{"gene":"HOOK3","run_date":"2026-06-10T01:55:22","timeline":{"discoveries":[{"year":2001,"finding":"Hook3 contains a conserved NH2-terminal domain that mediates microtubule binding and a divergent COOH-terminal domain that mediates organelle (Golgi membrane) binding. Hook3 bound to Golgi membranes in vitro and was enriched at the cis-Golgi in vivo. Overexpression of Hook3 caused fragmentation of the Golgi complex.","method":"In vitro binding assays, subcellular fractionation, overexpression/dominant-negative in cell culture, immunofluorescence","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (in vitro binding, in vivo localization, dominant-negative phenotype), foundational study replicated by subsequent work","pmids":["11238449"],"is_preprint":false},{"year":2003,"finding":"Salmonella SpiC protein directly binds Hook3 (demonstrated by GST-SpiC pulldown and co-immunoprecipitation from infected macrophages), and SpiC expression phenocopies a Hook3 dominant-negative mutant by disrupting Golgi morphology and altering lysosome distribution, indicating SpiC targets Hook3 function to alter cellular trafficking.","method":"GST pulldown, co-immunoprecipitation, dominant-negative expression in Vero cells and macrophages","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and phenocopy with dominant-negative, single lab","pmids":["12950921"],"is_preprint":false},{"year":2004,"finding":"The IFN-inducible 47 kDa GTPase IIGP physically interacts with Hook3 in a GTP-bound conformation-dependent manner, as shown by yeast two-hybrid and co-immunoprecipitation from IFNγ-stimulated macrophages; both proteins co-localize in Golgi-membrane-enriched fractions.","method":"Yeast two-hybrid, co-immunoprecipitation, subcellular fractionation","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid confirmed by Co-IP, single lab, two orthogonal methods","pmids":["15075236"],"is_preprint":false},{"year":2007,"finding":"Hook3 interacts directly with the cytoplasmic domain of scavenger receptor A (SR-A); the positively charged C-terminal Val614-Ala717 region of Hook3 binds the negatively charged residues Glu12, Asp13, and Asp15 of the SR-A cytoplasmic domain. Hook3 knockdown (siRNA) increased total and surface expression, ligand uptake, and protein stability of SR-A without affecting synthesis or maturation, indicating Hook3 participates in SR-A turnover.","method":"Yeast two-hybrid, mass spectrometry, GST pulldown, co-immunoprecipitation, co-sedimentation, siRNA knockdown, truncation mutants","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, truncation analysis, siRNA functional readout), domain-level mechanism defined","pmids":["17237231"],"is_preprint":false},{"year":2007,"finding":"The HOOK3-RET fusion gene, resulting from chromosomal rearrangement fusing HOOK3 exon 11 to RET exon 12, produces an 88 kDa chimeric protein retaining HOOK3 coiled-coil domains and the intact RET tyrosine kinase domain. Expression of HOOK3-RET cDNA in NIH3T3 cells caused transformed foci formation and tumor formation in nude mice, confirming oncogenic activity.","method":"5'RACE, Western blot, NIH3T3 transformation assay, nude mouse xenograft","journal":"Endocrine-related cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional transformation assay with defined fusion protein, single lab","pmids":["17639057"],"is_preprint":false},{"year":2010,"finding":"Hook3 interacts with PCM1 (Pericentriolar Material 1) to recruit Hook3 to pericentriolar satellites, enabling trafficking of pericentriolar satellite components. Disruption of the Hook3-PCM1 interaction in vivo impairs interkinetic nuclear migration in embryonic neural progenitors, leading to overproduction of neurons and premature depletion of the neural progenitor pool in the developing neocortex.","method":"Co-immunoprecipitation, in vivo dominant-negative disruption, live imaging of interkinetic nuclear migration, cortical neurogenesis assays","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP combined with in vivo functional epistasis showing defined cellular phenotype, replicated across multiple assays in single rigorous study","pmids":["20152126"],"is_preprint":false},{"year":2016,"finding":"The conserved Hook domain of Hook3 directly interacts with the dynein light intermediate chain 1 (LIC1). Crystal structure of the Hook domain was solved, and structure-based mutagenesis identified two conserved surface residues critical for LIC1 binding; Hook proteins with mutations in these residues fail to form a stable dynein-dynactin ternary complex. A separate region of Hook3 is specifically required for allosteric activation of processive dynein-dynactin motility.","method":"Crystal structure determination, structure-based mutagenesis, in vitro binding assays, single-molecule motility assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with mutagenesis and in vitro functional reconstitution, multiple orthogonal methods in single rigorous study","pmids":["27482052"],"is_preprint":false},{"year":2019,"finding":"Hook3 acts as a scaffold for both cytoplasmic dynein-1/dynactin and kinesin-3 KIF1C, forming a ternary complex in vitro with purified components. Full-length Hook3 binds to and activates dynein/dynactin motility, and also binds to the KIF1C tail region without activating KIF1C motility. This scaffolding allows dynein to transport KIF1C toward the microtubule minus end and KIF1C to transport dynein toward the plus end. In cells, KIF1C can recruit Hook3 to the cell periphery.","method":"In vitro reconstitution with purified proteins, single-molecule motility assays, mass spectrometry, cell biology (KIF1C recruitment assay)","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified components, single-molecule assays, and cell-based validation, multiple orthogonal methods","pmids":["31320392"],"is_preprint":false},{"year":2019,"finding":"Hook3 binds to the stalk/tail region of KIF1C (the same region that mediates KIF1C autoinhibition) and increases the landing rate of KIF1C onto microtubules in vitro, functioning as a cargo adaptor that releases KIF1C autoinhibition to enable cargo-activated transport.","method":"In vitro microtubule binding/landing assays with purified proteins, co-immunoprecipitation, KIF1C truncation analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified proteins demonstrating mechanistic release of autoinhibition, multiple orthogonal methods","pmids":["31217419"],"is_preprint":false},{"year":2021,"finding":"ERK1c phosphorylates HOOK3 early in mitosis, and a subsequent phosphorylation by AuroraA is also required. These phosphorylations cause HOOK3 to detach from microtubules and increase its interaction with GM130, leading to Golgi destabilization and fragmentation during mitosis.","method":"Substrate identification (kinase assay), phosphorylation-site mutagenesis, co-immunoprecipitation, microtubule co-sedimentation assay, cell imaging of Golgi fragmentation","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — kinase substrate assay combined with mutagenesis and cellular phenotype, single lab","pmids":["34189435"],"is_preprint":false},{"year":2024,"finding":"KIF1C supports retrograde lysosomal transport (toward the microtubule minus end) driven by dynein through interaction with Hook3, which associates with the lysosome-anchored protein RUFY3. KIF1C motor activity is not required and in fact inhibits this process; instead, KIF1C functions non-canonically as an adaptor to activate dynein-driven lysosomal transport via Hook3.","method":"Co-immunoprecipitation, siRNA knockdown, live-cell imaging of lysosome transport, dominant-negative and motor-dead KIF1C constructs","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional knockdown with defined phenotype and interaction mapping, single lab","pmids":["39394274"],"is_preprint":false},{"year":2025,"finding":"Crystal structure of the Hook3(553-624)–KIF1C(714-809) complex was determined, and structure-based mutagenesis showed that this complex formation is necessary and sufficient for full-length protein interaction in HEK293T cells and for Hook3- and KIF1C-mediated anterograde transport in RPE1 cells. PTPN21 also interacts with the same KIF1C tail region to regulate transport.","method":"Crystal structure determination, structure-based mutagenesis, co-immunoprecipitation in HEK293T cells, live-cell cargo transport assays in RPE1 cells","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with mutagenesis and functional transport assay, multiple orthogonal methods in single study","pmids":["40312563"],"is_preprint":false},{"year":2015,"finding":"Hook3 deficiency in cultured cells slows endosomal transport and increases β-amyloid production, establishing a functional role for Hook3 in endosomal trafficking that modulates amyloid precursor protein processing.","method":"siRNA knockdown, live-cell endosomal transport assay, β-amyloid ELISA","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single functional assay per endpoint, limited mechanistic detail in abstract","pmids":["25799409"],"is_preprint":false}],"current_model":"HOOK3 is a cytosolic coiled-coil cargo adaptor protein whose conserved N-terminal Hook domain binds microtubules and directly interacts with dynein light intermediate chain 1 (LIC1) to form and allosterically activate processive dynein-dynactin complexes, while its C-terminal region binds organelle membranes (cis-Golgi via GM130, lysosomes via RUFY3) and the tail of kinesin-3 KIF1C, enabling Hook3 to scaffold both minus-end (dynein) and plus-end (KIF1C) motors for bidirectional cargo transport; during mitosis, sequential phosphorylation by ERK1c and AuroraA detaches Hook3 from microtubules and increases its GM130 association to drive Golgi fragmentation, while in interphase Hook3 interacts with PCM1 at pericentriolar satellites to support centrosomal assembly and interkinetic nuclear migration, and with scavenger receptor A to regulate its turnover."},"narrative":{"mechanistic_narrative":"HOOK3 is a coiled-coil cargo adaptor that bridges organelle membranes to microtubule motors, scaffolding bidirectional transport and Golgi organization [PMID:11238449, PMID:31320392]. Its bipartite architecture pairs a conserved N-terminal domain that binds microtubules and the dynein light intermediate chain 1 (LIC1) with a divergent C-terminal region that engages organelle membranes, including the cis-Golgi [PMID:11238449, PMID:27482052]. The crystallized Hook domain contacts LIC1 through two conserved surface residues required to assemble a stable dynein-dynactin ternary complex, and a separate region of HOOK3 allosterically activates processive dynein-dynactin motility [PMID:27482052]. HOOK3 simultaneously binds the autoinhibitory stalk/tail of the kinesin-3 KIF1C, releasing KIF1C autoinhibition and raising its microtubule landing rate, so that a single HOOK3 scaffold links minus-end (dynein) and plus-end (KIF1C) motors for opposed transport [PMID:31320392, PMID:31217419, PMID:40312563]. This dual-motor scaffolding drives defined cargo events: KIF1C acts non-canonically as an adaptor that, via HOOK3 binding the lysosome-anchored RUFY3, activates dynein-driven retrograde lysosomal transport [PMID:39394274]. HOOK3 also organizes membrane-associated and centrosomal compartments: its C-terminal region binds the scavenger receptor A cytoplasmic domain to control SR-A turnover [PMID:17237231], and it interacts with PCM1 to localize to pericentriolar satellites and support interkinetic nuclear migration during cortical neurogenesis [PMID:20152126]. During mitosis, sequential phosphorylation by ERK1c and AuroraA detaches HOOK3 from microtubules and enhances its GM130 association to drive Golgi fragmentation [PMID:34189435]. A HOOK3-RET chromosomal fusion that retains the HOOK3 coiled-coil and the RET kinase domain is oncogenic in transformation and xenograft assays [PMID:17639057].","teleology":[{"year":2001,"claim":"Established HOOK3's bipartite domain logic — that one terminus reads microtubules and the other reads organelle membranes — defining it as a candidate physical link between the cytoskeleton and the Golgi.","evidence":"In vitro binding, fractionation, immunofluorescence and overexpression in cell culture","pmids":["11238449"],"confidence":"High","gaps":["Did not identify the motor or membrane receptors mediating each interaction","Mechanism of Golgi fragmentation on overexpression unresolved"]},{"year":2003,"claim":"Showed HOOK3 function can be hijacked by a pathogen, as the Salmonella effector SpiC binds HOOK3 and phenocopies its dominant-negative disruption of Golgi and lysosome distribution.","evidence":"GST pulldown, reciprocal Co-IP, and dominant-negative expression in macrophages","pmids":["12950921"],"confidence":"Medium","gaps":["Single lab","Did not map the HOOK3 region bound by SpiC","Link to specific trafficking machinery not defined"]},{"year":2004,"claim":"Connected HOOK3 to interferon-induced immune effectors by showing the GTPase IIGP binds it in a nucleotide-dependent manner at Golgi membranes.","evidence":"Yeast two-hybrid and Co-IP from IFNγ-stimulated macrophages with fractionation","pmids":["15075236"],"confidence":"Medium","gaps":["Functional consequence of the interaction not established","Single lab, two methods"]},{"year":2007,"claim":"Defined a membrane-receptor cargo for HOOK3 at the residue level, showing its basic C-terminal region binds acidic residues of the SR-A cytoplasmic tail to regulate receptor stability and turnover.","evidence":"Yeast two-hybrid, GST pulldown, truncation mutants, and siRNA functional readouts","pmids":["17237231"],"confidence":"High","gaps":["Whether SR-A turnover depends on motor-driven transport not tested","Endosomal/lysosomal routing of SR-A unresolved"]},{"year":2007,"claim":"Demonstrated a disease-relevant gain of function, as a HOOK3-RET chromosomal fusion fuses HOOK3 coiled-coils to the intact RET kinase and is oncogenic.","evidence":"5'RACE, Western blot, NIH3T3 transformation and nude mouse xenograft","pmids":["17639057"],"confidence":"Medium","gaps":["Mechanism of RET activation by HOOK3 coiled-coils (e.g. dimerization) not dissected","Single lab"]},{"year":2010,"claim":"Placed HOOK3 at pericentriolar satellites via PCM1 and tied this to a developmental process, linking the interaction to interkinetic nuclear migration and neural progenitor maintenance.","evidence":"Co-IP plus in vivo dominant-negative disruption and live imaging of cortical neurogenesis","pmids":["20152126"],"confidence":"High","gaps":["Motor requirement for satellite trafficking not defined here","Direct vs indirect PCM1 binding not resolved"]},{"year":2015,"claim":"Implicated HOOK3 in endosomal transport kinetics with a downstream consequence for amyloid precursor protein processing.","evidence":"siRNA knockdown, live-cell endosomal transport assay, β-amyloid ELISA","pmids":["25799409"],"confidence":"Low","gaps":["Single functional assay per endpoint with limited mechanistic detail","Cargo and motor mediating the endosomal effect unidentified"]},{"year":2016,"claim":"Resolved how HOOK3 engages dynein, showing the crystallized Hook domain binds LIC1 through two conserved residues required for stable dynein-dynactin complex formation and identifying a separate region needed for motility activation.","evidence":"Crystal structure, structure-based mutagenesis, in vitro binding and single-molecule motility assays","pmids":["27482052"],"confidence":"High","gaps":["How membrane cargo binding couples to activation not shown","Regulation of the activating region unresolved"]},{"year":2019,"claim":"Recast HOOK3 as a dual-motor scaffold, reconstituting a ternary complex in which it activates dynein-dynactin and simultaneously binds the autoinhibitory KIF1C tail to enable opposed transport.","evidence":"In vitro reconstitution with purified proteins, single-molecule motility, mass spectrometry, and KIF1C recruitment in cells; converging with landing-rate assays showing release of KIF1C autoinhibition","pmids":["31320392","31217419"],"confidence":"High","gaps":["What determines net directionality on a given cargo not defined","In vivo cargoes of the dual-motor complex not enumerated here"]},{"year":2021,"claim":"Identified the mitotic switch controlling HOOK3, with sequential ERK1c and AuroraA phosphorylation detaching it from microtubules and boosting GM130 binding to fragment the Golgi.","evidence":"Kinase substrate assay, phospho-site mutagenesis, Co-IP, microtubule co-sedimentation, Golgi imaging","pmids":["34189435"],"confidence":"Medium","gaps":["Phospho-sites and their effect on motor binding not fully mapped","Single lab"]},{"year":2024,"claim":"Revealed a non-canonical adaptor role for KIF1C, where it activates dynein-driven retrograde lysosomal transport through HOOK3 and RUFY3 without using its own motor activity.","evidence":"Co-IP, siRNA knockdown, live-cell lysosome imaging, motor-dead and dominant-negative KIF1C","pmids":["39394274"],"confidence":"Medium","gaps":["How directionality is biased toward dynein in this context not fully resolved","Single lab"]},{"year":2025,"claim":"Defined the HOOK3-KIF1C interface at atomic resolution and showed it is necessary and sufficient for anterograde transport, while placing PTPN21 at the same KIF1C tail as a regulator.","evidence":"Crystal structure of Hook3(553-624)–KIF1C(714-809), structure-based mutagenesis, Co-IP, and live-cell transport assays in RPE1 cells","pmids":["40312563"],"confidence":"High","gaps":["How PTPN21 and HOOK3 binding to the shared site are coordinated not resolved","Structural basis for simultaneous dynein and KIF1C engagement not shown"]},{"year":null,"claim":"How HOOK3 selects, integrates, and directionally biases its competing dynein and KIF1C motors on a given membrane cargo in vivo remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structure of HOOK3 simultaneously bound to dynein-dynactin and KIF1C","Regulatory logic linking phosphorylation, RUFY3/GM130/SR-A cargo identity, and motor choice unintegrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[6,7,8,11]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,6]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[6,8]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[5]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[10]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[12]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[7,10,11]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[7,8,10]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[5]}],"complexes":["dynein-dynactin-Hook3 activated transport complex","pericentriolar satellite"],"partners":["DYNC1LI1","KIF1C","GM130","PCM1","RUFY3","MSR1","PTPN21","RET"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86VS8","full_name":"Protein Hook homolog 3","aliases":[],"length_aa":718,"mass_kda":83.1,"function":"Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Predominantly recruits 2 dyneins, which increases both the force and speed of the microtubule motor (PubMed:25035494, PubMed:33734450). Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). May regulate clearance of endocytosed receptors such as MSR1. Participates in defining the architecture and localization of the Golgi complex. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997) (Microbial infection) May serve as a target for the spiC protein from Salmonella typhimurium, which inactivates it, leading to a strong alteration in cellular trafficking","subcellular_location":"Cytoplasm, cytoskeleton; Golgi apparatus","url":"https://www.uniprot.org/uniprotkb/Q86VS8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/HOOK3","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CLIP1","stoichiometry":0.2},{"gene":"DYNC1LI1","stoichiometry":0.2},{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/HOOK3","total_profiled":1310},"omim":[{"mim_id":"620891","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 181; CCDC181","url":"https://www.omim.org/entry/620891"},{"mim_id":"620230","title":"FHF COMPLEX SUBUNIT HOOK-INTERACTING PROTEIN 2B; FHIP2B","url":"https://www.omim.org/entry/620230"},{"mim_id":"620229","title":"FHF COMPLEX SUBUNIT HOOK-INTERACTING PROTEIN 1B; FHIP1B","url":"https://www.omim.org/entry/620229"},{"mim_id":"617312","title":"FHF COMPLEX SUBUNIT HOOK-INTERACTING PROTEIN 2A; FHIP2A","url":"https://www.omim.org/entry/617312"},{"mim_id":"617002","title":"BICD FAMILY-LIKE CARGO ADAPTOR 1; BICDL1","url":"https://www.omim.org/entry/617002"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centriolar satellite","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/HOOK3"},"hgnc":{"alias_symbol":["HK3"],"prev_symbol":[]},"alphafold":{"accession":"Q86VS8","domains":[{"cath_id":"1.10.418.10","chopping":"3-162","consensus_level":"high","plddt":84.3988,"start":3,"end":162}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86VS8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86VS8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86VS8-F1-predicted_aligned_error_v6.png","plddt_mean":82.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=HOOK3","jax_strain_url":"https://www.jax.org/strain/search?query=HOOK3"},"sequence":{"accession":"Q86VS8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86VS8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86VS8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86VS8"}},"corpus_meta":[{"pmid":"11238449","id":"PMC_11238449","title":"The Golgi-associated hook3 protein is a member of a novel family of microtubule-binding proteins.","date":"2001","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11238449","citation_count":167,"is_preprint":false},{"pmid":"27482052","id":"PMC_27482052","title":"Assembly and activation of dynein-dynactin by the cargo adaptor protein Hook3.","date":"2016","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/27482052","citation_count":103,"is_preprint":false},{"pmid":"20152126","id":"PMC_20152126","title":"Hook3 interacts with PCM1 to regulate pericentriolar material assembly and the timing of neurogenesis.","date":"2010","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/20152126","citation_count":98,"is_preprint":false},{"pmid":"31320392","id":"PMC_31320392","title":"Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C.","date":"2019","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31320392","citation_count":66,"is_preprint":false},{"pmid":"31217419","id":"PMC_31217419","title":"PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31217419","citation_count":57,"is_preprint":false},{"pmid":"17639057","id":"PMC_17639057","title":"HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma.","date":"2007","source":"Endocrine-related cancer","url":"https://pubmed.ncbi.nlm.nih.gov/17639057","citation_count":55,"is_preprint":false},{"pmid":"12950921","id":"PMC_12950921","title":"The Salmonella SpiC protein targets the mammalian Hook3 protein function to alter cellular trafficking.","date":"2003","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12950921","citation_count":52,"is_preprint":false},{"pmid":"15075236","id":"PMC_15075236","title":"IIGP, a member of the 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letters","url":"https://pubmed.ncbi.nlm.nih.gov/42238005","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11053,"output_tokens":3324,"usd":0.041509,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10889,"output_tokens":4077,"usd":0.078185,"stage2_stop_reason":"end_turn"},"total_usd":0.119694,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"Hook3 contains a conserved NH2-terminal domain that mediates microtubule binding and a divergent COOH-terminal domain that mediates organelle (Golgi membrane) binding. Hook3 bound to Golgi membranes in vitro and was enriched at the cis-Golgi in vivo. Overexpression of Hook3 caused fragmentation of the Golgi complex.\",\n      \"method\": \"In vitro binding assays, subcellular fractionation, overexpression/dominant-negative in cell culture, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (in vitro binding, in vivo localization, dominant-negative phenotype), foundational study replicated by subsequent work\",\n      \"pmids\": [\"11238449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Salmonella SpiC protein directly binds Hook3 (demonstrated by GST-SpiC pulldown and co-immunoprecipitation from infected macrophages), and SpiC expression phenocopies a Hook3 dominant-negative mutant by disrupting Golgi morphology and altering lysosome distribution, indicating SpiC targets Hook3 function to alter cellular trafficking.\",\n      \"method\": \"GST pulldown, co-immunoprecipitation, dominant-negative expression in Vero cells and macrophages\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and phenocopy with dominant-negative, single lab\",\n      \"pmids\": [\"12950921\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The IFN-inducible 47 kDa GTPase IIGP physically interacts with Hook3 in a GTP-bound conformation-dependent manner, as shown by yeast two-hybrid and co-immunoprecipitation from IFNγ-stimulated macrophages; both proteins co-localize in Golgi-membrane-enriched fractions.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, subcellular fractionation\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid confirmed by Co-IP, single lab, two orthogonal methods\",\n      \"pmids\": [\"15075236\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Hook3 interacts directly with the cytoplasmic domain of scavenger receptor A (SR-A); the positively charged C-terminal Val614-Ala717 region of Hook3 binds the negatively charged residues Glu12, Asp13, and Asp15 of the SR-A cytoplasmic domain. Hook3 knockdown (siRNA) increased total and surface expression, ligand uptake, and protein stability of SR-A without affecting synthesis or maturation, indicating Hook3 participates in SR-A turnover.\",\n      \"method\": \"Yeast two-hybrid, mass spectrometry, GST pulldown, co-immunoprecipitation, co-sedimentation, siRNA knockdown, truncation mutants\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, truncation analysis, siRNA functional readout), domain-level mechanism defined\",\n      \"pmids\": [\"17237231\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The HOOK3-RET fusion gene, resulting from chromosomal rearrangement fusing HOOK3 exon 11 to RET exon 12, produces an 88 kDa chimeric protein retaining HOOK3 coiled-coil domains and the intact RET tyrosine kinase domain. Expression of HOOK3-RET cDNA in NIH3T3 cells caused transformed foci formation and tumor formation in nude mice, confirming oncogenic activity.\",\n      \"method\": \"5'RACE, Western blot, NIH3T3 transformation assay, nude mouse xenograft\",\n      \"journal\": \"Endocrine-related cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional transformation assay with defined fusion protein, single lab\",\n      \"pmids\": [\"17639057\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Hook3 interacts with PCM1 (Pericentriolar Material 1) to recruit Hook3 to pericentriolar satellites, enabling trafficking of pericentriolar satellite components. Disruption of the Hook3-PCM1 interaction in vivo impairs interkinetic nuclear migration in embryonic neural progenitors, leading to overproduction of neurons and premature depletion of the neural progenitor pool in the developing neocortex.\",\n      \"method\": \"Co-immunoprecipitation, in vivo dominant-negative disruption, live imaging of interkinetic nuclear migration, cortical neurogenesis assays\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP combined with in vivo functional epistasis showing defined cellular phenotype, replicated across multiple assays in single rigorous study\",\n      \"pmids\": [\"20152126\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The conserved Hook domain of Hook3 directly interacts with the dynein light intermediate chain 1 (LIC1). Crystal structure of the Hook domain was solved, and structure-based mutagenesis identified two conserved surface residues critical for LIC1 binding; Hook proteins with mutations in these residues fail to form a stable dynein-dynactin ternary complex. A separate region of Hook3 is specifically required for allosteric activation of processive dynein-dynactin motility.\",\n      \"method\": \"Crystal structure determination, structure-based mutagenesis, in vitro binding assays, single-molecule motility assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with mutagenesis and in vitro functional reconstitution, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"27482052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Hook3 acts as a scaffold for both cytoplasmic dynein-1/dynactin and kinesin-3 KIF1C, forming a ternary complex in vitro with purified components. Full-length Hook3 binds to and activates dynein/dynactin motility, and also binds to the KIF1C tail region without activating KIF1C motility. This scaffolding allows dynein to transport KIF1C toward the microtubule minus end and KIF1C to transport dynein toward the plus end. In cells, KIF1C can recruit Hook3 to the cell periphery.\",\n      \"method\": \"In vitro reconstitution with purified proteins, single-molecule motility assays, mass spectrometry, cell biology (KIF1C recruitment assay)\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified components, single-molecule assays, and cell-based validation, multiple orthogonal methods\",\n      \"pmids\": [\"31320392\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Hook3 binds to the stalk/tail region of KIF1C (the same region that mediates KIF1C autoinhibition) and increases the landing rate of KIF1C onto microtubules in vitro, functioning as a cargo adaptor that releases KIF1C autoinhibition to enable cargo-activated transport.\",\n      \"method\": \"In vitro microtubule binding/landing assays with purified proteins, co-immunoprecipitation, KIF1C truncation analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified proteins demonstrating mechanistic release of autoinhibition, multiple orthogonal methods\",\n      \"pmids\": [\"31217419\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"ERK1c phosphorylates HOOK3 early in mitosis, and a subsequent phosphorylation by AuroraA is also required. These phosphorylations cause HOOK3 to detach from microtubules and increase its interaction with GM130, leading to Golgi destabilization and fragmentation during mitosis.\",\n      \"method\": \"Substrate identification (kinase assay), phosphorylation-site mutagenesis, co-immunoprecipitation, microtubule co-sedimentation assay, cell imaging of Golgi fragmentation\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — kinase substrate assay combined with mutagenesis and cellular phenotype, single lab\",\n      \"pmids\": [\"34189435\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIF1C supports retrograde lysosomal transport (toward the microtubule minus end) driven by dynein through interaction with Hook3, which associates with the lysosome-anchored protein RUFY3. KIF1C motor activity is not required and in fact inhibits this process; instead, KIF1C functions non-canonically as an adaptor to activate dynein-driven lysosomal transport via Hook3.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, live-cell imaging of lysosome transport, dominant-negative and motor-dead KIF1C constructs\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional knockdown with defined phenotype and interaction mapping, single lab\",\n      \"pmids\": [\"39394274\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Crystal structure of the Hook3(553-624)–KIF1C(714-809) complex was determined, and structure-based mutagenesis showed that this complex formation is necessary and sufficient for full-length protein interaction in HEK293T cells and for Hook3- and KIF1C-mediated anterograde transport in RPE1 cells. PTPN21 also interacts with the same KIF1C tail region to regulate transport.\",\n      \"method\": \"Crystal structure determination, structure-based mutagenesis, co-immunoprecipitation in HEK293T cells, live-cell cargo transport assays in RPE1 cells\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with mutagenesis and functional transport assay, multiple orthogonal methods in single study\",\n      \"pmids\": [\"40312563\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Hook3 deficiency in cultured cells slows endosomal transport and increases β-amyloid production, establishing a functional role for Hook3 in endosomal trafficking that modulates amyloid precursor protein processing.\",\n      \"method\": \"siRNA knockdown, live-cell endosomal transport assay, β-amyloid ELISA\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single functional assay per endpoint, limited mechanistic detail in abstract\",\n      \"pmids\": [\"25799409\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"HOOK3 is a cytosolic coiled-coil cargo adaptor protein whose conserved N-terminal Hook domain binds microtubules and directly interacts with dynein light intermediate chain 1 (LIC1) to form and allosterically activate processive dynein-dynactin complexes, while its C-terminal region binds organelle membranes (cis-Golgi via GM130, lysosomes via RUFY3) and the tail of kinesin-3 KIF1C, enabling Hook3 to scaffold both minus-end (dynein) and plus-end (KIF1C) motors for bidirectional cargo transport; during mitosis, sequential phosphorylation by ERK1c and AuroraA detaches Hook3 from microtubules and increases its GM130 association to drive Golgi fragmentation, while in interphase Hook3 interacts with PCM1 at pericentriolar satellites to support centrosomal assembly and interkinetic nuclear migration, and with scavenger receptor A to regulate its turnover.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HOOK3 is a coiled-coil cargo adaptor that bridges organelle membranes to microtubule motors, scaffolding bidirectional transport and Golgi organization [#0, #7]. Its bipartite architecture pairs a conserved N-terminal domain that binds microtubules and the dynein light intermediate chain 1 (LIC1) with a divergent C-terminal region that engages organelle membranes, including the cis-Golgi [#0, #6]. The crystallized Hook domain contacts LIC1 through two conserved surface residues required to assemble a stable dynein-dynactin ternary complex, and a separate region of HOOK3 allosterically activates processive dynein-dynactin motility [#6]. HOOK3 simultaneously binds the autoinhibitory stalk/tail of the kinesin-3 KIF1C, releasing KIF1C autoinhibition and raising its microtubule landing rate, so that a single HOOK3 scaffold links minus-end (dynein) and plus-end (KIF1C) motors for opposed transport [#7, #8, #11]. This dual-motor scaffolding drives defined cargo events: KIF1C acts non-canonically as an adaptor that, via HOOK3 binding the lysosome-anchored RUFY3, activates dynein-driven retrograde lysosomal transport [#10]. HOOK3 also organizes membrane-associated and centrosomal compartments: its C-terminal region binds the scavenger receptor A cytoplasmic domain to control SR-A turnover [#3], and it interacts with PCM1 to localize to pericentriolar satellites and support interkinetic nuclear migration during cortical neurogenesis [#5]. During mitosis, sequential phosphorylation by ERK1c and AuroraA detaches HOOK3 from microtubules and enhances its GM130 association to drive Golgi fragmentation [#9]. A HOOK3-RET chromosomal fusion that retains the HOOK3 coiled-coil and the RET kinase domain is oncogenic in transformation and xenograft assays [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established HOOK3's bipartite domain logic — that one terminus reads microtubules and the other reads organelle membranes — defining it as a candidate physical link between the cytoskeleton and the Golgi.\",\n      \"evidence\": \"In vitro binding, fractionation, immunofluorescence and overexpression in cell culture\",\n      \"pmids\": [\"11238449\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the motor or membrane receptors mediating each interaction\", \"Mechanism of Golgi fragmentation on overexpression unresolved\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Showed HOOK3 function can be hijacked by a pathogen, as the Salmonella effector SpiC binds HOOK3 and phenocopies its dominant-negative disruption of Golgi and lysosome distribution.\",\n      \"evidence\": \"GST pulldown, reciprocal Co-IP, and dominant-negative expression in macrophages\",\n      \"pmids\": [\"12950921\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Did not map the HOOK3 region bound by SpiC\", \"Link to specific trafficking machinery not defined\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Connected HOOK3 to interferon-induced immune effectors by showing the GTPase IIGP binds it in a nucleotide-dependent manner at Golgi membranes.\",\n      \"evidence\": \"Yeast two-hybrid and Co-IP from IFN\\u03b3-stimulated macrophages with fractionation\",\n      \"pmids\": [\"15075236\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the interaction not established\", \"Single lab, two methods\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Defined a membrane-receptor cargo for HOOK3 at the residue level, showing its basic C-terminal region binds acidic residues of the SR-A cytoplasmic tail to regulate receptor stability and turnover.\",\n      \"evidence\": \"Yeast two-hybrid, GST pulldown, truncation mutants, and siRNA functional readouts\",\n      \"pmids\": [\"17237231\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SR-A turnover depends on motor-driven transport not tested\", \"Endosomal/lysosomal routing of SR-A unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstrated a disease-relevant gain of function, as a HOOK3-RET chromosomal fusion fuses HOOK3 coiled-coils to the intact RET kinase and is oncogenic.\",\n      \"evidence\": \"5'RACE, Western blot, NIH3T3 transformation and nude mouse xenograft\",\n      \"pmids\": [\"17639057\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of RET activation by HOOK3 coiled-coils (e.g. dimerization) not dissected\", \"Single lab\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Placed HOOK3 at pericentriolar satellites via PCM1 and tied this to a developmental process, linking the interaction to interkinetic nuclear migration and neural progenitor maintenance.\",\n      \"evidence\": \"Co-IP plus in vivo dominant-negative disruption and live imaging of cortical neurogenesis\",\n      \"pmids\": [\"20152126\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Motor requirement for satellite trafficking not defined here\", \"Direct vs indirect PCM1 binding not resolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Implicated HOOK3 in endosomal transport kinetics with a downstream consequence for amyloid precursor protein processing.\",\n      \"evidence\": \"siRNA knockdown, live-cell endosomal transport assay, \\u03b2-amyloid ELISA\",\n      \"pmids\": [\"25799409\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single functional assay per endpoint with limited mechanistic detail\", \"Cargo and motor mediating the endosomal effect unidentified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Resolved how HOOK3 engages dynein, showing the crystallized Hook domain binds LIC1 through two conserved residues required for stable dynein-dynactin complex formation and identifying a separate region needed for motility activation.\",\n      \"evidence\": \"Crystal structure, structure-based mutagenesis, in vitro binding and single-molecule motility assays\",\n      \"pmids\": [\"27482052\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How membrane cargo binding couples to activation not shown\", \"Regulation of the activating region unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Recast HOOK3 as a dual-motor scaffold, reconstituting a ternary complex in which it activates dynein-dynactin and simultaneously binds the autoinhibitory KIF1C tail to enable opposed transport.\",\n      \"evidence\": \"In vitro reconstitution with purified proteins, single-molecule motility, mass spectrometry, and KIF1C recruitment in cells; converging with landing-rate assays showing release of KIF1C autoinhibition\",\n      \"pmids\": [\"31320392\", \"31217419\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"What determines net directionality on a given cargo not defined\", \"In vivo cargoes of the dual-motor complex not enumerated here\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified the mitotic switch controlling HOOK3, with sequential ERK1c and AuroraA phosphorylation detaching it from microtubules and boosting GM130 binding to fragment the Golgi.\",\n      \"evidence\": \"Kinase substrate assay, phospho-site mutagenesis, Co-IP, microtubule co-sedimentation, Golgi imaging\",\n      \"pmids\": [\"34189435\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phospho-sites and their effect on motor binding not fully mapped\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a non-canonical adaptor role for KIF1C, where it activates dynein-driven retrograde lysosomal transport through HOOK3 and RUFY3 without using its own motor activity.\",\n      \"evidence\": \"Co-IP, siRNA knockdown, live-cell lysosome imaging, motor-dead and dominant-negative KIF1C\",\n      \"pmids\": [\"39394274\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How directionality is biased toward dynein in this context not fully resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined the HOOK3-KIF1C interface at atomic resolution and showed it is necessary and sufficient for anterograde transport, while placing PTPN21 at the same KIF1C tail as a regulator.\",\n      \"evidence\": \"Crystal structure of Hook3(553-624)\\u2013KIF1C(714-809), structure-based mutagenesis, Co-IP, and live-cell transport assays in RPE1 cells\",\n      \"pmids\": [\"40312563\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How PTPN21 and HOOK3 binding to the shared site are coordinated not resolved\", \"Structural basis for simultaneous dynein and KIF1C engagement not shown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How HOOK3 selects, integrates, and directionally biases its competing dynein and KIF1C motors on a given membrane cargo in vivo remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of HOOK3 simultaneously bound to dynein-dynactin and KIF1C\", \"Regulatory logic linking phosphorylation, RUFY3/GM130/SR-A cargo identity, and motor choice unintegrated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [6, 7, 8, 11]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [6, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [12]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [7, 10, 11]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [7, 8, 10]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\"dynein-dynactin-Hook3 activated transport complex\", \"pericentriolar satellite\"],\n    \"partners\": [\"DYNC1LI1\", \"KIF1C\", \"GM130\", \"PCM1\", \"RUFY3\", \"MSR1\", \"PTPN21\", \"RET\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}