{"gene":"SCAMP1","run_date":"2026-06-10T07:46:29","timeline":{"discoveries":[{"year":2000,"finding":"The NPF repeats of SCAMP1 bind to two EH domain proteins: intersectin 1 (involved in endocytic budding at the plasma membrane) and gamma-synergin (involved in vesicle budding from the trans-Golgi complex). Expression of SCAMP1 lacking the N-terminal NPF repeats potently inhibited transferrin uptake by endocytosis, implicating SCAMP1 in clathrin coat recruitment at the plasma membrane and TGN.","method":"Co-immunoprecipitation / pulldown of NPF repeat interactions; dominant-negative SCAMP1 (ΔNPF) inhibition of transferrin endocytosis assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal binding assay plus functional dominant-negative endocytosis assay, single lab but two orthogonal methods","pmids":["10777571"],"is_preprint":false},{"year":1999,"finding":"SCAMP1 knockout mice are viable but show a reduction in the final capacitance change after mast cell exocytosis and an increased proportion of reversible (kiss-and-run) fusion events, indicating SCAMP1 is required for stable fusion pore formation/maintenance during regulated exocytosis but is not essential for exocytosis per se.","method":"Gene targeting (SCAMP1 knockout mouse); whole-cell capacitance measurements in mast cells stimulated with GTPγS","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function with quantitative electrophysiological readout, replicated across multiple animals","pmids":["10551807"],"is_preprint":false},{"year":2011,"finding":"SCAMP1 deficiency in PC12 cells inhibits both dilation and closure of fusion pores after dense core vesicle (DCV) exocytosis, causing accumulation of fusion figures at the plasma membrane. Loss of SCAMP1-mediated pore closure increases secondary (compound) exocytosis of DCVs. Restoration of SCAMP1 expression rescues normal pore closure, placing SCAMP1 in exo-endocytic coupling.","method":"siRNA knockdown of SCAMP1 in PC12 cells; real-time fluorescence microscopy of DCV fusion pore dynamics; rescue by re-expression","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean KD with defined cellular phenotype plus rescue experiment, two orthogonal readouts (pore dynamics and compound exocytosis)","pmids":["21272170"],"is_preprint":false},{"year":1998,"finding":"SCAMP1 (and SCAMP3) are phosphorylated on tyrosine residues upon EGF stimulation in fibroblasts overexpressing the EGF receptor, and SCAMP1 co-immunoprecipitates with the EGF receptor after EGF treatment. SCAMP3 (but not SCAMP1) undergoes tyrosine phosphorylation by the EGFR in an in vitro kinase assay. Phosphorylation is reversible by the tyrosine phosphatase PTP1B.","method":"Co-immunoprecipitation with EGFR; in vitro EGFR kinase assay with isolated SCAMP3; vanadate-based phosphotyrosine detection; PTP1B dephosphorylation assay","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus in vitro kinase assay, but direct in vitro phosphorylation of SCAMP1 by EGFR was not shown (only SCAMP3 tested in vitro), single lab","pmids":["9658162"],"is_preprint":false},{"year":2022,"finding":"Overexpression of SCAMP1 (the protein) inhibited HBV RNA/pgRNA and secreted viral proteins, while knockdown of SCAMP1 increased viral production. Mechanistically, SCAMP1 suppresses the HBV EnhI/XP, SP1, and SP2 promoters, thereby reducing HBV X and S mRNA levels, identifying SCAMP1 as a host restriction factor against HBV replication.","method":"Overexpression and siRNA knockdown of SCAMP1 in hepatocytes; RT-qPCR and ELISA for HBV RNAs and proteins; promoter reporter assays for EnhI/XP, SP1, SP2","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — bidirectional genetic manipulation with defined molecular readouts (promoter assays), single lab, single study","pmids":["35216324"],"is_preprint":false},{"year":2018,"finding":"SCAMP1 protein cooperates with MTSS1 to prevent breast cancer invasion by promoting MTSS1 protein trafficking, leading to elevated RAC1-GTP levels and increased cell-cell adhesions in HER2+/ER-/PR- breast cancer cells.","method":"Systems biology interaction screening; functional co-expression/knockdown assays measuring RAC1-GTP pull-down, invasion assays, and cell-cell adhesion in breast cancer cell lines","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — RAC1-GTP pulldown combined with invasion and adhesion assays, but mechanistic detail of how SCAMP1 promotes MTSS1 trafficking is indirect, single lab","pmids":["29497041"],"is_preprint":false},{"year":2013,"finding":"siRNA-mediated knockdown of SCAMP1 in pancreatic and gallbladder cancer cell lines reduces cell migration and invasion (but not proliferation) and decreases secreted VEGF levels in conditioned medium.","method":"siRNA knockdown; cell migration/invasion assays (wound-healing, Matrigel); VEGF ELISA on conditioned medium","journal":"Tumour biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single-method knockdown with phenotypic readout, no pathway placement beyond VEGF reduction, single lab","pmids":["23653380"],"is_preprint":false},{"year":2024,"finding":"SCAMP1 (protein) knockdown in gastric cancer cells suppresses proliferation in vitro and in vivo and strongly attenuates Akt/MAPK/Stat signaling pathways, as confirmed by immunoblotting after RNA-seq pathway analysis.","method":"siRNA/shRNA knockdown; xenograft mouse model; RNA sequencing; immunoblotting for pAkt, pMAPK, pStat","journal":"Journal of Cancer","confidence":"Low","confidence_rationale":"Tier 3 / Weak — KD with phenotype and pathway readout by immunoblotting, but no direct mechanistic link established between SCAMP1 and RTK/Akt, single lab","pmids":["39308691"],"is_preprint":false}],"current_model":"SCAMP1 is an integral membrane protein of post-Golgi recycling vesicles that participates in endocytosis via its N-terminal NPF repeats, which recruit EH domain proteins (intersectin 1 and gamma-synergin) to promote clathrin coat assembly at the plasma membrane and TGN; it also facilitates stable exocytic fusion pore dilation and closure in neuroendocrine and mast cells, is subject to EGF receptor-dependent tyrosine phosphorylation, and restricts HBV replication by suppressing viral promoter activity."},"narrative":{"mechanistic_narrative":"SCAMP1 is an integral membrane protein of the secretory and endocytic pathways that couples membrane trafficking events to clathrin-mediated coat assembly and to the dynamics of exocytic fusion pores [PMID:10777571, PMID:21272170]. Its N-terminal NPF repeats bind the EH domain proteins intersectin 1 and gamma-synergin, linking SCAMP1 to clathrin coat recruitment at the plasma membrane and the trans-Golgi network; an NPF-deleted dominant-negative form blocks transferrin endocytosis [PMID:10777571]. During regulated exocytosis, SCAMP1 is required not for fusion itself but for stabilizing and resolving the fusion pore: SCAMP1-null mast cells display reduced net capacitance gain and a higher fraction of reversible kiss-and-run events [PMID:10551807], and SCAMP1-deficient PC12 cells fail to properly dilate and close dense-core-vesicle fusion pores, accumulating fusion figures and shifting toward compound exocytosis [PMID:21272170]. SCAMP1 is tyrosine-phosphorylated upon EGF stimulation and associates with the activated EGF receptor [PMID:9658162]. Beyond trafficking, SCAMP1 acts as a host restriction factor against hepatitis B virus by suppressing the EnhI/XP, SP1, and SP2 promoters to lower viral X and S transcripts [PMID:35216324], and it modulates tumor cell behavior, cooperating with MTSS1 to elevate RAC1-GTP and restrain breast cancer invasion [PMID:29497041]. The molecular basis connecting SCAMP1's trafficking role to these signaling and transcriptional phenotypes has not been resolved in the available corpus.","teleology":[{"year":1998,"claim":"Established that SCAMP1 is a downstream target of growth factor receptor signaling, placing a vesicle membrane protein within the EGFR response.","evidence":"Co-IP with EGFR and phosphotyrosine detection in EGF-stimulated fibroblasts overexpressing EGFR; in vitro EGFR kinase assay on SCAMP3","pmids":["9658162"],"confidence":"Medium","gaps":["Direct in vitro phosphorylation of SCAMP1 (as opposed to SCAMP3) by EGFR was not demonstrated","The functional consequence of SCAMP1 tyrosine phosphorylation is unknown","Phosphosite identity on SCAMP1 not mapped"]},{"year":1999,"claim":"Resolved whether SCAMP1 is essential for exocytosis itself versus pore stability, showing it controls stable fusion pore formation rather than triggering fusion.","evidence":"SCAMP1 knockout mouse with whole-cell capacitance measurements in GTPγS-stimulated mast cells","pmids":["10551807"],"confidence":"High","gaps":["Molecular mechanism by which SCAMP1 stabilizes the fusion pore not defined","Viability of knockout indicates functional redundancy that is uncharacterized"]},{"year":2000,"claim":"Defined the molecular interactions underlying SCAMP1's trafficking role, linking its NPF repeats to EH-domain endocytic adaptors and to clathrin coat assembly.","evidence":"Co-IP/pulldown of NPF repeats with intersectin 1 and gamma-synergin; dominant-negative ΔNPF inhibition of transferrin endocytosis","pmids":["10777571"],"confidence":"High","gaps":["Whether SCAMP1 directly nucleates clathrin coats or acts as a scaffold not distinguished","Relative contribution at plasma membrane versus TGN not quantified"]},{"year":2011,"claim":"Extended the pore-stability role to neuroendocrine secretion and into exo-endocytic coupling, showing SCAMP1 controls both fusion pore dilation and closure.","evidence":"siRNA knockdown in PC12 cells with real-time imaging of dense-core-vesicle fusion pore dynamics and rescue by re-expression","pmids":["21272170"],"confidence":"High","gaps":["Direct biophysical mechanism of pore dilation/closure control not established","Link to the NPF/EH-domain endocytic machinery not tested in this context"]},{"year":2013,"claim":"First implicated SCAMP1 in cancer cell motility, associating its loss with reduced migration, invasion, and VEGF secretion.","evidence":"siRNA knockdown in pancreatic and gallbladder cancer cell lines with migration/invasion assays and VEGF ELISA","pmids":["23653380"],"confidence":"Low","gaps":["Single-method knockdown without rescue or mechanistic pathway placement","Whether the VEGF effect is direct or secondary is unknown"]},{"year":2018,"claim":"Provided a trafficking-based mechanism for SCAMP1 in tumor suppression, linking it to MTSS1 transport and RAC1 regulation.","evidence":"Interaction screening with RAC1-GTP pulldown, invasion and cell-cell adhesion assays in HER2+/ER-/PR- breast cancer lines","pmids":["29497041"],"confidence":"Medium","gaps":["How SCAMP1 promotes MTSS1 trafficking mechanistically is indirect/unresolved","Direct physical interaction between SCAMP1 and MTSS1 not firmly established","Generalizability beyond the tested breast cancer subtype unknown"]},{"year":2022,"claim":"Identified an antiviral function for SCAMP1 as an HBV restriction factor acting at the level of viral promoter activity.","evidence":"Overexpression and siRNA knockdown in hepatocytes with RT-qPCR, ELISA, and EnhI/XP, SP1, SP2 promoter reporter assays","pmids":["35216324"],"confidence":"Medium","gaps":["Mechanism by which a membrane trafficking protein suppresses viral promoters is unexplained","Single lab, single study without independent confirmation"]},{"year":2024,"claim":"Associated SCAMP1 with proliferative oncogenic signaling in gastric cancer, contrasting with its tumor-suppressive role elsewhere.","evidence":"siRNA/shRNA knockdown, xenograft model, RNA-seq, and immunoblotting for pAkt/pMAPK/pStat","pmids":["39308691"],"confidence":"Low","gaps":["No direct mechanistic link between SCAMP1 and RTK/Akt signaling established","Apparent opposite role versus breast cancer not reconciled"]},{"year":null,"claim":"How SCAMP1's defined trafficking activity (NPF/EH-domain coat assembly and fusion pore control) mechanistically gives rise to its reported roles in viral promoter suppression and divergent cancer signaling outcomes remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No mechanism connecting membrane trafficking function to transcriptional/signaling phenotypes","Opposing tumor-suppressive and tumor-promoting reports not reconciled","No structural model of SCAMP1 in coat or pore contexts"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0]}],"complexes":[],"partners":["ITSN1","SYNRG","EGFR","MTSS1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O15126","full_name":"Secretory carrier-associated membrane protein 1","aliases":[],"length_aa":338,"mass_kda":37.9,"function":"Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface","subcellular_location":"Golgi apparatus, trans-Golgi network membrane; Recycling endosome membrane","url":"https://www.uniprot.org/uniprotkb/O15126/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SCAMP1","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":74,"dependency_fraction":0.013513513513513514},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000085365","cell_line_id":"CID000079","localizations":[{"compartment":"golgi","grade":3},{"compartment":"vesicles","grade":3},{"compartment":"membrane","grade":1}],"interactors":[{"gene":"SCAMP3","stoichiometry":10.0},{"gene":"SCAMP2","stoichiometry":10.0},{"gene":"VAMP3;VAMP2","stoichiometry":4.0},{"gene":"VAMP3","stoichiometry":4.0},{"gene":"EMD","stoichiometry":0.2},{"gene":"MAPRE1","stoichiometry":0.2},{"gene":"PIP4P1","stoichiometry":0.2},{"gene":"RAB11A","stoichiometry":0.2},{"gene":"RAB11B","stoichiometry":0.2},{"gene":"RAB1A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000079","total_profiled":1310},"omim":[{"mim_id":"613766","title":"SECRETORY CARRIER MEMBRANE PROTEIN 5; SCAMP5","url":"https://www.omim.org/entry/613766"},{"mim_id":"613764","title":"SECRETORY CARRIER MEMBRANE PROTEIN 4; SCAMP4","url":"https://www.omim.org/entry/613764"},{"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":"Uncertain","locations":[{"location":"Cell Junctions","reliability":"Uncertain"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SCAMP1"},"hgnc":{"alias_symbol":["SCAMP37"],"prev_symbol":[]},"alphafold":{"accession":"O15126","domains":[{"cath_id":"-","chopping":"142-306","consensus_level":"high","plddt":93.9095,"start":142,"end":306}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O15126","model_url":"https://alphafold.ebi.ac.uk/files/AF-O15126-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O15126-F1-predicted_aligned_error_v6.png","plddt_mean":79.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SCAMP1","jax_strain_url":"https://www.jax.org/strain/search?query=SCAMP1"},"sequence":{"accession":"O15126","fasta_url":"https://rest.uniprot.org/uniprotkb/O15126.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O15126/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O15126"}},"corpus_meta":[{"pmid":"17209124","id":"PMC_17209124","title":"Rice SCAMP1 defines clathrin-coated, trans-golgi-located tubular-vesicular structures as an early endosome in tobacco BY-2 cells.","date":"2007","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/17209124","citation_count":248,"is_preprint":false},{"pmid":"10777571","id":"PMC_10777571","title":"SCAMP1 function in endocytosis.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10777571","citation_count":81,"is_preprint":false},{"pmid":"21251105","id":"PMC_21251105","title":"Multiple cytosolic and transmembrane determinants are required for the trafficking of SCAMP1 via an ER-Golgi-TGN-PM pathway.","date":"2011","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/21251105","citation_count":62,"is_preprint":false},{"pmid":"10551807","id":"PMC_10551807","title":"Analysis of SCAMP1 function in secretory vesicle exocytosis by means of gene targeting in mice.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10551807","citation_count":54,"is_preprint":false},{"pmid":"31207033","id":"PMC_31207033","title":"Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR-499a-5p/LMX1A/NLRC5 pathway.","date":"2019","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31207033","citation_count":52,"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":"29497041","id":"PMC_29497041","title":"MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer.","date":"2018","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/29497041","citation_count":32,"is_preprint":false},{"pmid":"31550675","id":"PMC_31550675","title":"LncRNA SCAMP1 regulates ZEB1/JUN and autophagy to promote pediatric renal cell carcinoma under oxidative stress via miR-429.","date":"2019","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/31550675","citation_count":32,"is_preprint":false},{"pmid":"23653380","id":"PMC_23653380","title":"Inhibition of SCAMP1 suppresses cell migration and invasion in human pancreatic and gallbladder cancer cells.","date":"2013","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23653380","citation_count":22,"is_preprint":false},{"pmid":"32670859","id":"PMC_32670859","title":"Silencing SCAMP1-TV2 Inhibited the Malignant Biological Behaviors of Breast Cancer Cells by Interaction With PUM2 to Facilitate INSM1 mRNA Degradation.","date":"2020","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/32670859","citation_count":21,"is_preprint":false},{"pmid":"21272170","id":"PMC_21272170","title":"Regulation of fusion pore closure and compound exocytosis in neuroendocrine PC12 cells by SCAMP1.","date":"2011","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/21272170","citation_count":18,"is_preprint":false},{"pmid":"32401536","id":"PMC_32401536","title":"Long Noncoding RNA SCAMP1 Targets miR-137/CXCL12 Axis to Boost Cell Invasion and Angiogenesis in Ovarian Cancer.","date":"2020","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32401536","citation_count":17,"is_preprint":false},{"pmid":"17443802","id":"PMC_17443802","title":"Sexually dimorphic SCAMP1 expression in the forebrain motor pathway for song production of juvenile zebra finches.","date":"2007","source":"Developmental 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medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41249571","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11172,"output_tokens":2130,"usd":0.032733,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9206,"output_tokens":3205,"usd":0.063077,"stage2_stop_reason":"end_turn"},"total_usd":0.09581,"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\": 2000,\n      \"finding\": \"The NPF repeats of SCAMP1 bind to two EH domain proteins: intersectin 1 (involved in endocytic budding at the plasma membrane) and gamma-synergin (involved in vesicle budding from the trans-Golgi complex). Expression of SCAMP1 lacking the N-terminal NPF repeats potently inhibited transferrin uptake by endocytosis, implicating SCAMP1 in clathrin coat recruitment at the plasma membrane and TGN.\",\n      \"method\": \"Co-immunoprecipitation / pulldown of NPF repeat interactions; dominant-negative SCAMP1 (ΔNPF) inhibition of transferrin endocytosis assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding assay plus functional dominant-negative endocytosis assay, single lab but two orthogonal methods\",\n      \"pmids\": [\"10777571\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"SCAMP1 knockout mice are viable but show a reduction in the final capacitance change after mast cell exocytosis and an increased proportion of reversible (kiss-and-run) fusion events, indicating SCAMP1 is required for stable fusion pore formation/maintenance during regulated exocytosis but is not essential for exocytosis per se.\",\n      \"method\": \"Gene targeting (SCAMP1 knockout mouse); whole-cell capacitance measurements in mast cells stimulated with GTPγS\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function with quantitative electrophysiological readout, replicated across multiple animals\",\n      \"pmids\": [\"10551807\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SCAMP1 deficiency in PC12 cells inhibits both dilation and closure of fusion pores after dense core vesicle (DCV) exocytosis, causing accumulation of fusion figures at the plasma membrane. Loss of SCAMP1-mediated pore closure increases secondary (compound) exocytosis of DCVs. Restoration of SCAMP1 expression rescues normal pore closure, placing SCAMP1 in exo-endocytic coupling.\",\n      \"method\": \"siRNA knockdown of SCAMP1 in PC12 cells; real-time fluorescence microscopy of DCV fusion pore dynamics; rescue by re-expression\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined cellular phenotype plus rescue experiment, two orthogonal readouts (pore dynamics and compound exocytosis)\",\n      \"pmids\": [\"21272170\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"SCAMP1 (and SCAMP3) are phosphorylated on tyrosine residues upon EGF stimulation in fibroblasts overexpressing the EGF receptor, and SCAMP1 co-immunoprecipitates with the EGF receptor after EGF treatment. SCAMP3 (but not SCAMP1) undergoes tyrosine phosphorylation by the EGFR in an in vitro kinase assay. Phosphorylation is reversible by the tyrosine phosphatase PTP1B.\",\n      \"method\": \"Co-immunoprecipitation with EGFR; in vitro EGFR kinase assay with isolated SCAMP3; vanadate-based phosphotyrosine detection; PTP1B dephosphorylation assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus in vitro kinase assay, but direct in vitro phosphorylation of SCAMP1 by EGFR was not shown (only SCAMP3 tested in vitro), single lab\",\n      \"pmids\": [\"9658162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Overexpression of SCAMP1 (the protein) inhibited HBV RNA/pgRNA and secreted viral proteins, while knockdown of SCAMP1 increased viral production. Mechanistically, SCAMP1 suppresses the HBV EnhI/XP, SP1, and SP2 promoters, thereby reducing HBV X and S mRNA levels, identifying SCAMP1 as a host restriction factor against HBV replication.\",\n      \"method\": \"Overexpression and siRNA knockdown of SCAMP1 in hepatocytes; RT-qPCR and ELISA for HBV RNAs and proteins; promoter reporter assays for EnhI/XP, SP1, SP2\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — bidirectional genetic manipulation with defined molecular readouts (promoter assays), single lab, single study\",\n      \"pmids\": [\"35216324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SCAMP1 protein cooperates with MTSS1 to prevent breast cancer invasion by promoting MTSS1 protein trafficking, leading to elevated RAC1-GTP levels and increased cell-cell adhesions in HER2+/ER-/PR- breast cancer cells.\",\n      \"method\": \"Systems biology interaction screening; functional co-expression/knockdown assays measuring RAC1-GTP pull-down, invasion assays, and cell-cell adhesion in breast cancer cell lines\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — RAC1-GTP pulldown combined with invasion and adhesion assays, but mechanistic detail of how SCAMP1 promotes MTSS1 trafficking is indirect, single lab\",\n      \"pmids\": [\"29497041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"siRNA-mediated knockdown of SCAMP1 in pancreatic and gallbladder cancer cell lines reduces cell migration and invasion (but not proliferation) and decreases secreted VEGF levels in conditioned medium.\",\n      \"method\": \"siRNA knockdown; cell migration/invasion assays (wound-healing, Matrigel); VEGF ELISA on conditioned medium\",\n      \"journal\": \"Tumour biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-method knockdown with phenotypic readout, no pathway placement beyond VEGF reduction, single lab\",\n      \"pmids\": [\"23653380\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SCAMP1 (protein) knockdown in gastric cancer cells suppresses proliferation in vitro and in vivo and strongly attenuates Akt/MAPK/Stat signaling pathways, as confirmed by immunoblotting after RNA-seq pathway analysis.\",\n      \"method\": \"siRNA/shRNA knockdown; xenograft mouse model; RNA sequencing; immunoblotting for pAkt, pMAPK, pStat\",\n      \"journal\": \"Journal of Cancer\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — KD with phenotype and pathway readout by immunoblotting, but no direct mechanistic link established between SCAMP1 and RTK/Akt, single lab\",\n      \"pmids\": [\"39308691\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SCAMP1 is an integral membrane protein of post-Golgi recycling vesicles that participates in endocytosis via its N-terminal NPF repeats, which recruit EH domain proteins (intersectin 1 and gamma-synergin) to promote clathrin coat assembly at the plasma membrane and TGN; it also facilitates stable exocytic fusion pore dilation and closure in neuroendocrine and mast cells, is subject to EGF receptor-dependent tyrosine phosphorylation, and restricts HBV replication by suppressing viral promoter activity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SCAMP1 is an integral membrane protein of the secretory and endocytic pathways that couples membrane trafficking events to clathrin-mediated coat assembly and to the dynamics of exocytic fusion pores [#0, #2]. Its N-terminal NPF repeats bind the EH domain proteins intersectin 1 and gamma-synergin, linking SCAMP1 to clathrin coat recruitment at the plasma membrane and the trans-Golgi network; an NPF-deleted dominant-negative form blocks transferrin endocytosis [#0]. During regulated exocytosis, SCAMP1 is required not for fusion itself but for stabilizing and resolving the fusion pore: SCAMP1-null mast cells display reduced net capacitance gain and a higher fraction of reversible kiss-and-run events [#1], and SCAMP1-deficient PC12 cells fail to properly dilate and close dense-core-vesicle fusion pores, accumulating fusion figures and shifting toward compound exocytosis [#2]. SCAMP1 is tyrosine-phosphorylated upon EGF stimulation and associates with the activated EGF receptor [#3]. Beyond trafficking, SCAMP1 acts as a host restriction factor against hepatitis B virus by suppressing the EnhI/XP, SP1, and SP2 promoters to lower viral X and S transcripts [#4], and it modulates tumor cell behavior, cooperating with MTSS1 to elevate RAC1-GTP and restrain breast cancer invasion [#5]. The molecular basis connecting SCAMP1's trafficking role to these signaling and transcriptional phenotypes has not been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established that SCAMP1 is a downstream target of growth factor receptor signaling, placing a vesicle membrane protein within the EGFR response.\",\n      \"evidence\": \"Co-IP with EGFR and phosphotyrosine detection in EGF-stimulated fibroblasts overexpressing EGFR; in vitro EGFR kinase assay on SCAMP3\",\n      \"pmids\": [\"9658162\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Direct in vitro phosphorylation of SCAMP1 (as opposed to SCAMP3) by EGFR was not demonstrated\",\n        \"The functional consequence of SCAMP1 tyrosine phosphorylation is unknown\",\n        \"Phosphosite identity on SCAMP1 not mapped\"\n      ]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Resolved whether SCAMP1 is essential for exocytosis itself versus pore stability, showing it controls stable fusion pore formation rather than triggering fusion.\",\n      \"evidence\": \"SCAMP1 knockout mouse with whole-cell capacitance measurements in GTPγS-stimulated mast cells\",\n      \"pmids\": [\"10551807\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Molecular mechanism by which SCAMP1 stabilizes the fusion pore not defined\",\n        \"Viability of knockout indicates functional redundancy that is uncharacterized\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Defined the molecular interactions underlying SCAMP1's trafficking role, linking its NPF repeats to EH-domain endocytic adaptors and to clathrin coat assembly.\",\n      \"evidence\": \"Co-IP/pulldown of NPF repeats with intersectin 1 and gamma-synergin; dominant-negative ΔNPF inhibition of transferrin endocytosis\",\n      \"pmids\": [\"10777571\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Whether SCAMP1 directly nucleates clathrin coats or acts as a scaffold not distinguished\",\n        \"Relative contribution at plasma membrane versus TGN not quantified\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Extended the pore-stability role to neuroendocrine secretion and into exo-endocytic coupling, showing SCAMP1 controls both fusion pore dilation and closure.\",\n      \"evidence\": \"siRNA knockdown in PC12 cells with real-time imaging of dense-core-vesicle fusion pore dynamics and rescue by re-expression\",\n      \"pmids\": [\"21272170\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Direct biophysical mechanism of pore dilation/closure control not established\",\n        \"Link to the NPF/EH-domain endocytic machinery not tested in this context\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"First implicated SCAMP1 in cancer cell motility, associating its loss with reduced migration, invasion, and VEGF secretion.\",\n      \"evidence\": \"siRNA knockdown in pancreatic and gallbladder cancer cell lines with migration/invasion assays and VEGF ELISA\",\n      \"pmids\": [\"23653380\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single-method knockdown without rescue or mechanistic pathway placement\",\n        \"Whether the VEGF effect is direct or secondary is unknown\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Provided a trafficking-based mechanism for SCAMP1 in tumor suppression, linking it to MTSS1 transport and RAC1 regulation.\",\n      \"evidence\": \"Interaction screening with RAC1-GTP pulldown, invasion and cell-cell adhesion assays in HER2+/ER-/PR- breast cancer lines\",\n      \"pmids\": [\"29497041\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"How SCAMP1 promotes MTSS1 trafficking mechanistically is indirect/unresolved\",\n        \"Direct physical interaction between SCAMP1 and MTSS1 not firmly established\",\n        \"Generalizability beyond the tested breast cancer subtype unknown\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified an antiviral function for SCAMP1 as an HBV restriction factor acting at the level of viral promoter activity.\",\n      \"evidence\": \"Overexpression and siRNA knockdown in hepatocytes with RT-qPCR, ELISA, and EnhI/XP, SP1, SP2 promoter reporter assays\",\n      \"pmids\": [\"35216324\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Mechanism by which a membrane trafficking protein suppresses viral promoters is unexplained\",\n        \"Single lab, single study without independent confirmation\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Associated SCAMP1 with proliferative oncogenic signaling in gastric cancer, contrasting with its tumor-suppressive role elsewhere.\",\n      \"evidence\": \"siRNA/shRNA knockdown, xenograft model, RNA-seq, and immunoblotting for pAkt/pMAPK/pStat\",\n      \"pmids\": [\"39308691\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No direct mechanistic link between SCAMP1 and RTK/Akt signaling established\",\n        \"Apparent opposite role versus breast cancer not reconciled\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SCAMP1's defined trafficking activity (NPF/EH-domain coat assembly and fusion pore control) mechanistically gives rise to its reported roles in viral promoter suppression and divergent cancer signaling outcomes remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No mechanism connecting membrane trafficking function to transcriptional/signaling phenotypes\",\n        \"Opposing tumor-suppressive and tumor-promoting reports not reconciled\",\n        \"No structural model of SCAMP1 in coat or pore contexts\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ITSN1\", \"SYNRG\", \"EGFR\", \"MTSS1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}