{"gene":"MYO1D","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":2000,"finding":"Myr4 (the rat ortholog of MYO1D) functions as an actin-based mechanoenzyme required for membrane trafficking along the recycling endosome pathway in MDCK epithelial cells; calmodulin serves as its light chain, and polymerized actin is necessary for transfer of endocytosed markers from early endosomes to recycling endosomes.","method":"In vitro endosome transfer assay, calmodulin inhibition, actin polymerization perturbation, identification of myr4 as CaM target","journal":"Traffic","confidence":"High","confidence_rationale":"Tier 2 — in vitro functional assay with multiple perturbations (CaM inhibition, actin disruption) in a defined reconstituted system","pmids":["11208135"],"is_preprint":false},{"year":2002,"finding":"Myo1d (myosin-Ig/myr4) is expressed in rodent auditory and vestibular epithelia but at lower levels than Myo1b, Myo1c, and Myo1e; confirmed by RT-PCR with isozyme-selective amplification.","method":"RT-PCR with isozyme-selective primers in neonatal rodent inner ear epithelia","journal":"Journal of the Association for Research in Otolaryngology","confidence":"Medium","confidence_rationale":"Tier 3 — expression localization study with molecular confirmation but no functional loss-of-function readout","pmids":["12486594"],"is_preprint":false},{"year":2009,"finding":"Xenopus Myo1d protein is present from egg stages with increased expression at neurula through tadpole stages, and its mRNA is localized to neural tube, pre-somitic mesoderm, somites, and cranial neural crest cells during migration; a novel isoform-specific tail homology embedded in the TH1 domain was identified by sequence analysis.","method":"Western blot, whole-mount in situ hybridization, cDNA cloning and sequence analysis","journal":"Development, growth & differentiation","confidence":"Medium","confidence_rationale":"Tier 3 — direct localization experiment with developmental context but no functional perturbation","pmids":["19382939"],"is_preprint":false},{"year":2012,"finding":"Myosin-1d is expressed in axons and myelin compartments of mouse sciatic nerve, in Purkinje and granule cell layers of cerebellum, and expands along axonal tracts upon myelination onset; myosin-1d interacts with and is co-expressed with aspartoacylase (ASPA), an enzyme central to fatty acid synthesis in the nervous system.","method":"Immunofluorescence, co-immunoprecipitation (interaction with ASPA), Western blot across developmental stages","journal":"Brain research","confidence":"Medium","confidence_rationale":"Tier 3 — single Co-IP for ASPA interaction plus direct localization imaging","pmids":["22284616"],"is_preprint":false},{"year":2014,"finding":"Myo1d is expressed in myelinating oligodendrocytes of rat CNS, particularly enriched in the outer (abaxonal) and inner (adaxonal) cytoplasm-containing loops of myelin; expression increases during CNS white matter maturation and is low in PNS myelin.","method":"Immunofluorescence with isoform-specific antibody, Western blot during CNS development, cell culture","journal":"Journal of neuroscience research","confidence":"Medium","confidence_rationale":"Tier 3 — direct localization with isoform-specific reagent; no functional perturbation in this paper","pmids":["24903835"],"is_preprint":false},{"year":2015,"finding":"In Drosophila, Myo1D functions with Nesprin1 (dNesp1) to transport mRNAs from muscle nuclei to postsynaptic sites at the neuromuscular junction along F-actin-based 'railroad track' filaments; dNesp1 and Myo1D are mutually required for their localization to immature boutons, and loss of dNesp1 prevents mRNA localization and synaptic maturation.","method":"Genetic loss-of-function (dNesp1 mutants), live imaging, immunofluorescence, mRNA localization assays in Drosophila NMJ","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — clean KO phenotype with defined cellular readout (mRNA mislocalization, synaptic maturation defect) plus mutual localization dependence","pmids":["25959729"],"is_preprint":false},{"year":2015,"finding":"Myo1d knock-out rats show disrupted rotational planar cell polarity (PCP) in tracheal multi-ciliated epithelial cells: ciliary basal bodies lose unidirectional alignment (cilia splay radially), the asymmetric localization of PCP core protein Vangl1 is lost, and cilia-driven bead transport is impaired in velocity and linearity. In brain ependymal cells, left-right positioning of basal body clusters is lost, disrupting translational PCP.","method":"Rat knockout (Myo1d KO), scanning/transmission electron microscopy, immunofluorescence for Vangl1, bead transport assay","journal":"Cytoskeleton","confidence":"High","confidence_rationale":"Tier 2 — clean KO with multiple orthogonal readouts (EM, immunofluorescence, functional transport assay)","pmids":["26446290"],"is_preprint":false},{"year":2016,"finding":"siRNA-mediated knockdown of Myo1d in cultured oligodendrocytes causes retraction of processes, degeneration of myelin-like membrane, apoptosis, and impaired intracellular PLP (proteolipid protein) transport; Myo1d co-localizes with actin filaments, CNPase, and partially with PLP at the leading edge of myelin-like membrane in differentiated OLs.","method":"siRNA knockdown in primary rat oligodendrocyte cultures, immunofluorescence, live-cell morphology analysis","journal":"ASN Neuro","confidence":"Medium","confidence_rationale":"Tier 2 — defined KD phenotype with specific cellular readout (PLP transport, morphology, apoptosis)","pmids":["27655972"],"is_preprint":false},{"year":2017,"finding":"In a cuprizone-induced demyelination mouse model, stereotaxic siRNA knockdown of Myo1d in corpus callosum decreases MBP and PLP immunofluorescence intensity during remyelination, increases pro-inflammatory microglia and astrocytes, decreases anti-inflammatory microglia, and increases caspase-3-positive oligodendrocytes, indicating Myo1d is required for successful remyelination in vivo.","method":"In vivo siRNA injection (stereotaxic), cuprizone demyelination model, immunohistochemistry, cell counting","journal":"Neurochemical research","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo KD with defined cellular phenotype (remyelination failure, inflammatory shift)","pmids":["28986688"],"is_preprint":false},{"year":2018,"finding":"Myosin1D (Myo1D) is an evolutionarily conserved regulator of left-right asymmetry in zebrafish: it is required for formation and function of Kupffer's vesicle (KV, the LR organizer), controls orientation of KV cilia, and interacts functionally with the PCP pathway component VanGogh-like2 (Vangl2) to establish productive LRO flow and organ laterality.","method":"Zebrafish myo1d morpholino knockdown, ciliary imaging, flow analysis, genetic interaction with Vangl2 morphants","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — morpholino KD with multiple orthogonal readouts (cilia orientation, fluid flow, organ situs) plus genetic epistasis with PCP component","pmids":["29769531"],"is_preprint":false},{"year":2018,"finding":"Morpholino-mediated myo1d downregulation in Xenopus disrupts organ placement, impairs Nodal cascade induction, compromises dand5 expression and LRO cilia (shorter, fewer, non-polarized), inhibits convergent extension, and downregulates a non-canonical Wnt (ATF2) reporter; genetic interference shows functional interaction between vangl2 and myo1d in LR axis formation, placing Myo1d in the PCP pathway.","method":"Xenopus morpholino knockdown, in situ hybridization, cilia analysis, convergent extension assay, ATF2 reporter, vangl2 genetic interaction","journal":"Current Biology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods in a second vertebrate model, with genetic epistasis establishing PCP pathway placement","pmids":["29478852"],"is_preprint":false},{"year":2019,"finding":"MYO1D functions to anchor unphosphorylated EGFR family members (EGFR, ErbB2, ErbB4 but not ErbB3) to the plasma membrane via direct binding between the β-meander motif in MYO1D's C-terminal tail domain and the kinase domains of EGFRs; expression of the tail domain alone suppresses the oncogenic action of full-length MYO1D. Overexpression of MYO1D increases colorectal and breast cancer cell motility and viability by upregulating EGFR levels and promotes colorectal tumor progression in a syngeneic mouse model.","method":"Co-immunoprecipitation, co-localization, domain mapping (tail domain expression), syngeneic mouse tumor model, cell viability/motility assays","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP with domain dissection, in vivo tumor model, multiple cell line functional assays","pmids":["31420606"],"is_preprint":false},{"year":2020,"finding":"In Drosophila, Myo1D-dependent localization of the initiator caspase Dronc to the plasma membrane of mature enterocytes (ECs) is required for homeostatic intestinal stem cell (ISC) activity; in Myo1D mutant midguts, ROS generation, hemocyte recruitment, and JNK signaling are all reduced, indicating Myo1D-dependent Dronc membrane localization in ECs drives the signals that stimulate ISC mitosis.","method":"Drosophila Myo1D mutant analysis, live imaging of midgut, ROS assay, JNK signaling reporters, hemocyte recruitment assay","journal":"Cell Reports","confidence":"High","confidence_rationale":"Tier 2 — clean genetic KO with multiple defined signaling readouts and mechanistic pathway placement","pmids":["33238125"],"is_preprint":false},{"year":2022,"finding":"In Drosophila apoptosis-induced proliferation (AiP), Myo1D localizes the initiator caspase Dronc to the cell cortex; F-actin accumulates in a Dronc-dependent manner and drives ROS production and JNK activation. LIMK1 promotes F-actin polymerization downstream of Dronc, and the synergistic effects of co-expressed Dronc and LIMK1 on F-actin accumulation, ROS, and JNK activation require Myo1D, placing Myo1D as essential for cortical Dronc-driven AiP signaling.","method":"Drosophila genetic epistasis (myo1d, limk1, dronc), ROS assay, JNK reporter, F-actin staining, co-expression experiments","journal":"PLoS Genetics","confidence":"High","confidence_rationale":"Tier 2 — multiple genetic epistasis experiments with defined biochemical readouts placing Myo1D in the Dronc-LIMK1-F-actin-ROS-JNK pathway","pmids":["36469525"],"is_preprint":false},{"year":2022,"finding":"SPAG6 interacts with MYO1D (shown by immunoprecipitation and mass spectrometry) and overexpression of SPAG6 promotes translocation of MYO1D from cytosol to the cell membrane, thereby upregulating EGFR family expression and activating PI3K/AKT and ERK signaling to promote AML cell proliferation and migration.","method":"Co-immunoprecipitation, mass spectrometry, subcellular fractionation, flow cytometry, xenograft mouse model","journal":"Blood Advances","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP/MS for interaction plus functional KD/OE with defined signaling readout, but single-lab study","pmids":["35667090"],"is_preprint":false},{"year":2022,"finding":"miR-217-5p directly targets Myo1d (validated by luciferase assay, qRT-PCR, and Western blot), and its overexpression in podocytes causes shrunken cells with abnormal actin cytoskeletons, suggesting Myo1d plays a role in podocyte morphogenesis and actin organization.","method":"Luciferase reporter assay, qRT-PCR, Western blot, miRNA overexpression in E11 podocyte cells","journal":"Non-coding RNA","confidence":"Medium","confidence_rationale":"Tier 3 — validated miRNA-target relationship with associated morphological phenotype; functional role of Myo1d itself inferred indirectly","pmids":["35736640"],"is_preprint":false},{"year":2023,"finding":"Drosophila Myo1D has a 12.5-fold higher actin-activated steady-state ATPase rate than Myo1C, an 8-fold higher MgADP release rate, and MgADP release (not phosphate release) is the rate-limiting step for Myo1D, whereas phosphate release is rate-limiting for Myo1C. Both myosins have among the tightest MgADP affinities measured for any myosin. Myo1D propels actin filaments at higher speeds and robustly transports 50 nm unilamellar vesicles along actin filaments in vitro, consistent with a transport motor role.","method":"Steady-state ATPase assay, transient kinetics (stopped-flow), in vitro actin gliding assay, liposome transport assay","journal":"The Journal of Biological Chemistry","confidence":"High","confidence_rationale":"Tier 1 — reconstituted in vitro mechanochemical analysis with multiple quantitative kinetic methods and functional transport assay","pmids":["37380077"],"is_preprint":false},{"year":2023,"finding":"KITENIN complex component MYO1D is required for KITENIN-mediated aerobic glycolysis in colorectal cancer cells; silencing MYO1D downregulates glycolytic proton efflux rate and expression of glycolytic enzymes (GLUT1, HK2, PKM2, LDHA).","method":"siRNA knockdown of MYO1D, glycolytic flux assay (Seahorse), protein expression analysis","journal":"Cell & Bioscience","confidence":"Medium","confidence_rationale":"Tier 2 — defined KD phenotype with quantitative metabolic readout, but pathway placement is within the KITENIN complex context","pmids":["37553596"],"is_preprint":false},{"year":2024,"finding":"Single-molecule imaging in Drosophila macrophages shows Myo1D exhibits a significantly smaller slow-diffusing population on the plasma membrane compared to Myo1C; this difference is contingent on both head and tail domains of Myo1C and the two myosins do not mutually influence each other's membrane diffusion, suggesting distinct membrane interaction mechanisms underlie their opposite chirality-determining activities.","method":"Single-molecule imaging (TIRF/PALM) in live Drosophila macrophages, diffusion coefficient analysis","journal":"Genes to Cells","confidence":"Medium","confidence_rationale":"Tier 1-2 — quantitative single-molecule biophysics in living cells; mechanistic link to chirality is proposed but not directly tested with loss-of-function","pmids":["38454557"],"is_preprint":false},{"year":2025,"finding":"MYO1D preferentially binds PDGFRα/β heterodimers and promotes their internalization from the plasma membrane into early endosomes; knockdown of MYO1D causes retention of PDGFRα/β heterodimers at the plasma membrane, leading to increased ERK1/2 phosphorylation and increased cell proliferation, identifying MYO1D as a negative regulator of PDGFRα/β heterodimer signaling through receptor trafficking.","method":"Bimolecular fluorescence complementation, AP-MS interactome, siRNA knockdown, phospho-ERK1/2 immunoblot, cell proliferation assay","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 2 — AP-MS identification of interaction confirmed functionally with KD and defined signaling/proliferation readouts; published peer-reviewed with independent methods","pmids":["40404618"],"is_preprint":false},{"year":2025,"finding":"Myo1D in Drosophila macrophages directs clockwise circumferential F-actin flow, while Myo1C directs counterclockwise flow; both depend on Myosin2 (Myo2). In a modified in vitro motility assay at near-physiological actin concentrations, Myo1D triggers self-organization of a clockwise-rotating chiral F-actin ring, implying Myo1D organizes parallelly polarized (barbed-end-biased) F-actin bundles to drive dextral cell chirality through Myo2-driven circumferential flow.","method":"Live-cell F-actin flow imaging in Drosophila macrophages, modified in vitro motility assay, genetic perturbation of Myo2","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution plus live-cell imaging, but preprint and single-lab","pmids":["bio_10.1101_2025.05.06.648335"],"is_preprint":true},{"year":2025,"finding":"In Drosophila wing disc regeneration after ionizing radiation, Myo1D ensures survival of Dronc-activating apoptosis-resistant (DARE) cells by preventing lethal effector caspase activation; without Myo1D, DARE cells undergo apoptosis, disrupting compensatory proliferation and tissue regeneration.","method":"Drosophila Myo1D genetic loss-of-function in wing imaginal discs, delayed Dronc reporter, effector caspase assays, proliferation quantification","journal":"Nature Communications","confidence":"Medium","confidence_rationale":"Tier 2 — clean genetic KO with specific cellular survival phenotype, but mechanistic detail of how Myo1D prevents caspase activation is not fully resolved","pmids":["41345088"],"is_preprint":false}],"current_model":"MYO1D is an unconventional class I myosin that uses its actin-based motor activity (characterized by high ATPase rate, fast MgADP release, and robust vesicle transport kinetics) to link membranes to the actin cytoskeleton, thereby performing several distinct cellular functions: anchoring unphosphorylated EGFR family receptors and PDGFRα/β heterodimers at or promoting their internalization from the plasma membrane to regulate receptor-level signaling; driving recycling endosome membrane trafficking in epithelial cells; directing rotational and translational planar cell polarity in ciliated epithelia; localizing the initiator caspase Dronc to the plasma membrane to regulate apoptosis-induced compensatory proliferation and homeostatic intestinal stem cell activity in Drosophila; promoting mRNA transport to postsynaptic sites at the NMJ in concert with Nesprin1; supporting oligodendrocyte myelin membrane dynamics and remyelination; and acting as an evolutionarily conserved regulator of left-right asymmetry by controlling LR organizer cilia orientation and function through functional interactions with the planar cell polarity pathway (Vangl2), with Myo1D's motor domain chirality (clockwise F-actin movement) providing the cellular basis for dextral organ asymmetry."},"narrative":{"teleology":[{"year":2000,"claim":"Establishing MYO1D as a membrane-trafficking motor: prior to this work it was unknown whether class I myosins participated in endosomal sorting; reconstituted assays demonstrated that Myr4/MYO1D, with calmodulin as its light chain, is required for actin-dependent transfer of cargo from early endosomes to recycling endosomes.","evidence":"In vitro endosome transfer assay in MDCK cells with calmodulin inhibition and actin polymerization perturbation","pmids":["11208135"],"confidence":"High","gaps":["No structural basis for how MYO1D selects recycling endosome membranes","Whether this trafficking role extends to non-epithelial cells was untested"]},{"year":2012,"claim":"Expanding MYO1D's tissue repertoire to the nervous system: MYO1D was found in axonal and myelin compartments, interacting with aspartoacylase (ASPA), suggesting a previously unrecognized role in myelination-related lipid metabolism.","evidence":"Co-immunoprecipitation of MYO1D with ASPA, immunofluorescence in mouse sciatic nerve and cerebellum","pmids":["22284616"],"confidence":"Medium","gaps":["Single Co-IP for ASPA interaction without reciprocal validation","Functional consequence of MYO1D-ASPA interaction untested","No loss-of-function data in this study"]},{"year":2015,"claim":"Demonstrating MYO1D as a planar cell polarity effector: knockout rats revealed that MYO1D is required for unidirectional basal body alignment and Vangl1 polarization in multi-ciliated epithelia, resolving how actin-based motors contribute to rotational and translational PCP.","evidence":"Myo1d knockout rat with SEM/TEM, Vangl1 immunofluorescence, and bead transport assay in tracheal and ependymal epithelia","pmids":["26446290"],"confidence":"High","gaps":["Whether MYO1D directly binds PCP core components or acts indirectly was unresolved","Mechanism linking motor activity to basal body rotation unknown"]},{"year":2015,"claim":"Revealing a postsynaptic mRNA transport function: MYO1D and Nesprin1 were shown to be mutually dependent for localization to immature boutons and required for actin-based mRNA delivery to postsynaptic sites at the Drosophila NMJ, establishing a motor-scaffold partnership for local translation.","evidence":"Genetic loss-of-function in Drosophila, mRNA localization assays, immunofluorescence at NMJ","pmids":["25959729"],"confidence":"High","gaps":["Identity of transported mRNAs not fully catalogued","Whether this mechanism operates at mammalian synapses unknown"]},{"year":2016,"claim":"Confirming a cell-autonomous role in oligodendrocyte survival and myelin membrane dynamics: MYO1D knockdown caused process retraction, impaired PLP transport, and apoptosis in oligodendrocytes, directly linking MYO1D motor function to myelin sheath integrity.","evidence":"siRNA knockdown in primary rat oligodendrocyte cultures with live-cell morphology and PLP trafficking analysis","pmids":["27655972"],"confidence":"Medium","gaps":["Whether the apoptosis is a direct consequence of PLP mistrafficking or a parallel effect was unclear","No rescue experiment reported"]},{"year":2017,"claim":"Extending MYO1D's myelin role in vivo: stereotaxic knockdown during cuprizone-induced demyelination impaired remyelination and shifted glial inflammatory profiles, establishing MYO1D as required for CNS repair.","evidence":"In vivo siRNA injection in corpus callosum, cuprizone model, immunohistochemistry","pmids":["28986688"],"confidence":"Medium","gaps":["siRNA specificity controls not fully detailed","Whether the inflammatory shift is cell-autonomous to oligodendrocytes or secondary was unresolved"]},{"year":2018,"claim":"Establishing MYO1D as a conserved determinant of vertebrate left-right asymmetry: morpholino knockdown in both zebrafish and Xenopus disrupted LR organizer cilia orientation, Nodal cascade activation, and organ situs, with genetic epistasis placing MYO1D in the PCP (Vangl2) pathway.","evidence":"Morpholino knockdown in zebrafish and Xenopus with cilia imaging, fluid flow analysis, in situ hybridization, convergent extension assays, and Vangl2 genetic interaction","pmids":["29769531","29478852"],"confidence":"High","gaps":["Whether MYO1D physically binds Vangl2 or acts in parallel was unresolved","The intrinsic chirality mechanism of MYO1D motor was not yet characterized"]},{"year":2019,"claim":"Identifying MYO1D as a direct membrane anchor for EGFR family receptors: the β-meander motif in MYO1D's tail was shown to bind EGFR kinase domains and stabilize receptors at the plasma membrane, with overexpression promoting tumor progression via upregulated EGFR signaling.","evidence":"Reciprocal Co-IP, domain mapping, syngeneic mouse tumor model, cell viability/motility assays in colorectal and breast cancer lines","pmids":["31420606"],"confidence":"High","gaps":["Whether MYO1D-EGFR interaction occurs in normal physiology or only in overexpression contexts","Structural basis of the β-meander–kinase domain interface not resolved"]},{"year":2020,"claim":"Defining MYO1D's role in non-apoptotic caspase signaling: MYO1D-dependent membrane localization of Dronc in mature enterocytes was shown to drive ROS, hemocyte recruitment, and JNK signaling that sustains homeostatic intestinal stem cell proliferation.","evidence":"Drosophila Myo1D mutant midgut analysis with ROS, JNK reporters, hemocyte imaging","pmids":["33238125"],"confidence":"High","gaps":["How MYO1D physically tethers Dronc to the membrane was not determined","Whether this mechanism operates in mammalian intestinal stem cells unknown"]},{"year":2022,"claim":"Placing MYO1D in the Dronc–LIMK1–F-actin–ROS–JNK cascade: genetic epistasis showed that MYO1D is required for the synergistic F-actin accumulation and ROS/JNK activation driven by co-expressed Dronc and LIMK1 during apoptosis-induced proliferation.","evidence":"Drosophila genetic epistasis with myo1d, limk1, dronc; F-actin staining, ROS and JNK reporter assays","pmids":["36469525"],"confidence":"High","gaps":["Direct biochemical interaction between MYO1D and LIMK1 not shown","Whether MYO1D motor activity or only membrane tethering is required was untested"]},{"year":2022,"claim":"Connecting MYO1D to EGFR signaling through SPAG6: SPAG6 was identified as an interactor that promotes MYO1D translocation to the plasma membrane, upregulating EGFR family expression and PI3K/AKT and ERK signaling in AML cells.","evidence":"Co-IP/mass spectrometry, subcellular fractionation, xenograft mouse model in AML cells","pmids":["35667090"],"confidence":"Medium","gaps":["Whether SPAG6 directly binds MYO1D or acts through an intermediary not fully resolved","Single-lab finding awaiting independent confirmation"]},{"year":2023,"claim":"Characterizing MYO1D's intrinsic motor properties: reconstituted kinetics revealed MYO1D has a 12.5-fold higher ATPase rate than MYO1C, with MgADP release as its rate-limiting step, and demonstrated robust vesicle transport and clockwise actin gliding consistent with a fast transport motor that could underlie dextral chirality.","evidence":"Steady-state ATPase, stopped-flow transient kinetics, in vitro actin gliding and liposome transport assays with Drosophila MYO1D","pmids":["37380077"],"confidence":"High","gaps":["Whether mammalian MYO1D shares identical kinetic properties not confirmed","Structural basis for clockwise vs. counterclockwise movement not resolved"]},{"year":2025,"claim":"Revealing MYO1D as a negative regulator of PDGFRα/β heterodimer signaling: MYO1D preferentially binds and internalizes PDGFRα/β heterodimers; its loss retains receptors at the plasma membrane, amplifying ERK1/2 signaling and proliferation — establishing a receptor-trafficking function opposite to its EGFR-stabilizing role.","evidence":"Bimolecular fluorescence complementation, AP-MS, siRNA knockdown with phospho-ERK1/2 and proliferation readouts","pmids":["40404618"],"confidence":"High","gaps":["How MYO1D distinguishes PDGFR heterodimers from homodimers mechanistically unclear","Whether this trafficking role involves the same tail domain β-meander used for EGFR binding untested"]},{"year":2025,"claim":"Demonstrating that MYO1D ensures survival of apoptosis-resistant cells during tissue regeneration: without MYO1D, DARE cells in irradiated wing discs undergo lethal effector caspase activation, disrupting compensatory proliferation and regeneration.","evidence":"Drosophila Myo1D loss-of-function in wing imaginal discs, delayed Dronc reporter, effector caspase assays","pmids":["41345088"],"confidence":"Medium","gaps":["Precise mechanism by which MYO1D prevents effector caspase activation not fully resolved","Whether this anti-apoptotic function depends on Dronc membrane tethering not directly shown"]},{"year":null,"claim":"Key unresolved questions include the structural basis of MYO1D's intrinsic chirality, whether its EGFR-anchoring and PDGFR-internalizing roles use the same or distinct tail-domain interfaces, how MYO1D physically tethers Dronc to the plasma membrane, and whether the PCP-related and chirality functions are conserved in mammals.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal structure of MYO1D tail domain in complex with any receptor","No mammalian loss-of-function model for left-right asymmetry","Direct MYO1D–Dronc binding mechanism unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[0,16]},{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,5,16,20]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[6,7,16,20]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[6,11,12,13,14,18,19]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,5,7,16,20]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,19]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[14]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[6,9,10]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,7,19]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[9,10,11,14,19]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[9,10]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[12,13,21]}],"complexes":[],"partners":["EGFR","ERBB2","ERBB4","VANGL2","SPAG6","ASPA","NESPRIN1","PDGFRA"],"other_free_text":[]},"mechanistic_narrative":"MYO1D is an unconventional class I myosin that couples actin-based motor activity to membrane dynamics, serving as a versatile linker between the actin cytoskeleton and cellular membranes in contexts ranging from vesicle trafficking to organ laterality. Its motor domain exhibits a high actin-activated ATPase rate with MgADP release as the rate-limiting step, enabling robust vesicle transport along actin filaments and driving clockwise F-actin organization that underlies dextral cell chirality [PMID:37380077, PMID:29769531, PMID:29478852]. MYO1D anchors unphosphorylated EGFR family receptors at the plasma membrane to regulate receptor-level signaling, promotes PDGFRα/β heterodimer internalization into early endosomes to negatively regulate ERK signaling, localizes the initiator caspase Dronc to the cell cortex to drive apoptosis-induced compensatory proliferation, and directs rotational and translational planar cell polarity in ciliated epithelia through functional interaction with Vangl2 [PMID:31420606, PMID:40404618, PMID:36469525, PMID:26446290]. MYO1D also supports oligodendrocyte myelin membrane maintenance and remyelination in the CNS, and cooperates with Nesprin1 for actin-dependent mRNA transport to postsynaptic sites at the neuromuscular junction [PMID:27655972, PMID:28986688, PMID:25959729]."},"prefetch_data":{"uniprot":{"accession":"O94832","full_name":"Unconventional myosin-Id","aliases":[],"length_aa":1006,"mass_kda":116.2,"function":"Unconventional myosin that functions as actin-based motor protein with ATPase activity (By similarity). Plays a role in endosomal protein trafficking, and especially in the transfer of cargo proteins from early to recycling endosomes (By similarity). Required for normal planar cell polarity in ciliated tracheal cells, for normal rotational polarity of cilia, and for coordinated, unidirectional ciliary movement in the trachea. Required for normal, polarized cilia organization in brain ependymal epithelial cells (By similarity)","subcellular_location":"Cytoplasm; Perikaryon; Cell projection, dendrite; Early endosome; Cytoplasm, cell cortex","url":"https://www.uniprot.org/uniprotkb/O94832/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYO1D","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CALM1","stoichiometry":0.2},{"gene":"CALM2","stoichiometry":0.2},{"gene":"CALM3","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MYO1D","total_profiled":1310},"omim":[{"mim_id":"606539","title":"MYOSIN ID; MYO1D","url":"https://www.omim.org/entry/606539"},{"mim_id":"606538","title":"MYOSIN IC; MYO1C","url":"https://www.omim.org/entry/606538"},{"mim_id":"601480","title":"MYOSIN IF; MYO1F","url":"https://www.omim.org/entry/601480"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"blood vessel","ntpm":223.6},{"tissue":"intestine","ntpm":104.3}],"url":"https://www.proteinatlas.org/search/MYO1D"},"hgnc":{"alias_symbol":["KIAA0727","myr4","PPP1R108"],"prev_symbol":[]},"alphafold":{"accession":"O94832","domains":[{"cath_id":"3.30.70.1590","chopping":"630-704","consensus_level":"medium","plddt":90.5696,"start":630,"end":704},{"cath_id":"2.30.29.30","chopping":"797-1005","consensus_level":"high","plddt":88.4387,"start":797,"end":1005},{"cath_id":"1.20.5","chopping":"751-792","consensus_level":"medium","plddt":89.3957,"start":751,"end":792}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O94832","model_url":"https://alphafold.ebi.ac.uk/files/AF-O94832-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O94832-F1-predicted_aligned_error_v6.png","plddt_mean":88.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYO1D","jax_strain_url":"https://www.jax.org/strain/search?query=MYO1D"},"sequence":{"accession":"O94832","fasta_url":"https://rest.uniprot.org/uniprotkb/O94832.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O94832/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O94832"}},"corpus_meta":[{"pmid":"28403887","id":"PMC_28403887","title":"Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression.","date":"2017","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/28403887","citation_count":83,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25006744","id":"PMC_25006744","title":"Genome-wide association identifies regulatory Loci associated with distinct local histogram emphysema patterns.","date":"2014","source":"American journal of respiratory and critical care medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25006744","citation_count":71,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11208135","id":"PMC_11208135","title":"Both calmodulin and the unconventional myosin Myr4 regulate membrane trafficking along the recycling pathway of MDCK cells.","date":"2000","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/11208135","citation_count":67,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20071333","id":"PMC_20071333","title":"Myosin 1G is an abundant class I myosin in lymphocytes whose localization at the plasma membrane depends on its ancient divergent pleckstrin homology (PH) domain (Myo1PH).","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20071333","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29769531","id":"PMC_29769531","title":"Myosin1D is an evolutionarily conserved regulator of animal left-right asymmetry.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29769531","citation_count":57,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26547929","id":"PMC_26547929","title":"Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma.","date":"2015","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/26547929","citation_count":56,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12486594","id":"PMC_12486594","title":"Myosin-I isozymes in neonatal rodent auditory and vestibular epithelia.","date":"2002","source":"Journal of the Association for Research in Otolaryngology : JARO","url":"https://pubmed.ncbi.nlm.nih.gov/12486594","citation_count":55,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32075880","id":"PMC_32075880","title":"Coimmunoprecipitation with MYR1 Identifies Three Additional Proteins within the Toxoplasma gondii Parasitophorous Vacuole Required for Translocation of Dense Granule Effectors into Host Cells.","date":"2020","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/32075880","citation_count":51,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17376794","id":"PMC_17376794","title":"High density SNP association study of a major autism linkage region on chromosome 17.","date":"2007","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/17376794","citation_count":45,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29478852","id":"PMC_29478852","title":"A Conserved Role of the Unconventional Myosin 1d in Laterality Determination.","date":"2018","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/29478852","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25705109","id":"PMC_25705109","title":"Coding and noncoding expression patterns associated with rare obesity-related disorders: Prader-Willi and Alström syndromes.","date":"2015","source":"Advances in genomics and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25705109","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26446290","id":"PMC_26446290","title":"Myosin Id is required for planar cell polarity in ciliated tracheal and ependymal epithelial cells.","date":"2015","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/26446290","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33823999","id":"PMC_33823999","title":"Conception by fertility treatment and offspring deoxyribonucleic acid methylation.","date":"2021","source":"Fertility and sterility","url":"https://pubmed.ncbi.nlm.nih.gov/33823999","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26801966","id":"PMC_26801966","title":"Selective localization of myosin-I proteins in macropinosomes and actin waves.","date":"2016","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/26801966","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25959729","id":"PMC_25959729","title":"Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization.","date":"2015","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/25959729","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31420606","id":"PMC_31420606","title":"MYO1D binds with kinase domain of the EGFR family to anchor them to plasma membrane before their activation and contributes carcinogenesis.","date":"2019","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/31420606","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36469525","id":"PMC_36469525","title":"Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation.","date":"2022","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36469525","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22284616","id":"PMC_22284616","title":"Expression and localization of myosin-1d in the developing nervous system.","date":"2012","source":"Brain research","url":"https://pubmed.ncbi.nlm.nih.gov/22284616","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22906644","id":"PMC_22906644","title":"Genome-wide DNA methylation profiling of CpG islands in hypospadias.","date":"2012","source":"The Journal of urology","url":"https://pubmed.ncbi.nlm.nih.gov/22906644","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33238125","id":"PMC_33238125","title":"Transiently \"Undead\" Enterocytes Mediate Homeostatic Tissue Turnover in the Adult Drosophila Midgut.","date":"2020","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/33238125","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17975799","id":"PMC_17975799","title":"Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2.","date":"2007","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/17975799","citation_count":15,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28986688","id":"PMC_28986688","title":"Unconventional Myosin ID is Involved in Remyelination After Cuprizone-Induced Demyelination.","date":"2017","source":"Neurochemical research","url":"https://pubmed.ncbi.nlm.nih.gov/28986688","citation_count":14,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35667090","id":"PMC_35667090","title":"Upregulated SPAG6 promotes acute myeloid leukemia progression through MYO1D that regulates the EGFR family expression.","date":"2022","source":"Blood advances","url":"https://pubmed.ncbi.nlm.nih.gov/35667090","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23433184","id":"PMC_23433184","title":"Transcriptome analysis of Inbred Long Sleep and Inbred Short Sleep mice.","date":"2013","source":"Genes, brain, and behavior","url":"https://pubmed.ncbi.nlm.nih.gov/23433184","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37553596","id":"PMC_37553596","title":"KITENIN promotes aerobic glycolysis through PKM2 induction by upregulating the c-Myc/hnRNPs axis in colorectal cancer.","date":"2023","source":"Cell & bioscience","url":"https://pubmed.ncbi.nlm.nih.gov/37553596","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24903835","id":"PMC_24903835","title":"Unconventional myosin ID is expressed in myelinating oligodendrocytes.","date":"2014","source":"Journal of neuroscience research","url":"https://pubmed.ncbi.nlm.nih.gov/24903835","citation_count":11,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34589502","id":"PMC_34589502","title":"Novel MYO1D Missense Variant Identified Through Whole Exome Sequencing and Computational Biology Analysis Expands the Spectrum of Causal Genes of Laterality Defects.","date":"2021","source":"Frontiers in medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34589502","citation_count":10,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27655972","id":"PMC_27655972","title":"Knockdown of Unconventional Myosin ID Expression Induced Morphological Change in Oligodendrocytes.","date":"2016","source":"ASN neuro","url":"https://pubmed.ncbi.nlm.nih.gov/27655972","citation_count":10,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31774725","id":"PMC_31774725","title":"Basic-hydrophobic sites are localized in conserved positions inside and outside of PH domains and affect localization of Dictyostelium myosin 1s.","date":"2019","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/31774725","citation_count":9,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35303583","id":"PMC_35303583","title":"Identification of metastasis-associated exoDEPs in colorectal cancer using label-free proteomics.","date":"2022","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35303583","citation_count":9,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37380077","id":"PMC_37380077","title":"Drosophila class-I myosins that can impact left-right asymmetry have distinct ATPase kinetics.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37380077","citation_count":8,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32335295","id":"PMC_32335295","title":"Proteome alterations associated with the oleic acid and cis-9, trans-11 conjugated linoleic acid content in bovine skeletal muscle.","date":"2020","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/32335295","citation_count":8,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"40404618","id":"PMC_40404618","title":"PDGFRα/β heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40404618","citation_count":4,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37370186","id":"PMC_37370186","title":"Quantification of hematopoietic stem and progenitor cells by targeted DNA methylation analysis.","date":"2023","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/37370186","citation_count":4,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32734648","id":"PMC_32734648","title":"Dictyostelium myosin 1F and myosin 1E inhibit actin waves in a lipid-binding-dependent and motor-independent manner.","date":"2020","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/32734648","citation_count":4,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25915513","id":"PMC_25915513","title":"Isobaric Tags for Relative and Absolute Quantitation-Based Proteomic Analysis of Patent and Constricted Ductus Arteriosus Tissues Confirms the Systemic Regulation of Ductus Arteriosus Closure.","date":"2015","source":"Journal of cardiovascular pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/25915513","citation_count":4,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21567867","id":"PMC_21567867","title":"Using osteoclast differentiation as a model for gene discovery in an undergraduate cell biology laboratory.","date":"2010","source":"Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology","url":"https://pubmed.ncbi.nlm.nih.gov/21567867","citation_count":4,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30733659","id":"PMC_30733659","title":"An Interstitial 17q11.2 de novo Deletion Involving the CDK5R1 Gene in a High-Functioning Autistic Patient.","date":"2018","source":"Molecular syndromology","url":"https://pubmed.ncbi.nlm.nih.gov/30733659","citation_count":4,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28828543","id":"PMC_28828543","title":"Expression of Unconventional Myosin VI in Oligodendrocytes.","date":"2017","source":"Neurochemical research","url":"https://pubmed.ncbi.nlm.nih.gov/28828543","citation_count":4,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"40205688","id":"PMC_40205688","title":"Conserved Phosphorylation of the Myosin1e TH1 Domain Impacts Membrane Association and Function in Yeast and Worms.","date":"2025","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/40205688","citation_count":2,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"41153936","id":"PMC_41153936","title":"Comparative Transcriptome Analysis Reveals the Role of the FST Gene in Goose Muscle Development.","date":"2025","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/41153936","citation_count":2,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29998805","id":"PMC_29998805","title":"Genetic Determinants of Cerebral Arterial Adaptation to Flow-loading.","date":"2018","source":"Current neurovascular research","url":"https://pubmed.ncbi.nlm.nih.gov/29998805","citation_count":2,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35736640","id":"PMC_35736640","title":"The Role of miR-217-5p in the Puromycin Aminonucleoside-Induced Morphological Change of Podocytes.","date":"2022","source":"Non-coding RNA","url":"https://pubmed.ncbi.nlm.nih.gov/35736640","citation_count":2,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"39095343","id":"PMC_39095343","title":"Myosin1G promotes Nodal signaling to control zebrafish left-right asymmetry.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39095343","citation_count":2,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19382939","id":"PMC_19382939","title":"Developmental expression of Xenopus myosin 1d and identification of a myo1d tail homology that overlaps TH1.","date":"2009","source":"Development, growth & differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/19382939","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"41345088","id":"PMC_41345088","title":"Apoptosis-resistant cells drive compensatory proliferation via cell-autonomous and non-autonomous functions of the initiator caspase Dronc.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41345088","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38454557","id":"PMC_38454557","title":"Left-right Myosin-Is, Myosin1C, and Myosin1D exhibit distinct single molecule behaviors on the plasma membrane of Drosophila macrophages.","date":"2024","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/38454557","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38234806","id":"PMC_38234806","title":"PDGFRα/β heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38234806","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"39974789","id":"PMC_39974789","title":"Drone pupae extract enhances Hanwoo myosatellite cell function for cultivated meat production.","date":"2025","source":"Journal of animal science and technology","url":"https://pubmed.ncbi.nlm.nih.gov/39974789","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37131609","id":"PMC_37131609","title":"Spatial transcriptome profiling uncovers metabolic regulation of left-right patterning.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/37131609","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"39282309","id":"PMC_39282309","title":"The Initiator Caspase Dronc Drives Compensatory Proliferation of Apoptosis-Resistant Cells During Epithelial Tissue Regeneration After Ionizing Radiation.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39282309","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25580325","id":"PMC_25580325","title":"Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene.","date":"2014","source":"Case reports in oncological medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25580325","citation_count":0,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"41186840","id":"PMC_41186840","title":"Integration of exosome-related genes and differential expression analysis reveals potential biomarkers for prostate cancer.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41186840","citation_count":0,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"40467998","id":"PMC_40467998","title":"The prevalence of laterality defects in patients with congenital heart disease.","date":"2025","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40467998","citation_count":0,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"40884622","id":"PMC_40884622","title":"Knockoff-Based Fine Mapping of MS-Associated SNPs in Sardinian Trios.","date":"2025","source":"Biochemical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40884622","citation_count":0,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":null,"id":"bio_10.1101_2025.05.06.648335","title":"Class I myosins direct circumferential F-actin flows to define cell chirality","date":"2025-05-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.06.648335","citation_count":0,"is_preprint":true,"source_track":"pubmed_title"},{"pmid":"12477932","id":"PMC_12477932","title":"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12477932","citation_count":1479,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26186194","id":"PMC_26186194","title":"The BioPlex Network: A Systematic Exploration of the Human Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29507755","id":"PMC_29507755","title":"VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.","date":"2018","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/29507755","citation_count":829,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"17353931","id":"PMC_17353931","title":"Large-scale mapping of human protein-protein interactions by mass spectrometry.","date":"2007","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/17353931","citation_count":733,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33961781","id":"PMC_33961781","title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33961781","citation_count":705,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21873635","id":"PMC_21873635","title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.","date":"2011","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/21873635","citation_count":656,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19056867","id":"PMC_19056867","title":"Large-scale proteomics and phosphoproteomics of urinary exosomes.","date":"2008","source":"Journal of the American Society of Nephrology : JASN","url":"https://pubmed.ncbi.nlm.nih.gov/19056867","citation_count":607,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15489334","id":"PMC_15489334","title":"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).","date":"2004","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/15489334","citation_count":438,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35271311","id":"PMC_35271311","title":"OpenCell: Endogenous tagging for the cartography of human cellular organization.","date":"2022","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/35271311","citation_count":432,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16344560","id":"PMC_16344560","title":"Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.","date":"2005","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/16344560","citation_count":409,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23396134","id":"PMC_23396134","title":"Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.","date":"2013","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23396134","citation_count":387,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34079125","id":"PMC_34079125","title":"A proximity-dependent biotinylation map of a human cell.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34079125","citation_count":339,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21145461","id":"PMC_21145461","title":"Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.","date":"2010","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/21145461","citation_count":318,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19389623","id":"PMC_19389623","title":"Docking motif-guided mapping of the interactome of protein phosphatase-1.","date":"2009","source":"Chemistry & biology","url":"https://pubmed.ncbi.nlm.nih.gov/19389623","citation_count":269,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19199708","id":"PMC_19199708","title":"Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).","date":"2009","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/19199708","citation_count":237,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26618866","id":"PMC_26618866","title":"∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis.","date":"2015","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/26618866","citation_count":209,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29568061","id":"PMC_29568061","title":"An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29568061","citation_count":201,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32807901","id":"PMC_32807901","title":"UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination.","date":"2020","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32807901","citation_count":168,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19913121","id":"PMC_19913121","title":"Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.","date":"2009","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19913121","citation_count":164,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19165527","id":"PMC_19165527","title":"Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.","date":"2009","source":"European archives of psychiatry and clinical neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/19165527","citation_count":159,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"31995728","id":"PMC_31995728","title":"AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System.","date":"2020","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/31995728","citation_count":152,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32877691","id":"PMC_32877691","title":"A High-Density Human Mitochondrial Proximity Interaction Network.","date":"2020","source":"Cell metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/32877691","citation_count":148,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22586326","id":"PMC_22586326","title":"Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription.","date":"2012","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/22586326","citation_count":145,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"36217030","id":"PMC_36217030","title":"A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets.","date":"2022","source":"Nature biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/36217030","citation_count":140,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23533145","id":"PMC_23533145","title":"In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.","date":"2013","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/23533145","citation_count":138,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19380743","id":"PMC_19380743","title":"Charting the molecular network of the drug target Bcr-Abl.","date":"2009","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/19380743","citation_count":137,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"31871319","id":"PMC_31871319","title":"Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms.","date":"2019","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31871319","citation_count":137,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23376485","id":"PMC_23376485","title":"Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.","date":"2013","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/23376485","citation_count":126,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35140242","id":"PMC_35140242","title":"Human transcription factor protein interaction networks.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/35140242","citation_count":123,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":29976,"output_tokens":4153,"usd":0.076111},"stage2":{"model":"claude-opus-4-6","input_tokens":7653,"output_tokens":3508,"usd":0.188947},"total_usd":0.589303,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":42883,"output_tokens":5726,"usd":0.10727},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":9535,"output_tokens":3879,"usd":0.216975}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"Myr4 (Myo1D ortholog) functions as an actin-based mechanoenzyme using calmodulin as a light chain to mediate membrane trafficking from early endosomes to recycling endosomes in MDCK epithelial cells; calmodulin function and polymerized actin are both required for this transfer.\",\n      \"method\": \"In vitro endosome transfer assay, actin polymerization perturbation experiments\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro reconstitution assay with multiple perturbation conditions, replicated across conditions\",\n      \"pmids\": [\"11208135\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Myosin-1d (Myo1d) is required for planar cell polarity (PCP) in ciliated tracheal and ependymal epithelial cells: Myo1d knockout rats show disrupted rotational PCP with disordered cilia orientation, loss of asymmetric Vangl1 localization, impaired cilia-driven bead transport, and disrupted translational PCP in ependymal cells.\",\n      \"method\": \"Myo1d knockout rat model, scanning and transmission electron microscopy, immunofluorescence, bead transport assay\",\n      \"journal\": \"Cytoskeleton\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with multiple specific phenotypic readouts and pathway placement via Vangl1\",\n      \"pmids\": [\"26446290\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Myosin1D (Myo1D) is an evolutionarily conserved regulator of left-right asymmetry in zebrafish; it controls the orientation of LR organizer (Kupffer's vesicle) cilia and interacts functionally with the PCP pathway component VanGogh-like2 (Vangl2) to shape productive LRO fluid flow.\",\n      \"method\": \"Zebrafish loss-of-function (morpholino/mutants), cilia orientation analysis, genetic epistasis with Vangl2\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis, multiple phenotypic readouts, replicated across organisms\",\n      \"pmids\": [\"29769531\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Myo1d is required for left-right axis formation in Xenopus; morpholino knockdown disrupts organ placement, Nodal cascade induction, dand5 expression, and LRO cilia length, number, and polarity. Myo1d acts in the context of the PCP pathway (convergent extension and non-canonical Wnt/ATF2 signaling), and genetic interference confirms functional interaction with vangl2.\",\n      \"method\": \"Morpholino knockdown in Xenopus, whole-mount in situ hybridization, gastrula explant cultures, ATF2 reporter assay, genetic epistasis with vangl2\",\n      \"journal\": \"Current biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods, epistasis, replicated across organisms with parallel zebrafish data\",\n      \"pmids\": [\"29478852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MYO1D binds directly to the kinase domains of unphosphorylated EGFR family members (EGFR, ErbB2, ErbB4 but not ErbB3) via a β-meander motif in its C-terminal tail domain, anchoring them to the underlying actin cytoskeleton at the plasma membrane before ligand-induced activation; overexpressed MYO1D increases EGFR levels and cancer cell motility/viability.\",\n      \"method\": \"Co-immunoprecipitation, co-localization, tail domain expression/mutagenesis, syngeneic mouse tumor model\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, mutagenesis identifying critical domain, multiple functional phenotype assays\",\n      \"pmids\": [\"31420606\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In Drosophila midgut enterocytes, Myo1D is required for membrane localization of the initiator caspase Dronc; loss of Myo1D in mature enterocytes affects ROS generation, hemocyte recruitment, and JNK signaling that normally drive intestinal stem cell mitotic activity.\",\n      \"method\": \"Drosophila genetics, fluorescence imaging, mutant analysis\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean mutant analysis with defined cellular phenotype, but single lab\",\n      \"pmids\": [\"33238125\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In Drosophila imaginal discs, Myo1D-dependent localization of initiator caspase Dronc to the plasma membrane is critical for apoptosis-induced proliferation (AiP); F-actin remodeling via LIMK1 downstream of Dronc drives ROS production and JNK activation, and this synergy between Dronc and LIMK1 depends on Myo1D.\",\n      \"method\": \"Drosophila genetics, RNAi knockdown, epistasis with LIMK1/Cofilin/Dronc, ROS measurement\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis across multiple components, single lab\",\n      \"pmids\": [\"36469525\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Drosophila Myo1D has a 12.5-fold higher actin-activated ATPase rate and 8-fold higher MgADP release rate than Myo1C; MgADP release is rate-limiting for Myo1D (vs. phosphate release for Myo1C); Myo1D propels actin filaments at higher speeds and robustly transports unilamellar vesicles along actin, whereas Myo1C cannot transport vesicles.\",\n      \"method\": \"Steady-state ATPase assay, transient kinetic experiments, in vitro actin gliding assay, vesicle transport assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted in vitro biochemistry with multiple assays characterizing ATPase mechanism\",\n      \"pmids\": [\"37380077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Myo1D interacts with and is mutually required for co-localization with the giant nuclear-associated protein Nesprin1 (dNesp1) at immature postsynaptic boutons in Drosophila NMJ; both are required for transport of mRNAs from the nucleus to postsynaptic sites during synaptic maturation.\",\n      \"method\": \"Drosophila genetics, fluorescence imaging, co-localization analysis, mutant analysis\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — genetic co-dependence of localization demonstrated, single lab\",\n      \"pmids\": [\"25959729\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Myo1d knockdown in oligodendrocytes induces retraction of processes, degeneration of myelin-like membrane, apoptosis, and impairment of intracellular PLP transport; Myo1d localizes at the leading edge of myelin-like membrane colocalizing with actin filaments and PLP.\",\n      \"method\": \"siRNA knockdown, immunofluorescence, morphological analysis\",\n      \"journal\": \"ASN neuro\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — specific phenotypic readout with defined cellular process, single lab\",\n      \"pmids\": [\"27655972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In vivo siRNA knockdown of Myo1d in the corpus callosum during cuprizone-induced demyelination decreases myelin basic protein and PLP immunofluorescence, increases pro-inflammatory microglia/astrocytes and caspase 3-positive oligodendrocytes, without altering OPC or mature OL numbers, indicating Myo1d is required for remyelination.\",\n      \"method\": \"Stereotaxic siRNA injection, immunohistochemistry, cuprizone demyelination mouse model\",\n      \"journal\": \"Neurochemical research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo knockdown with specific cellular phenotype, single lab\",\n      \"pmids\": [\"28986688\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Myo1d interacts with and is co-expressed with aspartoacylase in the nervous system; Myo1d is expressed in the ensheathing myelin compartment along sciatic nerve axons and in the Purkinje cell and granule cell layers of the cerebellum, with enrichment along axonal tracts upon onset of myelination.\",\n      \"method\": \"Co-immunoprecipitation, immunocytochemistry, Western blot\",\n      \"journal\": \"Brain research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP identifying interacting partner, complemented by localization data\",\n      \"pmids\": [\"22284616\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SPAG6 interacts with MYO1D (shown by immunoprecipitation and mass spectrometry), and SPAG6 overexpression promotes translocation of MYO1D from cytosol to the cell membrane, thereby upregulating EGFR family expression and activating PI3K/AKT and ERK signaling to promote AML progression.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, subcellular fractionation, xenograft mouse model\",\n      \"journal\": \"Blood advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — MS-confirmed interaction plus functional consequence, single lab\",\n      \"pmids\": [\"35667090\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO1D preferentially binds PDGFRα/β heterodimers (identified by PDGFR dimer-specific interactome analysis); knockdown of MYO1D causes retention of PDGFRα/β heterodimers at the plasma membrane, leading to increased ERK1/2 phosphorylation and increased cell proliferation, indicating MYO1D promotes internalization of PDGFRα/β heterodimers from the plasma membrane.\",\n      \"method\": \"Bimolecular fluorescence complementation, interactome proteomics, siRNA knockdown, phospho-Western blot, proliferation assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal approach with multiple orthogonal methods, functional consequences demonstrated\",\n      \"pmids\": [\"40404618\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Single-molecule imaging in Drosophila macrophages reveals that Myo1D has a significantly greater proportion of fast-diffusing molecules at the plasma membrane compared to Myo1C, and this difference in membrane diffusion depends on both the head and tail domains of each myosin, potentially contributing to their opposing chirality effects.\",\n      \"method\": \"Single-molecule imaging, fluorescence microscopy\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — single-molecule quantitative analysis, single lab\",\n      \"pmids\": [\"38454557\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Myo1D directs clockwise circumferential F-actin flow in Drosophila macrophages, driving clockwise cytoplasm flows in a Myosin2 (Myo2)-dependent manner; in a modified in vitro motility assay at near-physiological actin concentrations, Myo1D triggers self-organization of a clockwise-rotating chiral F-actin ring, consistent with Myo1D organizing parallelly polarized F-actin to establish dextral cell chirality.\",\n      \"method\": \"Live imaging of F-actin flows, modified in vitro motility assay, genetic epistasis with Myo2\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro reconstitution plus live-cell imaging, but preprint\",\n      \"pmids\": [\"bio_10.1101_2025.05.06.648335\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"miR-217-5p directly targets Myo1d mRNA in rat podocytes (validated by luciferase reporter assay, qRT-PCR, and Western blot); miR-217-5p overexpression induces cell shrinkage with abnormal actin cytoskeleton, phenocopying Myo1d loss, suggesting Myo1d is required for normal podocyte morphology.\",\n      \"method\": \"Luciferase reporter assay, qRT-PCR, Western blot, overexpression phenotype analysis\",\n      \"journal\": \"Non-coding RNA\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — validated miRNA-target relationship with functional phenotype, single lab\",\n      \"pmids\": [\"35736640\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Myo1D ensures survival of apoptosis-resistant DARE cells during compensatory proliferation by preventing lethal effector caspase activation; Myo1D interacts with the initiator caspase Dronc and is essential for maintaining the sub-lethal caspase activity state that enables DARE cells to drive regeneration.\",\n      \"method\": \"Drosophila genetics, delayed caspase reporter, mutant analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic evidence with defined mechanistic context, single lab\",\n      \"pmids\": [\"41345088\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYO1D is an unconventional class I myosin that uses its actin-based motor activity and lipid/tail-binding domains to link the plasma membrane to the actin cytoskeleton, where it performs several mechanistic roles: it anchors unphosphorylated EGFR family receptor tyrosine kinases at the plasma membrane via its β-meander tail domain and promotes their internalization upon dimerization (including PDGFRα/β heterodimers); it mediates endosomal recycling membrane trafficking in epithelial cells using calmodulin as a light chain; it establishes and maintains planar cell polarity in ciliated epithelia through functional interaction with core PCP components (Vangl1/Vangl2); it controls left-right body asymmetry by orienting LRO cilia and driving productive fluid flow in a PCP-dependent manner conserved from Drosophila to vertebrates; and in Drosophila it drives dextral cell chirality by directing clockwise circumferential F-actin flows and mediating membrane localization of the initiator caspase Dronc to regulate apoptosis-induced compensatory proliferation.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"Myr4 (the rat ortholog of MYO1D) functions as an actin-based mechanoenzyme required for membrane trafficking along the recycling endosome pathway in MDCK epithelial cells; calmodulin serves as its light chain, and polymerized actin is necessary for transfer of endocytosed markers from early endosomes to recycling endosomes.\",\n      \"method\": \"In vitro endosome transfer assay, calmodulin inhibition, actin polymerization perturbation, identification of myr4 as CaM target\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vitro functional assay with multiple perturbations (CaM inhibition, actin disruption) in a defined reconstituted system\",\n      \"pmids\": [\"11208135\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Myo1d (myosin-Ig/myr4) is expressed in rodent auditory and vestibular epithelia but at lower levels than Myo1b, Myo1c, and Myo1e; confirmed by RT-PCR with isozyme-selective amplification.\",\n      \"method\": \"RT-PCR with isozyme-selective primers in neonatal rodent inner ear epithelia\",\n      \"journal\": \"Journal of the Association for Research in Otolaryngology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — expression localization study with molecular confirmation but no functional loss-of-function readout\",\n      \"pmids\": [\"12486594\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Xenopus Myo1d protein is present from egg stages with increased expression at neurula through tadpole stages, and its mRNA is localized to neural tube, pre-somitic mesoderm, somites, and cranial neural crest cells during migration; a novel isoform-specific tail homology embedded in the TH1 domain was identified by sequence analysis.\",\n      \"method\": \"Western blot, whole-mount in situ hybridization, cDNA cloning and sequence analysis\",\n      \"journal\": \"Development, growth & differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct localization experiment with developmental context but no functional perturbation\",\n      \"pmids\": [\"19382939\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Myosin-1d is expressed in axons and myelin compartments of mouse sciatic nerve, in Purkinje and granule cell layers of cerebellum, and expands along axonal tracts upon myelination onset; myosin-1d interacts with and is co-expressed with aspartoacylase (ASPA), an enzyme central to fatty acid synthesis in the nervous system.\",\n      \"method\": \"Immunofluorescence, co-immunoprecipitation (interaction with ASPA), Western blot across developmental stages\",\n      \"journal\": \"Brain research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP for ASPA interaction plus direct localization imaging\",\n      \"pmids\": [\"22284616\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Myo1d is expressed in myelinating oligodendrocytes of rat CNS, particularly enriched in the outer (abaxonal) and inner (adaxonal) cytoplasm-containing loops of myelin; expression increases during CNS white matter maturation and is low in PNS myelin.\",\n      \"method\": \"Immunofluorescence with isoform-specific antibody, Western blot during CNS development, cell culture\",\n      \"journal\": \"Journal of neuroscience research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct localization with isoform-specific reagent; no functional perturbation in this paper\",\n      \"pmids\": [\"24903835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In Drosophila, Myo1D functions with Nesprin1 (dNesp1) to transport mRNAs from muscle nuclei to postsynaptic sites at the neuromuscular junction along F-actin-based 'railroad track' filaments; dNesp1 and Myo1D are mutually required for their localization to immature boutons, and loss of dNesp1 prevents mRNA localization and synaptic maturation.\",\n      \"method\": \"Genetic loss-of-function (dNesp1 mutants), live imaging, immunofluorescence, mRNA localization assays in Drosophila NMJ\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO phenotype with defined cellular readout (mRNA mislocalization, synaptic maturation defect) plus mutual localization dependence\",\n      \"pmids\": [\"25959729\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Myo1d knock-out rats show disrupted rotational planar cell polarity (PCP) in tracheal multi-ciliated epithelial cells: ciliary basal bodies lose unidirectional alignment (cilia splay radially), the asymmetric localization of PCP core protein Vangl1 is lost, and cilia-driven bead transport is impaired in velocity and linearity. In brain ependymal cells, left-right positioning of basal body clusters is lost, disrupting translational PCP.\",\n      \"method\": \"Rat knockout (Myo1d KO), scanning/transmission electron microscopy, immunofluorescence for Vangl1, bead transport assay\",\n      \"journal\": \"Cytoskeleton\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with multiple orthogonal readouts (EM, immunofluorescence, functional transport assay)\",\n      \"pmids\": [\"26446290\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"siRNA-mediated knockdown of Myo1d in cultured oligodendrocytes causes retraction of processes, degeneration of myelin-like membrane, apoptosis, and impaired intracellular PLP (proteolipid protein) transport; Myo1d co-localizes with actin filaments, CNPase, and partially with PLP at the leading edge of myelin-like membrane in differentiated OLs.\",\n      \"method\": \"siRNA knockdown in primary rat oligodendrocyte cultures, immunofluorescence, live-cell morphology analysis\",\n      \"journal\": \"ASN Neuro\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — defined KD phenotype with specific cellular readout (PLP transport, morphology, apoptosis)\",\n      \"pmids\": [\"27655972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In a cuprizone-induced demyelination mouse model, stereotaxic siRNA knockdown of Myo1d in corpus callosum decreases MBP and PLP immunofluorescence intensity during remyelination, increases pro-inflammatory microglia and astrocytes, decreases anti-inflammatory microglia, and increases caspase-3-positive oligodendrocytes, indicating Myo1d is required for successful remyelination in vivo.\",\n      \"method\": \"In vivo siRNA injection (stereotaxic), cuprizone demyelination model, immunohistochemistry, cell counting\",\n      \"journal\": \"Neurochemical research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo KD with defined cellular phenotype (remyelination failure, inflammatory shift)\",\n      \"pmids\": [\"28986688\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Myosin1D (Myo1D) is an evolutionarily conserved regulator of left-right asymmetry in zebrafish: it is required for formation and function of Kupffer's vesicle (KV, the LR organizer), controls orientation of KV cilia, and interacts functionally with the PCP pathway component VanGogh-like2 (Vangl2) to establish productive LRO flow and organ laterality.\",\n      \"method\": \"Zebrafish myo1d morpholino knockdown, ciliary imaging, flow analysis, genetic interaction with Vangl2 morphants\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — morpholino KD with multiple orthogonal readouts (cilia orientation, fluid flow, organ situs) plus genetic epistasis with PCP component\",\n      \"pmids\": [\"29769531\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Morpholino-mediated myo1d downregulation in Xenopus disrupts organ placement, impairs Nodal cascade induction, compromises dand5 expression and LRO cilia (shorter, fewer, non-polarized), inhibits convergent extension, and downregulates a non-canonical Wnt (ATF2) reporter; genetic interference shows functional interaction between vangl2 and myo1d in LR axis formation, placing Myo1d in the PCP pathway.\",\n      \"method\": \"Xenopus morpholino knockdown, in situ hybridization, cilia analysis, convergent extension assay, ATF2 reporter, vangl2 genetic interaction\",\n      \"journal\": \"Current Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods in a second vertebrate model, with genetic epistasis establishing PCP pathway placement\",\n      \"pmids\": [\"29478852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MYO1D functions to anchor unphosphorylated EGFR family members (EGFR, ErbB2, ErbB4 but not ErbB3) to the plasma membrane via direct binding between the β-meander motif in MYO1D's C-terminal tail domain and the kinase domains of EGFRs; expression of the tail domain alone suppresses the oncogenic action of full-length MYO1D. Overexpression of MYO1D increases colorectal and breast cancer cell motility and viability by upregulating EGFR levels and promotes colorectal tumor progression in a syngeneic mouse model.\",\n      \"method\": \"Co-immunoprecipitation, co-localization, domain mapping (tail domain expression), syngeneic mouse tumor model, cell viability/motility assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP with domain dissection, in vivo tumor model, multiple cell line functional assays\",\n      \"pmids\": [\"31420606\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In Drosophila, Myo1D-dependent localization of the initiator caspase Dronc to the plasma membrane of mature enterocytes (ECs) is required for homeostatic intestinal stem cell (ISC) activity; in Myo1D mutant midguts, ROS generation, hemocyte recruitment, and JNK signaling are all reduced, indicating Myo1D-dependent Dronc membrane localization in ECs drives the signals that stimulate ISC mitosis.\",\n      \"method\": \"Drosophila Myo1D mutant analysis, live imaging of midgut, ROS assay, JNK signaling reporters, hemocyte recruitment assay\",\n      \"journal\": \"Cell Reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean genetic KO with multiple defined signaling readouts and mechanistic pathway placement\",\n      \"pmids\": [\"33238125\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In Drosophila apoptosis-induced proliferation (AiP), Myo1D localizes the initiator caspase Dronc to the cell cortex; F-actin accumulates in a Dronc-dependent manner and drives ROS production and JNK activation. LIMK1 promotes F-actin polymerization downstream of Dronc, and the synergistic effects of co-expressed Dronc and LIMK1 on F-actin accumulation, ROS, and JNK activation require Myo1D, placing Myo1D as essential for cortical Dronc-driven AiP signaling.\",\n      \"method\": \"Drosophila genetic epistasis (myo1d, limk1, dronc), ROS assay, JNK reporter, F-actin staining, co-expression experiments\",\n      \"journal\": \"PLoS Genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple genetic epistasis experiments with defined biochemical readouts placing Myo1D in the Dronc-LIMK1-F-actin-ROS-JNK pathway\",\n      \"pmids\": [\"36469525\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SPAG6 interacts with MYO1D (shown by immunoprecipitation and mass spectrometry) and overexpression of SPAG6 promotes translocation of MYO1D from cytosol to the cell membrane, thereby upregulating EGFR family expression and activating PI3K/AKT and ERK signaling to promote AML cell proliferation and migration.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, subcellular fractionation, flow cytometry, xenograft mouse model\",\n      \"journal\": \"Blood Advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP/MS for interaction plus functional KD/OE with defined signaling readout, but single-lab study\",\n      \"pmids\": [\"35667090\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"miR-217-5p directly targets Myo1d (validated by luciferase assay, qRT-PCR, and Western blot), and its overexpression in podocytes causes shrunken cells with abnormal actin cytoskeletons, suggesting Myo1d plays a role in podocyte morphogenesis and actin organization.\",\n      \"method\": \"Luciferase reporter assay, qRT-PCR, Western blot, miRNA overexpression in E11 podocyte cells\",\n      \"journal\": \"Non-coding RNA\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — validated miRNA-target relationship with associated morphological phenotype; functional role of Myo1d itself inferred indirectly\",\n      \"pmids\": [\"35736640\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Drosophila Myo1D has a 12.5-fold higher actin-activated steady-state ATPase rate than Myo1C, an 8-fold higher MgADP release rate, and MgADP release (not phosphate release) is the rate-limiting step for Myo1D, whereas phosphate release is rate-limiting for Myo1C. Both myosins have among the tightest MgADP affinities measured for any myosin. Myo1D propels actin filaments at higher speeds and robustly transports 50 nm unilamellar vesicles along actin filaments in vitro, consistent with a transport motor role.\",\n      \"method\": \"Steady-state ATPase assay, transient kinetics (stopped-flow), in vitro actin gliding assay, liposome transport assay\",\n      \"journal\": \"The Journal of Biological Chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted in vitro mechanochemical analysis with multiple quantitative kinetic methods and functional transport assay\",\n      \"pmids\": [\"37380077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KITENIN complex component MYO1D is required for KITENIN-mediated aerobic glycolysis in colorectal cancer cells; silencing MYO1D downregulates glycolytic proton efflux rate and expression of glycolytic enzymes (GLUT1, HK2, PKM2, LDHA).\",\n      \"method\": \"siRNA knockdown of MYO1D, glycolytic flux assay (Seahorse), protein expression analysis\",\n      \"journal\": \"Cell & Bioscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — defined KD phenotype with quantitative metabolic readout, but pathway placement is within the KITENIN complex context\",\n      \"pmids\": [\"37553596\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Single-molecule imaging in Drosophila macrophages shows Myo1D exhibits a significantly smaller slow-diffusing population on the plasma membrane compared to Myo1C; this difference is contingent on both head and tail domains of Myo1C and the two myosins do not mutually influence each other's membrane diffusion, suggesting distinct membrane interaction mechanisms underlie their opposite chirality-determining activities.\",\n      \"method\": \"Single-molecule imaging (TIRF/PALM) in live Drosophila macrophages, diffusion coefficient analysis\",\n      \"journal\": \"Genes to Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — quantitative single-molecule biophysics in living cells; mechanistic link to chirality is proposed but not directly tested with loss-of-function\",\n      \"pmids\": [\"38454557\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO1D preferentially binds PDGFRα/β heterodimers and promotes their internalization from the plasma membrane into early endosomes; knockdown of MYO1D causes retention of PDGFRα/β heterodimers at the plasma membrane, leading to increased ERK1/2 phosphorylation and increased cell proliferation, identifying MYO1D as a negative regulator of PDGFRα/β heterodimer signaling through receptor trafficking.\",\n      \"method\": \"Bimolecular fluorescence complementation, AP-MS interactome, siRNA knockdown, phospho-ERK1/2 immunoblot, cell proliferation assay\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — AP-MS identification of interaction confirmed functionally with KD and defined signaling/proliferation readouts; published peer-reviewed with independent methods\",\n      \"pmids\": [\"40404618\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Myo1D in Drosophila macrophages directs clockwise circumferential F-actin flow, while Myo1C directs counterclockwise flow; both depend on Myosin2 (Myo2). In a modified in vitro motility assay at near-physiological actin concentrations, Myo1D triggers self-organization of a clockwise-rotating chiral F-actin ring, implying Myo1D organizes parallelly polarized (barbed-end-biased) F-actin bundles to drive dextral cell chirality through Myo2-driven circumferential flow.\",\n      \"method\": \"Live-cell F-actin flow imaging in Drosophila macrophages, modified in vitro motility assay, genetic perturbation of Myo2\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution plus live-cell imaging, but preprint and single-lab\",\n      \"pmids\": [\"bio_10.1101_2025.05.06.648335\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In Drosophila wing disc regeneration after ionizing radiation, Myo1D ensures survival of Dronc-activating apoptosis-resistant (DARE) cells by preventing lethal effector caspase activation; without Myo1D, DARE cells undergo apoptosis, disrupting compensatory proliferation and tissue regeneration.\",\n      \"method\": \"Drosophila Myo1D genetic loss-of-function in wing imaginal discs, delayed Dronc reporter, effector caspase assays, proliferation quantification\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean genetic KO with specific cellular survival phenotype, but mechanistic detail of how Myo1D prevents caspase activation is not fully resolved\",\n      \"pmids\": [\"41345088\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYO1D is an unconventional class I myosin that uses its actin-based motor activity (characterized by high ATPase rate, fast MgADP release, and robust vesicle transport kinetics) to link membranes to the actin cytoskeleton, thereby performing several distinct cellular functions: anchoring unphosphorylated EGFR family receptors and PDGFRα/β heterodimers at or promoting their internalization from the plasma membrane to regulate receptor-level signaling; driving recycling endosome membrane trafficking in epithelial cells; directing rotational and translational planar cell polarity in ciliated epithelia; localizing the initiator caspase Dronc to the plasma membrane to regulate apoptosis-induced compensatory proliferation and homeostatic intestinal stem cell activity in Drosophila; promoting mRNA transport to postsynaptic sites at the NMJ in concert with Nesprin1; supporting oligodendrocyte myelin membrane dynamics and remyelination; and acting as an evolutionarily conserved regulator of left-right asymmetry by controlling LR organizer cilia orientation and function through functional interactions with the planar cell polarity pathway (Vangl2), with Myo1D's motor domain chirality (clockwise F-actin movement) providing the cellular basis for dextral organ asymmetry.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MYO1D is an unconventional class I myosin that couples actin-based motor activity with membrane and cargo binding to serve diverse roles in membrane trafficking, receptor regulation, planar cell polarity, left–right body axis determination, and apoptosis-induced proliferation. Its motor domain exhibits a high actin-activated ATPase rate with MgADP release as the rate-limiting step, enabling robust vesicle transport along actin filaments; using calmodulin as a light chain, it mediates transfer from early endosomes to recycling endosomes in epithelial cells and promotes internalization of receptor tyrosine kinases including EGFR family members and PDGFRα/β heterodimers via a β-meander tail domain that directly binds unphosphorylated kinase domains [PMID:37380077, PMID:11208135, PMID:31420606, PMID:40404618]. MYO1D is an evolutionarily conserved determinant of left–right asymmetry: in vertebrates it orients LR organizer cilia and shapes productive fluid flow through functional interaction with the PCP pathway component Vangl2, and in ciliated epithelia it is required for rotational planar cell polarity and asymmetric Vangl1 localization [PMID:29769531, PMID:29478852, PMID:26446290]. In Drosophila, MYO1D drives dextral cell chirality by directing clockwise circumferential F-actin flows and mediates plasma membrane localization of the initiator caspase Dronc, which is essential for apoptosis-induced compensatory proliferation and the survival of apoptosis-resistant regenerative cells [PMID:36469525, PMID:41345088, PMID:33238125].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing MYO1D as a membrane-trafficking motor: it was unknown how early-to-recycling endosome transfer was powered, and this work showed Myr4/Myo1D uses calmodulin-dependent, actin-based motility to drive this step in epithelial cells.\",\n      \"evidence\": \"In vitro endosome transfer assay in MDCK cells with actin and calmodulin perturbations\",\n      \"pmids\": [\"11208135\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of cargo adaptors mediating endosome recruitment unknown\", \"Whether this trafficking role is conserved outside kidney epithelial cells was untested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linking MYO1D to the nervous system: Myo1D was found enriched in myelinating compartments and to interact with aspartoacylase, suggesting a role in myelin biology, though the functional consequence was unclear.\",\n      \"evidence\": \"Co-immunoprecipitation and immunohistochemistry in mouse nervous tissue\",\n      \"pmids\": [\"22284616\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation for the aspartoacylase interaction\", \"Functional consequence of the interaction not demonstrated\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Two parallel discoveries expanded MYO1D's roles: (1) it was shown to be required for planar cell polarity in ciliated epithelia via Vangl1 localization, and (2) it was found to cooperate with Nesprin1 for mRNA transport at Drosophila synapses, revealing functions in tissue-level polarity and synaptic maturation.\",\n      \"evidence\": \"Myo1d knockout rat with EM and bead transport (PCP); Drosophila NMJ genetic and imaging analysis (synaptic)\",\n      \"pmids\": [\"26446290\", \"25959729\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the PCP function is direct or via cytoskeletal remodeling was unresolved\", \"Mechanism of Myo1D–Nesprin1 co-dependence not biochemically defined\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extending the myelination connection: Myo1d knockdown in oligodendrocytes caused process retraction, myelin-like membrane degeneration, impaired PLP transport, and apoptosis, establishing a cell-autonomous requirement in myelination.\",\n      \"evidence\": \"siRNA knockdown in cultured oligodendrocytes with morphological and immunofluorescence analysis\",\n      \"pmids\": [\"27655972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab siRNA study; off-target effects not fully excluded\", \"In vivo relevance during developmental myelination not yet shown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"In vivo knockdown confirmed MYO1D's requirement for remyelination: silencing Myo1d in the corpus callosum during cuprizone-induced demyelination reduced myelin protein levels and increased inflammation and oligodendrocyte apoptosis.\",\n      \"evidence\": \"Stereotaxic siRNA injection in cuprizone mouse model with immunohistochemistry\",\n      \"pmids\": [\"28986688\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stereotaxic siRNA approach limits spatial precision; genetic conditional KO not performed\", \"Whether Myo1d acts in myelin membrane extension versus PLP trafficking was unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"MYO1D was established as a conserved determinant of left–right body asymmetry: independent studies in zebrafish and Xenopus showed it orients LR organizer cilia, shapes fluid flow, and genetically interacts with Vangl2 in the PCP pathway to control organ laterality.\",\n      \"evidence\": \"Morpholino/mutant loss-of-function in zebrafish and Xenopus with cilia orientation analysis and Vangl2 epistasis\",\n      \"pmids\": [\"29769531\", \"29478852\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MYO1D directly positions the basal body or acts indirectly through cytoskeletal remodeling was unknown\", \"Mammalian LR asymmetry phenotype in Myo1d KO not reported\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defining MYO1D as an RTK anchor: the β-meander tail domain was shown to bind unphosphorylated EGFR family kinase domains directly, tethering receptors to the actin cortex at the plasma membrane and modulating receptor levels and cancer cell behavior.\",\n      \"evidence\": \"Reciprocal Co-IP, tail domain mutagenesis, syngeneic mouse tumor model\",\n      \"pmids\": [\"31420606\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MYO1D actively internalizes EGFR or simply anchors it was ambiguous\", \"Structural basis of β-meander–kinase domain interaction not resolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A new function in apoptosis-induced proliferation emerged: Myo1D was found to localize the initiator caspase Dronc to the plasma membrane in Drosophila gut enterocytes, linking it to ROS generation, hemocyte recruitment, and JNK-driven stem cell proliferation.\",\n      \"evidence\": \"Drosophila mutant analysis and fluorescence imaging in midgut\",\n      \"pmids\": [\"33238125\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether Myo1D directly binds Dronc or acts through an adaptor was unknown\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Three advances refined MYO1D biology: (1) the Dronc–Myo1D axis in apoptosis-induced proliferation was extended to imaginal discs with LIMK1/Cofilin epistasis; (2) SPAG6 was identified as a partner that promotes MYO1D membrane translocation to activate EGFR/PI3K/AKT signaling in AML; (3) miR-217-5p was validated as a direct regulator of Myo1d mRNA in podocytes.\",\n      \"evidence\": \"Drosophila genetic epistasis (AiP); Co-IP/MS plus xenograft model (SPAG6); luciferase reporter assay (miRNA)\",\n      \"pmids\": [\"36469525\", \"35667090\", \"35736640\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"SPAG6–MYO1D interaction awaits reciprocal validation outside AML context\", \"Physiological relevance of miR-217-5p regulation of Myo1d in vivo not demonstrated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Biochemical characterization revealed the kinetic basis for MYO1D's transport capability: its ATPase rate and MgADP release rate are 12.5-fold and 8-fold higher than MYO1C, respectively, enabling robust vesicle transport that MYO1C cannot perform.\",\n      \"evidence\": \"Reconstituted steady-state ATPase, transient kinetics, in vitro gliding and vesicle transport assays with Drosophila proteins\",\n      \"pmids\": [\"37380077\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinetics determined for Drosophila isoforms; human MYO1D kinetics not directly measured\", \"How kinetic differences relate to chirality function versus trafficking function unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Single-molecule imaging showed MYO1D exhibits faster membrane diffusion than MYO1C, with both head and tail domains contributing, providing a biophysical correlate for their opposing effects on cell chirality.\",\n      \"evidence\": \"Single-molecule fluorescence imaging in Drosophila macrophages\",\n      \"pmids\": [\"38454557\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal link between diffusion dynamics and chirality generation not established\", \"Single-lab observation\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Three studies in 2025 advanced distinct aspects of MYO1D function: (1) MYO1D was shown to promote internalization of PDGFRα/β heterodimers, with its loss causing receptor retention and enhanced ERK signaling; (2) Myo1D was found to direct clockwise F-actin flows that establish dextral cell chirality via self-organized chiral actin rings; (3) Myo1D was shown to maintain sub-lethal caspase activity in DARE cells during regeneration by interacting with Dronc.\",\n      \"evidence\": \"BiFC interactome proteomics and siRNA (PDGFR); live imaging plus in vitro motility assay (chirality, preprint); Drosophila genetics with delayed caspase reporter (DARE cells)\",\n      \"pmids\": [\"40404618\", \"bio_10.1101_2025.05.06.648335\", \"41345088\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of β-meander recognition of PDGFRα/β versus EGFR not compared\", \"In vitro chiral ring finding is a preprint awaiting peer review\", \"Whether mammalian MYO1D has a chirality function is untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include: the structural basis for MYO1D's chiral actin organization, whether its chirality function is conserved in mammals, how it distinguishes different RTK substrates via the β-meander domain, and whether its trafficking, polarity, and caspase-regulatory functions reflect a unified membrane-cortex coupling mechanism.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No crystal structure of MYO1D tail domain with any binding partner\", \"Mammalian Myo1d conditional KO phenotype for LR asymmetry not reported\", \"Unified mechanistic model linking trafficking, PCP, chirality, and caspase functions is lacking\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 7, 15]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [7, 15]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [4, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4, 5, 6, 12, 13, 14]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 7, 9, 15]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [12]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 12, 13]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 13]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [5, 6, 17]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"VANGL1\",\n      \"VANGL2\",\n      \"EGFR\",\n      \"ERBB2\",\n      \"ERBB4\",\n      \"SPAG6\",\n      \"SYNE1\",\n      \"ASPA\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"MYO1D is an unconventional class I myosin that couples actin-based motor activity to membrane dynamics, serving as a versatile linker between the actin cytoskeleton and cellular membranes in contexts ranging from vesicle trafficking to organ laterality. Its motor domain exhibits a high actin-activated ATPase rate with MgADP release as the rate-limiting step, enabling robust vesicle transport along actin filaments and driving clockwise F-actin organization that underlies dextral cell chirality [PMID:37380077, PMID:29769531, PMID:29478852]. MYO1D anchors unphosphorylated EGFR family receptors at the plasma membrane to regulate receptor-level signaling, promotes PDGFRα/β heterodimer internalization into early endosomes to negatively regulate ERK signaling, localizes the initiator caspase Dronc to the cell cortex to drive apoptosis-induced compensatory proliferation, and directs rotational and translational planar cell polarity in ciliated epithelia through functional interaction with Vangl2 [PMID:31420606, PMID:40404618, PMID:36469525, PMID:26446290]. MYO1D also supports oligodendrocyte myelin membrane maintenance and remyelination in the CNS, and cooperates with Nesprin1 for actin-dependent mRNA transport to postsynaptic sites at the neuromuscular junction [PMID:27655972, PMID:28986688, PMID:25959729].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing MYO1D as a membrane-trafficking motor: prior to this work it was unknown whether class I myosins participated in endosomal sorting; reconstituted assays demonstrated that Myr4/MYO1D, with calmodulin as its light chain, is required for actin-dependent transfer of cargo from early endosomes to recycling endosomes.\",\n      \"evidence\": \"In vitro endosome transfer assay in MDCK cells with calmodulin inhibition and actin polymerization perturbation\",\n      \"pmids\": [\"11208135\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural basis for how MYO1D selects recycling endosome membranes\", \"Whether this trafficking role extends to non-epithelial cells was untested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Expanding MYO1D's tissue repertoire to the nervous system: MYO1D was found in axonal and myelin compartments, interacting with aspartoacylase (ASPA), suggesting a previously unrecognized role in myelination-related lipid metabolism.\",\n      \"evidence\": \"Co-immunoprecipitation of MYO1D with ASPA, immunofluorescence in mouse sciatic nerve and cerebellum\",\n      \"pmids\": [\"22284616\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP for ASPA interaction without reciprocal validation\", \"Functional consequence of MYO1D-ASPA interaction untested\", \"No loss-of-function data in this study\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstrating MYO1D as a planar cell polarity effector: knockout rats revealed that MYO1D is required for unidirectional basal body alignment and Vangl1 polarization in multi-ciliated epithelia, resolving how actin-based motors contribute to rotational and translational PCP.\",\n      \"evidence\": \"Myo1d knockout rat with SEM/TEM, Vangl1 immunofluorescence, and bead transport assay in tracheal and ependymal epithelia\",\n      \"pmids\": [\"26446290\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MYO1D directly binds PCP core components or acts indirectly was unresolved\", \"Mechanism linking motor activity to basal body rotation unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealing a postsynaptic mRNA transport function: MYO1D and Nesprin1 were shown to be mutually dependent for localization to immature boutons and required for actin-based mRNA delivery to postsynaptic sites at the Drosophila NMJ, establishing a motor-scaffold partnership for local translation.\",\n      \"evidence\": \"Genetic loss-of-function in Drosophila, mRNA localization assays, immunofluorescence at NMJ\",\n      \"pmids\": [\"25959729\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of transported mRNAs not fully catalogued\", \"Whether this mechanism operates at mammalian synapses unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Confirming a cell-autonomous role in oligodendrocyte survival and myelin membrane dynamics: MYO1D knockdown caused process retraction, impaired PLP transport, and apoptosis in oligodendrocytes, directly linking MYO1D motor function to myelin sheath integrity.\",\n      \"evidence\": \"siRNA knockdown in primary rat oligodendrocyte cultures with live-cell morphology and PLP trafficking analysis\",\n      \"pmids\": [\"27655972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the apoptosis is a direct consequence of PLP mistrafficking or a parallel effect was unclear\", \"No rescue experiment reported\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extending MYO1D's myelin role in vivo: stereotaxic knockdown during cuprizone-induced demyelination impaired remyelination and shifted glial inflammatory profiles, establishing MYO1D as required for CNS repair.\",\n      \"evidence\": \"In vivo siRNA injection in corpus callosum, cuprizone model, immunohistochemistry\",\n      \"pmids\": [\"28986688\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"siRNA specificity controls not fully detailed\", \"Whether the inflammatory shift is cell-autonomous to oligodendrocytes or secondary was unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing MYO1D as a conserved determinant of vertebrate left-right asymmetry: morpholino knockdown in both zebrafish and Xenopus disrupted LR organizer cilia orientation, Nodal cascade activation, and organ situs, with genetic epistasis placing MYO1D in the PCP (Vangl2) pathway.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish and Xenopus with cilia imaging, fluid flow analysis, in situ hybridization, convergent extension assays, and Vangl2 genetic interaction\",\n      \"pmids\": [\"29769531\", \"29478852\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MYO1D physically binds Vangl2 or acts in parallel was unresolved\", \"The intrinsic chirality mechanism of MYO1D motor was not yet characterized\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identifying MYO1D as a direct membrane anchor for EGFR family receptors: the β-meander motif in MYO1D's tail was shown to bind EGFR kinase domains and stabilize receptors at the plasma membrane, with overexpression promoting tumor progression via upregulated EGFR signaling.\",\n      \"evidence\": \"Reciprocal Co-IP, domain mapping, syngeneic mouse tumor model, cell viability/motility assays in colorectal and breast cancer lines\",\n      \"pmids\": [\"31420606\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MYO1D-EGFR interaction occurs in normal physiology or only in overexpression contexts\", \"Structural basis of the β-meander–kinase domain interface not resolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defining MYO1D's role in non-apoptotic caspase signaling: MYO1D-dependent membrane localization of Dronc in mature enterocytes was shown to drive ROS, hemocyte recruitment, and JNK signaling that sustains homeostatic intestinal stem cell proliferation.\",\n      \"evidence\": \"Drosophila Myo1D mutant midgut analysis with ROS, JNK reporters, hemocyte imaging\",\n      \"pmids\": [\"33238125\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How MYO1D physically tethers Dronc to the membrane was not determined\", \"Whether this mechanism operates in mammalian intestinal stem cells unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placing MYO1D in the Dronc–LIMK1–F-actin–ROS–JNK cascade: genetic epistasis showed that MYO1D is required for the synergistic F-actin accumulation and ROS/JNK activation driven by co-expressed Dronc and LIMK1 during apoptosis-induced proliferation.\",\n      \"evidence\": \"Drosophila genetic epistasis with myo1d, limk1, dronc; F-actin staining, ROS and JNK reporter assays\",\n      \"pmids\": [\"36469525\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical interaction between MYO1D and LIMK1 not shown\", \"Whether MYO1D motor activity or only membrane tethering is required was untested\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connecting MYO1D to EGFR signaling through SPAG6: SPAG6 was identified as an interactor that promotes MYO1D translocation to the plasma membrane, upregulating EGFR family expression and PI3K/AKT and ERK signaling in AML cells.\",\n      \"evidence\": \"Co-IP/mass spectrometry, subcellular fractionation, xenograft mouse model in AML cells\",\n      \"pmids\": [\"35667090\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SPAG6 directly binds MYO1D or acts through an intermediary not fully resolved\", \"Single-lab finding awaiting independent confirmation\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Characterizing MYO1D's intrinsic motor properties: reconstituted kinetics revealed MYO1D has a 12.5-fold higher ATPase rate than MYO1C, with MgADP release as its rate-limiting step, and demonstrated robust vesicle transport and clockwise actin gliding consistent with a fast transport motor that could underlie dextral chirality.\",\n      \"evidence\": \"Steady-state ATPase, stopped-flow transient kinetics, in vitro actin gliding and liposome transport assays with Drosophila MYO1D\",\n      \"pmids\": [\"37380077\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether mammalian MYO1D shares identical kinetic properties not confirmed\", \"Structural basis for clockwise vs. counterclockwise movement not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealing MYO1D as a negative regulator of PDGFRα/β heterodimer signaling: MYO1D preferentially binds and internalizes PDGFRα/β heterodimers; its loss retains receptors at the plasma membrane, amplifying ERK1/2 signaling and proliferation — establishing a receptor-trafficking function opposite to its EGFR-stabilizing role.\",\n      \"evidence\": \"Bimolecular fluorescence complementation, AP-MS, siRNA knockdown with phospho-ERK1/2 and proliferation readouts\",\n      \"pmids\": [\"40404618\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How MYO1D distinguishes PDGFR heterodimers from homodimers mechanistically unclear\", \"Whether this trafficking role involves the same tail domain β-meander used for EGFR binding untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrating that MYO1D ensures survival of apoptosis-resistant cells during tissue regeneration: without MYO1D, DARE cells in irradiated wing discs undergo lethal effector caspase activation, disrupting compensatory proliferation and regeneration.\",\n      \"evidence\": \"Drosophila Myo1D loss-of-function in wing imaginal discs, delayed Dronc reporter, effector caspase assays\",\n      \"pmids\": [\"41345088\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Precise mechanism by which MYO1D prevents effector caspase activation not fully resolved\", \"Whether this anti-apoptotic function depends on Dronc membrane tethering not directly shown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of MYO1D's intrinsic chirality, whether its EGFR-anchoring and PDGFR-internalizing roles use the same or distinct tail-domain interfaces, how MYO1D physically tethers Dronc to the plasma membrane, and whether the PCP-related and chirality functions are conserved in mammals.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No crystal structure of MYO1D tail domain in complex with any receptor\", \"No mammalian loss-of-function model for left-right asymmetry\", \"Direct MYO1D–Dronc binding mechanism unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 16]},\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 5, 16, 20]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [6, 7, 16, 20]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [6, 11, 12, 13, 14, 18, 19]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 5, 7, 16, 20]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 19]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [14]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [6, 9, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 7, 19]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [9, 10, 11, 14, 19]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [9, 10]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [12, 13, 21]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"EGFR\", \"ERBB2\", \"ERBB4\", \"VANGL2\", \"SPAG6\", \"ASPA\", \"NESPRIN1\", \"PDGFRA\"],\n    \"other_free_text\": []\n  }\n}\n```"}