{"gene":"SCAMP3","run_date":"2026-06-10T07:46:29","timeline":{"discoveries":[{"year":2009,"finding":"SCAMP3 is multimonoubiquitylated and associates with Nedd4 HECT ubiquitin ligases via its PY motif and with ESCRT-I subunit Tsg101 via its PSAP motif, and also associates with ESCRT-0 subunit Hrs. These interactions negatively regulate EGFR degradation and promote receptor recycling from early endosomes.","method":"Co-immunoprecipitation, inhibitory RNA depletion, overexpression with PY/PSAP/ubiquitylatable-lysine mutants, immunoelectron microscopy of EGFR-containing MVBs","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP, multiple site-directed mutants (PY, PSAP, lysine), RNA depletion with defined phenotypic readout, dual-depletion epistasis, and immuno-EM, all in one study","pmids":["19158374"],"is_preprint":false},{"year":1998,"finding":"SCAMP3 (and SCAMP1) are tyrosine-phosphorylated in an EGF-dependent manner; EGF stimulation induces SCAMP3–EGFR co-immunoprecipitation, and EGFR directly phosphorylates SCAMP3 in vitro, suggesting EGFR is the upstream kinase for SCAMP3 tyrosine phosphorylation.","method":"Co-immunoprecipitation, in vitro kinase assay with recombinant EGFR, vanadate-treatment phosphorylation assays, recombinant phosphatase (PTP1B) dephosphorylation","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase assay with recombinant proteins plus co-IP and cell-based phosphorylation in a single study with multiple orthogonal methods","pmids":["9658162"],"is_preprint":false},{"year":2011,"finding":"SCAMP3 positively regulates biogenesis of multivesicular endosomes (MVBs): it promotes EGF receptor sorting into MVBs and formation of intralumenal vesicles (ILVs) in vitro, thereby controlling EGFR targeting to lysosomes.","method":"Cell-free MVB biogenesis assay (in vitro), SCAMP3 depletion with defined ILV-formation readout, EGF-dependent MVB biogenesis assay","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-free in vitro biogenesis assay plus depletion experiments, single lab","pmids":["21951651"],"is_preprint":false},{"year":2009,"finding":"SCAMP3 accumulates on the trans-Golgi network in uninfected cells and marks Salmonella-induced tubules distinct from late-endosomal SIFs; siRNA screen showed SCAMP3 (and SCAMP2) contribute to maintenance of Salmonella-containing vacuoles in the Golgi region of HeLa cells, implicating SCAMP3 in post-Golgi trafficking dynamics exploited by Salmonella.","method":"siRNA screen, fluorescence microscopy/colocalization in HeLa cells infected with Salmonella","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — siRNA knockdown with defined subcellular localization readout, single lab but replicated across multiple SCAMP family members","pmids":["19438519"],"is_preprint":false},{"year":2021,"finding":"Activated (mutant) EGFR phosphorylates SCAMP3 at Y86, and this phosphorylation increases the interaction of SCAMP3 with both wild-type and mutant EGFRs. Phospho-Y86 is required for SCAMP3's ability to promote EGFR degradation and attenuate MAP kinase signaling; SCAMP3 Y86F mutant fails to rescue the enhanced growth, reduced EGFR degradation, and multinucleation phenotypes caused by SCAMP3 knockdown.","method":"Quantitative mass-spectrometry-based phosphoproteomics, site-directed mutagenesis (Y86F), co-immunoprecipitation, knockdown rescue assays, EGFR degradation assay, xenograft tumor growth","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Strong — phosphoproteomics identification, site-directed mutagenesis with functional rescue, co-IP, in vivo xenograft, multiple orthogonal methods in one study","pmids":["33850265"],"is_preprint":false},{"year":2022,"finding":"SCAMP3 colocalizes with EGFR and redistributes it from the cytoplasm to the perinucleus; SCAMP3 knockout reduces EGFR degradation and attenuates AKT, ERK, and STAT3 signaling in triple-negative breast cancer cells.","method":"EGFR internalization/colocalization assay, SCAMP3 knockout (CRISPR), immunoblot degradation assay, xenograft models","journal":"Cancers","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — internalization assay plus KO with defined signaling readouts, single lab","pmids":["35681787"],"is_preprint":false},{"year":2025,"finding":"SCAMP3 is required for proper formation and content of neutrophil primary, secondary, and tertiary granules; Scamp3 knockout reduces granule protein levels and degranulation in Hoxb8-derived neutrophils in vitro and reduces neutrophil granularity in zebrafish in vivo, impairing E. coli killing.","method":"Scamp3 knockout (Hoxb8 cell-derived neutrophils and zebrafish), mass spectrometry proteomics, Western blot, killing assay, degranulation assay","journal":"Journal of leukocyte biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO in two independent model systems (mammalian cell-derived neutrophils + zebrafish), mass spectrometry, and functional readouts","pmids":["41187789"],"is_preprint":false},{"year":2024,"finding":"SCAMP3 is an insulin secretory granule (ISG)-associated protein; Scamp3 knockdown in INS-1 cells reduces insulin content and causes dysfunctional insulin secretion, establishing a role for SCAMP3 in regulating insulin granule function in pancreatic β-cells.","method":"ISG isolation and mass spectrometry-based proteomics, confocal colocalization in MIN6 and human β-cells, Scamp3 siRNA knockdown in INS-1 cells with insulin content and secretion assays","journal":"Diabetes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomic identification with colocalization validation and knockdown functional assays, single lab","pmids":["39320956"],"is_preprint":false},{"year":2025,"finding":"SCAMP3 recruits the ER membrane lipid transfer protein BLTP2 to ER–MVB membrane contact sites (MCSs) in a Rab5-dependent manner, and this recruitment is inhibited by NEDD4-mediated ubiquitination of SCAMP3. This SCAMP3-dependent ER–MVB contact facilitates BMP/LBPA precursor (phosphatidylglycerol) transfer to MVBs for ILV/exosome formation.","method":"Co-immunoprecipitation, BLTP2 depletion, SCAMP3 depletion, lipidomic analysis of endosomes, Rab5 dependency experiments, ubiquitination assays (NEDD4)","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — co-IP and depletion experiments with lipid and functional readouts, preprint (not yet peer-reviewed), single lab","pmids":["bio_10.1101_2025.04.17.649455"],"is_preprint":true},{"year":2019,"finding":"miR-27a/b-3p suppresses SCAMP3 expression directly; knockdown of PPARG downregulates SCAMP3 at the late phase of adipogenesis; reduction of SCAMP3 mRNA increases PPARG expression at early phase, placing SCAMP3 downstream of PPARG in a feed-forward loop with an anti-adipogenic role.","method":"miRNA overexpression, siRNA knockdown of PPARG and SCAMP3, gene expression analysis during adipocyte differentiation, correlation with adipocyte phenotypes","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — siRNA knockdown with defined gene-expression readouts and functional context in adipogenesis, single lab, no direct binding assay","pmids":["31554889"],"is_preprint":false},{"year":2025,"finding":"SCAMP3 knockout in TNBC cells abolishes residual ERK activity under ERK inhibitor MK-8353, reduces phosphorylation of ERK feedback regulators Raf-1 (S43) and MEK2 (T394), impairs mTORC1 signaling, and disrupts autophagic flux (elevated SQSTM1/p62 and LC3B-II with reduced Rab7A), identifying SCAMP3 as a coordinator of ERK signaling and autophagy.","method":"TMT-based LC-MS/MS phosphoproteomics of SCAMP3 KO vs. WT TNBC cells under basal, EGF-stimulated, and ERK-inhibitor conditions; Western blot validation","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative phosphoproteomics with orthogonal Western blot validation in KO cells, single lab","pmids":["41096842"],"is_preprint":false},{"year":2025,"finding":"SCAMP3 and EPS8 form a protein complex with EGFR and AR-V7 upon EGF stimulation; knockdown of either SCAMP3 or EPS8 reduces EGFR expression and attenuates STAT3, AKT, and ERK signaling, while overexpression increases EGFR levels and downstream signaling, demonstrating cooperative maintenance of EGFR stability.","method":"Co-immunoprecipitation, shRNA knockdown, overexpression (pcDNA vectors), Western blotting, EGF stimulation assays","journal":"Cancer genomics & proteomics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP plus bidirectional gain/loss-of-function with defined signaling readouts, single lab","pmids":["41151858"],"is_preprint":false}],"current_model":"SCAMP3 is a multi-spanning transmembrane protein of post-Golgi vesicles and endosomes that regulates EGFR trafficking by interacting with EGFR (whose kinase phosphorylates SCAMP3 at Y86), undergoing multimonoubiquitylation via Nedd4 HECT ligases, and engaging ESCRT-0 (Hrs) and ESCRT-I (Tsg101) through PY and PSAP motifs to balance EGFR recycling versus lysosomal degradation; it also localizes to ER–MVB membrane contact sites where it recruits BLTP2 in a Rab5-dependent, NEDD4-regulated manner to support intraluminal vesicle and exosome biogenesis, is required for neutrophil granule formation and degranulation, regulates insulin secretory granule content and insulin secretion in β-cells, and participates in a miR-27a/b-3p–PPARG feed-forward loop that controls adipogenesis."},"narrative":{"mechanistic_narrative":"SCAMP3 is a multi-spanning transmembrane protein of the trans-Golgi network and post-Golgi endosomal membranes that governs the sorting decision between recycling and lysosomal degradation of the EGF receptor [PMID:19158374, PMID:19438519]. Activated EGFR co-immunoprecipitates with SCAMP3 and directly phosphorylates it on tyrosine, with Y86 identified as the functional site; phospho-Y86 strengthens the SCAMP3–EGFR interaction and is required for SCAMP3 to drive EGFR degradation and attenuate downstream MAP kinase signaling [PMID:9658162, PMID:33850265]. SCAMP3 couples to the ESCRT machinery, associating with the Nedd4 HECT ubiquitin ligases through its PY motif, with ESCRT-I subunit Tsg101 through its PSAP motif, and with ESCRT-0 subunit Hrs, and is itself multimonoubiquitylated; these interactions tune EGFR recycling from early endosomes against its sorting into intralumenal vesicles of multivesicular bodies and onward delivery to lysosomes [PMID:19158374, PMID:21951651]. In cancer cells SCAMP3 redistributes EGFR to the perinuclear region and cooperates with EPS8 to maintain EGFR stability, with its loss reducing EGFR degradation yet attenuating AKT, ERK, and STAT3 output and disrupting mTORC1 signaling and autophagic flux [PMID:35681787, PMID:41096842, PMID:41151858]. Beyond EGFR trafficking, SCAMP3 is required for regulated secretory and granule biology: it is needed for neutrophil granule formation, content, and degranulation [PMID:41187789], associates with insulin secretory granules to control insulin content and secretion in β-cells [PMID:39320956], and acts as an anti-adipogenic factor downstream of PPARG [PMID:31554889].","teleology":[{"year":1998,"claim":"Established the first molecular link between SCAMP3 and a signaling receptor by showing it is an EGF-responsive phosphoprotein and a direct EGFR substrate, defining EGFR as its upstream kinase.","evidence":"Co-IP, in vitro kinase assay with recombinant EGFR, and vanadate/PTP1B phosphorylation assays","pmids":["9658162"],"confidence":"High","gaps":["Did not map the phosphorylated tyrosine residue","Functional consequence of phosphorylation for trafficking not established"]},{"year":2009,"claim":"Defined how SCAMP3 mechanistically engages the endosomal sorting machinery, showing it links Nedd4 ligases and ESCRT components to bias EGFR toward recycling over degradation.","evidence":"Reciprocal co-IP, PY/PSAP/lysine mutants, RNAi depletion with dual-depletion epistasis, and immuno-EM of EGFR-containing MVBs","pmids":["19158374"],"confidence":"High","gaps":["The specific Nedd4 family member acting in vivo not resolved","Did not establish which ubiquitylated lysines are functionally critical"]},{"year":2009,"claim":"Localized SCAMP3 to the trans-Golgi network and implicated it in post-Golgi trafficking dynamics by showing it maintains Salmonella-containing vacuoles.","evidence":"siRNA screen and fluorescence colocalization in Salmonella-infected HeLa cells","pmids":["19438519"],"confidence":"Medium","gaps":["Mechanism of SCAMP3 contribution to vacuole maintenance unknown","Relationship between TGN pool and endosomal EGFR-sorting pool not defined"]},{"year":2011,"claim":"Resolved an apparent paradox by showing SCAMP3 also positively promotes MVB/ILV biogenesis and EGFR sorting into MVBs, indicating it acts at multiple steps of the degradative pathway.","evidence":"Cell-free MVB biogenesis assay and SCAMP3 depletion with ILV-formation readout","pmids":["21951651"],"confidence":"Medium","gaps":["Molecular determinants on SCAMP3 driving ILV formation not mapped","Single-lab in vitro assay"]},{"year":2021,"claim":"Identified Y86 as the functional phosphosite and tied it causally to EGFR degradation and signaling attenuation, converting the 1998 phosphorylation observation into a defined regulatory mechanism with tumor relevance.","evidence":"Phosphoproteomics, Y86F mutagenesis with knockdown rescue, EGFR degradation assays, and xenograft growth","pmids":["33850265"],"confidence":"High","gaps":["Structural basis for how phospho-Y86 strengthens EGFR binding unknown","Phosphatase that reverses Y86 in cells not identified"]},{"year":2022,"claim":"Confirmed in a cancer-cell context that SCAMP3 controls EGFR subcellular distribution and degradation and shapes AKT/ERK/STAT3 output.","evidence":"EGFR internalization/colocalization assays and CRISPR knockout with signaling readouts and xenograft models in TNBC","pmids":["35681787"],"confidence":"Medium","gaps":["Reconciliation of reduced degradation with attenuated signaling not fully mechanistic","Single lab"]},{"year":2024,"claim":"Extended SCAMP3 function beyond EGFR trafficking to regulated secretion, establishing it as an insulin secretory granule protein required for normal insulin content and secretion.","evidence":"ISG proteomics, confocal colocalization in β-cells, and siRNA knockdown with insulin content/secretion assays","pmids":["39320956"],"confidence":"Medium","gaps":["Molecular mechanism by which SCAMP3 affects granule content unknown","ESCRT/EGFR machinery relevance to ISG biology untested"]},{"year":2025,"claim":"Demonstrated a broad requirement for SCAMP3 in granule biogenesis across cell types by showing it is essential for neutrophil granule formation, content, and antimicrobial degranulation.","evidence":"Scamp3 knockout in Hoxb8-derived neutrophils and zebrafish with proteomics and bacterial killing/degranulation assays","pmids":["41187789"],"confidence":"High","gaps":["Whether the same trafficking machinery used for EGFR operates in granule biogenesis untested","Direct cargo or sorting partners in neutrophils not identified"]},{"year":2025,"claim":"Provided a lipid-transfer mechanism for SCAMP3 in ILV/exosome biogenesis, showing it recruits BLTP2 to ER–MVB contact sites in a Rab5-dependent, NEDD4-regulated manner.","evidence":"Co-IP, BLTP2/SCAMP3 depletion, endosomal lipidomics, Rab5 dependency, and NEDD4 ubiquitination assays (preprint)","pmids":["bio_10.1101_2025.04.17.649455"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed; single lab","Direct contact-site topology of SCAMP3–BLTP2 not structurally defined"]},{"year":2025,"claim":"Broadened the cancer signaling role by showing SCAMP3 coordinates residual ERK activity, mTORC1 signaling, and autophagic flux, and cooperates with EPS8 to stabilize EGFR.","evidence":"TMT phosphoproteomics in SCAMP3 KO TNBC cells under inhibitor conditions and co-IP/knockdown/overexpression with EPS8 and AR-V7","pmids":["41096842","41151858"],"confidence":"Medium","gaps":["Direct vs indirect effects on ERK feedback regulators not separated","Whether EPS8 interaction is direct not established"]},{"year":null,"claim":"It remains unresolved how SCAMP3's transmembrane topology and motif-based interactions are mechanistically shared across its distinct roles in EGFR sorting, ILV/exosome biogenesis, and regulated granule secretion.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of SCAMP3 in any membrane context","Unknown whether ESCRT/Nedd4 engagement applies to insulin and neutrophil granule biology","Native stoichiometry of SCAMP3–EGFR–ESCRT assemblies undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,8]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,4]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[3]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,2]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[6,7]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,5,10]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[10]}],"complexes":["ESCRT-0 (Hrs)","ESCRT-I (Tsg101)"],"partners":["EGFR","TSG101","HGS","NEDD4","BLTP2","EPS8","AR-V7"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O14828","full_name":"Secretory carrier-associated membrane protein 3","aliases":[],"length_aa":347,"mass_kda":38.3,"function":"Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/O14828/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SCAMP3","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"RAB11A","stoichiometry":10.0},{"gene":"SCAMP1","stoichiometry":10.0},{"gene":"SCAMP2","stoichiometry":10.0},{"gene":"RAB1A","stoichiometry":4.0},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"LAMP1","stoichiometry":0.2},{"gene":"LAMTOR2","stoichiometry":0.2},{"gene":"RAB11B","stoichiometry":0.2},{"gene":"RAB7A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SCAMP3","total_profiled":1310},"omim":[{"mim_id":"619726","title":"HYALURONAN AND PROTEOGLYCAN LINK PROTEIN 2; HAPLN2","url":"https://www.omim.org/entry/619726"},{"mim_id":"606913","title":"SECRETORY CARRIER MEMBRANE PROTEIN 3; SCAMP3","url":"https://www.omim.org/entry/606913"},{"mim_id":"606912","title":"SECRETORY CARRIER MEMBRANE PROTEIN 2; SCAMP2","url":"https://www.omim.org/entry/606912"},{"mim_id":"606911","title":"SECRETORY CARRIER MEMBRANE PROTEIN 1; SCAMP1","url":"https://www.omim.org/entry/606911"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SCAMP3"},"hgnc":{"alias_symbol":[],"prev_symbol":["C1orf3"]},"alphafold":{"accession":"O14828","domains":[{"cath_id":"-","chopping":"173-325","consensus_level":"high","plddt":93.5154,"start":173,"end":325}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O14828","model_url":"https://alphafold.ebi.ac.uk/files/AF-O14828-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O14828-F1-predicted_aligned_error_v6.png","plddt_mean":76.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SCAMP3","jax_strain_url":"https://www.jax.org/strain/search?query=SCAMP3"},"sequence":{"accession":"O14828","fasta_url":"https://rest.uniprot.org/uniprotkb/O14828.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O14828/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O14828"}},"corpus_meta":[{"pmid":"19438519","id":"PMC_19438519","title":"SCAMP3 is a component of the Salmonella-induced tubular network and reveals an interaction between bacterial effectors and post-Golgi trafficking.","date":"2009","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/19438519","citation_count":60,"is_preprint":false},{"pmid":"19158374","id":"PMC_19158374","title":"SCAMP3 negatively regulates epidermal growth factor receptor degradation and promotes receptor recycling.","date":"2009","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/19158374","citation_count":57,"is_preprint":false},{"pmid":"9658162","id":"PMC_9658162","title":"Tyrosine phosphorylation of selected secretory carrier membrane proteins, SCAMP1 and SCAMP3, and association with the EGF receptor.","date":"1998","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/9658162","citation_count":34,"is_preprint":false},{"pmid":"21951651","id":"PMC_21951651","title":"Regulation of the MVB pathway by SCAMP3.","date":"2011","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/21951651","citation_count":32,"is_preprint":false},{"pmid":"31554889","id":"PMC_31554889","title":"MicroRNA-27a/b-3p and PPARG regulate SCAMP3 through a feed-forward loop during adipogenesis.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31554889","citation_count":20,"is_preprint":false},{"pmid":"33850265","id":"PMC_33850265","title":"SCAMP3 is a mutant EGFR phosphorylation target and a tumor suppressor in lung adenocarcinoma.","date":"2021","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/33850265","citation_count":12,"is_preprint":false},{"pmid":"33437366","id":"PMC_33437366","title":"SCAMP3 is regulated by miR-128-3p and promotes the metastasis of hepatocellular carcinoma cells through EGFR-MAPK p38 signaling pathway.","date":"2020","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/33437366","citation_count":10,"is_preprint":false},{"pmid":"35681787","id":"PMC_35681787","title":"SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/35681787","citation_count":9,"is_preprint":false},{"pmid":"36627007","id":"PMC_36627007","title":"SCAMP3 promotes breast cancer progression through the c-MYC-β-Catenin-SQSTM1 growth and stemness axis.","date":"2023","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/36627007","citation_count":6,"is_preprint":false},{"pmid":"33116758","id":"PMC_33116758","title":"Comprehensive Evaluation of Endocytosis-Associated Protein SCAMP3 in Hepatocellular Carcinoma.","date":"2020","source":"Pharmacogenomics and personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33116758","citation_count":6,"is_preprint":false},{"pmid":"39320956","id":"PMC_39320956","title":"Optimized Proteomic Analysis of Insulin Granules From MIN6 Cells Identifies Scamp3, a Novel Regulator of Insulin Secretion and Content.","date":"2024","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/39320956","citation_count":6,"is_preprint":false},{"pmid":"41096842","id":"PMC_41096842","title":"SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41096842","citation_count":2,"is_preprint":false},{"pmid":"41151858","id":"PMC_41151858","title":"SCAMP3 and EPS8 Cooperatively Regulate EGFR Signaling to Promote Enzalutamide Resistance and Metastatic Potential in Prostate Cancer.","date":"2025","source":"Cancer genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/41151858","citation_count":0,"is_preprint":false},{"pmid":"41187789","id":"PMC_41187789","title":"SCAMP3 is essential for proper formation and function of neutrophil granules.","date":"2025","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/41187789","citation_count":0,"is_preprint":false},{"pmid":"35035772","id":"PMC_35035772","title":"SCAMP3 is regulated by miR-128-3p and promotes the metastasis of hepatocellular carcinoma cells through EGFR-MAPK p38 signaling pathway [Retraction].","date":"2021","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/35035772","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.04.17.649455","title":"BLTP2 orchestrates lysobisphosphatidic acid synthesis and exosome biogenesis via SCAMP3-dependent ER contacts in tumorigenesis","date":"2025-04-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.17.649455","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10419,"output_tokens":3350,"usd":0.040753,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10829,"output_tokens":3676,"usd":0.073023,"stage2_stop_reason":"end_turn"},"total_usd":0.113776,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"SCAMP3 is multimonoubiquitylated and associates with Nedd4 HECT ubiquitin ligases via its PY motif and with ESCRT-I subunit Tsg101 via its PSAP motif, and also associates with ESCRT-0 subunit Hrs. These interactions negatively regulate EGFR degradation and promote receptor recycling from early endosomes.\",\n      \"method\": \"Co-immunoprecipitation, inhibitory RNA depletion, overexpression with PY/PSAP/ubiquitylatable-lysine mutants, immunoelectron microscopy of EGFR-containing MVBs\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP, multiple site-directed mutants (PY, PSAP, lysine), RNA depletion with defined phenotypic readout, dual-depletion epistasis, and immuno-EM, all in one study\",\n      \"pmids\": [\"19158374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"SCAMP3 (and SCAMP1) are tyrosine-phosphorylated in an EGF-dependent manner; EGF stimulation induces SCAMP3–EGFR co-immunoprecipitation, and EGFR directly phosphorylates SCAMP3 in vitro, suggesting EGFR is the upstream kinase for SCAMP3 tyrosine phosphorylation.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay with recombinant EGFR, vanadate-treatment phosphorylation assays, recombinant phosphatase (PTP1B) dephosphorylation\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase assay with recombinant proteins plus co-IP and cell-based phosphorylation in a single study with multiple orthogonal methods\",\n      \"pmids\": [\"9658162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SCAMP3 positively regulates biogenesis of multivesicular endosomes (MVBs): it promotes EGF receptor sorting into MVBs and formation of intralumenal vesicles (ILVs) in vitro, thereby controlling EGFR targeting to lysosomes.\",\n      \"method\": \"Cell-free MVB biogenesis assay (in vitro), SCAMP3 depletion with defined ILV-formation readout, EGF-dependent MVB biogenesis assay\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-free in vitro biogenesis assay plus depletion experiments, single lab\",\n      \"pmids\": [\"21951651\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SCAMP3 accumulates on the trans-Golgi network in uninfected cells and marks Salmonella-induced tubules distinct from late-endosomal SIFs; siRNA screen showed SCAMP3 (and SCAMP2) contribute to maintenance of Salmonella-containing vacuoles in the Golgi region of HeLa cells, implicating SCAMP3 in post-Golgi trafficking dynamics exploited by Salmonella.\",\n      \"method\": \"siRNA screen, fluorescence microscopy/colocalization in HeLa cells infected with Salmonella\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — siRNA knockdown with defined subcellular localization readout, single lab but replicated across multiple SCAMP family members\",\n      \"pmids\": [\"19438519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Activated (mutant) EGFR phosphorylates SCAMP3 at Y86, and this phosphorylation increases the interaction of SCAMP3 with both wild-type and mutant EGFRs. Phospho-Y86 is required for SCAMP3's ability to promote EGFR degradation and attenuate MAP kinase signaling; SCAMP3 Y86F mutant fails to rescue the enhanced growth, reduced EGFR degradation, and multinucleation phenotypes caused by SCAMP3 knockdown.\",\n      \"method\": \"Quantitative mass-spectrometry-based phosphoproteomics, site-directed mutagenesis (Y86F), co-immunoprecipitation, knockdown rescue assays, EGFR degradation assay, xenograft tumor growth\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — phosphoproteomics identification, site-directed mutagenesis with functional rescue, co-IP, in vivo xenograft, multiple orthogonal methods in one study\",\n      \"pmids\": [\"33850265\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SCAMP3 colocalizes with EGFR and redistributes it from the cytoplasm to the perinucleus; SCAMP3 knockout reduces EGFR degradation and attenuates AKT, ERK, and STAT3 signaling in triple-negative breast cancer cells.\",\n      \"method\": \"EGFR internalization/colocalization assay, SCAMP3 knockout (CRISPR), immunoblot degradation assay, xenograft models\",\n      \"journal\": \"Cancers\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — internalization assay plus KO with defined signaling readouts, single lab\",\n      \"pmids\": [\"35681787\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SCAMP3 is required for proper formation and content of neutrophil primary, secondary, and tertiary granules; Scamp3 knockout reduces granule protein levels and degranulation in Hoxb8-derived neutrophils in vitro and reduces neutrophil granularity in zebrafish in vivo, impairing E. coli killing.\",\n      \"method\": \"Scamp3 knockout (Hoxb8 cell-derived neutrophils and zebrafish), mass spectrometry proteomics, Western blot, killing assay, degranulation assay\",\n      \"journal\": \"Journal of leukocyte biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO in two independent model systems (mammalian cell-derived neutrophils + zebrafish), mass spectrometry, and functional readouts\",\n      \"pmids\": [\"41187789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SCAMP3 is an insulin secretory granule (ISG)-associated protein; Scamp3 knockdown in INS-1 cells reduces insulin content and causes dysfunctional insulin secretion, establishing a role for SCAMP3 in regulating insulin granule function in pancreatic β-cells.\",\n      \"method\": \"ISG isolation and mass spectrometry-based proteomics, confocal colocalization in MIN6 and human β-cells, Scamp3 siRNA knockdown in INS-1 cells with insulin content and secretion assays\",\n      \"journal\": \"Diabetes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomic identification with colocalization validation and knockdown functional assays, single lab\",\n      \"pmids\": [\"39320956\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SCAMP3 recruits the ER membrane lipid transfer protein BLTP2 to ER–MVB membrane contact sites (MCSs) in a Rab5-dependent manner, and this recruitment is inhibited by NEDD4-mediated ubiquitination of SCAMP3. This SCAMP3-dependent ER–MVB contact facilitates BMP/LBPA precursor (phosphatidylglycerol) transfer to MVBs for ILV/exosome formation.\",\n      \"method\": \"Co-immunoprecipitation, BLTP2 depletion, SCAMP3 depletion, lipidomic analysis of endosomes, Rab5 dependency experiments, ubiquitination assays (NEDD4)\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — co-IP and depletion experiments with lipid and functional readouts, preprint (not yet peer-reviewed), single lab\",\n      \"pmids\": [\"bio_10.1101_2025.04.17.649455\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"miR-27a/b-3p suppresses SCAMP3 expression directly; knockdown of PPARG downregulates SCAMP3 at the late phase of adipogenesis; reduction of SCAMP3 mRNA increases PPARG expression at early phase, placing SCAMP3 downstream of PPARG in a feed-forward loop with an anti-adipogenic role.\",\n      \"method\": \"miRNA overexpression, siRNA knockdown of PPARG and SCAMP3, gene expression analysis during adipocyte differentiation, correlation with adipocyte phenotypes\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — siRNA knockdown with defined gene-expression readouts and functional context in adipogenesis, single lab, no direct binding assay\",\n      \"pmids\": [\"31554889\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SCAMP3 knockout in TNBC cells abolishes residual ERK activity under ERK inhibitor MK-8353, reduces phosphorylation of ERK feedback regulators Raf-1 (S43) and MEK2 (T394), impairs mTORC1 signaling, and disrupts autophagic flux (elevated SQSTM1/p62 and LC3B-II with reduced Rab7A), identifying SCAMP3 as a coordinator of ERK signaling and autophagy.\",\n      \"method\": \"TMT-based LC-MS/MS phosphoproteomics of SCAMP3 KO vs. WT TNBC cells under basal, EGF-stimulated, and ERK-inhibitor conditions; Western blot validation\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative phosphoproteomics with orthogonal Western blot validation in KO cells, single lab\",\n      \"pmids\": [\"41096842\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SCAMP3 and EPS8 form a protein complex with EGFR and AR-V7 upon EGF stimulation; knockdown of either SCAMP3 or EPS8 reduces EGFR expression and attenuates STAT3, AKT, and ERK signaling, while overexpression increases EGFR levels and downstream signaling, demonstrating cooperative maintenance of EGFR stability.\",\n      \"method\": \"Co-immunoprecipitation, shRNA knockdown, overexpression (pcDNA vectors), Western blotting, EGF stimulation assays\",\n      \"journal\": \"Cancer genomics & proteomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP plus bidirectional gain/loss-of-function with defined signaling readouts, single lab\",\n      \"pmids\": [\"41151858\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SCAMP3 is a multi-spanning transmembrane protein of post-Golgi vesicles and endosomes that regulates EGFR trafficking by interacting with EGFR (whose kinase phosphorylates SCAMP3 at Y86), undergoing multimonoubiquitylation via Nedd4 HECT ligases, and engaging ESCRT-0 (Hrs) and ESCRT-I (Tsg101) through PY and PSAP motifs to balance EGFR recycling versus lysosomal degradation; it also localizes to ER–MVB membrane contact sites where it recruits BLTP2 in a Rab5-dependent, NEDD4-regulated manner to support intraluminal vesicle and exosome biogenesis, is required for neutrophil granule formation and degranulation, regulates insulin secretory granule content and insulin secretion in β-cells, and participates in a miR-27a/b-3p–PPARG feed-forward loop that controls adipogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SCAMP3 is a multi-spanning transmembrane protein of the trans-Golgi network and post-Golgi endosomal membranes that governs the sorting decision between recycling and lysosomal degradation of the EGF receptor [#0, #3]. Activated EGFR co-immunoprecipitates with SCAMP3 and directly phosphorylates it on tyrosine, with Y86 identified as the functional site; phospho-Y86 strengthens the SCAMP3–EGFR interaction and is required for SCAMP3 to drive EGFR degradation and attenuate downstream MAP kinase signaling [#1, #4]. SCAMP3 couples to the ESCRT machinery, associating with the Nedd4 HECT ubiquitin ligases through its PY motif, with ESCRT-I subunit Tsg101 through its PSAP motif, and with ESCRT-0 subunit Hrs, and is itself multimonoubiquitylated; these interactions tune EGFR recycling from early endosomes against its sorting into intralumenal vesicles of multivesicular bodies and onward delivery to lysosomes [#0, #2]. In cancer cells SCAMP3 redistributes EGFR to the perinuclear region and cooperates with EPS8 to maintain EGFR stability, with its loss reducing EGFR degradation yet attenuating AKT, ERK, and STAT3 output and disrupting mTORC1 signaling and autophagic flux [#5, #10, #11]. Beyond EGFR trafficking, SCAMP3 is required for regulated secretory and granule biology: it is needed for neutrophil granule formation, content, and degranulation [#6], associates with insulin secretory granules to control insulin content and secretion in β-cells [#7], and acts as an anti-adipogenic factor downstream of PPARG [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established the first molecular link between SCAMP3 and a signaling receptor by showing it is an EGF-responsive phosphoprotein and a direct EGFR substrate, defining EGFR as its upstream kinase.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay with recombinant EGFR, and vanadate/PTP1B phosphorylation assays\",\n      \"pmids\": [\"9658162\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not map the phosphorylated tyrosine residue\", \"Functional consequence of phosphorylation for trafficking not established\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Defined how SCAMP3 mechanistically engages the endosomal sorting machinery, showing it links Nedd4 ligases and ESCRT components to bias EGFR toward recycling over degradation.\",\n      \"evidence\": \"Reciprocal co-IP, PY/PSAP/lysine mutants, RNAi depletion with dual-depletion epistasis, and immuno-EM of EGFR-containing MVBs\",\n      \"pmids\": [\"19158374\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The specific Nedd4 family member acting in vivo not resolved\", \"Did not establish which ubiquitylated lysines are functionally critical\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Localized SCAMP3 to the trans-Golgi network and implicated it in post-Golgi trafficking dynamics by showing it maintains Salmonella-containing vacuoles.\",\n      \"evidence\": \"siRNA screen and fluorescence colocalization in Salmonella-infected HeLa cells\",\n      \"pmids\": [\"19438519\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of SCAMP3 contribution to vacuole maintenance unknown\", \"Relationship between TGN pool and endosomal EGFR-sorting pool not defined\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Resolved an apparent paradox by showing SCAMP3 also positively promotes MVB/ILV biogenesis and EGFR sorting into MVBs, indicating it acts at multiple steps of the degradative pathway.\",\n      \"evidence\": \"Cell-free MVB biogenesis assay and SCAMP3 depletion with ILV-formation readout\",\n      \"pmids\": [\"21951651\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular determinants on SCAMP3 driving ILV formation not mapped\", \"Single-lab in vitro assay\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified Y86 as the functional phosphosite and tied it causally to EGFR degradation and signaling attenuation, converting the 1998 phosphorylation observation into a defined regulatory mechanism with tumor relevance.\",\n      \"evidence\": \"Phosphoproteomics, Y86F mutagenesis with knockdown rescue, EGFR degradation assays, and xenograft growth\",\n      \"pmids\": [\"33850265\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis for how phospho-Y86 strengthens EGFR binding unknown\", \"Phosphatase that reverses Y86 in cells not identified\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirmed in a cancer-cell context that SCAMP3 controls EGFR subcellular distribution and degradation and shapes AKT/ERK/STAT3 output.\",\n      \"evidence\": \"EGFR internalization/colocalization assays and CRISPR knockout with signaling readouts and xenograft models in TNBC\",\n      \"pmids\": [\"35681787\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reconciliation of reduced degradation with attenuated signaling not fully mechanistic\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended SCAMP3 function beyond EGFR trafficking to regulated secretion, establishing it as an insulin secretory granule protein required for normal insulin content and secretion.\",\n      \"evidence\": \"ISG proteomics, confocal colocalization in β-cells, and siRNA knockdown with insulin content/secretion assays\",\n      \"pmids\": [\"39320956\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism by which SCAMP3 affects granule content unknown\", \"ESCRT/EGFR machinery relevance to ISG biology untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated a broad requirement for SCAMP3 in granule biogenesis across cell types by showing it is essential for neutrophil granule formation, content, and antimicrobial degranulation.\",\n      \"evidence\": \"Scamp3 knockout in Hoxb8-derived neutrophils and zebrafish with proteomics and bacterial killing/degranulation assays\",\n      \"pmids\": [\"41187789\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the same trafficking machinery used for EGFR operates in granule biogenesis untested\", \"Direct cargo or sorting partners in neutrophils not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Provided a lipid-transfer mechanism for SCAMP3 in ILV/exosome biogenesis, showing it recruits BLTP2 to ER–MVB contact sites in a Rab5-dependent, NEDD4-regulated manner.\",\n      \"evidence\": \"Co-IP, BLTP2/SCAMP3 depletion, endosomal lipidomics, Rab5 dependency, and NEDD4 ubiquitination assays (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.04.17.649455\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed; single lab\", \"Direct contact-site topology of SCAMP3–BLTP2 not structurally defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Broadened the cancer signaling role by showing SCAMP3 coordinates residual ERK activity, mTORC1 signaling, and autophagic flux, and cooperates with EPS8 to stabilize EGFR.\",\n      \"evidence\": \"TMT phosphoproteomics in SCAMP3 KO TNBC cells under inhibitor conditions and co-IP/knockdown/overexpression with EPS8 and AR-V7\",\n      \"pmids\": [\"41096842\", \"41151858\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect effects on ERK feedback regulators not separated\", \"Whether EPS8 interaction is direct not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how SCAMP3's transmembrane topology and motif-based interactions are mechanistically shared across its distinct roles in EGFR sorting, ILV/exosome biogenesis, and regulated granule secretion.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of SCAMP3 in any membrane context\", \"Unknown whether ESCRT/Nedd4 engagement applies to insulin and neutrophil granule biology\", \"Native stoichiometry of SCAMP3–EGFR–ESCRT assemblies undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [6, 7]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 5, 10]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\"ESCRT-0 (Hrs)\", \"ESCRT-I (Tsg101)\"],\n    \"partners\": [\"EGFR\", \"TSG101\", \"HGS\", \"NEDD4\", \"BLTP2\", \"EPS8\", \"AR-V7\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}