{"gene":"KIF13A","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2000,"finding":"KIF13A is a plus end-directed microtubule-dependent motor protein that directly interacts with β1-adaptin (a subunit of the AP-1 adaptor complex) to transport mannose-6-phosphate receptor (M6PR)-containing vesicles from the TGN to the plasma membrane; overexpression mislocalizes AP-1 and M6PR, while functional blockade reduces cell-surface M6PR expression.","method":"Co-immunoprecipitation, overexpression/dominant-negative functional blockade, cell-surface expression assay","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP and functional blockade with defined cargo phenotype, foundational study independently replicated by multiple subsequent labs","pmids":["11106728"],"is_preprint":false},{"year":2010,"finding":"KIF13A is required for translocation of FYVE-CENT (ZFYVE26) and its binding partner TTC19 from the centrosome to the midbody during cytokinesis; this translocation is dependent on PtdIns(3)P produced by PI(3)K-III, and KIF13A depletion causes cytokinesis arrest and multinucleation similar to depletion of FYVE-CENT or VPS34.","method":"siRNA knockdown with cytokinesis phenotype readout (binucleate/multinucleate cell counting), live-cell imaging, Co-IP","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (knockdown, imaging, epistasis), published in high-impact journal with rigorous controls","pmids":["20208530"],"is_preprint":false},{"year":2009,"finding":"KIF13A cooperates with the clathrin adaptor AP-1 to create peripheral recycling endosomal subdomains in melanocytes required for delivery of melanosomal cargo (e.g., Tyrp1) to maturing melanosomes; depletion of either AP-1 or KIF13A redistributes recycling endosomes to pericentriolar clusters and inhibits melanin synthesis.","method":"siRNA knockdown, immunocytochemistry, live-cell imaging, electron tomography","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods including electron tomography and live imaging, replicated in subsequent studies","pmids":["19841138"],"is_preprint":false},{"year":2014,"finding":"KIF13A associates with recycling endosome tubules and is required for their morphogenesis from vacuolar sorting endosomes (SEs); loss of KIF13A function impairs endosomal tubule formation, causing defects in endosome homeostasis and cargo recycling. KIF13A also interacts and cooperates with RAB11 to generate endosomal tubules.","method":"siRNA knockdown, dominant-negative expression, live-cell imaging, Co-IP/pulldown with RAB11","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (KD, DN, imaging, pulldown), specific phenotypic readout, replicated across studies","pmids":["24462287"],"is_preprint":false},{"year":2019,"finding":"Rab10 localizes to tubular endosomes and interacts with KIF13A (and KIF13B); knockout of Rab10 abolishes tubular endosomal structures. Both the Rab10-binding homology domain and the motor domain of KIF13A are required for Rab10-positive tubular endosome formation.","method":"EGFP-Rab GTPase localization screen, Rab10 knockout, domain deletion analysis, in silico screening confirmed by interaction assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain deletion and KO with defined phenotype, single lab, two orthogonal approaches","pmids":["30700496"],"is_preprint":false},{"year":2013,"finding":"KIF13A transports serotonin type 1A receptor (5HT1AR) to the cell surface via direct interaction between its forkhead-associated (FHA) domain and an intracellular loop of 5HT1AR; a minimotor comprising the motor and FHA domains reconstitutes transport of 5HT1AR-carrying organelles in vitro. KIF13A-deficient mice exhibit elevated anxiety-related behavior coinciding with reduced 5HT1AR surface expression.","method":"Kif13a knockout mice (behavioral phenotype), KIF13A knockdown in neuroblastoma cells (surface receptor assay), biochemical domain-mapping, in vitro reconstitution assay","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution plus domain mutagenesis plus KO mouse phenotype, multiple orthogonal methods","pmids":["23438369"],"is_preprint":false},{"year":2018,"finding":"KIF13A controls RhoB plasma membrane localization by mediating trafficking of RhoB through Rab11-positive recycling endosomes; KIF13A depletion inhibits RhoB plasma membrane localization, membrane blebbing, and 3D amoeboid migration of ALL cells.","method":"siRNA knockdown, live-cell imaging, 3D migration assay, endosomal trafficking analysis with Rab5/Rab11 markers","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD with defined cargo (RhoB) and cellular phenotype (blebbing, 3D migration), single lab, multiple imaging approaches","pmids":["30049714"],"is_preprint":false},{"year":2017,"finding":"KIF13A mediates transport of influenza A virus ribonucleoproteins (vRNPs) on Rab11-positive vesicles to the cell surface; KIF13A depletion reduces viral titers and vRNP accumulation at the cell surface without affecting other viral proteins at assembly sites.","method":"siRNA knockdown, overexpression, immunofluorescence, viral titer assay","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD and OE with specific cargo (vRNP) readout, single lab, two complementary approaches","pmids":["29061883"],"is_preprint":false},{"year":2013,"finding":"KIF13A interacts with the Lassa virus (LASV) matrix protein Z and mediates its microtubule-dependent transport to the plasma membrane; KIF13A overexpression relocalizes Z to the cell periphery, while dominant-negative or siRNA knockdown causes perinuclear accumulation and decreased production of Z-induced VLPs and infectious LASV. This interaction extends to Z proteins from both Old and New World arenaviruses.","method":"Co-immunoprecipitation, overexpression, dominant-negative expression, siRNA knockdown, VLP production assay, infectious virus titer","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional blockade with defined viral output phenotype, single lab","pmids":["23279019"],"is_preprint":false},{"year":2017,"finding":"mTORC1 regulates KIF13A expression downstream of IL-2 and IL-7 signaling to control cell-surface M6PR levels on T cells; rapamycin-mediated mTORC1 inhibition or siRNA knockdown of KIF13A reduces surface M6PR expression and renders T cells resistant to Treg granzyme-B-mediated killing.","method":"Signaling inhibitors (rapamycin), siRNA knockdown of KIF13A, flow cytometry for surface M6PR, functional cytotoxicity assay","journal":"Cell discovery","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pathway inhibitor plus KD with defined functional readout, single lab","pmids":["28496990"],"is_preprint":false},{"year":2021,"finding":"KIF13A exists as inactive monomers in cells due to a conserved proline residue between the neck coil and coiled-coil 1 (NC-CC1) domains that creates steric hindrance. Rab22A binds to the NC-CC1 domains of KIF13A, relieves proline-mediated inhibition, and facilitates motor dimerization, enabling balanced motility and force generation against dyneins for recycling endosome tubulation.","method":"Single-molecule assays, biochemical dimerization assays, domain mutagenesis (proline substitution), Co-IP with Rab22A, live-cell imaging of RE tubulation","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — single-molecule reconstitution plus domain mutagenesis plus Rab22A binding assays, multiple orthogonal methods in one rigorous study","pmids":["33536208"],"is_preprint":false},{"year":2018,"finding":"A 5-amino-acid β1-adaptin AP-1 subunit-derived peptide blocks the KIF13A–AP-1 interaction in melanocytes and decreases pigmentation by impacting melanosome maturation, confirming that the KIF13A–β1-adaptin interaction is functionally required for melanosome biogenesis.","method":"Blocking peptide treatment, pigmentation assay, 3D-reconstructed pigmented epidermis model","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — peptide interference with defined functional readout (pigmentation, melanosome maturation), single lab","pmids":["29443872"],"is_preprint":false},{"year":2021,"finding":"KIF13A is specifically required for delivery of AMPA receptors (AMPARs) to the spine surface during LTP induction; KIF13A depletion abolishes LTP expression. KIF13A interacts with centaurin-α1 as part of the transport machinery engaged with AMPARs upon LTP induction, and is responsible for remodeling Rab11-FIP2 endosomal structures in the dendritic shaft during LTP.","method":"Electrophysiology (LTP recording), biochemistry (Co-IP with centaurin-α1/AMPARs), imaging of Rab11-FIP2 endosomes, KIF13A depletion from hippocampal slices","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — electrophysiology plus Co-IP plus live imaging plus KD, multiple orthogonal methods establishing mechanism and pathway position","pmids":["33999113"],"is_preprint":false},{"year":2022,"finding":"KIF13A and KIF3A coordinate to transport MT1-MMP-containing vesicles from the trans-Golgi to endosomes, while KIF13A alone transports vesicles from the endosome to the plasma membrane; KIF13A knockdown inhibits MT1-MMP-dependent collagen degradation and cancer cell invasion.","method":"siRNA knockdown, live-cell imaging (vesicle tracking), collagen degradation assay, invasion assay","journal":"Matrix biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD with specific functional readout plus live-cell imaging, single lab","pmids":["35122963"],"is_preprint":false},{"year":2024,"finding":"KIF13A is a dedicated dendrite-selective kinesin in neurons; both KIF13A and KIF13B are maintained at the trans-Golgi network by interactions with the AP-1 adaptor complex, and interference with KIF13 binding to AP-1 disrupts dendrite- and axon-selective trafficking.","method":"Live-cell imaging in cultured hippocampal neurons, AP-1 interaction interference assay, polarized transport assays","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live-cell imaging plus AP-1 interaction interference with defined trafficking phenotype, single lab","pmids":["38446634"],"is_preprint":false},{"year":2024,"finding":"MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening KIF13A interaction with 14-3-3 proteins and causing KIF13A to dissociate from transferrin receptor (TfR)-containing vesicles at the proximal axon, thereby restricting TfR vesicle transport exclusively to dendrites. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles.","method":"Live-cell imaging, KIF13A knockout, BioID proximity labeling assay, MARK2 knockout, overexpression studies","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO plus BioID plus live imaging, multiple methods identifying phosphorylation-based regulatory mechanism, single lab","pmids":["38709923"],"is_preprint":false},{"year":2023,"finding":"MARK2 phosphorylates KIF13A at a 14-3-3 binding site to dissociate KIF13A from TfR-containing vesicles, preventing their axonal transport (preprint version of the published PNAS study).","method":"Live-cell imaging, KIF13A knockout, BioID assay","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 2 / Weak — preprint duplicating published PNAS findings; not independently replicated as preprint","pmids":["38105964"],"is_preprint":true}],"current_model":"KIF13A is a plus end-directed, kinesin-3 family microtubule motor that transports diverse membrane cargoes—including M6PR, 5HT1AR, AMPA receptors, RhoB, MT1-MMP, and viral proteins—from the TGN and recycling endosomes to the plasma membrane via direct interaction with the AP-1 adaptor complex (through β1-adaptin) and Rab GTPases (RAB11, Rab22A, Rab10); Rab22A activates KIF13A by relieving proline-mediated autoinhibition to drive motor dimerization, while MARK2 phosphorylates KIF13A at a 14-3-3 binding site to restrict its cargo transport to dendrites, and KIF13A also drives recycling endosome tubule morphogenesis and is required for cytokinesis via midbody recruitment of FYVE-CENT."},"narrative":{"mechanistic_narrative":"KIF13A is a plus end-directed, microtubule-dependent kinesin motor that transports diverse membrane cargoes from the trans-Golgi network (TGN) and recycling endosomes to the plasma membrane [PMID:11106728]. Its founding cargo route is established through a direct interaction with the AP-1 clathrin adaptor complex via β1-adaptin, which couples the motor to mannose-6-phosphate receptor (M6PR)-containing vesicles and controls cell-surface M6PR levels [PMID:11106728, PMID:29443872]. Beyond M6PR, KIF13A carries a broad cargo repertoire to the cell surface—the serotonin 5HT1A receptor through its FHA domain [PMID:23438369], AMPA receptors during long-term potentiation [PMID:33999113], RhoB through Rab11 recycling endosomes [PMID:30049714], and MT1-MMP for collagen degradation and invasion [PMID:35122963]—and is hijacked by influenza A vRNPs and arenavirus Z matrix proteins for delivery to the plasma membrane [PMID:29061883, PMID:23279019]. KIF13A is also required to generate and morphologically shape recycling endosome tubules, cooperating with RAB11, Rab10, and Rab22A [PMID:24462287, PMID:30700496, PMID:33536208], and Rab22A activates the motor by binding its NC-CC1 region to relieve a proline-mediated autoinhibition that otherwise holds KIF13A as an inactive monomer, thereby licensing dimerization and processive force generation [PMID:33536208]. In polarized neurons, KIF13A is held at the TGN by AP-1 and functions as a dendrite-selective motor whose cargo specificity is gated by MARK2 phosphorylation at a 14-3-3 binding motif, which strips the motor from transferrin-receptor vesicles to confine their transport to dendrites [PMID:38446634, PMID:38709923]. Independently, KIF13A is required for cytokinesis, translocating the FYVE-CENT (ZFYVE26)–TTC19 complex from the centrosome to the midbody in a PtdIns(3)P-dependent manner [PMID:20208530].","teleology":[{"year":2000,"claim":"Established KIF13A as a motor that links the AP-1 adaptor to cargo, answering how M6PR vesicles are delivered from the TGN to the cell surface.","evidence":"Reciprocal Co-IP with β1-adaptin, dominant-negative blockade, and cell-surface M6PR assay","pmids":["11106728"],"confidence":"High","gaps":["Did not resolve the motor's regulatory state (autoinhibition)","Cargo repertoire beyond M6PR unknown at this stage"]},{"year":2009,"claim":"Extended KIF13A–AP-1 cooperation to a tissue-specific role, showing it builds peripheral recycling endosomal subdomains required for melanosome cargo delivery.","evidence":"siRNA knockdown, immunocytochemistry, live imaging, and electron tomography in melanocytes","pmids":["19841138"],"confidence":"High","gaps":["Molecular basis of subdomain positioning not defined","Did not identify the activating signal for the motor"]},{"year":2010,"claim":"Identified an unexpected cell-division role, showing KIF13A delivers FYVE-CENT–TTC19 to the midbody, linking the motor to cytokinesis completion.","evidence":"siRNA knockdown with multinucleation readout, live imaging, Co-IP, and PI(3)K-III epistasis","pmids":["20208530"],"confidence":"High","gaps":["How PtdIns(3)P recruits the KIF13A cargo to microtubules is unresolved","Direct vs indirect FYVE-CENT binding not mapped"]},{"year":2013,"claim":"Defined a cargo-recognition module and an in vivo phenotype, showing the FHA domain directly binds 5HT1AR and that loss elevates anxiety in mice.","evidence":"In vitro reconstitution with motor+FHA minimotor, domain mapping, KO mouse behavior, knockdown surface-receptor assay","pmids":["23438369"],"confidence":"High","gaps":["FHA-domain phospho-dependence of cargo binding not addressed","Behavioral phenotype not mechanistically tied to single neuronal circuit"]},{"year":2013,"claim":"Showed viral exploitation of KIF13A, with arenavirus Z matrix protein using the motor for plasma-membrane delivery and virion production.","evidence":"Co-IP, overexpression, dominant-negative and siRNA blockade, VLP and infectious-titer assays","pmids":["23279019"],"confidence":"Medium","gaps":["Z-binding interface on KIF13A not mapped","Single lab"]},{"year":2014,"claim":"Reframed KIF13A as a tubule-morphogenesis factor, demonstrating it generates recycling-endosome tubules from vacuolar sorting endosomes together with RAB11.","evidence":"siRNA knockdown, dominant-negative expression, live imaging, RAB11 pulldown","pmids":["24462287"],"confidence":"High","gaps":["Mechanical model for tubule pulling not yet established","RAB11 binding region not mapped here"]},{"year":2017,"claim":"Connected KIF13A to upstream signaling and immune function, placing its expression downstream of mTORC1/IL-2/IL-7 to set surface M6PR on T cells.","evidence":"Rapamycin inhibition, siRNA knockdown, flow cytometry, Treg cytotoxicity assay","pmids":["28496990"],"confidence":"Medium","gaps":["Transcriptional vs post-transcriptional control by mTORC1 not distinguished","Single lab"]},{"year":2017,"claim":"Showed influenza A virus uses KIF13A on Rab11 vesicles to deliver vRNPs to the cell surface, generalizing the motor's viral-hijack role.","evidence":"siRNA knockdown, overexpression, immunofluorescence, viral titer assay","pmids":["29061883"],"confidence":"Medium","gaps":["Direct vRNP-motor link vs Rab11-mediated coupling not separated","Single lab"]},{"year":2018,"claim":"Linked KIF13A to cell-shape and motility control by routing RhoB through Rab11 endosomes to drive amoeboid migration of leukemia cells.","evidence":"siRNA knockdown, live imaging, 3D migration assay, Rab5/Rab11 trafficking analysis","pmids":["30049714"],"confidence":"Medium","gaps":["Whether RhoB is a direct cargo or indirect passenger unresolved","Single lab"]},{"year":2018,"claim":"Provided causal proof that the KIF13A–AP-1 interface is functionally essential, using a short β1-adaptin peptide to block pigmentation.","evidence":"Blocking-peptide treatment, pigmentation assay, 3D pigmented epidermis model","pmids":["29443872"],"confidence":"Medium","gaps":["Peptide specificity for KIF13A vs KIF13B not fully resolved","Single lab"]},{"year":2019,"claim":"Identified Rab10 as a tubular-endosome partner requiring both the motor and Rab-binding homology domains of KIF13A for tubule formation.","evidence":"EGFP-Rab localization screen, Rab10 knockout, domain-deletion analysis, interaction assays","pmids":["30700496"],"confidence":"Medium","gaps":["Functional distinction between Rab10, Rab11 and Rab22A inputs not integrated","Single lab"]},{"year":2021,"claim":"Resolved the activation mechanism, showing KIF13A is autoinhibited monomer relieved by Rab22A binding at NC-CC1 to permit dimerization and force generation.","evidence":"Single-molecule motility, dimerization assays, proline-substitution mutagenesis, Rab22A Co-IP, RE tubulation imaging","pmids":["33536208"],"confidence":"High","gaps":["Whether other Rabs (RAB11, Rab10) activate via the same mechanism not tested","Structural model of the autoinhibited state not solved"]},{"year":2021,"claim":"Placed KIF13A in synaptic plasticity, showing it is required for AMPAR delivery and LTP and remodels dendritic Rab11-FIP2 endosomes via centaurin-α1.","evidence":"LTP electrophysiology, Co-IP with centaurin-α1/AMPARs, endosome imaging, knockdown in hippocampal slices","pmids":["33999113"],"confidence":"High","gaps":["Direct AMPAR-motor contact not defined","Activity-dependent activation signal upstream unknown"]},{"year":2022,"claim":"Showed division of labor with KIF3A in two-step MT1-MMP delivery, tying KIF13A to invasive collagen degradation.","evidence":"siRNA knockdown, vesicle tracking, collagen degradation and invasion assays","pmids":["35122963"],"confidence":"Medium","gaps":["Cargo handoff mechanism between KIF3A and KIF13A unresolved","Single lab"]},{"year":2024,"claim":"Established KIF13A as a dendrite-selective neuronal motor held at the TGN by AP-1, with AP-1 binding required for polarized trafficking.","evidence":"Live imaging in hippocampal neurons, AP-1 interference, polarized transport assays","pmids":["38446634"],"confidence":"Medium","gaps":["How AP-1 retention is released for transport not defined","Single lab"]},{"year":2024,"claim":"Defined the polarity-determining switch, showing MARK2 phosphorylation creates a 14-3-3 motif that strips KIF13A from TfR vesicles to confine transport to dendrites.","evidence":"Live imaging, KIF13A and MARK2 knockouts, BioID proximity labeling, overexpression","pmids":["38709923"],"confidence":"Medium","gaps":["Structural basis of the 14-3-3-driven cargo release not solved","Single lab"]},{"year":null,"claim":"How the multiple Rab inputs (RAB11, Rab10, Rab22A), AP-1 retention, and MARK2/14-3-3 phosphoregulation are integrated to select among the diverse cargoes in a given cell type remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking activation, cargo selection, and polarity","Structure of full-length autoinhibited and cargo-bound motor not solved","Direct vs Rab-bridged cargo binding undefined for most cargoes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,5,10]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[10]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,5]},{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0,5,13]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,13,14]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[2,3,4,6]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,5,8]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,6,7]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,5,13]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,2,3,7]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[5,12,15]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[7,8,13]}],"complexes":[],"partners":["AP1B1","RAB11","RAB22A","RAB10","ZFYVE26","MARK2","YWHA","KIF3A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H1H9","full_name":"Kinesin-like protein KIF13A","aliases":["Kinesin-like protein RBKIN"],"length_aa":1805,"mass_kda":202.3,"function":"Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis and cytokinesis. Mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. Also required for the abscission step in cytokinesis: mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Midbody; Endosome membrane; Golgi apparatus membrane","url":"https://www.uniprot.org/uniprotkb/Q9H1H9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF13A","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KIF13A","total_profiled":1310},"omim":[{"mim_id":"605433","title":"KINESIN FAMILY MEMBER 13A; KIF13A","url":"https://www.omim.org/entry/605433"},{"mim_id":"600526","title":"MAP/MICROTUBULE AFFINITY-REGULATING KINASE 2; MARK2","url":"https://www.omim.org/entry/600526"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Mid piece","reliability":"Approved"},{"location":"Principal piece","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"skeletal muscle","ntpm":97.9}],"url":"https://www.proteinatlas.org/search/KIF13A"},"hgnc":{"alias_symbol":["bA500C11.2","RBKIN"],"prev_symbol":[]},"alphafold":{"accession":"Q9H1H9","domains":[{"cath_id":"3.40.850.10","chopping":"3-361","consensus_level":"medium","plddt":83.5331,"start":3,"end":361},{"cath_id":"-","chopping":"362-430","consensus_level":"medium","plddt":73.2503,"start":362,"end":430},{"cath_id":"2.60.200.20","chopping":"433-551","consensus_level":"medium","plddt":75.4129,"start":433,"end":551},{"cath_id":"-","chopping":"982-1074_1166-1312","consensus_level":"high","plddt":81.1903,"start":982,"end":1312}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H1H9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H1H9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H1H9-F1-predicted_aligned_error_v6.png","plddt_mean":65.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIF13A","jax_strain_url":"https://www.jax.org/strain/search?query=KIF13A"},"sequence":{"accession":"Q9H1H9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H1H9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H1H9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H1H9"}},"corpus_meta":[{"pmid":"11106728","id":"PMC_11106728","title":"A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex.","date":"2000","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/11106728","citation_count":229,"is_preprint":false},{"pmid":"20208530","id":"PMC_20208530","title":"PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody.","date":"2010","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/20208530","citation_count":185,"is_preprint":false},{"pmid":"19841138","id":"PMC_19841138","title":"AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis.","date":"2009","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19841138","citation_count":145,"is_preprint":false},{"pmid":"24462287","id":"PMC_24462287","title":"Recycling endosome tubule morphogenesis from sorting endosomes requires the kinesin motor KIF13A.","date":"2014","source":"Cell 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RhoB plasma membrane localization governs membrane blebbing and blebby amoeboid cell migration.","date":"2018","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/30049714","citation_count":29,"is_preprint":false},{"pmid":"29061883","id":"PMC_29061883","title":"KIF13A mediates trafficking of influenza A virus ribonucleoproteins.","date":"2017","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/29061883","citation_count":22,"is_preprint":false},{"pmid":"28496990","id":"PMC_28496990","title":"mTORC1 regulates mannose-6-phosphate receptor transport and T-cell vulnerability to regulatory T cells by controlling kinesin KIF13A.","date":"2017","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/28496990","citation_count":19,"is_preprint":false},{"pmid":"35547822","id":"PMC_35547822","title":"KIF13A-A Key Regulator of Recycling Endosome Dynamics.","date":"2022","source":"Frontiers in cell and developmental 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reduces cell-surface M6PR expression.\",\n      \"method\": \"Co-immunoprecipitation, overexpression/dominant-negative functional blockade, cell-surface expression assay\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP and functional blockade with defined cargo phenotype, foundational study independently replicated by multiple subsequent labs\",\n      \"pmids\": [\"11106728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"KIF13A is required for translocation of FYVE-CENT (ZFYVE26) and its binding partner TTC19 from the centrosome to the midbody during cytokinesis; this translocation is dependent on PtdIns(3)P produced by PI(3)K-III, and KIF13A depletion causes cytokinesis arrest and multinucleation similar to depletion of FYVE-CENT or VPS34.\",\n      \"method\": \"siRNA knockdown with cytokinesis phenotype readout (binucleate/multinucleate cell counting), live-cell imaging, Co-IP\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (knockdown, imaging, epistasis), published in high-impact journal with rigorous controls\",\n      \"pmids\": [\"20208530\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"KIF13A cooperates with the clathrin adaptor AP-1 to create peripheral recycling endosomal subdomains in melanocytes required for delivery of melanosomal cargo (e.g., Tyrp1) to maturing melanosomes; depletion of either AP-1 or KIF13A redistributes recycling endosomes to pericentriolar clusters and inhibits melanin synthesis.\",\n      \"method\": \"siRNA knockdown, immunocytochemistry, live-cell imaging, electron tomography\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods including electron tomography and live imaging, replicated in subsequent studies\",\n      \"pmids\": [\"19841138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KIF13A associates with recycling endosome tubules and is required for their morphogenesis from vacuolar sorting endosomes (SEs); loss of KIF13A function impairs endosomal tubule formation, causing defects in endosome homeostasis and cargo recycling. KIF13A also interacts and cooperates with RAB11 to generate endosomal tubules.\",\n      \"method\": \"siRNA knockdown, dominant-negative expression, live-cell imaging, Co-IP/pulldown with RAB11\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (KD, DN, imaging, pulldown), specific phenotypic readout, replicated across studies\",\n      \"pmids\": [\"24462287\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Rab10 localizes to tubular endosomes and interacts with KIF13A (and KIF13B); knockout of Rab10 abolishes tubular endosomal structures. Both the Rab10-binding homology domain and the motor domain of KIF13A are required for Rab10-positive tubular endosome formation.\",\n      \"method\": \"EGFP-Rab GTPase localization screen, Rab10 knockout, domain deletion analysis, in silico screening confirmed by interaction assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain deletion and KO with defined phenotype, single lab, two orthogonal approaches\",\n      \"pmids\": [\"30700496\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF13A transports serotonin type 1A receptor (5HT1AR) to the cell surface via direct interaction between its forkhead-associated (FHA) domain and an intracellular loop of 5HT1AR; a minimotor comprising the motor and FHA domains reconstitutes transport of 5HT1AR-carrying organelles in vitro. KIF13A-deficient mice exhibit elevated anxiety-related behavior coinciding with reduced 5HT1AR surface expression.\",\n      \"method\": \"Kif13a knockout mice (behavioral phenotype), KIF13A knockdown in neuroblastoma cells (surface receptor assay), biochemical domain-mapping, in vitro reconstitution assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution plus domain mutagenesis plus KO mouse phenotype, multiple orthogonal methods\",\n      \"pmids\": [\"23438369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KIF13A controls RhoB plasma membrane localization by mediating trafficking of RhoB through Rab11-positive recycling endosomes; KIF13A depletion inhibits RhoB plasma membrane localization, membrane blebbing, and 3D amoeboid migration of ALL cells.\",\n      \"method\": \"siRNA knockdown, live-cell imaging, 3D migration assay, endosomal trafficking analysis with Rab5/Rab11 markers\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD with defined cargo (RhoB) and cellular phenotype (blebbing, 3D migration), single lab, multiple imaging approaches\",\n      \"pmids\": [\"30049714\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KIF13A mediates transport of influenza A virus ribonucleoproteins (vRNPs) on Rab11-positive vesicles to the cell surface; KIF13A depletion reduces viral titers and vRNP accumulation at the cell surface without affecting other viral proteins at assembly sites.\",\n      \"method\": \"siRNA knockdown, overexpression, immunofluorescence, viral titer assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD and OE with specific cargo (vRNP) readout, single lab, two complementary approaches\",\n      \"pmids\": [\"29061883\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF13A interacts with the Lassa virus (LASV) matrix protein Z and mediates its microtubule-dependent transport to the plasma membrane; KIF13A overexpression relocalizes Z to the cell periphery, while dominant-negative or siRNA knockdown causes perinuclear accumulation and decreased production of Z-induced VLPs and infectious LASV. This interaction extends to Z proteins from both Old and New World arenaviruses.\",\n      \"method\": \"Co-immunoprecipitation, overexpression, dominant-negative expression, siRNA knockdown, VLP production assay, infectious virus titer\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional blockade with defined viral output phenotype, single lab\",\n      \"pmids\": [\"23279019\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"mTORC1 regulates KIF13A expression downstream of IL-2 and IL-7 signaling to control cell-surface M6PR levels on T cells; rapamycin-mediated mTORC1 inhibition or siRNA knockdown of KIF13A reduces surface M6PR expression and renders T cells resistant to Treg granzyme-B-mediated killing.\",\n      \"method\": \"Signaling inhibitors (rapamycin), siRNA knockdown of KIF13A, flow cytometry for surface M6PR, functional cytotoxicity assay\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pathway inhibitor plus KD with defined functional readout, single lab\",\n      \"pmids\": [\"28496990\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KIF13A exists as inactive monomers in cells due to a conserved proline residue between the neck coil and coiled-coil 1 (NC-CC1) domains that creates steric hindrance. Rab22A binds to the NC-CC1 domains of KIF13A, relieves proline-mediated inhibition, and facilitates motor dimerization, enabling balanced motility and force generation against dyneins for recycling endosome tubulation.\",\n      \"method\": \"Single-molecule assays, biochemical dimerization assays, domain mutagenesis (proline substitution), Co-IP with Rab22A, live-cell imaging of RE tubulation\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — single-molecule reconstitution plus domain mutagenesis plus Rab22A binding assays, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"33536208\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"A 5-amino-acid β1-adaptin AP-1 subunit-derived peptide blocks the KIF13A–AP-1 interaction in melanocytes and decreases pigmentation by impacting melanosome maturation, confirming that the KIF13A–β1-adaptin interaction is functionally required for melanosome biogenesis.\",\n      \"method\": \"Blocking peptide treatment, pigmentation assay, 3D-reconstructed pigmented epidermis model\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — peptide interference with defined functional readout (pigmentation, melanosome maturation), single lab\",\n      \"pmids\": [\"29443872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KIF13A is specifically required for delivery of AMPA receptors (AMPARs) to the spine surface during LTP induction; KIF13A depletion abolishes LTP expression. KIF13A interacts with centaurin-α1 as part of the transport machinery engaged with AMPARs upon LTP induction, and is responsible for remodeling Rab11-FIP2 endosomal structures in the dendritic shaft during LTP.\",\n      \"method\": \"Electrophysiology (LTP recording), biochemistry (Co-IP with centaurin-α1/AMPARs), imaging of Rab11-FIP2 endosomes, KIF13A depletion from hippocampal slices\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — electrophysiology plus Co-IP plus live imaging plus KD, multiple orthogonal methods establishing mechanism and pathway position\",\n      \"pmids\": [\"33999113\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"KIF13A and KIF3A coordinate to transport MT1-MMP-containing vesicles from the trans-Golgi to endosomes, while KIF13A alone transports vesicles from the endosome to the plasma membrane; KIF13A knockdown inhibits MT1-MMP-dependent collagen degradation and cancer cell invasion.\",\n      \"method\": \"siRNA knockdown, live-cell imaging (vesicle tracking), collagen degradation assay, invasion assay\",\n      \"journal\": \"Matrix biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD with specific functional readout plus live-cell imaging, single lab\",\n      \"pmids\": [\"35122963\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIF13A is a dedicated dendrite-selective kinesin in neurons; both KIF13A and KIF13B are maintained at the trans-Golgi network by interactions with the AP-1 adaptor complex, and interference with KIF13 binding to AP-1 disrupts dendrite- and axon-selective trafficking.\",\n      \"method\": \"Live-cell imaging in cultured hippocampal neurons, AP-1 interaction interference assay, polarized transport assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live-cell imaging plus AP-1 interaction interference with defined trafficking phenotype, single lab\",\n      \"pmids\": [\"38446634\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening KIF13A interaction with 14-3-3 proteins and causing KIF13A to dissociate from transferrin receptor (TfR)-containing vesicles at the proximal axon, thereby restricting TfR vesicle transport exclusively to dendrites. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles.\",\n      \"method\": \"Live-cell imaging, KIF13A knockout, BioID proximity labeling assay, MARK2 knockout, overexpression studies\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO plus BioID plus live imaging, multiple methods identifying phosphorylation-based regulatory mechanism, single lab\",\n      \"pmids\": [\"38709923\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MARK2 phosphorylates KIF13A at a 14-3-3 binding site to dissociate KIF13A from TfR-containing vesicles, preventing their axonal transport (preprint version of the published PNAS study).\",\n      \"method\": \"Live-cell imaging, KIF13A knockout, BioID assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — preprint duplicating published PNAS findings; not independently replicated as preprint\",\n      \"pmids\": [\"38105964\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"KIF13A is a plus end-directed, kinesin-3 family microtubule motor that transports diverse membrane cargoes—including M6PR, 5HT1AR, AMPA receptors, RhoB, MT1-MMP, and viral proteins—from the TGN and recycling endosomes to the plasma membrane via direct interaction with the AP-1 adaptor complex (through β1-adaptin) and Rab GTPases (RAB11, Rab22A, Rab10); Rab22A activates KIF13A by relieving proline-mediated autoinhibition to drive motor dimerization, while MARK2 phosphorylates KIF13A at a 14-3-3 binding site to restrict its cargo transport to dendrites, and KIF13A also drives recycling endosome tubule morphogenesis and is required for cytokinesis via midbody recruitment of FYVE-CENT.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF13A is a plus end-directed, microtubule-dependent kinesin motor that transports diverse membrane cargoes from the trans-Golgi network (TGN) and recycling endosomes to the plasma membrane [#0]. Its founding cargo route is established through a direct interaction with the AP-1 clathrin adaptor complex via \\u03b21-adaptin, which couples the motor to mannose-6-phosphate receptor (M6PR)-containing vesicles and controls cell-surface M6PR levels [#0, #11]. Beyond M6PR, KIF13A carries a broad cargo repertoire to the cell surface\\u2014the serotonin 5HT1A receptor through its FHA domain [#5], AMPA receptors during long-term potentiation [#12], RhoB through Rab11 recycling endosomes [#6], and MT1-MMP for collagen degradation and invasion [#13]\\u2014and is hijacked by influenza A vRNPs and arenavirus Z matrix proteins for delivery to the plasma membrane [#7, #8]. KIF13A is also required to generate and morphologically shape recycling endosome tubules, cooperating with RAB11, Rab10, and Rab22A [#3, #4, #10], and Rab22A activates the motor by binding its NC-CC1 region to relieve a proline-mediated autoinhibition that otherwise holds KIF13A as an inactive monomer, thereby licensing dimerization and processive force generation [#10]. In polarized neurons, KIF13A is held at the TGN by AP-1 and functions as a dendrite-selective motor whose cargo specificity is gated by MARK2 phosphorylation at a 14-3-3 binding motif, which strips the motor from transferrin-receptor vesicles to confine their transport to dendrites [#14, #15]. Independently, KIF13A is required for cytokinesis, translocating the FYVE-CENT (ZFYVE26)\\u2013TTC19 complex from the centrosome to the midbody in a PtdIns(3)P-dependent manner [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established KIF13A as a motor that links the AP-1 adaptor to cargo, answering how M6PR vesicles are delivered from the TGN to the cell surface.\",\n      \"evidence\": \"Reciprocal Co-IP with \\u03b21-adaptin, dominant-negative blockade, and cell-surface M6PR assay\",\n      \"pmids\": [\"11106728\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the motor's regulatory state (autoinhibition)\", \"Cargo repertoire beyond M6PR unknown at this stage\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Extended KIF13A\\u2013AP-1 cooperation to a tissue-specific role, showing it builds peripheral recycling endosomal subdomains required for melanosome cargo delivery.\",\n      \"evidence\": \"siRNA knockdown, immunocytochemistry, live imaging, and electron tomography in melanocytes\",\n      \"pmids\": [\"19841138\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of subdomain positioning not defined\", \"Did not identify the activating signal for the motor\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified an unexpected cell-division role, showing KIF13A delivers FYVE-CENT\\u2013TTC19 to the midbody, linking the motor to cytokinesis completion.\",\n      \"evidence\": \"siRNA knockdown with multinucleation readout, live imaging, Co-IP, and PI(3)K-III epistasis\",\n      \"pmids\": [\"20208530\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How PtdIns(3)P recruits the KIF13A cargo to microtubules is unresolved\", \"Direct vs indirect FYVE-CENT binding not mapped\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined a cargo-recognition module and an in vivo phenotype, showing the FHA domain directly binds 5HT1AR and that loss elevates anxiety in mice.\",\n      \"evidence\": \"In vitro reconstitution with motor+FHA minimotor, domain mapping, KO mouse behavior, knockdown surface-receptor assay\",\n      \"pmids\": [\"23438369\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"FHA-domain phospho-dependence of cargo binding not addressed\", \"Behavioral phenotype not mechanistically tied to single neuronal circuit\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showed viral exploitation of KIF13A, with arenavirus Z matrix protein using the motor for plasma-membrane delivery and virion production.\",\n      \"evidence\": \"Co-IP, overexpression, dominant-negative and siRNA blockade, VLP and infectious-titer assays\",\n      \"pmids\": [\"23279019\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Z-binding interface on KIF13A not mapped\", \"Single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Reframed KIF13A as a tubule-morphogenesis factor, demonstrating it generates recycling-endosome tubules from vacuolar sorting endosomes together with RAB11.\",\n      \"evidence\": \"siRNA knockdown, dominant-negative expression, live imaging, RAB11 pulldown\",\n      \"pmids\": [\"24462287\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanical model for tubule pulling not yet established\", \"RAB11 binding region not mapped here\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected KIF13A to upstream signaling and immune function, placing its expression downstream of mTORC1/IL-2/IL-7 to set surface M6PR on T cells.\",\n      \"evidence\": \"Rapamycin inhibition, siRNA knockdown, flow cytometry, Treg cytotoxicity assay\",\n      \"pmids\": [\"28496990\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcriptional vs post-transcriptional control by mTORC1 not distinguished\", \"Single lab\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showed influenza A virus uses KIF13A on Rab11 vesicles to deliver vRNPs to the cell surface, generalizing the motor's viral-hijack role.\",\n      \"evidence\": \"siRNA knockdown, overexpression, immunofluorescence, viral titer assay\",\n      \"pmids\": [\"29061883\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vRNP-motor link vs Rab11-mediated coupling not separated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linked KIF13A to cell-shape and motility control by routing RhoB through Rab11 endosomes to drive amoeboid migration of leukemia cells.\",\n      \"evidence\": \"siRNA knockdown, live imaging, 3D migration assay, Rab5/Rab11 trafficking analysis\",\n      \"pmids\": [\"30049714\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether RhoB is a direct cargo or indirect passenger unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Provided causal proof that the KIF13A\\u2013AP-1 interface is functionally essential, using a short \\u03b21-adaptin peptide to block pigmentation.\",\n      \"evidence\": \"Blocking-peptide treatment, pigmentation assay, 3D pigmented epidermis model\",\n      \"pmids\": [\"29443872\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Peptide specificity for KIF13A vs KIF13B not fully resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified Rab10 as a tubular-endosome partner requiring both the motor and Rab-binding homology domains of KIF13A for tubule formation.\",\n      \"evidence\": \"EGFP-Rab localization screen, Rab10 knockout, domain-deletion analysis, interaction assays\",\n      \"pmids\": [\"30700496\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional distinction between Rab10, Rab11 and Rab22A inputs not integrated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Resolved the activation mechanism, showing KIF13A is autoinhibited monomer relieved by Rab22A binding at NC-CC1 to permit dimerization and force generation.\",\n      \"evidence\": \"Single-molecule motility, dimerization assays, proline-substitution mutagenesis, Rab22A Co-IP, RE tubulation imaging\",\n      \"pmids\": [\"33536208\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether other Rabs (RAB11, Rab10) activate via the same mechanism not tested\", \"Structural model of the autoinhibited state not solved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Placed KIF13A in synaptic plasticity, showing it is required for AMPAR delivery and LTP and remodels dendritic Rab11-FIP2 endosomes via centaurin-\\u03b11.\",\n      \"evidence\": \"LTP electrophysiology, Co-IP with centaurin-\\u03b11/AMPARs, endosome imaging, knockdown in hippocampal slices\",\n      \"pmids\": [\"33999113\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct AMPAR-motor contact not defined\", \"Activity-dependent activation signal upstream unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed division of labor with KIF3A in two-step MT1-MMP delivery, tying KIF13A to invasive collagen degradation.\",\n      \"evidence\": \"siRNA knockdown, vesicle tracking, collagen degradation and invasion assays\",\n      \"pmids\": [\"35122963\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo handoff mechanism between KIF3A and KIF13A unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established KIF13A as a dendrite-selective neuronal motor held at the TGN by AP-1, with AP-1 binding required for polarized trafficking.\",\n      \"evidence\": \"Live imaging in hippocampal neurons, AP-1 interference, polarized transport assays\",\n      \"pmids\": [\"38446634\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How AP-1 retention is released for transport not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined the polarity-determining switch, showing MARK2 phosphorylation creates a 14-3-3 motif that strips KIF13A from TfR vesicles to confine transport to dendrites.\",\n      \"evidence\": \"Live imaging, KIF13A and MARK2 knockouts, BioID proximity labeling, overexpression\",\n      \"pmids\": [\"38709923\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of the 14-3-3-driven cargo release not solved\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the multiple Rab inputs (RAB11, Rab10, Rab22A), AP-1 retention, and MARK2/14-3-3 phosphoregulation are integrated to select among the diverse cargoes in a given cell type remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking activation, cargo selection, and polarity\", \"Structure of full-length autoinhibited and cargo-bound motor not solved\", \"Direct vs Rab-bridged cargo binding undefined for most cargoes\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 5, 10]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0, 5, 13]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 13, 14]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [2, 3, 4, 6]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 5, 8]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 6, 7]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 5, 13]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2, 3, 7]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [5, 12, 15]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [7, 8, 13]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"AP1B1\", \"RAB11\", \"RAB22A\", \"RAB10\", \"ZFYVE26\", \"MARK2\", \"YWHA\", \"KIF3A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}