{"gene":"PTGFRN","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2000,"finding":"PTGFRN (FPRP) associates specifically with CD81 and CD9 tetraspanins at very high stoichiometry (essentially 100% of cell-surface FPRP is CD81/CD9-associated), forming discrete complexes distinct from integrin-containing CD81 complexes, as determined by immunoprecipitation, immunodepletion, and gel permeation chromatography.","method":"Co-immunoprecipitation, immunodepletion, gel permeation chromatography, methyl-β-cyclodextrin cholesterol disruption","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP and immunodepletion with orthogonal sizing experiments, replicated across multiple cell types","pmids":["11087758"],"is_preprint":false},{"year":1996,"finding":"PTGFRN (FPRP) expressed in COS cells inhibits [3H]PGF2α binding to the FP receptor in a dose-dependent, non-competitive manner (decreasing receptor number rather than affinity), demonstrating its role as a negative regulator of prostaglandin F2α receptor activity.","method":"cDNA transfection in COS cells, radioligand binding assay, Scatchard analysis, molecular dissection of FPRP protein domains","journal":"Prostaglandins, leukotrienes, and essential fatty acids","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional in-cell assay with Scatchard analysis and domain dissection, single lab","pmids":["8804121"],"is_preprint":false},{"year":2006,"finding":"PTGFRN (EWI-F) directly interacts with ezrin-radixin-moesin (ERM) proteins through a stretch of basic charged amino acids in its cytoplasmic domain, linking tetraspanin-associated microdomains to the actin cytoskeleton; this interaction regulates cell motility and polarity.","method":"Co-immunoprecipitation, GST pulldown with cytoplasmic domain fusion proteins, confocal microscopy colocalization, dominant-negative moesin N-terminal domain expression, siRNA knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct in vitro binding reconstituted with GST fusion proteins plus co-IP in vivo, functional validation by dominant-negative and siRNA, multiple orthogonal methods","pmids":["16690612"],"is_preprint":false},{"year":2009,"finding":"PTGFRN (CD9P-1) acts as a negative regulator of Plasmodium yoelii sporozoite infection of hepatocytes by interacting with CD81 through their transmembrane regions; CD9P-1 chimeras that no longer associate with CD81 lose this inhibitory effect.","method":"siRNA knockdown, overexpression, chimeric molecule analysis, infection assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional epistasis using chimeric molecules and knockdown/overexpression, single lab","pmids":["19762465"],"is_preprint":false},{"year":2009,"finding":"PTGFRN (CD9P-1) forms cis-oligomers at the cell surface independently of its association with tetraspanins CD9 or CD81; tetraspanin expression levels positively modulate the efficiency of CD9P-1 oligomerization.","method":"In situ chemical cross-linking on living cells, affinity purification, LC-MS/MS, western blot with differential tags","journal":"Journal of proteomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cross-linking proteomics plus Western blot with differential tags, single lab","pmids":["19703604"],"is_preprint":false},{"year":2007,"finding":"PTGFRN (CD9P-1) is targeted into exosomes and remains associated with CD81 in exosomes after TPA treatment; CD9P-1 can be targeted to exosomes independently of CD81 and CD9.","method":"TPA treatment of K562 cells, exosome isolation, co-immunoprecipitation, surface labeling and internalization assays","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct fractionation and co-IP in exosomes, single lab with multiple conditions tested","pmids":["17407154"],"is_preprint":false},{"year":2007,"finding":"PTGFRN (CD9P-1) carries at least 9 engaged N-glycosylation sites bearing more than 40 different N-glycan structures (complex and high-mannose type), and exists as at least 17 glycosylated isoforms at the cell surface, all of which associate with CD9.","method":"PNGase F deglycosylation, FTICR-MS, MALDI-TOF MS, ESI-MS/MS, GC-MS, 2D-PAGE, lectin blot","journal":"Proteomics","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — multiple MS-based structural characterization methods, single lab","pmids":["17960739"],"is_preprint":false},{"year":2011,"finding":"IFITM5 expression causes CD9 to dissociate from a FKBP11-CD81-[FPRP/CD9] complex, and this dissociation leads to increased expression of interferon-induced genes in osteoblasts.","method":"Co-immunoprecipitation, expression analysis of interferon-induced genes after complex perturbation","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP experiment with expression readout, single lab","pmids":["21600883"],"is_preprint":false},{"year":2011,"finding":"A truncated form of PTGFRN (GS-168AT2) corresponding to the region by which CD9P-1 physiologically associates with CD81 depletes CD151, CD9, and CD9P-1 from the endothelial cell surface, inhibiting VEGF-dependent angiogenesis, cell migration, and proliferation in vitro and tumor-associated angiogenesis in vivo.","method":"Co-precipitation, flow cytometry, in vitro angiogenesis/migration/proliferation assays, in vivo tumor xenograft model","journal":"British journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-precipitation plus multiple functional assays in vitro and in vivo, single lab","pmids":["21863033"],"is_preprint":false},{"year":2020,"finding":"Cryo-EM structure of CD9 in complex with EWI-F (PTGFRN) reveals a tetrameric arrangement: two central EWI-F molecules dimerized through their ectodomains, and two CD9 molecules each bound to one EWI-F transmembrane helix via CD9 helices h3 and h4, with a flexible ~50° range of conformational arrangements providing a 'concatenation model' for tetraspanin-enriched microdomain formation.","method":"Cryo-EM structure determination, crystal structures of CD9 large extracellular loop bound to nanobodies","journal":"Life science alliance","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure with crystallographic validation, defines precise molecular interface","pmids":["32958604"],"is_preprint":false},{"year":2019,"finding":"PTGFRN inhibition in GBM cells reduces PI3K p110β protein stability and decreases phosphorylated AKT levels, and also decreases nuclear p110β leading to reduced DNA damage sensing and repair.","method":"shRNA knockdown, western blot for p110β and p-AKT, nuclear fractionation, DNA damage repair assays","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockdown with multiple pathway readouts, single lab","pmids":["31377205"],"is_preprint":false},{"year":2022,"finding":"PTGFRN silencing in glioma cells reduces ERK, AKT, and mTOR signaling; also reduces stemness transcription factors (Olig2, Pou3f2, Sall2, Sox2) in glioma stem-like cells.","method":"shRNA stable knockdown, western blot for signaling pathway components, neurosphere and limiting dilution assays","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — stable knockdown with multiple pathway readouts, single lab","pmids":["35690717"],"is_preprint":false},{"year":2024,"finding":"PTGFRN directly binds Integrin β1 and E-Cadherin (identified as a novel direct binding partner), and PTGFRN knockdown impacts autophagy in cancer cells.","method":"Co-immunoprecipitation, shRNA knockdown, cDNA overexpression, autophagy assays","journal":"Journal of cellular biochemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP experiment per partner, single lab, limited mechanistic follow-up","pmids":["38924562"],"is_preprint":false},{"year":2024,"finding":"PTGFRN co-immunoprecipitates with proteins involved in VEGF signaling and protein processing/metabolism in A431 cells; PTGFRN knockdown increases innate immune response pathways and decreases metabolic precursor synthesis and protein processing pathways.","method":"Co-immunoprecipitation followed by mass spectrometry (proteomics), shRNA knockdown with proteomic profiling","journal":"ACS omega","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP/MS experiment without validation of specific interactions, single lab","pmids":["38559916"],"is_preprint":false},{"year":2025,"finding":"PTGFRN interacts with STAT3 and inhibits its degradation; accumulation of STAT3 enhances its binding to the BCAT1 gene promoter, boosting BCAT1 expression and branched-chain amino acid metabolism in non-small cell lung cancer cells.","method":"Co-immunoprecipitation, siRNA knockdown, chromatin immunoprecipitation (STAT3 binding to BCAT1 promoter), metabolic assays, western blot","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus ChIP plus metabolic readout, single lab, multiple orthogonal methods","pmids":["41130302"],"is_preprint":false}],"current_model":"PTGFRN is a transmembrane Ig-superfamily protein that functions as a highly stoichiometric partner of tetraspanins CD9 and CD81, directly binding CD81 via transmembrane interactions and forming flexible heterotetrameric complexes (as resolved by cryo-EM) that organize tetraspanin-enriched microdomains; through its cytoplasmic basic-charge domain it directly recruits ERM proteins to link these microdomains to the actin cytoskeleton, regulating cell polarity and migration; it negatively regulates prostaglandin F2α receptor (FP) activity by reducing receptor number; it modulates the PI3K p110β/AKT and ERK/mTOR survival pathways, interacts with STAT3 to prevent its degradation and thereby upregulate BCAT1-driven branched-chain amino acid metabolism, and binds Integrin β1 and E-Cadherin, collectively positioning PTGFRN as a signaling scaffold that coordinates membrane organization, cytoskeletal dynamics, and oncogenic signaling."},"narrative":{"mechanistic_narrative":"PTGFRN is a transmembrane Ig-superfamily protein that serves as a near-stoichiometric organizing partner of the tetraspanins CD9 and CD81, with essentially all cell-surface PTGFRN found in discrete CD81/CD9-associated complexes distinct from integrin-containing tetraspanin assemblies [PMID:11087758]. Cryo-EM resolves the structural basis of this organization: two PTGFRN molecules dimerize through their ectodomains while each engages a CD9 transmembrane helix, generating a conformationally flexible heterotetramer that provides a concatenation model for tetraspanin-enriched microdomain formation [PMID:32958604]. Through a stretch of basic residues in its cytoplasmic domain, PTGFRN directly recruits ERM (ezrin-radixin-moesin) proteins, linking these microdomains to the actin cytoskeleton and governing cell motility and polarity [PMID:16690612]. PTGFRN can also self-associate into tetraspanin-independent cis-oligomers and is heavily N-glycosylated across multiple surface isoforms [PMID:19703604, PMID:17960739]. Functionally, it acts as a negative regulator of the prostaglandin F2α (FP) receptor by reducing receptor number in a non-competitive manner [PMID:8804121]. In cancer, PTGFRN supports oncogenic signaling: its loss destabilizes PI3K p110β and lowers AKT phosphorylation [PMID:31377205], reduces ERK/AKT/mTOR signaling and stemness factors in glioma [PMID:35690717], and stabilizes STAT3 to drive BCAT1-dependent branched-chain amino acid metabolism in lung cancer [PMID:41130302]. Truncated PTGFRN that retains CD81-binding depletes tetraspanins and PTGFRN from the endothelial surface and inhibits VEGF-dependent angiogenesis and tumor growth [PMID:21863033].","teleology":[{"year":1996,"claim":"Established the first functional role for PTGFRN by showing it suppresses prostaglandin F2α receptor signaling, defining it as a receptor-modulating membrane protein rather than a passive surface antigen.","evidence":"cDNA transfection in COS cells with radioligand binding and Scatchard analysis of FP receptor","pmids":["8804121"],"confidence":"Medium","gaps":["Mechanism by which PTGFRN reduces FP receptor number is undefined","No structural or interaction data linking PTGFRN to the FP receptor","Single lab"]},{"year":2000,"claim":"Resolved which surface complexes PTGFRN occupies, showing it is an obligate, high-stoichiometry partner of CD9/CD81 in complexes separable from integrin-tetraspanin assemblies.","evidence":"Co-IP, immunodepletion, and gel permeation chromatography across multiple cell types","pmids":["11087758"],"confidence":"High","gaps":["Did not define the molecular interface","Functional consequence of the association not tested"]},{"year":2006,"claim":"Connected the tetraspanin microdomain to the cytoskeleton by demonstrating PTGFRN directly recruits ERM proteins through a basic cytoplasmic motif, providing a mechanistic basis for its role in motility and polarity.","evidence":"GST pulldown with cytoplasmic fusion proteins, co-IP, confocal colocalization, dominant-negative moesin and siRNA","pmids":["16690612"],"confidence":"High","gaps":["Quantitative contribution to actin linkage versus other ERM recruiters unknown","Regulation of the ERM interaction not addressed"]},{"year":2007,"claim":"Characterized PTGFRN as extensively N-glycosylated and exosome-targeted, indicating post-translational diversity and a route into secreted vesicles partly independent of tetraspanins.","evidence":"MS-based glycan structural analysis and exosome fractionation with co-IP after TPA treatment","pmids":["17960739","17407154"],"confidence":"Medium","gaps":["Functional role of specific glycoforms not tested","Determinants of exosomal sorting unresolved"]},{"year":2009,"claim":"Mapped the CD81 interaction to transmembrane regions and revealed tetraspanin-independent cis-oligomerization, refining how PTGFRN assembles within and beyond the tetraspanin web.","evidence":"Chimeric molecule analysis with infection assays; in situ cross-linking with LC-MS/MS","pmids":["19762465","19703604"],"confidence":"Medium","gaps":["Stoichiometry of oligomers not defined at the time","Link between Plasmodium restriction and oligomerization unexplored"]},{"year":2011,"claim":"Demonstrated therapeutic-relevant disruption: a CD81-binding truncated PTGFRN depletes tetraspanins from endothelium and blocks angiogenesis, implicating the complex in vascular and tumor biology.","evidence":"Co-precipitation, flow cytometry, in vitro angiogenesis assays, and in vivo tumor xenografts","pmids":["21863033"],"confidence":"Medium","gaps":["Direct signaling pathway downstream of complex depletion not defined","IFITM5-induced CD9 dissociation finding rests on a single co-IP"]},{"year":2020,"claim":"Provided the atomic-level model for tetraspanin microdomain assembly, showing PTGFRN ectodomain dimers bridge two CD9 molecules in a flexible tetramer that can concatenate.","evidence":"Cryo-EM of the CD9–EWI-F complex with crystallographic validation of CD9 loop–nanobody binding","pmids":["32958604"],"confidence":"High","gaps":["Structure with CD81 not determined","Cytoplasmic ERM-binding region not resolved in the structure"]},{"year":2025,"claim":"Extended PTGFRN into oncogenic signaling, showing it stabilizes signaling effectors (p110β, STAT3) and drives downstream pathways including BCAT1-mediated amino acid metabolism, ERK/AKT/mTOR, and stemness programs.","evidence":"shRNA/siRNA knockdown with western blot, nuclear fractionation, ChIP of STAT3 on BCAT1 promoter, and metabolic assays across GBM, glioma, and NSCLC models","pmids":["31377205","35690717","41130302"],"confidence":"Medium","gaps":["Direct biochemical mechanism linking surface PTGFRN to intracellular p110β/STAT3 stabilization unclear","Whether these effects depend on tetraspanin association untested","Each readout from a single lab"]},{"year":null,"claim":"How PTGFRN's structurally defined membrane-organizing role mechanistically connects to its reported intracellular signaling effects (p110β, STAT3, ERK/mTOR) and to direct binding of Integrin β1/E-Cadherin remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["Integrin β1 and E-Cadherin binding rest on single unreciprocated co-IPs","No mechanism links transmembrane scaffolding to cytoplasmic signaling stabilization","Autophagy and innate-immune effects defined only by proteomic profiling"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,9]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,4,6]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[5]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,10,11]},{"term_id":"R-HSA-1500931","term_label":"Cell-Cell communication","supporting_discovery_ids":[0,9]}],"complexes":["CD9/CD81 tetraspanin-enriched microdomain","CD9–EWI-F (PTGFRN) heterotetramer"],"partners":["CD81","CD9","EZR","STAT3","PIK3CB","ITGB1","CDH1","CD151"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9P2B2","full_name":"Prostaglandin F2 receptor negative regulator","aliases":["CD9 partner 1","CD9P-1","Glu-Trp-Ile EWI motif-containing protein F","EWI-F","Prostaglandin F2-alpha receptor regulatory protein","Prostaglandin F2-alpha receptor-associated protein"],"length_aa":879,"mass_kda":98.6,"function":"Inhibits the binding of prostaglandin F2-alpha (PGF2-alpha) to its specific FP receptor, by decreasing the receptor number rather than the affinity constant. Functional coupling with the prostaglandin F2-alpha receptor seems to occur (By similarity). In myoblasts, associates with tetraspanins CD9 and CD81 to prevent myotube fusion during muscle regeneration (By similarity)","subcellular_location":"Endoplasmic reticulum membrane; Golgi apparatus, trans-Golgi network membrane","url":"https://www.uniprot.org/uniprotkb/Q9P2B2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PTGFRN","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CD81","stoichiometry":0.2},{"gene":"CD9","stoichiometry":0.2},{"gene":"SLC25A17","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PTGFRN","total_profiled":1310},"omim":[{"mim_id":"612875","title":"GONADOTROPIN-RELEASING HORMONE RECEPTOR 2; GNRHR2","url":"https://www.omim.org/entry/612875"},{"mim_id":"601204","title":"PROSTAGLANDIN F2 RECEPTOR NEGATIVE REGULATOR; PTGFRN","url":"https://www.omim.org/entry/601204"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PTGFRN"},"hgnc":{"alias_symbol":["FPRP","EWI-F","CD9P-1","FLJ11001","KIAA1436","SMAP-6","CD315"],"prev_symbol":[]},"alphafold":{"accession":"Q9P2B2","domains":[{"cath_id":"2.60.40.10","chopping":"21-142","consensus_level":"high","plddt":93.4602,"start":21,"end":142},{"cath_id":"2.60.40.10","chopping":"147-276","consensus_level":"high","plddt":90.7534,"start":147,"end":276},{"cath_id":"2.60.40.10","chopping":"280-401","consensus_level":"high","plddt":86.393,"start":280,"end":401},{"cath_id":"2.60.40.10","chopping":"410-542","consensus_level":"high","plddt":83.9335,"start":410,"end":542},{"cath_id":"2.60.40.10","chopping":"550-682","consensus_level":"high","plddt":80.9204,"start":550,"end":682},{"cath_id":"2.60.40.10","chopping":"690-826","consensus_level":"high","plddt":86.5188,"start":690,"end":826}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2B2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2B2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2B2-F1-predicted_aligned_error_v6.png","plddt_mean":84.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PTGFRN","jax_strain_url":"https://www.jax.org/strain/search?query=PTGFRN"},"sequence":{"accession":"Q9P2B2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9P2B2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9P2B2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2B2"}},"corpus_meta":[{"pmid":"16690612","id":"PMC_16690612","title":"EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16690612","citation_count":165,"is_preprint":false},{"pmid":"11087758","id":"PMC_11087758","title":"FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11087758","citation_count":118,"is_preprint":false},{"pmid":"21600883","id":"PMC_21600883","title":"Osteoblast-enriched membrane protein IFITM5 regulates the association of CD9 with an FKBP11-CD81-FPRP complex and stimulates expression of interferon-induced genes.","date":"2011","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/21600883","citation_count":40,"is_preprint":false},{"pmid":"17407154","id":"PMC_17407154","title":"The transferrin receptor and the tetraspanin web molecules CD9, CD81, and CD9P-1 are differentially sorted into exosomes after TPA treatment of K562 cells.","date":"2007","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17407154","citation_count":37,"is_preprint":false},{"pmid":"32958604","id":"PMC_32958604","title":"Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F.","date":"2020","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/32958604","citation_count":31,"is_preprint":false},{"pmid":"31377205","id":"PMC_31377205","title":"The Ig superfamily protein PTGFRN coordinates survival signaling in glioblastoma multiforme.","date":"2019","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/31377205","citation_count":28,"is_preprint":false},{"pmid":"35690717","id":"PMC_35690717","title":"Integrative analysis of cell adhesion molecules in glioblastoma identified prostaglandin F2 receptor inhibitor (PTGFRN) as an essential gene.","date":"2022","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/35690717","citation_count":27,"is_preprint":false},{"pmid":"8804121","id":"PMC_8804121","title":"Negative regulatory activity of a prostaglandin F2 alpha receptor associated protein (FPRP).","date":"1996","source":"Prostaglandins, leukotrienes, and essential fatty acids","url":"https://pubmed.ncbi.nlm.nih.gov/8804121","citation_count":27,"is_preprint":false},{"pmid":"19762465","id":"PMC_19762465","title":"The Ig domain protein CD9P-1 down-regulates CD81 ability to support Plasmodium yoelii infection.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19762465","citation_count":20,"is_preprint":false},{"pmid":"21863033","id":"PMC_21863033","title":"A truncated form of CD9-partner 1 (CD9P-1), GS-168AT2, potently inhibits in vivo tumour-induced angiogenesis and tumour growth.","date":"2011","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/21863033","citation_count":20,"is_preprint":false},{"pmid":"21206492","id":"PMC_21206492","title":"CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth.","date":"2011","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/21206492","citation_count":18,"is_preprint":false},{"pmid":"17960739","id":"PMC_17960739","title":"Glycosylation status of the membrane protein CD9P-1.","date":"2007","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/17960739","citation_count":16,"is_preprint":false},{"pmid":"19703604","id":"PMC_19703604","title":"In situ chemical cross-linking on living cells reveals CD9P-1 cis-oligomer at cell surface.","date":"2009","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/19703604","citation_count":16,"is_preprint":false},{"pmid":"27265091","id":"PMC_27265091","title":"The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27265091","citation_count":15,"is_preprint":false},{"pmid":"26629098","id":"PMC_26629098","title":"The MIF -173G/C gene polymorphism increase gastrointestinal cancer and hematological malignancy risk: evidence from a meta-analysis and FPRP test.","date":"2015","source":"International journal of clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26629098","citation_count":11,"is_preprint":false},{"pmid":"27472712","id":"PMC_27472712","title":"The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility: A meta-analysis including FPRP test of 8710 participants.","date":"2016","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/27472712","citation_count":9,"is_preprint":false},{"pmid":"38559916","id":"PMC_38559916","title":"Effect of PTFGRN Expression on the Proteomic Profile of A431 Cells and Determination of the PTGFRN Interactome.","date":"2024","source":"ACS omega","url":"https://pubmed.ncbi.nlm.nih.gov/38559916","citation_count":9,"is_preprint":false},{"pmid":"33503070","id":"PMC_33503070","title":"Identification of Prostaglandin F2 Receptor Negative Regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development.","date":"2021","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/33503070","citation_count":7,"is_preprint":false},{"pmid":"38924562","id":"PMC_38924562","title":"Prostaglandin F2 Receptor Negative Regulator (PTGFRN) Expression Correlates With a Metastatic-like Phenotype in Epidermoid Carcinoma, Pediatric Medulloblastoma, and Mesothelioma.","date":"2024","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38924562","citation_count":5,"is_preprint":false},{"pmid":"41130302","id":"PMC_41130302","title":"PTGFRN promotes non-small cell lung cancer malignant progression and reprograms BCAA metabolism by activating STAT3/BCAT1 pathway.","date":"2025","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41130302","citation_count":2,"is_preprint":false},{"pmid":"40551322","id":"PMC_40551322","title":"8C7: A Fully Human Anti-PTGFRN Monoclonal Antibody-Drug Conjugate Inhibiting Tumour Growth of Mesothelioma and Paediatric Medulloblastoma Cell Lines.","date":"2025","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40551322","citation_count":1,"is_preprint":false},{"pmid":"41748870","id":"PMC_41748870","title":"Pan-cancer analysis reveals the oncogenic and immunomodulatory roles of PTGFRN across human cancers.","date":"2026","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41748870","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13738,"output_tokens":3373,"usd":0.045905,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10972,"output_tokens":3329,"usd":0.069043,"stage2_stop_reason":"end_turn"},"total_usd":0.114948,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"PTGFRN (FPRP) associates specifically with CD81 and CD9 tetraspanins at very high stoichiometry (essentially 100% of cell-surface FPRP is CD81/CD9-associated), forming discrete complexes distinct from integrin-containing CD81 complexes, as determined by immunoprecipitation, immunodepletion, and gel permeation chromatography.\",\n      \"method\": \"Co-immunoprecipitation, immunodepletion, gel permeation chromatography, methyl-β-cyclodextrin cholesterol disruption\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP and immunodepletion with orthogonal sizing experiments, replicated across multiple cell types\",\n      \"pmids\": [\"11087758\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"PTGFRN (FPRP) expressed in COS cells inhibits [3H]PGF2α binding to the FP receptor in a dose-dependent, non-competitive manner (decreasing receptor number rather than affinity), demonstrating its role as a negative regulator of prostaglandin F2α receptor activity.\",\n      \"method\": \"cDNA transfection in COS cells, radioligand binding assay, Scatchard analysis, molecular dissection of FPRP protein domains\",\n      \"journal\": \"Prostaglandins, leukotrienes, and essential fatty acids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional in-cell assay with Scatchard analysis and domain dissection, single lab\",\n      \"pmids\": [\"8804121\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"PTGFRN (EWI-F) directly interacts with ezrin-radixin-moesin (ERM) proteins through a stretch of basic charged amino acids in its cytoplasmic domain, linking tetraspanin-associated microdomains to the actin cytoskeleton; this interaction regulates cell motility and polarity.\",\n      \"method\": \"Co-immunoprecipitation, GST pulldown with cytoplasmic domain fusion proteins, confocal microscopy colocalization, dominant-negative moesin N-terminal domain expression, siRNA knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct in vitro binding reconstituted with GST fusion proteins plus co-IP in vivo, functional validation by dominant-negative and siRNA, multiple orthogonal methods\",\n      \"pmids\": [\"16690612\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PTGFRN (CD9P-1) acts as a negative regulator of Plasmodium yoelii sporozoite infection of hepatocytes by interacting with CD81 through their transmembrane regions; CD9P-1 chimeras that no longer associate with CD81 lose this inhibitory effect.\",\n      \"method\": \"siRNA knockdown, overexpression, chimeric molecule analysis, infection assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional epistasis using chimeric molecules and knockdown/overexpression, single lab\",\n      \"pmids\": [\"19762465\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PTGFRN (CD9P-1) forms cis-oligomers at the cell surface independently of its association with tetraspanins CD9 or CD81; tetraspanin expression levels positively modulate the efficiency of CD9P-1 oligomerization.\",\n      \"method\": \"In situ chemical cross-linking on living cells, affinity purification, LC-MS/MS, western blot with differential tags\",\n      \"journal\": \"Journal of proteomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cross-linking proteomics plus Western blot with differential tags, single lab\",\n      \"pmids\": [\"19703604\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"PTGFRN (CD9P-1) is targeted into exosomes and remains associated with CD81 in exosomes after TPA treatment; CD9P-1 can be targeted to exosomes independently of CD81 and CD9.\",\n      \"method\": \"TPA treatment of K562 cells, exosome isolation, co-immunoprecipitation, surface labeling and internalization assays\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct fractionation and co-IP in exosomes, single lab with multiple conditions tested\",\n      \"pmids\": [\"17407154\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"PTGFRN (CD9P-1) carries at least 9 engaged N-glycosylation sites bearing more than 40 different N-glycan structures (complex and high-mannose type), and exists as at least 17 glycosylated isoforms at the cell surface, all of which associate with CD9.\",\n      \"method\": \"PNGase F deglycosylation, FTICR-MS, MALDI-TOF MS, ESI-MS/MS, GC-MS, 2D-PAGE, lectin blot\",\n      \"journal\": \"Proteomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple MS-based structural characterization methods, single lab\",\n      \"pmids\": [\"17960739\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"IFITM5 expression causes CD9 to dissociate from a FKBP11-CD81-[FPRP/CD9] complex, and this dissociation leads to increased expression of interferon-induced genes in osteoblasts.\",\n      \"method\": \"Co-immunoprecipitation, expression analysis of interferon-induced genes after complex perturbation\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP experiment with expression readout, single lab\",\n      \"pmids\": [\"21600883\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"A truncated form of PTGFRN (GS-168AT2) corresponding to the region by which CD9P-1 physiologically associates with CD81 depletes CD151, CD9, and CD9P-1 from the endothelial cell surface, inhibiting VEGF-dependent angiogenesis, cell migration, and proliferation in vitro and tumor-associated angiogenesis in vivo.\",\n      \"method\": \"Co-precipitation, flow cytometry, in vitro angiogenesis/migration/proliferation assays, in vivo tumor xenograft model\",\n      \"journal\": \"British journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-precipitation plus multiple functional assays in vitro and in vivo, single lab\",\n      \"pmids\": [\"21863033\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Cryo-EM structure of CD9 in complex with EWI-F (PTGFRN) reveals a tetrameric arrangement: two central EWI-F molecules dimerized through their ectodomains, and two CD9 molecules each bound to one EWI-F transmembrane helix via CD9 helices h3 and h4, with a flexible ~50° range of conformational arrangements providing a 'concatenation model' for tetraspanin-enriched microdomain formation.\",\n      \"method\": \"Cryo-EM structure determination, crystal structures of CD9 large extracellular loop bound to nanobodies\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure with crystallographic validation, defines precise molecular interface\",\n      \"pmids\": [\"32958604\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PTGFRN inhibition in GBM cells reduces PI3K p110β protein stability and decreases phosphorylated AKT levels, and also decreases nuclear p110β leading to reduced DNA damage sensing and repair.\",\n      \"method\": \"shRNA knockdown, western blot for p110β and p-AKT, nuclear fractionation, DNA damage repair assays\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockdown with multiple pathway readouts, single lab\",\n      \"pmids\": [\"31377205\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PTGFRN silencing in glioma cells reduces ERK, AKT, and mTOR signaling; also reduces stemness transcription factors (Olig2, Pou3f2, Sall2, Sox2) in glioma stem-like cells.\",\n      \"method\": \"shRNA stable knockdown, western blot for signaling pathway components, neurosphere and limiting dilution assays\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — stable knockdown with multiple pathway readouts, single lab\",\n      \"pmids\": [\"35690717\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PTGFRN directly binds Integrin β1 and E-Cadherin (identified as a novel direct binding partner), and PTGFRN knockdown impacts autophagy in cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, shRNA knockdown, cDNA overexpression, autophagy assays\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP experiment per partner, single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"38924562\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PTGFRN co-immunoprecipitates with proteins involved in VEGF signaling and protein processing/metabolism in A431 cells; PTGFRN knockdown increases innate immune response pathways and decreases metabolic precursor synthesis and protein processing pathways.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry (proteomics), shRNA knockdown with proteomic profiling\",\n      \"journal\": \"ACS omega\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP/MS experiment without validation of specific interactions, single lab\",\n      \"pmids\": [\"38559916\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PTGFRN interacts with STAT3 and inhibits its degradation; accumulation of STAT3 enhances its binding to the BCAT1 gene promoter, boosting BCAT1 expression and branched-chain amino acid metabolism in non-small cell lung cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, chromatin immunoprecipitation (STAT3 binding to BCAT1 promoter), metabolic assays, western blot\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus ChIP plus metabolic readout, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41130302\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PTGFRN is a transmembrane Ig-superfamily protein that functions as a highly stoichiometric partner of tetraspanins CD9 and CD81, directly binding CD81 via transmembrane interactions and forming flexible heterotetrameric complexes (as resolved by cryo-EM) that organize tetraspanin-enriched microdomains; through its cytoplasmic basic-charge domain it directly recruits ERM proteins to link these microdomains to the actin cytoskeleton, regulating cell polarity and migration; it negatively regulates prostaglandin F2α receptor (FP) activity by reducing receptor number; it modulates the PI3K p110β/AKT and ERK/mTOR survival pathways, interacts with STAT3 to prevent its degradation and thereby upregulate BCAT1-driven branched-chain amino acid metabolism, and binds Integrin β1 and E-Cadherin, collectively positioning PTGFRN as a signaling scaffold that coordinates membrane organization, cytoskeletal dynamics, and oncogenic signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PTGFRN is a transmembrane Ig-superfamily protein that serves as a near-stoichiometric organizing partner of the tetraspanins CD9 and CD81, with essentially all cell-surface PTGFRN found in discrete CD81/CD9-associated complexes distinct from integrin-containing tetraspanin assemblies [#0]. Cryo-EM resolves the structural basis of this organization: two PTGFRN molecules dimerize through their ectodomains while each engages a CD9 transmembrane helix, generating a conformationally flexible heterotetramer that provides a concatenation model for tetraspanin-enriched microdomain formation [#9]. Through a stretch of basic residues in its cytoplasmic domain, PTGFRN directly recruits ERM (ezrin-radixin-moesin) proteins, linking these microdomains to the actin cytoskeleton and governing cell motility and polarity [#2]. PTGFRN can also self-associate into tetraspanin-independent cis-oligomers and is heavily N-glycosylated across multiple surface isoforms [#4, #6]. Functionally, it acts as a negative regulator of the prostaglandin F2\\u03b1 (FP) receptor by reducing receptor number in a non-competitive manner [#1]. In cancer, PTGFRN supports oncogenic signaling: its loss destabilizes PI3K p110\\u03b2 and lowers AKT phosphorylation [#10], reduces ERK/AKT/mTOR signaling and stemness factors in glioma [#11], and stabilizes STAT3 to drive BCAT1-dependent branched-chain amino acid metabolism in lung cancer [#14]. Truncated PTGFRN that retains CD81-binding depletes tetraspanins and PTGFRN from the endothelial surface and inhibits VEGF-dependent angiogenesis and tumor growth [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Established the first functional role for PTGFRN by showing it suppresses prostaglandin F2\\u03b1 receptor signaling, defining it as a receptor-modulating membrane protein rather than a passive surface antigen.\",\n      \"evidence\": \"cDNA transfection in COS cells with radioligand binding and Scatchard analysis of FP receptor\",\n      \"pmids\": [\"8804121\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism by which PTGFRN reduces FP receptor number is undefined\", \"No structural or interaction data linking PTGFRN to the FP receptor\", \"Single lab\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Resolved which surface complexes PTGFRN occupies, showing it is an obligate, high-stoichiometry partner of CD9/CD81 in complexes separable from integrin-tetraspanin assemblies.\",\n      \"evidence\": \"Co-IP, immunodepletion, and gel permeation chromatography across multiple cell types\",\n      \"pmids\": [\"11087758\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Did not define the molecular interface\", \"Functional consequence of the association not tested\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Connected the tetraspanin microdomain to the cytoskeleton by demonstrating PTGFRN directly recruits ERM proteins through a basic cytoplasmic motif, providing a mechanistic basis for its role in motility and polarity.\",\n      \"evidence\": \"GST pulldown with cytoplasmic fusion proteins, co-IP, confocal colocalization, dominant-negative moesin and siRNA\",\n      \"pmids\": [\"16690612\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Quantitative contribution to actin linkage versus other ERM recruiters unknown\", \"Regulation of the ERM interaction not addressed\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Characterized PTGFRN as extensively N-glycosylated and exosome-targeted, indicating post-translational diversity and a route into secreted vesicles partly independent of tetraspanins.\",\n      \"evidence\": \"MS-based glycan structural analysis and exosome fractionation with co-IP after TPA treatment\",\n      \"pmids\": [\"17960739\", \"17407154\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional role of specific glycoforms not tested\", \"Determinants of exosomal sorting unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Mapped the CD81 interaction to transmembrane regions and revealed tetraspanin-independent cis-oligomerization, refining how PTGFRN assembles within and beyond the tetraspanin web.\",\n      \"evidence\": \"Chimeric molecule analysis with infection assays; in situ cross-linking with LC-MS/MS\",\n      \"pmids\": [\"19762465\", \"19703604\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Stoichiometry of oligomers not defined at the time\", \"Link between Plasmodium restriction and oligomerization unexplored\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrated therapeutic-relevant disruption: a CD81-binding truncated PTGFRN depletes tetraspanins from endothelium and blocks angiogenesis, implicating the complex in vascular and tumor biology.\",\n      \"evidence\": \"Co-precipitation, flow cytometry, in vitro angiogenesis assays, and in vivo tumor xenografts\",\n      \"pmids\": [\"21863033\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct signaling pathway downstream of complex depletion not defined\", \"IFITM5-induced CD9 dissociation finding rests on a single co-IP\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Provided the atomic-level model for tetraspanin microdomain assembly, showing PTGFRN ectodomain dimers bridge two CD9 molecules in a flexible tetramer that can concatenate.\",\n      \"evidence\": \"Cryo-EM of the CD9\\u2013EWI-F complex with crystallographic validation of CD9 loop\\u2013nanobody binding\",\n      \"pmids\": [\"32958604\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Structure with CD81 not determined\", \"Cytoplasmic ERM-binding region not resolved in the structure\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended PTGFRN into oncogenic signaling, showing it stabilizes signaling effectors (p110\\u03b2, STAT3) and drives downstream pathways including BCAT1-mediated amino acid metabolism, ERK/AKT/mTOR, and stemness programs.\",\n      \"evidence\": \"shRNA/siRNA knockdown with western blot, nuclear fractionation, ChIP of STAT3 on BCAT1 promoter, and metabolic assays across GBM, glioma, and NSCLC models\",\n      \"pmids\": [\"31377205\", \"35690717\", \"41130302\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct biochemical mechanism linking surface PTGFRN to intracellular p110\\u03b2/STAT3 stabilization unclear\", \"Whether these effects depend on tetraspanin association untested\", \"Each readout from a single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PTGFRN's structurally defined membrane-organizing role mechanistically connects to its reported intracellular signaling effects (p110\\u03b2, STAT3, ERK/mTOR) and to direct binding of Integrin \\u03b21/E-Cadherin remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Integrin \\u03b21 and E-Cadherin binding rest on single unreciprocated co-IPs\", \"No mechanism links transmembrane scaffolding to cytoplasmic signaling stabilization\", \"Autophagy and innate-immune effects defined only by proteomic profiling\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 9]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 4, 6]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 10, 11]},\n      {\"term_id\": \"R-HSA-1500931\", \"supporting_discovery_ids\": [0, 9]}\n    ],\n    \"complexes\": [\"CD9/CD81 tetraspanin-enriched microdomain\", \"CD9\\u2013EWI-F (PTGFRN) heterotetramer\"],\n    \"partners\": [\"CD81\", \"CD9\", \"EZR\", \"STAT3\", \"PIK3CB\", \"ITGB1\", \"CDH1\", \"CD151\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}