; vDED deletion mutants; Ca2+ imaging; apoptosis assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal biochemical and cell-biological methods, reciprocal Co-IP, domain mutagenesis, functional readouts; highly cited\",\n      \"pmids\": [\"21183955\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"BAP31 and the ER chaperone BiP are essential for ER-to-cytosol dislocation of SV40 during viral infection; both proteins co-localise with incoming virus in discrete ER foci and promote virus crossing of the ER membrane, implicating them as ERAD factors required for SV40 retrotranslocation.\",\n      \"method\": \"siRNA screen; co-localisation by immunofluorescence; infection assays with VP2-deficient virus-like particles\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — siRNA screen followed by co-localisation and functional rescue, published in Nature Cell Biology\",\n      \"pmids\": [\"21947079\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The proapoptotic p53 target CDIP1 interacts with BAP31 at the ER membrane upon ER stress; CDIP1 binding to BAP31 is required for BAP31 cleavage and BAP31-Bcl-2 association; the CDIP1-BAP31 complex recruits Bcl-2 and activates caspase-8/tBid, driving BAX oligomerisation and mitochondrial apoptosis; genetic knockout of CDIP1 in mice impairs ER-stress-mediated apoptosis.\",\n      \"method\": \"Co-immunoprecipitation; CDIP1 genetic knockout mouse; caspase-8/tBid activation assays; BAX oligomerisation assay; ER stress induction\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vivo genetic knockout combined with multiple biochemical Co-IP and functional assays\",\n      \"pmids\": [\"24139803\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Crystal structures of the BAP31 vDED (variant death effector domain) cytoplasmic region show that it forms a dimeric parallel coiled coil with no structural similarity to canonical DED domains; solution studies indicate a second α-helical coiled-coil domain in the C-terminal cytoplasmic region; no direct interaction was detected between the cytoplasmic domains of BAP29 and BAP31.\",\n      \"method\": \"X-ray crystallography (two crystal forms); biophysical solution studies (SEC, CD, DLS, analytical ultracentrifugation)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structures with solution validation; directly refutes predicted DED fold\",\n      \"pmids\": [\"23967155\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Loss-of-function mutations in BCAP31 in humans cause ER morphology disruption and Golgi disorganisation in patient fibroblasts without activating the unfolded protein response or cell-death effectors, demonstrating a role for BAP31 in ER-to-Golgi crosstalk in vivo.\",\n      \"method\": \"Patient-derived primary fibroblasts; electron microscopy; UPR marker analysis; Golgi morphology by immunofluorescence\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — human loss-of-function genetics with direct cellular phenotype characterisation\",\n      \"pmids\": [\"24011989\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"BAP31 directly interacts with RSV small hydrophobic (SH) protein; co-localisation was shown in transfected cells; direct interaction of the BAP31 C-terminal endodomain with SH protein was demonstrated by NMR titration of purified proteins in detergent micelles.\",\n      \"method\": \"Membrane-based yeast two-hybrid screen; co-immunoprecipitation; NMR titration of purified proteins\",\n      \"journal\": \"Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-3 — NMR provides direct biophysical evidence but single lab; pulldown confirmed\",\n      \"pmids\": [\"25854864\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"BAP31 conditional knockout in the mouse thymus reduces T cell numbers; BAP31-deficient T cells show decreased proliferation upon TCR stimulation; BAP31 regulates phosphorylation of Zap70, Lck, and Lat (upstream TCR signal members) and Akt, GSK, JNK, and ERK (downstream members), and controls expression of CD3/TCRα/TCRβ and cytokines IL-2, IFN-γ, IL-6, and TNF-α.\",\n      \"method\": \"Cre/LoxP conditional knockdown mouse; T cell proliferation assays; Western blot for TCR pathway phosphorylation; flow cytometry; ELISA\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo conditional KO with multiple pathway readouts; single lab\",\n      \"pmids\": [\"28333124\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Hepatocyte-specific BAP31 deletion in mice increases SREBP1C expression and its target genes (ACC1, SCD1), promotes hepatic lipid accumulation and steatosis; BAP31 interacts with SREBP1C and INSIG1 by co-immunoprecipitation, and BAP31 deletion reduces INSIG1 levels, suggesting BAP31 regulates SREBP1C via INSIG1.\",\n      \"method\": \"Hepatocyte-specific conditional knockout mice; high-fat diet challenge; co-immunoprecipitation; Western blot; glucose/insulin tolerance tests\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo KO with Co-IP interaction data; single lab\",\n      \"pmids\": [\"29113994\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"BAP31 binds RTN3 and positively regulates its stability; BAP31 conditional knockout in hippocampus/cortex of APP/PS1 mice decreases RTN3 monomer levels, increases RTN3 aggregates, enhances BACE1 activity and APP processing, and increases amyloid-β plaque deposition.\",\n      \"method\": \"Co-immunoprecipitation; conditional knockout mouse crossed with AD model mice; hippocampal neuron cultures; amyloid plaque quantification\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic model with biochemical interaction, single lab\",\n      \"pmids\": [\"30596517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"BAP31 interacts with Tom40 (mitochondrial outer membrane import channel) within ER-mitochondria contact sites; this BAP31-Tom40 complex stimulates translocation of NDUFS4 (complex I subunit) from the cytosol to mitochondria; disruption of the complex reduces mitochondrial complex I activity and oxygen consumption.\",\n      \"method\": \"Co-immunoprecipitation; BAP31 knockdown; NDUFS4 mitochondrial localisation assay; oxygen consumption measurement\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP establishing interaction, loss-of-function with two functional readouts (NDUFS4 import and respiration), published in Science Advances\",\n      \"pmids\": [\"31206022\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"BAP31 negatively regulates autophagy by forming a complex with STX17 (a SNARE required for autophagosome formation); loss of BAP31 stimulates autophagy, promotes adaptation to ER stress, and enhances tumour cell invasion; BAP31 thus acts as a tumour suppressor by inhibiting autophagy-mediated ER stress adaptation.\",\n      \"method\": \"Co-immunoprecipitation of BAP31-STX17 complex; BAP31 knockdown/knockout; autophagy flux assays; in vivo tumour growth assay\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP interaction and KO functional data, single lab\",\n      \"pmids\": [\"31671609\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"BAP31 deficiency upregulates LPS-induced proinflammatory cytokines in microglia by increasing IRAK1 protein levels, which in turn increases NF-κB p65 and c-Jun nuclear translocation and transcriptional activity; knockdown of IRAK1 or use of an IRAK1 inhibitor reverses these effects.\",\n      \"method\": \"BAP31 conditional knockdown mice (Cre/LoxP); BV2 cell knockdown; ELISA; Western blot; immunofluorescence; IRAK1 inhibitor treatment; cognitive behavioural tests\",\n      \"journal\": \"Journal of neuroinflammation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo and in vitro KD with pathway epistasis (IRAK1 inhibitor rescue); single lab\",\n      \"pmids\": [\"31883536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"BCAP31 interacts with EGFR and inhibits ligand-independent EGFR recycling, thereby sustaining EGFR autophosphorylation and downstream signalling activation in triple-negative breast cancer cells.\",\n      \"method\": \"Co-immunoprecipitation; BCAP31 knockdown; surface EGFR trafficking assays; EGFR phosphorylation analysis\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP with functional trafficking and signalling readouts; single lab\",\n      \"pmids\": [\"31588230\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"BAP31 specifically interacts with and protects the cyclin kinase inhibitor p27kip1 from proteasomal degradation; an intrabody (VH-D1) targeting BAP31 blocks the BAP31-p27kip1 interaction, increases p27kip1 stability, inhibits gastric cancer cell proliferation, and activates caspase-dependent apoptosis.\",\n      \"method\": \"Co-immunoprecipitation; intrabody expression; proteasome inhibitor assay; xenograft tumour model\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP interaction with intrabody blocking and functional rescue; single lab\",\n      \"pmids\": [\"30338855\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"BAP31 directly binds VDAC1 and affects VDAC1 oligomerisation and polyubiquitination, thereby regulating cell proliferation and ferroptosis (lipid peroxidation); HNF4A binds the BAP31 promoter and drives its transcription.\",\n      \"method\": \"Co-immunoprecipitation; BAP31 knockdown; VDAC1 oligomerisation assay; lipid peroxidation assay; ChIP assay for HNF4A at BAP31 promoter; xenograft model\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP and ChIP with functional knockdown data; single lab\",\n      \"pmids\": [\"37296105\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Limited caspase cleavage of BAP31 during apoptosis (by TNF, staurosporine, Fas) occurs selectively at only the more carboxy-terminal of the two caspase recognition sites, removing eight amino acids including the KKXX COPI-binding motif; this cleavage redistributes Golgi mannosidase II and blocks ER-to-Golgi transport of viral glycoproteins.\",\n      \"method\": \"In-cell apoptosis induction (multiple stimuli); Western blot with site-specific antibodies; Golgi morphology imaging; viral glycoprotein trafficking assay\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple stimuli and orthogonal functional readouts; single lab\",\n      \"pmids\": [\"11078879\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"BAP31 interacts with Perilipin1 via its C-terminal cytoplasmic domain on lipid droplet surfaces; BAP31 depletion in adipocytes represses Perilipin1 proteasomal degradation, enhancing Perilipin1 levels, blocking lipid droplet degradation, and promoting super-sized lipid droplet formation, while inhibiting adipogenesis and lipolysis.\",\n      \"method\": \"Adipocyte-specific BAP31 conditional knockout mice; co-immunoprecipitation; proteasomal degradation assays; lipid droplet imaging; lipolysis assays\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo KO with biochemical interaction and multiple functional readouts; single lab\",\n      \"pmids\": [\"37063427\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BAP31 promotes PINK1 phosphorylation by directly binding to PINK1, thereby activating PINK1/Parkin-mediated mitophagy; BAP31 downregulation reduces PINK1 phosphorylation, impairs mitophagy, increases mitochondrial ROS, and activates the mROS/ROS/NF-κB pathway, leading to alveolar epithelial cell apoptosis and inflammation in ALI.\",\n      \"method\": \"BCAP31 transgenic and conditional knockout mice (Sftpc-Cre); co-immunoprecipitation of BAP31-PINK1; PINK1 phosphorylation assays; mitophagy flux assays; mitochondrial membrane permeability and ROS measurements; LPS-ALI model\",\n      \"journal\": \"Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo transgenic/KO mouse with Co-IP interaction and multiple functional pathway readouts; single lab\",\n      \"pmids\": [\"39381793\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"The specificity of BAP31/BAP29 association with membrane IgD (but not IgM) resides in specific amino acids within the transmembrane sequence of the δm heavy chain; full-length murine and human BAP31 cDNAs encode 245/246 aa proteins with N-terminal hydrophobic region and C-terminal α-helical domain ending in a KKXX ER-retention motif; BAP31 is encoded on the X chromosome.\",\n      \"method\": \"Mutational analysis of IgD transmembrane sequence; BAP31 cDNA cloning; transfection co-immunoprecipitation; chromosomal mapping\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — mutagenesis defining transmembrane interaction specificity; foundational structural and genetic characterisation\",\n      \"pmids\": [\"8612576\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"BAP31 is a ubiquitously expressed polytopic ER integral membrane protein that functions as a broad-specificity cargo receptor/chaperone (controlling ER retention, export, and ERAD of client membrane proteins including IgD, cellubrevin, MHC class I, CFTR, CD9/CD81, P450 2C2, and EGFR), a mitochondria-associated membrane (MAM) tetherer (via a Fis1-BAP31 ARCosome complex and a BAP31-Tom40 bridge that supports mitochondrial complex I assembly), and a central apoptosis regulator (forming an ER complex with Bcl-2/Bcl-XL and procaspase-8/procaspase-8L; upon death-receptor signalling, caspase-8 cleaves BAP31 at AAVD/G sites to generate p20-BAP31, which releases ER Ca2+, recruits Drp1, and drives mitochondrial fission and cytochrome c release, while full-length BAP31 is itself anti-apoptotic).\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"BAP31 is a polytopic ER integral membrane protein that functions as a broad-specificity cargo receptor and quality-control factor governing ER retention, export, and degradation of diverse transmembrane clients, while simultaneously serving as a central platform linking ER stress and death-receptor signaling to mitochondrial apoptosis. As a cargo receptor, BAP31 retains membrane IgD via transmembrane-domain interactions [PMID:8612576, PMID:12886015], promotes ER export of cellubrevin, MHC class I, and tetraspanins CD9/CD81 [PMID:9396746, PMID:15946936, PMID:17056546], and channels misfolded CFTR∆F508 through the Sec61/Derlin-1 retrotranslocation machinery for proteasomal degradation [PMID:18555783]. In apoptosis, BAP31 forms an ER-localized complex with Bcl-2/Bcl-XL and procaspase-8; caspase-8 cleaves BAP31 at AAVD sites to generate the p20 fragment, which triggers ER Ca²⁺ release, Drp1-dependent mitochondrial fission, and cytochrome c release, whereas uncleaved BAP31 is itself anti-apoptotic [PMID:9334338, PMID:12668660, PMID:10958671]. BAP31 also tethers ER to mitochondria through a Fis1–BAP31 ARCosome complex that activates caspase-8 and through a BAP31–Tom40 bridge that facilitates mitochondrial complex I subunit import [PMID:21183955, PMID:31206022]; loss-of-function mutations in humans cause ER and Golgi disorganization [PMID:24011989].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Cloning of BAP31 established it as an ER-resident integral membrane protein with a C-terminal KKXX motif whose transmembrane domain confers selective binding to membrane IgD but not IgM, defining it as a cargo-selective ER-retention factor.\",\n      \"evidence\": \"cDNA cloning, transmembrane mutagenesis, Co-IP, chromosomal mapping\",\n      \"pmids\": [\"8612576\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No trafficking assay directly showing retention versus retrieval\", \"Interaction partners beyond Ig not explored\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Discovery that BAP31 forms a ternary complex with Bcl-2/Bcl-XL and procaspase-8, and that caspase-8 cleaves BAP31 at two AAVD sites to generate a pro-apoptotic p20 fragment, established BAP31 as a direct molecular link between ER and apoptosis signaling.\",\n      \"evidence\": \"Co-IP in 293T cells; in vitro caspase cleavage; ectopic p20 expression\",\n      \"pmids\": [\"9334338\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which p20 induces death not yet resolved\", \"Physiological stoichiometry of the complex unknown\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"BAP31 was shown to control ER export of cellubrevin in a cargo-specific manner dependent on its cytoplasmic tail, extending its role from ER retention to active forward trafficking.\",\n      \"evidence\": \"Affinity pulldown, Co-IP, BAP31 tail truncation mutants, nocodazole treatment in fibroblasts\",\n      \"pmids\": [\"9396746\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Coat machinery engaged by BAP31 tail not identified\", \"Whether BAP31 acts catalytically or stoichiometrically unclear\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Expression of caspase-resistant BAP31 (crBAP31) demonstrated that cleavage of BAP31 is required for Fas-induced ER-to-mitochondria apoptotic cross-talk, and that intact BAP31 is itself an inhibitor of cytochrome c release, resolving the dual pro-/anti-apoptotic roles of BAP31.\",\n      \"evidence\": \"Site-directed mutagenesis of cleavage sites; crBAP31 stable expression in KB cells and Bap31-null mouse cells; cytochrome c release, BAX oligomerization, membrane potential assays\",\n      \"pmids\": [\"10958671\", \"11078879\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the ER-to-mitochondria signal downstream of uncleaved BAP31 unknown\", \"Whether limited C-terminal clipping versus full cleavage have distinct outputs remained unclear\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"The p20 fragment was shown to trigger ER Ca²⁺ release, mitochondrial Ca²⁺ uptake, Drp1 recruitment, and mitochondrial fission, establishing the mechanistic pathway from BAP31 cleavage to mitochondrial fragmentation and cytochrome c release.\",\n      \"evidence\": \"Adenoviral p20 expression; Ca²⁺ imaging; dominant-negative Drp1; mitochondrial morphology analysis\",\n      \"pmids\": [\"12668660\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Channel or mechanism of p20-induced ER Ca²⁺ release not identified\", \"Whether p20 forms a pore or activates an existing channel unknown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"BAP29/BAP31 heteromeric complexes were shown to retain membrane IgD in the ER by a true retention rather than retrieval mechanism, and the ER partner A4 was identified as a constitutive BAP31-binding protein that contributes to anti-apoptotic function, broadening the repertoire of BAP31 quality-control complexes.\",\n      \"evidence\": \"Blue native PAGE; heterologous expression in Drosophila S2 cells; split-ubiquitin screen; Bap31-null reconstitution\",\n      \"pmids\": [\"12886015\", \"12529377\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity and stoichiometry of high-MW BAP31 complexes not fully resolved\", \"Mechanism by which A4 contributes to anti-apoptotic signaling unclear\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstration that BAP31 stabilizes the ER membrane protein PTPLB and traffics with CD11b/CD18 integrins expanded BAP31's client repertoire to include non-immunoglobulin cargo, confirming a general chaperone/quality-control function.\",\n      \"evidence\": \"Bap31-null mouse ES cells; proteasomal degradation assays for PTPLB; Co-IP and fractionation in neutrophils for CD11b/CD18\",\n      \"pmids\": [\"15024066\", \"15294914\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether BAP31 directly stabilizes PTPLB via folding assistance or by shielding from ERAD unknown\", \"Functional consequence of BAP31-CD11b interaction on immune function not tested\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"BAP31 was shown to be required for surface expression of tetraspanins CD9/CD81 and for ER retention of cytochrome P450 2C2, establishing that BAP31 can either promote or prevent ER exit depending on the cargo.\",\n      \"evidence\": \"Bap31-null cells with reconstitution; flow cytometry; BiFC and immunofluorescence for P450 2C2\",\n      \"pmids\": [\"15946936\", \"16332681\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Determinants within cargo that dictate export versus retention by BAP31 not defined\", \"Structural basis for bidirectional sorting unknown\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"BAP31 was found to associate with the Sec61 translocon and Derlin-1 dislocation complex and to channel misfolded CFTR∆F508 for proteasomal degradation, directly placing BAP31 within the ERAD retrotranslocation machinery.\",\n      \"evidence\": \"Co-IP of BAP31 with Sec61β, TRAM, Derlin-1; siRNA depletion; pulse-chase and surface biotinylation for CFTR∆F508\",\n      \"pmids\": [\"18555783\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether BAP31 serves as a receptor that hands off substrates to Derlin-1 or acts within the channel complex not resolved\", \"ERAD substrates beyond CFTR not systematically cataloged\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Live-cell imaging revealed BAP31 cycles between peripheral ER and a juxtanuclear quality-control compartment in a microtubule/dynein-dependent manner, providing a dynamic trafficking framework for its cargo-sorting functions.\",\n      \"evidence\": \"FRAP; nocodazole and dynein-dynactin inhibition; TM domain deletion mutants; dominant-negative Sar1/Arf1\",\n      \"pmids\": [\"18287538\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Nature and identity of the juxtanuclear QC compartment not fully characterized\", \"How BAP31 cycling is regulated under stress conditions unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Discovery of the Fis1–BAP31 ARCosome complex at ER–mitochondria contact sites showed that BAP31 physically tethers these organelles and recruits procaspase-8 for activation, providing the structural basis for ER–mitochondria apoptotic signaling.\",\n      \"evidence\": \"Co-IP; split-ubiquitin two-hybrid; vDED deletion mutants; Ca²⁺ imaging; apoptosis assays\",\n      \"pmids\": [\"21183955\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and ultrastructure of the ARCosome not determined\", \"Whether ARCosome has non-apoptotic functions at MAMs unclear\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Crystal structures of the BAP31 cytoplasmic region revealed a dimeric parallel coiled-coil rather than a canonical DED fold, overturning the structural model of procaspase-8 recruitment, while CDIP1 was identified as a p53-dependent activator that engages BAP31 to trigger ER-stress-to-mitochondria apoptotic signaling.\",\n      \"evidence\": \"X-ray crystallography and biophysical studies for structure; CDIP1 knockout mouse with Co-IP and caspase activation assays\",\n      \"pmids\": [\"23967155\", \"24139803\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How a coiled-coil mediates procaspase-8 recruitment without a DED fold is structurally unresolved\", \"Whether CDIP1 is the sole p53-dependent activator of BAP31 cleavage unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Human loss-of-function mutations in BCAP31 were shown to cause ER morphology disruption and Golgi disorganization without activating the UPR, establishing BCAP31 as a disease gene and demonstrating its in vivo requirement for ER–Golgi homeostasis.\",\n      \"evidence\": \"Patient-derived fibroblasts; electron microscopy; UPR marker analysis; Golgi immunofluorescence\",\n      \"pmids\": [\"24011989\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full clinical phenotypic spectrum not delineated in this study\", \"Whether Golgi disruption is secondary to ER cargo mis-sorting not tested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"A BAP31–Tom40 bridge at ER–mitochondria contacts was shown to facilitate import of NDUFS4 into mitochondria and sustain complex I activity, revealing a non-apoptotic tethering function of BAP31 in mitochondrial bioenergetics.\",\n      \"evidence\": \"Co-IP of BAP31–Tom40; BAP31 knockdown; NDUFS4 import and oxygen consumption assays\",\n      \"pmids\": [\"31206022\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural interface between BAP31 and Tom40 not mapped\", \"Whether other mitochondrial import substrates depend on this bridge unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"BAP31 was found to interact with STX17, EGFR, and p27kip1, extending its regulatory reach to autophagy, receptor trafficking, and cell-cycle control beyond its canonical ER quality-control and apoptosis functions.\",\n      \"evidence\": \"Co-IP; BAP31 knockdown/KO with autophagy flux, EGFR recycling, and p27 stability assays\",\n      \"pmids\": [\"31671609\", \"31588230\", \"30338855\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanisms linking ER-localized BAP31 to cytosolic p27 stability are unclear\", \"Whether STX17 and EGFR interactions are direct or bridged not fully resolved\", \"Findings from single labs await independent replication\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"BAP31 was shown to bind VDAC1 and Perilipin1, regulating ferroptosis and lipid-droplet dynamics, further implicating BAP31 at membrane contact sites beyond the ER–mitochondria axis.\",\n      \"evidence\": \"Co-IP; adipocyte-specific KO mice; VDAC1 oligomerization and lipid peroxidation assays; lipid droplet imaging\",\n      \"pmids\": [\"37296105\", \"37063427\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether BAP31 localizes to lipid droplet surfaces directly or acts via ER–LD contacts not established\", \"Mechanism of BAP31 regulation of VDAC1 oligomerization unclear\", \"Single-lab findings\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"BAP31 was found to promote PINK1 phosphorylation and PINK1/Parkin-mediated mitophagy, linking BAP31's MAM-tethering function to mitochondrial quality control beyond the previously known apoptotic pathway.\",\n      \"evidence\": \"BAP31 transgenic and conditional KO mice; Co-IP of BAP31–PINK1; mitophagy flux and ROS assays; LPS-ALI model\",\n      \"pmids\": [\"39381793\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether BAP31 stabilizes PINK1 directly or facilitates its import/retention on the OMM is unresolved\", \"Single lab; awaits independent confirmation\", \"Relationship to the Tom40 bridge unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How BAP31 discriminates between cargo destined for ER retention, forward transport, or ERAD remains structurally and mechanistically undefined; the atomic basis of its interactions with procaspase-8 (given the non-DED coiled-coil fold) and with Tom40/Fis1 at MAMs has not been determined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No full-length BAP31 structure available\", \"Sorting code within cargo transmembrane domains not systematically defined\", \"Coiled-coil–procaspase-8 binding mechanism unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0038024\", \"supporting_discovery_ids\": [1, 7, 12, 13, 14, 15, 17]},\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [10, 13, 25, 26]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 3, 5, 8, 20, 28]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 1, 7, 13, 15, 16, 36]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [22, 33]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [0, 3, 5, 9, 18, 20]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1, 7, 12, 14, 15, 16, 17]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [10, 15, 16]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [18, 27]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [28, 35]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [14, 17, 24, 29]}\n    ],\n    \"complexes\": [\n      \"BAP31–Bcl-2/Bcl-XL–procaspase-8 ER complex\",\n      \"Fis1–BAP31 ARCosome\",\n      \"BAP31–Tom40 MAM bridge\",\n      \"BAP29/BAP31 heteromeric quality-control complex\"\n    ],\n    \"partners\": [\n      \"FIS1\",\n      \"TOMM40\",\n      \"BCL2\",\n      \"CASP8\",\n      \"DERL1\",\n      \"STX17\",\n      \"CDIP1\",\n      \"BAP29\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}