{"gene":"DAD1","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":1993,"finding":"DAD1 encodes a novel hydrophobic (integral membrane) protein whose loss triggers apoptosis; a point mutation in DAD1 is responsible for the temperature-sensitive apoptotic phenotype of tsBN7 hamster cells, and disappearance of the DAD1 protein at non-permissive temperature precedes cell death.","method":"DNA-mediated gene transfer complementation cloning; sequence comparison of parental and mutant cDNAs; Western blot showing protein disappearance","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — functional complementation cloning with mutation identification, replicated in subsequent studies","pmids":["8413235"],"is_preprint":false},{"year":1995,"finding":"The yeast OST2 gene (DAD1 ortholog) encodes the ε-subunit of the oligosaccharyltransferase (OST); OST2 is essential for viability, and ost2 mutants show pleiotropic underglycosylation of soluble and membrane-bound glycoproteins and reduced in vitro OST activity. Overexpression of Ost2p suppresses the temperature-sensitive wbp1-2 allele and increases OST activity.","method":"Genomic disruption (lethal in haploid yeast); conditional ost2 mutant analysis; in vitro OST activity assay with lipid-linked oligosaccharide substrate; sequence analysis linking Ost2p to DAD1","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic assay, genetic epistasis, loss-of-function lethality, multiple orthogonal methods in one rigorous study","pmids":["7593165"],"is_preprint":false},{"year":1995,"finding":"C. elegans Ce-dad-1 and human dad-1, when overexpressed under a heat-shock promoter in C. elegans, reduce the number of programmed cell death corpses in embryos, demonstrating that DAD1 is sufficient to suppress developmentally programmed cell death. Ce-dad-1 also rescues tsBN7 hamster cells from apoptosis.","method":"Transgenic C. elegans expressing human or Ce-dad-1 under inducible promoter; cell death corpse counting; cross-species rescue of tsBN7 cells","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — functional rescue across species, multiple orthogonal readouts (corpse counting and mammalian cell rescue)","pmids":["7556086"],"is_preprint":false},{"year":1997,"finding":"DAD1 is a tightly associated subunit of the mammalian oligosaccharyltransferase (OST) complex, present in roughly equimolar amounts with ribophorin I, ribophorin II, and OST48 in the purified enzyme. DAD1 cosediments with OST activity and can be crosslinked to OST48 in intact microsomes; higher-order crosslinked heterotrimers and heterotetramers (DAD1–ribophorin II–OST48; DAD1–ribophorin I–ribophorin II–OST48) are detected.","method":"Sedimentation velocity analysis; radioiodination of purified OST; chemical crosslinking (dithiobis(succinimidylpropionate)) in intact microsomes","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — purified enzyme analysis, equimolar stoichiometry, chemical crosslinking, multiple orthogonal biochemical methods","pmids":["9144178"],"is_preprint":false},{"year":1997,"finding":"DAD1 is an integral ER membrane protein with both N- and C-termini located in the cytosol (middle portions embedded in membrane, as shown by proteinase K protection). Loss of DAD1 function at non-permissive temperature causes a defect in N-linked glycosylation in tsBN7 cells, leading to apoptosis.","method":"Differential centrifugation; carbonate extraction; proteinase K digestion topology mapping; Western blot glycosylation analysis","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — direct topology mapping with proteinase K, membrane fractionation, functional glycosylation assay, single lab with multiple orthogonal methods","pmids":["9167970"],"is_preprint":false},{"year":1998,"finding":"Loss of DAD1 (in tsBN7 cells at non-permissive temperature) destabilizes the entire OST complex: steady-state levels of OST48 become nearly undetectable and ribophorins are reduced ~50%, while other ER translocon components (TRAP α-subunit, Sec61) are unaffected. N-glycosylation of the ribophorins and a secretory glycoprotein is severely impaired, demonstrating that DAD1 is required for both structural integrity and enzymatic function of the OST complex.","method":"Western blot of cell lysates at permissive/non-permissive temperatures; pulse-chase glycosylation assay of secretory glycoprotein","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean temperature-sensitive KO system, multiple substrate readouts, comparison to unaffected controls; single lab","pmids":["9748289"],"is_preprint":false},{"year":2000,"finding":"DAD1 interacts with Mcl-1 (a Bcl-2 family member) via a two-hybrid screen and co-immunoprecipitation in COS cells. The C-terminal domain of Mcl-1 containing the BH2 domain is required for interaction with DAD1, and the C-terminal half of DAD1 mediates binding. A ΔC-DAD1 mutant lacking 4 C-terminal residues fails to complement the tsBN7 mutation (cannot restore N-linked glycosylation) but retains Mcl-1 binding, indicating the DAD1 C-terminus is specifically required for OST function.","method":"Yeast two-hybrid screen; co-immunoprecipitation in COS cells; deletion mutagenesis; tsBN7 complementation assay","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Y2H plus co-IP in overexpression system; deletion analysis separating OST function from Mcl-1 binding; single lab","pmids":["10965038"],"is_preprint":false},{"year":2000,"finding":"Homozygous Dad1-null mouse embryos express abnormal N-glycosylated proteins and undergo increased apoptosis in specific tissues, are developmentally delayed by E7.5, exhibit impaired mesodermal development, fail to turn the posterior axis, and die by E10.5. This establishes that Dad1 is required in vivo for proper N-linked glycoprotein processing and for cell survival during mouse embryogenesis.","method":"Gene targeting (null allele); Western blot for N-glycoproteins; histological and TUNEL analysis of embryos","journal":"Developmental biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — independently generated null mice with biochemical (glycoprotein) and cellular (apoptosis) phenotypic readouts; replicated by two separate knockout studies","pmids":["10720432","10748466","10336695"],"is_preprint":false},{"year":2002,"finding":"GFP-Dad1, when functionally incorporated into translocon complexes (TCs) in the ER, diffuses extremely slowly (Deff ~7-fold lower than free ER membrane proteins), as measured by FRAP, reflecting its assembly into large membrane-bound polysome arrays. Termination of protein synthesis increases GFP-Dad1 lateral mobility but not to the level of free protein, indicating DAD1/OST remains associated with inactive TCs after ribosome release.","method":"FRAP of GFP-Dad1 in live cells (tsBN7 rescue system); comparison to free ER membrane proteins; protein synthesis inhibition experiments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct live-cell FRAP with functional validation (GFP-Dad1 rescues ts phenotype), mechanistic inhibition experiments; single lab","pmids":["12163472"],"is_preprint":false},{"year":2012,"finding":"Knockdown of DAD1 (or OST48) disrupts the assembly of both STT3A- and STT3B-containing OST complexes, causing pronounced hypoglycosylation of multiple substrates. Thus DAD1 is a global structural modulator required for the integrity and activity of both mammalian OST complexes.","method":"Subunit-specific siRNA knockdowns; analysis of OST complex assembly and enzymatic activity; glycosylation profiling","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean siRNA knockdown with OST complex assembly and activity readouts, two distinct OST complexes tested; single lab with multiple orthogonal methods","pmids":["22467853"],"is_preprint":false},{"year":2024,"finding":"DAD1 knockdown in neonatal rat cardiomyocytes impairs N-glycosylation of integrins α5 and β1, reduces focal adhesion kinase activation, impairs cell spreading and myofibrillogenesis, and induces anoikis (apoptosis from disrupted cell-matrix interaction). Enhancing cell adhesion (with adhesamine, fibronectin, or collagen IV) rescues cardiomyocyte death caused by Dad1 knockdown. Additionally, Dad1 and Stt3A (catalytic OST subunit) mutually stabilize each other's expression.","method":"siRNA knockdown in neonatal rat cardiomyocytes; caspase-3 cleavage assay; N-glycosylation assay of integrins; focal adhesion kinase activation assay; rescue with adhesion-promoting agents; cross-knockdown of Stt3A","journal":"American journal of physiology. Cell physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA KD with multiple orthogonal readouts (glycosylation, FAK signaling, morphology, rescue), single lab","pmids":["39611549"],"is_preprint":false},{"year":2006,"finding":"In S. cerevisiae, the Gly58Arg mutation in Ost2p (corresponding to the apoptosis-causing Gly38Arg in hamster DAD1) causes temperature-sensitive growth arrest with decreased cell viability and phosphatidylserine exposure (apoptosis marker) at 37°C, without clear DNA fragmentation. High sorbitol rescues the temperature sensitivity, suggesting that ost2 mutant cell death is a secondary consequence of reduced protein N-linked glycosylation rather than a direct pro-apoptotic function.","method":"Site-directed mutagenesis (Gly58Arg, Gly86Arg, Glu113Val Ost2 alleles); growth and viability assays; phosphatidylserine exposure assay; DNA fragmentation assay; osmotic suppression with sorbitol","journal":"Bioscience, biotechnology, and biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — active-site equivalent mutagenesis with multiple phenotypic readouts and osmotic suppression; single lab","pmids":["16717427"],"is_preprint":false}],"current_model":"DAD1 (also known as OST2) is an essential integral ER membrane protein that functions as a non-catalytic structural subunit of the oligosaccharyltransferase (OST) complex, required for the assembly and stability of both STT3A- and STT3B-containing OST complexes and for efficient N-linked glycosylation of nascent polypeptides; loss of DAD1 destabilizes the entire OST complex (including OST48 and the ribophorins), causes global hypoglycosylation, impairs N-glycosylation of cell-adhesion molecules such as integrins, disrupts cell-matrix signaling, and ultimately triggers anoikis/apoptosis, while in intact ER membranes DAD1-containing OST complexes are tethered within slowly diffusing ribosome-translocon arrays."},"narrative":{"mechanistic_narrative":"DAD1 is an essential integral ER membrane protein that functions as a non-catalytic subunit of the oligosaccharyltransferase (OST) complex and is required for efficient N-linked glycosylation of nascent polypeptides [PMID:7593165, PMID:9144178, PMID:9167970]. Identified through complementation cloning as the gene whose loss triggers apoptosis in temperature-sensitive tsBN7 hamster cells [PMID:8413235], it is the mammalian ortholog of the yeast OST ε-subunit Ost2p, which is essential for viability and OST activity [PMID:7593165]. In purified mammalian OST, DAD1 is present in roughly equimolar amounts with OST48 and the ribophorins and can be chemically crosslinked into OST48-containing heteromers, defining it as a tightly associated structural subunit [PMID:9144178]; topologically it spans the ER membrane with both termini in the cytosol [PMID:9167970]. DAD1 is required for the structural integrity and enzymatic function of the complex: its loss destabilizes the entire OST (rendering OST48 nearly undetectable and reducing ribophorins) and disrupts assembly of both STT3A- and STT3B-containing complexes, producing global hypoglycosylation [PMID:9748289, PMID:22467853]. Consequent failure to glycosylate substrates is the proximate cause of death—loss of DAD1 in vivo causes abnormal N-glycoproteins, increased tissue apoptosis, and embryonic lethality in mice [PMID:10720432, PMID:10748466, PMID:10336695], and in cardiomyocytes impairs N-glycosylation of integrins α5/β1, reduces focal adhesion kinase signaling, and induces anoikis that is rescued by restoring cell adhesion [PMID:39611549]. Within intact ER membranes, functionally incorporated DAD1 diffuses very slowly, reflecting assembly into large ribosome-translocon polysome arrays from which it does not fully dissociate after translation terminates [PMID:12163472].","teleology":[{"year":1993,"claim":"Established DAD1 as a gene whose loss causes apoptosis, framing a novel suppressor of cell death and identifying the causative point mutation in tsBN7 cells.","evidence":"DNA-mediated complementation cloning, cDNA sequencing, and Western blot in tsBN7 hamster cells","pmids":["8413235"],"confidence":"High","gaps":["Molecular function of the protein not defined","Mechanism linking protein loss to apoptosis unknown"]},{"year":1995,"claim":"Assigned DAD1 a biochemical function by showing its yeast ortholog Ost2p is the essential ε-subunit of oligosaccharyltransferase, reframing the apoptosis phenotype as a glycosylation defect.","evidence":"Genomic disruption (lethality), conditional ost2 mutants, in vitro OST activity assays, and genetic suppression of wbp1-2 in S. cerevisiae","pmids":["7593165"],"confidence":"High","gaps":["Direct demonstration of mammalian DAD1 in the OST complex not yet shown","Catalytic vs structural role unresolved"]},{"year":1995,"claim":"Demonstrated that DAD1 expression is sufficient to suppress programmed cell death and that function is conserved across species.","evidence":"Inducible overexpression of human and Ce-dad-1 in transgenic C. elegans with corpse counting and cross-species rescue of tsBN7 cells","pmids":["7556086"],"confidence":"High","gaps":["Whether suppression reflects glycosylation function rather than a direct anti-apoptotic activity not distinguished"]},{"year":1997,"claim":"Confirmed mammalian DAD1 as a tightly associated, equimolar subunit of purified OST and mapped its membrane topology.","evidence":"Sedimentation velocity, radioiodination, chemical crosslinking in microsomes, and proteinase K protection topology mapping","pmids":["9144178","9167970"],"confidence":"High","gaps":["Precise interaction interfaces within the complex not resolved","No high-resolution structure"]},{"year":1998,"claim":"Showed DAD1 is required for both structural integrity and enzymatic activity of the OST complex, not merely an accessory factor.","evidence":"Western blot of OST subunits and pulse-chase glycosylation in tsBN7 cells at permissive/non-permissive temperatures","pmids":["9748289"],"confidence":"High","gaps":["Mechanism by which DAD1 stabilizes OST48/ribophorins not defined at molecular level"]},{"year":2000,"claim":"Tested whether DAD1 has a direct anti-apoptotic role via Bcl-2 family interaction, and dissociated OST function from Mcl-1 binding.","evidence":"Yeast two-hybrid, co-IP in COS cells, deletion mutagenesis, and tsBN7 complementation","pmids":["10965038"],"confidence":"Medium","gaps":["Co-IP performed in overexpression system without reciprocal endogenous validation","Physiological significance of Mcl-1 interaction unestablished"]},{"year":2000,"claim":"Established the in vivo requirement of Dad1 for N-glycoprotein processing and cell survival during mammalian development.","evidence":"Targeted null mice analyzed by Western blot for N-glycoproteins, histology, and TUNEL","pmids":["10720432","10748466","10336695"],"confidence":"High","gaps":["Tissue-specific apoptosis sensitivity not mechanistically explained","Specific glycoprotein substrates driving lethality not identified"]},{"year":2002,"claim":"Revealed the supramolecular context of DAD1, showing functional OST is tethered within slowly diffusing ribosome-translocon arrays.","evidence":"FRAP of functional GFP-Dad1 in live cells with protein synthesis inhibition","pmids":["12163472"],"confidence":"High","gaps":["Molecular basis of OST retention in inactive translocons unknown"]},{"year":2006,"claim":"Tested whether the apoptosis-causing mutation reflects a direct pro-apoptotic function, concluding death is secondary to glycosylation loss.","evidence":"Site-directed Ost2 mutagenesis, viability and phosphatidylserine assays, and osmotic suppression with sorbitol in S. cerevisiae","pmids":["16717427"],"confidence":"Medium","gaps":["Single-organism (yeast) inference about mammalian apoptosis mechanism","Lack of DNA fragmentation leaves death pathway incompletely defined"]},{"year":2012,"claim":"Generalized DAD1's structural role to both mammalian OST isoforms, defining it as required for STT3A- and STT3B-containing complex integrity.","evidence":"Subunit-specific siRNA knockdowns with OST assembly, activity, and glycosylation profiling","pmids":["22467853"],"confidence":"High","gaps":["Whether DAD1 contributes differentially to co- vs post-translational glycosylation not resolved"]},{"year":2024,"claim":"Connected DAD1 loss to a specific physiological pathway, showing hypoglycosylation of integrins disrupts adhesion signaling and triggers anoikis.","evidence":"siRNA knockdown in neonatal rat cardiomyocytes with integrin glycosylation, FAK activation, morphology, adhesion-rescue, and Stt3A cross-knockdown assays","pmids":["39611549"],"confidence":"Medium","gaps":["Single cell-type and single lab","Whether integrin hypoglycosylation is the dominant death trigger in other tissues unknown"]},{"year":null,"claim":"How DAD1 mechanistically stabilizes the OST complex and is retained in translocon arrays, and the full substrate spectrum whose hypoglycosylation drives apoptosis, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of DAD1 within human OST in the corpus","Substrates linking hypoglycosylation to tissue-specific apoptosis incompletely defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[1,3,5,9]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[3,5,9]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[4,8]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1,3,5,9]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[0,7,10]}],"complexes":["oligosaccharyltransferase (OST) complex"],"partners":["OST48","RPN1","RPN2","STT3A","MCL1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P61803","full_name":"Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1","aliases":["Defender against cell death 1","DAD-1"],"length_aa":113,"mass_kda":12.5,"function":"Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (PubMed:22467853, PubMed:31831667). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity (By similarity). Required for the assembly of both SST3A- and SS3B-containing OST complexes. Loss of the DAD1 protein triggers apoptosis (PubMed:22467853)","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/P61803/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DAD1","classification":"Common Essential","n_dependent_lines":1206,"n_total_lines":1208,"dependency_fraction":0.9983443708609272},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000129562","cell_line_id":"CID000186","localizations":[{"compartment":"er","grade":3}],"interactors":[{"gene":"KRTCAP2","stoichiometry":10.0},{"gene":"C4ORF32","stoichiometry":10.0},{"gene":"STT3B","stoichiometry":10.0},{"gene":"MLEC","stoichiometry":10.0},{"gene":"FKBP8","stoichiometry":10.0},{"gene":"DDOST","stoichiometry":10.0},{"gene":"MAGT1","stoichiometry":10.0},{"gene":"CANX","stoichiometry":10.0},{"gene":"TIA1","stoichiometry":10.0},{"gene":"POR","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000186","total_profiled":1310},"omim":[{"mim_id":"609860","title":"DAD1-RELATED GENE","url":"https://www.omim.org/entry/609860"},{"mim_id":"600243","title":"DEFENDER AGAINST CELL DEATH 1; DAD1","url":"https://www.omim.org/entry/600243"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Cytosol","reliability":"Uncertain"},{"location":"Endoplasmic reticulum","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DAD1"},"hgnc":{"alias_symbol":["OST2"],"prev_symbol":[]},"alphafold":{"accession":"P61803","domains":[{"cath_id":"-","chopping":"21-109","consensus_level":"high","plddt":96.4755,"start":21,"end":109}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P61803","model_url":"https://alphafold.ebi.ac.uk/files/AF-P61803-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P61803-F1-predicted_aligned_error_v6.png","plddt_mean":95.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DAD1","jax_strain_url":"https://www.jax.org/strain/search?query=DAD1"},"sequence":{"accession":"P61803","fasta_url":"https://rest.uniprot.org/uniprotkb/P61803.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P61803/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P61803"}},"corpus_meta":[{"pmid":"17655651","id":"PMC_17655651","title":"DWARF10, an RMS1/MAX4/DAD1 ortholog, controls lateral bud outgrowth in rice.","date":"2007","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17655651","citation_count":393,"is_preprint":false},{"pmid":"8413235","id":"PMC_8413235","title":"Molecular cloning of a human cDNA encoding a novel protein, DAD1, whose defect causes apoptotic cell death in hamster BHK21 cells.","date":"1993","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8413235","citation_count":188,"is_preprint":false},{"pmid":"9144178","id":"PMC_9144178","title":"DAD1, the defender against apoptotic cell death, is a subunit of the mammalian oligosaccharyltransferase.","date":"1997","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/9144178","citation_count":143,"is_preprint":false},{"pmid":"12226274","id":"PMC_12226274","title":"Highly Branched Phenotype of the Petunia dad1-1 Mutant Is Reversed by Grafting.","date":"1996","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/12226274","citation_count":122,"is_preprint":false},{"pmid":"7593165","id":"PMC_7593165","title":"The essential OST2 gene encodes the 16-kD subunit of the yeast oligosaccharyltransferase, a highly conserved protein expressed in diverse eukaryotic organisms.","date":"1995","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/7593165","citation_count":103,"is_preprint":false},{"pmid":"7556086","id":"PMC_7556086","title":"dad-1, an endogenous programmed cell death suppressor in Caenorhabditis elegans and vertebrates.","date":"1995","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/7556086","citation_count":90,"is_preprint":false},{"pmid":"22467853","id":"PMC_22467853","title":"The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 function as ubiquitous and selective modulators of mammalian N-glycosylation.","date":"2012","source":"Journal of cell 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2000)","url":"https://pubmed.ncbi.nlm.nih.gov/10748466","citation_count":38,"is_preprint":false},{"pmid":"9150612","id":"PMC_9150612","title":"dad-1, A putative programmed cell death suppressor gene in rice.","date":"1997","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/9150612","citation_count":38,"is_preprint":false},{"pmid":"15082712","id":"PMC_15082712","title":"Both CTCF-dependent and -independent insulators are found between the mouse T cell receptor alpha and Dad1 genes.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15082712","citation_count":37,"is_preprint":false},{"pmid":"9121464","id":"PMC_9121464","title":"A targeted mutation at the T-cell receptor alpha/delta locus impairs T-cell development and reveals the presence of the nearby antiapoptosis gene Dad1.","date":"1997","source":"Molecular and cellular 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1950)","url":"https://pubmed.ncbi.nlm.nih.gov/10438923","citation_count":18,"is_preprint":false},{"pmid":"34671425","id":"PMC_34671425","title":"Emerging role of BAD and DAD1 as potential targets and biomarkers in cancer.","date":"2021","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/34671425","citation_count":17,"is_preprint":false},{"pmid":"15602820","id":"PMC_15602820","title":"A homolog of the defender against apoptotic death gene (DAD1) in senescing gladiolus petals is down-regulated prior to the onset of programmed cell death.","date":"2004","source":"Journal of plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/15602820","citation_count":17,"is_preprint":false},{"pmid":"12781979","id":"PMC_12781979","title":"cDNA cloning of a defender against apoptotic cell death 1 (DAD1) homologue, responsive to external temperature stimulus from the spider, Araneus ventricosus.","date":"2003","source":"Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12781979","citation_count":16,"is_preprint":false},{"pmid":"18083552","id":"PMC_18083552","title":"Down-regulation of defender against apoptotic death (DAD1) after yellow head virus (YHV) challenge in black tiger shrimp Penaeus monodon.","date":"2007","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18083552","citation_count":15,"is_preprint":false},{"pmid":"11564801","id":"PMC_11564801","title":"Function and factor interactions of a locus control region element in the mouse T cell receptor-alpha/Dad1 gene locus.","date":"2001","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/11564801","citation_count":13,"is_preprint":false},{"pmid":"30800138","id":"PMC_30800138","title":"GmDAD1, a Conserved Defender Against Cell Death 1 (DAD1) From Soybean, Positively Regulates Plant Resistance Against Phytophthora Pathogens.","date":"2019","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/30800138","citation_count":13,"is_preprint":false},{"pmid":"38164146","id":"PMC_38164146","title":"Targeting DAD1 gene with CRISPR-Cas9 system transmucosally delivered by fluorinated polylysine nanoparticles for bladder cancer intravesical gene therapy.","date":"2024","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/38164146","citation_count":12,"is_preprint":false},{"pmid":"30032071","id":"PMC_30032071","title":"Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population.","date":"2018","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30032071","citation_count":11,"is_preprint":false},{"pmid":"17294251","id":"PMC_17294251","title":"Molecular cloning and responsive expression to injury stimulus of a defender against cell death 1 (DAD1) gene from bay scallops Argopecten irradians.","date":"2007","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/17294251","citation_count":11,"is_preprint":false},{"pmid":"16717427","id":"PMC_16717427","title":"Yeast cell death caused by mutation of the OST2 gene encoding the epsilon-subunit of Saccharomyces cerevisiae oligosaccharyltransferase.","date":"2006","source":"Bioscience, biotechnology, and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16717427","citation_count":7,"is_preprint":false},{"pmid":"10786637","id":"PMC_10786637","title":"Molecular cloning of a homologue of dad-1 gene in citrus: distinctive expression during fruit development.","date":"2000","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/10786637","citation_count":5,"is_preprint":false},{"pmid":"39611549","id":"PMC_39611549","title":"Suppression of Dad1 induces cardiomyocyte death by weakening cell adhesion.","date":"2024","source":"American journal of physiology. 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Overexpression of Ost2p suppresses the temperature-sensitive wbp1-2 allele and increases OST activity.\",\n      \"method\": \"Genomic disruption (lethal in haploid yeast); conditional ost2 mutant analysis; in vitro OST activity assay with lipid-linked oligosaccharide substrate; sequence analysis linking Ost2p to DAD1\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic assay, genetic epistasis, loss-of-function lethality, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"7593165\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"C. elegans Ce-dad-1 and human dad-1, when overexpressed under a heat-shock promoter in C. elegans, reduce the number of programmed cell death corpses in embryos, demonstrating that DAD1 is sufficient to suppress developmentally programmed cell death. Ce-dad-1 also rescues tsBN7 hamster cells from apoptosis.\",\n      \"method\": \"Transgenic C. elegans expressing human or Ce-dad-1 under inducible promoter; cell death corpse counting; cross-species rescue of tsBN7 cells\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — functional rescue across species, multiple orthogonal readouts (corpse counting and mammalian cell rescue)\",\n      \"pmids\": [\"7556086\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"DAD1 is a tightly associated subunit of the mammalian oligosaccharyltransferase (OST) complex, present in roughly equimolar amounts with ribophorin I, ribophorin II, and OST48 in the purified enzyme. DAD1 cosediments with OST activity and can be crosslinked to OST48 in intact microsomes; higher-order crosslinked heterotrimers and heterotetramers (DAD1–ribophorin II–OST48; DAD1–ribophorin I–ribophorin II–OST48) are detected.\",\n      \"method\": \"Sedimentation velocity analysis; radioiodination of purified OST; chemical crosslinking (dithiobis(succinimidylpropionate)) in intact microsomes\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — purified enzyme analysis, equimolar stoichiometry, chemical crosslinking, multiple orthogonal biochemical methods\",\n      \"pmids\": [\"9144178\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"DAD1 is an integral ER membrane protein with both N- and C-termini located in the cytosol (middle portions embedded in membrane, as shown by proteinase K protection). Loss of DAD1 function at non-permissive temperature causes a defect in N-linked glycosylation in tsBN7 cells, leading to apoptosis.\",\n      \"method\": \"Differential centrifugation; carbonate extraction; proteinase K digestion topology mapping; Western blot glycosylation analysis\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — direct topology mapping with proteinase K, membrane fractionation, functional glycosylation assay, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"9167970\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Loss of DAD1 (in tsBN7 cells at non-permissive temperature) destabilizes the entire OST complex: steady-state levels of OST48 become nearly undetectable and ribophorins are reduced ~50%, while other ER translocon components (TRAP α-subunit, Sec61) are unaffected. N-glycosylation of the ribophorins and a secretory glycoprotein is severely impaired, demonstrating that DAD1 is required for both structural integrity and enzymatic function of the OST complex.\",\n      \"method\": \"Western blot of cell lysates at permissive/non-permissive temperatures; pulse-chase glycosylation assay of secretory glycoprotein\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean temperature-sensitive KO system, multiple substrate readouts, comparison to unaffected controls; single lab\",\n      \"pmids\": [\"9748289\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"DAD1 interacts with Mcl-1 (a Bcl-2 family member) via a two-hybrid screen and co-immunoprecipitation in COS cells. The C-terminal domain of Mcl-1 containing the BH2 domain is required for interaction with DAD1, and the C-terminal half of DAD1 mediates binding. A ΔC-DAD1 mutant lacking 4 C-terminal residues fails to complement the tsBN7 mutation (cannot restore N-linked glycosylation) but retains Mcl-1 binding, indicating the DAD1 C-terminus is specifically required for OST function.\",\n      \"method\": \"Yeast two-hybrid screen; co-immunoprecipitation in COS cells; deletion mutagenesis; tsBN7 complementation assay\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Y2H plus co-IP in overexpression system; deletion analysis separating OST function from Mcl-1 binding; single lab\",\n      \"pmids\": [\"10965038\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Homozygous Dad1-null mouse embryos express abnormal N-glycosylated proteins and undergo increased apoptosis in specific tissues, are developmentally delayed by E7.5, exhibit impaired mesodermal development, fail to turn the posterior axis, and die by E10.5. This establishes that Dad1 is required in vivo for proper N-linked glycoprotein processing and for cell survival during mouse embryogenesis.\",\n      \"method\": \"Gene targeting (null allele); Western blot for N-glycoproteins; histological and TUNEL analysis of embryos\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — independently generated null mice with biochemical (glycoprotein) and cellular (apoptosis) phenotypic readouts; replicated by two separate knockout studies\",\n      \"pmids\": [\"10720432\", \"10748466\", \"10336695\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"GFP-Dad1, when functionally incorporated into translocon complexes (TCs) in the ER, diffuses extremely slowly (Deff ~7-fold lower than free ER membrane proteins), as measured by FRAP, reflecting its assembly into large membrane-bound polysome arrays. Termination of protein synthesis increases GFP-Dad1 lateral mobility but not to the level of free protein, indicating DAD1/OST remains associated with inactive TCs after ribosome release.\",\n      \"method\": \"FRAP of GFP-Dad1 in live cells (tsBN7 rescue system); comparison to free ER membrane proteins; protein synthesis inhibition experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct live-cell FRAP with functional validation (GFP-Dad1 rescues ts phenotype), mechanistic inhibition experiments; single lab\",\n      \"pmids\": [\"12163472\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Knockdown of DAD1 (or OST48) disrupts the assembly of both STT3A- and STT3B-containing OST complexes, causing pronounced hypoglycosylation of multiple substrates. Thus DAD1 is a global structural modulator required for the integrity and activity of both mammalian OST complexes.\",\n      \"method\": \"Subunit-specific siRNA knockdowns; analysis of OST complex assembly and enzymatic activity; glycosylation profiling\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean siRNA knockdown with OST complex assembly and activity readouts, two distinct OST complexes tested; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"22467853\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DAD1 knockdown in neonatal rat cardiomyocytes impairs N-glycosylation of integrins α5 and β1, reduces focal adhesion kinase activation, impairs cell spreading and myofibrillogenesis, and induces anoikis (apoptosis from disrupted cell-matrix interaction). Enhancing cell adhesion (with adhesamine, fibronectin, or collagen IV) rescues cardiomyocyte death caused by Dad1 knockdown. Additionally, Dad1 and Stt3A (catalytic OST subunit) mutually stabilize each other's expression.\",\n      \"method\": \"siRNA knockdown in neonatal rat cardiomyocytes; caspase-3 cleavage assay; N-glycosylation assay of integrins; focal adhesion kinase activation assay; rescue with adhesion-promoting agents; cross-knockdown of Stt3A\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA KD with multiple orthogonal readouts (glycosylation, FAK signaling, morphology, rescue), single lab\",\n      \"pmids\": [\"39611549\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"In S. cerevisiae, the Gly58Arg mutation in Ost2p (corresponding to the apoptosis-causing Gly38Arg in hamster DAD1) causes temperature-sensitive growth arrest with decreased cell viability and phosphatidylserine exposure (apoptosis marker) at 37°C, without clear DNA fragmentation. High sorbitol rescues the temperature sensitivity, suggesting that ost2 mutant cell death is a secondary consequence of reduced protein N-linked glycosylation rather than a direct pro-apoptotic function.\",\n      \"method\": \"Site-directed mutagenesis (Gly58Arg, Gly86Arg, Glu113Val Ost2 alleles); growth and viability assays; phosphatidylserine exposure assay; DNA fragmentation assay; osmotic suppression with sorbitol\",\n      \"journal\": \"Bioscience, biotechnology, and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — active-site equivalent mutagenesis with multiple phenotypic readouts and osmotic suppression; single lab\",\n      \"pmids\": [\"16717427\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DAD1 (also known as OST2) is an essential integral ER membrane protein that functions as a non-catalytic structural subunit of the oligosaccharyltransferase (OST) complex, required for the assembly and stability of both STT3A- and STT3B-containing OST complexes and for efficient N-linked glycosylation of nascent polypeptides; loss of DAD1 destabilizes the entire OST complex (including OST48 and the ribophorins), causes global hypoglycosylation, impairs N-glycosylation of cell-adhesion molecules such as integrins, disrupts cell-matrix signaling, and ultimately triggers anoikis/apoptosis, while in intact ER membranes DAD1-containing OST complexes are tethered within slowly diffusing ribosome-translocon arrays.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DAD1 is an essential integral ER membrane protein that functions as a non-catalytic subunit of the oligosaccharyltransferase (OST) complex and is required for efficient N-linked glycosylation of nascent polypeptides [#1, #3, #4]. Identified through complementation cloning as the gene whose loss triggers apoptosis in temperature-sensitive tsBN7 hamster cells [#0], it is the mammalian ortholog of the yeast OST \\u03b5-subunit Ost2p, which is essential for viability and OST activity [#1]. In purified mammalian OST, DAD1 is present in roughly equimolar amounts with OST48 and the ribophorins and can be chemically crosslinked into OST48-containing heteromers, defining it as a tightly associated structural subunit [#3]; topologically it spans the ER membrane with both termini in the cytosol [#4]. DAD1 is required for the structural integrity and enzymatic function of the complex: its loss destabilizes the entire OST (rendering OST48 nearly undetectable and reducing ribophorins) and disrupts assembly of both STT3A- and STT3B-containing complexes, producing global hypoglycosylation [#5, #9]. Consequent failure to glycosylate substrates is the proximate cause of death\\u2014loss of DAD1 in vivo causes abnormal N-glycoproteins, increased tissue apoptosis, and embryonic lethality in mice [#7], and in cardiomyocytes impairs N-glycosylation of integrins \\u03b15/\\u03b21, reduces focal adhesion kinase signaling, and induces anoikis that is rescued by restoring cell adhesion [#10]. Within intact ER membranes, functionally incorporated DAD1 diffuses very slowly, reflecting assembly into large ribosome-translocon polysome arrays from which it does not fully dissociate after translation terminates [#8].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Established DAD1 as a gene whose loss causes apoptosis, framing a novel suppressor of cell death and identifying the causative point mutation in tsBN7 cells.\",\n      \"evidence\": \"DNA-mediated complementation cloning, cDNA sequencing, and Western blot in tsBN7 hamster cells\",\n      \"pmids\": [\"8413235\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular function of the protein not defined\", \"Mechanism linking protein loss to apoptosis unknown\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Assigned DAD1 a biochemical function by showing its yeast ortholog Ost2p is the essential \\u03b5-subunit of oligosaccharyltransferase, reframing the apoptosis phenotype as a glycosylation defect.\",\n      \"evidence\": \"Genomic disruption (lethality), conditional ost2 mutants, in vitro OST activity assays, and genetic suppression of wbp1-2 in S. cerevisiae\",\n      \"pmids\": [\"7593165\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct demonstration of mammalian DAD1 in the OST complex not yet shown\", \"Catalytic vs structural role unresolved\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Demonstrated that DAD1 expression is sufficient to suppress programmed cell death and that function is conserved across species.\",\n      \"evidence\": \"Inducible overexpression of human and Ce-dad-1 in transgenic C. elegans with corpse counting and cross-species rescue of tsBN7 cells\",\n      \"pmids\": [\"7556086\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether suppression reflects glycosylation function rather than a direct anti-apoptotic activity not distinguished\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Confirmed mammalian DAD1 as a tightly associated, equimolar subunit of purified OST and mapped its membrane topology.\",\n      \"evidence\": \"Sedimentation velocity, radioiodination, chemical crosslinking in microsomes, and proteinase K protection topology mapping\",\n      \"pmids\": [\"9144178\", \"9167970\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise interaction interfaces within the complex not resolved\", \"No high-resolution structure\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Showed DAD1 is required for both structural integrity and enzymatic activity of the OST complex, not merely an accessory factor.\",\n      \"evidence\": \"Western blot of OST subunits and pulse-chase glycosylation in tsBN7 cells at permissive/non-permissive temperatures\",\n      \"pmids\": [\"9748289\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which DAD1 stabilizes OST48/ribophorins not defined at molecular level\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Tested whether DAD1 has a direct anti-apoptotic role via Bcl-2 family interaction, and dissociated OST function from Mcl-1 binding.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP in COS cells, deletion mutagenesis, and tsBN7 complementation\",\n      \"pmids\": [\"10965038\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-IP performed in overexpression system without reciprocal endogenous validation\", \"Physiological significance of Mcl-1 interaction unestablished\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Established the in vivo requirement of Dad1 for N-glycoprotein processing and cell survival during mammalian development.\",\n      \"evidence\": \"Targeted null mice analyzed by Western blot for N-glycoproteins, histology, and TUNEL\",\n      \"pmids\": [\"10720432\", \"10748466\", \"10336695\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue-specific apoptosis sensitivity not mechanistically explained\", \"Specific glycoprotein substrates driving lethality not identified\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Revealed the supramolecular context of DAD1, showing functional OST is tethered within slowly diffusing ribosome-translocon arrays.\",\n      \"evidence\": \"FRAP of functional GFP-Dad1 in live cells with protein synthesis inhibition\",\n      \"pmids\": [\"12163472\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of OST retention in inactive translocons unknown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Tested whether the apoptosis-causing mutation reflects a direct pro-apoptotic function, concluding death is secondary to glycosylation loss.\",\n      \"evidence\": \"Site-directed Ost2 mutagenesis, viability and phosphatidylserine assays, and osmotic suppression with sorbitol in S. cerevisiae\",\n      \"pmids\": [\"16717427\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-organism (yeast) inference about mammalian apoptosis mechanism\", \"Lack of DNA fragmentation leaves death pathway incompletely defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Generalized DAD1's structural role to both mammalian OST isoforms, defining it as required for STT3A- and STT3B-containing complex integrity.\",\n      \"evidence\": \"Subunit-specific siRNA knockdowns with OST assembly, activity, and glycosylation profiling\",\n      \"pmids\": [\"22467853\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether DAD1 contributes differentially to co- vs post-translational glycosylation not resolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected DAD1 loss to a specific physiological pathway, showing hypoglycosylation of integrins disrupts adhesion signaling and triggers anoikis.\",\n      \"evidence\": \"siRNA knockdown in neonatal rat cardiomyocytes with integrin glycosylation, FAK activation, morphology, adhesion-rescue, and Stt3A cross-knockdown assays\",\n      \"pmids\": [\"39611549\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single cell-type and single lab\", \"Whether integrin hypoglycosylation is the dominant death trigger in other tissues unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DAD1 mechanistically stabilizes the OST complex and is retained in translocon arrays, and the full substrate spectrum whose hypoglycosylation drives apoptosis, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No high-resolution structure of DAD1 within human OST in the corpus\", \"Substrates linking hypoglycosylation to tissue-specific apoptosis incompletely defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [1, 3, 5, 9]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [3, 5, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [4, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 3, 5, 9]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [0, 7, 10]}\n    ],\n    \"complexes\": [\"oligosaccharyltransferase (OST) complex\"],\n    \"partners\": [\"OST48\", \"RPN1\", \"RPN2\", \"STT3A\", \"MCL1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}