{"gene":"OSTC","run_date":"2026-06-10T05:19:53","timeline":{"discoveries":[{"year":2017,"finding":"DC2 and KCP2 mediate the physical interaction between the STT3A oligosaccharyltransferase complex and the Sec61 protein translocation channel in the ER. Loss of DC2 causes a defect in co-translational N-glycosylation that mimics an STT3A phenotype. DC2- and KCP2-deficient STT3A complexes remain stable and enzymatically active, indicating DC2/KCP2 are specifically required for translocon docking rather than OST catalytic activity. Deletion mutagenesis showed a conserved C-terminal tail motif of DC2 is critical for assembly into the STT3A complex, while the lumenal loop and N-terminal cytoplasmic segment are necessary for the functional interaction between STT3A and Sec61 complexes.","method":"Genetically modified human cells deficient in DC2 or KCP2; biochemical co-immunoprecipitation; deletion mutagenesis; N-glycosylation assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal biochemical analysis, genetic KO cells with defined phenotype, domain mutagenesis, multiple orthogonal methods in a single focused study","pmids":["28860277"],"is_preprint":false},{"year":2011,"finding":"DC2 and KCP2 depletion affects processing of amyloid precursor protein (APP) in a substrate-specific manner without globally blocking N-glycosylation or OST activity. Knockdown causes accumulation of APP C-terminal fragments (C99 and C83) and reduction in full-length mature APP, while secreted sAPPα levels are unaffected. The mechanism involves a specific effect on the γ-secretase complex, reducing the PS1 active fragment and blocking Aβ production. Conversely, overexpression of DC2 and KCP2 increases the active γ-secretase complex (particularly PS1 N-terminal fragment generated by endoproteolysis), stimulating Aβ production. DC2 and KCP2 were shown to interact with the γ-secretase complex.","method":"siRNA knockdown and overexpression of DC2 and KCP2 in cell lines; Western blot analysis of APP processing intermediates; ELISA for sAPPα and Aβ; co-immunoprecipitation with γ-secretase components","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — single lab, multiple orthogonal methods (KD, OE, Co-IP, biochemical assays), but no structural or in vitro reconstitution validation","pmids":["21768116"],"is_preprint":false},{"year":2014,"finding":"OSTC/DC2 protein expression is upregulated following acute heat shock both in human glioblastoma U87MG cells in vitro and in mouse tissues in vivo. Northern blot showed OSTC/DC2 mRNA is ubiquitously expressed in human tissues with highest levels in placenta and liver. In cerebellum, the time course of OSTC/DC2 upregulation after heat shock paralleled AKT activation, suggesting OSTC/DC2 induction is part of the heat shock stress response.","method":"Western blot of OSTC/DC2 protein in heat-shocked cells and animal tissues; Northern blot for mRNA tissue distribution; in vivo mouse heat shock model","journal":"The Kaohsiung journal of medical sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, descriptive expression data with limited mechanistic follow-up; AKT correlation is associative only","pmids":["24751383"],"is_preprint":false},{"year":2021,"finding":"miR-1307 weakens the binding ability of OSTC to CDK2, CDK4, CyclinD1, and CyclinE while enhancing CALR binding to these cell cycle regulators, with downstream decreases in p21WAF1/CIP1, GADD45, pRB, and p18. miR-1307 also reduces the binding of OSTC to ATG4, while enhancing CALR-ATG4 binding, thereby reducing autophagy. These findings place OSTC in a competitive binding relationship with CALR for cell cycle and autophagy regulators.","method":"Co-immunoprecipitation assays for OSTC and CALR binding partners; autophagy pathway analysis; miR-1307 overexpression in liver cancer cells","journal":"iScience","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, Co-IP data without reciprocal validation; mechanistic claims are embedded in a complex miRNA study with limited direct validation of OSTC-specific interactions","pmids":["34761190"],"is_preprint":false}],"current_model":"OSTC (DC2) is a non-catalytic subunit of the STT3A oligosaccharyltransferase complex that, together with KCP2, physically bridges the OST complex to the Sec61 translocon to enable efficient co-translational N-linked glycosylation; specific domain elements of DC2 (C-terminal tail for STT3A assembly; lumenal loop and N-terminal segment for Sec61 interaction) are required for this docking function, while the OST catalytic activity itself is preserved in DC2-deficient complexes."},"narrative":{"mechanistic_narrative":"OSTC (DC2) is a non-catalytic subunit of the STT3A oligosaccharyltransferase complex that enables efficient co-translational N-linked glycosylation in the ER [PMID:28860277]. Together with KCP2, OSTC physically bridges the STT3A OST complex to the Sec61 protein translocation channel, and its loss produces a co-translational glycosylation defect that mimics loss of STT3A; STT3A complexes lacking OSTC remain stable and catalytically active, establishing that OSTC functions specifically in translocon docking rather than in catalysis [PMID:28860277]. Distinct domain elements mediate this role: a conserved C-terminal tail is required for assembly into the STT3A complex, while the lumenal loop and N-terminal cytoplasmic segment mediate the functional interaction with Sec61 [PMID:28860277]. OSTC and KCP2 also act on the γ-secretase complex in a substrate-specific manner, interacting with γ-secretase components, modulating PS1 endoproteolysis and the active PS1 fragment, and thereby influencing APP processing and Aβ production without globally blocking N-glycosylation [PMID:21768116]. Beyond these roles, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2011,"claim":"Before this work it was unclear whether OSTC/DC2 had substrate-selective effects on protein processing; the study showed that DC2 and KCP2 modulate APP processing via the γ-secretase complex rather than through a global glycosylation block, establishing a substrate-specific functional output.","evidence":"siRNA knockdown and overexpression of DC2/KCP2 in cell lines with Western blot of APP fragments, ELISA for sAPPα and Aβ, and co-immunoprecipitation with γ-secretase components","pmids":["21768116"],"confidence":"Medium","gaps":["No reconstitution showing direct OSTC-γ-secretase interaction is structural rather than indirect","Mechanism linking OSTC to PS1 endoproteolysis not defined","Relationship to the OST/Sec61 docking role not yet integrated"]},{"year":2014,"claim":"To place OSTC in a physiological context, expression profiling addressed whether it responds to cellular stress; OSTC was found to be upregulated by acute heat shock in cells and tissues, implicating it in the stress response, though only associatively.","evidence":"Western blot of OSTC protein in heat-shocked cells and mouse tissues, Northern blot for tissue mRNA distribution, and an in vivo mouse heat shock model","pmids":["24751383"],"confidence":"Low","gaps":["AKT correlation is associative only with no causal link","No mechanism connecting heat shock induction to OST or Sec61 function","Descriptive expression data without functional follow-up"]},{"year":2017,"claim":"The central mechanistic question of how the STT3A OST complex is positioned for co-translational glycosylation was answered by showing OSTC/DC2 and KCP2 bridge STT3A to the Sec61 translocon, and that OSTC is dispensable for catalysis but essential for translocon docking.","evidence":"DC2/KCP2-deficient human cells, co-immunoprecipitation, deletion mutagenesis mapping C-terminal, lumenal loop, and N-terminal segments, and N-glycosylation assays","pmids":["28860277"],"confidence":"High","gaps":["No structural model of the STT3A-OSTC-Sec61 interface","Reconstitution of docking in vitro not performed","Relationship between docking role and APP/γ-secretase effects unresolved"]},{"year":2021,"claim":"A candidate role for OSTC in cell cycle and autophagy regulation was raised by showing miR-1307 shifts binding of cell cycle regulators and ATG4 between OSTC and CALR, placing OSTC in competitive binding with CALR.","evidence":"Co-immunoprecipitation of OSTC and CALR binding partners, autophagy pathway analysis, and miR-1307 overexpression in liver cancer cells","pmids":["34761190"],"confidence":"Low","gaps":["Co-IP data without reciprocal validation","OSTC-specific interactions embedded in a complex miRNA study with limited direct validation","No functional demonstration that OSTC binding drives the cell cycle/autophagy phenotypes"]},{"year":null,"claim":"How OSTC's role in STT3A-Sec61 translocon docking mechanistically relates to its reported effects on γ-secretase, stress response, and cell cycle/autophagy regulators remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of the docking complex","No unifying mechanism connecting glycosylation docking to the other reported functions","Direct physical partners outside STT3A/Sec61 not validated reciprocally"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]}],"complexes":["STT3A oligosaccharyltransferase complex"],"partners":["KCP2","STT3A","SEC61"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NRP0","full_name":"Oligosaccharyltransferase complex subunit OSTC","aliases":["Hydrophobic protein HSF-28"],"length_aa":149,"mass_kda":16.8,"function":"Subunit of STT3A-containing oligosaccharyl transferase (OST-A) 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:28860277, PubMed:31831667, PubMed:39509507). 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) (PubMed:28860277, PubMed:31831667, PubMed:39509507). Within the OST-A complex, acts as an adapter that anchors the OST-A complex to the Sec61 complex (PubMed:28860277). May be involved in N-glycosylation of APP (amyloid-beta precursor protein) (PubMed:21768116). Can modulate gamma-secretase cleavage of APP by enhancing endoprotelysis of PSEN1 (PubMed:21768116)","subcellular_location":"Endoplasmic reticulum; Membrane","url":"https://www.uniprot.org/uniprotkb/Q9NRP0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/OSTC","classification":"Common Essential","n_dependent_lines":887,"n_total_lines":1208,"dependency_fraction":0.734271523178808},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000198856","cell_line_id":"CID000178","localizations":[{"compartment":"er","grade":3}],"interactors":[{"gene":"PICALM","stoichiometry":10.0},{"gene":"MLEC","stoichiometry":10.0},{"gene":"FKBP8","stoichiometry":10.0},{"gene":"KAT6A;MYST3","stoichiometry":10.0},{"gene":"STT3A","stoichiometry":10.0},{"gene":"PGRMC1","stoichiometry":10.0},{"gene":"DDOST","stoichiometry":0.2},{"gene":"KRTCAP2","stoichiometry":0.2},{"gene":"OST4","stoichiometry":0.2},{"gene":"TIA1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000178","total_profiled":1310},"omim":[{"mim_id":"619023","title":"OLIGOSACCHARYLTRANSFERASE COMPLEX, NONCATALYTIC SUBUNIT; OSTC","url":"https://www.omim.org/entry/619023"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/OSTC"},"hgnc":{"alias_symbol":["DC2"],"prev_symbol":[]},"alphafold":{"accession":"Q9NRP0","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NRP0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NRP0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NRP0-F1-predicted_aligned_error_v6.png","plddt_mean":86.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=OSTC","jax_strain_url":"https://www.jax.org/strain/search?query=OSTC"},"sequence":{"accession":"Q9NRP0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NRP0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NRP0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NRP0"}},"corpus_meta":[{"pmid":"11120774","id":"PMC_11120774","title":"Id2 and Id3 inhibit development of CD34(+) stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. 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Yi xue ban = Journal of Sichuan University. Medical science edition","url":"https://pubmed.ncbi.nlm.nih.gov/31950794","citation_count":0,"is_preprint":false},{"pmid":"21722529","id":"PMC_21722529","title":"[A preliminary study on the effect of lincomycin on the immune function of dendritic cell line DC2.4].","date":"2011","source":"Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/21722529","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.04.686640","title":"Bispecific CD20xCD40 Antibodies Achieve Multi-Lineage Modulation of Humoral and Cellular Immunity","date":"2025-11-06","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.04.686640","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.17.600758","title":"Distinct tissue-niche localization and function of synovial tissue myeloid DC subsets in health, and in active and remission Rheumatoid Arthritis","date":"2024-07-19","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.17.600758","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.09.11.612410","title":"Intestinal helminth skews DC2 development towards regulatory phenotype to counter the anti-helminth immune response","date":"2024-09-15","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.11.612410","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.11.12.623329","title":"Newly found rat CD103  <sup>-</sup>  dendritic cells are the highly immunogenic conventional DC2 subpopulation, corresponding to the known DC subsets in mice and humans","date":"2024-11-15","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.12.623329","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.03.05.641653","title":"Immune signaling mediates stromal changes to support epithelial reprogramming in Celiac duodenum","date":"2025-03-10","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.05.641653","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.29.25321332","title":"Revitalizing systemic immune responses in advanced NSCLC using FLT3L and SBRT","date":"2025-02-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.29.25321332","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.09.05.674429","title":"Histone methyltransferase DOT1L differentially affects the development of dendritic cell subsets","date":"2025-09-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.05.674429","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.13.664342","title":"Mgl2  <sup>+</sup>  cDC2 triggering of fungal allergic inflammation depends on a spore induced glycolytic shift fuelled by local availability of glucose","date":"2025-07-18","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.13.664342","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":29724,"output_tokens":1722,"usd":0.057501,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8150,"output_tokens":2028,"usd":0.045725,"stage2_stop_reason":"end_turn"},"total_usd":0.103226,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the canonical OSTC/DC2 protein (oligosaccharyltransferase complex subunit, also known as DC2). This is a subunit of the oligosaccharyltransferase (OST) complex in the ER.\n\nMost papers in this corpus are about \"DC2\" as a dendritic cell type, or other unrelated uses of \"DC2\" (bacterial strains, zebrafish neurons, Chlamydomonas, C. elegans galectin, etc.). I need to focus only on the OSTC/DC2 protein.\n\nRelevant papers:\n- PMID 28860277: DC2 and KCP2 mediate the interaction between OST and ER translocon\n- PMID 21768116: DC2 and KCP2 are regulators of gamma-secretase-directed processing of APP\n- PMID 34761190: miR-1307 and OSTC binding to CDK2, CDK4, CyclinD1, CyclinE, ATG4\n- PMID 24751383: Heat shock induces expression of OSTC/DC2\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"DC2 and KCP2 mediate the physical interaction between the STT3A oligosaccharyltransferase complex and the Sec61 protein translocation channel in the ER. Loss of DC2 causes a defect in co-translational N-glycosylation that mimics an STT3A phenotype. DC2- and KCP2-deficient STT3A complexes remain stable and enzymatically active, indicating DC2/KCP2 are specifically required for translocon docking rather than OST catalytic activity. Deletion mutagenesis showed a conserved C-terminal tail motif of DC2 is critical for assembly into the STT3A complex, while the lumenal loop and N-terminal cytoplasmic segment are necessary for the functional interaction between STT3A and Sec61 complexes.\",\n      \"method\": \"Genetically modified human cells deficient in DC2 or KCP2; biochemical co-immunoprecipitation; deletion mutagenesis; N-glycosylation assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal biochemical analysis, genetic KO cells with defined phenotype, domain mutagenesis, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"28860277\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"DC2 and KCP2 depletion affects processing of amyloid precursor protein (APP) in a substrate-specific manner without globally blocking N-glycosylation or OST activity. Knockdown causes accumulation of APP C-terminal fragments (C99 and C83) and reduction in full-length mature APP, while secreted sAPPα levels are unaffected. The mechanism involves a specific effect on the γ-secretase complex, reducing the PS1 active fragment and blocking Aβ production. Conversely, overexpression of DC2 and KCP2 increases the active γ-secretase complex (particularly PS1 N-terminal fragment generated by endoproteolysis), stimulating Aβ production. DC2 and KCP2 were shown to interact with the γ-secretase complex.\",\n      \"method\": \"siRNA knockdown and overexpression of DC2 and KCP2 in cell lines; Western blot analysis of APP processing intermediates; ELISA for sAPPα and Aβ; co-immunoprecipitation with γ-secretase components\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — single lab, multiple orthogonal methods (KD, OE, Co-IP, biochemical assays), but no structural or in vitro reconstitution validation\",\n      \"pmids\": [\"21768116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"OSTC/DC2 protein expression is upregulated following acute heat shock both in human glioblastoma U87MG cells in vitro and in mouse tissues in vivo. Northern blot showed OSTC/DC2 mRNA is ubiquitously expressed in human tissues with highest levels in placenta and liver. In cerebellum, the time course of OSTC/DC2 upregulation after heat shock paralleled AKT activation, suggesting OSTC/DC2 induction is part of the heat shock stress response.\",\n      \"method\": \"Western blot of OSTC/DC2 protein in heat-shocked cells and animal tissues; Northern blot for mRNA tissue distribution; in vivo mouse heat shock model\",\n      \"journal\": \"The Kaohsiung journal of medical sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, descriptive expression data with limited mechanistic follow-up; AKT correlation is associative only\",\n      \"pmids\": [\"24751383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"miR-1307 weakens the binding ability of OSTC to CDK2, CDK4, CyclinD1, and CyclinE while enhancing CALR binding to these cell cycle regulators, with downstream decreases in p21WAF1/CIP1, GADD45, pRB, and p18. miR-1307 also reduces the binding of OSTC to ATG4, while enhancing CALR-ATG4 binding, thereby reducing autophagy. These findings place OSTC in a competitive binding relationship with CALR for cell cycle and autophagy regulators.\",\n      \"method\": \"Co-immunoprecipitation assays for OSTC and CALR binding partners; autophagy pathway analysis; miR-1307 overexpression in liver cancer cells\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, Co-IP data without reciprocal validation; mechanistic claims are embedded in a complex miRNA study with limited direct validation of OSTC-specific interactions\",\n      \"pmids\": [\"34761190\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"OSTC (DC2) is a non-catalytic subunit of the STT3A oligosaccharyltransferase complex that, together with KCP2, physically bridges the OST complex to the Sec61 translocon to enable efficient co-translational N-linked glycosylation; specific domain elements of DC2 (C-terminal tail for STT3A assembly; lumenal loop and N-terminal segment for Sec61 interaction) are required for this docking function, while the OST catalytic activity itself is preserved in DC2-deficient complexes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"OSTC (DC2) is a non-catalytic subunit of the STT3A oligosaccharyltransferase complex that enables efficient co-translational N-linked glycosylation in the ER [#0]. Together with KCP2, OSTC physically bridges the STT3A OST complex to the Sec61 protein translocation channel, and its loss produces a co-translational glycosylation defect that mimics loss of STT3A; STT3A complexes lacking OSTC remain stable and catalytically active, establishing that OSTC functions specifically in translocon docking rather than in catalysis [#0]. Distinct domain elements mediate this role: a conserved C-terminal tail is required for assembly into the STT3A complex, while the lumenal loop and N-terminal cytoplasmic segment mediate the functional interaction with Sec61 [#0]. OSTC and KCP2 also act on the γ-secretase complex in a substrate-specific manner, interacting with γ-secretase components, modulating PS1 endoproteolysis and the active PS1 fragment, and thereby influencing APP processing and Aβ production without globally blocking N-glycosylation [#1]. Beyond these roles, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Before this work it was unclear whether OSTC/DC2 had substrate-selective effects on protein processing; the study showed that DC2 and KCP2 modulate APP processing via the γ-secretase complex rather than through a global glycosylation block, establishing a substrate-specific functional output.\",\n      \"evidence\": \"siRNA knockdown and overexpression of DC2/KCP2 in cell lines with Western blot of APP fragments, ELISA for sAPPα and Aβ, and co-immunoprecipitation with γ-secretase components\",\n      \"pmids\": [\"21768116\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconstitution showing direct OSTC-γ-secretase interaction is structural rather than indirect\", \"Mechanism linking OSTC to PS1 endoproteolysis not defined\", \"Relationship to the OST/Sec61 docking role not yet integrated\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"To place OSTC in a physiological context, expression profiling addressed whether it responds to cellular stress; OSTC was found to be upregulated by acute heat shock in cells and tissues, implicating it in the stress response, though only associatively.\",\n      \"evidence\": \"Western blot of OSTC protein in heat-shocked cells and mouse tissues, Northern blot for tissue mRNA distribution, and an in vivo mouse heat shock model\",\n      \"pmids\": [\"24751383\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"AKT correlation is associative only with no causal link\", \"No mechanism connecting heat shock induction to OST or Sec61 function\", \"Descriptive expression data without functional follow-up\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The central mechanistic question of how the STT3A OST complex is positioned for co-translational glycosylation was answered by showing OSTC/DC2 and KCP2 bridge STT3A to the Sec61 translocon, and that OSTC is dispensable for catalysis but essential for translocon docking.\",\n      \"evidence\": \"DC2/KCP2-deficient human cells, co-immunoprecipitation, deletion mutagenesis mapping C-terminal, lumenal loop, and N-terminal segments, and N-glycosylation assays\",\n      \"pmids\": [\"28860277\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of the STT3A-OSTC-Sec61 interface\", \"Reconstitution of docking in vitro not performed\", \"Relationship between docking role and APP/γ-secretase effects unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"A candidate role for OSTC in cell cycle and autophagy regulation was raised by showing miR-1307 shifts binding of cell cycle regulators and ATG4 between OSTC and CALR, placing OSTC in competitive binding with CALR.\",\n      \"evidence\": \"Co-immunoprecipitation of OSTC and CALR binding partners, autophagy pathway analysis, and miR-1307 overexpression in liver cancer cells\",\n      \"pmids\": [\"34761190\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Co-IP data without reciprocal validation\", \"OSTC-specific interactions embedded in a complex miRNA study with limited direct validation\", \"No functional demonstration that OSTC binding drives the cell cycle/autophagy phenotypes\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How OSTC's role in STT3A-Sec61 translocon docking mechanistically relates to its reported effects on γ-secretase, stress response, and cell cycle/autophagy regulators remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of the docking complex\", \"No unifying mechanism connecting glycosylation docking to the other reported functions\", \"Direct physical partners outside STT3A/Sec61 not validated reciprocally\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"STT3A oligosaccharyltransferase complex\"],\n    \"partners\": [\"KCP2\", \"STT3A\", \"SEC61\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}