{"gene":"DYNC1LI1","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2009,"finding":"DYNC1LI1 (DLIC-1) directly interacts with the Rab11 GTPase effector protein Rab11-FIP3, and together with Rab11a forms a ternary complex. FIP3 recruits DLIC-1 onto membranes at the cell periphery preceding minus-end-directed microtubule-based transport, and knockdown of DLIC-1 inhibits pericentrosomal accumulation of endosomal-recycling compartment (ERC) proteins.","method":"Co-immunoprecipitation, pulldown, co-localization, RNAi knockdown, dominant-negative truncation mutant expression","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP establishing ternary complex, RNAi loss-of-function with defined trafficking phenotype, dominant-negative confirmation, multiple orthogonal methods in single study","pmids":["20026645"],"is_preprint":false},{"year":2009,"finding":"RNAi depletion of LIC1 (DYNC1LI1), but not LIC2, specifically recapitulates a block of ER-to-Golgi transport, demonstrating that LIC1 defines a distinct dynein complex required to maintain Golgi steady-state composition. Conversely, LIC2 depletion but not LIC1 depletion disrupts recycling endosome distribution and cytokinesis, indicating that LIC1 and LIC2 define functionally distinct dynein complexes.","method":"RNAi depletion with automated image analysis of membrane-trafficking phenotypes; biochemical fractionation","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — isoform-specific RNAi with defined trafficking phenotypes and biochemical analyses, multiple orthogonal methods, functionally distinguishes LIC1 from LIC2","pmids":["19386764"],"is_preprint":false},{"year":2010,"finding":"LIC1 (DYNC1LI1) and LIC2 are both present on late endosomes and lysosomes; isoform-specific RNAi of LIC1 disrupts late endosome/lysosome distribution and reverses RILP-stimulated late-endosomal transport by displacing dynein (but not dynactin) from these structures, revealing a specific role for LICs in dynein recruitment to the late endocytic pathway.","method":"Isoform-specific antibodies, RNAi, subcellular fractionation, dynein/dynactin displacement assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — isoform-specific antibodies, RNAi loss-of-function, complementary approaches including RILP stimulation assay and dynamitin/ΔN-RILP controls","pmids":["21169557"],"is_preprint":false},{"year":2011,"finding":"During mitosis, LIC1 (DYNC1LI1) localizes to the mitotic spindle from metaphase through anaphase and concentrates within the midbody during abscission, whereas LIC2 localizes to spindle poles, indicating distinct spatial roles for the two LIC-containing dynein complexes during cell division.","method":"Immunofluorescence microscopy of endogenous LIC1 and LIC2 across mitotic stages","journal":"Cell biology international","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment across mitotic stages, single lab, single method (immunofluorescence), no functional perturbation","pmids":["20964624"],"is_preprint":false},{"year":2011,"finding":"An N235Y point mutation in mouse Dync1li1 results in altered neuronal cortical development and electrophysiological defects in vivo, and mutant mice display increased anxiety, linking dynein LIC1 function to neuronal development and behavior.","method":"Genotype-driven mouse mutant analysis; in vivo cortical development assays; electrophysiology; behavioral testing","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo point-mutation mouse model with multiple phenotypic readouts (cortical development, electrophysiology, behavior), single lab","pmids":["21471385"],"is_preprint":false},{"year":2014,"finding":"Depletion of dynein light intermediate chains (including DYNC1LI1) by siRNA in human cells or morpholinos in Xenopus embryos causes formation of multipolar spindles with single centrioles at poles, demonstrating that LICs are required for centriole cohesion and bipolar spindle maintenance during mitosis. Dynein lacking LICs still drives microtubule gliding at normal rates, indicating LICs are not required for core motor activity. Multipolar spindle formation after LIC depletion was rescued by inhibiting the kinesin Eg5, placing LIC1 in opposition to Eg5 at centrosomes.","method":"siRNA depletion in human cell lines, morpholino knockdown in Xenopus embryos, in vitro microtubule gliding assay, Eg5 inhibitor epistasis","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro motor assay plus genetic epistasis with Eg5 inhibitor, replicated across two organisms (human cells and Xenopus), multiple orthogonal methods","pmids":["25422374"],"is_preprint":false},{"year":2023,"finding":"KASH5 interacts directly with the C-terminal domain of dynein light intermediate chains (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminus; this same region is required for dynein recruitment to other cellular membranes. KASH5 promotes dynein motility in vitro and acts as an activating adaptor. LIS1 is essential for dynactin incorporation into the KASH5-dynein complex, while dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin.","method":"In vitro motility assays, co-immunoprecipitation, site-directed mutagenesis of KASH5 EF-hand calcium-binding residues, dominant-negative cytosolic KASH5 expression","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of motility, mutagenesis defining binding interface, multiple functional readouts in single rigorous study","pmids":["36946995"],"is_preprint":false},{"year":2022,"finding":"Knockout of Dync1li1 in mice leads to progressive cochlear hair cell loss via apoptosis and hearing loss. Loss of Dync1li1 destabilizes the dynein complex, causes Golgi thinning, and results in accumulation of LC3+ autophagic vacuoles. Knockdown in OC1 cells increases autophagosomes while decreasing autolysosomes, demonstrating that DYNC1LI1 is required for retrograde transport of autophagosomes to lysosomes.","method":"DYNC1LI1 knockout mouse, siRNA knockdown in OC1 cells, immunofluorescence, autophagy flux assays (LC3 puncta, autolysosome quantification)","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo KO mouse with defined phenotype plus in vitro KD with autophagy flux assay, multiple orthogonal methods, single lab","pmids":["35727824"],"is_preprint":false},{"year":2023,"finding":"CRISPR-Cas9 knockout of dync1li1 in zebrafish causes progressive degeneration of retinal cone photoreceptors (especially blue cones) with abnormal cone opsin localization and apoptosis. Mechanistically, Rab8-mediated transport (but not Rab11 transport) is specifically disrupted in dync1li1−/− retinas, indicating DYNC1LI1 is required for Rab8-dependent cargo transport in cone photoreceptors.","method":"CRISPR-Cas9 knockout zebrafish, immunofluorescence for opsins, TUNEL apoptosis assay, Rab8/Rab11 transport analysis","journal":"Biochimica et biophysica acta. Molecular basis of disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with defined cellular phenotype and Rab8-specific transport disruption, single lab, single organism model","pmids":["36682603"],"is_preprint":false},{"year":2024,"finding":"LIC1 (DYNC1LI1) restricts angiogenesis by promoting lysosomal degradation of VEGFR2-containing recycling endosomes via interaction with Rab adaptor proteins RILPL1/2. Loss of LIC1 in zebrafish or human endothelial cells increases VEGFR2 cell surface levels, SRC phosphorylation, and Rab11-mediated endosomal recycling, leading to excessive angiogenesis. Endothelial-specific constitutively active Rab11a phenocopies the dync1li1 mutant.","method":"Zebrafish dync1li1 mutant (premature stop codon), siRNA knockdown in human endothelial cells, flow cytometry for VEGFR2 surface levels, phospho-SRC immunoblotting, constitutively active Rab11a in vivo expression, rilpl1/2 zebrafish mutants","journal":"Angiogenesis","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo zebrafish mutant plus in vitro human cell knockdown, multiple orthogonal methods, genetic epistasis with Rab11a and rilpl1/2 mutants, two complementary publications","pmids":["39356418","38903077"],"is_preprint":false}],"current_model":"DYNC1LI1 (LIC1) is a core subunit of the cytoplasmic dynein-1 complex that, via its C-terminal domain, docks activating adaptors (including Rab11-FIP3 and KASH5) and Rab-adaptor proteins (RILPL1/2) to couple dynein to specific membrane cargoes; it defines a functionally distinct dynein complex (separate from LIC2-containing complexes) required for ER-to-Golgi transport, retrograde trafficking of late endosomes/lysosomes, lysosomal degradation of recycling endosomes (restraining VEGFR2 recycling and angiogenesis), autophagosome transport to lysosomes in hair cells, Rab8-dependent cone photoreceptor cargo transport, and centriole cohesion during mitosis—while being dispensable for the core microtubule-gliding activity of the motor itself."},"narrative":{"mechanistic_narrative":"DYNC1LI1 (LIC1) is a light intermediate chain of the cytoplasmic dynein-1 motor that defines a functionally specialized dynein complex distinct from its paralog LIC2, coupling the motor to specific membrane cargoes for minus-end-directed transport [PMID:19386764, PMID:21169557]. Through its C-terminal domain it docks activating adaptors and Rab-effector proteins — including the Rab11 effector Rab11-FIP3 to form a ternary complex with Rab11a [PMID:20026645], the nuclear-envelope adaptor KASH5 via a conserved C-terminal helix [PMID:36946995], and the Rab adaptors RILPL1/2 [PMID:39356418, PMID:38903077] — thereby selecting cargo while being dispensable for the core microtubule-gliding activity of the motor [PMID:25422374]. This LIC1-specific dynein supports ER-to-Golgi transport [PMID:19386764], retrograde positioning of late endosomes and lysosomes [PMID:21169557], retrograde delivery of autophagosomes to lysosomes [PMID:35727824], and Rab8-dependent cargo transport in cone photoreceptors [PMID:36682603]. By promoting lysosomal degradation of VEGFR2-containing recycling endosomes through RILPL1/2, LIC1 restrains Rab11-mediated VEGFR2 recycling and limits angiogenesis [PMID:39356418, PMID:38903077]. In mitosis, LIC1-containing dynein is required for centriole cohesion and bipolar spindle maintenance, acting in opposition to the kinesin Eg5 at centrosomes [PMID:25422374]. Loss of DYNC1LI1 in animal models causes cochlear hair-cell degeneration and hearing loss [PMID:35727824], retinal cone degeneration [PMID:36682603], and neuronal developmental and behavioral defects [PMID:21471385].","teleology":[{"year":2009,"claim":"Established that LIC1 is not a generic motor subunit but defines a dynein complex functionally separable from LIC2, by showing each isoform controls distinct membrane-trafficking routes.","evidence":"Isoform-specific RNAi with automated imaging of trafficking phenotypes and biochemical fractionation in human cells","pmids":["19386764"],"confidence":"High","gaps":["Did not define the molecular features distinguishing LIC1 from LIC2 cargo selection","Mechanism of how LIC1 reads ER-to-Golgi cargo not resolved"]},{"year":2009,"claim":"Identified a direct cargo-coupling mechanism: LIC1 binds the Rab11 effector FIP3, linking dynein to recycling-endosome membranes for minus-end transport.","evidence":"Reciprocal Co-IP, pulldown, co-localization, RNAi, and dominant-negative truncation in cells","pmids":["20026645"],"confidence":"High","gaps":["Binding interface on LIC1 not mapped at residue level","Did not establish whether FIP3 acts as an activating adaptor for processive motility"]},{"year":2010,"claim":"Defined LIC1 as the determinant of dynein recruitment to the late endocytic pathway, showing it is needed to load dynein (not dynactin) onto late endosomes/lysosomes downstream of RILP.","evidence":"Isoform-specific antibodies, RNAi, subcellular fractionation, and dynein/dynactin displacement assays with RILP stimulation","pmids":["21169557"],"confidence":"High","gaps":["Direct physical link between LIC1 and RILP not biochemically defined here","Selectivity of dynein vs dynactin recruitment mechanism left open"]},{"year":2011,"claim":"Showed LIC1 and LIC2 occupy distinct mitotic locations (spindle/midbody vs spindle poles), extending isoform specialization to cell division.","evidence":"Immunofluorescence of endogenous LIC1 and LIC2 across mitotic stages","pmids":["20964624"],"confidence":"Medium","gaps":["No functional perturbation to test the localization's role","Single method, single lab"]},{"year":2011,"claim":"Connected LIC1 function to organismal physiology, demonstrating a point mutation perturbs neuronal cortical development and behavior in vivo.","evidence":"Genotype-driven Dync1li1 N235Y mouse model with cortical, electrophysiological, and behavioral assays","pmids":["21471385"],"confidence":"Medium","gaps":["Molecular consequence of N235Y on dynein assembly or cargo binding not defined","Causal trafficking defect underlying the phenotype not identified"]},{"year":2014,"claim":"Separated LIC function from core motor mechanics: LICs are required for centriole cohesion and bipolar spindles but not for microtubule gliding, with the defect ascribed to imbalance against Eg5.","evidence":"siRNA in human cells, morpholino in Xenopus, in vitro microtubule gliding assay, and Eg5-inhibitor epistasis","pmids":["25422374"],"confidence":"High","gaps":["LIC1-specific contribution versus pan-LIC effect not fully separated in this assay","Cargo or adaptor mediating centriole cohesion not identified"]},{"year":2022,"claim":"Demonstrated LIC1 is required for retrograde autophagosome-to-lysosome transport, linking its loss to autophagic-flux failure and hair-cell death.","evidence":"Dync1li1 knockout mouse plus OC1 cell knockdown with LC3/autolysosome flux assays","pmids":["35727824"],"confidence":"High","gaps":["Adaptor coupling LIC1 to autophagosomes not identified","Whether Golgi thinning is cause or consequence of complex destabilization unresolved"]},{"year":2023,"claim":"Established the structural basis and functional role of an activating adaptor interaction: KASH5 binds a conserved helix in the LIC C-terminus and activates dynein motility, with LIS1 required for dynactin incorporation.","evidence":"In vitro motility reconstitution, Co-IP, KASH5 EF-hand mutagenesis, and dominant-negative cytosolic KASH5 in cells","pmids":["36946995"],"confidence":"High","gaps":["Whether other LIC1 adaptors use the same helix competitively not addressed","Calcium regulation of the interaction physiology not resolved"]},{"year":2023,"claim":"Revealed cargo-pathway specificity in vivo, showing LIC1 supports Rab8-dependent but not Rab11-dependent transport in cone photoreceptors.","evidence":"CRISPR-Cas9 dync1li1 knockout zebrafish with opsin immunofluorescence, TUNEL, and Rab8/Rab11 transport analysis","pmids":["36682603"],"confidence":"Medium","gaps":["Direct LIC1-Rab8 coupling mechanism not biochemically defined","Single organism model"]},{"year":2024,"claim":"Defined a physiological output for LIC1 cargo selection: it routes VEGFR2 recycling endosomes to lysosomal degradation via RILPL1/2, restraining angiogenesis.","evidence":"Zebrafish dync1li1 and rilpl1/2 mutants, endothelial-cell knockdown, VEGFR2 surface flow cytometry, phospho-SRC immunoblot, and constitutively active Rab11a epistasis","pmids":["39356418","38903077"],"confidence":"High","gaps":["Direct LIC1-RILPL1/2 binding interface not mapped","How LIC1 balances degradative vs recycling fate of endosomes mechanistically unresolved"]},{"year":null,"claim":"How LIC1 discriminates among its multiple adaptors (FIP3, KASH5, RILPL1/2) to achieve cargo- and tissue-specific transport, and the structural rules governing this selectivity versus LIC2, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No unified structural model of competitive adaptor binding on the LIC1 C-terminus","Determinants of LIC1 vs LIC2 cargo partitioning unknown","Regulation of adaptor switching across cell types not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,6,9]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[2,5]}],"localization":[{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[2,7]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,2,9]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[5]},{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[6]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,7]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[7]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3,5]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1,9]}],"complexes":["cytoplasmic dynein-1 complex"],"partners":["RAB11FIP3","RAB11A","KASH5","RILPL1","RILPL2","RILP","LIS1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y6G9","full_name":"Cytoplasmic dynein 1 light intermediate chain 1","aliases":["Dynein light chain A","DLC-A","Dynein light intermediate chain 1, cytosolic","DLIC-1"],"length_aa":523,"mass_kda":56.6,"function":"Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. Probably involved in the microtubule-dependent transport of pericentrin. Is required for progress through the spindle assembly checkpoint. The phosphorylated form appears to be involved in the selective removal of MAD1L1 and MAD1L2 but not BUB1B from kinetochores. Forms a functional Rab11/RAB11FIP3/dynein complex onto endosomal membrane that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (PubMed:20026645)","subcellular_location":"Cytoplasm; Chromosome, centromere, kinetochore; Cytoplasm, cytoskeleton, spindle pole; Recycling endosome membrane","url":"https://www.uniprot.org/uniprotkb/Q9Y6G9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DYNC1LI1","classification":"Not Classified","n_dependent_lines":80,"n_total_lines":1208,"dependency_fraction":0.06622516556291391},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000144635","cell_line_id":"CID001407","localizations":[{"compartment":"cytoplasmic","grade":3},{"compartment":"centrosome","grade":2},{"compartment":"cytoskeleton","grade":1}],"interactors":[{"gene":"DCTN2","stoichiometry":10.0},{"gene":"DYNC1H1","stoichiometry":10.0},{"gene":"DYNC1I2","stoichiometry":10.0},{"gene":"DYNLT1","stoichiometry":10.0},{"gene":"ACTR1A","stoichiometry":10.0},{"gene":"DCTN1;DKFZP686E0752","stoichiometry":10.0},{"gene":"DYNLRB1","stoichiometry":10.0},{"gene":"DYNLT3","stoichiometry":10.0},{"gene":"PAFAH1B1","stoichiometry":10.0},{"gene":"DYNC1LI2","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID001407","total_profiled":1310},"omim":[{"mim_id":"617088","title":"SHORT-RIB THORACIC DYSPLASIA 15 WITH POLYDACTYLY; SRTD15","url":"https://www.omim.org/entry/617088"},{"mim_id":"617083","title":"DYNEIN, CYTOPLASMIC 2, LIGHT INTERMEDIATE CHAIN 1; DYNC2LI1","url":"https://www.omim.org/entry/617083"},{"mim_id":"615890","title":"DYNEIN, CYTOPLASMIC 1, LIGHT INTERMEDIATE CHAIN 1; DYNC1LI1","url":"https://www.omim.org/entry/615890"},{"mim_id":"611406","title":"DYNEIN, CYTOPLASMIC 1, LIGHT INTERMEDIATE CHAIN 2; DYNC1LI2","url":"https://www.omim.org/entry/611406"},{"mim_id":"179511","title":"RAS-ASSOCIATED PROTEIN RAB4A; RAB4A","url":"https://www.omim.org/entry/179511"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Centrosome","reliability":"Uncertain"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DYNC1LI1"},"hgnc":{"alias_symbol":[],"prev_symbol":["DNCLI1"]},"alphafold":{"accession":"Q9Y6G9","domains":[{"cath_id":"3.40.50.300","chopping":"70-200_229-353","consensus_level":"medium","plddt":72.7144,"start":70,"end":353}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y6G9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y6G9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y6G9-F1-predicted_aligned_error_v6.png","plddt_mean":59.34},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DYNC1LI1","jax_strain_url":"https://www.jax.org/strain/search?query=DYNC1LI1"},"sequence":{"accession":"Q9Y6G9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y6G9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y6G9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y6G9"}},"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":"19386764","id":"PMC_19386764","title":"Specificity of cytoplasmic dynein subunits in discrete membrane-trafficking steps.","date":"2009","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/19386764","citation_count":101,"is_preprint":false},{"pmid":"33223314","id":"PMC_33223314","title":"Developmental toxicity of the novel PFOS alternative OBS in developing zebrafish: An emphasis on cilia disruption.","date":"2020","source":"Journal of hazardous materials","url":"https://pubmed.ncbi.nlm.nih.gov/33223314","citation_count":73,"is_preprint":false},{"pmid":"21169557","id":"PMC_21169557","title":"Recruitment of dynein to late endosomes and lysosomes through light intermediate chains.","date":"2010","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/21169557","citation_count":71,"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":"25422374","id":"PMC_25422374","title":"Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion.","date":"2014","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/25422374","citation_count":27,"is_preprint":false},{"pmid":"33431066","id":"PMC_33431066","title":"A pilot radiogenomic study of DIPG reveals distinct subgroups with unique clinical trajectories and therapeutic targets.","date":"2021","source":"Acta neuropathologica communications","url":"https://pubmed.ncbi.nlm.nih.gov/33431066","citation_count":23,"is_preprint":false},{"pmid":"36946995","id":"PMC_36946995","title":"The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein.","date":"2023","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/36946995","citation_count":20,"is_preprint":false},{"pmid":"21471385","id":"PMC_21471385","title":"Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse.","date":"2011","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/21471385","citation_count":18,"is_preprint":false},{"pmid":"20964624","id":"PMC_20964624","title":"Dynein LIC1 localizes to the mitotic spindle and midbody and LIC2 localizes to spindle poles during cell division.","date":"2011","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/20964624","citation_count":18,"is_preprint":false},{"pmid":"34643468","id":"PMC_34643468","title":"DYNC1LI2 regulates localization of the chaperone-mediated autophagy receptor LAMP2A and improves cellular homeostasis in cystinosis.","date":"2021","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/34643468","citation_count":14,"is_preprint":false},{"pmid":"35727824","id":"PMC_35727824","title":"Dync1li1 is required for the survival of mammalian cochlear hair cells by regulating the transportation of autophagosomes.","date":"2022","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35727824","citation_count":13,"is_preprint":false},{"pmid":"32901070","id":"PMC_32901070","title":"A CRISPR-based method for testing the essentiality of a gene.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32901070","citation_count":8,"is_preprint":false},{"pmid":"36456625","id":"PMC_36456625","title":"Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36456625","citation_count":8,"is_preprint":false},{"pmid":"36224025","id":"PMC_36224025","title":"Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions.","date":"2022","source":"Frontiers in bioscience (Landmark edition)","url":"https://pubmed.ncbi.nlm.nih.gov/36224025","citation_count":5,"is_preprint":false},{"pmid":"39356418","id":"PMC_39356418","title":"Angiogenesis is limited by LIC1-mediated lysosomal trafficking.","date":"2024","source":"Angiogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/39356418","citation_count":3,"is_preprint":false},{"pmid":"36682603","id":"PMC_36682603","title":"Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish.","date":"2023","source":"Biochimica et biophysica acta. Molecular basis of disease","url":"https://pubmed.ncbi.nlm.nih.gov/36682603","citation_count":2,"is_preprint":false},{"pmid":"41514609","id":"PMC_41514609","title":"Stool- and Blood-Associated Colorectal Cancer Biomarkers: A Systematic Review.","date":"2025","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/41514609","citation_count":0,"is_preprint":false},{"pmid":"38903077","id":"PMC_38903077","title":"Regulation of angiogenesis by endocytic trafficking mediated by cytoplasmic dynein 1 light intermediate chain 1.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38903077","citation_count":0,"is_preprint":false},{"pmid":"38525916","id":"PMC_38525916","title":"Dynein Light Intermediate Chains Exhibit Different Arginine Methylation Patterns.","date":"2024","source":"Journal of clinical laboratory analysis","url":"https://pubmed.ncbi.nlm.nih.gov/38525916","citation_count":0,"is_preprint":false},{"pmid":"41840478","id":"PMC_41840478","title":"Proteomics of human duodenum in pre-diabetes and type 2 diabetes reveals potential novel therapeutic targets for aetiology and therapeutics.","date":"2026","source":"Clinical proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/41840478","citation_count":0,"is_preprint":false},{"pmid":"41847015","id":"PMC_41847015","title":"A spatial and temporal atlas of tubulin isotype expression during neural crest EMT.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41847015","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13542,"output_tokens":3031,"usd":0.043046,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10327,"output_tokens":3640,"usd":0.071318,"stage2_stop_reason":"end_turn"},"total_usd":0.114364,"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\": 2009,\n      \"finding\": \"DYNC1LI1 (DLIC-1) directly interacts with the Rab11 GTPase effector protein Rab11-FIP3, and together with Rab11a forms a ternary complex. FIP3 recruits DLIC-1 onto membranes at the cell periphery preceding minus-end-directed microtubule-based transport, and knockdown of DLIC-1 inhibits pericentrosomal accumulation of endosomal-recycling compartment (ERC) proteins.\",\n      \"method\": \"Co-immunoprecipitation, pulldown, co-localization, RNAi knockdown, dominant-negative truncation mutant expression\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP establishing ternary complex, RNAi loss-of-function with defined trafficking phenotype, dominant-negative confirmation, multiple orthogonal methods in single study\",\n      \"pmids\": [\"20026645\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"RNAi depletion of LIC1 (DYNC1LI1), but not LIC2, specifically recapitulates a block of ER-to-Golgi transport, demonstrating that LIC1 defines a distinct dynein complex required to maintain Golgi steady-state composition. Conversely, LIC2 depletion but not LIC1 depletion disrupts recycling endosome distribution and cytokinesis, indicating that LIC1 and LIC2 define functionally distinct dynein complexes.\",\n      \"method\": \"RNAi depletion with automated image analysis of membrane-trafficking phenotypes; biochemical fractionation\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — isoform-specific RNAi with defined trafficking phenotypes and biochemical analyses, multiple orthogonal methods, functionally distinguishes LIC1 from LIC2\",\n      \"pmids\": [\"19386764\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"LIC1 (DYNC1LI1) and LIC2 are both present on late endosomes and lysosomes; isoform-specific RNAi of LIC1 disrupts late endosome/lysosome distribution and reverses RILP-stimulated late-endosomal transport by displacing dynein (but not dynactin) from these structures, revealing a specific role for LICs in dynein recruitment to the late endocytic pathway.\",\n      \"method\": \"Isoform-specific antibodies, RNAi, subcellular fractionation, dynein/dynactin displacement assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — isoform-specific antibodies, RNAi loss-of-function, complementary approaches including RILP stimulation assay and dynamitin/ΔN-RILP controls\",\n      \"pmids\": [\"21169557\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"During mitosis, LIC1 (DYNC1LI1) localizes to the mitotic spindle from metaphase through anaphase and concentrates within the midbody during abscission, whereas LIC2 localizes to spindle poles, indicating distinct spatial roles for the two LIC-containing dynein complexes during cell division.\",\n      \"method\": \"Immunofluorescence microscopy of endogenous LIC1 and LIC2 across mitotic stages\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment across mitotic stages, single lab, single method (immunofluorescence), no functional perturbation\",\n      \"pmids\": [\"20964624\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"An N235Y point mutation in mouse Dync1li1 results in altered neuronal cortical development and electrophysiological defects in vivo, and mutant mice display increased anxiety, linking dynein LIC1 function to neuronal development and behavior.\",\n      \"method\": \"Genotype-driven mouse mutant analysis; in vivo cortical development assays; electrophysiology; behavioral testing\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo point-mutation mouse model with multiple phenotypic readouts (cortical development, electrophysiology, behavior), single lab\",\n      \"pmids\": [\"21471385\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Depletion of dynein light intermediate chains (including DYNC1LI1) by siRNA in human cells or morpholinos in Xenopus embryos causes formation of multipolar spindles with single centrioles at poles, demonstrating that LICs are required for centriole cohesion and bipolar spindle maintenance during mitosis. Dynein lacking LICs still drives microtubule gliding at normal rates, indicating LICs are not required for core motor activity. Multipolar spindle formation after LIC depletion was rescued by inhibiting the kinesin Eg5, placing LIC1 in opposition to Eg5 at centrosomes.\",\n      \"method\": \"siRNA depletion in human cell lines, morpholino knockdown in Xenopus embryos, in vitro microtubule gliding assay, Eg5 inhibitor epistasis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro motor assay plus genetic epistasis with Eg5 inhibitor, replicated across two organisms (human cells and Xenopus), multiple orthogonal methods\",\n      \"pmids\": [\"25422374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KASH5 interacts directly with the C-terminal domain of dynein light intermediate chains (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminus; this same region is required for dynein recruitment to other cellular membranes. KASH5 promotes dynein motility in vitro and acts as an activating adaptor. LIS1 is essential for dynactin incorporation into the KASH5-dynein complex, while dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin.\",\n      \"method\": \"In vitro motility assays, co-immunoprecipitation, site-directed mutagenesis of KASH5 EF-hand calcium-binding residues, dominant-negative cytosolic KASH5 expression\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of motility, mutagenesis defining binding interface, multiple functional readouts in single rigorous study\",\n      \"pmids\": [\"36946995\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Knockout of Dync1li1 in mice leads to progressive cochlear hair cell loss via apoptosis and hearing loss. Loss of Dync1li1 destabilizes the dynein complex, causes Golgi thinning, and results in accumulation of LC3+ autophagic vacuoles. Knockdown in OC1 cells increases autophagosomes while decreasing autolysosomes, demonstrating that DYNC1LI1 is required for retrograde transport of autophagosomes to lysosomes.\",\n      \"method\": \"DYNC1LI1 knockout mouse, siRNA knockdown in OC1 cells, immunofluorescence, autophagy flux assays (LC3 puncta, autolysosome quantification)\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo KO mouse with defined phenotype plus in vitro KD with autophagy flux assay, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"35727824\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CRISPR-Cas9 knockout of dync1li1 in zebrafish causes progressive degeneration of retinal cone photoreceptors (especially blue cones) with abnormal cone opsin localization and apoptosis. Mechanistically, Rab8-mediated transport (but not Rab11 transport) is specifically disrupted in dync1li1−/− retinas, indicating DYNC1LI1 is required for Rab8-dependent cargo transport in cone photoreceptors.\",\n      \"method\": \"CRISPR-Cas9 knockout zebrafish, immunofluorescence for opsins, TUNEL apoptosis assay, Rab8/Rab11 transport analysis\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular basis of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with defined cellular phenotype and Rab8-specific transport disruption, single lab, single organism model\",\n      \"pmids\": [\"36682603\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"LIC1 (DYNC1LI1) restricts angiogenesis by promoting lysosomal degradation of VEGFR2-containing recycling endosomes via interaction with Rab adaptor proteins RILPL1/2. Loss of LIC1 in zebrafish or human endothelial cells increases VEGFR2 cell surface levels, SRC phosphorylation, and Rab11-mediated endosomal recycling, leading to excessive angiogenesis. Endothelial-specific constitutively active Rab11a phenocopies the dync1li1 mutant.\",\n      \"method\": \"Zebrafish dync1li1 mutant (premature stop codon), siRNA knockdown in human endothelial cells, flow cytometry for VEGFR2 surface levels, phospho-SRC immunoblotting, constitutively active Rab11a in vivo expression, rilpl1/2 zebrafish mutants\",\n      \"journal\": \"Angiogenesis\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo zebrafish mutant plus in vitro human cell knockdown, multiple orthogonal methods, genetic epistasis with Rab11a and rilpl1/2 mutants, two complementary publications\",\n      \"pmids\": [\"39356418\", \"38903077\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DYNC1LI1 (LIC1) is a core subunit of the cytoplasmic dynein-1 complex that, via its C-terminal domain, docks activating adaptors (including Rab11-FIP3 and KASH5) and Rab-adaptor proteins (RILPL1/2) to couple dynein to specific membrane cargoes; it defines a functionally distinct dynein complex (separate from LIC2-containing complexes) required for ER-to-Golgi transport, retrograde trafficking of late endosomes/lysosomes, lysosomal degradation of recycling endosomes (restraining VEGFR2 recycling and angiogenesis), autophagosome transport to lysosomes in hair cells, Rab8-dependent cone photoreceptor cargo transport, and centriole cohesion during mitosis—while being dispensable for the core microtubule-gliding activity of the motor itself.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DYNC1LI1 (LIC1) is a light intermediate chain of the cytoplasmic dynein-1 motor that defines a functionally specialized dynein complex distinct from its paralog LIC2, coupling the motor to specific membrane cargoes for minus-end-directed transport [#1, #2]. Through its C-terminal domain it docks activating adaptors and Rab-effector proteins — including the Rab11 effector Rab11-FIP3 to form a ternary complex with Rab11a [#0], the nuclear-envelope adaptor KASH5 via a conserved C-terminal helix [#6], and the Rab adaptors RILPL1/2 [#9] — thereby selecting cargo while being dispensable for the core microtubule-gliding activity of the motor [#5]. This LIC1-specific dynein supports ER-to-Golgi transport [#1], retrograde positioning of late endosomes and lysosomes [#2], retrograde delivery of autophagosomes to lysosomes [#7], and Rab8-dependent cargo transport in cone photoreceptors [#8]. By promoting lysosomal degradation of VEGFR2-containing recycling endosomes through RILPL1/2, LIC1 restrains Rab11-mediated VEGFR2 recycling and limits angiogenesis [#9]. In mitosis, LIC1-containing dynein is required for centriole cohesion and bipolar spindle maintenance, acting in opposition to the kinesin Eg5 at centrosomes [#5]. Loss of DYNC1LI1 in animal models causes cochlear hair-cell degeneration and hearing loss [#7], retinal cone degeneration [#8], and neuronal developmental and behavioral defects [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established that LIC1 is not a generic motor subunit but defines a dynein complex functionally separable from LIC2, by showing each isoform controls distinct membrane-trafficking routes.\",\n      \"evidence\": \"Isoform-specific RNAi with automated imaging of trafficking phenotypes and biochemical fractionation in human cells\",\n      \"pmids\": [\"19386764\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the molecular features distinguishing LIC1 from LIC2 cargo selection\", \"Mechanism of how LIC1 reads ER-to-Golgi cargo not resolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identified a direct cargo-coupling mechanism: LIC1 binds the Rab11 effector FIP3, linking dynein to recycling-endosome membranes for minus-end transport.\",\n      \"evidence\": \"Reciprocal Co-IP, pulldown, co-localization, RNAi, and dominant-negative truncation in cells\",\n      \"pmids\": [\"20026645\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Binding interface on LIC1 not mapped at residue level\", \"Did not establish whether FIP3 acts as an activating adaptor for processive motility\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Defined LIC1 as the determinant of dynein recruitment to the late endocytic pathway, showing it is needed to load dynein (not dynactin) onto late endosomes/lysosomes downstream of RILP.\",\n      \"evidence\": \"Isoform-specific antibodies, RNAi, subcellular fractionation, and dynein/dynactin displacement assays with RILP stimulation\",\n      \"pmids\": [\"21169557\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct physical link between LIC1 and RILP not biochemically defined here\", \"Selectivity of dynein vs dynactin recruitment mechanism left open\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed LIC1 and LIC2 occupy distinct mitotic locations (spindle/midbody vs spindle poles), extending isoform specialization to cell division.\",\n      \"evidence\": \"Immunofluorescence of endogenous LIC1 and LIC2 across mitotic stages\",\n      \"pmids\": [\"20964624\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional perturbation to test the localization's role\", \"Single method, single lab\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Connected LIC1 function to organismal physiology, demonstrating a point mutation perturbs neuronal cortical development and behavior in vivo.\",\n      \"evidence\": \"Genotype-driven Dync1li1 N235Y mouse model with cortical, electrophysiological, and behavioral assays\",\n      \"pmids\": [\"21471385\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular consequence of N235Y on dynein assembly or cargo binding not defined\", \"Causal trafficking defect underlying the phenotype not identified\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Separated LIC function from core motor mechanics: LICs are required for centriole cohesion and bipolar spindles but not for microtubule gliding, with the defect ascribed to imbalance against Eg5.\",\n      \"evidence\": \"siRNA in human cells, morpholino in Xenopus, in vitro microtubule gliding assay, and Eg5-inhibitor epistasis\",\n      \"pmids\": [\"25422374\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"LIC1-specific contribution versus pan-LIC effect not fully separated in this assay\", \"Cargo or adaptor mediating centriole cohesion not identified\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrated LIC1 is required for retrograde autophagosome-to-lysosome transport, linking its loss to autophagic-flux failure and hair-cell death.\",\n      \"evidence\": \"Dync1li1 knockout mouse plus OC1 cell knockdown with LC3/autolysosome flux assays\",\n      \"pmids\": [\"35727824\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Adaptor coupling LIC1 to autophagosomes not identified\", \"Whether Golgi thinning is cause or consequence of complex destabilization unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established the structural basis and functional role of an activating adaptor interaction: KASH5 binds a conserved helix in the LIC C-terminus and activates dynein motility, with LIS1 required for dynactin incorporation.\",\n      \"evidence\": \"In vitro motility reconstitution, Co-IP, KASH5 EF-hand mutagenesis, and dominant-negative cytosolic KASH5 in cells\",\n      \"pmids\": [\"36946995\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether other LIC1 adaptors use the same helix competitively not addressed\", \"Calcium regulation of the interaction physiology not resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed cargo-pathway specificity in vivo, showing LIC1 supports Rab8-dependent but not Rab11-dependent transport in cone photoreceptors.\",\n      \"evidence\": \"CRISPR-Cas9 dync1li1 knockout zebrafish with opsin immunofluorescence, TUNEL, and Rab8/Rab11 transport analysis\",\n      \"pmids\": [\"36682603\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct LIC1-Rab8 coupling mechanism not biochemically defined\", \"Single organism model\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined a physiological output for LIC1 cargo selection: it routes VEGFR2 recycling endosomes to lysosomal degradation via RILPL1/2, restraining angiogenesis.\",\n      \"evidence\": \"Zebrafish dync1li1 and rilpl1/2 mutants, endothelial-cell knockdown, VEGFR2 surface flow cytometry, phospho-SRC immunoblot, and constitutively active Rab11a epistasis\",\n      \"pmids\": [\"39356418\", \"38903077\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct LIC1-RILPL1/2 binding interface not mapped\", \"How LIC1 balances degradative vs recycling fate of endosomes mechanistically unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How LIC1 discriminates among its multiple adaptors (FIP3, KASH5, RILPL1/2) to achieve cargo- and tissue-specific transport, and the structural rules governing this selectivity versus LIC2, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No unified structural model of competitive adaptor binding on the LIC1 C-terminus\", \"Determinants of LIC1 vs LIC2 cargo partitioning unknown\", \"Regulation of adaptor switching across cell types not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 6, 9]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [2, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [2, 7]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 2, 9]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3, 5]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1, 9]}\n    ],\n    \"complexes\": [\"cytoplasmic dynein-1 complex\"],\n    \"partners\": [\"RAB11FIP3\", \"RAB11A\", \"KASH5\", \"RILPL1\", \"RILPL2\", \"RILP\", \"LIS1\"],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}