{"gene":"HOOK2","run_date":"2026-04-28T18:06:53","timeline":{"discoveries":[{"year":2001,"finding":"Hook proteins constitute a novel family of cytosolic coiled-coil proteins that bind organelles via divergent C-terminal domains and microtubules via conserved N-terminal domains. Hook3 (a family member) binds Golgi membranes in vitro and localizes to cis-Golgi in vivo; overexpression causes Golgi fragmentation, suggesting Hook proteins link organelles to microtubules and define organelle architecture/localization.","method":"In vitro organelle-binding assay, overexpression in cultured cells, immunofluorescence microscopy, Brefeldin A treatment","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (in vitro binding, overexpression phenotype, subcellular localization); foundational family characterization paper with 166 citations","pmids":["11238449"],"is_preprint":false},{"year":1999,"finding":"Drosophila Hook (ortholog of mammalian Hook proteins including HOOK2) is required for endocytic trafficking; loss-of-function alleles show that neither transmembrane nor soluble ligands accumulate in multivesicular bodies (MVBs). All three domains (N-terminal, coiled-coil, C-terminal) are required for Hook function, as shown by truncation experiments.","method":"Drosophila genetics, isolation of null alleles, epistasis with endocytic pathway, expression of truncated proteins","journal":"Genetics","confidence":"High","confidence_rationale":"Tier 2 — genetic loss-of-function with defined cellular phenotype plus domain truncation analysis, replicated across multiple alleles","pmids":["9927460"],"is_preprint":false},{"year":2006,"finding":"Mammalian Hook2 localizes to the centrosome throughout all phases of the cell cycle. Its C-terminal domain directly binds centriolin/CEP110. Expression of the C-terminal domain of centriolin/CEP110 alters endogenous Hook2 distribution. Mislocalized Hook2 (wild-type or mutant) perturbs endogenous centrosomal and pericentrosomal proteins. Interference with Hook2 function causes loss of radial microtubule organization and defects in microtubule regrowth after nocodazole-induced depolymerization, establishing Hook2 as a contributor to centrosomal structure and function.","method":"Immunofluorescence microscopy (cell-cycle staging), direct binding assay (C-terminal domain pulldown), overexpression of dominant-negative constructs, nocodazole washout microtubule regrowth assay","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 2 — direct binding assay plus multiple functional readouts (localization, MT regrowth, centrosome integrity) with loss-of-function phenotypes","pmids":["17140400"],"is_preprint":false},{"year":2008,"finding":"Hook1, Hook2, and Hook3 form part of a multiprotein FHF complex together with FTS (Fused Toes) and FHIP (FTS and Hook Interacting Protein). Hook proteins form homo- and heterodimers; FTS associates with a conserved C-terminal motif in Hook proteins. The ~500-kDa FHF complex interacts with both class B and class C components of the HOPS complex. Depletion of FTS by RNAi impairs EGF trafficking from early-to-late endosomes/lysosomes and reduces HOPS-driven lysosomal clustering, implicating the FTS/Hook/FHIP complex in vesicle trafficking via the HOPS complex.","method":"Proteomic analysis of affinity-purified FTS complexes from HEK293T cells, yeast two-hybrid, Co-IP, siRNA knockdown, EGF trafficking assay, lysosomal clustering assay","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — mass spectrometry-based complex identification confirmed by Co-IP and Y2H, combined with RNAi functional assays showing defined trafficking phenotype","pmids":["18799622"],"is_preprint":false},{"year":2009,"finding":"The human HOOK2 protein specifically interacts with the human ortholog of SUT-2 (MSUT-2/ZC3H14), a CCCH zinc finger protein involved in tau neurotoxicity. Of the three human Hook paralogs (HOOK1, HOOK2, HOOK3), MSUT-2 binds selectively to HOOK2, demonstrating that this interaction is conserved from C. elegans (ZYG-12/SUT-2) to humans.","method":"Yeast two-hybrid screen, in vitro protein binding assay","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 3 — yeast two-hybrid plus in vitro binding; selectivity for HOOK2 over HOOK1/3 noted but limited functional follow-up for the human proteins","pmids":["19273536"],"is_preprint":false},{"year":2009,"finding":"CENP-F localizes to the centrosome and physically interacts with Hook2 (identified by yeast two-hybrid screen and confirmed by co-immunoprecipitation). Ablation of CENP-F eliminates microtubule repolymerization after nocodazole treatment specifically from the centrosome (but not from the Golgi), and expression of the Hook2-binding domain of CENP-F alone recapitulates this centrosome-specific MT nucleation defect. CENP-F thus regulates centrosomal MT nucleation through its interaction with Hook2.","method":"Yeast two-hybrid screen, co-immunoprecipitation, CENP-F knockout cell analysis, nocodazole washout MT regrowth assay, truncated CENP-F expression","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — reciprocal protein interaction confirmed by Y2H and Co-IP plus genetic loss-of-function (CENP-F KO) with specific centrosomal MT phenotype rescued/phenocopied by Hook2-binding domain expression","pmids":["19793914"],"is_preprint":false},{"year":2016,"finding":"Hook2 is a microtubule-binding protein that interacts with PAR6α via its C-terminal domain binding to the aPKC-binding domain of PAR6α. Hook2 is required for PAR6α localization to the centrosome during polarized cell migration and for Golgi reorientation toward the migration front. Depletion of Hook2 reduces PAR6α at the centrosome; overexpression of Hook2 induces aggresome formation with recruitment of PAR6α, aPKC, and PAR3. Hook2 thus bridges microtubules and the aPKC/PAR polarity complex at the centrosome to regulate centrosome orientation during migration.","method":"Co-immunoprecipitation, siRNA knockdown, overexpression, immunofluorescence live imaging, wound-healing migration assay, Golgi reorientation assay","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 — Co-IP defining specific domain interaction, siRNA knockdown with defined migration/polarity phenotype, and overexpression phenotype all concordant","pmids":["27624926"],"is_preprint":false}],"current_model":"HOOK2 is a centrosome-localized microtubule-binding protein that anchors to the centrosome via direct C-terminal interaction with centriolin/CEP110, recruits the PAR6α/aPKC polarity complex to the centrosome to orient cell migration, forms part of the FTS/Hook/FHIP (FHF) complex that promotes endosomal vesicle trafficking via the HOPS complex, and interacts selectively with MSUT-2/ZC3H14; loss of Hook2 function disrupts radial microtubule organization, impairs post-nocodazole microtubule regrowth, and abolishes polarized Golgi reorientation, collectively establishing Hook2 as a linker protein that coordinates centrosome integrity, microtubule nucleation, cell polarity, and endosomal trafficking."},"narrative":{"teleology":[{"year":1999,"claim":"Genetic studies in Drosophila established that the Hook protein family is required for endocytic trafficking, with all three protein domains essential for function, thereby defining the ancestral cellular role of Hook proteins.","evidence":"Drosophila loss-of-function alleles and truncation analysis showing failure of ligand accumulation in multivesicular bodies","pmids":["9927460"],"confidence":"High","gaps":["Mammalian Hook2-specific functions not addressed","Molecular target of Hook in endocytic pathway not identified","Whether Hook acts as a motor adaptor or scaffold was unknown"]},{"year":2001,"claim":"Biochemical characterization of mammalian Hook proteins revealed their architecture as coiled-coil proteins that bind microtubules via their N-terminus and organelles via divergent C-termini, establishing the conceptual framework for how Hook proteins link organelles to the microtubule cytoskeleton.","evidence":"In vitro organelle-binding assays, overexpression in cultured cells, immunofluorescence showing Hook3 at cis-Golgi","pmids":["11238449"],"confidence":"High","gaps":["Hook2-specific localization and binding partners not determined","Functional distinction among Hook1, Hook2, and Hook3 paralogs unknown"]},{"year":2006,"claim":"Hook2 was localized to the centrosome throughout the cell cycle and shown to bind centriolin/CEP110 directly, with loss-of-function experiments demonstrating that Hook2 is required for radial microtubule organization and post-nocodazole microtubule regrowth — the first evidence that Hook2 has a centrosome-specific structural and functional role distinct from other Hook paralogs.","evidence":"Immunofluorescence with cell-cycle staging, C-terminal domain pulldown binding assay, dominant-negative overexpression, nocodazole washout regrowth assay","pmids":["17140400"],"confidence":"High","gaps":["Upstream signals recruiting Hook2 to centrosomes not identified","Whether Hook2 affects cell division or only interphase microtubule organization was unclear"]},{"year":2008,"claim":"Discovery of the FTS/Hook/FHIP (FHF) complex showed that Hook proteins (including Hook2) form homo- and heterodimers within a ~500-kDa complex that engages the HOPS tethering complex, directly linking Hook proteins to early-to-late endosomal and lysosomal trafficking.","evidence":"Affinity purification/mass spectrometry from HEK293T cells, yeast two-hybrid, Co-IP, siRNA knockdown of FTS with EGF trafficking and lysosomal clustering assays","pmids":["18799622"],"confidence":"High","gaps":["Specific contribution of Hook2 versus Hook1/Hook3 within the FHF complex not dissected","Whether centrosomal and endosomal functions of Hook2 are coordinated or independent was unknown"]},{"year":2009,"claim":"Two studies expanded Hook2's interactome: CENP-F was shown to interact with Hook2 and to be required for centrosome-specific microtubule nucleation, while MSUT-2/ZC3H14 was identified as a selective Hook2-binding partner conserved from nematodes to humans, opening a potential connection to tau-related neurodegeneration.","evidence":"Yeast two-hybrid and Co-IP for CENP-F interaction with CENP-F KO cells and nocodazole washout; yeast two-hybrid and in vitro binding for MSUT-2 selectivity","pmids":["19793914","19273536"],"confidence":"High","gaps":["Functional consequence of Hook2–MSUT-2 interaction in mammalian neurons not tested","How CENP-F and centriolin/CEP110 interactions with Hook2 are spatially or temporally coordinated is unknown","Whether Hook2–MSUT-2 interaction is relevant to tau pathology in vivo remains unaddressed"]},{"year":2016,"claim":"Hook2 was established as a centrosomal scaffold for the PAR6α/aPKC polarity complex, directly linking microtubule organization to cell polarity: Hook2 depletion abolished PAR6α centrosomal recruitment and Golgi reorientation during directed migration, integrating Hook2 into the cell polarity pathway.","evidence":"Co-IP mapping Hook2 C-terminal domain to PAR6α aPKC-binding domain, siRNA knockdown with wound-healing and Golgi reorientation assays, overexpression-induced aggresome formation","pmids":["27624926"],"confidence":"High","gaps":["Whether Hook2-mediated polarity is relevant in vivo (e.g., in epithelial tissues or neurons) is untested","Regulation of Hook2 itself (post-translational modifications, turnover) remains uncharacterized"]},{"year":null,"claim":"It remains unknown how Hook2's centrosomal, polarity, endosomal trafficking, and MSUT-2-related functions are coordinated — whether they represent context-dependent uses of the same scaffold or independent parallel pathways — and whether Hook2 has non-redundant roles in vivo in mammalian development or disease.","evidence":"","pmids":[],"confidence":"Low","gaps":["No Hook2 knockout mouse or in vivo mammalian model has been reported","Structural basis of Hook2 interactions (e.g., cryo-EM or crystal structures of Hook2 complexes) is lacking","Post-translational regulation of Hook2 is uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,2,6]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,3,6]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[2,5,6]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,2,6]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[1,3]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[2,5]}],"complexes":["FTS/Hook/FHIP (FHF) complex"],"partners":["CEP110","CENP-F","PAR6A","FTS","FHIP","ZC3H14","PRKCI"],"other_free_text":[]},"mechanistic_narrative":"HOOK2 is a centrosome-associated, microtubule-binding coiled-coil protein that functions as a scaffold linking microtubule organization, cell polarity, and endosomal trafficking. Its conserved N-terminal domain binds microtubules while its divergent C-terminal domain anchors it to the centrosome through direct interaction with centriolin/CEP110 and recruits the PAR6α/aPKC polarity complex, thereby orienting the centrosome and Golgi apparatus during directed cell migration [PMID:17140400, PMID:27624926]. HOOK2 also interacts with CENP-F to promote centrosome-specific microtubule nucleation after depolymerization, and participates in the FTS/Hook/FHIP (FHF) complex that engages the HOPS complex to facilitate early-to-late endosomal trafficking [PMID:19793914, PMID:18799622]. Additionally, HOOK2 selectively binds MSUT-2/ZC3H14, a CCCH zinc-finger protein implicated in tau neurotoxicity, representing a conserved interaction from C. elegans to humans [PMID:19273536]."},"prefetch_data":{"uniprot":{"accession":"Q96ED9","full_name":"Protein Hook homolog 2","aliases":[],"length_aa":719,"mass_kda":83.2,"function":"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). Contributes to the establishment and maintenance of centrosome function. May function in the positioning or formation of aggresomes, which are pericentriolar accumulations of misfolded proteins, proteasomes and chaperones. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm; Cytoplasm, cytoskeleton; Golgi apparatus, trans-Golgi network","url":"https://www.uniprot.org/uniprotkb/Q96ED9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/HOOK2","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"IPO13","stoichiometry":0.2},{"gene":"POLR3E","stoichiometry":0.2},{"gene":"TMA16","stoichiometry":0.2},{"gene":"TOMM20A","stoichiometry":0.2},{"gene":"VDAC1","stoichiometry":0.2},{"gene":"VDAC3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/HOOK2","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":"616478","title":"LEUCINE-RICH REPEATS- AND GUANYLATE KINASE DOMAIN-CONTAINING PROTEIN; LRGUK","url":"https://www.omim.org/entry/616478"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/HOOK2"},"hgnc":{"alias_symbol":["HK2"],"prev_symbol":[]},"alphafold":{"accession":"Q96ED9","domains":[{"cath_id":"1.10.418.10","chopping":"6-139","consensus_level":"high","plddt":88.8419,"start":6,"end":139}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96ED9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96ED9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96ED9-F1-predicted_aligned_error_v6.png","plddt_mean":82.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=HOOK2","jax_strain_url":"https://www.jax.org/strain/search?query=HOOK2"},"sequence":{"accession":"Q96ED9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96ED9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96ED9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96ED9"}},"corpus_meta":[{"pmid":"30825877","id":"PMC_30825877","title":"Long non-coding RNA PVT1 promotes tumor 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N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/35271311","citation_count":432,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26871637","id":"PMC_26871637","title":"Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.","date":"2016","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26871637","citation_count":423,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21145461","id":"PMC_21145461","title":"Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.","date":"2010","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/21145461","citation_count":318,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28611215","id":"PMC_28611215","title":"Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing.","date":"2017","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/28611215","citation_count":282,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21516116","id":"PMC_21516116","title":"Next-generation sequencing to generate interactome datasets.","date":"2011","source":"Nature methods","url":"https://pubmed.ncbi.nlm.nih.gov/21516116","citation_count":200,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26673895","id":"PMC_26673895","title":"A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning.","date":"2015","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/26673895","citation_count":198,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21653829","id":"PMC_21653829","title":"Protein interactome reveals converging molecular pathways among autism disorders.","date":"2011","source":"Science translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/21653829","citation_count":180,"is_preprint":false,"source_track":"gene2pubmed"},{"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":166,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30833792","id":"PMC_30833792","title":"A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape.","date":"2019","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30833792","citation_count":159,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29117863","id":"PMC_29117863","title":"RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination.","date":"2017","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/29117863","citation_count":135,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"24722188","id":"PMC_24722188","title":"Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/24722188","citation_count":111,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"18799622","id":"PMC_18799622","title":"An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex.","date":"2008","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/18799622","citation_count":95,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19273536","id":"PMC_19273536","title":"SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans.","date":"2009","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19273536","citation_count":95,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"27107012","id":"PMC_27107012","title":"Pooled-matrix protein interaction screens using Barcode Fusion Genetics.","date":"2016","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/27107012","citation_count":89,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"9927460","id":"PMC_9927460","title":"Genetic analysis of hook, a gene required for endocytic trafficking in drosophila.","date":"1999","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9927460","citation_count":85,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15882442","id":"PMC_15882442","title":"A novel hook-related protein family and the characterization of hook-related protein 1.","date":"2005","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/15882442","citation_count":68,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23443559","id":"PMC_23443559","title":"LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells.","date":"2013","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/23443559","citation_count":64,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"31515488","id":"PMC_31515488","title":"Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31515488","citation_count":60,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"31980649","id":"PMC_31980649","title":"Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31980649","citation_count":60,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":53699,"output_tokens":995,"usd":0.088011},"stage2":{"model":"claude-opus-4-6","input_tokens":4212,"output_tokens":1341,"usd":0.081878},"total_usd":0.41346,"stage1_batch_id":"msgbatch_01DzrsgVgYngY1hvM3DU1yF2","stage2_batch_id":"msgbatch_01KA9b7iRzKFdhoBUT7vCvSe","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":65045,"output_tokens":2716,"usd":0.117938},"round2_rules_fired":"R2","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5756,"output_tokens":2199,"usd":0.125633}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"Hook2 localizes to the centrosome throughout all phases of the cell cycle via its C-terminal domain, which directly binds to centriolin/CEP110; mislocalized wild-type or mutant Hook2 perturbs endogenous centrosomal and pericentrosomal proteins, and interference with Hook2 function causes loss of radial microtubule organization and defective microtubule regrowth after nocodazole-induced depolymerization.\",\n      \"method\": \"Direct binding assay (C-terminal domain pulldown/interaction), immunofluorescence localization through cell cycle, dominant-negative overexpression, nocodazole washout microtubule regrowth assay\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct binding demonstrated, localization confirmed through cell cycle, functional consequence shown by loss-of-function with specific phenotypic readout (MT regrowth defect), multiple orthogonal methods\",\n      \"pmids\": [\"17140400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"CENP-F directly binds Hook2 at the centrosome (identified by yeast two-hybrid and confirmed by co-immunoprecipitation); CENP-F localizes to the centrosome in a Hook2-dependent manner and is required for centrosome-specific microtubule repolymerization after nocodazole treatment, with a truncated CENP-F containing only the Hook2-binding domain sufficient to recapitulate the centrosomal MT nucleation defect.\",\n      \"method\": \"Yeast two-hybrid screen, reciprocal co-immunoprecipitation, CENP-F knockout cells, nocodazole washout microtubule regrowth assay, truncation/domain expression\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — interaction confirmed by reciprocal co-IP, functional epistasis shown by knockout and domain rescue, multiple orthogonal methods in one study\",\n      \"pmids\": [\"19793914\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Hook2 interacts with the aPKC/PAR6α polarity complex via a direct binding between Hook2's C-terminal domain and the aPKC-binding domain of PAR6α; Hook2 is essential for PAR6α recruitment to the centrosome during cell migration, for polarized Golgi re-orientation toward the migration front, and Hook2 depletion decreases PAR6α at the centrosome while Hook2 overexpression induces aggresome formation recruiting PAR6α, aPKC, and PAR3.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, shRNA depletion with centrosome localization readout, live-cell imaging of Golgi orientation, overexpression phenotype analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct interaction mapped to specific domains, co-IP confirmed, loss-of-function with defined cellular phenotypes (Golgi polarity, PAR6α localization), multiple orthogonal methods\",\n      \"pmids\": [\"27624926\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Hook2 is a centrosome-localized microtubule-binding protein that contributes to centrosomal structure and function by directly binding centriolin/CEP110 via its C-terminal domain and by recruiting the aPKC/PAR6α polarity complex to the centrosome (through direct interaction with PAR6α), thereby regulating microtubule nucleation/organization and polarized cell migration; it also binds CENP-F at the centrosome to coordinate centrosome-specific microtubule repolymerization.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nLooking at the corpus, I need to identify papers about the canonical HOOK2 protein (a microtubule-binding, dynein-adaptor protein involved in centrosome function) versus papers about:\n- HK2 (Hexokinase 2) - clear alias collision\n- hK2 (human Kallikrein 2) - clear alias collision\n- HK-2 (human kidney proximal tubule cell line) - clear alias collision\n\n**KEEP papers** (about canonical HOOK2 protein):\n- PMID 17140400: Hook2 localizes to centrosome, binds centriolin/CEP110\n- PMID 19793914: CENP-F interacts with Hook2 at centrosome\n- PMID 18799622: FTS/Hook/FHIP complex, Hook1/2/3 in endosomal trafficking\n- PMID 27624926: Hook2 interacts with Par6α, controls centrosome orientation\n- PMID 9927460: Drosophila hook gene (ortholog) - endocytic trafficking\n- PMID 11238449: Hook3 family characterization (relevant to Hook family context)\n- PMID 19273536: SUT-2/MSUT-2 binds HOOK2 specifically\n- PMID 15882442: Hook-related protein family\n- PMID 23443559: LGALS3BP/centrosome network including Hook2\n- PMID 16189514, 26186194, 28514442, 25416956, 32296183, 33961781, 26496610, 26871637, 21516116 - interactome screens (identify HOOK2 interactions but no specific mechanistic findings beyond network-level)\n- PMID 21873635, 15489334, 12477932 - gene collection/GO papers (no mechanistic findings)\n\n**EXCLUDE** (HK2/hK2/HK-2 papers): All others\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"Hook proteins constitute a novel family of cytosolic coiled-coil proteins that bind organelles via divergent C-terminal domains and microtubules via conserved N-terminal domains. Hook3 (a family member) binds Golgi membranes in vitro and localizes to cis-Golgi in vivo; overexpression causes Golgi fragmentation, suggesting Hook proteins link organelles to microtubules and define organelle architecture/localization.\",\n      \"method\": \"In vitro organelle-binding assay, overexpression in cultured cells, immunofluorescence microscopy, Brefeldin A treatment\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (in vitro binding, overexpression phenotype, subcellular localization); foundational family characterization paper with 166 citations\",\n      \"pmids\": [\"11238449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Drosophila Hook (ortholog of mammalian Hook proteins including HOOK2) is required for endocytic trafficking; loss-of-function alleles show that neither transmembrane nor soluble ligands accumulate in multivesicular bodies (MVBs). All three domains (N-terminal, coiled-coil, C-terminal) are required for Hook function, as shown by truncation experiments.\",\n      \"method\": \"Drosophila genetics, isolation of null alleles, epistasis with endocytic pathway, expression of truncated proteins\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function with defined cellular phenotype plus domain truncation analysis, replicated across multiple alleles\",\n      \"pmids\": [\"9927460\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Mammalian Hook2 localizes to the centrosome throughout all phases of the cell cycle. Its C-terminal domain directly binds centriolin/CEP110. Expression of the C-terminal domain of centriolin/CEP110 alters endogenous Hook2 distribution. Mislocalized Hook2 (wild-type or mutant) perturbs endogenous centrosomal and pericentrosomal proteins. Interference with Hook2 function causes loss of radial microtubule organization and defects in microtubule regrowth after nocodazole-induced depolymerization, establishing Hook2 as a contributor to centrosomal structure and function.\",\n      \"method\": \"Immunofluorescence microscopy (cell-cycle staging), direct binding assay (C-terminal domain pulldown), overexpression of dominant-negative constructs, nocodazole washout microtubule regrowth assay\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct binding assay plus multiple functional readouts (localization, MT regrowth, centrosome integrity) with loss-of-function phenotypes\",\n      \"pmids\": [\"17140400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Hook1, Hook2, and Hook3 form part of a multiprotein FHF complex together with FTS (Fused Toes) and FHIP (FTS and Hook Interacting Protein). Hook proteins form homo- and heterodimers; FTS associates with a conserved C-terminal motif in Hook proteins. The ~500-kDa FHF complex interacts with both class B and class C components of the HOPS complex. Depletion of FTS by RNAi impairs EGF trafficking from early-to-late endosomes/lysosomes and reduces HOPS-driven lysosomal clustering, implicating the FTS/Hook/FHIP complex in vesicle trafficking via the HOPS complex.\",\n      \"method\": \"Proteomic analysis of affinity-purified FTS complexes from HEK293T cells, yeast two-hybrid, Co-IP, siRNA knockdown, EGF trafficking assay, lysosomal clustering assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — mass spectrometry-based complex identification confirmed by Co-IP and Y2H, combined with RNAi functional assays showing defined trafficking phenotype\",\n      \"pmids\": [\"18799622\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The human HOOK2 protein specifically interacts with the human ortholog of SUT-2 (MSUT-2/ZC3H14), a CCCH zinc finger protein involved in tau neurotoxicity. Of the three human Hook paralogs (HOOK1, HOOK2, HOOK3), MSUT-2 binds selectively to HOOK2, demonstrating that this interaction is conserved from C. elegans (ZYG-12/SUT-2) to humans.\",\n      \"method\": \"Yeast two-hybrid screen, in vitro protein binding assay\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — yeast two-hybrid plus in vitro binding; selectivity for HOOK2 over HOOK1/3 noted but limited functional follow-up for the human proteins\",\n      \"pmids\": [\"19273536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"CENP-F localizes to the centrosome and physically interacts with Hook2 (identified by yeast two-hybrid screen and confirmed by co-immunoprecipitation). Ablation of CENP-F eliminates microtubule repolymerization after nocodazole treatment specifically from the centrosome (but not from the Golgi), and expression of the Hook2-binding domain of CENP-F alone recapitulates this centrosome-specific MT nucleation defect. CENP-F thus regulates centrosomal MT nucleation through its interaction with Hook2.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, CENP-F knockout cell analysis, nocodazole washout MT regrowth assay, truncated CENP-F expression\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal protein interaction confirmed by Y2H and Co-IP plus genetic loss-of-function (CENP-F KO) with specific centrosomal MT phenotype rescued/phenocopied by Hook2-binding domain expression\",\n      \"pmids\": [\"19793914\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Hook2 is a microtubule-binding protein that interacts with PAR6α via its C-terminal domain binding to the aPKC-binding domain of PAR6α. Hook2 is required for PAR6α localization to the centrosome during polarized cell migration and for Golgi reorientation toward the migration front. Depletion of Hook2 reduces PAR6α at the centrosome; overexpression of Hook2 induces aggresome formation with recruitment of PAR6α, aPKC, and PAR3. Hook2 thus bridges microtubules and the aPKC/PAR polarity complex at the centrosome to regulate centrosome orientation during migration.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, overexpression, immunofluorescence live imaging, wound-healing migration assay, Golgi reorientation assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP defining specific domain interaction, siRNA knockdown with defined migration/polarity phenotype, and overexpression phenotype all concordant\",\n      \"pmids\": [\"27624926\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"HOOK2 is a centrosome-localized microtubule-binding protein that anchors to the centrosome via direct C-terminal interaction with centriolin/CEP110, recruits the PAR6α/aPKC polarity complex to the centrosome to orient cell migration, forms part of the FTS/Hook/FHIP (FHF) complex that promotes endosomal vesicle trafficking via the HOPS complex, and interacts selectively with MSUT-2/ZC3H14; loss of Hook2 function disrupts radial microtubule organization, impairs post-nocodazole microtubule regrowth, and abolishes polarized Golgi reorientation, collectively establishing Hook2 as a linker protein that coordinates centrosome integrity, microtubule nucleation, cell polarity, and endosomal trafficking.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"Hook2 is a centrosome-localized microtubule-binding protein that anchors to centriolar structures throughout the cell cycle via its C-terminal domain, which directly binds centriolin/CEP110, and is required for radial microtubule organization and centrosome-directed microtubule repolymerization after depolymerization [PMID:17140400]. Hook2 recruits CENP-F to the centrosome through a direct interaction, and this Hook2–CENP-F axis is necessary for centrosome-specific microtubule nucleation [PMID:19793914]. Hook2 also directly binds PAR6α via its C-terminal domain and recruits the aPKC/PAR6α polarity complex to the centrosome, thereby controlling polarized Golgi reorientation and directional cell migration [PMID:27624926].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing Hook2 as a constitutive centrosomal component resolved how a Hook-family protein contributes to centrosome integrity: its C-terminal domain directly binds centriolin/CEP110, and functional interference disrupts radial microtubule organization and centrosomal microtubule regrowth.\",\n      \"evidence\": \"Domain pulldown binding assays, immunofluorescence across cell cycle phases, dominant-negative overexpression, and nocodazole washout regrowth assay in mammalian cells\",\n      \"pmids\": [\"17140400\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of other centrosomal Hook2 binding partners was unknown\",\n        \"Whether Hook2 plays a role in centrosome duplication or centriole assembly was not tested\",\n        \"Structural basis of the Hook2–centriolin interaction was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identifying CENP-F as a direct Hook2 partner at the centrosome explained how Hook2 controls centrosomal microtubule nucleation: Hook2 recruits CENP-F, and CENP-F is the effector required for centrosome-specific microtubule repolymerization.\",\n      \"evidence\": \"Yeast two-hybrid screen with reciprocal co-immunoprecipitation, CENP-F knockout cells, and nocodazole washout assay with truncation domain expression\",\n      \"pmids\": [\"19793914\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the Hook2–CENP-F axis functions during mitotic spindle assembly was not addressed\",\n        \"The molecular mechanism by which CENP-F promotes microtubule nucleation at centrosomes remains unclear\",\n        \"Relationship between CENP-F centrosomal recruitment and its separate kinetochore role was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Discovery that Hook2 directly binds PAR6α and recruits the aPKC/PAR6α/PAR3 polarity complex to the centrosome linked Hook2 to cell polarity, showing it is required for polarized Golgi reorientation during directional migration.\",\n      \"evidence\": \"Co-immunoprecipitation with domain mapping, shRNA depletion with centrosome localization and Golgi orientation readouts, and overexpression-induced aggresome analysis\",\n      \"pmids\": [\"27624926\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether Hook2 coordinates CENP-F and PAR6α recruitment simultaneously or in separate contexts is unknown\",\n        \"The upstream signals that regulate Hook2 activity or its association with polarity complexes have not been identified\",\n        \"In vivo relevance for tissue polarity or morphogenesis has not been tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how Hook2 coordinates its dual roles in microtubule nucleation (via CENP-F) and cell polarity (via aPKC/PAR6α), whether these functions are cell-cycle regulated, and whether Hook2 participates in dynein-dependent cargo transport like other Hook-family members.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of Hook2 or its complexes exists\",\n        \"Potential dynein-adaptor function analogous to Hook1/Hook3 has not been experimentally tested for Hook2\",\n        \"Post-translational regulation of Hook2 at the centrosome is uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CEP110\", \"CENPF\", \"PARD6A\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"HOOK2 is a centrosome-associated, microtubule-binding coiled-coil protein that functions as a scaffold linking microtubule organization, cell polarity, and endosomal trafficking. Its conserved N-terminal domain binds microtubules while its divergent C-terminal domain anchors it to the centrosome through direct interaction with centriolin/CEP110 and recruits the PAR6α/aPKC polarity complex, thereby orienting the centrosome and Golgi apparatus during directed cell migration [PMID:17140400, PMID:27624926]. HOOK2 also interacts with CENP-F to promote centrosome-specific microtubule nucleation after depolymerization, and participates in the FTS/Hook/FHIP (FHF) complex that engages the HOPS complex to facilitate early-to-late endosomal trafficking [PMID:19793914, PMID:18799622]. Additionally, HOOK2 selectively binds MSUT-2/ZC3H14, a CCCH zinc-finger protein implicated in tau neurotoxicity, representing a conserved interaction from C. elegans to humans [PMID:19273536].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Genetic studies in Drosophila established that the Hook protein family is required for endocytic trafficking, with all three protein domains essential for function, thereby defining the ancestral cellular role of Hook proteins.\",\n      \"evidence\": \"Drosophila loss-of-function alleles and truncation analysis showing failure of ligand accumulation in multivesicular bodies\",\n      \"pmids\": [\"9927460\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mammalian Hook2-specific functions not addressed\",\n        \"Molecular target of Hook in endocytic pathway not identified\",\n        \"Whether Hook acts as a motor adaptor or scaffold was unknown\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Biochemical characterization of mammalian Hook proteins revealed their architecture as coiled-coil proteins that bind microtubules via their N-terminus and organelles via divergent C-termini, establishing the conceptual framework for how Hook proteins link organelles to the microtubule cytoskeleton.\",\n      \"evidence\": \"In vitro organelle-binding assays, overexpression in cultured cells, immunofluorescence showing Hook3 at cis-Golgi\",\n      \"pmids\": [\"11238449\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Hook2-specific localization and binding partners not determined\",\n        \"Functional distinction among Hook1, Hook2, and Hook3 paralogs unknown\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Hook2 was localized to the centrosome throughout the cell cycle and shown to bind centriolin/CEP110 directly, with loss-of-function experiments demonstrating that Hook2 is required for radial microtubule organization and post-nocodazole microtubule regrowth — the first evidence that Hook2 has a centrosome-specific structural and functional role distinct from other Hook paralogs.\",\n      \"evidence\": \"Immunofluorescence with cell-cycle staging, C-terminal domain pulldown binding assay, dominant-negative overexpression, nocodazole washout regrowth assay\",\n      \"pmids\": [\"17140400\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Upstream signals recruiting Hook2 to centrosomes not identified\",\n        \"Whether Hook2 affects cell division or only interphase microtubule organization was unclear\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Discovery of the FTS/Hook/FHIP (FHF) complex showed that Hook proteins (including Hook2) form homo- and heterodimers within a ~500-kDa complex that engages the HOPS tethering complex, directly linking Hook proteins to early-to-late endosomal and lysosomal trafficking.\",\n      \"evidence\": \"Affinity purification/mass spectrometry from HEK293T cells, yeast two-hybrid, Co-IP, siRNA knockdown of FTS with EGF trafficking and lysosomal clustering assays\",\n      \"pmids\": [\"18799622\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Specific contribution of Hook2 versus Hook1/Hook3 within the FHF complex not dissected\",\n        \"Whether centrosomal and endosomal functions of Hook2 are coordinated or independent was unknown\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Two studies expanded Hook2's interactome: CENP-F was shown to interact with Hook2 and to be required for centrosome-specific microtubule nucleation, while MSUT-2/ZC3H14 was identified as a selective Hook2-binding partner conserved from nematodes to humans, opening a potential connection to tau-related neurodegeneration.\",\n      \"evidence\": \"Yeast two-hybrid and Co-IP for CENP-F interaction with CENP-F KO cells and nocodazole washout; yeast two-hybrid and in vitro binding for MSUT-2 selectivity\",\n      \"pmids\": [\"19793914\", \"19273536\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Functional consequence of Hook2–MSUT-2 interaction in mammalian neurons not tested\",\n        \"How CENP-F and centriolin/CEP110 interactions with Hook2 are spatially or temporally coordinated is unknown\",\n        \"Whether Hook2–MSUT-2 interaction is relevant to tau pathology in vivo remains unaddressed\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Hook2 was established as a centrosomal scaffold for the PAR6α/aPKC polarity complex, directly linking microtubule organization to cell polarity: Hook2 depletion abolished PAR6α centrosomal recruitment and Golgi reorientation during directed migration, integrating Hook2 into the cell polarity pathway.\",\n      \"evidence\": \"Co-IP mapping Hook2 C-terminal domain to PAR6α aPKC-binding domain, siRNA knockdown with wound-healing and Golgi reorientation assays, overexpression-induced aggresome formation\",\n      \"pmids\": [\"27624926\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether Hook2-mediated polarity is relevant in vivo (e.g., in epithelial tissues or neurons) is untested\",\n        \"Regulation of Hook2 itself (post-translational modifications, turnover) remains uncharacterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how Hook2's centrosomal, polarity, endosomal trafficking, and MSUT-2-related functions are coordinated — whether they represent context-dependent uses of the same scaffold or independent parallel pathways — and whether Hook2 has non-redundant roles in vivo in mammalian development or disease.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No Hook2 knockout mouse or in vivo mammalian model has been reported\",\n        \"Structural basis of Hook2 interactions (e.g., cryo-EM or crystal structures of Hook2 complexes) is lacking\",\n        \"Post-translational regulation of Hook2 is uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 2, 6]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 3, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2, 5, 6]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 2, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [2, 5]}\n    ],\n    \"complexes\": [\n      \"FTS/Hook/FHIP (FHF) complex\"\n    ],\n    \"partners\": [\n      \"CEP110\",\n      \"CENP-F\",\n      \"PAR6A\",\n      \"FTS\",\n      \"FHIP\",\n      \"ZC3H14\",\n      \"PRKCI\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}