{"gene":"CDC42EP1","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":1992,"finding":"CDC42EP1 (MSE55) was identified as a novel secreted protein expressed specifically in bone marrow stromal and endothelial cells, with a circulating serum form of ~55 kDa, suggesting a functional role in hematopoiesis.","method":"cDNA cloning, immunoblotting, Northern blot analysis, recombinant protein expression in E. coli","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (cloning, immunoblot, Northern blot) in single study establishing identity and localization","pmids":["1629197"],"is_preprint":false},{"year":1999,"finding":"CDC42EP1 (MSE55) binds to Cdc42 in a GTP-dependent manner through its CRIB domain; this interaction is required for MSE55-induced actin cytoskeleton reorganization, including membrane ruffle formation in COS-7 cells and long actin-based protrusions in NIH 3T3 cells. MSE55-induced protrusion formation was blocked by dominant-negative N17Cdc42 but not by dominant-negative N17Rac, placing MSE55 downstream of Cdc42 specifically.","method":"GST pulldown, CRIB domain mutagenesis, dominant-negative Cdc42/Rac overexpression, immunofluorescence, live-cell video microscopy","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 — GST capture assay with mutagenesis, epistasis via dominant-negatives, multiple cell readouts in single study","pmids":["10430899"],"is_preprint":false},{"year":2016,"finding":"CDC42EP1 is required for directed migration of cranial neural crest cells; loss of Cdc42ep1 leads to rounder cell shapes, membrane blebbing, disrupted actin organization, and loss of focal adhesion alignment. Cdc42 directly interacts with Cdc42ep1 via the CRIB domain and regulates its subcellular localization: Cdc42ep1 is found in membrane protrusions (together with Cdc42) and in perinuclear patches (where Cdc42 is absent), and changes in Cdc42 level shift Cdc42ep1 distribution between these locations to control protrusion formation and migration directionality.","method":"Morpholino-mediated knockdown in Xenopus embryos, immunofluorescence, CRIB domain interaction assay, traction force measurements, live imaging","journal":"Journal of molecular cell biology","confidence":"High","confidence_rationale":"Tier 2 — loss-of-function with defined cellular phenotypes, direct interaction via CRIB domain, subcellular localization tied to functional consequence, multiple orthogonal methods","pmids":["29040749"],"is_preprint":false},{"year":2023,"finding":"Cdc42ep1 colocalizes with septin filaments at the cell center in neural crest cells and interacts with septins in a reciprocal manner: septin filaments recruit Cdc42ep1 to the cell center, and Cdc42ep1 supports the formation of septin filaments. This Cdc42ep1–septin interaction is required for the stability, contractility, and persistent orientation of actin stress fibers during directed cell migration.","method":"Morpholino knockdown, colocalization analysis, live imaging, genetic epistasis between Cdc42ep1 and septin","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with defined phenotype, colocalization and epistasis, single lab","pmids":["36923257"],"is_preprint":false},{"year":2024,"finding":"Epithelial Borg5/Cdc42EP1 limits actomyosin contractility, cell-cell adhesion tension, and motility in MDCK monolayers; Borg5 depletion inhibits lateral F-actin cortex development and stimulates radial stress fibers. Borg5 interacts with the rod domain of myosin IIA (MYH9 heavy chain), and this interaction is reduced in the presence of septins. Borg5 also limits septin colocalization with microtubules, suggesting that Borg5 restricts contractility partly by counteracting septin-associated myosin activity.","method":"Borg5 depletion (KD) in MDCK cells, co-immunoprecipitation with myosin IIA rod domain, immunofluorescence, mass spectrometry (Überheide), functional contractility assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP with myosin IIA, KD with defined cellular phenotype, multiple readouts in single study","pmids":["39503295"],"is_preprint":false},{"year":2023,"finding":"CDC42EP1 expression is upregulated in ectopic endometriosis lesions and acts downstream of hsa_circ_0005991 via sponging of miR-30b-3p; elevated CDC42EP1 promotes epithelial-mesenchymal transition (EMT), and proliferation, migration, and invasion in Ishikawa cells.","method":"CircRNA/miRNA overexpression and knockdown, co-transfection rescue experiments, Western blot for EMT markers, cell function assays","journal":"Genomics","confidence":"Low","confidence_rationale":"Tier 3 — single lab, indirect pathway placement via sponge mechanism without direct biochemical demonstration of CDC42EP1 mechanism","pmids":["37757976"],"is_preprint":false}],"current_model":"CDC42EP1 (also known as MSE55/Borg5) is a CRIB domain-containing effector that binds active (GTP-bound) Cdc42 to regulate actin cytoskeleton organization and cell migration; it localizes to both membrane protrusions (with Cdc42) and perinuclear regions (without Cdc42), and its distribution between these compartments is controlled by Cdc42 levels to direct protrusion formation; it also interacts reciprocally with septin filaments to maintain actin stress fiber stability and orientation during directed migration, and interacts with the myosin IIA rod domain to limit actomyosin contractility in epithelial cells."},"narrative":{"teleology":[{"year":1992,"claim":"The initial discovery of CDC42EP1 (MSE55) as a novel secreted protein of bone marrow stroma established its molecular identity but left its signaling function unknown.","evidence":"cDNA cloning, immunoblotting, and Northern blot in bone marrow stromal/endothelial cells","pmids":["1629197"],"confidence":"Medium","gaps":["No signaling pathway placement","Functional role beyond expression in hematopoietic niche unresolved","Secreted form has not been functionally characterized in subsequent studies"]},{"year":1999,"claim":"Demonstrating that MSE55 binds GTP-Cdc42 via its CRIB domain and that this interaction is required for actin reorganization and protrusion formation established CDC42EP1 as a bona fide Cdc42 effector governing cytoskeletal remodeling.","evidence":"GST pulldown, CRIB domain mutagenesis, dominant-negative Cdc42/Rac epistasis, immunofluorescence, and live-cell microscopy in COS-7 and NIH 3T3 cells","pmids":["10430899"],"confidence":"High","gaps":["Downstream effector mechanism linking CRIB engagement to actin remodeling not defined","Relevance in a physiological tissue context not established"]},{"year":2016,"claim":"Showing that Cdc42 levels control CDC42EP1 partitioning between membrane protrusions and perinuclear patches, and that loss of CDC42EP1 disrupts directed neural crest migration, connected the Cdc42–CDC42EP1 axis to cell polarity and migration in vivo.","evidence":"Morpholino knockdown in Xenopus cranial neural crest, immunofluorescence, CRIB interaction assay, traction force measurements, live imaging","pmids":["29040749"],"confidence":"High","gaps":["Identity of perinuclear interaction partners unknown","Mechanism by which CDC42EP1 organizes focal adhesion alignment not resolved"]},{"year":2023,"claim":"Revealing a reciprocal interaction between CDC42EP1 and septin filaments that maintains actin stress fiber stability and orientation identified septins as a key structural partner bridging CDC42EP1 to the contractile cytoskeleton during directed migration.","evidence":"Morpholino knockdown, colocalization analysis, live imaging, and genetic epistasis between Cdc42ep1 and septins in neural crest cells","pmids":["36923257"],"confidence":"Medium","gaps":["Direct biochemical binding interface between CDC42EP1 and septins not mapped","Whether septin interaction is CRIB-domain-dependent or -independent is untested","Single-lab finding not independently replicated"]},{"year":2024,"claim":"Identifying myosin IIA (MYH9) rod domain as a direct CDC42EP1-binding partner whose interaction is antagonized by septins provided a molecular mechanism by which CDC42EP1 limits actomyosin contractility in epithelial sheets.","evidence":"Co-immunoprecipitation, mass spectrometry, Borg5 depletion in MDCK monolayers, functional contractility and adhesion assays","pmids":["39503295"],"confidence":"Medium","gaps":["Structural basis of CDC42EP1–myosin IIA rod interaction unknown","How septin competition for CDC42EP1 is spatiotemporally regulated is unresolved","Single-lab finding; reciprocal validation performed but independent replication pending"]},{"year":null,"claim":"A unified structural and regulatory model explaining how Cdc42, septins, and myosin IIA compete for CDC42EP1 binding to coordinate protrusion, polarity, and contractility remains to be established.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structural data for CDC42EP1 or its complexes","Relative binding affinities among Cdc42, septins, and myosin IIA not quantified","In vivo relevance in mammalian tissues beyond neural crest and epithelia not tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,2,3,4]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[2]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,2,3]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["CDC42","MYH9"],"other_free_text":[]},"mechanistic_narrative":"CDC42EP1 (also known as MSE55/Borg5) is a CRIB domain-containing effector of GTP-bound Cdc42 that reorganizes the actin cytoskeleton to regulate cell shape, protrusion formation, and directed migration [PMID:10430899, PMID:29040749]. Cdc42 binding through the CRIB domain controls CDC42EP1 subcellular distribution between membrane protrusions and perinuclear patches, thereby directing protrusion formation and migration polarity; loss of CDC42EP1 causes rounding, membrane blebbing, and disrupted focal adhesion alignment in cranial neural crest cells [PMID:29040749]. CDC42EP1 reciprocally interacts with septin filaments at the cell center to maintain actin stress fiber stability, contractility, and persistent orientation during directed migration [PMID:36923257]. In epithelial monolayers, CDC42EP1 interacts with the myosin IIA rod domain and limits actomyosin contractility and cell–cell adhesion tension, with this interaction modulated by septin availability [PMID:39503295]."},"prefetch_data":{"uniprot":{"accession":"Q00587","full_name":"Cdc42 effector protein 1","aliases":["Binder of Rho GTPases 5","Serum protein MSE55"],"length_aa":391,"mass_kda":40.3,"function":"Probably involved in the organization of the actin cytoskeleton. Induced membrane extensions in fibroblasts","subcellular_location":"Endomembrane system; Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q00587/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CDC42EP1","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2},{"gene":"CDC42","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CDC42EP1","total_profiled":1310},"omim":[{"mim_id":"609171","title":"CDC42 EFFECTOR PROTEIN 5; CDC42EP5","url":"https://www.omim.org/entry/609171"},{"mim_id":"606084","title":"CDC42 EFFECTOR PROTEIN 1; CDC42EP1","url":"https://www.omim.org/entry/606084"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Actin filaments","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CDC42EP1"},"hgnc":{"alias_symbol":["MSE55","CEP1","Borg5"],"prev_symbol":[]},"alphafold":{"accession":"Q00587","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q00587","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q00587-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q00587-F1-predicted_aligned_error_v6.png","plddt_mean":54.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CDC42EP1","jax_strain_url":"https://www.jax.org/strain/search?query=CDC42EP1"},"sequence":{"accession":"Q00587","fasta_url":"https://rest.uniprot.org/uniprotkb/Q00587.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q00587/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q00587"}},"corpus_meta":[{"pmid":"24259455","id":"PMC_24259455","title":"The peptide-encoding CEP1 gene modulates lateral root and nodule numbers in Medicago truncatula.","date":"2013","source":"Journal of experimental botany","url":"https://pubmed.ncbi.nlm.nih.gov/24259455","citation_count":167,"is_preprint":false},{"pmid":"25035401","id":"PMC_25035401","title":"The cysteine protease CEP1, a key executor involved in tapetal programmed cell death, regulates pollen development in Arabidopsis.","date":"2014","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/25035401","citation_count":163,"is_preprint":false},{"pmid":"17895432","id":"PMC_17895432","title":"Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity.","date":"2007","source":"The journals of gerontology. 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America","url":"https://pubmed.ncbi.nlm.nih.gov/10430899","citation_count":37,"is_preprint":false},{"pmid":"30376110","id":"PMC_30376110","title":"The papain-like cysteine protease CEP1 is involved in programmed cell death and secondary wall thickening during xylem development in Arabidopsis.","date":"2019","source":"Journal of experimental botany","url":"https://pubmed.ncbi.nlm.nih.gov/30376110","citation_count":35,"is_preprint":false},{"pmid":"16879608","id":"PMC_16879608","title":"A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene.","date":"2006","source":"European journal of haematology","url":"https://pubmed.ncbi.nlm.nih.gov/16879608","citation_count":23,"is_preprint":false},{"pmid":"35046980","id":"PMC_35046980","title":"Application of Synthetic Peptide CEP1 Increases Nutrient Uptake Rates Along Plant Roots.","date":"2022","source":"Frontiers in plant 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(MSE55) was identified as a novel secreted protein expressed specifically in bone marrow stromal and endothelial cells, with a circulating serum form of ~55 kDa, suggesting a functional role in hematopoiesis.\",\n      \"method\": \"cDNA cloning, immunoblotting, Northern blot analysis, recombinant protein expression in E. coli\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (cloning, immunoblot, Northern blot) in single study establishing identity and localization\",\n      \"pmids\": [\"1629197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"CDC42EP1 (MSE55) binds to Cdc42 in a GTP-dependent manner through its CRIB domain; this interaction is required for MSE55-induced actin cytoskeleton reorganization, including membrane ruffle formation in COS-7 cells and long actin-based protrusions in NIH 3T3 cells. MSE55-induced protrusion formation was blocked by dominant-negative N17Cdc42 but not by dominant-negative N17Rac, placing MSE55 downstream of Cdc42 specifically.\",\n      \"method\": \"GST pulldown, CRIB domain mutagenesis, dominant-negative Cdc42/Rac overexpression, immunofluorescence, live-cell video microscopy\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — GST capture assay with mutagenesis, epistasis via dominant-negatives, multiple cell readouts in single study\",\n      \"pmids\": [\"10430899\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CDC42EP1 is required for directed migration of cranial neural crest cells; loss of Cdc42ep1 leads to rounder cell shapes, membrane blebbing, disrupted actin organization, and loss of focal adhesion alignment. Cdc42 directly interacts with Cdc42ep1 via the CRIB domain and regulates its subcellular localization: Cdc42ep1 is found in membrane protrusions (together with Cdc42) and in perinuclear patches (where Cdc42 is absent), and changes in Cdc42 level shift Cdc42ep1 distribution between these locations to control protrusion formation and migration directionality.\",\n      \"method\": \"Morpholino-mediated knockdown in Xenopus embryos, immunofluorescence, CRIB domain interaction assay, traction force measurements, live imaging\",\n      \"journal\": \"Journal of molecular cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined cellular phenotypes, direct interaction via CRIB domain, subcellular localization tied to functional consequence, multiple orthogonal methods\",\n      \"pmids\": [\"29040749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Cdc42ep1 colocalizes with septin filaments at the cell center in neural crest cells and interacts with septins in a reciprocal manner: septin filaments recruit Cdc42ep1 to the cell center, and Cdc42ep1 supports the formation of septin filaments. This Cdc42ep1–septin interaction is required for the stability, contractility, and persistent orientation of actin stress fibers during directed cell migration.\",\n      \"method\": \"Morpholino knockdown, colocalization analysis, live imaging, genetic epistasis between Cdc42ep1 and septin\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined phenotype, colocalization and epistasis, single lab\",\n      \"pmids\": [\"36923257\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Epithelial Borg5/Cdc42EP1 limits actomyosin contractility, cell-cell adhesion tension, and motility in MDCK monolayers; Borg5 depletion inhibits lateral F-actin cortex development and stimulates radial stress fibers. Borg5 interacts with the rod domain of myosin IIA (MYH9 heavy chain), and this interaction is reduced in the presence of septins. Borg5 also limits septin colocalization with microtubules, suggesting that Borg5 restricts contractility partly by counteracting septin-associated myosin activity.\",\n      \"method\": \"Borg5 depletion (KD) in MDCK cells, co-immunoprecipitation with myosin IIA rod domain, immunofluorescence, mass spectrometry (Überheide), functional contractility assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP with myosin IIA, KD with defined cellular phenotype, multiple readouts in single study\",\n      \"pmids\": [\"39503295\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CDC42EP1 expression is upregulated in ectopic endometriosis lesions and acts downstream of hsa_circ_0005991 via sponging of miR-30b-3p; elevated CDC42EP1 promotes epithelial-mesenchymal transition (EMT), and proliferation, migration, and invasion in Ishikawa cells.\",\n      \"method\": \"CircRNA/miRNA overexpression and knockdown, co-transfection rescue experiments, Western blot for EMT markers, cell function assays\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, indirect pathway placement via sponge mechanism without direct biochemical demonstration of CDC42EP1 mechanism\",\n      \"pmids\": [\"37757976\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CDC42EP1 (also known as MSE55/Borg5) is a CRIB domain-containing effector that binds active (GTP-bound) Cdc42 to regulate actin cytoskeleton organization and cell migration; it localizes to both membrane protrusions (with Cdc42) and perinuclear regions (without Cdc42), and its distribution between these compartments is controlled by Cdc42 levels to direct protrusion formation; it also interacts reciprocally with septin filaments to maintain actin stress fiber stability and orientation during directed migration, and interacts with the myosin IIA rod domain to limit actomyosin contractility in epithelial cells.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CDC42EP1 (also known as MSE55/Borg5) is a CRIB domain-containing effector of GTP-bound Cdc42 that reorganizes the actin cytoskeleton to regulate cell shape, protrusion formation, and directed migration [PMID:10430899, PMID:29040749]. Cdc42 binding through the CRIB domain controls CDC42EP1 subcellular distribution between membrane protrusions and perinuclear patches, thereby directing protrusion formation and migration polarity; loss of CDC42EP1 causes rounding, membrane blebbing, and disrupted focal adhesion alignment in cranial neural crest cells [PMID:29040749]. CDC42EP1 reciprocally interacts with septin filaments at the cell center to maintain actin stress fiber stability, contractility, and persistent orientation during directed migration [PMID:36923257]. In epithelial monolayers, CDC42EP1 interacts with the myosin IIA rod domain and limits actomyosin contractility and cell–cell adhesion tension, with this interaction modulated by septin availability [PMID:39503295].\",\n  \"teleology\": [\n    {\n      \"year\": 1992,\n      \"claim\": \"The initial discovery of CDC42EP1 (MSE55) as a novel secreted protein of bone marrow stroma established its molecular identity but left its signaling function unknown.\",\n      \"evidence\": \"cDNA cloning, immunoblotting, and Northern blot in bone marrow stromal/endothelial cells\",\n      \"pmids\": [\"1629197\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No signaling pathway placement\",\n        \"Functional role beyond expression in hematopoietic niche unresolved\",\n        \"Secreted form has not been functionally characterized in subsequent studies\"\n      ]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Demonstrating that MSE55 binds GTP-Cdc42 via its CRIB domain and that this interaction is required for actin reorganization and protrusion formation established CDC42EP1 as a bona fide Cdc42 effector governing cytoskeletal remodeling.\",\n      \"evidence\": \"GST pulldown, CRIB domain mutagenesis, dominant-negative Cdc42/Rac epistasis, immunofluorescence, and live-cell microscopy in COS-7 and NIH 3T3 cells\",\n      \"pmids\": [\"10430899\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Downstream effector mechanism linking CRIB engagement to actin remodeling not defined\",\n        \"Relevance in a physiological tissue context not established\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showing that Cdc42 levels control CDC42EP1 partitioning between membrane protrusions and perinuclear patches, and that loss of CDC42EP1 disrupts directed neural crest migration, connected the Cdc42–CDC42EP1 axis to cell polarity and migration in vivo.\",\n      \"evidence\": \"Morpholino knockdown in Xenopus cranial neural crest, immunofluorescence, CRIB interaction assay, traction force measurements, live imaging\",\n      \"pmids\": [\"29040749\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of perinuclear interaction partners unknown\",\n        \"Mechanism by which CDC42EP1 organizes focal adhesion alignment not resolved\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealing a reciprocal interaction between CDC42EP1 and septin filaments that maintains actin stress fiber stability and orientation identified septins as a key structural partner bridging CDC42EP1 to the contractile cytoskeleton during directed migration.\",\n      \"evidence\": \"Morpholino knockdown, colocalization analysis, live imaging, and genetic epistasis between Cdc42ep1 and septins in neural crest cells\",\n      \"pmids\": [\"36923257\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical binding interface between CDC42EP1 and septins not mapped\",\n        \"Whether septin interaction is CRIB-domain-dependent or -independent is untested\",\n        \"Single-lab finding not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identifying myosin IIA (MYH9) rod domain as a direct CDC42EP1-binding partner whose interaction is antagonized by septins provided a molecular mechanism by which CDC42EP1 limits actomyosin contractility in epithelial sheets.\",\n      \"evidence\": \"Co-immunoprecipitation, mass spectrometry, Borg5 depletion in MDCK monolayers, functional contractility and adhesion assays\",\n      \"pmids\": [\"39503295\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural basis of CDC42EP1–myosin IIA rod interaction unknown\",\n        \"How septin competition for CDC42EP1 is spatiotemporally regulated is unresolved\",\n        \"Single-lab finding; reciprocal validation performed but independent replication pending\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unified structural and regulatory model explaining how Cdc42, septins, and myosin IIA compete for CDC42EP1 binding to coordinate protrusion, polarity, and contractility remains to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structural data for CDC42EP1 or its complexes\",\n        \"Relative binding affinities among Cdc42, septins, and myosin IIA not quantified\",\n        \"In vivo relevance in mammalian tissues beyond neural crest and epithelia not tested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 2, 3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"CDC42\",\n      \"MYH9\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}