{"gene":"DENND10","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2019,"finding":"FAM45A (DENND10) localizes to late/multivesicular endosomes, and its depletion causes perinuclear clustering of endosomes, impaired EGF receptor endocytosis due to a delay in early-to-late endosome transition, and attenuated secretion of selected exosome subpopulations.","method":"Knockdown (siRNA/shRNA), fluorescence microscopy/colocalization, endocytosis assays","journal":"Biochimica et biophysica acta. Molecular cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined cellular phenotypes (endosomal positioning, maturation, exosome secretion) and multiple orthogonal assays in a single lab","pmids":["30771381"],"is_preprint":false},{"year":2019,"finding":"FAM45A (DENND10) co-localizes with Rab27a and Rab27b and forms a complex with them in a nucleotide-dependent manner, placing Rab27a/b downstream of FAM45A in endosome motility and exosome biogenesis pathways.","method":"Co-immunoprecipitation, colocalization by fluorescence microscopy, nucleotide-loading experiments","journal":"Biochimica et biophysica acta. Molecular cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP demonstrating nucleotide-dependent complex formation and epistasis placing Rab27a/b downstream, single lab","pmids":["30771381"],"is_preprint":false},{"year":2024,"finding":"Cryo-EM structure of the endogenous human Commander complex reveals that DENND10 is part of an 'effector' module together with the Retriever subcomplex (VPS26C, VPS29, VPS35L), and this effector is scaffolded to the COMMD1-10 core by CCDC22 and CCDC93; key interaction interfaces were mapped.","method":"Cryogenic electron microscopy (cryo-EM) and mass spectrometry-based proteomics of endogenous complex","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure of endogenous complex with MS-based proteomics validation, published in high-impact journal","pmids":["38459129"],"is_preprint":false},{"year":2024,"finding":"DENND10 knockout in breast cancer cells causes defective EV biogenesis due to impaired endolysosomal trafficking, reduced cell spreading, migration, invasion, and metastatic potential in vivo; wild-type conditioned medium or EVs restore migratory ability and cytoskeletal organization, and global proteomics shows remodeled ECM and adhesion molecule profiles in EVs from KO cells.","method":"CRISPR knockout, in vitro migration/invasion assays, in vivo metastasis assay, conditioned medium rescue, global proteomic profiling","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with multiple functional readouts (EV biogenesis, motility, in vivo metastasis), rescue experiments, and proteomics; single lab","pmids":["38987765"],"is_preprint":false},{"year":2025,"finding":"Loss of DENND10 in a neuronal cell culture model results in shortened neurites; mechanistically, both Rab27 and CCC complex subunit CCDC22 act downstream of DENND10 to support neurite extension, establishing DENND10 upstream of the CCC/Retriever endosomal complex in neuronal morphogenesis.","method":"DENND10 loss-of-function in neuronal cell culture and primary cortical neurons, quantitative proteomics, genetic epistasis (Rab27 and CCDC22 rescue/KD experiments)","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined morphological phenotype and epistasis placing Rab27 and CCDC22 downstream; single lab, multiple orthogonal methods","pmids":["40330880"],"is_preprint":false}],"current_model":"DENND10 (FAM45A) is an endosomal DENN-domain protein that localizes to late/multivesicular endosomes and functions as a component of the 16-subunit Commander complex—where cryo-EM places it in an effector module with the Retriever subcomplex, scaffolded by CCDC22/CCDC93 onto the COMMD1-10 core—and acts upstream of Rab27a/b and the CCC complex subunit CCDC22 to regulate endolysosomal trafficking, exosome/EV biogenesis, cell migration, and neurite extension."},"narrative":{"mechanistic_narrative":"DENND10 (FAM45A) is an endosomal DENN-domain protein that governs endolysosomal trafficking and extracellular vesicle biogenesis [PMID:30771381, PMID:38987765]. It localizes to late/multivesicular endosomes, where its loss causes perinuclear endosome clustering and a delay in the early-to-late endosome transition that impairs EGF receptor endocytosis and attenuates secretion of selected exosome subpopulations [PMID:30771381]. DENND10 acts upstream of Rab27a/b, with which it forms a nucleotide-dependent complex, positioning these Rab GTPases as downstream effectors in endosome motility and exosome biogenesis [PMID:30771381]. Structurally, DENND10 is an integral subunit of the 16-subunit Commander complex, where cryo-EM places it within an effector module alongside the Retriever subcomplex (VPS26C, VPS29, VPS35L), scaffolded onto the COMMD1-10 core by CCDC22 and CCDC93 [PMID:38459129]. Through this trafficking machinery DENND10 controls cell-physiological outputs: its knockout in breast cancer cells disrupts EV biogenesis and remodels the ECM/adhesion content of secreted EVs, reducing cell spreading, migration, invasion, and metastasis—defects rescued by wild-type conditioned medium or EVs [PMID:38987765]—and in neurons it supports neurite extension via downstream Rab27 and the CCC subunit CCDC22 [PMID:40330880].","teleology":[{"year":2019,"claim":"Establishing where DENND10 acts and what it does, defining it as a late/multivesicular endosome protein required for endosome maturation and exosome secretion.","evidence":"siRNA/shRNA knockdown with colocalization microscopy and endocytosis assays","pmids":["30771381"],"confidence":"Medium","gaps":["Molecular activity of the DENN domain not biochemically defined","Mechanism linking endosome maturation delay to exosome defect not resolved"]},{"year":2019,"claim":"Connecting DENND10 to a downstream effector by showing it forms a nucleotide-dependent complex with Rab27a/b, placing these GTPases below DENND10 in endosome motility and exosome pathways.","evidence":"Co-immunoprecipitation, colocalization, and nucleotide-loading experiments","pmids":["30771381"],"confidence":"Medium","gaps":["Whether DENND10 acts as a GEF toward Rab27 not demonstrated","Direct vs indirect nature of the complex not established"]},{"year":2024,"claim":"Resolving DENND10's molecular context by placing it structurally within the Commander complex as part of a Retriever-containing effector module scaffolded by CCDC22/CCDC93.","evidence":"Cryo-EM of endogenous human Commander complex with MS-based proteomics","pmids":["38459129"],"confidence":"High","gaps":["Functional contribution of DENND10 within the assembled complex not tested","How Commander assembly relates to the Rab27 pathway unresolved"]},{"year":2024,"claim":"Linking DENND10-dependent trafficking to disease-relevant cell behavior, showing its loss impairs EV biogenesis and reduces migration, invasion, and metastasis through altered EV cargo.","evidence":"CRISPR knockout in breast cancer cells, in vitro/in vivo motility and metastasis assays, EV/conditioned-medium rescue, global proteomics","pmids":["38987765"],"confidence":"Medium","gaps":["Specific EV cargo responsible for migratory rescue not pinpointed","Single-lab, single cancer model"]},{"year":2025,"claim":"Generalizing DENND10's trafficking role to neuronal morphogenesis and placing it genetically upstream of both Rab27 and the CCC subunit CCDC22.","evidence":"Loss-of-function in neuronal cultures and primary cortical neurons, quantitative proteomics, epistasis with Rab27 and CCDC22","pmids":["40330880"],"confidence":"Medium","gaps":["Cargo whose trafficking drives neurite extension not identified","In vivo neuronal relevance not tested"]},{"year":null,"claim":"The biochemical activity of the DENND10 DENN domain and whether it functions as a guanine nucleotide exchange factor for Rab27 remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted GEF or enzymatic assay","No structural model of the DENN domain engaging a Rab","Relationship between Commander membership and Rab27 regulation unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,3]}],"complexes":["Commander complex"],"partners":["RAB27A","RAB27B","VPS26C","VPS29","VPS35L","CCDC22","CCDC93"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8TCE6","full_name":"DENN domain-containing protein 10","aliases":["Protein FAM45A"],"length_aa":357,"mass_kda":40.5,"function":"Guanine nucleotide exchange factor (GEF) regulating homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as RAB27A and RAB27B (PubMed:38459129). Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB27A and RAB27B into their active GTP-bound form (PubMed:30771381, PubMed:38459129)","subcellular_location":"Late endosome","url":"https://www.uniprot.org/uniprotkb/Q8TCE6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DENND10","classification":"Not Classified","n_dependent_lines":16,"n_total_lines":1208,"dependency_fraction":0.013245033112582781},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DENND10","total_profiled":1310},"omim":[{"mim_id":"620553","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 93; CCDC93","url":"https://www.omim.org/entry/620553"},{"mim_id":"618981","title":"VPS35 ENDOSOMAL PROTEIN-SORTING FACTOR-LIKE; VPS35L","url":"https://www.omim.org/entry/618981"},{"mim_id":"607238","title":"COMM DOMAIN-CONTAINING PROTEIN 1; COMMD1","url":"https://www.omim.org/entry/607238"},{"mim_id":"606932","title":"VPS29 RETROMER COMPLEX COMPONENT; VPS29","url":"https://www.omim.org/entry/606932"},{"mim_id":"605298","title":"VPS26 ENDOSOMAL PROTEIN-SORTING FACTOR C; VPS26C","url":"https://www.omim.org/entry/605298"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DENND10"},"hgnc":{"alias_symbol":[],"prev_symbol":["FAM45A"]},"alphafold":{"accession":"Q8TCE6","domains":[{"cath_id":"3.30.450,3.30.450","chopping":"2-153","consensus_level":"high","plddt":88.958,"start":2,"end":153},{"cath_id":"3.40.50.11500","chopping":"155-271","consensus_level":"medium","plddt":96.6132,"start":155,"end":271},{"cath_id":"1.10.10","chopping":"275-353","consensus_level":"medium","plddt":86.0099,"start":275,"end":353}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TCE6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TCE6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TCE6-F1-predicted_aligned_error_v6.png","plddt_mean":90.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DENND10","jax_strain_url":"https://www.jax.org/strain/search?query=DENND10"},"sequence":{"accession":"Q8TCE6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8TCE6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8TCE6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TCE6"}},"corpus_meta":[{"pmid":"38459129","id":"PMC_38459129","title":"Structure and interactions of the endogenous human Commander complex.","date":"2024","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/38459129","citation_count":35,"is_preprint":false},{"pmid":"30771381","id":"PMC_30771381","title":"DENN domain-containing protein FAM45A regulates the homeostasis of late/multivesicular endosomes.","date":"2019","source":"Biochimica et biophysica acta. Molecular cell research","url":"https://pubmed.ncbi.nlm.nih.gov/30771381","citation_count":23,"is_preprint":false},{"pmid":"34943955","id":"PMC_34943955","title":"Commander Complex-A Multifaceted Operator in Intracellular Signaling and Cargo.","date":"2021","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/34943955","citation_count":17,"is_preprint":false},{"pmid":"27685995","id":"PMC_27685995","title":"Genome Analysis of Osteosarcoma Progression Samples Identifies FGFR1 Overexpression as a Potential Treatment Target and CHM as a Candidate Tumor Suppressor Gene.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27685995","citation_count":14,"is_preprint":false},{"pmid":"31732251","id":"PMC_31732251","title":"Study of proteins with mercury in fish from the Amazon region.","date":"2019","source":"Food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31732251","citation_count":12,"is_preprint":false},{"pmid":"38987765","id":"PMC_38987765","title":"Endosomal protein DENND10/FAM45A integrates extracellular vesicle release with cancer cell migration.","date":"2024","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/38987765","citation_count":4,"is_preprint":false},{"pmid":"40330880","id":"PMC_40330880","title":"Endosomal protein DENND10 promotes developmental competence of neurite extension.","date":"2025","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/40330880","citation_count":0,"is_preprint":false},{"pmid":"40995562","id":"PMC_40995562","title":"Epigenetic modifications in developmental coordination disorder: association between DNA methylation and motor performance.","date":"2025","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/40995562","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5455,"output_tokens":1361,"usd":0.01839,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7979,"output_tokens":1995,"usd":0.044885,"stage2_stop_reason":"end_turn"},"total_usd":0.063275,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"FAM45A (DENND10) localizes to late/multivesicular endosomes, and its depletion causes perinuclear clustering of endosomes, impaired EGF receptor endocytosis due to a delay in early-to-late endosome transition, and attenuated secretion of selected exosome subpopulations.\",\n      \"method\": \"Knockdown (siRNA/shRNA), fluorescence microscopy/colocalization, endocytosis assays\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined cellular phenotypes (endosomal positioning, maturation, exosome secretion) and multiple orthogonal assays in a single lab\",\n      \"pmids\": [\"30771381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"FAM45A (DENND10) co-localizes with Rab27a and Rab27b and forms a complex with them in a nucleotide-dependent manner, placing Rab27a/b downstream of FAM45A in endosome motility and exosome biogenesis pathways.\",\n      \"method\": \"Co-immunoprecipitation, colocalization by fluorescence microscopy, nucleotide-loading experiments\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP demonstrating nucleotide-dependent complex formation and epistasis placing Rab27a/b downstream, single lab\",\n      \"pmids\": [\"30771381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Cryo-EM structure of the endogenous human Commander complex reveals that DENND10 is part of an 'effector' module together with the Retriever subcomplex (VPS26C, VPS29, VPS35L), and this effector is scaffolded to the COMMD1-10 core by CCDC22 and CCDC93; key interaction interfaces were mapped.\",\n      \"method\": \"Cryogenic electron microscopy (cryo-EM) and mass spectrometry-based proteomics of endogenous complex\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure of endogenous complex with MS-based proteomics validation, published in high-impact journal\",\n      \"pmids\": [\"38459129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DENND10 knockout in breast cancer cells causes defective EV biogenesis due to impaired endolysosomal trafficking, reduced cell spreading, migration, invasion, and metastatic potential in vivo; wild-type conditioned medium or EVs restore migratory ability and cytoskeletal organization, and global proteomics shows remodeled ECM and adhesion molecule profiles in EVs from KO cells.\",\n      \"method\": \"CRISPR knockout, in vitro migration/invasion assays, in vivo metastasis assay, conditioned medium rescue, global proteomic profiling\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with multiple functional readouts (EV biogenesis, motility, in vivo metastasis), rescue experiments, and proteomics; single lab\",\n      \"pmids\": [\"38987765\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of DENND10 in a neuronal cell culture model results in shortened neurites; mechanistically, both Rab27 and CCC complex subunit CCDC22 act downstream of DENND10 to support neurite extension, establishing DENND10 upstream of the CCC/Retriever endosomal complex in neuronal morphogenesis.\",\n      \"method\": \"DENND10 loss-of-function in neuronal cell culture and primary cortical neurons, quantitative proteomics, genetic epistasis (Rab27 and CCDC22 rescue/KD experiments)\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined morphological phenotype and epistasis placing Rab27 and CCDC22 downstream; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"40330880\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DENND10 (FAM45A) is an endosomal DENN-domain protein that localizes to late/multivesicular endosomes and functions as a component of the 16-subunit Commander complex—where cryo-EM places it in an effector module with the Retriever subcomplex, scaffolded by CCDC22/CCDC93 onto the COMMD1-10 core—and acts upstream of Rab27a/b and the CCC complex subunit CCDC22 to regulate endolysosomal trafficking, exosome/EV biogenesis, cell migration, and neurite extension.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DENND10 (FAM45A) is an endosomal DENN-domain protein that governs endolysosomal trafficking and extracellular vesicle biogenesis [#0, #3]. It localizes to late/multivesicular endosomes, where its loss causes perinuclear endosome clustering and a delay in the early-to-late endosome transition that impairs EGF receptor endocytosis and attenuates secretion of selected exosome subpopulations [#0]. DENND10 acts upstream of Rab27a/b, with which it forms a nucleotide-dependent complex, positioning these Rab GTPases as downstream effectors in endosome motility and exosome biogenesis [#1]. Structurally, DENND10 is an integral subunit of the 16-subunit Commander complex, where cryo-EM places it within an effector module alongside the Retriever subcomplex (VPS26C, VPS29, VPS35L), scaffolded onto the COMMD1-10 core by CCDC22 and CCDC93 [#2]. Through this trafficking machinery DENND10 controls cell-physiological outputs: its knockout in breast cancer cells disrupts EV biogenesis and remodels the ECM/adhesion content of secreted EVs, reducing cell spreading, migration, invasion, and metastasis—defects rescued by wild-type conditioned medium or EVs [#3]—and in neurons it supports neurite extension via downstream Rab27 and the CCC subunit CCDC22 [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing where DENND10 acts and what it does, defining it as a late/multivesicular endosome protein required for endosome maturation and exosome secretion.\",\n      \"evidence\": \"siRNA/shRNA knockdown with colocalization microscopy and endocytosis assays\",\n      \"pmids\": [\"30771381\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular activity of the DENN domain not biochemically defined\", \"Mechanism linking endosome maturation delay to exosome defect not resolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connecting DENND10 to a downstream effector by showing it forms a nucleotide-dependent complex with Rab27a/b, placing these GTPases below DENND10 in endosome motility and exosome pathways.\",\n      \"evidence\": \"Co-immunoprecipitation, colocalization, and nucleotide-loading experiments\",\n      \"pmids\": [\"30771381\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether DENND10 acts as a GEF toward Rab27 not demonstrated\", \"Direct vs indirect nature of the complex not established\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Resolving DENND10's molecular context by placing it structurally within the Commander complex as part of a Retriever-containing effector module scaffolded by CCDC22/CCDC93.\",\n      \"evidence\": \"Cryo-EM of endogenous human Commander complex with MS-based proteomics\",\n      \"pmids\": [\"38459129\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional contribution of DENND10 within the assembled complex not tested\", \"How Commander assembly relates to the Rab27 pathway unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linking DENND10-dependent trafficking to disease-relevant cell behavior, showing its loss impairs EV biogenesis and reduces migration, invasion, and metastasis through altered EV cargo.\",\n      \"evidence\": \"CRISPR knockout in breast cancer cells, in vitro/in vivo motility and metastasis assays, EV/conditioned-medium rescue, global proteomics\",\n      \"pmids\": [\"38987765\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific EV cargo responsible for migratory rescue not pinpointed\", \"Single-lab, single cancer model\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Generalizing DENND10's trafficking role to neuronal morphogenesis and placing it genetically upstream of both Rab27 and the CCC subunit CCDC22.\",\n      \"evidence\": \"Loss-of-function in neuronal cultures and primary cortical neurons, quantitative proteomics, epistasis with Rab27 and CCDC22\",\n      \"pmids\": [\"40330880\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo whose trafficking drives neurite extension not identified\", \"In vivo neuronal relevance not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of the DENND10 DENN domain and whether it functions as a guanine nucleotide exchange factor for Rab27 remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconstituted GEF or enzymatic assay\", \"No structural model of the DENN domain engaging a Rab\", \"Relationship between Commander membership and Rab27 regulation unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\"Commander complex\"],\n    \"partners\": [\"RAB27A\", \"RAB27B\", \"VPS26C\", \"VPS29\", \"VPS35L\", \"CCDC22\", \"CCDC93\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}