{"gene":"TAPBP","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2002,"finding":"TAPBP (tapasin) was identified as a V-C1 immunoglobulin superfamily molecule that links MHC class I molecules to the transporter associated with antigen processing (TAP) in the endoplasmic reticulum (ER), and is encoded near the MHC at 6p21.3. A related gene TAPBP-R was identified at 12p13.3; its product TAPASIN-R shares structural motifs with tapasin but differs in V domain, transmembrane, and cytoplasmic regions. Subcellular localization experiments showed the bulk of TAPASIN-R resides in the ER, with some cell-surface expression detected by biotinylation.","method":"Genomic/sequence analysis, subcellular localization by fractionation and biotinylation experiments","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, direct localization experiment with functional context; confirms ER residency of related protein and establishes TAPBP's role in TAP-MHC I linkage as background","pmids":["11920573"],"is_preprint":false},{"year":2002,"finding":"Crystal structures of rat MHC class Ia molecules (RT1-Aa and RT1-A1c) revealed the molecular basis of peptide-MHC assembly and how tapasin participates in the MHC class I peptide-loading complex in the ER, with the structures showing how peptide C-termini match the F-pocket chemistry and providing structural context for tapasin-associated loading.","method":"X-ray crystallography of MHC class Ia molecules, biochemical analysis of peptide-MHC assembly rates","journal":"Journal of molecular biology","confidence":"Low","confidence_rationale":"Tier 1 / Weak — crystal structures of MHC partners, tapasin mentioned as component of loading complex but not directly studied structurally in this paper; single study","pmids":["12470953"],"is_preprint":false},{"year":2016,"finding":"Disruption of TAPBP (tapasin) in human embryonic stem cells (hESCs) using TALEN-mediated genome editing resulted in deficient MHC class I expression on the cell surface and reduced immunogenicity, while pluripotency, karyotype, and differentiation ability were maintained. This experimentally established that TAPBP is required for normal MHC class I surface expression.","method":"TALEN-mediated gene knockout in hESCs, flow cytometry for MHC class I surface expression, pluripotency and differentiation assays","journal":"Bioscience, biotechnology, and biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype (loss of MHC class I surface expression), single lab with multiple orthogonal readouts","pmids":["27068360"],"is_preprint":false},{"year":2024,"finding":"A risk SNP rs1059288 (A>G) in the 3' UTR of TAPBP increases m6A modification of TAPBP mRNA, facilitated by the m6A methyltransferase METTL14 and reader protein YTHDF2. Upregulation of TAPBP promoted cervical cancer cell growth, migration, tumor-forming ability, and chemotherapy resistance, and knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway while upregulating immune genes including HLA-A.","method":"MeRIP-seq, RNA-seq, TCGA/JENGER database analysis, case-control study, immunohistochemistry, siRNA knockdown, overexpression assays, pathway analysis","journal":"Archives of toxicology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, pathway placement inferred from knockdown with multiple readouts but no direct biochemical reconstitution of TAPBP in JAK/STAT pathway; m6A mechanism supported by correlation not direct enzymatic reconstitution","pmids":["38992170"],"is_preprint":false}],"current_model":"TAPBP (tapasin) is an immunoglobulin superfamily transmembrane protein that resides in the endoplasmic reticulum where it bridges MHC class I molecules to the TAP peptide transporter within the peptide-loading complex, and is required for normal MHC class I surface expression as demonstrated by TAPBP knockout leading to deficient MHC class I display on human cells."},"narrative":{"mechanistic_narrative":"TAPBP (tapasin) is a V-C1 immunoglobulin superfamily molecule of the endoplasmic reticulum that links MHC class I molecules to the transporter associated with antigen processing (TAP) within the peptide-loading complex [PMID:11920573]. Consistent with this bridging role, TALEN-mediated disruption of TAPBP in human embryonic stem cells abolishes normal MHC class I surface expression and reduces immunogenicity without perturbing pluripotency, karyotype, or differentiation, establishing TAPBP as required for MHC class I display [PMID:27068360]. Beyond its function in antigen presentation, no further direct mechanistic detail on the tapasin protein has been characterized in the available corpus.","teleology":[{"year":2002,"claim":"Established the molecular role of tapasin by placing it as the bridge linking MHC class I to the TAP transporter in the ER, defining its position in the peptide-loading machinery.","evidence":"Genomic/sequence analysis with subcellular localization by fractionation and biotinylation","pmids":["11920573"],"confidence":"Medium","gaps":["Bridging activity inferred from sequence/localization context, not from direct reconstitution of the TAP-MHC I interaction","Localization data shown directly for the related TAPASIN-R, not exhaustively for tapasin itself"]},{"year":2002,"claim":"Provided structural context for how peptide-MHC assembly occurs within the tapasin-associated loading complex, clarifying the chemistry that tapasin-assisted loading must satisfy.","evidence":"X-ray crystallography of rat MHC class Ia molecules and peptide-MHC assembly analysis","pmids":["12470953"],"confidence":"Low","gaps":["Tapasin was not directly studied structurally; only its MHC partners were crystallized","No structure of tapasin bound to MHC class I or TAP"]},{"year":2016,"claim":"Demonstrated causally that TAPBP is required for MHC class I surface expression by loss-of-function, moving its role from inferred to experimentally established in human cells.","evidence":"TALEN-mediated knockout in human embryonic stem cells with flow cytometry and pluripotency/differentiation assays","pmids":["27068360"],"confidence":"Medium","gaps":["Phenotype defined at the level of surface MHC class I, without dissection of which loading-complex step fails","Single cell type; no rescue with point mutants to map functional residues"]},{"year":2024,"claim":"Linked TAPBP expression regulation to m6A modification and explored a downstream signaling role in cancer, expanding context beyond antigen loading.","evidence":"MeRIP-seq, RNA-seq, case-control and database analysis, siRNA knockdown and overexpression in cervical cancer cells","pmids":["38992170"],"confidence":"Low","gaps":["Pathway placement in JAK/STAT/MICB inferred from knockdown readouts without direct biochemical reconstitution","m6A mechanism supported by correlation rather than direct enzymatic reconstitution","Causal contribution of the 3' UTR SNP to tumor phenotype not established by editing"]},{"year":null,"claim":"How tapasin mechanistically catalyzes or stabilizes peptide editing within the loading complex, and the structural basis of its MHC class I and TAP contacts, remain unresolved in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct structure of tapasin with its binding partners in the timeline","No reconstitution defining tapasin's peptide-editing activity","Functional residues required for MHC class I support not mapped"]}],"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-168256","term_label":"Immune System","supporting_discovery_ids":[2]}],"complexes":["MHC class I peptide-loading complex"],"partners":["TAP","MHC CLASS I"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O15533","full_name":"Tapasin","aliases":["NGS-17","TAP-associated protein","TAP-binding protein"],"length_aa":448,"mass_kda":47.6,"function":"Involved in the association of MHC class I with transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading)","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/O15533/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TAPBP","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TAPBP","total_profiled":1310},"omim":[{"mim_id":"620814","title":"MHC CLASS I DEFICIENCY 3; MHC1D3","url":"https://www.omim.org/entry/620814"},{"mim_id":"611440","title":"WD REPEAT-CONTAINING PROTEIN 46; WDR46","url":"https://www.omim.org/entry/611440"},{"mim_id":"607081","title":"TAP-BINDING PROTEIN-LIKE; TAPBPL","url":"https://www.omim.org/entry/607081"},{"mim_id":"605660","title":"PREFOLDIN 6; PFDN6","url":"https://www.omim.org/entry/605660"},{"mim_id":"604571","title":"MHC CLASS I DEFICIENCY 1; MHC1D1","url":"https://www.omim.org/entry/604571"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAPBP"},"hgnc":{"alias_symbol":["TAPA","TPN","TPSN","NGS17"],"prev_symbol":[]},"alphafold":{"accession":"O15533","domains":[{"cath_id":"2.60.40.10","chopping":"23-108_119-187_199-288","consensus_level":"medium","plddt":92.3533,"start":23,"end":288},{"cath_id":"2.60.40.10","chopping":"292-401","consensus_level":"high","plddt":90.4322,"start":292,"end":401}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O15533","model_url":"https://alphafold.ebi.ac.uk/files/AF-O15533-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O15533-F1-predicted_aligned_error_v6.png","plddt_mean":87.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAPBP","jax_strain_url":"https://www.jax.org/strain/search?query=TAPBP"},"sequence":{"accession":"O15533","fasta_url":"https://rest.uniprot.org/uniprotkb/O15533.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O15533/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O15533"}},"corpus_meta":[{"pmid":"2501509","id":"PMC_2501509","title":"TEN versus TPN following major abdominal trauma--reduced septic morbidity.","date":"1989","source":"The Journal of trauma","url":"https://pubmed.ncbi.nlm.nih.gov/2501509","citation_count":609,"is_preprint":false},{"pmid":"9597125","id":"PMC_9597125","title":"CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system.","date":"1998","source":"Annual review of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/9597125","citation_count":419,"is_preprint":false},{"pmid":"7542009","id":"PMC_7542009","title":"The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity.","date":"1995","source":"Annual review of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/7542009","citation_count":396,"is_preprint":false},{"pmid":"1695320","id":"PMC_1695320","title":"TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins.","date":"1990","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/1695320","citation_count":357,"is_preprint":false},{"pmid":"9566977","id":"PMC_9566977","title":"Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions.","date":"1998","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9566977","citation_count":227,"is_preprint":false},{"pmid":"8757325","id":"PMC_8757325","title":"Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29).","date":"1996","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/8757325","citation_count":200,"is_preprint":false},{"pmid":"7690834","id":"PMC_7690834","title":"Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes.","date":"1993","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/7690834","citation_count":196,"is_preprint":false},{"pmid":"8119731","id":"PMC_8119731","title":"Association of four antigens of the tetraspans family (CD37, CD53, TAPA-1, and R2/C33) with MHC class II glycoproteins.","date":"1994","source":"Immunogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/8119731","citation_count":166,"is_preprint":false},{"pmid":"12851879","id":"PMC_12851879","title":"GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1.","date":"2003","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/12851879","citation_count":163,"is_preprint":false},{"pmid":"11093948","id":"PMC_11093948","title":"GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis.","date":"2000","source":"American journal of physiology. 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Deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu 13.","date":"1993","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/7690791","citation_count":101,"is_preprint":false},{"pmid":"15173413","id":"PMC_15173413","title":"Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets.","date":"2004","source":"The Journal of nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/15173413","citation_count":98,"is_preprint":false},{"pmid":"9403534","id":"PMC_9403534","title":"A temporal study of TPN-induced changes in gut-associated lymphoid tissue and mucosal immunity.","date":"1997","source":"Archives of surgery (Chicago, Ill. : 1960)","url":"https://pubmed.ncbi.nlm.nih.gov/9403534","citation_count":88,"is_preprint":false},{"pmid":"3102754","id":"PMC_3102754","title":"Failure of TPN supplementation to improve liver function, immunity, and 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Formation constants for the copper(II)--histidine ternary complexes with threonine, lysine, glycine, phenylalanine, valine, and cystine, and discussion of their implications regarding the copper distribution in blood plasma during TPN and the evaluation of the daily dose of copper.","date":"1984","source":"Journal of inorganic biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/6425456","citation_count":14,"is_preprint":false},{"pmid":"8668914","id":"PMC_8668914","title":"Triggering of target of an antiproliferative antibody-1 (TAPA-1/CD81) up-regulates the release of tumour necrosis factor-alpha by the EBV-B lymphoblastoid cell line JY.","date":"1996","source":"Scandinavian journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/8668914","citation_count":14,"is_preprint":false},{"pmid":"19160716","id":"PMC_19160716","title":"Pyrogen testing of lipid-based TPN using Mono Mac 6 monocyte cell line and DELFIA.","date":"1997","source":"Journal of clinical pharmacy and therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/19160716","citation_count":14,"is_preprint":false},{"pmid":"30371005","id":"PMC_30371005","title":"The Bacterial Extracellular Matrix Protein TapA Is a Two-Domain Partially Disordered Protein.","date":"2018","source":"Chembiochem : a European journal of chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/30371005","citation_count":13,"is_preprint":false},{"pmid":"10619563","id":"PMC_10619563","title":"The expression of TAPA (CD81) correlates with the reactive response of astrocytes in the developing rat CNS.","date":"1999","source":"Experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/10619563","citation_count":13,"is_preprint":false},{"pmid":"9485486","id":"PMC_9485486","title":"The target of the antiproliferative antibody (TAPA) in the normal and injured rat retina.","date":"1998","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/9485486","citation_count":13,"is_preprint":false},{"pmid":"6406651","id":"PMC_6406651","title":"Cellular localization of liver vitamin A in rats given total parenteral nutrition (TPN) solutions intravenously or orally.","date":"1983","source":"The Journal of nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/6406651","citation_count":13,"is_preprint":false},{"pmid":"20683583","id":"PMC_20683583","title":"Lack of a rewarding effect and a locomotor-enhancing effect of the selective μ-opioid receptor agonist amidino-TAPA.","date":"2010","source":"Psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/20683583","citation_count":12,"is_preprint":false},{"pmid":"1380797","id":"PMC_1380797","title":"Expression of TAPA-1 in preimplantation mouse embryos.","date":"1992","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/1380797","citation_count":12,"is_preprint":false},{"pmid":"17307162","id":"PMC_17307162","title":"Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA.","date":"2007","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/17307162","citation_count":12,"is_preprint":false},{"pmid":"239945","id":"PMC_239945","title":"Alpha-methylisocitrate. A selective inhibitor of TPN-linked isocitrate dehydrogenase from bovine heart and rat liver.","date":"1975","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/239945","citation_count":12,"is_preprint":false},{"pmid":"11773042","id":"PMC_11773042","title":"Retinal pigment epithelium of the rat express CD81, the target of the anti-proliferative antibody (TAPA).","date":"2002","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/11773042","citation_count":11,"is_preprint":false},{"pmid":"16831738","id":"PMC_16831738","title":"Post-operative substrate utilisation and gas exchange using two different TPN-systems: glucose versus fat.","date":"1985","source":"Clinical nutrition (Edinburgh, Scotland)","url":"https://pubmed.ncbi.nlm.nih.gov/16831738","citation_count":11,"is_preprint":false},{"pmid":"12470953","id":"PMC_12470953","title":"Crystal structures of two rat MHC class Ia (RT1-A) molecules that are associated differentially with peptide transporter alleles TAP-A and TAP-B.","date":"2002","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12470953","citation_count":11,"is_preprint":false},{"pmid":"32779018","id":"PMC_32779018","title":"Computational investigation for modeling the protein-protein interaction of TasA(28-261)-TapA(33-253): a decisive process in biofilm formation by Bacillus subtilis.","date":"2020","source":"Journal of molecular modeling","url":"https://pubmed.ncbi.nlm.nih.gov/32779018","citation_count":10,"is_preprint":false},{"pmid":"18030236","id":"PMC_18030236","title":"Variations in metabolic response to TPN are influenced more by sex than by light exposure.","date":"2007","source":"Journal of pediatric gastroenterology and nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/18030236","citation_count":10,"is_preprint":false},{"pmid":"11404235","id":"PMC_11404235","title":"TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release.","date":"2001","source":"American journal of physiology. Endocrinology and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/11404235","citation_count":10,"is_preprint":false},{"pmid":"19044","id":"PMC_19044","title":"Structure-function relationships in TPN-dependent isocitrate dehydrogenase. I. Electron paramagnetic resonance studies of the interaction of enzyme-bound Mn(II) with substrates, cofactors, and substrate analogues.","date":"1977","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19044","citation_count":9,"is_preprint":false},{"pmid":"27273879","id":"PMC_27273879","title":"Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial.","date":"2016","source":"Physiological reports","url":"https://pubmed.ncbi.nlm.nih.gov/27273879","citation_count":9,"is_preprint":false},{"pmid":"15912897","id":"PMC_15912897","title":"Postoperative nutritional management after esophagectomy: is TPN the standard of nutritional care?","date":"2005","source":"International surgery","url":"https://pubmed.ncbi.nlm.nih.gov/15912897","citation_count":9,"is_preprint":false},{"pmid":"3125565","id":"PMC_3125565","title":"The effect of total parenteral nutrition (TPN) on gastrin release in the rat.","date":"1987","source":"Regulatory peptides","url":"https://pubmed.ncbi.nlm.nih.gov/3125565","citation_count":8,"is_preprint":false},{"pmid":"15066740","id":"PMC_15066740","title":"Candida parapsilosis detected in TPN using the BacT/Alert system and characterized by randomly amplified polymorphic DNA.","date":"2004","source":"The Journal of hospital infection","url":"https://pubmed.ncbi.nlm.nih.gov/15066740","citation_count":8,"is_preprint":false},{"pmid":"6434177","id":"PMC_6434177","title":"Does total parenteral nutrition (TPN) really promote tumor growth? A morphometric study.","date":"1984","source":"Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/6434177","citation_count":8,"is_preprint":false},{"pmid":"26694804","id":"PMC_26694804","title":"A peptide tetramer Tk-tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll-like receptor 2 signal-promoted activation of the MCP1 gene.","date":"2016","source":"Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/26694804","citation_count":7,"is_preprint":false},{"pmid":"3922014","id":"PMC_3922014","title":"The effect of total parenteral nutrition (TPN) on the enteroinsular axis in the rat.","date":"1985","source":"Regulatory peptides","url":"https://pubmed.ncbi.nlm.nih.gov/3922014","citation_count":7,"is_preprint":false},{"pmid":"16274854","id":"PMC_16274854","title":"The role of polyamines in glucagon-like peptide-2 prevention of TPN-induced gut hypoplasia.","date":"2005","source":"Peptides","url":"https://pubmed.ncbi.nlm.nih.gov/16274854","citation_count":6,"is_preprint":false},{"pmid":"16839892","id":"PMC_16839892","title":"Nitrogen and energy balance in depleted patients undergoing major gastrointestinal surgery: response to TPN.","date":"1991","source":"Clinical nutrition (Edinburgh, Scotland)","url":"https://pubmed.ncbi.nlm.nih.gov/16839892","citation_count":6,"is_preprint":false},{"pmid":"7488177","id":"PMC_7488177","title":"Induction of heat-shock proteins and accumulation of trehalose by TPN in Saccharomyces cerevisiae.","date":"1995","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/7488177","citation_count":6,"is_preprint":false},{"pmid":"35456327","id":"PMC_35456327","title":"Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) for Shoulder Mobility Improvement in Women with Upper Limb Lymphedema Secondary to Breast Cancer: A Multicenter Controlled Clinical Trial.","date":"2022","source":"Journal of clinical medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35456327","citation_count":5,"is_preprint":false},{"pmid":"21047509","id":"PMC_21047509","title":"Involvement of mouse μ-opioid receptor splice variants in the spinal antinociception induced by the dermorphin tetrapeptide analog amidino-TAPA.","date":"2010","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/21047509","citation_count":5,"is_preprint":false},{"pmid":"12548054","id":"PMC_12548054","title":"Homocysteine prevents total parenteral nutrition (TPN)-induced cholestasis without changes in hepatic oxidative stress in the rat.","date":"2003","source":"Journal of pediatric gastroenterology and nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/12548054","citation_count":5,"is_preprint":false},{"pmid":"20691983","id":"PMC_20691983","title":"Dose variation of hepatocyte growth factor and its effects on an animal model of TPN-induced liver injury.","date":"2010","source":"The Journal of surgical research","url":"https://pubmed.ncbi.nlm.nih.gov/20691983","citation_count":5,"is_preprint":false},{"pmid":"37168746","id":"PMC_37168746","title":"Inadvertent Acute Lipid Injectable Emulsion Overdose Resulting in Fat Overload Syndrome and Pancreatitis in a Patient with TPN Dependence.","date":"2021","source":"JPGN reports","url":"https://pubmed.ncbi.nlm.nih.gov/37168746","citation_count":5,"is_preprint":false},{"pmid":"16837362","id":"PMC_16837362","title":"Glucose-based versus fat-based total parenteral nutrition (TPN): effects on hepatic function in septic patients complicated with cholestatic jaundice.","date":"1990","source":"Clinical nutrition (Edinburgh, Scotland)","url":"https://pubmed.ncbi.nlm.nih.gov/16837362","citation_count":5,"is_preprint":false},{"pmid":"38992170","id":"PMC_38992170","title":"A genetic variant in the TAPBP gene enhances cervical cancer susceptibility by increasing m6A modification.","date":"2024","source":"Archives of toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/38992170","citation_count":4,"is_preprint":false},{"pmid":"24126280","id":"PMC_24126280","title":"Involvement of spinal release of α-neo-endorphin on the antinociceptive effect of TAPA.","date":"2013","source":"Peptides","url":"https://pubmed.ncbi.nlm.nih.gov/24126280","citation_count":4,"is_preprint":false},{"pmid":"3080557","id":"PMC_3080557","title":"Effect of DL-3-hydroxybutyrate infusions on leucine and glucose kinetics in burned rats receiving TPN.","date":"1986","source":"The Journal of nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/3080557","citation_count":4,"is_preprint":false},{"pmid":"3138500","id":"PMC_3138500","title":"Effect of TPN on bone marrow kinetics--therapeutic implications.","date":"1988","source":"The Journal of surgical research","url":"https://pubmed.ncbi.nlm.nih.gov/3138500","citation_count":3,"is_preprint":false},{"pmid":"27348965","id":"PMC_27348965","title":"In-vitro detection of mannan and galactomannan in components of total parenteral nutrition (TPN).","date":"2016","source":"Die Pharmazie","url":"https://pubmed.ncbi.nlm.nih.gov/27348965","citation_count":3,"is_preprint":false},{"pmid":"23623932","id":"PMC_23623932","title":"Distinct physiological role of amidino-TAPA-sensitive and DAMGO-insensitive μ-opioid receptor splice variants in the mouse spinal cord.","date":"2013","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/23623932","citation_count":2,"is_preprint":false},{"pmid":"9456439","id":"PMC_9456439","title":"Effects of total parental nutrition (TPN) during high-dose interleukin-2 treatment for metastatic cancer.","date":"1998","source":"Journal of immunotherapy (Hagerstown, Md. : 1997)","url":"https://pubmed.ncbi.nlm.nih.gov/9456439","citation_count":2,"is_preprint":false},{"pmid":"16831739","id":"PMC_16831739","title":"Glucose balance and muscle glycogen during TPN in the early post-operative phase.","date":"1985","source":"Clinical nutrition (Edinburgh, Scotland)","url":"https://pubmed.ncbi.nlm.nih.gov/16831739","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":50518,"output_tokens":1676,"usd":0.088347,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7805,"output_tokens":1634,"usd":0.039938,"stage2_stop_reason":"end_turn"},"total_usd":0.128285,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the canonical human TAPBP gene (also known as TAPA, TPN, TPSN, NGS17) — specifically the tapasin protein involved in MHC class I antigen presentation in the endoplasmic reticulum.\n\nKey assessment:\n- The vast majority of papers are about \"TPN\" = Total Parenteral Nutrition, or \"TAPA\" = various other meanings (opioid peptides, bacterial proteins TapA, tetraspanin CD81/TAPA-1, lymphedema therapy)\n- TAPBP/tapasin papers: PMID 11920573 (TAPBP-R related gene), PMID 27068360 (TAPBP disruption in hESCs), PMID 38992170 (TAPBP SNP and m6A), PMID 12470953 (tapasin mentioned in MHC class I loading complex context)\n- CD81/TAPA-1 papers are about the tetraspanin CD81 gene (CD81/TAPA-1), NOT TAPBP/tapasin. These are a completely different protein. The HGNC aliases listed (TAPA, TPN, TPSN, NGS17) for TAPBP refer to tapasin, not CD81.\n\nWait — let me reconsider. The aliases TAPA, TPN, TPSN, NGS17 for TAPBP... TAPBP encodes tapasin (also called TPSN). These aliases do NOT refer to CD81 (which is also called TAPA-1). I need to be careful not to include CD81 papers as TAPBP papers.\n\nRelevant papers for TAPBP (tapasin): PMID 11920573, PMID 27068360, PMID 38992170, PMID 12470953.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"TAPBP (tapasin) was identified as a V-C1 immunoglobulin superfamily molecule that links MHC class I molecules to the transporter associated with antigen processing (TAP) in the endoplasmic reticulum (ER), and is encoded near the MHC at 6p21.3. A related gene TAPBP-R was identified at 12p13.3; its product TAPASIN-R shares structural motifs with tapasin but differs in V domain, transmembrane, and cytoplasmic regions. Subcellular localization experiments showed the bulk of TAPASIN-R resides in the ER, with some cell-surface expression detected by biotinylation.\",\n      \"method\": \"Genomic/sequence analysis, subcellular localization by fractionation and biotinylation experiments\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, direct localization experiment with functional context; confirms ER residency of related protein and establishes TAPBP's role in TAP-MHC I linkage as background\",\n      \"pmids\": [\"11920573\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Crystal structures of rat MHC class Ia molecules (RT1-Aa and RT1-A1c) revealed the molecular basis of peptide-MHC assembly and how tapasin participates in the MHC class I peptide-loading complex in the ER, with the structures showing how peptide C-termini match the F-pocket chemistry and providing structural context for tapasin-associated loading.\",\n      \"method\": \"X-ray crystallography of MHC class Ia molecules, biochemical analysis of peptide-MHC assembly rates\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structures of MHC partners, tapasin mentioned as component of loading complex but not directly studied structurally in this paper; single study\",\n      \"pmids\": [\"12470953\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Disruption of TAPBP (tapasin) in human embryonic stem cells (hESCs) using TALEN-mediated genome editing resulted in deficient MHC class I expression on the cell surface and reduced immunogenicity, while pluripotency, karyotype, and differentiation ability were maintained. This experimentally established that TAPBP is required for normal MHC class I surface expression.\",\n      \"method\": \"TALEN-mediated gene knockout in hESCs, flow cytometry for MHC class I surface expression, pluripotency and differentiation assays\",\n      \"journal\": \"Bioscience, biotechnology, and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype (loss of MHC class I surface expression), single lab with multiple orthogonal readouts\",\n      \"pmids\": [\"27068360\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A risk SNP rs1059288 (A>G) in the 3' UTR of TAPBP increases m6A modification of TAPBP mRNA, facilitated by the m6A methyltransferase METTL14 and reader protein YTHDF2. Upregulation of TAPBP promoted cervical cancer cell growth, migration, tumor-forming ability, and chemotherapy resistance, and knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway while upregulating immune genes including HLA-A.\",\n      \"method\": \"MeRIP-seq, RNA-seq, TCGA/JENGER database analysis, case-control study, immunohistochemistry, siRNA knockdown, overexpression assays, pathway analysis\",\n      \"journal\": \"Archives of toxicology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, pathway placement inferred from knockdown with multiple readouts but no direct biochemical reconstitution of TAPBP in JAK/STAT pathway; m6A mechanism supported by correlation not direct enzymatic reconstitution\",\n      \"pmids\": [\"38992170\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAPBP (tapasin) is an immunoglobulin superfamily transmembrane protein that resides in the endoplasmic reticulum where it bridges MHC class I molecules to the TAP peptide transporter within the peptide-loading complex, and is required for normal MHC class I surface expression as demonstrated by TAPBP knockout leading to deficient MHC class I display on human cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TAPBP (tapasin) is a V-C1 immunoglobulin superfamily molecule of the endoplasmic reticulum that links MHC class I molecules to the transporter associated with antigen processing (TAP) within the peptide-loading complex [#0]. Consistent with this bridging role, TALEN-mediated disruption of TAPBP in human embryonic stem cells abolishes normal MHC class I surface expression and reduces immunogenicity without perturbing pluripotency, karyotype, or differentiation, establishing TAPBP as required for MHC class I display [#2]. Beyond its function in antigen presentation, no further direct mechanistic detail on the tapasin protein has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established the molecular role of tapasin by placing it as the bridge linking MHC class I to the TAP transporter in the ER, defining its position in the peptide-loading machinery.\",\n      \"evidence\": \"Genomic/sequence analysis with subcellular localization by fractionation and biotinylation\",\n      \"pmids\": [\"11920573\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Bridging activity inferred from sequence/localization context, not from direct reconstitution of the TAP-MHC I interaction\",\n        \"Localization data shown directly for the related TAPASIN-R, not exhaustively for tapasin itself\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Provided structural context for how peptide-MHC assembly occurs within the tapasin-associated loading complex, clarifying the chemistry that tapasin-assisted loading must satisfy.\",\n      \"evidence\": \"X-ray crystallography of rat MHC class Ia molecules and peptide-MHC assembly analysis\",\n      \"pmids\": [\"12470953\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Tapasin was not directly studied structurally; only its MHC partners were crystallized\",\n        \"No structure of tapasin bound to MHC class I or TAP\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrated causally that TAPBP is required for MHC class I surface expression by loss-of-function, moving its role from inferred to experimentally established in human cells.\",\n      \"evidence\": \"TALEN-mediated knockout in human embryonic stem cells with flow cytometry and pluripotency/differentiation assays\",\n      \"pmids\": [\"27068360\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phenotype defined at the level of surface MHC class I, without dissection of which loading-complex step fails\",\n        \"Single cell type; no rescue with point mutants to map functional residues\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linked TAPBP expression regulation to m6A modification and explored a downstream signaling role in cancer, expanding context beyond antigen loading.\",\n      \"evidence\": \"MeRIP-seq, RNA-seq, case-control and database analysis, siRNA knockdown and overexpression in cervical cancer cells\",\n      \"pmids\": [\"38992170\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Pathway placement in JAK/STAT/MICB inferred from knockdown readouts without direct biochemical reconstitution\",\n        \"m6A mechanism supported by correlation rather than direct enzymatic reconstitution\",\n        \"Causal contribution of the 3' UTR SNP to tumor phenotype not established by editing\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How tapasin mechanistically catalyzes or stabilizes peptide editing within the loading complex, and the structural basis of its MHC class I and TAP contacts, remain unresolved in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct structure of tapasin with its binding partners in the timeline\",\n        \"No reconstitution defining tapasin's peptide-editing activity\",\n        \"Functional residues required for MHC class I support not mapped\"\n      ]\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-168256\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"MHC class I peptide-loading complex\"],\n    \"partners\": [\"TAP\", \"MHC class I\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":2,"faith_total":2,"faith_pct":100.0}}