{"gene":"KIF17","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2000,"finding":"KIF17 directly interacts with the PDZ domain of mLin-10 (Mint1/X11) via its tail domain, linking it to a large protein complex (mLin-2/CASK, mLin-7/MALS/Velis, NR2B) to transport NR2B-containing vesicles along microtubules in neuronal dendrites.","method":"Co-immunoprecipitation, direct binding assay (tail-PDZ interaction), vesicle transport reconstitution in neurons","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP plus direct binding assay, replicated across multiple subsequent labs","pmids":["10846156"],"is_preprint":false},{"year":2003,"finding":"KIF17 vesicles move processively along dendrites at ~0.76 µm/sec and are associated with extrasynaptic NR2B; knockdown or dominant-negative blockade of KIF17 reduces NR2B expression and its synaptic localization, accompanied by a compensatory increase in synaptic NR2A.","method":"Live-cell imaging of GFP-tagged KIF17 in hippocampal neurons, siRNA knockdown, dominant-negative overexpression, immunostaining","journal":"The Journal of Neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (live imaging, KD, dominant negative) in a single rigorous study, replicated by subsequent knockout work","pmids":["12514209"],"is_preprint":false},{"year":2002,"finding":"Overexpression of KIF17 in transgenic mice upregulates NR2B expression and increases CREB phosphorylation, demonstrating that KIF17 motor activity drives in vivo NR2B transport and influences downstream transcriptional programs linked to learning and memory.","method":"Transgenic mouse overexpression (GFP-KIF17), behavioral assays, Western blot, CREB phosphorylation analysis","journal":"PNAS","confidence":"High","confidence_rationale":"Tier 2 / Strong — transgenic animal model with behavioral, biochemical, and molecular readouts; replicated by kif17 knockout study","pmids":["12391294"],"is_preprint":false},{"year":2007,"finding":"CaMKII phosphorylates KIF17 at Ser1029 in its tail domain, disrupting the KIF17–Mint1 interaction and releasing transported NR2B-containing cargo from the motor.","method":"FRET (direct visualization of protein-protein interaction), in vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation","journal":"Nature Cell Biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro kinase assay with mutagenesis, FRET-based direct interaction measurement, multiple orthogonal methods in a single rigorous study","pmids":["18066053"],"is_preprint":false},{"year":2011,"finding":"Genetic deletion of kif17 in mice impairs NR2B transport and reduces nr2b transcription; it also reduces NR2A levels via accelerated ubiquitin-proteasome degradation. Synaptic NMDAR-mediated currents, LTP, LTD, CREB responses, and hippocampus-dependent memory are all attenuated in kif17−/− mice.","method":"Kif17 knockout mouse, electrophysiology, behavioral testing, Western blot, ubiquitin-proteasome inhibitor rescue experiments","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockout with multiple orthogonal cellular, electrophysiological, and behavioral readouts","pmids":["21521616"],"is_preprint":false},{"year":2012,"finding":"Phosphorylation of KIF17 at Ser1029 by CaMKII is required bidirectionally for normal NR2B transport in vivo: phospho-null (S1029A) mice cannot load GluN2B cargo onto KIF17, while phospho-mimetic (S1029D) mice cannot unload it; both result in reduced synaptic NMDA receptors, impaired synaptic plasticity, and spatial memory deficits.","method":"Transgenic mice expressing S1029A or S1029D KIF17 in kif17−/− background, electrophysiology, behavioral assays, immunostaining","journal":"The Journal of Neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — phospho-mimetic and phospho-null knock-in animals with multiple orthogonal readouts, mechanistically validates the CaMKII phosphorylation site identified in vitro","pmids":["22514311"],"is_preprint":false},{"year":2010,"finding":"KIF17 contains a ciliary localization signal (CLS) in its tail domain that is necessary and sufficient for ciliary targeting. The CLS is recognized by importin-β2, and this interaction is inhibited by RanGTP. Cytoplasmic expression of GTP-locked Ran(G19V) abolishes ciliary entry of KIF17, establishing that a Ran-GTP gradient (analogous to nuclear import) regulates KIF17 ciliary entry.","method":"CLS deletion/fusion constructs, importin-β2 co-immunoprecipitation, dominant-negative RanG19V expression, live-cell imaging","journal":"Nature Cell Biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (truncation mapping, Co-IP, dominant-negative GTPase), mechanistically rigorous single study","pmids":["20526328"],"is_preprint":false},{"year":2006,"finding":"KIF17 is required for ciliary targeting of olfactory CNG channels in mammalian olfactory sensory neurons; dominant-negative KIF17 disrupts CNG channel localization to olfactory cilia.","method":"Dominant-negative KIF17 expression, immunofluorescence in olfactory sensory neurons","journal":"Current Biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dominant-negative functional assay with clear ciliary localization readout, single lab","pmids":["16782012"],"is_preprint":false},{"year":2006,"finding":"In C. elegans, OSM-3 (KIF17 ortholog) and kinesin-II cooperate via a mechanical competition mechanism to move IFT particles along microtubule doublets; purified OSM-3 and kinesin-II alone can recapitulate cooperative movement in vitro without additional regulatory factors.","method":"Competitive in vitro MT gliding assays with purified motors, in vivo IFT transport assays in BBS and motor mutants, quantitative modeling","journal":"The Journal of Cell Biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified proteins combined with in vivo genetic analysis in multiple mutant backgrounds","pmids":["17000880"],"is_preprint":false},{"year":2006,"finding":"OSM-3 (C. elegans KIF17 ortholog) motility is autoinhibited in solution via intramolecular folding at a central hinge; a G444E point mutation in the hinge or hinge deletion relieves autoinhibition, activating ATPase and processive movement. Cargo attachment (bead in optical trap) also activates wild-type OSM-3 motility.","method":"Single-molecule fluorescence assay, MT-stimulated ATPase assay, optical trap, site-directed mutagenesis (G444E), EM/conformational analysis","journal":"The Journal of Cell Biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — single-molecule reconstitution, mutagenesis, ATPase assay, and optical trap in a single rigorous study","pmids":["17000874"],"is_preprint":false},{"year":2016,"finding":"Polarized dendritic sorting of KIF17 requires three steps: (1) cargo binding relieves KIF17 autoinhibition and initiates microtubule transport; (2) the actin cytoskeleton at the axon initial segment (AIS) acts as a filter preventing KIF17-coupled vesicles from progressing into the axon; (3) dynein-based activity redirects KIF17 cargo into dendrites.","method":"Live-cell imaging, inducible trafficking assays (rapamycin-based), actin depolymerization, dynein inhibition in cultured neurons","journal":"Current Biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal perturbations (actin disruption, dynein inhibition) with live-cell inducible cargo assay, mechanistically defines each step","pmids":["27265394"],"is_preprint":false},{"year":2008,"finding":"KIF17 (zebrafish Kif17) is essential for photoreceptor outer segment (OS) development; Kif17 knockdown severely disrupts OS formation and visual pigment targeting. Kif17 co-immunoprecipitates with IFT proteins within photoreceptor OS, establishing it as part of the IFT machinery in vertebrate photoreceptors.","method":"Morpholino knockdown in zebrafish, co-immunoprecipitation with IFT proteins, immunofluorescence","journal":"Developmental Biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with clear cellular phenotype plus reciprocal Co-IP establishing IFT complex membership","pmids":["18304522"],"is_preprint":false},{"year":2005,"finding":"KIF17 transports the K+ channel Kv4.2 to dendrites; dominant-negative KIF17 (but not dominant-negatives of other kinesins) dramatically inhibits dendritic localization of endogenous and introduced Kv4.2. Kv4.2 and KIF17 co-immunoprecipitate from brain lysate and from co-transfected COS cells, indicating direct or indirect interaction through the extreme C-terminus of Kv4.2.","method":"Dominant-negative constructs, co-immunoprecipitation from brain lysate and COS cells, colocalization in cortical neurons","journal":"The Journal of Biological Chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dominant-negative functional assay plus Co-IP from brain, single lab, two orthogonal methods","pmids":["16257958"],"is_preprint":false},{"year":2006,"finding":"KIF17 interacts with kainate receptor subunits GluR6 and KA2 and is required for localization of GluR5 to distal dendrites; coimmunoprecipitation from hippocampal neurons and dominant-negative KIF17 experiments established this interaction and functional requirement.","method":"Co-immunoprecipitation from hippocampal neurons, dominant-negative KIF17 expression, immunofluorescence","journal":"Molecular and Cellular Neurosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus dominant-negative functional assay, single lab","pmids":["17174564"],"is_preprint":false},{"year":2005,"finding":"KIF17b (testis-specific isoform) controls the subcellular localization of the CREM transcriptional coactivator ACT between nucleus and cytoplasm in a manner that is independent of its motor domain and microtubules but dependent on protein kinase A-mediated phosphorylation of KIF17b.","method":"Truncation/deletion constructs, microtubule depolymerization (nocodazole), PKA inhibitor/activator experiments, subcellular fractionation","journal":"The Journal of Biological Chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple pharmacological and genetic perturbations in a single lab, two orthogonal methods","pmids":["16002395"],"is_preprint":false},{"year":2003,"finding":"KIF17b (testis-specific isoform) co-immunoprecipitates with TB-RBP (Translin) in an RNA-protein complex that contains specific CREM-regulated mRNAs, and KIF17b serves as the motor component transporting these mRNPs in postmeiotic male germ cells; dissociation of KIF17b and TB-RBP from mRNA is temporally linked to the time of translation.","method":"Co-immunoprecipitation, in vivo RNA-protein crosslinking, in situ hybridization combined with immunohistochemistry at EM level","journal":"PNAS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, RNA crosslinking, and EM-level combined histochemistry in a single study; single lab","pmids":["14673085"],"is_preprint":false},{"year":2006,"finding":"KIF17b physically interacts with the PIWI/Argonaute family protein MIWI in chromatoid bodies of round spermatids; KIF17b localizes to chromatoid bodies and may provide microtubule-dependent mobility to these structures and facilitate loading of haploid RNAs.","method":"Co-immunoprecipitation (KIF17b–MIWI), immunofluorescence localization, analysis of miwi-null mouse spermatids","journal":"Journal of Cell Science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and localization with genetic loss-of-function analysis in a single lab","pmids":["16787948"],"is_preprint":false},{"year":2017,"finding":"KIF17 ciliary entry requires two independent determinants: (1) binding to the IFT46–IFT56 dimer of the IFT-B complex through a C-terminal sequence just upstream of the NLS, and (2) the NLS itself, to which importin-α proteins bind. KIF17 reaches the ciliary tip independently of its motor domain and is dispensable for ciliogenesis and IFT-B trafficking in mammalian cells.","method":"Visible immunoprecipitation (VIP) assay, deletion mutant analysis, importin-α co-immunoprecipitation, live-cell imaging of ciliary tip accumulation","journal":"Molecular Biology of the Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — VIP assay for direct interaction mapping plus multiple deletion constructs and localization assays, mechanistically dissects two independent requirements","pmids":["28077622"],"is_preprint":false},{"year":2015,"finding":"Ciliary delivery of D1-type dopamine receptors from the extra-ciliary plasma membrane requires IFT-B, KIF17, and Rab23; Rab23 depletion prevents receptor ciliary access, and fusion of Rab23 to a non-ciliary receptor drives nucleotide-dependent mis-localization to cilia.","method":"siRNA knockdown of IFT-B, KIF17, Rab23; constitutively active/dominant-negative Rab23 fusions; live-cell imaging of receptor trafficking","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple independent RNAi depletions plus gain-of-function Rab23 fusion constructs with quantitative live-cell readout","pmids":["26182404"],"is_preprint":false},{"year":2015,"finding":"Rab23 forms a complex with KIF17 and importin-β2, and Rab23 depletion disrupts ciliary localization of KIF17; wild-type and constitutively active Rab23(Q68L) enrich at the primary cilium, suggesting Rab23 acts as an effector regulating KIF17 ciliary transport.","method":"Co-immunoprecipitation, affinity-binding assay (Rab23–KIF17–importin-β2 complex), siRNA knockdown, immunofluorescence","journal":"Journal of Cell Science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP and affinity binding with siRNA knockdown phenotype, single lab, two orthogonal methods","pmids":["26136363"],"is_preprint":false},{"year":2013,"finding":"The KIF17 motor domain (K370) directly stabilizes microtubule plus-ends and inhibits depolymerization independently of EB1; the KIF17 autoinhibitory tail domain binds microtubules and tubulin dimers and delays initial MT polymerization. EB1 and the KIF17 tail competitively interact with the motor domain and have opposing effects on MT-stimulated ATPase activity.","method":"In vitro MT dynamic instability assay, MT-stimulated ATPase assay, MT dilution depolymerization assay, MT cosedimentation, nocodazole washout in cells","journal":"The Journal of Biological Chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — multiple in vitro biochemical reconstitution assays with purified domains, single lab","pmids":["24072717"],"is_preprint":false},{"year":2016,"finding":"KIF17 localizes at epithelial cell-cell adhesions where it activates RhoA signaling through its motor domain (independently of microtubule binding), promoting junctional actin accumulation via the RhoA–ROCK–LIMK–cofilin pathway and stabilizing the apical junctional complex.","method":"KIF17 depletion (siRNA), overexpression of full-length and truncation mutants, dominant-negative RhoA, ROCK inhibitor, kinase-dead LIMK1, activated cofilin(S3A), GFP-actin incorporation assay, 3D organotypic culture","journal":"Journal of Cell Science","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal perturbations (KD, OE, pathway inhibitors, activated mutants) with quantitative actin and E-cadherin readouts in two culture systems","pmids":["26759174"],"is_preprint":false},{"year":2016,"finding":"Septin 9 (SEPT9) directly associates with the C-terminal tail of KIF17 (preferentially in the extended cargo-binding conformation), competes with the PDZ1 domain of mLin-10/Mint1 for KIF17 tail binding, and thereby down-regulates NR2B transport into hippocampal neuron dendrites without affecting KIF17 microtubule-based motility.","method":"Direct binding assay (GST pulldown with purified proteins), co-immunoprecipitation, live-cell imaging of KIF17 motility, NR2B immunostaining in neurons, siRNA knockdown","journal":"Molecular Biology of the Cell","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — direct binding with purified proteins plus reciprocal Co-IP and live motility assay, single lab with multiple orthogonal methods","pmids":["26823018"],"is_preprint":false},{"year":2013,"finding":"TTC30B (mouse ortholog of C. elegans DYF-1) interacts directly with KIF17 as shown by co-immunoprecipitation and cell-free in vitro expression co-IP, and also associates with multiple IFT-B complex proteins, suggesting a physical link between TTC30B and KIF17 within the IFT machinery.","method":"Co-immunoprecipitation from mouse pituitary cells, in vitro cell-free expression followed by Co-IP, mass spectrometry","journal":"Experimental Cell Research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus in vitro binding confirmation, single lab","pmids":["23810713"],"is_preprint":false},{"year":2018,"finding":"CaMKII-dependent phosphorylation of KIF17 at Ser815 (zebrafish equivalent of mouse Ser1029) promotes KIF17 localization along cone outer segments and drives outer segment disc shedding in a cell-autonomous manner; kif17 genetic mutants in zebrafish and mice exhibit diminished disc shedding, and constitutively active CaMKII increases disc shedding in a kif17-dependent manner.","method":"Transgenic zebrafish expressing phospho-mimetic/phospho-null KIF17, kif17 genetic mutants in zebrafish and mice, constitutively active CaMKII transgene, quantitative disc shedding assay","journal":"BMC Cell Biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — phospho-mimetic and phospho-null transgenics plus independent genetic knockouts in two species and epistasis with CaMKII","pmids":["30458707"],"is_preprint":false},{"year":2019,"finding":"GTP-bound Rab23 promotes migration of Kif17 to spindle poles during mouse oocyte meiosis. Depletion of Rab23 or Kif17 causes polar body extrusion failure, perturbs spindle formation, and disrupts tubulin acetylation via altered αTAT and Sirt2 expression. The Kif17 tail domain associates with constituents of the RhoA–ROCK–LIMK–cofilin pathway to regulate cytoplasmic actin and spindle migration.","method":"siRNA depletion of Rab23 and Kif17 in mouse oocytes, immunofluorescence for spindle markers, Western blot for αTAT/Sirt2, Co-immunoprecipitation of Kif17 tail with RhoA pathway components","journal":"Development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA depletion with multiple readouts and Co-IP, single lab","pmids":["30696709"],"is_preprint":false},{"year":2020,"finding":"KIF17 is locally degraded and synthesized in dendrites in an NMDAR-activity-dependent manner; activity-dependent local synthesis is driven by the KIF17 3'UTR at dendritic shafts, and newly synthesized KIF17 engages in dendritic transport. Hippocampus-specific deletion of Kif17 3'UTR impairs fear memory extinction by disrupting activity-dependent KIF17 synthesis.","method":"Live imaging of GFP-KIF17 synthesis in dendrites, 3'UTR reporter assays, NMDAR antagonist/agonist treatments, hippocampus-specific 3'UTR deletion mouse, fear conditioning and extinction behavioral assay","journal":"Science Advances","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (live imaging, reporter assays, conditional knockout) with behavioral and molecular readouts in a single rigorous study","pmids":["33328231"],"is_preprint":false},{"year":2021,"finding":"Crystal structures of the OSM-3 (C. elegans KIF17 ortholog) motor domain in ADP-bound, nucleotide-free, and ATP-analog-bound states show that the nucleotide-binding site is virtually identical to that of Eg5 in the ATP-like state, demonstrating that a two-water-molecule ATP hydrolysis mechanism is conserved in kinesin-2.","method":"X-ray crystallography (structures 7A3Z, 7A40, 7A5E), structural comparison with Eg5","journal":"FEBS Open Bio","confidence":"High","confidence_rationale":"Tier 1 / Moderate — three crystal structures along the nucleotide cycle with explicit functional interpretation, single lab","pmids":["33513284"],"is_preprint":false},{"year":2017,"finding":"KIF17 interacts with estrogen-related receptor alpha (ERRα) via its C-terminal tail (containing an LXXLL nuclear receptor box) and the ERRα ligand-binding/AF2 domain; KIF17 tail expression attenuates nuclear accumulation of newly synthesized ERRα and inhibits ERRα transcriptional activity, while KIF17 knockout elevates ERRα activity.","method":"Yeast-2-hybrid screen, in vitro binding assay, KIF17 knockout cells, nuclear fractionation, reporter gene (transcriptional activity) assay, deletion/peptide constructs","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast-2-hybrid confirmed by in vitro binding, KO phenotype, and reporter assay, single lab with multiple orthogonal methods","pmids":["28881568"],"is_preprint":false},{"year":2024,"finding":"KIF17 has dual and opposing roles in Hedgehog (HH)-dependent cerebellar development: in Purkinje cells (HH-producing), KIF17 promotes SHH protein levels and its cell-type-specific deletion reduces SHH and CGNP proliferation; in CGNPs (HH-responding), KIF17 deletion increases CGNP proliferation and HH target gene expression by altering GLI transcription factor processing.","method":"Germline Kif17 knockout mice, Purkinje cell-specific and CGNP-specific conditional Kif17 deletion, cerebellar morphometry, HH pathway target gene expression (qPCR/Western blot), GLI processing analysis","journal":"Science Advances","confidence":"High","confidence_rationale":"Tier 2 / Strong — three independent genetic deletion models (germline, Purkinje cell-specific, CGNP-specific) with molecular pathway readouts dissecting opposing cell-type roles","pmids":["38669326"],"is_preprint":false},{"year":2025,"finding":"In C. elegans, NEKL-3 (a NIMA-related kinase) directly phosphorylates the motor domain of OSM-3 (KIF17 ortholog), inhibiting its in vitro ATPase activity; NEKL-3 and NEKL-4 localize at the ciliary base and restrict OSM-3 activation to the distal ciliary region. Elevated protein phosphatase 2A at the transition zone triggers premature OSM-3 activation, while PP2A deficiency reduces OSM-3 activity and cilia length.","method":"In vitro kinase assay (NEKL-3 phosphorylation of OSM-3), fluorescence lifetime imaging microscopy (FLIM) for OSM-3 conformational state in vivo, genetic analysis of NEKL-3/4 and PP2A mutants, FRAP","journal":"The Journal of Cell Biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro kinase assay plus FLIM-based in vivo conformational analysis and genetic epistasis in a single rigorous study","pmids":["40272473"],"is_preprint":false},{"year":1993,"finding":"osm-3 encodes a kinesin heavy chain-like protein with conserved ATPase and microtubule-binding domains; osm-3 mutants accumulate dense matrix material in amphid sheath cytoplasm and have shortened distal cilia segments, establishing a kinesin-like role in axonal/ciliary transport in C. elegans chemosensory neurons.","method":"Germline transformation rescue, DNA sequencing, Northern blot, electron microscopy of cilia ultrastructure","journal":"Neuroreport","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic rescue and structural EM analysis, foundational characterization study","pmids":["7690265"],"is_preprint":false},{"year":2022,"finding":"KIF17 is modified by SUMOylation, which stabilizes and maintains KIF17 protein levels in epileptic neurons; KIF17 overexpression increases severity of KA-induced epileptic activity and elevates membrane NR2B expression, while KIF17 knockdown has the opposite effect.","method":"KIF17 overexpression/knockdown in mouse epilepsy model, SUMO modification assay, electrophysiology, NR2B membrane fractionation","journal":"Neuroscience Bulletin","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD/OE with electrophysiology and SUMOylation assay, single lab","pmids":["35678994"],"is_preprint":false},{"year":2010,"finding":"Nuclear respiratory factor 1 (NRF-1) directly binds conserved sites in the Kif17 gene promoter and functionally regulates Kif17 transcription; NRF-1 silencing blocks KCl-depolarization-induced Kif17 upregulation, while NRF-1 overexpression rescues TTX-suppressed Kif17 expression, co-regulating KIF17 with its cargo NR2B.","method":"EMSA, supershift assay, chromatin immunoprecipitation (ChIP), promoter mutation assay, NRF-1 siRNA knockdown and overexpression, real-time qPCR","journal":"Biochimica et Biophysica Acta","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — EMSA, supershift, ChIP, and functional promoter mutants with gain/loss-of-function in a single rigorous study","pmids":["21171239"],"is_preprint":false}],"current_model":"KIF17 is a homodimeric kinesin-2 motor that transports NR2B-containing NMDA receptor vesicles, Kv4.2 K+ channels, and kainate receptor complexes exclusively into neuronal dendrites via its tail domain's interaction with the mLin-10/Mint1 PDZ scaffold; cargo loading and release are regulated by CaMKII phosphorylation at Ser1029, which disrupts the KIF17–Mint1 interaction, while polarized dendritic sorting involves relief of autoinhibition by cargo binding, actin-dependent filtering at the axon initial segment, and dynein-mediated redirection. In ciliated cells, KIF17 enters cilia via a dual mechanism requiring both its NLS-like ciliary localization signal (recognized by importin-β2 and regulated by a Ran-GTP gradient) and direct binding to the IFT46–IFT56 dimer of the IFT-B complex, functioning in intraflagellar transport to build photoreceptor outer segments and deliver olfactory CNG channels and dopamine receptors to cilia. In epithelial cells, KIF17 stabilizes microtubule plus-ends, activates RhoA–ROCK–LIMK–cofilin signaling at cell junctions to reinforce the apical junctional complex, and modulates ERRα nuclear localization via an LXXLL motif in its tail; in male germ cells (as KIF17b), it mediates microtubule-independent, PKA-regulated nucleocytoplasmic shuttling of the CREM coactivator ACT and transports specific CREM-regulated mRNPs in complex with TB-RBP."},"narrative":{"mechanistic_narrative":"KIF17 is a homodimeric kinesin-2 motor with two principal cellular roles: microtubule-based cargo transport into neuronal dendrites and intraflagellar transport within cilia [PMID:10846156, PMID:20526328]. In neurons, KIF17 links to NR2B-containing NMDA receptor vesicles through a direct interaction between its tail domain and the PDZ domain of mLin-10/Mint1 within a larger Mint1/CASK/MALS scaffold, and moves these vesicles processively along dendrites [PMID:10846156, PMID:12514209]; loss of KIF17 reduces NR2B transport, transcription, synaptic NMDAR currents, LTP/LTD, and hippocampus-dependent memory [PMID:21521616]. Cargo loading and release are gated by CaMKII phosphorylation of the tail at Ser1029, which disrupts the KIF17–Mint1 interaction, and both phospho-null and phospho-mimetic states impair synaptic plasticity, establishing that bidirectional phospho-cycling is required for productive transport [PMID:18066053, PMID:22514311]. KIF17 also transports the Kv4.2 K+ channel and kainate receptor subunits to dendrites [PMID:16257958, PMID:17174564], and its abundance is controlled by NRF-1-driven transcription co-regulated with NR2B and by activity-dependent local dendritic synthesis directed by its 3'UTR [PMID:21171239, PMID:33328231]. Motor output is regulated by autoinhibitory folding that is relieved by cargo binding, while polarized dendritic delivery additionally requires an actin filter at the axon initial segment and dynein-based redirection [PMID:17000874, PMID:27265394]. In cilia, KIF17 enters via a tail ciliary localization signal recognized by importins under control of a Ran-GTP gradient and by direct binding to the IFT46–IFT56 dimer of the IFT-B complex, functioning in intraflagellar transport to build photoreceptor outer segments and deliver ciliary membrane receptors [PMID:20526328, PMID:28077622, PMID:18304522, PMID:26182404]; the C. elegans ortholog OSM-3 cooperates mechanically with kinesin-II and is activated specifically in the distal ciliary segment through NEKL kinase/PP2A control of its motor domain [PMID:17000880, PMID:40272473]. Beyond transport, the KIF17 motor domain directly stabilizes microtubule plus-ends and activates RhoA–ROCK–LIMK–cofilin signaling to reinforce epithelial junctions, and the tail modulates ERRα and Hedgehog/GLI-dependent transcriptional programs in development [PMID:24072717, PMID:26759174, PMID:28881568, PMID:38669326].","teleology":[{"year":2000,"claim":"Established how a kinesin selects a specific dendritic cargo, by showing KIF17 binds the Mint1 PDZ scaffold to transport NR2B vesicles.","evidence":"Co-IP and direct tail–PDZ binding assay with vesicle transport in neurons","pmids":["10846156"],"confidence":"High","gaps":["Did not define how cargo binding is regulated","Did not address polarized dendrite-versus-axon sorting"]},{"year":2002,"claim":"Demonstrated in vivo that KIF17 motor activity drives NR2B transport and downstream CREB-linked transcription relevant to memory.","evidence":"Transgenic GFP-KIF17 overexpression mice with behavioral and biochemical readouts","pmids":["12391294"],"confidence":"High","gaps":["Overexpression may not reflect endogenous stoichiometry","Did not establish loss-of-function requirement"]},{"year":2003,"claim":"Quantified KIF17 dendritic motility and showed its requirement for NR2B synaptic delivery with compensatory NR2A changes.","evidence":"Live imaging, siRNA knockdown and dominant-negative in hippocampal neurons","pmids":["12514209"],"confidence":"High","gaps":["Did not define the unloading signal at synapses"]},{"year":2007,"claim":"Identified the molecular switch for cargo release: CaMKII phosphorylation of Ser1029 disrupts the KIF17–Mint1 interaction.","evidence":"In vitro kinase assay, FRET, mutagenesis and Co-IP","pmids":["18066053"],"confidence":"High","gaps":["In vitro/cell-based; in vivo physiological role established only later"]},{"year":2011,"claim":"A clean knockout confirmed KIF17 controls NR2B transport and transcription plus NR2A stability, and is required for plasticity and memory.","evidence":"Kif17 knockout mice with electrophysiology, behavior, and proteasome rescue","pmids":["21521616"],"confidence":"High","gaps":["Mechanism coupling transport to nr2b transcription not resolved"]},{"year":2012,"claim":"Showed Ser1029 phospho-cycling is bidirectionally essential in vivo: phospho-null blocks loading, phospho-mimetic blocks unloading.","evidence":"S1029A/S1029D knock-in mice in kif17-null background","pmids":["22514311"],"confidence":"High","gaps":["Spatial cues controlling where CaMKII acts not defined"]},{"year":2005,"claim":"Extended KIF17 cargo repertoire to the Kv4.2 K+ channel, broadening its role in dendritic membrane protein delivery.","evidence":"Dominant-negative constructs and Co-IP from brain and COS cells","pmids":["16257958"],"confidence":"Medium","gaps":["Direct versus indirect interaction not resolved","No reconstitution"]},{"year":2006,"claim":"Added kainate receptor subunits as KIF17 cargo, further generalizing its dendritic glutamate-receptor transport function.","evidence":"Co-IP from hippocampal neurons and dominant-negative KIF17","pmids":["17174564"],"confidence":"Medium","gaps":["Adaptor linking KIF17 to kainate receptors unknown","Single lab"]},{"year":2003,"claim":"Defined a germline transport role: testis isoform KIF17b moves CREM-regulated mRNPs in complex with TB-RBP.","evidence":"Co-IP, RNA crosslinking and EM-level in situ hybridization in male germ cells","pmids":["14673085"],"confidence":"Medium","gaps":["mRNA selectivity determinants unknown","Single lab"]},{"year":2005,"claim":"Revealed a non-canonical, motor-independent KIF17b function: PKA-regulated nucleocytoplasmic shuttling of the CREM coactivator ACT.","evidence":"Truncations, nocodazole, PKA modulation and fractionation","pmids":["16002395"],"confidence":"Medium","gaps":["Mechanism of microtubule-independent transport undefined","Single lab"]},{"year":2006,"claim":"Connected KIF17b to germ-cell RNA granules through interaction with the PIWI protein MIWI in chromatoid bodies.","evidence":"Co-IP, localization, and miwi-null spermatid analysis","pmids":["16787948"],"confidence":"Medium","gaps":["Functional consequence of MIWI association not quantified"]},{"year":2006,"claim":"First placed the mammalian motor in ciliary transport, showing KIF17 is needed to deliver olfactory CNG channels to cilia.","evidence":"Dominant-negative KIF17 in olfactory sensory neurons","pmids":["16782012"],"confidence":"Medium","gaps":["Dominant-negative only; no endogenous knockout","Direct cargo interaction unmapped"]},{"year":2006,"claim":"Reconstituted the core ciliary mechanism in C. elegans: OSM-3 and kinesin-II cooperate by mechanical competition to drive IFT.","evidence":"In vitro gliding with purified motors plus in vivo IFT in mutants","pmids":["17000880"],"confidence":"High","gaps":["Generalization to mammalian KIF17 not directly tested here"]},{"year":2006,"claim":"Defined the autoregulatory logic of the motor: OSM-3 is autoinhibited by hinge folding and activated by cargo or hinge mutation.","evidence":"Single-molecule, ATPase, optical trap and G444E mutagenesis","pmids":["17000874"],"confidence":"High","gaps":["Physiological activating cargo in vivo not identified here"]},{"year":2008,"claim":"Showed vertebrate KIF17 is part of the photoreceptor IFT machinery and required for outer segment formation.","evidence":"Zebrafish morpholino knockdown and Co-IP with IFT proteins","pmids":["18304522"],"confidence":"High","gaps":["Specific IFT subunit contacts not mapped here"]},{"year":2010,"claim":"Identified a ciliary localization signal in the tail recognized by importin-β2 under Ran-GTP control, paralleling nuclear import.","evidence":"CLS fusion/deletion, importin-β2 Co-IP, dominant-negative RanG19V imaging","pmids":["20526328"],"confidence":"High","gaps":["Did not show direct IFT-complex binding (resolved 2017)"]},{"year":2010,"claim":"Linked KIF17 transcription to neuronal activity by identifying NRF-1 as a direct promoter regulator co-regulating KIF17 and NR2B.","evidence":"EMSA, ChIP, promoter mutants, NRF-1 knockdown/overexpression","pmids":["21171239"],"confidence":"High","gaps":["Other transcriptional inputs not excluded"]},{"year":2013,"claim":"Showed the motor doubles as a microtubule plus-end stabilizer competing with EB1, separating its enzymatic and lattice-regulating activities.","evidence":"In vitro dynamic instability, ATPase, cosedimentation with purified domains","pmids":["24072717"],"confidence":"High","gaps":["In-cell physiological relevance of plus-end stabilization not fully defined"]},{"year":2013,"claim":"Added a candidate IFT-linking adaptor by showing TTC30B/DYF-1 directly binds KIF17 and associates with IFT-B.","evidence":"Co-IP from pituitary cells and cell-free expression Co-IP with MS","pmids":["23810713"],"confidence":"Medium","gaps":["Functional consequence of the interaction untested","Single lab"]},{"year":2015,"claim":"Defined a Rab23-dependent route for ciliary membrane receptor delivery requiring IFT-B and KIF17.","evidence":"siRNA of IFT-B/KIF17/Rab23 plus Rab23 fusion mis-targeting, live imaging","pmids":["26182404"],"confidence":"High","gaps":["Direct KIF17–receptor contact not established"]},{"year":2015,"claim":"Placed Rab23 upstream of KIF17 ciliary entry as part of a Rab23–KIF17–importin-β2 complex.","evidence":"Co-IP, affinity binding, siRNA knockdown and immunofluorescence","pmids":["26136363"],"confidence":"Medium","gaps":["Whether Rab23 directly contacts KIF17 versus via importin unresolved","Single lab"]},{"year":2016,"claim":"Resolved the dendrite-targeting logic into three steps: cargo-activated transport, an AIS actin filter, and dynein-mediated redirection.","evidence":"Inducible cargo trafficking, actin depolymerization and dynein inhibition imaging","pmids":["27265394"],"confidence":"High","gaps":["Molecular identity of the AIS filtering machinery unspecified"]},{"year":2016,"claim":"Identified SEPT9 as a negative regulator competing with Mint1 for the KIF17 tail to throttle NR2B transport.","evidence":"GST pulldown with purified proteins, Co-IP, live motility and NR2B imaging","pmids":["26823018"],"confidence":"High","gaps":["Upstream control of SEPT9–KIF17 competition unknown"]},{"year":2016,"claim":"Uncovered a transport-independent epithelial role: KIF17 motor domain activates RhoA–ROCK–LIMK–cofilin to reinforce junctions.","evidence":"siRNA/OE, pathway inhibitors and activated mutants, 3D organotypic culture","pmids":["26759174"],"confidence":"High","gaps":["How the motor domain engages RhoA signaling biochemically not defined"]},{"year":2017,"claim":"Mapped a second ciliary-entry determinant: direct KIF17 binding to the IFT46–IFT56 dimer, independent of the NLS and motor domain.","evidence":"Visible immunoprecipitation, deletion mutants, importin-α Co-IP, tip imaging","pmids":["28077622"],"confidence":"High","gaps":["Relative contribution of the two determinants in different cilia unresolved"]},{"year":2017,"claim":"Extended the tail's regulatory reach to transcription, showing an LXXLL motif binds ERRα and restrains its nuclear accumulation and activity.","evidence":"Yeast-2-hybrid, in vitro binding, KO cells, fractionation and reporter assays","pmids":["28881568"],"confidence":"Medium","gaps":["Physiological context of ERRα regulation unclear","Single lab"]},{"year":2018,"claim":"Showed the conserved CaMKII/Ser phospho-switch also governs ciliary KIF17 by driving photoreceptor disc shedding.","evidence":"Phospho-mimetic/null zebrafish, kif17 mutants in two species, CaMKII epistasis","pmids":["30458707"],"confidence":"High","gaps":["Mechanism linking KIF17 localization to disc shedding undefined"]},{"year":2019,"claim":"Implicated KIF17 in meiotic spindle migration downstream of GTP-Rab23 and via RhoA-pathway components in oocytes.","evidence":"siRNA of Rab23/Kif17, spindle imaging, αTAT/Sirt2 blots and Co-IP","pmids":["30696709"],"confidence":"Medium","gaps":["Direct versus indirect RhoA-pathway engagement unresolved","Single lab"]},{"year":2020,"claim":"Revealed activity-dependent local control of KIF17 abundance through 3'UTR-driven dendritic synthesis required for fear memory extinction.","evidence":"Live imaging of synthesis, 3'UTR reporters, NMDAR modulation, conditional 3'UTR deletion mice with behavior","pmids":["33328231"],"confidence":"High","gaps":["RNA-binding factors directing local synthesis not identified"]},{"year":2021,"claim":"Provided structural basis for the conserved kinesin-2 ATP hydrolysis mechanism via crystallized OSM-3 motor states.","evidence":"X-ray structures along the nucleotide cycle compared with Eg5","pmids":["33513284"],"confidence":"High","gaps":["Structures of cargo-bound or autoinhibited full-length motor lacking"]},{"year":2022,"claim":"Linked KIF17 stability to disease by showing SUMOylation maintains KIF17 levels and modulates epileptic NR2B membrane expression.","evidence":"KD/OE in epilepsy model, SUMO assay, electrophysiology, NR2B fractionation","pmids":["35678994"],"confidence":"Medium","gaps":["SUMO sites and ligases not mapped","Single lab"]},{"year":2024,"claim":"Demonstrated opposing cell-type-specific roles for KIF17 in Hedgehog-driven cerebellar development through SHH levels and GLI processing.","evidence":"Germline and cell-type-specific Kif17 deletion mice with HH pathway and GLI readouts","pmids":["38669326"],"confidence":"High","gaps":["Molecular mechanism by which KIF17 influences GLI processing undefined"]},{"year":2025,"claim":"Defined spatial control of motor activation: NEKL-3 phosphorylates the OSM-3 motor domain and NEKL/PP2A restrict activation to the distal cilium.","evidence":"In vitro kinase assay, in vivo FLIM conformational imaging, NEKL/PP2A genetics, FRAP","pmids":["40272473"],"confidence":"High","gaps":["Conservation of NEKL regulation for mammalian KIF17 untested"]},{"year":null,"claim":"How KIF17's diverse tail-mediated functions—cargo transport, transcriptional modulation, junctional signaling, and ciliary entry—are coordinated and selected within a single cell remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of cargo-bound full-length mammalian KIF17","Mechanism switching between motor-dependent and motor-independent functions undefined","Direct disease-causing human mutations not established in this corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,1,9,27]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[9,20,27,30]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[20]},{"term_id":"GO:0060090","term_label":"molecular adaptor 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In association with the Apba1-containing complex (LIN-10-LIN-2-LIN-7 complex), transports vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules","subcellular_location":"Cytoplasm, cytoskeleton; Cell projection, cilium; Cell projection, dendrite","url":"https://www.uniprot.org/uniprotkb/Q9P2E2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF17","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":[],"url":"https://opencell.sf.czbiohub.org/search/KIF17","total_profiled":1310},"omim":[{"mim_id":"620742","title":"INTRAFLAGELLAR TRANSPORT 70B; IFT70B","url":"https://www.omim.org/entry/620742"},{"mim_id":"620741","title":"INTRAFLAGELLAR TRANSPORT 70A; 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research","url":"https://pubmed.ncbi.nlm.nih.gov/17961552","citation_count":9,"is_preprint":false},{"pmid":"29393422","id":"PMC_29393422","title":"KIF17 mediates the learning and memory impairment in offspring induced by maternal exposure to propofol during middle pregnancy.","date":"2018","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/29393422","citation_count":9,"is_preprint":false},{"pmid":"26421900","id":"PMC_26421900","title":"A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia.","date":"2015","source":"Psychiatry research","url":"https://pubmed.ncbi.nlm.nih.gov/26421900","citation_count":7,"is_preprint":false},{"pmid":"25664020","id":"PMC_25664020","title":"The cyclic AMP response element-binding protein antisense oligonucleotide induced anti-nociception and decreased the expression of KIF17 in spinal cord after peripheral nerve injury in mice.","date":"2014","source":"International journal of clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25664020","citation_count":7,"is_preprint":false},{"pmid":"36367842","id":"PMC_36367842","title":"Betaine Attenuates Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Inhibiting KIF17-Mediated Nociception.","date":"2022","source":"ACS chemical neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/36367842","citation_count":7,"is_preprint":false},{"pmid":"34124335","id":"PMC_34124335","title":"R869C mutation in molecular motor KIF17 gene is involved in dementia with Lewy bodies.","date":"2021","source":"Alzheimer's & dementia (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/34124335","citation_count":6,"is_preprint":false},{"pmid":"28881568","id":"PMC_28881568","title":"Modulation of estrogen related receptor alpha activity by the kinesin KIF17.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/28881568","citation_count":6,"is_preprint":false},{"pmid":"10819327","id":"PMC_10819327","title":"C. elegans KLP-11/OSM-3/KAP-1: orthologs of the sea urchin kinesin-II, and mouse KIF3A/KIFB/KAP3 kinesin complexes.","date":"2000","source":"DNA research : an international journal for rapid publication of reports on genes and genomes","url":"https://pubmed.ncbi.nlm.nih.gov/10819327","citation_count":6,"is_preprint":false},{"pmid":"37640257","id":"PMC_37640257","title":"Sida cordifolia L. attenuates behavioral hypersensitivity by interfering with KIF17-NR2B signaling in rat model of neuropathic pain.","date":"2023","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/37640257","citation_count":6,"is_preprint":false},{"pmid":"40272473","id":"PMC_40272473","title":"Phosphorylation-dependent regional motility of the ciliary kinesin OSM-3.","date":"2025","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/40272473","citation_count":5,"is_preprint":false},{"pmid":"33513284","id":"PMC_33513284","title":"Structural snapshots of the kinesin-2 OSM-3 along its nucleotide cycle: implications for the ATP hydrolysis mechanism.","date":"2021","source":"FEBS open bio","url":"https://pubmed.ncbi.nlm.nih.gov/33513284","citation_count":5,"is_preprint":false},{"pmid":"33922911","id":"PMC_33922911","title":"Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33922911","citation_count":5,"is_preprint":false},{"pmid":"35538183","id":"PMC_35538183","title":"The potential function of KIF17 in large yellow croaker (Larimichthys crocea) spermatid remodeling: molecular characterization and expression pattern during spermiogenesis.","date":"2022","source":"Fish physiology and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35538183","citation_count":4,"is_preprint":false},{"pmid":"38669326","id":"PMC_38669326","title":"Dual and opposing roles for the kinesin-2 motor, KIF17, in Hedgehog-dependent cerebellar development.","date":"2024","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/38669326","citation_count":3,"is_preprint":false},{"pmid":"38203305","id":"PMC_38203305","title":"Expression Dynamics Indicate Potential Roles of KIF17 for Nuclear Reshaping and Tail Formation during Spermiogenesis in Phascolosoma esculenta.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38203305","citation_count":3,"is_preprint":false},{"pmid":"36089118","id":"PMC_36089118","title":"KIF17 maintains the epithelial phenotype of breast cancer cells and curbs tumour metastasis.","date":"2022","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/36089118","citation_count":2,"is_preprint":false},{"pmid":"40568341","id":"PMC_40568341","title":"GRIN2B alleviates mid-gestational sevoflurane exposure-induced early differentiation of rat neural stem cells by interacting with KIF17.","date":"2025","source":"Journal of cell communication and signaling","url":"https://pubmed.ncbi.nlm.nih.gov/40568341","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.12.02.626415","title":"KIF3C Regulates Bergmann Glia Density and Patterning during Cerebellar Development","date":"2024-12-02","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.02.626415","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":31078,"output_tokens":8634,"usd":0.111372,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":18525,"output_tokens":7508,"usd":0.140162,"stage2_stop_reason":"end_turn"},"total_usd":0.251534,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"KIF17 directly interacts with the PDZ domain of mLin-10 (Mint1/X11) via its tail domain, linking it to a large protein complex (mLin-2/CASK, mLin-7/MALS/Velis, NR2B) to transport NR2B-containing vesicles along microtubules in neuronal dendrites.\",\n      \"method\": \"Co-immunoprecipitation, direct binding assay (tail-PDZ interaction), vesicle transport reconstitution in neurons\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP plus direct binding assay, replicated across multiple subsequent labs\",\n      \"pmids\": [\"10846156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"KIF17 vesicles move processively along dendrites at ~0.76 µm/sec and are associated with extrasynaptic NR2B; knockdown or dominant-negative blockade of KIF17 reduces NR2B expression and its synaptic localization, accompanied by a compensatory increase in synaptic NR2A.\",\n      \"method\": \"Live-cell imaging of GFP-tagged KIF17 in hippocampal neurons, siRNA knockdown, dominant-negative overexpression, immunostaining\",\n      \"journal\": \"The Journal of Neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (live imaging, KD, dominant negative) in a single rigorous study, replicated by subsequent knockout work\",\n      \"pmids\": [\"12514209\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Overexpression of KIF17 in transgenic mice upregulates NR2B expression and increases CREB phosphorylation, demonstrating that KIF17 motor activity drives in vivo NR2B transport and influences downstream transcriptional programs linked to learning and memory.\",\n      \"method\": \"Transgenic mouse overexpression (GFP-KIF17), behavioral assays, Western blot, CREB phosphorylation analysis\",\n      \"journal\": \"PNAS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — transgenic animal model with behavioral, biochemical, and molecular readouts; replicated by kif17 knockout study\",\n      \"pmids\": [\"12391294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CaMKII phosphorylates KIF17 at Ser1029 in its tail domain, disrupting the KIF17–Mint1 interaction and releasing transported NR2B-containing cargo from the motor.\",\n      \"method\": \"FRET (direct visualization of protein-protein interaction), in vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation\",\n      \"journal\": \"Nature Cell Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro kinase assay with mutagenesis, FRET-based direct interaction measurement, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"18066053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Genetic deletion of kif17 in mice impairs NR2B transport and reduces nr2b transcription; it also reduces NR2A levels via accelerated ubiquitin-proteasome degradation. Synaptic NMDAR-mediated currents, LTP, LTD, CREB responses, and hippocampus-dependent memory are all attenuated in kif17−/− mice.\",\n      \"method\": \"Kif17 knockout mouse, electrophysiology, behavioral testing, Western blot, ubiquitin-proteasome inhibitor rescue experiments\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockout with multiple orthogonal cellular, electrophysiological, and behavioral readouts\",\n      \"pmids\": [\"21521616\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Phosphorylation of KIF17 at Ser1029 by CaMKII is required bidirectionally for normal NR2B transport in vivo: phospho-null (S1029A) mice cannot load GluN2B cargo onto KIF17, while phospho-mimetic (S1029D) mice cannot unload it; both result in reduced synaptic NMDA receptors, impaired synaptic plasticity, and spatial memory deficits.\",\n      \"method\": \"Transgenic mice expressing S1029A or S1029D KIF17 in kif17−/− background, electrophysiology, behavioral assays, immunostaining\",\n      \"journal\": \"The Journal of Neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — phospho-mimetic and phospho-null knock-in animals with multiple orthogonal readouts, mechanistically validates the CaMKII phosphorylation site identified in vitro\",\n      \"pmids\": [\"22514311\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"KIF17 contains a ciliary localization signal (CLS) in its tail domain that is necessary and sufficient for ciliary targeting. The CLS is recognized by importin-β2, and this interaction is inhibited by RanGTP. Cytoplasmic expression of GTP-locked Ran(G19V) abolishes ciliary entry of KIF17, establishing that a Ran-GTP gradient (analogous to nuclear import) regulates KIF17 ciliary entry.\",\n      \"method\": \"CLS deletion/fusion constructs, importin-β2 co-immunoprecipitation, dominant-negative RanG19V expression, live-cell imaging\",\n      \"journal\": \"Nature Cell Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (truncation mapping, Co-IP, dominant-negative GTPase), mechanistically rigorous single study\",\n      \"pmids\": [\"20526328\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"KIF17 is required for ciliary targeting of olfactory CNG channels in mammalian olfactory sensory neurons; dominant-negative KIF17 disrupts CNG channel localization to olfactory cilia.\",\n      \"method\": \"Dominant-negative KIF17 expression, immunofluorescence in olfactory sensory neurons\",\n      \"journal\": \"Current Biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dominant-negative functional assay with clear ciliary localization readout, single lab\",\n      \"pmids\": [\"16782012\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"In C. elegans, OSM-3 (KIF17 ortholog) and kinesin-II cooperate via a mechanical competition mechanism to move IFT particles along microtubule doublets; purified OSM-3 and kinesin-II alone can recapitulate cooperative movement in vitro without additional regulatory factors.\",\n      \"method\": \"Competitive in vitro MT gliding assays with purified motors, in vivo IFT transport assays in BBS and motor mutants, quantitative modeling\",\n      \"journal\": \"The Journal of Cell Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified proteins combined with in vivo genetic analysis in multiple mutant backgrounds\",\n      \"pmids\": [\"17000880\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"OSM-3 (C. elegans KIF17 ortholog) motility is autoinhibited in solution via intramolecular folding at a central hinge; a G444E point mutation in the hinge or hinge deletion relieves autoinhibition, activating ATPase and processive movement. Cargo attachment (bead in optical trap) also activates wild-type OSM-3 motility.\",\n      \"method\": \"Single-molecule fluorescence assay, MT-stimulated ATPase assay, optical trap, site-directed mutagenesis (G444E), EM/conformational analysis\",\n      \"journal\": \"The Journal of Cell Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — single-molecule reconstitution, mutagenesis, ATPase assay, and optical trap in a single rigorous study\",\n      \"pmids\": [\"17000874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Polarized dendritic sorting of KIF17 requires three steps: (1) cargo binding relieves KIF17 autoinhibition and initiates microtubule transport; (2) the actin cytoskeleton at the axon initial segment (AIS) acts as a filter preventing KIF17-coupled vesicles from progressing into the axon; (3) dynein-based activity redirects KIF17 cargo into dendrites.\",\n      \"method\": \"Live-cell imaging, inducible trafficking assays (rapamycin-based), actin depolymerization, dynein inhibition in cultured neurons\",\n      \"journal\": \"Current Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal perturbations (actin disruption, dynein inhibition) with live-cell inducible cargo assay, mechanistically defines each step\",\n      \"pmids\": [\"27265394\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"KIF17 (zebrafish Kif17) is essential for photoreceptor outer segment (OS) development; Kif17 knockdown severely disrupts OS formation and visual pigment targeting. Kif17 co-immunoprecipitates with IFT proteins within photoreceptor OS, establishing it as part of the IFT machinery in vertebrate photoreceptors.\",\n      \"method\": \"Morpholino knockdown in zebrafish, co-immunoprecipitation with IFT proteins, immunofluorescence\",\n      \"journal\": \"Developmental Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with clear cellular phenotype plus reciprocal Co-IP establishing IFT complex membership\",\n      \"pmids\": [\"18304522\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"KIF17 transports the K+ channel Kv4.2 to dendrites; dominant-negative KIF17 (but not dominant-negatives of other kinesins) dramatically inhibits dendritic localization of endogenous and introduced Kv4.2. Kv4.2 and KIF17 co-immunoprecipitate from brain lysate and from co-transfected COS cells, indicating direct or indirect interaction through the extreme C-terminus of Kv4.2.\",\n      \"method\": \"Dominant-negative constructs, co-immunoprecipitation from brain lysate and COS cells, colocalization in cortical neurons\",\n      \"journal\": \"The Journal of Biological Chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dominant-negative functional assay plus Co-IP from brain, single lab, two orthogonal methods\",\n      \"pmids\": [\"16257958\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"KIF17 interacts with kainate receptor subunits GluR6 and KA2 and is required for localization of GluR5 to distal dendrites; coimmunoprecipitation from hippocampal neurons and dominant-negative KIF17 experiments established this interaction and functional requirement.\",\n      \"method\": \"Co-immunoprecipitation from hippocampal neurons, dominant-negative KIF17 expression, immunofluorescence\",\n      \"journal\": \"Molecular and Cellular Neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus dominant-negative functional assay, single lab\",\n      \"pmids\": [\"17174564\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"KIF17b (testis-specific isoform) controls the subcellular localization of the CREM transcriptional coactivator ACT between nucleus and cytoplasm in a manner that is independent of its motor domain and microtubules but dependent on protein kinase A-mediated phosphorylation of KIF17b.\",\n      \"method\": \"Truncation/deletion constructs, microtubule depolymerization (nocodazole), PKA inhibitor/activator experiments, subcellular fractionation\",\n      \"journal\": \"The Journal of Biological Chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple pharmacological and genetic perturbations in a single lab, two orthogonal methods\",\n      \"pmids\": [\"16002395\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"KIF17b (testis-specific isoform) co-immunoprecipitates with TB-RBP (Translin) in an RNA-protein complex that contains specific CREM-regulated mRNAs, and KIF17b serves as the motor component transporting these mRNPs in postmeiotic male germ cells; dissociation of KIF17b and TB-RBP from mRNA is temporally linked to the time of translation.\",\n      \"method\": \"Co-immunoprecipitation, in vivo RNA-protein crosslinking, in situ hybridization combined with immunohistochemistry at EM level\",\n      \"journal\": \"PNAS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, RNA crosslinking, and EM-level combined histochemistry in a single study; single lab\",\n      \"pmids\": [\"14673085\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"KIF17b physically interacts with the PIWI/Argonaute family protein MIWI in chromatoid bodies of round spermatids; KIF17b localizes to chromatoid bodies and may provide microtubule-dependent mobility to these structures and facilitate loading of haploid RNAs.\",\n      \"method\": \"Co-immunoprecipitation (KIF17b–MIWI), immunofluorescence localization, analysis of miwi-null mouse spermatids\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and localization with genetic loss-of-function analysis in a single lab\",\n      \"pmids\": [\"16787948\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KIF17 ciliary entry requires two independent determinants: (1) binding to the IFT46–IFT56 dimer of the IFT-B complex through a C-terminal sequence just upstream of the NLS, and (2) the NLS itself, to which importin-α proteins bind. KIF17 reaches the ciliary tip independently of its motor domain and is dispensable for ciliogenesis and IFT-B trafficking in mammalian cells.\",\n      \"method\": \"Visible immunoprecipitation (VIP) assay, deletion mutant analysis, importin-α co-immunoprecipitation, live-cell imaging of ciliary tip accumulation\",\n      \"journal\": \"Molecular Biology of the Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — VIP assay for direct interaction mapping plus multiple deletion constructs and localization assays, mechanistically dissects two independent requirements\",\n      \"pmids\": [\"28077622\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Ciliary delivery of D1-type dopamine receptors from the extra-ciliary plasma membrane requires IFT-B, KIF17, and Rab23; Rab23 depletion prevents receptor ciliary access, and fusion of Rab23 to a non-ciliary receptor drives nucleotide-dependent mis-localization to cilia.\",\n      \"method\": \"siRNA knockdown of IFT-B, KIF17, Rab23; constitutively active/dominant-negative Rab23 fusions; live-cell imaging of receptor trafficking\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple independent RNAi depletions plus gain-of-function Rab23 fusion constructs with quantitative live-cell readout\",\n      \"pmids\": [\"26182404\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Rab23 forms a complex with KIF17 and importin-β2, and Rab23 depletion disrupts ciliary localization of KIF17; wild-type and constitutively active Rab23(Q68L) enrich at the primary cilium, suggesting Rab23 acts as an effector regulating KIF17 ciliary transport.\",\n      \"method\": \"Co-immunoprecipitation, affinity-binding assay (Rab23–KIF17–importin-β2 complex), siRNA knockdown, immunofluorescence\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP and affinity binding with siRNA knockdown phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"26136363\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The KIF17 motor domain (K370) directly stabilizes microtubule plus-ends and inhibits depolymerization independently of EB1; the KIF17 autoinhibitory tail domain binds microtubules and tubulin dimers and delays initial MT polymerization. EB1 and the KIF17 tail competitively interact with the motor domain and have opposing effects on MT-stimulated ATPase activity.\",\n      \"method\": \"In vitro MT dynamic instability assay, MT-stimulated ATPase assay, MT dilution depolymerization assay, MT cosedimentation, nocodazole washout in cells\",\n      \"journal\": \"The Journal of Biological Chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple in vitro biochemical reconstitution assays with purified domains, single lab\",\n      \"pmids\": [\"24072717\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KIF17 localizes at epithelial cell-cell adhesions where it activates RhoA signaling through its motor domain (independently of microtubule binding), promoting junctional actin accumulation via the RhoA–ROCK–LIMK–cofilin pathway and stabilizing the apical junctional complex.\",\n      \"method\": \"KIF17 depletion (siRNA), overexpression of full-length and truncation mutants, dominant-negative RhoA, ROCK inhibitor, kinase-dead LIMK1, activated cofilin(S3A), GFP-actin incorporation assay, 3D organotypic culture\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal perturbations (KD, OE, pathway inhibitors, activated mutants) with quantitative actin and E-cadherin readouts in two culture systems\",\n      \"pmids\": [\"26759174\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Septin 9 (SEPT9) directly associates with the C-terminal tail of KIF17 (preferentially in the extended cargo-binding conformation), competes with the PDZ1 domain of mLin-10/Mint1 for KIF17 tail binding, and thereby down-regulates NR2B transport into hippocampal neuron dendrites without affecting KIF17 microtubule-based motility.\",\n      \"method\": \"Direct binding assay (GST pulldown with purified proteins), co-immunoprecipitation, live-cell imaging of KIF17 motility, NR2B immunostaining in neurons, siRNA knockdown\",\n      \"journal\": \"Molecular Biology of the Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — direct binding with purified proteins plus reciprocal Co-IP and live motility assay, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"26823018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TTC30B (mouse ortholog of C. elegans DYF-1) interacts directly with KIF17 as shown by co-immunoprecipitation and cell-free in vitro expression co-IP, and also associates with multiple IFT-B complex proteins, suggesting a physical link between TTC30B and KIF17 within the IFT machinery.\",\n      \"method\": \"Co-immunoprecipitation from mouse pituitary cells, in vitro cell-free expression followed by Co-IP, mass spectrometry\",\n      \"journal\": \"Experimental Cell Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus in vitro binding confirmation, single lab\",\n      \"pmids\": [\"23810713\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CaMKII-dependent phosphorylation of KIF17 at Ser815 (zebrafish equivalent of mouse Ser1029) promotes KIF17 localization along cone outer segments and drives outer segment disc shedding in a cell-autonomous manner; kif17 genetic mutants in zebrafish and mice exhibit diminished disc shedding, and constitutively active CaMKII increases disc shedding in a kif17-dependent manner.\",\n      \"method\": \"Transgenic zebrafish expressing phospho-mimetic/phospho-null KIF17, kif17 genetic mutants in zebrafish and mice, constitutively active CaMKII transgene, quantitative disc shedding assay\",\n      \"journal\": \"BMC Cell Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — phospho-mimetic and phospho-null transgenics plus independent genetic knockouts in two species and epistasis with CaMKII\",\n      \"pmids\": [\"30458707\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"GTP-bound Rab23 promotes migration of Kif17 to spindle poles during mouse oocyte meiosis. Depletion of Rab23 or Kif17 causes polar body extrusion failure, perturbs spindle formation, and disrupts tubulin acetylation via altered αTAT and Sirt2 expression. The Kif17 tail domain associates with constituents of the RhoA–ROCK–LIMK–cofilin pathway to regulate cytoplasmic actin and spindle migration.\",\n      \"method\": \"siRNA depletion of Rab23 and Kif17 in mouse oocytes, immunofluorescence for spindle markers, Western blot for αTAT/Sirt2, Co-immunoprecipitation of Kif17 tail with RhoA pathway components\",\n      \"journal\": \"Development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA depletion with multiple readouts and Co-IP, single lab\",\n      \"pmids\": [\"30696709\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF17 is locally degraded and synthesized in dendrites in an NMDAR-activity-dependent manner; activity-dependent local synthesis is driven by the KIF17 3'UTR at dendritic shafts, and newly synthesized KIF17 engages in dendritic transport. Hippocampus-specific deletion of Kif17 3'UTR impairs fear memory extinction by disrupting activity-dependent KIF17 synthesis.\",\n      \"method\": \"Live imaging of GFP-KIF17 synthesis in dendrites, 3'UTR reporter assays, NMDAR antagonist/agonist treatments, hippocampus-specific 3'UTR deletion mouse, fear conditioning and extinction behavioral assay\",\n      \"journal\": \"Science Advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (live imaging, reporter assays, conditional knockout) with behavioral and molecular readouts in a single rigorous study\",\n      \"pmids\": [\"33328231\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Crystal structures of the OSM-3 (C. elegans KIF17 ortholog) motor domain in ADP-bound, nucleotide-free, and ATP-analog-bound states show that the nucleotide-binding site is virtually identical to that of Eg5 in the ATP-like state, demonstrating that a two-water-molecule ATP hydrolysis mechanism is conserved in kinesin-2.\",\n      \"method\": \"X-ray crystallography (structures 7A3Z, 7A40, 7A5E), structural comparison with Eg5\",\n      \"journal\": \"FEBS Open Bio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — three crystal structures along the nucleotide cycle with explicit functional interpretation, single lab\",\n      \"pmids\": [\"33513284\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KIF17 interacts with estrogen-related receptor alpha (ERRα) via its C-terminal tail (containing an LXXLL nuclear receptor box) and the ERRα ligand-binding/AF2 domain; KIF17 tail expression attenuates nuclear accumulation of newly synthesized ERRα and inhibits ERRα transcriptional activity, while KIF17 knockout elevates ERRα activity.\",\n      \"method\": \"Yeast-2-hybrid screen, in vitro binding assay, KIF17 knockout cells, nuclear fractionation, reporter gene (transcriptional activity) assay, deletion/peptide constructs\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast-2-hybrid confirmed by in vitro binding, KO phenotype, and reporter assay, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"28881568\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIF17 has dual and opposing roles in Hedgehog (HH)-dependent cerebellar development: in Purkinje cells (HH-producing), KIF17 promotes SHH protein levels and its cell-type-specific deletion reduces SHH and CGNP proliferation; in CGNPs (HH-responding), KIF17 deletion increases CGNP proliferation and HH target gene expression by altering GLI transcription factor processing.\",\n      \"method\": \"Germline Kif17 knockout mice, Purkinje cell-specific and CGNP-specific conditional Kif17 deletion, cerebellar morphometry, HH pathway target gene expression (qPCR/Western blot), GLI processing analysis\",\n      \"journal\": \"Science Advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — three independent genetic deletion models (germline, Purkinje cell-specific, CGNP-specific) with molecular pathway readouts dissecting opposing cell-type roles\",\n      \"pmids\": [\"38669326\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In C. elegans, NEKL-3 (a NIMA-related kinase) directly phosphorylates the motor domain of OSM-3 (KIF17 ortholog), inhibiting its in vitro ATPase activity; NEKL-3 and NEKL-4 localize at the ciliary base and restrict OSM-3 activation to the distal ciliary region. Elevated protein phosphatase 2A at the transition zone triggers premature OSM-3 activation, while PP2A deficiency reduces OSM-3 activity and cilia length.\",\n      \"method\": \"In vitro kinase assay (NEKL-3 phosphorylation of OSM-3), fluorescence lifetime imaging microscopy (FLIM) for OSM-3 conformational state in vivo, genetic analysis of NEKL-3/4 and PP2A mutants, FRAP\",\n      \"journal\": \"The Journal of Cell Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro kinase assay plus FLIM-based in vivo conformational analysis and genetic epistasis in a single rigorous study\",\n      \"pmids\": [\"40272473\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1993,\n      \"finding\": \"osm-3 encodes a kinesin heavy chain-like protein with conserved ATPase and microtubule-binding domains; osm-3 mutants accumulate dense matrix material in amphid sheath cytoplasm and have shortened distal cilia segments, establishing a kinesin-like role in axonal/ciliary transport in C. elegans chemosensory neurons.\",\n      \"method\": \"Germline transformation rescue, DNA sequencing, Northern blot, electron microscopy of cilia ultrastructure\",\n      \"journal\": \"Neuroreport\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic rescue and structural EM analysis, foundational characterization study\",\n      \"pmids\": [\"7690265\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"KIF17 is modified by SUMOylation, which stabilizes and maintains KIF17 protein levels in epileptic neurons; KIF17 overexpression increases severity of KA-induced epileptic activity and elevates membrane NR2B expression, while KIF17 knockdown has the opposite effect.\",\n      \"method\": \"KIF17 overexpression/knockdown in mouse epilepsy model, SUMO modification assay, electrophysiology, NR2B membrane fractionation\",\n      \"journal\": \"Neuroscience Bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD/OE with electrophysiology and SUMOylation assay, single lab\",\n      \"pmids\": [\"35678994\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nuclear respiratory factor 1 (NRF-1) directly binds conserved sites in the Kif17 gene promoter and functionally regulates Kif17 transcription; NRF-1 silencing blocks KCl-depolarization-induced Kif17 upregulation, while NRF-1 overexpression rescues TTX-suppressed Kif17 expression, co-regulating KIF17 with its cargo NR2B.\",\n      \"method\": \"EMSA, supershift assay, chromatin immunoprecipitation (ChIP), promoter mutation assay, NRF-1 siRNA knockdown and overexpression, real-time qPCR\",\n      \"journal\": \"Biochimica et Biophysica Acta\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — EMSA, supershift, ChIP, and functional promoter mutants with gain/loss-of-function in a single rigorous study\",\n      \"pmids\": [\"21171239\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KIF17 is a homodimeric kinesin-2 motor that transports NR2B-containing NMDA receptor vesicles, Kv4.2 K+ channels, and kainate receptor complexes exclusively into neuronal dendrites via its tail domain's interaction with the mLin-10/Mint1 PDZ scaffold; cargo loading and release are regulated by CaMKII phosphorylation at Ser1029, which disrupts the KIF17–Mint1 interaction, while polarized dendritic sorting involves relief of autoinhibition by cargo binding, actin-dependent filtering at the axon initial segment, and dynein-mediated redirection. In ciliated cells, KIF17 enters cilia via a dual mechanism requiring both its NLS-like ciliary localization signal (recognized by importin-β2 and regulated by a Ran-GTP gradient) and direct binding to the IFT46–IFT56 dimer of the IFT-B complex, functioning in intraflagellar transport to build photoreceptor outer segments and deliver olfactory CNG channels and dopamine receptors to cilia. In epithelial cells, KIF17 stabilizes microtubule plus-ends, activates RhoA–ROCK–LIMK–cofilin signaling at cell junctions to reinforce the apical junctional complex, and modulates ERRα nuclear localization via an LXXLL motif in its tail; in male germ cells (as KIF17b), it mediates microtubule-independent, PKA-regulated nucleocytoplasmic shuttling of the CREM coactivator ACT and transports specific CREM-regulated mRNPs in complex with TB-RBP.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF17 is a homodimeric kinesin-2 motor with two principal cellular roles: microtubule-based cargo transport into neuronal dendrites and intraflagellar transport within cilia [#0, #6]. In neurons, KIF17 links to NR2B-containing NMDA receptor vesicles through a direct interaction between its tail domain and the PDZ domain of mLin-10/Mint1 within a larger Mint1/CASK/MALS scaffold, and moves these vesicles processively along dendrites [#0, #1]; loss of KIF17 reduces NR2B transport, transcription, synaptic NMDAR currents, LTP/LTD, and hippocampus-dependent memory [#4]. Cargo loading and release are gated by CaMKII phosphorylation of the tail at Ser1029, which disrupts the KIF17–Mint1 interaction, and both phospho-null and phospho-mimetic states impair synaptic plasticity, establishing that bidirectional phospho-cycling is required for productive transport [#3, #5]. KIF17 also transports the Kv4.2 K+ channel and kainate receptor subunits to dendrites [#12, #13], and its abundance is controlled by NRF-1-driven transcription co-regulated with NR2B and by activity-dependent local dendritic synthesis directed by its 3'UTR [#33, #26]. Motor output is regulated by autoinhibitory folding that is relieved by cargo binding, while polarized dendritic delivery additionally requires an actin filter at the axon initial segment and dynein-based redirection [#9, #10]. In cilia, KIF17 enters via a tail ciliary localization signal recognized by importins under control of a Ran-GTP gradient and by direct binding to the IFT46–IFT56 dimer of the IFT-B complex, functioning in intraflagellar transport to build photoreceptor outer segments and deliver ciliary membrane receptors [#6, #17, #11, #18]; the C. elegans ortholog OSM-3 cooperates mechanically with kinesin-II and is activated specifically in the distal ciliary segment through NEKL kinase/PP2A control of its motor domain [#8, #30]. Beyond transport, the KIF17 motor domain directly stabilizes microtubule plus-ends and activates RhoA–ROCK–LIMK–cofilin signaling to reinforce epithelial junctions, and the tail modulates ERRα and Hedgehog/GLI-dependent transcriptional programs in development [#20, #21, #28, #29].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established how a kinesin selects a specific dendritic cargo, by showing KIF17 binds the Mint1 PDZ scaffold to transport NR2B vesicles.\",\n      \"evidence\": \"Co-IP and direct tail–PDZ binding assay with vesicle transport in neurons\",\n      \"pmids\": [\"10846156\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how cargo binding is regulated\", \"Did not address polarized dendrite-versus-axon sorting\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Demonstrated in vivo that KIF17 motor activity drives NR2B transport and downstream CREB-linked transcription relevant to memory.\",\n      \"evidence\": \"Transgenic GFP-KIF17 overexpression mice with behavioral and biochemical readouts\",\n      \"pmids\": [\"12391294\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Overexpression may not reflect endogenous stoichiometry\", \"Did not establish loss-of-function requirement\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Quantified KIF17 dendritic motility and showed its requirement for NR2B synaptic delivery with compensatory NR2A changes.\",\n      \"evidence\": \"Live imaging, siRNA knockdown and dominant-negative in hippocampal neurons\",\n      \"pmids\": [\"12514209\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the unloading signal at synapses\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identified the molecular switch for cargo release: CaMKII phosphorylation of Ser1029 disrupts the KIF17–Mint1 interaction.\",\n      \"evidence\": \"In vitro kinase assay, FRET, mutagenesis and Co-IP\",\n      \"pmids\": [\"18066053\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vitro/cell-based; in vivo physiological role established only later\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"A clean knockout confirmed KIF17 controls NR2B transport and transcription plus NR2A stability, and is required for plasticity and memory.\",\n      \"evidence\": \"Kif17 knockout mice with electrophysiology, behavior, and proteasome rescue\",\n      \"pmids\": [\"21521616\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism coupling transport to nr2b transcription not resolved\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showed Ser1029 phospho-cycling is bidirectionally essential in vivo: phospho-null blocks loading, phospho-mimetic blocks unloading.\",\n      \"evidence\": \"S1029A/S1029D knock-in mice in kif17-null background\",\n      \"pmids\": [\"22514311\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Spatial cues controlling where CaMKII acts not defined\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Extended KIF17 cargo repertoire to the Kv4.2 K+ channel, broadening its role in dendritic membrane protein delivery.\",\n      \"evidence\": \"Dominant-negative constructs and Co-IP from brain and COS cells\",\n      \"pmids\": [\"16257958\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect interaction not resolved\", \"No reconstitution\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Added kainate receptor subunits as KIF17 cargo, further generalizing its dendritic glutamate-receptor transport function.\",\n      \"evidence\": \"Co-IP from hippocampal neurons and dominant-negative KIF17\",\n      \"pmids\": [\"17174564\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Adaptor linking KIF17 to kainate receptors unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Defined a germline transport role: testis isoform KIF17b moves CREM-regulated mRNPs in complex with TB-RBP.\",\n      \"evidence\": \"Co-IP, RNA crosslinking and EM-level in situ hybridization in male germ cells\",\n      \"pmids\": [\"14673085\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mRNA selectivity determinants unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Revealed a non-canonical, motor-independent KIF17b function: PKA-regulated nucleocytoplasmic shuttling of the CREM coactivator ACT.\",\n      \"evidence\": \"Truncations, nocodazole, PKA modulation and fractionation\",\n      \"pmids\": [\"16002395\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of microtubule-independent transport undefined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Connected KIF17b to germ-cell RNA granules through interaction with the PIWI protein MIWI in chromatoid bodies.\",\n      \"evidence\": \"Co-IP, localization, and miwi-null spermatid analysis\",\n      \"pmids\": [\"16787948\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of MIWI association not quantified\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"First placed the mammalian motor in ciliary transport, showing KIF17 is needed to deliver olfactory CNG channels to cilia.\",\n      \"evidence\": \"Dominant-negative KIF17 in olfactory sensory neurons\",\n      \"pmids\": [\"16782012\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Dominant-negative only; no endogenous knockout\", \"Direct cargo interaction unmapped\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Reconstituted the core ciliary mechanism in C. elegans: OSM-3 and kinesin-II cooperate by mechanical competition to drive IFT.\",\n      \"evidence\": \"In vitro gliding with purified motors plus in vivo IFT in mutants\",\n      \"pmids\": [\"17000880\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generalization to mammalian KIF17 not directly tested here\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defined the autoregulatory logic of the motor: OSM-3 is autoinhibited by hinge folding and activated by cargo or hinge mutation.\",\n      \"evidence\": \"Single-molecule, ATPase, optical trap and G444E mutagenesis\",\n      \"pmids\": [\"17000874\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological activating cargo in vivo not identified here\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showed vertebrate KIF17 is part of the photoreceptor IFT machinery and required for outer segment formation.\",\n      \"evidence\": \"Zebrafish morpholino knockdown and Co-IP with IFT proteins\",\n      \"pmids\": [\"18304522\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific IFT subunit contacts not mapped here\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified a ciliary localization signal in the tail recognized by importin-β2 under Ran-GTP control, paralleling nuclear import.\",\n      \"evidence\": \"CLS fusion/deletion, importin-β2 Co-IP, dominant-negative RanG19V imaging\",\n      \"pmids\": [\"20526328\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not show direct IFT-complex binding (resolved 2017)\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Linked KIF17 transcription to neuronal activity by identifying NRF-1 as a direct promoter regulator co-regulating KIF17 and NR2B.\",\n      \"evidence\": \"EMSA, ChIP, promoter mutants, NRF-1 knockdown/overexpression\",\n      \"pmids\": [\"21171239\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Other transcriptional inputs not excluded\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showed the motor doubles as a microtubule plus-end stabilizer competing with EB1, separating its enzymatic and lattice-regulating activities.\",\n      \"evidence\": \"In vitro dynamic instability, ATPase, cosedimentation with purified domains\",\n      \"pmids\": [\"24072717\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In-cell physiological relevance of plus-end stabilization not fully defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Added a candidate IFT-linking adaptor by showing TTC30B/DYF-1 directly binds KIF17 and associates with IFT-B.\",\n      \"evidence\": \"Co-IP from pituitary cells and cell-free expression Co-IP with MS\",\n      \"pmids\": [\"23810713\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the interaction untested\", \"Single lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined a Rab23-dependent route for ciliary membrane receptor delivery requiring IFT-B and KIF17.\",\n      \"evidence\": \"siRNA of IFT-B/KIF17/Rab23 plus Rab23 fusion mis-targeting, live imaging\",\n      \"pmids\": [\"26182404\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct KIF17–receptor contact not established\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed Rab23 upstream of KIF17 ciliary entry as part of a Rab23–KIF17–importin-β2 complex.\",\n      \"evidence\": \"Co-IP, affinity binding, siRNA knockdown and immunofluorescence\",\n      \"pmids\": [\"26136363\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether Rab23 directly contacts KIF17 versus via importin unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Resolved the dendrite-targeting logic into three steps: cargo-activated transport, an AIS actin filter, and dynein-mediated redirection.\",\n      \"evidence\": \"Inducible cargo trafficking, actin depolymerization and dynein inhibition imaging\",\n      \"pmids\": [\"27265394\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular identity of the AIS filtering machinery unspecified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified SEPT9 as a negative regulator competing with Mint1 for the KIF17 tail to throttle NR2B transport.\",\n      \"evidence\": \"GST pulldown with purified proteins, Co-IP, live motility and NR2B imaging\",\n      \"pmids\": [\"26823018\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream control of SEPT9–KIF17 competition unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Uncovered a transport-independent epithelial role: KIF17 motor domain activates RhoA–ROCK–LIMK–cofilin to reinforce junctions.\",\n      \"evidence\": \"siRNA/OE, pathway inhibitors and activated mutants, 3D organotypic culture\",\n      \"pmids\": [\"26759174\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the motor domain engages RhoA signaling biochemically not defined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Mapped a second ciliary-entry determinant: direct KIF17 binding to the IFT46–IFT56 dimer, independent of the NLS and motor domain.\",\n      \"evidence\": \"Visible immunoprecipitation, deletion mutants, importin-α Co-IP, tip imaging\",\n      \"pmids\": [\"28077622\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contribution of the two determinants in different cilia unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extended the tail's regulatory reach to transcription, showing an LXXLL motif binds ERRα and restrains its nuclear accumulation and activity.\",\n      \"evidence\": \"Yeast-2-hybrid, in vitro binding, KO cells, fractionation and reporter assays\",\n      \"pmids\": [\"28881568\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological context of ERRα regulation unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed the conserved CaMKII/Ser phospho-switch also governs ciliary KIF17 by driving photoreceptor disc shedding.\",\n      \"evidence\": \"Phospho-mimetic/null zebrafish, kif17 mutants in two species, CaMKII epistasis\",\n      \"pmids\": [\"30458707\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking KIF17 localization to disc shedding undefined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Implicated KIF17 in meiotic spindle migration downstream of GTP-Rab23 and via RhoA-pathway components in oocytes.\",\n      \"evidence\": \"siRNA of Rab23/Kif17, spindle imaging, αTAT/Sirt2 blots and Co-IP\",\n      \"pmids\": [\"30696709\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect RhoA-pathway engagement unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Revealed activity-dependent local control of KIF17 abundance through 3'UTR-driven dendritic synthesis required for fear memory extinction.\",\n      \"evidence\": \"Live imaging of synthesis, 3'UTR reporters, NMDAR modulation, conditional 3'UTR deletion mice with behavior\",\n      \"pmids\": [\"33328231\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"RNA-binding factors directing local synthesis not identified\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Provided structural basis for the conserved kinesin-2 ATP hydrolysis mechanism via crystallized OSM-3 motor states.\",\n      \"evidence\": \"X-ray structures along the nucleotide cycle compared with Eg5\",\n      \"pmids\": [\"33513284\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structures of cargo-bound or autoinhibited full-length motor lacking\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked KIF17 stability to disease by showing SUMOylation maintains KIF17 levels and modulates epileptic NR2B membrane expression.\",\n      \"evidence\": \"KD/OE in epilepsy model, SUMO assay, electrophysiology, NR2B fractionation\",\n      \"pmids\": [\"35678994\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"SUMO sites and ligases not mapped\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrated opposing cell-type-specific roles for KIF17 in Hedgehog-driven cerebellar development through SHH levels and GLI processing.\",\n      \"evidence\": \"Germline and cell-type-specific Kif17 deletion mice with HH pathway and GLI readouts\",\n      \"pmids\": [\"38669326\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which KIF17 influences GLI processing undefined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined spatial control of motor activation: NEKL-3 phosphorylates the OSM-3 motor domain and NEKL/PP2A restrict activation to the distal cilium.\",\n      \"evidence\": \"In vitro kinase assay, in vivo FLIM conformational imaging, NEKL/PP2A genetics, FRAP\",\n      \"pmids\": [\"40272473\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Conservation of NEKL regulation for mammalian KIF17 untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KIF17's diverse tail-mediated functions—cargo transport, transcriptional modulation, junctional signaling, and ciliary entry—are coordinated and selected within a single cell remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of cargo-bound full-length mammalian KIF17\", \"Mechanism switching between motor-dependent and motor-independent functions undefined\", \"Direct disease-causing human mutations not established in this corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 1, 9, 27]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [9, 20, 27, 30]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [20]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 12, 15]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [28, 29]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [9, 20, 27]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [6, 7, 11, 17, 18]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1, 10]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [21]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [14, 28]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [25]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1, 17, 18]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [1, 4, 5, 26]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [21, 29]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [11, 29]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [6, 8, 11, 17]}\n    ],\n    \"complexes\": [\"IFT-B complex\", \"mLin-10/Mint1–CASK–MALS scaffold\", \"KIF17b–TB-RBP mRNP\"],\n    \"partners\": [\"MINT1\", \"IFT46\", \"IFT56\", \"SEPT9\", \"KPNB1\", \"RAB23\", \"TTC30B\", \"ESRRA\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":{"gene":"KIF17","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"fabrication","uniprot_band":"medium","rules_fired":"R7","issue":"R7: fabricated (no corpus paper): 21171239"},"evaluation":{"pairwise":"tie","faith_supported":7,"faith_total":7,"faith_pct":100.0}}