{"gene":"MYO1F","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":2006,"finding":"Myo1f co-localizes with cortical actin in immune cells; Myo1f-deficient neutrophils show augmented exocytosis of β2 integrin-containing granules, increased adhesion, and reduced motility, establishing Myo1f as a regulator of granule exocytosis and cortical actin organization in immune cells.","method":"Myo1f knockout mouse model with traction force microscopy, FACS-based adhesion assays, and exocytosis measurements","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 — clean KO mouse with multiple orthogonal phenotypic readouts, replicated in vivo infection model","pmids":["17023661"],"is_preprint":false},{"year":2019,"finding":"Myo1f directly interacts with the adaptor protein 3BP2 in mast cells; this interaction is modulated by KIT (SCF receptor) signaling, and Myo1f colocalizes with cortical actin. Myo1f silencing reduces β1 and β7 integrin surface expression, SCF-dependent adhesion to fibronectin, and Rac2/Cdc42 GTPase activity, placing Myo1f downstream of KIT in mast cell migration.","method":"Co-immunoprecipitation, shRNA knockdown, flow cytometry for integrin surface expression, GTPase activity assays, migration assays","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP plus KD with multiple functional readouts, single lab","pmids":["31143189"],"is_preprint":false},{"year":2021,"finding":"MYO1F acts as an adaptor that recruits both AP2A1 and α-tubulin N-acetyltransferase 1 (αTAT1) to α-tubulin upon Dectin-1 stimulation, promoting α-tubulin acetylation and controlling membrane-to-cytoplasm trafficking of SYK and CARD9 for antifungal innate immune signaling.","method":"Co-immunoprecipitation, Myo1f knockout mouse macrophages, Dectin-1 stimulation assays, tubulin acetylation western blot, in vivo Candida albicans infection model","journal":"Proceedings of the National Academy of Sciences of the USA","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, KO mouse with defined molecular mechanism, in vivo validation","pmids":["34301894"],"is_preprint":false},{"year":2021,"finding":"MYO1F is required for full mast cell degranulation via IgE/FcεRI crosslinking and MRGPRX2 stimulation; MYO1F knockdown impairs Cdc42 GTPase activation, reduces cortical actin ring reassembly after activation, and diminishes mitochondria translocation to exocytic sites along with reduced AKT and DRP1 phosphorylation.","method":"shRNA knockdown of MYO1F in human mast cells (LAD2), degranulation assays, Cdc42 GTPase activation assays, confocal imaging of actin and mitochondria, western blot for AKT/DRP1 phosphorylation","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 — KD with multiple orthogonal mechanistic readouts, single lab","pmids":["33941653"],"is_preprint":false},{"year":2023,"finding":"Myo1f deficiency in γδT intraepithelial lymphocytes reduces CCR9 and α4β7 surface expression, impairs chemokine receptor and integrin polarization, reduces tyrosine phosphorylation, and results in defective CCL25-dependent and independent migration and homing to the small intestine intraepithelial compartment.","method":"Myo1f KO mouse model, flow cytometry for surface receptor expression, in vitro migration assays, immunofluorescence for receptor polarization","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 — KO mouse with defined cellular and molecular phenotypes, single lab","pmids":["37207213"],"is_preprint":false},{"year":2024,"finding":"During viral infection, SYK phosphorylates MYO1F at the plasma membrane, which facilitates recruitment of KAT2A acetyltransferase to cGAS; KAT2A then acetylates cGAS at lysines 421, 292, and 131, essential for cGAS activation and type I interferon production. Membrane-localized cGAS (anchored by MYO1F) is required for signaling triggered by virus-cell fusion.","method":"Co-immunoprecipitation, mutagenesis of MYO1F and cGAS acetylation sites, proximity ligation assays, KO macrophages, in vitro kinase assays, type I IFN production assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1-2 — Co-IP, mutagenesis, in vitro kinase assay, KO cells with defined molecular mechanism","pmids":["39694035"],"is_preprint":false},{"year":2024,"finding":"After TCR stimulation, LCK phosphorylates MYO1F at tyrosines 607 and 634; phosphorylated MYO1F then facilitates αTAT1-mediated acetylation of GAPDH at Lys84, 86, and 227, enhancing GAPDH enzymatic activity, glycolysis, and T-cell effector function. The oncogenic VAV1-MYO1F fusion causes hyperacetylation of GAPDH and aberrant glycolysis.","method":"T-cell-specific Myo1f KO mice, phosphomutant and acetylation-site mutagenesis, in vitro kinase assays, GAPDH activity assays, glycolysis measurements (Seahorse), Co-IP, human PTCL patient sample validation","journal":"Cellular & molecular immunology","confidence":"High","confidence_rationale":"Tier 1-2 — in vitro kinase assay, mutagenesis, KO mouse, patient sample validation with multiple orthogonal methods","pmids":["39668163"],"is_preprint":false},{"year":2025,"finding":"MYO1F interacts with a SH3-domain-dependent adaptor module (CASS complex: CD2AP, ASAP1, SH3BP2, SH3KBP1) via multivalent proline-rich motif interactions with the MYO1F SH3 domain, and with additional partners via its PH domain; these interactions mediate MYO1F localization to podosomes and phagocytic cups in macrophages and microglia. MYO1F recruitment to the phagocytic cup requires motor activity and intact PH and SH3 domains.","method":"In situ proximity labeling proteomics (BioID), structural modeling, site-directed mutagenesis of SH3/PH domains, co-immunoprecipitation, immunofluorescence, functional phagocytosis assays","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1-2 — proximity proteomics plus mutagenesis plus functional assays in a single rigorous study","pmids":["41208482"],"is_preprint":false},{"year":2026,"finding":"Myo1f promotes actin polymerization by recruiting EPLINα (epithelial protein lost in neoplasm), which stabilizes F-actin and reduces G-actin availability; this leads to nuclear translocation of MRTFA and transcriptional upregulation of ITGB2 (integrin β2), thereby enhancing monocyte adhesion to vascular endothelium.","method":"Co-immunoprecipitation mass spectrometry, Myo1f KO mouse/Apoe-/- atherosclerosis model, bone marrow transplantation, actin polymerization assays, nuclear fractionation for MRTFA, ITGB2 expression assays, MRTFA inhibitor (CCG-1423) treatment","journal":"Redox biology","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP-MS, KO mouse, multiple mechanistic assays, single lab","pmids":["41610517"],"is_preprint":false},{"year":2025,"finding":"Myo1f (together with Myo1e) localizes specifically to the base of podosomes, underneath the actin core near the ventral plasma membrane, mediated by the TH2 domain; loss of Myo1e/f increases podosome size and alters turnover and lateral mobility, consistent with a role in attaching core actin filaments to the plasma membrane. Double-KO macrophages show reduced 2D and 3D migration.","method":"shRNA knockdown and CRISPR KO of Myo1e/f in macrophages, live-cell fluorescence imaging, FRAP for podosome turnover, 2D/3D migration assays, TH2-domain deletion constructs","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — KO/KD with multiple live-imaging and functional readouts; preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.04.28.651090"],"is_preprint":true},{"year":2025,"finding":"MYO1F in tumor-associated neutrophils restrains STAT3 activity to inhibit immunosuppression; tumor-derived TGF-β1 suppresses Myo1f transcription via SPI1 displacement from intron 8 through DNA methylation, decreasing MYO1F and reprogramming neutrophils to an immunosuppressive STAT3-dependent state.","method":"ChIP, bisulfite sequencing, MYO1F KO mice, STAT3 inhibition assays, TGF-β1 treatment of neutrophils, tumor models","journal":"Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2 — epigenetic mechanism validated by ChIP and bisulfite sequencing plus KO mouse model, single lab","pmids":["40202509"],"is_preprint":false},{"year":2018,"finding":"A missense mutation (Gly134Ser) in the MYO1F motor head domain (near the ATP-binding site) alters mitochondrial network morphology, increases mitochondrial mass and ROS, and confers increased colony formation and invasion in thyroid cells; overexpression in zebrafish embryos induces cell proliferation, indicating the motor domain integrity is required for normal mitochondrial regulation.","method":"Stable expression of WT vs. mutant MYO1F in FRTL-5 thyroid cells, mitochondrial staining, ROS measurement, colony formation/invasion assays, zebrafish overexpression model","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2-3 — mutagenesis with multiple cellular phenotypic readouts plus in vivo zebrafish validation, single lab","pmids":["29672841"],"is_preprint":false}],"current_model":"MYO1F is a long-tailed class I unconventional myosin expressed predominantly in immune cells that functions at the cortical actin–plasma membrane interface to regulate cell adhesion, migration, and exocytosis; mechanistically, it acts as a scaffold/adaptor recruiting acetyltransferases (αTAT1/KAT2A) to their substrates (α-tubulin, cGAS, GAPDH) downstream of kinases (SYK, LCK), recruits EPLINα to stabilize F-actin and drive MRTFA-dependent integrin transcription, and localizes to podosomes and phagocytic cups via SH3-domain interactions with the CASS adaptor complex (CD2AP, ASAP1, SH3BP2, SH3KBP1) and PH-domain membrane contacts, collectively coordinating innate immune signaling, integrin trafficking, and cytoskeletal dynamics in myeloid and lymphoid cells."},"narrative":{"teleology":[{"year":2006,"claim":"Establishing the foundational role: Myo1f knockout mice revealed that this class I myosin negatively regulates neutrophil granule exocytosis and positively supports cell motility, providing the first evidence that a myosin-I controls immune cell adhesion–migration balance at the cortical actin interface.","evidence":"Myo1f KO mouse with FACS adhesion assays, exocytosis measurements, and in vivo infection model (Science)","pmids":["17023661"],"confidence":"High","gaps":["Molecular mechanism by which Myo1f restrains granule fusion was not identified","Whether Myo1f directly contacts integrin-containing vesicles or acts indirectly through cortical actin was unclear"]},{"year":2018,"claim":"A motor-domain missense mutation (Gly134Ser) near the ATP-binding site demonstrated that MYO1F motor integrity influences mitochondrial morphology, ROS levels, and cellular proliferation, broadening its functional scope beyond canonical actin-based roles.","evidence":"Stable expression of WT vs. mutant MYO1F in thyroid cells with mitochondrial staining, ROS assays, and zebrafish overexpression","pmids":["29672841"],"confidence":"Medium","gaps":["Whether MYO1F directly localizes to mitochondria or acts indirectly was not resolved","Relevance to immune cell biology was not tested","No structural model of how G134S alters ATPase activity"]},{"year":2019,"claim":"Identification of SH3BP2 (3BP2) as a direct MYO1F interactor downstream of KIT signaling in mast cells linked MYO1F to receptor tyrosine kinase pathways and provided the first evidence that it controls integrin surface expression and Rac2/Cdc42 activation.","evidence":"Co-immunoprecipitation and shRNA knockdown in mast cells with flow cytometry, GTPase assays, and migration assays","pmids":["31143189"],"confidence":"Medium","gaps":["Reciprocal Co-IP was not shown","Whether MYO1F–3BP2 interaction is direct or bridged by additional adaptors was not confirmed","Mechanism by which MYO1F controls integrin surface levels was not defined"]},{"year":2021,"claim":"A critical mechanistic advance showed MYO1F functions as an adaptor that recruits αTAT1 acetyltransferase to α-tubulin upon Dectin-1 stimulation, with the resulting tubulin acetylation controlling SYK/CARD9 membrane-to-cytoplasm trafficking for antifungal innate immunity—establishing its scaffold/adaptor paradigm.","evidence":"Reciprocal Co-IP, Myo1f KO macrophages, Dectin-1 stimulation, tubulin acetylation blots, in vivo Candida infection model (PNAS)","pmids":["34301894"],"confidence":"High","gaps":["Whether MYO1F motor activity is required for αTAT1 recruitment was not tested","Structural basis for the MYO1F–αTAT1–tubulin ternary complex was not determined"]},{"year":2021,"claim":"MYO1F was shown to be required for full mast cell degranulation through IgE/FcεRI and MRGPRX2, controlling Cdc42 activation, cortical actin reassembly, and mitochondrial translocation to exocytic sites, extending the exocytosis phenotype to a defined signaling cascade.","evidence":"shRNA knockdown in human LAD2 mast cells with degranulation assays, Cdc42 activation, confocal imaging, AKT/DRP1 phosphorylation blots","pmids":["33941653"],"confidence":"Medium","gaps":["Direct versus indirect effect on mitochondrial translocation was not resolved","Whether MYO1F interacts directly with DRP1 or mitochondrial fission machinery was not tested"]},{"year":2023,"claim":"Myo1f KO γδT intraepithelial lymphocytes showed reduced CCR9 and α4β7 surface expression with defective chemokine receptor polarization, demonstrating MYO1F controls integrin/receptor polarization and homing across lymphoid lineages beyond myeloid cells.","evidence":"Myo1f KO mouse, flow cytometry, in vitro migration, immunofluorescence for receptor polarization","pmids":["37207213"],"confidence":"Medium","gaps":["Molecular mechanism linking MYO1F to receptor polarization machinery was not identified","Whether the αTAT1 scaffold mechanism operates in γδT cells was not tested"]},{"year":2024,"claim":"Two studies defined the kinase-scaffold-acetyltransferase paradigm in new contexts: SYK phosphorylates MYO1F to recruit KAT2A for cGAS acetylation and type I IFN production during viral infection, while LCK phosphorylates MYO1F to facilitate αTAT1-mediated GAPDH acetylation enhancing glycolysis in T cells—generalizing MYO1F as a phosphorylation-activated acetyltransferase scaffold.","evidence":"Co-IP, mutagenesis of phospho-sites and acetylation sites, in vitro kinase assays, KO macrophages and T-cell-specific KO mice, GAPDH activity/Seahorse assays, human PTCL patient validation","pmids":["39694035","39668163"],"confidence":"High","gaps":["Whether MYO1F recruits yet additional acetyltransferases to other substrates is unknown","How phosphorylation conformationally enables acetyltransferase binding is structurally unresolved","The oncogenic VAV1-MYO1F fusion's precise structural mechanism for hyperacetylation was not determined"]},{"year":2025,"claim":"Proximity proteomics and mutagenesis identified MYO1F's SH3 domain as the hub for a multivalent CASS adaptor complex (CD2AP, ASAP1, SH3BP2, SH3KBP1) and its PH domain as essential for membrane targeting, together mediating localization to podosomes and phagocytic cups in macrophages—providing the structural logic for MYO1F recruitment.","evidence":"BioID proximity labeling, SH3/PH domain mutagenesis, Co-IP, immunofluorescence, phagocytosis assays in macrophages and microglia (J Cell Sci)","pmids":["41208482"],"confidence":"High","gaps":["Quantitative affinities for individual SH3-PRM interactions were not measured","Whether the CASS complex is required for the acetyltransferase scaffold functions is untested"]},{"year":2025,"claim":"In tumor-associated neutrophils, TGF-β1 suppresses MYO1F transcription through SPI1 displacement via DNA methylation at intron 8, and MYO1F loss derepresses STAT3-dependent immunosuppression, revealing an epigenetic axis by which tumors exploit MYO1F downregulation.","evidence":"ChIP, bisulfite sequencing, MYO1F KO mice, TGF-β1 treatment, STAT3 inhibition, tumor models (J Exp Med)","pmids":["40202509"],"confidence":"Medium","gaps":["Direct mechanism by which MYO1F restrains STAT3 activity was not identified","Whether the acetyltransferase scaffold function mediates STAT3 regulation is unknown"]},{"year":2026,"claim":"MYO1F was shown to recruit EPLINα to stabilize F-actin, reducing G-actin availability and enabling MRTFA nuclear translocation that transcriptionally upregulates integrin β2 (ITGB2), providing a direct mechanistic link from MYO1F's actin-binding functions to integrin expression and monocyte-endothelial adhesion in atherosclerosis.","evidence":"Co-IP-MS, Myo1f KO/Apoe−/− atherosclerosis mouse model, bone marrow transplant, actin polymerization assays, MRTFA nuclear fractionation, MRTFA inhibitor (Redox Biol)","pmids":["41610517"],"confidence":"Medium","gaps":["Whether EPLINα recruitment requires MYO1F motor activity or the tail domains was not dissected","Relationship between the EPLINα–MRTFA pathway and the αTAT1 acetyltransferase scaffold function is unexplored"]},{"year":null,"claim":"Key unresolved questions include: (1) how phosphorylation-induced conformational changes in MYO1F enable acetyltransferase recruitment, (2) whether the CASS adaptor complex and the acetyltransferase scaffold functions are interdependent or parallel, (3) the structural basis for MYO1F's selectivity among acetyltransferases (αTAT1 vs. KAT2A) and substrates, and (4) how MYO1F motor activity versus scaffold activity are coordinated in vivo.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of MYO1F tail domains in complex with partners","No reconstituted system testing motor-scaffold coupling","Functional redundancy with MYO1E at podosomes not fully resolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,7,8,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,5,6,8]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[7,11]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1,5,7]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,7,8,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2,6]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,2,3,4,5,10]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,2,5,6]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[6]}],"complexes":["CASS adaptor complex (CD2AP/ASAP1/SH3BP2/SH3KBP1)"],"partners":["ATAT1","KAT2A","SH3BP2","CD2AP","ASAP1","SH3KBP1","LIMA1"],"other_free_text":[]},"mechanistic_narrative":"MYO1F is a long-tailed class I unconventional myosin expressed predominantly in immune cells that functions at the cortical actin–plasma membrane interface to coordinate cell adhesion, migration, exocytosis, and innate immune signaling. It acts as a kinase-responsive scaffold: SYK and LCK phosphorylate MYO1F, which then recruits acetyltransferases (αTAT1, KAT2A) to specific substrates—α-tubulin for Dectin-1/CARD9 antifungal signaling, cGAS for type I interferon production, and GAPDH for glycolytic reprogramming in T cells [PMID:34301894, PMID:39694035, PMID:39668163]. MYO1F localizes to podosomes and phagocytic cups through SH3-domain interactions with the CASS adaptor complex (CD2AP, ASAP1, SH3BP2, SH3KBP1) and PH-domain membrane contacts, and recruits EPLINα to stabilize F-actin and drive MRTFA-dependent integrin β2 transcription, linking cortical cytoskeletal dynamics to integrin-mediated adhesion and migration [PMID:41208482, PMID:41610517]. Loss of Myo1f in neutrophils causes augmented granule exocytosis with increased adhesion and reduced motility, while in tumor-associated neutrophils its epigenetic silencing by TGF-β1 derepresses STAT3-dependent immunosuppression [PMID:17023661, PMID:40202509]."},"prefetch_data":{"uniprot":{"accession":"O00160","full_name":"Unconventional myosin-If","aliases":["Myosin-Ie"],"length_aa":1098,"mass_kda":124.8,"function":"Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/O00160/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYO1F","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MYO1F","total_profiled":1310},"omim":[{"mim_id":"619995","title":"NEURODEVELOPMENTAL DISORDER WITH INTENTION TREMOR, PYRAMIDAL SIGNS, DYSPRAXIA, AND OCULAR ANOMALIES; NEDITPO","url":"https://www.omim.org/entry/619995"},{"mim_id":"616920","title":"HEART AND BRAIN MALFORMATION SYNDROME; HBMS","url":"https://www.omim.org/entry/616920"},{"mim_id":"613176","title":"SMG9 NONSENSE-MEDIATED mRNA DECAY FACTOR; SMG9","url":"https://www.omim.org/entry/613176"},{"mim_id":"601869","title":"DEAFNESS, AUTOSOMAL RECESSIVE 15; DFNB15","url":"https://www.omim.org/entry/601869"},{"mim_id":"601480","title":"MYOSIN IF; MYO1F","url":"https://www.omim.org/entry/601480"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Cytosol","reliability":"Enhanced"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":90.7},{"tissue":"lung","ntpm":29.3},{"tissue":"lymphoid tissue","ntpm":93.0}],"url":"https://www.proteinatlas.org/search/MYO1F"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"O00160","domains":[{"cath_id":"3.40.850.10","chopping":"13-103_588-620","consensus_level":"medium","plddt":86.6806,"start":13,"end":620},{"cath_id":"1.20.58.530","chopping":"402-523_559-569","consensus_level":"high","plddt":84.3667,"start":402,"end":569},{"cath_id":"3.30.70.1590","chopping":"622-680","consensus_level":"high","plddt":88.0656,"start":622,"end":680},{"cath_id":"2.30.29.30","chopping":"725-916","consensus_level":"high","plddt":90.4524,"start":725,"end":916},{"cath_id":"2.30.30.40","chopping":"1046-1098","consensus_level":"high","plddt":90.0177,"start":1046,"end":1098}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O00160","model_url":"https://alphafold.ebi.ac.uk/files/AF-O00160-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O00160-F1-predicted_aligned_error_v6.png","plddt_mean":80.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYO1F","jax_strain_url":"https://www.jax.org/strain/search?query=MYO1F"},"sequence":{"accession":"O00160","fasta_url":"https://rest.uniprot.org/uniprotkb/O00160.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O00160/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O00160"}},"corpus_meta":[{"pmid":"17023661","id":"PMC_17023661","title":"Modulation of cell adhesion and motility in the immune system by Myo1f.","date":"2006","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/17023661","citation_count":98,"is_preprint":false},{"pmid":"29672841","id":"PMC_29672841","title":"Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer.","date":"2018","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/29672841","citation_count":35,"is_preprint":false},{"pmid":"15897884","id":"PMC_15897884","title":"The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22.","date":"2005","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/15897884","citation_count":35,"is_preprint":false},{"pmid":"19027848","id":"PMC_19027848","title":"Are MYO1C and MYO1F associated with hearing loss?","date":"2008","source":"Biochimica et biophysica 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reports","url":"https://pubmed.ncbi.nlm.nih.gov/35443168","citation_count":18,"is_preprint":false},{"pmid":"33941653","id":"PMC_33941653","title":"MYO1F Regulates IgE and MRGPRX2-Dependent Mast Cell Exocytosis.","date":"2021","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/33941653","citation_count":13,"is_preprint":false},{"pmid":"31143189","id":"PMC_31143189","title":"Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration.","date":"2019","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/31143189","citation_count":13,"is_preprint":false},{"pmid":"39694035","id":"PMC_39694035","title":"MYO1F positions cGAS on the plasma membrane to ensure full and functional signaling.","date":"2024","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/39694035","citation_count":11,"is_preprint":false},{"pmid":"37207213","id":"PMC_37207213","title":"Myo1f has an essential role in γδT intraepithelial lymphocyte adhesion and migration.","date":"2023","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/37207213","citation_count":6,"is_preprint":false},{"pmid":"39276460","id":"PMC_39276460","title":"Role of MYO1F in neutrophil and macrophage recruitment and pro-inflammatory cytokine production in Aspergillus fumigatus keratitis.","date":"2024","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/39276460","citation_count":3,"is_preprint":false},{"pmid":"36541400","id":"PMC_36541400","title":"The fusion oncogene VAV1-MYO1F triggers aberrant T-cell receptor signaling in vivo and drives peripheral T-cell lymphoma in mice.","date":"2023","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36541400","citation_count":3,"is_preprint":false},{"pmid":"39668163","id":"PMC_39668163","title":"MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH.","date":"2024","source":"Cellular & molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/39668163","citation_count":2,"is_preprint":false},{"pmid":"41208482","id":"PMC_41208482","title":"The MYO1F interactome reveals ASAP1, CD2AP and SH3KBP1 as novel adaptor proteins in podosomes and phagosomes.","date":"2025","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/41208482","citation_count":2,"is_preprint":false},{"pmid":"40202509","id":"PMC_40202509","title":"MYO1F in neutrophils is required for the response to immune checkpoint blockade therapy.","date":"2025","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40202509","citation_count":1,"is_preprint":false},{"pmid":"41610517","id":"PMC_41610517","title":"Myo1f regulates monocyte adhesion and contributes to atherosclerosis via MRTFA-dependent ITGB2 expression.","date":"2026","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/41610517","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.07.04.663186","title":"MYO1F interactome reveals the SH3-domain linked CASS complex at podosomes and the phagocytic cup","date":"2025-07-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.04.663186","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.28.651090","title":"Myo1e/f at the podosome base regulate podosome dynamics and promote macrophage migration","date":"2025-04-29","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.28.651090","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11038,"output_tokens":3375,"usd":0.041869},"stage2":{"model":"claude-opus-4-6","input_tokens":6794,"output_tokens":3510,"usd":0.18258},"total_usd":0.224449,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"Myo1f co-localizes with cortical actin in immune cells; Myo1f-deficient neutrophils show augmented exocytosis of β2 integrin-containing granules, increased adhesion, and reduced motility, establishing Myo1f as a regulator of granule exocytosis and cortical actin organization in immune cells.\",\n      \"method\": \"Myo1f knockout mouse model with traction force microscopy, FACS-based adhesion assays, and exocytosis measurements\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO mouse with multiple orthogonal phenotypic readouts, replicated in vivo infection model\",\n      \"pmids\": [\"17023661\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Myo1f directly interacts with the adaptor protein 3BP2 in mast cells; this interaction is modulated by KIT (SCF receptor) signaling, and Myo1f colocalizes with cortical actin. Myo1f silencing reduces β1 and β7 integrin surface expression, SCF-dependent adhesion to fibronectin, and Rac2/Cdc42 GTPase activity, placing Myo1f downstream of KIT in mast cell migration.\",\n      \"method\": \"Co-immunoprecipitation, shRNA knockdown, flow cytometry for integrin surface expression, GTPase activity assays, migration assays\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP plus KD with multiple functional readouts, single lab\",\n      \"pmids\": [\"31143189\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MYO1F acts as an adaptor that recruits both AP2A1 and α-tubulin N-acetyltransferase 1 (αTAT1) to α-tubulin upon Dectin-1 stimulation, promoting α-tubulin acetylation and controlling membrane-to-cytoplasm trafficking of SYK and CARD9 for antifungal innate immune signaling.\",\n      \"method\": \"Co-immunoprecipitation, Myo1f knockout mouse macrophages, Dectin-1 stimulation assays, tubulin acetylation western blot, in vivo Candida albicans infection model\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the USA\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, KO mouse with defined molecular mechanism, in vivo validation\",\n      \"pmids\": [\"34301894\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MYO1F is required for full mast cell degranulation via IgE/FcεRI crosslinking and MRGPRX2 stimulation; MYO1F knockdown impairs Cdc42 GTPase activation, reduces cortical actin ring reassembly after activation, and diminishes mitochondria translocation to exocytic sites along with reduced AKT and DRP1 phosphorylation.\",\n      \"method\": \"shRNA knockdown of MYO1F in human mast cells (LAD2), degranulation assays, Cdc42 GTPase activation assays, confocal imaging of actin and mitochondria, western blot for AKT/DRP1 phosphorylation\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — KD with multiple orthogonal mechanistic readouts, single lab\",\n      \"pmids\": [\"33941653\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Myo1f deficiency in γδT intraepithelial lymphocytes reduces CCR9 and α4β7 surface expression, impairs chemokine receptor and integrin polarization, reduces tyrosine phosphorylation, and results in defective CCL25-dependent and independent migration and homing to the small intestine intraepithelial compartment.\",\n      \"method\": \"Myo1f KO mouse model, flow cytometry for surface receptor expression, in vitro migration assays, immunofluorescence for receptor polarization\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO mouse with defined cellular and molecular phenotypes, single lab\",\n      \"pmids\": [\"37207213\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"During viral infection, SYK phosphorylates MYO1F at the plasma membrane, which facilitates recruitment of KAT2A acetyltransferase to cGAS; KAT2A then acetylates cGAS at lysines 421, 292, and 131, essential for cGAS activation and type I interferon production. Membrane-localized cGAS (anchored by MYO1F) is required for signaling triggered by virus-cell fusion.\",\n      \"method\": \"Co-immunoprecipitation, mutagenesis of MYO1F and cGAS acetylation sites, proximity ligation assays, KO macrophages, in vitro kinase assays, type I IFN production assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — Co-IP, mutagenesis, in vitro kinase assay, KO cells with defined molecular mechanism\",\n      \"pmids\": [\"39694035\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"After TCR stimulation, LCK phosphorylates MYO1F at tyrosines 607 and 634; phosphorylated MYO1F then facilitates αTAT1-mediated acetylation of GAPDH at Lys84, 86, and 227, enhancing GAPDH enzymatic activity, glycolysis, and T-cell effector function. The oncogenic VAV1-MYO1F fusion causes hyperacetylation of GAPDH and aberrant glycolysis.\",\n      \"method\": \"T-cell-specific Myo1f KO mice, phosphomutant and acetylation-site mutagenesis, in vitro kinase assays, GAPDH activity assays, glycolysis measurements (Seahorse), Co-IP, human PTCL patient sample validation\",\n      \"journal\": \"Cellular & molecular immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro kinase assay, mutagenesis, KO mouse, patient sample validation with multiple orthogonal methods\",\n      \"pmids\": [\"39668163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO1F interacts with a SH3-domain-dependent adaptor module (CASS complex: CD2AP, ASAP1, SH3BP2, SH3KBP1) via multivalent proline-rich motif interactions with the MYO1F SH3 domain, and with additional partners via its PH domain; these interactions mediate MYO1F localization to podosomes and phagocytic cups in macrophages and microglia. MYO1F recruitment to the phagocytic cup requires motor activity and intact PH and SH3 domains.\",\n      \"method\": \"In situ proximity labeling proteomics (BioID), structural modeling, site-directed mutagenesis of SH3/PH domains, co-immunoprecipitation, immunofluorescence, functional phagocytosis assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — proximity proteomics plus mutagenesis plus functional assays in a single rigorous study\",\n      \"pmids\": [\"41208482\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Myo1f promotes actin polymerization by recruiting EPLINα (epithelial protein lost in neoplasm), which stabilizes F-actin and reduces G-actin availability; this leads to nuclear translocation of MRTFA and transcriptional upregulation of ITGB2 (integrin β2), thereby enhancing monocyte adhesion to vascular endothelium.\",\n      \"method\": \"Co-immunoprecipitation mass spectrometry, Myo1f KO mouse/Apoe-/- atherosclerosis model, bone marrow transplantation, actin polymerization assays, nuclear fractionation for MRTFA, ITGB2 expression assays, MRTFA inhibitor (CCG-1423) treatment\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP-MS, KO mouse, multiple mechanistic assays, single lab\",\n      \"pmids\": [\"41610517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Myo1f (together with Myo1e) localizes specifically to the base of podosomes, underneath the actin core near the ventral plasma membrane, mediated by the TH2 domain; loss of Myo1e/f increases podosome size and alters turnover and lateral mobility, consistent with a role in attaching core actin filaments to the plasma membrane. Double-KO macrophages show reduced 2D and 3D migration.\",\n      \"method\": \"shRNA knockdown and CRISPR KO of Myo1e/f in macrophages, live-cell fluorescence imaging, FRAP for podosome turnover, 2D/3D migration assays, TH2-domain deletion constructs\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO/KD with multiple live-imaging and functional readouts; preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.04.28.651090\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO1F in tumor-associated neutrophils restrains STAT3 activity to inhibit immunosuppression; tumor-derived TGF-β1 suppresses Myo1f transcription via SPI1 displacement from intron 8 through DNA methylation, decreasing MYO1F and reprogramming neutrophils to an immunosuppressive STAT3-dependent state.\",\n      \"method\": \"ChIP, bisulfite sequencing, MYO1F KO mice, STAT3 inhibition assays, TGF-β1 treatment of neutrophils, tumor models\",\n      \"journal\": \"Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — epigenetic mechanism validated by ChIP and bisulfite sequencing plus KO mouse model, single lab\",\n      \"pmids\": [\"40202509\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"A missense mutation (Gly134Ser) in the MYO1F motor head domain (near the ATP-binding site) alters mitochondrial network morphology, increases mitochondrial mass and ROS, and confers increased colony formation and invasion in thyroid cells; overexpression in zebrafish embryos induces cell proliferation, indicating the motor domain integrity is required for normal mitochondrial regulation.\",\n      \"method\": \"Stable expression of WT vs. mutant MYO1F in FRTL-5 thyroid cells, mitochondrial staining, ROS measurement, colony formation/invasion assays, zebrafish overexpression model\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — mutagenesis with multiple cellular phenotypic readouts plus in vivo zebrafish validation, single lab\",\n      \"pmids\": [\"29672841\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYO1F is a long-tailed class I unconventional myosin expressed predominantly in immune cells that functions at the cortical actin–plasma membrane interface to regulate cell adhesion, migration, and exocytosis; mechanistically, it acts as a scaffold/adaptor recruiting acetyltransferases (αTAT1/KAT2A) to their substrates (α-tubulin, cGAS, GAPDH) downstream of kinases (SYK, LCK), recruits EPLINα to stabilize F-actin and drive MRTFA-dependent integrin transcription, and localizes to podosomes and phagocytic cups via SH3-domain interactions with the CASS adaptor complex (CD2AP, ASAP1, SH3BP2, SH3KBP1) and PH-domain membrane contacts, collectively coordinating innate immune signaling, integrin trafficking, and cytoskeletal dynamics in myeloid and lymphoid cells.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MYO1F is a long-tailed class I unconventional myosin expressed predominantly in immune cells that functions at the cortical actin–plasma membrane interface to coordinate cell adhesion, migration, exocytosis, and innate immune signaling. It acts as a kinase-responsive scaffold: SYK and LCK phosphorylate MYO1F, which then recruits acetyltransferases (αTAT1, KAT2A) to specific substrates—α-tubulin for Dectin-1/CARD9 antifungal signaling, cGAS for type I interferon production, and GAPDH for glycolytic reprogramming in T cells [PMID:34301894, PMID:39694035, PMID:39668163]. MYO1F localizes to podosomes and phagocytic cups through SH3-domain interactions with the CASS adaptor complex (CD2AP, ASAP1, SH3BP2, SH3KBP1) and PH-domain membrane contacts, and recruits EPLINα to stabilize F-actin and drive MRTFA-dependent integrin β2 transcription, linking cortical cytoskeletal dynamics to integrin-mediated adhesion and migration [PMID:41208482, PMID:41610517]. Loss of Myo1f in neutrophils causes augmented granule exocytosis with increased adhesion and reduced motility, while in tumor-associated neutrophils its epigenetic silencing by TGF-β1 derepresses STAT3-dependent immunosuppression [PMID:17023661, PMID:40202509].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing the foundational role: Myo1f knockout mice revealed that this class I myosin negatively regulates neutrophil granule exocytosis and positively supports cell motility, providing the first evidence that a myosin-I controls immune cell adhesion–migration balance at the cortical actin interface.\",\n      \"evidence\": \"Myo1f KO mouse with FACS adhesion assays, exocytosis measurements, and in vivo infection model (Science)\",\n      \"pmids\": [\"17023661\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism by which Myo1f restrains granule fusion was not identified\",\n        \"Whether Myo1f directly contacts integrin-containing vesicles or acts indirectly through cortical actin was unclear\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"A motor-domain missense mutation (Gly134Ser) near the ATP-binding site demonstrated that MYO1F motor integrity influences mitochondrial morphology, ROS levels, and cellular proliferation, broadening its functional scope beyond canonical actin-based roles.\",\n      \"evidence\": \"Stable expression of WT vs. mutant MYO1F in thyroid cells with mitochondrial staining, ROS assays, and zebrafish overexpression\",\n      \"pmids\": [\"29672841\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether MYO1F directly localizes to mitochondria or acts indirectly was not resolved\",\n        \"Relevance to immune cell biology was not tested\",\n        \"No structural model of how G134S alters ATPase activity\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identification of SH3BP2 (3BP2) as a direct MYO1F interactor downstream of KIT signaling in mast cells linked MYO1F to receptor tyrosine kinase pathways and provided the first evidence that it controls integrin surface expression and Rac2/Cdc42 activation.\",\n      \"evidence\": \"Co-immunoprecipitation and shRNA knockdown in mast cells with flow cytometry, GTPase assays, and migration assays\",\n      \"pmids\": [\"31143189\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Reciprocal Co-IP was not shown\",\n        \"Whether MYO1F–3BP2 interaction is direct or bridged by additional adaptors was not confirmed\",\n        \"Mechanism by which MYO1F controls integrin surface levels was not defined\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"A critical mechanistic advance showed MYO1F functions as an adaptor that recruits αTAT1 acetyltransferase to α-tubulin upon Dectin-1 stimulation, with the resulting tubulin acetylation controlling SYK/CARD9 membrane-to-cytoplasm trafficking for antifungal innate immunity—establishing its scaffold/adaptor paradigm.\",\n      \"evidence\": \"Reciprocal Co-IP, Myo1f KO macrophages, Dectin-1 stimulation, tubulin acetylation blots, in vivo Candida infection model (PNAS)\",\n      \"pmids\": [\"34301894\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether MYO1F motor activity is required for αTAT1 recruitment was not tested\",\n        \"Structural basis for the MYO1F–αTAT1–tubulin ternary complex was not determined\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"MYO1F was shown to be required for full mast cell degranulation through IgE/FcεRI and MRGPRX2, controlling Cdc42 activation, cortical actin reassembly, and mitochondrial translocation to exocytic sites, extending the exocytosis phenotype to a defined signaling cascade.\",\n      \"evidence\": \"shRNA knockdown in human LAD2 mast cells with degranulation assays, Cdc42 activation, confocal imaging, AKT/DRP1 phosphorylation blots\",\n      \"pmids\": [\"33941653\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect effect on mitochondrial translocation was not resolved\",\n        \"Whether MYO1F interacts directly with DRP1 or mitochondrial fission machinery was not tested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Myo1f KO γδT intraepithelial lymphocytes showed reduced CCR9 and α4β7 surface expression with defective chemokine receptor polarization, demonstrating MYO1F controls integrin/receptor polarization and homing across lymphoid lineages beyond myeloid cells.\",\n      \"evidence\": \"Myo1f KO mouse, flow cytometry, in vitro migration, immunofluorescence for receptor polarization\",\n      \"pmids\": [\"37207213\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism linking MYO1F to receptor polarization machinery was not identified\",\n        \"Whether the αTAT1 scaffold mechanism operates in γδT cells was not tested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Two studies defined the kinase-scaffold-acetyltransferase paradigm in new contexts: SYK phosphorylates MYO1F to recruit KAT2A for cGAS acetylation and type I IFN production during viral infection, while LCK phosphorylates MYO1F to facilitate αTAT1-mediated GAPDH acetylation enhancing glycolysis in T cells—generalizing MYO1F as a phosphorylation-activated acetyltransferase scaffold.\",\n      \"evidence\": \"Co-IP, mutagenesis of phospho-sites and acetylation sites, in vitro kinase assays, KO macrophages and T-cell-specific KO mice, GAPDH activity/Seahorse assays, human PTCL patient validation\",\n      \"pmids\": [\"39694035\", \"39668163\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether MYO1F recruits yet additional acetyltransferases to other substrates is unknown\",\n        \"How phosphorylation conformationally enables acetyltransferase binding is structurally unresolved\",\n        \"The oncogenic VAV1-MYO1F fusion's precise structural mechanism for hyperacetylation was not determined\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proximity proteomics and mutagenesis identified MYO1F's SH3 domain as the hub for a multivalent CASS adaptor complex (CD2AP, ASAP1, SH3BP2, SH3KBP1) and its PH domain as essential for membrane targeting, together mediating localization to podosomes and phagocytic cups in macrophages—providing the structural logic for MYO1F recruitment.\",\n      \"evidence\": \"BioID proximity labeling, SH3/PH domain mutagenesis, Co-IP, immunofluorescence, phagocytosis assays in macrophages and microglia (J Cell Sci)\",\n      \"pmids\": [\"41208482\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Quantitative affinities for individual SH3-PRM interactions were not measured\",\n        \"Whether the CASS complex is required for the acetyltransferase scaffold functions is untested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"In tumor-associated neutrophils, TGF-β1 suppresses MYO1F transcription through SPI1 displacement via DNA methylation at intron 8, and MYO1F loss derepresses STAT3-dependent immunosuppression, revealing an epigenetic axis by which tumors exploit MYO1F downregulation.\",\n      \"evidence\": \"ChIP, bisulfite sequencing, MYO1F KO mice, TGF-β1 treatment, STAT3 inhibition, tumor models (J Exp Med)\",\n      \"pmids\": [\"40202509\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct mechanism by which MYO1F restrains STAT3 activity was not identified\",\n        \"Whether the acetyltransferase scaffold function mediates STAT3 regulation is unknown\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"MYO1F was shown to recruit EPLINα to stabilize F-actin, reducing G-actin availability and enabling MRTFA nuclear translocation that transcriptionally upregulates integrin β2 (ITGB2), providing a direct mechanistic link from MYO1F's actin-binding functions to integrin expression and monocyte-endothelial adhesion in atherosclerosis.\",\n      \"evidence\": \"Co-IP-MS, Myo1f KO/Apoe−/− atherosclerosis mouse model, bone marrow transplant, actin polymerization assays, MRTFA nuclear fractionation, MRTFA inhibitor (Redox Biol)\",\n      \"pmids\": [\"41610517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether EPLINα recruitment requires MYO1F motor activity or the tail domains was not dissected\",\n        \"Relationship between the EPLINα–MRTFA pathway and the αTAT1 acetyltransferase scaffold function is unexplored\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: (1) how phosphorylation-induced conformational changes in MYO1F enable acetyltransferase recruitment, (2) whether the CASS adaptor complex and the acetyltransferase scaffold functions are interdependent or parallel, (3) the structural basis for MYO1F's selectivity among acetyltransferases (αTAT1 vs. KAT2A) and substrates, and (4) how MYO1F motor activity versus scaffold activity are coordinated in vivo.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of MYO1F tail domains in complex with partners\",\n        \"No reconstituted system testing motor-scaffold coupling\",\n        \"Functional redundancy with MYO1E at podosomes not fully resolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 7, 8, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 5, 6, 8]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [7, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 5, 7]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 7, 8, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 2, 3, 4, 5, 10]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 2, 5, 6]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [\n      \"CASS adaptor complex (CD2AP/ASAP1/SH3BP2/SH3KBP1)\"\n    ],\n    \"partners\": [\n      \"ATAT1\",\n      \"KAT2A\",\n      \"SH3BP2\",\n      \"CD2AP\",\n      \"ASAP1\",\n      \"SH3KBP1\",\n      \"LIMA1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}