{"gene":"RAB11FIP3","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2001,"finding":"Eferin (RAB11FIP3) was identified as a novel Rab11 effector protein. A 20-amino acid domain at the C-terminus of Eferin (and related Rab11/25-interacting proteins Rip11 and nRip11) was shown to be necessary and sufficient for Rab11 binding in vitro and required for correct localization of Rab11 effector proteins in vivo.","method":"Biochemical binding assays (in vitro Rab11 binding), mutagenesis of the C-terminal domain, in vivo localization studies","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with domain mutagenesis, in vivo localization validation, and identification of shared domain across protein family","pmids":["11481332"],"is_preprint":false},{"year":2004,"finding":"RAB11FIP3 localizes to a Rab11-positive pericentrosomal compartment during interphase and to the cleavage furrow during cytokinesis. This localization is dependent on both microtubule and actin filament integrity. Expression of an N-terminally truncated mutant (Rab11-FIP3(244-756)) did not inhibit transferrin recycling, suggesting RAB11FIP3 is not required for transferrin recycling.","method":"Immunofluorescence microscopy with specific polyclonal antibody, cytoskeletal disruption experiments, dominant-negative mutant expression, transferrin recycling assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiments with functional cytoskeletal perturbations and mutant expression, single lab","pmids":["15158446"],"is_preprint":false},{"year":2007,"finding":"RAB11FIP3 is critical for the structural integrity of the endosomal recycling compartment (ERC). Knockdown of RAB11FIP3 or expression of a Rab11-binding-deficient mutant caused loss of all ERC-marker protein staining from the pericentrosomal region and blocked fluorophore-labelled transferrin from accessing the pericentrosomal region. A coiled-coil region between residues 463–692 that exists as a dimer in solution is critical for RAB11FIP3 function on the ERC.","method":"siRNA knockdown, Rab11-binding-deficient mutant expression, immunofluorescence microscopy, transferrin trafficking assay, biochemical analysis of coiled-coil domain dimerization","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal KD and dominant-negative mutant approaches with specific phenotypic readouts, plus biochemical domain characterization, single lab but multiple orthogonal methods","pmids":["17394487"],"is_preprint":false},{"year":2007,"finding":"RAB11FIP3 predominantly interacts with Arf6 (over Arf4/5) in vitro and in vivo. FIP3 binds to the Arf6 C-terminus rather than the switch motifs. Arf6 binding to FIP3 is required for targeting Arf6 to the cleavage furrow during cytokinesis, and FIP3 acts as a scaffolding protein for Arf6 recruitment to the midbody during late telophase.","method":"Biochemical affinity measurements (various Arf GTPases), co-immunoprecipitation, domain mapping/mutagenesis, live-cell imaging during cytokinesis","journal":"European journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro biochemical affinity assays combined with domain mutagenesis and in vivo functional validation, single lab with multiple orthogonal methods","pmids":["17628206"],"is_preprint":false},{"year":2009,"finding":"RAB11FIP3 directly interacts with dynein light intermediate chain 1 (DLIC-1, DYNC1LI1), a subunit of cytoplasmic dynein 1. Rab11a, FIP3, and DLIC-1 form a ternary complex. FIP3 recruits DLIC-1 onto membranes, and association between FIP3 and DLIC-1 at the cell periphery precedes minus-end-directed microtubule-based transport. Knockdown of DLIC-1 inhibits pericentrosomal accumulation of ERC proteins. A DLIC-1-binding truncation mutant of FIP3 disrupts ERC protein pericentrosomal accumulation.","method":"Co-immunoprecipitation, GST pulldown, immunofluorescence co-localization, siRNA knockdown, dominant-negative mutant expression","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP demonstrating ternary complex, membrane recruitment assay, KD with specific ERC phenotype, and mutant expression; multiple orthogonal methods","pmids":["20026645"],"is_preprint":false},{"year":2009,"finding":"RAB11FIP3 is associated with recycling endosomes at the leading edge of motile breast carcinoma cells. FIP3 is required for motility of MDA-MB-231 cells, regulates Rac1-dependent actin cytoskeleton dynamics and lamellipodia formation/ruffling, and controls Arf6 localization at the plasma membrane of migrating cells.","method":"siRNA knockdown, cell motility assays, immunofluorescence microscopy, actin dynamics assessment","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD with defined cellular phenotype (motility, actin dynamics, Arf6 localization), single lab, multiple readouts","pmids":["19327867"],"is_preprint":false},{"year":2010,"finding":"RAB11FIP3 also binds dynein light intermediate chain 2 (DLIC-2, DYNC1LI2) via its N-terminal 435 amino acids and links Rab11a to DLIC-2. FIP3 recruits DLIC-2 onto membranes. DLIC-2 is necessary for pericentrosomal accumulation of endocytosed transferrin at the ERC. Overexpression of FIP3 fragments the Golgi complex by sequestering cytoplasmic dynein-1.","method":"Co-immunoprecipitation, membrane recruitment assay, siRNA knockdown of DLIC-2, transferrin trafficking assay, overexpression with Golgi morphology assessment","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with domain mapping, membrane recruitment assay, and KD phenotype; single lab with multiple methods","pmids":["20214888"],"is_preprint":false},{"year":2011,"finding":"FIP3 localization to recycling endosomes in interphase and their transport to the intercellular bridge during cytokinesis depend on Rab11. Targeting of FIP3-positive endosomal vesicles to the Flemming body (midbody) in the abscission phase depends on Arf6. After abscission, FIP3 and Arf6 are incorporated into one daughter cell as a Flemming body remnant.","method":"Detection of endogenous proteins by immunofluorescence, time-lapse analysis of FIP3, Rab11, and Arf6 localization during cytokinesis","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — time-lapse imaging with endogenous protein detection establishes sequential dependency on Rab11 then Arf6; single lab","pmids":["21790911"],"is_preprint":false},{"year":2012,"finding":"RAB11FIP3 is a cell cycle-regulated phosphoprotein with four in vivo phosphorylation sites (S-102, S-280, S-347, S-450). S-102 is a Cdk1-cyclin B substrate in vitro, is phosphorylated in metaphase, and dephosphorylated as cells enter telophase. Expression of FIP3-S102D increased binucleate cell frequency. Dephosphorylation of FIP3 accompanies its translocation from the cytosol to membranes during telophase, but the identified phospho-acceptor sites do not control spatial recycling endosome distribution.","method":"Mass spectrometry phosphosite identification, in vitro Cdk1-cyclin B kinase assay, phospho-specific analysis across cell cycle stages, phosphomimetic/phospho-dead mutant expression, binucleate cell frequency scoring","journal":"BMC cell biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase assay identifying Cdk1 as writer, in vivo phosphorylation mapping, and functional phosphomimetic mutant analysis; single lab","pmids":["22401586"],"is_preprint":false},{"year":2016,"finding":"RAB11FIP3 controls Rac1 intracellular localization and targeting to the immunological synapse. A significant fraction of Rac1 associates with Rab11-positive recycling endosomes, and FIP3 mediates this association. FIP3 regulates T-cell spreading, synapse symmetry, and T-cell activation leading to cytokine production in a Rac1-dependent manner.","method":"Overexpression and siRNA silencing of FIP3, co-localization studies (Rac1 with Rab11-positive endosomes), live-cell imaging, T-cell activation assays (cytokine production)","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FIP3 KD/OE with defined T-cell phenotypes and Rac1 localization readout, Rac1-dependency tested; single lab with multiple methods","pmids":["27154205"],"is_preprint":false},{"year":2017,"finding":"RAB11FIP3-dependent endosomal trafficking of Lck controls its delivery to the immunological synapse and modulates early TCR signaling events including tyrosine phosphorylation of TCRζ, ZAP70, and LAT, intracellular calcium levels, and IL-2 gene expression. FIP3's interaction with Rab11 is required for proper Lck subcellular localization. FIP3 modulates TCR-CD3 cell surface expression via regulation of steady-state Lck-mediated TCRζ phosphorylation.","method":"FIP3 overexpression and siRNA silencing, Rab11-interaction mutants, immunofluorescence localization of Lck, phosphotyrosine western blotting, calcium flux assays, IL-2 reporter assays","journal":"Journal of immunology (Baltimore, Md. : 1950)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FIP3 KD/OE with Rab11-interaction mutants and multiple signaling readouts; single lab with multiple orthogonal methods","pmids":["28235866"],"is_preprint":false},{"year":2024,"finding":"RAB11FIP3 facilitates endosomal recycling of PD-L1 to the cell membrane of gastric cancer cells. The transcription factors IKZF4 and NONO synergistically upregulate RAB11FIP3 expression. Silencing of RAB11FIP3 reduces PD-L1 surface expression, promotes T-cell proliferation and cytotoxicity towards gastric cancer cells, and inhibits tumor immune evasion in vivo.","method":"RAB11FIP3 overexpression and siRNA silencing, PD-L1 cell-surface expression assay, T-cell cytotoxicity assays, in vivo mouse tumor experiments with CD8+ T-cell infiltration analysis, transcription factor KO experiments","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined PD-L1 recycling phenotype and in vivo validation; single lab with multiple methods","pmids":["38211652"],"is_preprint":false}],"current_model":"RAB11FIP3 (Eferin/Rab11-FIP3) is a dual Rab11/Arf6 effector and scaffolding protein that links Rab11-positive recycling endosomes to cytoplasmic dynein (via direct binding to both DLIC-1 and DLIC-2) to drive minus-end-directed microtubule transport of endosomal cargo to the pericentrosomal endosomal recycling compartment (ERC); it is essential for ERC structural integrity via its dimerizing coiled-coil domain; it recruits Arf6 to the cleavage furrow and midbody to regulate cytokinesis abscission; it is cell cycle-regulated by Cdk1-mediated phosphorylation at S-102; and it controls polarized Rac1 and Lck delivery to the immunological synapse, thereby modulating actin dynamics, TCR signaling, and T-cell activation, as well as PD-L1 recycling in cancer cells."},"narrative":{"mechanistic_narrative":"RAB11FIP3 (Eferin/Rab11-FIP3) is a Rab11/Arf6 dual-effector scaffolding protein that couples Rab11-positive recycling endosomes to the cytoplasmic dynein motor to organize the pericentrosomal endosomal recycling compartment (ERC) and to direct endosome-driven processes including cytokinesis and immune-synapse signaling [PMID:11481332, PMID:17394487, PMID:20026645]. A C-terminal 20-residue domain mediates direct Rab11 binding, and this interaction is required for correct effector localization to a Rab11-positive pericentrosomal compartment [PMID:11481332, PMID:15158446]. RAB11FIP3 is essential for ERC structural integrity: loss of RAB11FIP3 or Rab11-binding-deficient mutants disperses ERC markers and blocks transferrin delivery to the pericentrosomal region, a function that depends on a dimerizing coiled-coil region (residues 463–692) [PMID:17394487]. It establishes minus-end-directed transport by directly binding cytoplasmic dynein light intermediate chains DLIC-1 (DYNC1LI1) and DLIC-2 (DYNC1LI2), forming Rab11a–FIP3–DLIC ternary complexes and recruiting dynein onto endosomal membranes [PMID:20026645, PMID:20214888]. In parallel, RAB11FIP3 preferentially binds the Arf6 C-terminus and acts as a scaffold delivering Arf6 to the cleavage furrow and midbody during cytokinesis, with sequential Rab11- then Arf6-dependent targeting of FIP3 vesicles to the Flemming body during abscission [PMID:17628206, PMID:21790911]. Its activity is cell-cycle gated by Cdk1–cyclin B phosphorylation at S-102, which is high in metaphase and removed at telophase as FIP3 translocates from cytosol to membranes [PMID:22401586]. Through Rab11-dependent endosomal recycling, RAB11FIP3 targets Rac1 and Lck to the immunological synapse to control actin dynamics, TCR proximal signaling and T-cell activation [PMID:27154205, PMID:28235866], and drives endosomal recycling of PD-L1 to the cancer-cell surface to promote tumor immune evasion [PMID:38211652].","teleology":[{"year":2001,"claim":"Established RAB11FIP3 as a Rab11 effector and defined the minimal binding determinant, answering how the protein is recruited to recycling-endosome machinery.","evidence":"In vitro Rab11 binding assays with C-terminal domain mutagenesis and in vivo localization across the Rab11/25-interacting protein family","pmids":["11481332"],"confidence":"High","gaps":["Did not define downstream effector function","No structural model of the Rab11-binding interface"]},{"year":2004,"claim":"Placed RAB11FIP3 at a pericentrosomal Rab11 compartment in interphase and the cleavage furrow in cytokinesis, linking it to cytoskeleton-dependent positioning rather than bulk transferrin recycling.","evidence":"Immunofluorescence with cytoskeletal disruption and N-terminal truncation mutant; transferrin recycling assay","pmids":["15158446"],"confidence":"Medium","gaps":["Mechanism linking FIP3 to microtubule/actin not identified","Truncation result based on single dominant-negative construct"]},{"year":2007,"claim":"Demonstrated RAB11FIP3 is required for ERC structural integrity and mapped a dimerizing coiled-coil domain as the functional element, defining its scaffolding role at the recycling compartment.","evidence":"siRNA knockdown, Rab11-binding-deficient mutant, transferrin trafficking, and biochemical coiled-coil dimerization analysis","pmids":["17394487"],"confidence":"High","gaps":["Did not identify the motor or partners driving pericentrosomal accumulation","Single-lab phenotype"]},{"year":2007,"claim":"Identified Arf6 as a second effector partner and showed FIP3 scaffolds Arf6 recruitment to the furrow and midbody, connecting FIP3 to cytokinetic membrane delivery.","evidence":"Biochemical affinity comparison among Arf GTPases, Co-IP, domain mapping, and live-cell cytokinesis imaging","pmids":["17628206"],"confidence":"High","gaps":["Functional consequence of Arf6 binding for abscission completion not quantified here","Did not resolve coordination with Rab11 binding"]},{"year":2009,"claim":"Resolved the motor link by showing direct FIP3–DLIC-1 binding and Rab11a–FIP3–DLIC-1 ternary complex formation, explaining minus-end-directed transport of recycling endosomes to the ERC.","evidence":"Reciprocal Co-IP, GST pulldown, membrane recruitment, DLIC-1 knockdown, and truncation mutant disrupting ERC accumulation","pmids":["20026645"],"confidence":"High","gaps":["Did not address whether DLIC-2 contributes","Regulation of motor engagement timing unresolved"]},{"year":2009,"claim":"Extended FIP3 function to cell migration, showing it controls Rac1-dependent actin dynamics and Arf6 localization at the leading edge of carcinoma cells.","evidence":"siRNA knockdown with motility, actin dynamics, and Arf6 localization readouts in MDA-MB-231 cells","pmids":["19327867"],"confidence":"Medium","gaps":["Direct vs indirect control of Rac1 not distinguished here","Single cell-line model"]},{"year":2010,"claim":"Showed FIP3 also binds DLIC-2 via its N-terminal region, broadening the dynein-coupling repertoire and demonstrating dynein-sequestering effects on Golgi morphology.","evidence":"Co-IP with domain mapping, membrane recruitment, DLIC-2 knockdown transferrin assay, and overexpression Golgi morphology assessment","pmids":["20214888"],"confidence":"Medium","gaps":["Relative roles of DLIC-1 vs DLIC-2 not delineated","Golgi fragmentation may be an overexpression artifact"]},{"year":2011,"claim":"Established the temporal logic of cytokinetic targeting: Rab11 governs endosome recruitment and transport while Arf6 governs midbody targeting during abscission.","evidence":"Endogenous-protein immunofluorescence and time-lapse imaging of FIP3, Rab11, and Arf6 through cytokinesis","pmids":["21790911"],"confidence":"Medium","gaps":["Molecular trigger of the Rab11-to-Arf6 handoff unknown","Fate of Flemming body remnant function not addressed"]},{"year":2012,"claim":"Identified FIP3 as a cell-cycle-regulated phosphoprotein with Cdk1-cyclin B phosphorylating S-102, linking mitotic kinase activity to FIP3 cytosol-to-membrane translocation.","evidence":"Mass spectrometry phosphosite mapping, in vitro Cdk1-cyclin B kinase assay, phospho-staging, and phosphomimetic mutant binucleation scoring","pmids":["22401586"],"confidence":"Medium","gaps":["Identified sites do not control spatial endosome distribution","Phosphatase responsible for telophase dephosphorylation unknown"]},{"year":2016,"claim":"Demonstrated FIP3 mediates Rac1 association with Rab11 endosomes and its delivery to the immunological synapse, controlling T-cell spreading, synapse symmetry, and activation.","evidence":"FIP3 knockdown/overexpression, Rac1 co-localization, live imaging, and Rac1-dependent T-cell cytokine assays","pmids":["27154205"],"confidence":"Medium","gaps":["Direct FIP3–Rac1 binding vs endosome co-trafficking not separated","Single-lab T-cell model"]},{"year":2017,"claim":"Showed FIP3-dependent endosomal trafficking of Lck controls proximal TCR signaling and IL-2 expression, extending FIP3's synapse role to kinase delivery.","evidence":"FIP3 KD/OE with Rab11-interaction mutants, Lck localization, phosphotyrosine blotting, calcium flux, and IL-2 reporter assays","pmids":["28235866"],"confidence":"Medium","gaps":["Whether Lck is direct cargo or co-trafficked with Rab11 endosomes unresolved","Quantitative contribution to surface TCR-CD3 levels not fully defined"]},{"year":2024,"claim":"Connected FIP3 recycling activity to immune evasion by showing it recycles PD-L1 to the gastric cancer-cell surface under IKZF4/NONO transcriptional control.","evidence":"FIP3 KD/OE, PD-L1 surface assays, T-cell cytotoxicity, in vivo tumor experiments, and transcription-factor knockout","pmids":["38211652"],"confidence":"Medium","gaps":["Direct molecular link between FIP3 and PD-L1 cargo selection not defined","Single cancer-type model"]},{"year":null,"claim":"How RAB11FIP3 integrates competing Rab11- and Arf6-dependent functions and selects specific cargo (Rac1, Lck, PD-L1) for synapse versus midbody delivery remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the full FIP3 scaffold with simultaneous effector engagement","Cargo-selection mechanism for distinct trafficking routes unknown","Switch coordinating motor recruitment with phosphorylation state undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,4,6]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[4,6]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1,4,7]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[8]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[5,11]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,4,6]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3,7,8]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[9,10,11]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[4,6]}],"complexes":[],"partners":["RAB11A","ARF6","DYNC1LI1","DYNC1LI2","RAC1","LCK"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O75154","full_name":"Rab11 family-interacting protein 3","aliases":["Arfophilin-1","EF hands-containing Rab-interacting protein","Eferin","MU-MB-17.148"],"length_aa":756,"mass_kda":82.4,"function":"Downstream effector molecule for Rab11 GTPase which is involved in endocytic trafficking, cytokinesis and intracellular ciliogenesis by participating in membrane delivery (PubMed:15601896, PubMed:16148947, PubMed:17394487, PubMed:17628206, PubMed:18511905, PubMed:19327867, PubMed:20026645, PubMed:25673879, PubMed:26258637, PubMed:31204173). Recruited by Rab11 to endosomes where it links Rab11 to dynein motor complex (PubMed:20026645). The functional Rab11-RAB11FIP3-dynein complex regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endocytic recycling compartment (ERC) during interphase of cell cycle (PubMed:17394487, PubMed:20026645). Facilitates the interaction between dynein and dynactin and activates dynein processivity (PubMed:25035494). Binding with ASAP1 is needed to regulate the pericentrosomal localization of recycling endosomes (By similarity). The Rab11-RAB11FIP3 complex is also implicated in the transport during telophase of vesicles derived from recycling endosomes to the cleavage furrow via centrosome-anchored microtubules, where the vesicles function to deliver membrane during late cytokinesis and abscission (PubMed:15601896, PubMed:16148947). The recruitment of Rab11-RAB11FIP3-containing endosomes to the cleavage furrow and tethering to the midbody is co-mediated by RAB11FIP3 interaction with ARF6-exocyst and RACGAP1-MKLP1 tethering complexes (PubMed:17628206, PubMed:18511905). Also involved in the Rab11-Rabin8-Rab8 ciliogenesis cascade by facilitating the orderly assembly of a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which directs preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (PubMed:26258637, PubMed:31204173). Also promotes the activity of Rab11 and ASAP1 in the ARF4-dependent Golgi-to-cilia transport of the sensory receptor rhodopsin (PubMed:25673879). Competes with WDR44 for binding to Rab11, which controls intracellular ciliogenesis pathway (PubMed:31204173). May play a role in breast cancer cell motility by regulating actin cytoskeleton (PubMed:19327867)","subcellular_location":"Endosome membrane; Recycling endosome membrane; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cleavage furrow; Midbody; Golgi apparatus membrane; Golgi apparatus, trans-Golgi network membrane","url":"https://www.uniprot.org/uniprotkb/O75154/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RAB11FIP3","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RAB11FIP3","total_profiled":1310},"omim":[{"mim_id":"611999","title":"RAB11 FAMILY-INTERACTING PROTEIN 4; RAB11FIP4","url":"https://www.omim.org/entry/611999"},{"mim_id":"608738","title":"RAB11 FAMILY-INTERACTING PROTEIN 3; RAB11FIP3","url":"https://www.omim.org/entry/608738"},{"mim_id":"608737","title":"RAB11 FAMILY-INTERACTING PROTEIN 1; RAB11FIP1","url":"https://www.omim.org/entry/608737"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Centriolar satellite","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Cytokinetic bridge","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"kidney","ntpm":151.2}],"url":"https://www.proteinatlas.org/search/RAB11FIP3"},"hgnc":{"alias_symbol":["KIAA0665","Rab11-FIP3","eferin"],"prev_symbol":[]},"alphafold":{"accession":"O75154","domains":[{"cath_id":"1.10.238.10","chopping":"203-268","consensus_level":"medium","plddt":85.7661,"start":203,"end":268}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75154","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75154-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75154-F1-predicted_aligned_error_v6.png","plddt_mean":65.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RAB11FIP3","jax_strain_url":"https://www.jax.org/strain/search?query=RAB11FIP3"},"sequence":{"accession":"O75154","fasta_url":"https://rest.uniprot.org/uniprotkb/O75154.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75154/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75154"}},"corpus_meta":[{"pmid":"20026645","id":"PMC_20026645","title":"Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment.","date":"2009","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/20026645","citation_count":160,"is_preprint":false},{"pmid":"11481332","id":"PMC_11481332","title":"Identification of a novel Rab11/25 binding domain present in Eferin and Rip proteins.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11481332","citation_count":94,"is_preprint":false},{"pmid":"15158446","id":"PMC_15158446","title":"Rab11-FIP3 localises to a Rab11-positive pericentrosomal compartment during interphase and to the cleavage furrow during cytokinesis.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15158446","citation_count":87,"is_preprint":false},{"pmid":"17394487","id":"PMC_17394487","title":"Rab11-FIP3 is critical for the structural integrity of the endosomal recycling compartment.","date":"2007","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/17394487","citation_count":61,"is_preprint":false},{"pmid":"20214888","id":"PMC_20214888","title":"Rab11-FIP3 binds dynein light intermediate chain 2 and its overexpression fragments the Golgi complex.","date":"2010","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/20214888","citation_count":56,"is_preprint":false},{"pmid":"27154205","id":"PMC_27154205","title":"Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation.","date":"2016","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/27154205","citation_count":47,"is_preprint":false},{"pmid":"17628206","id":"PMC_17628206","title":"Molecular characterization of Rab11-FIP3 binding to ARF GTPases.","date":"2007","source":"European journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17628206","citation_count":44,"is_preprint":false},{"pmid":"19327867","id":"PMC_19327867","title":"Rab11-FIP3 is a Rab11-binding protein that regulates breast cancer cell motility by modulating the actin cytoskeleton.","date":"2009","source":"European journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19327867","citation_count":41,"is_preprint":false},{"pmid":"21790911","id":"PMC_21790911","title":"Distinct roles of Rab11 and Arf6 in the regulation of Rab11-FIP3/arfophilin-1 localization in mitotic cells.","date":"2011","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/21790911","citation_count":33,"is_preprint":false},{"pmid":"28235866","id":"PMC_28235866","title":"Rab11-FIP3 Regulation of Lck Endosomal Traffic Controls TCR Signal Transduction.","date":"2017","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/28235866","citation_count":24,"is_preprint":false},{"pmid":"28215104","id":"PMC_28215104","title":"Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.","date":"2017","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/28215104","citation_count":24,"is_preprint":false},{"pmid":"16473615","id":"PMC_16473615","title":"Purification and functional properties of Rab11-FIP3.","date":"2005","source":"Methods in enzymology","url":"https://pubmed.ncbi.nlm.nih.gov/16473615","citation_count":18,"is_preprint":false},{"pmid":"38211652","id":"PMC_38211652","title":"IKZF4/NONO-RAB11FIP3 axis promotes immune evasion in gastric cancer via facilitating PD-L1 endosome recycling.","date":"2024","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/38211652","citation_count":17,"is_preprint":false},{"pmid":"27533792","id":"PMC_27533792","title":"The functional interplay of Rab11, FIP3 and Rho proteins on the endosomal recycling pathway controls cell shape and symmetry.","date":"2016","source":"Small GTPases","url":"https://pubmed.ncbi.nlm.nih.gov/27533792","citation_count":13,"is_preprint":false},{"pmid":"22401586","id":"PMC_22401586","title":"Rab11-FIP3 is a cell cycle-regulated phosphoprotein.","date":"2012","source":"BMC cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/22401586","citation_count":12,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.01.678241","title":"The genetic architecture of trabecular bone score and association with fracture: a genome-wide association and meta-analysis","date":"2025-10-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.01.678241","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10303,"output_tokens":3686,"usd":0.043099,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11237,"output_tokens":4245,"usd":0.081155,"stage2_stop_reason":"end_turn"},"total_usd":0.124254,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"Eferin (RAB11FIP3) was identified as a novel Rab11 effector protein. A 20-amino acid domain at the C-terminus of Eferin (and related Rab11/25-interacting proteins Rip11 and nRip11) was shown to be necessary and sufficient for Rab11 binding in vitro and required for correct localization of Rab11 effector proteins in vivo.\",\n      \"method\": \"Biochemical binding assays (in vitro Rab11 binding), mutagenesis of the C-terminal domain, in vivo localization studies\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with domain mutagenesis, in vivo localization validation, and identification of shared domain across protein family\",\n      \"pmids\": [\"11481332\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"RAB11FIP3 localizes to a Rab11-positive pericentrosomal compartment during interphase and to the cleavage furrow during cytokinesis. This localization is dependent on both microtubule and actin filament integrity. Expression of an N-terminally truncated mutant (Rab11-FIP3(244-756)) did not inhibit transferrin recycling, suggesting RAB11FIP3 is not required for transferrin recycling.\",\n      \"method\": \"Immunofluorescence microscopy with specific polyclonal antibody, cytoskeletal disruption experiments, dominant-negative mutant expression, transferrin recycling assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiments with functional cytoskeletal perturbations and mutant expression, single lab\",\n      \"pmids\": [\"15158446\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"RAB11FIP3 is critical for the structural integrity of the endosomal recycling compartment (ERC). Knockdown of RAB11FIP3 or expression of a Rab11-binding-deficient mutant caused loss of all ERC-marker protein staining from the pericentrosomal region and blocked fluorophore-labelled transferrin from accessing the pericentrosomal region. A coiled-coil region between residues 463–692 that exists as a dimer in solution is critical for RAB11FIP3 function on the ERC.\",\n      \"method\": \"siRNA knockdown, Rab11-binding-deficient mutant expression, immunofluorescence microscopy, transferrin trafficking assay, biochemical analysis of coiled-coil domain dimerization\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal KD and dominant-negative mutant approaches with specific phenotypic readouts, plus biochemical domain characterization, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"17394487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"RAB11FIP3 predominantly interacts with Arf6 (over Arf4/5) in vitro and in vivo. FIP3 binds to the Arf6 C-terminus rather than the switch motifs. Arf6 binding to FIP3 is required for targeting Arf6 to the cleavage furrow during cytokinesis, and FIP3 acts as a scaffolding protein for Arf6 recruitment to the midbody during late telophase.\",\n      \"method\": \"Biochemical affinity measurements (various Arf GTPases), co-immunoprecipitation, domain mapping/mutagenesis, live-cell imaging during cytokinesis\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro biochemical affinity assays combined with domain mutagenesis and in vivo functional validation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"17628206\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"RAB11FIP3 directly interacts with dynein light intermediate chain 1 (DLIC-1, DYNC1LI1), a subunit of cytoplasmic dynein 1. Rab11a, FIP3, and DLIC-1 form a ternary complex. FIP3 recruits DLIC-1 onto membranes, and association between FIP3 and DLIC-1 at the cell periphery precedes minus-end-directed microtubule-based transport. Knockdown of DLIC-1 inhibits pericentrosomal accumulation of ERC proteins. A DLIC-1-binding truncation mutant of FIP3 disrupts ERC protein pericentrosomal accumulation.\",\n      \"method\": \"Co-immunoprecipitation, GST pulldown, immunofluorescence co-localization, siRNA knockdown, dominant-negative mutant expression\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP demonstrating ternary complex, membrane recruitment assay, KD with specific ERC phenotype, and mutant expression; multiple orthogonal methods\",\n      \"pmids\": [\"20026645\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"RAB11FIP3 is associated with recycling endosomes at the leading edge of motile breast carcinoma cells. FIP3 is required for motility of MDA-MB-231 cells, regulates Rac1-dependent actin cytoskeleton dynamics and lamellipodia formation/ruffling, and controls Arf6 localization at the plasma membrane of migrating cells.\",\n      \"method\": \"siRNA knockdown, cell motility assays, immunofluorescence microscopy, actin dynamics assessment\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD with defined cellular phenotype (motility, actin dynamics, Arf6 localization), single lab, multiple readouts\",\n      \"pmids\": [\"19327867\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"RAB11FIP3 also binds dynein light intermediate chain 2 (DLIC-2, DYNC1LI2) via its N-terminal 435 amino acids and links Rab11a to DLIC-2. FIP3 recruits DLIC-2 onto membranes. DLIC-2 is necessary for pericentrosomal accumulation of endocytosed transferrin at the ERC. Overexpression of FIP3 fragments the Golgi complex by sequestering cytoplasmic dynein-1.\",\n      \"method\": \"Co-immunoprecipitation, membrane recruitment assay, siRNA knockdown of DLIC-2, transferrin trafficking assay, overexpression with Golgi morphology assessment\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with domain mapping, membrane recruitment assay, and KD phenotype; single lab with multiple methods\",\n      \"pmids\": [\"20214888\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"FIP3 localization to recycling endosomes in interphase and their transport to the intercellular bridge during cytokinesis depend on Rab11. Targeting of FIP3-positive endosomal vesicles to the Flemming body (midbody) in the abscission phase depends on Arf6. After abscission, FIP3 and Arf6 are incorporated into one daughter cell as a Flemming body remnant.\",\n      \"method\": \"Detection of endogenous proteins by immunofluorescence, time-lapse analysis of FIP3, Rab11, and Arf6 localization during cytokinesis\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — time-lapse imaging with endogenous protein detection establishes sequential dependency on Rab11 then Arf6; single lab\",\n      \"pmids\": [\"21790911\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"RAB11FIP3 is a cell cycle-regulated phosphoprotein with four in vivo phosphorylation sites (S-102, S-280, S-347, S-450). S-102 is a Cdk1-cyclin B substrate in vitro, is phosphorylated in metaphase, and dephosphorylated as cells enter telophase. Expression of FIP3-S102D increased binucleate cell frequency. Dephosphorylation of FIP3 accompanies its translocation from the cytosol to membranes during telophase, but the identified phospho-acceptor sites do not control spatial recycling endosome distribution.\",\n      \"method\": \"Mass spectrometry phosphosite identification, in vitro Cdk1-cyclin B kinase assay, phospho-specific analysis across cell cycle stages, phosphomimetic/phospho-dead mutant expression, binucleate cell frequency scoring\",\n      \"journal\": \"BMC cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase assay identifying Cdk1 as writer, in vivo phosphorylation mapping, and functional phosphomimetic mutant analysis; single lab\",\n      \"pmids\": [\"22401586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"RAB11FIP3 controls Rac1 intracellular localization and targeting to the immunological synapse. A significant fraction of Rac1 associates with Rab11-positive recycling endosomes, and FIP3 mediates this association. FIP3 regulates T-cell spreading, synapse symmetry, and T-cell activation leading to cytokine production in a Rac1-dependent manner.\",\n      \"method\": \"Overexpression and siRNA silencing of FIP3, co-localization studies (Rac1 with Rab11-positive endosomes), live-cell imaging, T-cell activation assays (cytokine production)\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FIP3 KD/OE with defined T-cell phenotypes and Rac1 localization readout, Rac1-dependency tested; single lab with multiple methods\",\n      \"pmids\": [\"27154205\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RAB11FIP3-dependent endosomal trafficking of Lck controls its delivery to the immunological synapse and modulates early TCR signaling events including tyrosine phosphorylation of TCRζ, ZAP70, and LAT, intracellular calcium levels, and IL-2 gene expression. FIP3's interaction with Rab11 is required for proper Lck subcellular localization. FIP3 modulates TCR-CD3 cell surface expression via regulation of steady-state Lck-mediated TCRζ phosphorylation.\",\n      \"method\": \"FIP3 overexpression and siRNA silencing, Rab11-interaction mutants, immunofluorescence localization of Lck, phosphotyrosine western blotting, calcium flux assays, IL-2 reporter assays\",\n      \"journal\": \"Journal of immunology (Baltimore, Md. : 1950)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FIP3 KD/OE with Rab11-interaction mutants and multiple signaling readouts; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"28235866\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RAB11FIP3 facilitates endosomal recycling of PD-L1 to the cell membrane of gastric cancer cells. The transcription factors IKZF4 and NONO synergistically upregulate RAB11FIP3 expression. Silencing of RAB11FIP3 reduces PD-L1 surface expression, promotes T-cell proliferation and cytotoxicity towards gastric cancer cells, and inhibits tumor immune evasion in vivo.\",\n      \"method\": \"RAB11FIP3 overexpression and siRNA silencing, PD-L1 cell-surface expression assay, T-cell cytotoxicity assays, in vivo mouse tumor experiments with CD8+ T-cell infiltration analysis, transcription factor KO experiments\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined PD-L1 recycling phenotype and in vivo validation; single lab with multiple methods\",\n      \"pmids\": [\"38211652\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RAB11FIP3 (Eferin/Rab11-FIP3) is a dual Rab11/Arf6 effector and scaffolding protein that links Rab11-positive recycling endosomes to cytoplasmic dynein (via direct binding to both DLIC-1 and DLIC-2) to drive minus-end-directed microtubule transport of endosomal cargo to the pericentrosomal endosomal recycling compartment (ERC); it is essential for ERC structural integrity via its dimerizing coiled-coil domain; it recruits Arf6 to the cleavage furrow and midbody to regulate cytokinesis abscission; it is cell cycle-regulated by Cdk1-mediated phosphorylation at S-102; and it controls polarized Rac1 and Lck delivery to the immunological synapse, thereby modulating actin dynamics, TCR signaling, and T-cell activation, as well as PD-L1 recycling in cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RAB11FIP3 (Eferin/Rab11-FIP3) is a Rab11/Arf6 dual-effector scaffolding protein that couples Rab11-positive recycling endosomes to the cytoplasmic dynein motor to organize the pericentrosomal endosomal recycling compartment (ERC) and to direct endosome-driven processes including cytokinesis and immune-synapse signaling [#0, #2, #4]. A C-terminal 20-residue domain mediates direct Rab11 binding, and this interaction is required for correct effector localization to a Rab11-positive pericentrosomal compartment [#0, #1]. RAB11FIP3 is essential for ERC structural integrity: loss of RAB11FIP3 or Rab11-binding-deficient mutants disperses ERC markers and blocks transferrin delivery to the pericentrosomal region, a function that depends on a dimerizing coiled-coil region (residues 463\\u2013692) [#2]. It establishes minus-end-directed transport by directly binding cytoplasmic dynein light intermediate chains DLIC-1 (DYNC1LI1) and DLIC-2 (DYNC1LI2), forming Rab11a\\u2013FIP3\\u2013DLIC ternary complexes and recruiting dynein onto endosomal membranes [#4, #6]. In parallel, RAB11FIP3 preferentially binds the Arf6 C-terminus and acts as a scaffold delivering Arf6 to the cleavage furrow and midbody during cytokinesis, with sequential Rab11- then Arf6-dependent targeting of FIP3 vesicles to the Flemming body during abscission [#3, #7]. Its activity is cell-cycle gated by Cdk1\\u2013cyclin B phosphorylation at S-102, which is high in metaphase and removed at telophase as FIP3 translocates from cytosol to membranes [#8]. Through Rab11-dependent endosomal recycling, RAB11FIP3 targets Rac1 and Lck to the immunological synapse to control actin dynamics, TCR proximal signaling and T-cell activation [#9, #10], and drives endosomal recycling of PD-L1 to the cancer-cell surface to promote tumor immune evasion [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established RAB11FIP3 as a Rab11 effector and defined the minimal binding determinant, answering how the protein is recruited to recycling-endosome machinery.\",\n      \"evidence\": \"In vitro Rab11 binding assays with C-terminal domain mutagenesis and in vivo localization across the Rab11/25-interacting protein family\",\n      \"pmids\": [\"11481332\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define downstream effector function\", \"No structural model of the Rab11-binding interface\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Placed RAB11FIP3 at a pericentrosomal Rab11 compartment in interphase and the cleavage furrow in cytokinesis, linking it to cytoskeleton-dependent positioning rather than bulk transferrin recycling.\",\n      \"evidence\": \"Immunofluorescence with cytoskeletal disruption and N-terminal truncation mutant; transferrin recycling assay\",\n      \"pmids\": [\"15158446\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking FIP3 to microtubule/actin not identified\", \"Truncation result based on single dominant-negative construct\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstrated RAB11FIP3 is required for ERC structural integrity and mapped a dimerizing coiled-coil domain as the functional element, defining its scaffolding role at the recycling compartment.\",\n      \"evidence\": \"siRNA knockdown, Rab11-binding-deficient mutant, transferrin trafficking, and biochemical coiled-coil dimerization analysis\",\n      \"pmids\": [\"17394487\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the motor or partners driving pericentrosomal accumulation\", \"Single-lab phenotype\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identified Arf6 as a second effector partner and showed FIP3 scaffolds Arf6 recruitment to the furrow and midbody, connecting FIP3 to cytokinetic membrane delivery.\",\n      \"evidence\": \"Biochemical affinity comparison among Arf GTPases, Co-IP, domain mapping, and live-cell cytokinesis imaging\",\n      \"pmids\": [\"17628206\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of Arf6 binding for abscission completion not quantified here\", \"Did not resolve coordination with Rab11 binding\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Resolved the motor link by showing direct FIP3\\u2013DLIC-1 binding and Rab11a\\u2013FIP3\\u2013DLIC-1 ternary complex formation, explaining minus-end-directed transport of recycling endosomes to the ERC.\",\n      \"evidence\": \"Reciprocal Co-IP, GST pulldown, membrane recruitment, DLIC-1 knockdown, and truncation mutant disrupting ERC accumulation\",\n      \"pmids\": [\"20026645\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address whether DLIC-2 contributes\", \"Regulation of motor engagement timing unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Extended FIP3 function to cell migration, showing it controls Rac1-dependent actin dynamics and Arf6 localization at the leading edge of carcinoma cells.\",\n      \"evidence\": \"siRNA knockdown with motility, actin dynamics, and Arf6 localization readouts in MDA-MB-231 cells\",\n      \"pmids\": [\"19327867\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect control of Rac1 not distinguished here\", \"Single cell-line model\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Showed FIP3 also binds DLIC-2 via its N-terminal region, broadening the dynein-coupling repertoire and demonstrating dynein-sequestering effects on Golgi morphology.\",\n      \"evidence\": \"Co-IP with domain mapping, membrane recruitment, DLIC-2 knockdown transferrin assay, and overexpression Golgi morphology assessment\",\n      \"pmids\": [\"20214888\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relative roles of DLIC-1 vs DLIC-2 not delineated\", \"Golgi fragmentation may be an overexpression artifact\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Established the temporal logic of cytokinetic targeting: Rab11 governs endosome recruitment and transport while Arf6 governs midbody targeting during abscission.\",\n      \"evidence\": \"Endogenous-protein immunofluorescence and time-lapse imaging of FIP3, Rab11, and Arf6 through cytokinesis\",\n      \"pmids\": [\"21790911\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular trigger of the Rab11-to-Arf6 handoff unknown\", \"Fate of Flemming body remnant function not addressed\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identified FIP3 as a cell-cycle-regulated phosphoprotein with Cdk1-cyclin B phosphorylating S-102, linking mitotic kinase activity to FIP3 cytosol-to-membrane translocation.\",\n      \"evidence\": \"Mass spectrometry phosphosite mapping, in vitro Cdk1-cyclin B kinase assay, phospho-staging, and phosphomimetic mutant binucleation scoring\",\n      \"pmids\": [\"22401586\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identified sites do not control spatial endosome distribution\", \"Phosphatase responsible for telophase dephosphorylation unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrated FIP3 mediates Rac1 association with Rab11 endosomes and its delivery to the immunological synapse, controlling T-cell spreading, synapse symmetry, and activation.\",\n      \"evidence\": \"FIP3 knockdown/overexpression, Rac1 co-localization, live imaging, and Rac1-dependent T-cell cytokine assays\",\n      \"pmids\": [\"27154205\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct FIP3\\u2013Rac1 binding vs endosome co-trafficking not separated\", \"Single-lab T-cell model\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showed FIP3-dependent endosomal trafficking of Lck controls proximal TCR signaling and IL-2 expression, extending FIP3's synapse role to kinase delivery.\",\n      \"evidence\": \"FIP3 KD/OE with Rab11-interaction mutants, Lck localization, phosphotyrosine blotting, calcium flux, and IL-2 reporter assays\",\n      \"pmids\": [\"28235866\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether Lck is direct cargo or co-trafficked with Rab11 endosomes unresolved\", \"Quantitative contribution to surface TCR-CD3 levels not fully defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected FIP3 recycling activity to immune evasion by showing it recycles PD-L1 to the gastric cancer-cell surface under IKZF4/NONO transcriptional control.\",\n      \"evidence\": \"FIP3 KD/OE, PD-L1 surface assays, T-cell cytotoxicity, in vivo tumor experiments, and transcription-factor knockout\",\n      \"pmids\": [\"38211652\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular link between FIP3 and PD-L1 cargo selection not defined\", \"Single cancer-type model\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RAB11FIP3 integrates competing Rab11- and Arf6-dependent functions and selects specific cargo (Rac1, Lck, PD-L1) for synapse versus midbody delivery remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the full FIP3 scaffold with simultaneous effector engagement\", \"Cargo-selection mechanism for distinct trafficking routes unknown\", \"Switch coordinating motor recruitment with phosphorylation state undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 4, 6]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [4, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1, 4, 7]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [5, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 4, 6]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3, 7, 8]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [9, 10, 11]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [4, 6]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"RAB11A\", \"ARF6\", \"DYNC1LI1\", \"DYNC1LI2\", \"RAC1\", \"LCK\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}