Affinage

MYO1F

Unconventional myosin-If · UniProt O00160

Length
1098 aa
Mass
124.8 kDa
Annotated
2026-06-10
17 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYO1F is a class I unconventional myosin expressed in immune cells that governs cortical actin dynamics, integrin trafficking, and leukocyte motility (PMID:17023661). Genetic loss in mice causes excessive surface delivery of β2-integrin-containing granules with reduced cortical actin and impaired neutrophil motility, establishing its core role in coupling the actin cytoskeleton to integrin exocytosis (PMID:17023661); consistent with this, MYO1F controls surface integrin and chemokine-receptor display required for γδT intraepithelial lymphocyte homing and for SCF-driven mast cell adhesion and migration, the latter through physical association with the adaptor 3BP2/SH3BP2 (PMID:31143189, PMID:37207213). MYO1F localizes to cortical actin, podosomes, and phagocytic cups, where it engages a multivalent CASS adaptor module (CD2AP, ASAP1, SH3BP2, SH3KBP1) through its SH3 domain and additional adaptors through its PH domain; its recruitment to the phagocytic cup requires motor activity and intact SH3 and PH domains (PMID:41208482). Beyond its structural role, MYO1F functions as a phosphorylation-gated adaptor that recruits acetyltransferases to direct innate and adaptive immune signaling: upon Dectin-1 stimulation it brings α-TAT1 and AP2A1 to α-tubulin to drive acetylation that controls SYK/CARD9 trafficking and antifungal defense (PMID:34301894); during viral infection SYK-phosphorylated MYO1F recruits KAT2A to acetylate and activate plasma-membrane cGAS for type I interferon production (PMID:39694035); and following TCR engagement LCK phosphorylates MYO1F at Tyr607/Tyr634, recruiting α-TAT1 to acetylate and activate GAPDH, thereby licensing glycolysis for T-cell effector function (PMID:39668163). MYO1F also regulates immune-cell gene expression and metabolism, promoting MRTFA-dependent ITGB2 transcription via EPLINα-mediated actin polymerization in monocytes (PMID:41610517) and restraining STAT3-driven neutrophil immunosuppression (PMID:40202509). A VAV1-MYO1F fusion drives GAPDH hyperacetylation and aberrant T-cell proliferation, and a motor-domain p.Gly134Ser mutation confers transforming properties, linking MYO1F dysregulation to oncogenic phenotypes (PMID:39668163, PMID:29672841).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2006 High

    Established MYO1F's foundational cellular role by asking how immune-cell adhesion and motility are balanced, showing it restrains integrin exocytosis through cortical actin.

    Evidence Myo1f knockout mouse neutrophils with adhesion/motility, exocytosis, and cortical actin imaging assays

    PMID:17023661

    Open questions at the time
    • Molecular link between MYO1F motor activity and the granule exocytosis machinery not resolved
    • Domain requirements for cortical actin localization not defined here
  2. 2019 Medium

    Identified a direct adaptor partner (3BP2) connecting MYO1F to receptor signaling, addressing how MYO1F is integrated into integrin-dependent mast cell migration.

    Evidence Co-IP, shRNA silencing, adhesion/migration, and flow cytometry in mast cells

    PMID:31143189

    Open questions at the time
    • Co-IP without reciprocal structural mapping of the interaction interface
    • How KIT/SCF signaling modulates the interaction mechanistically unclear
  3. 2021 Medium

    Extended MYO1F's role to regulated secretion and metabolism, showing it is required for Cdc42 activation, cortical actin ring reassembly, granule positioning, and mitochondrial dynamics during mast cell degranulation.

    Evidence shRNA knockdown with degranulation, GTPase activation, imaging, and phospho-western assays in human mast cells

    PMID:33941653

    Open questions at the time
    • Direct biochemical link between MYO1F and Cdc42/DRP1 regulation not established
    • Single-lab knockdown without rescue
  4. 2021 High

    Revealed MYO1F as a phosphorylation-independent acetyltransferase-recruiting adaptor in antifungal immunity, defining how it links Dectin-1 signaling to microtubule acetylation and SYK/CARD9 trafficking.

    Evidence Myo1f KO mice, Co-IP, tubulin acetylation and trafficking assays, Candida infection model

    PMID:34301894

    Open questions at the time
    • Structural basis of the α-TAT1/AP2A1 recruitment not resolved
    • Whether motor activity is required for acetyltransferase delivery untested
  5. 2023 Medium

    Generalized the integrin/chemokine-receptor trafficking role to lymphocyte homing, showing MYO1F is required for γδT IEL surface receptor polarization and gut homing.

    Evidence Myo1f KO mice with in vivo homing, adhesion/migration, and flow cytometry assays

    PMID:37207213

    Open questions at the time
    • Direct molecular partners mediating receptor polarization not identified
    • Single-lab study
  6. 2024 High

    Defined a kinase-gated acetylation cascade in antiviral defense, showing SYK-phosphorylated MYO1F recruits KAT2A to acetylate and activate plasma-membrane cGAS.

    Evidence Co-IP, proximity ligation, site mutagenesis, kinase assays, KO macrophages, viral infection and IFN assays

    PMID:39694035

    Open questions at the time
    • How virus-cell fusion couples to SYK activation of MYO1F not fully resolved
    • Stoichiometry of the MYO1F-KAT2A-cGAS complex unknown
  7. 2024 High

    Mapped a TCR-driven branch of the same scaffold logic, showing LCK phosphorylates MYO1F at Tyr607/634 to recruit α-TAT1 and acetylate GAPDH, linking MYO1F to T-cell glycolysis and to oncogenic VAV1-MYO1F fusions.

    Evidence T-cell-specific KO mice, site mutagenesis, kinase and GAPDH acetylation assays, ECAR metabolism, PTCL patient samples

    PMID:39668163

    Open questions at the time
    • Structural mechanism of phospho-MYO1F binding α-TAT1 not solved
    • Contribution of MYO1F motor/actin function vs scaffolding to glycolysis not dissected
  8. 2025 High

    Resolved the adaptor architecture targeting MYO1F to actin-rich structures, defining SH3-domain CASS module and PH-domain interactions and the domain/motor requirements for phagocytic cup recruitment.

    Evidence Proximity labelling proteomics, structural modelling, SH3/PH mutagenesis, co-localization, phagocytosis assays in macrophages/microglia

    PMID:41208482

    Open questions at the time
    • Functional consequence of each individual CASS partner not separated
    • How adaptor binding is regulated by signaling not addressed
  9. 2025 Medium

    Positioned MYO1F at the podosome base as a membrane-actin tether, distinguishing its mechanical role from its signaling role and linking it to macrophage migration.

    Evidence KO/KD macrophages, TIRF/live imaging, podosome turnover and migration assays, domain truncations (preprint)

    PMID:bio_10.1101_2025.04.28.651090

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Functional overlap vs distinct roles of Myo1e and Myo1f not fully separated
  10. 2025 Medium

    Connected MYO1F to transcriptional control of neutrophil state, showing it restrains STAT3-driven immunosuppression and is silenced by tumor TGF-β1 via intron-8 DNA methylation.

    Evidence KO/KD neutrophils, STAT3 activity assays, methylation/chromatin analysis, tumor and ICB mouse models

    PMID:40202509

    Open questions at the time
    • Mechanistic link between MYO1F and STAT3 regulation not biochemically defined
    • Single-lab study
  11. 2026 Medium

    Defined a MYO1F actin-to-transcription axis controlling integrin expression, showing EPLINα recruitment drives MRTFA nuclear translocation and ITGB2 upregulation in monocyte adhesion and atherosclerosis.

    Evidence Myo1f KO;Apoe-/- mice, bone marrow transplant, Co-IP MS, actin polymerization and MRTFA localization assays, MRTFA inhibitor

    PMID:41610517

    Open questions at the time
    • Direct MYO1F-EPLINα binding interface not mapped
    • Generality beyond monocyte/atherosclerosis context unknown
  12. 2018 Medium

    Provided an early gain-of-function link to transformation, showing a motor-domain p.Gly134Ser mutation alters mitochondrial morphology/ROS and confers oncogenic phenotypes.

    Evidence Stable mutant vs WT cell lines, mitochondrial/ROS assays, colony/invasion assays, zebrafish overexpression

    PMID:29672841

    Open questions at the time
    • Mechanism linking motor-domain mutation to mitochondrial/ROS phenotype unclear
    • Relationship to MYO1F's normal immune functions not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MYO1F's mechanical motor activity is mechanistically integrated with its phosphorylation-gated acetyltransferase-scaffolding function remains unresolved.
  • No structure of MYO1F bound to its kinase or acetyltransferase partners
  • Whether motor force generation is required for acetyltransferase delivery untested
  • Unifying model linking cortical actin tethering, integrin trafficking, and immune signaling not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0003774 cytoskeletal motor activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 2
Complex memberships
CASS adaptor module (CD2AP/ASAP1/SH3BP2/SH3KBP1)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Myo1f-deficient mouse immune cells (neutrophils) exhibit abnormally increased adhesion and reduced motility due to augmented exocytosis of β2 integrin-containing granules; cortical actin co-localizing with Myo1f is reduced in Myo1f-deficient cells, establishing Myo1f as a regulator of cortical actin and integrin trafficking in immune cells. Myo1f knockout mouse model, cell adhesion/motility assays, exocytosis measurement, cortical actin imaging Science High 17023661
2019 Myo1f interacts physically with the adaptor protein 3BP2 in mast cells; this interaction is modulated by KIT/SCF signaling. Myo1f co-localizes with cortical actin, and Myo1f silencing reduces SCF-dependent mast cell adhesion and migration through fibronectin and decreases surface expression of β1 and β7 integrins. Co-immunoprecipitation, shRNA silencing, migration and adhesion assays, flow cytometry, immunofluorescence Frontiers in immunology Medium 31143189
2021 MYO1F knockdown in human mast cells reduces IgE-crosslinking- and MRGPRX2-stimulated degranulation; MYO1F is required for full Cdc42 GTPase activation, cortical actin ring reassembly after activation, proper granule localization at the cell membrane, mitochondrial fission, and mitochondrial translocation to exocytic sites; AKT and DRP1 phosphorylation are diminished upon MYO1F knockdown. shRNA knockdown, β-hexosaminidase release assay, Cdc42 GTPase activation assay, immunofluorescence, mitochondria imaging, western blot for AKT/DRP1 phosphorylation Journal of immunology Medium 33941653
2021 MYO1F acts as an adaptor that recruits both AP2A1 and α-tubulin N-acetyltransferase 1 (α-TAT1) to α-tubulin upon Dectin-1 stimulation, thereby promoting α-tubulin acetylation; this acetylation controls membrane-to-cytoplasm trafficking of SYK and CARD9, which is required for antifungal innate immune gene expression. Myo1f-deficient mice are more susceptible to systemic Candida albicans infection. Myo1f knockout mice, co-immunoprecipitation, α-tubulin acetylation assays, SYK/CARD9 trafficking assays, in vivo infection model, inhibitor studies Proceedings of the National Academy of Sciences of the United States of America High 34301894
2023 Myo1f deficiency in mice reduces migration of γδT intraepithelial lymphocytes to the small intestine, reduces surface CCR9 and α4β7 integrin expression, impairs polarization of chemokine receptors and integrins, and reduces tyrosine phosphorylation, establishing Myo1f as required for γδT IEL homing and adhesion/migration via integrin and chemokine receptor surface trafficking. Myo1f KO mice, in vivo homing assays, in vitro adhesion and migration assays, flow cytometry, immunofluorescence Frontiers in immunology Medium 37207213
2024 MYO1F associates with cGAS at the plasma membrane of macrophages; during viral infection, SYK phosphorylates MYO1F, which then recruits lysine acetyltransferase KAT2A to acetylate cGAS at lysines 421, 292, and 131, enabling cGAS activation; membrane-localized cGAS is essential for type I interferon production triggered by virus-cell fusion via Mn2+ release. Co-immunoprecipitation, proximity ligation, mutagenesis of phosphorylation/acetylation sites, kinase assays, KO macrophages, viral infection assays, type I IFN measurement Molecular cell High 39694035
2024 After TCR stimulation, LCK phosphorylates MYO1F at tyrosines 607 and 634; phosphorylated MYO1F recruits α-TAT1, which acetylates GAPDH at Lys84, 86, and 227, activating GAPDH enzymatic activity and glycolysis required for T-cell effector function. The VAV1-MYO1F fusion protein causes hyperacetylation of GAPDH, aberrant glycolysis, and T-cell proliferation. T-cell-specific Myo1f KO mice, site-directed mutagenesis of phosphorylation sites, kinase assay, GAPDH acetylation assay, glycolysis (ECAR) measurement, co-immunoprecipitation, human PTCL patient sample analysis Cellular & molecular immunology High 39668163
2025 MYO1F interacts via its SH3 domain with a CASS adaptor module comprising CD2AP, ASAP1, SH3BP2, and SH3KBP1 through multivalent proline-rich motif interactions; a second group of adaptors binds the MYO1F pleckstrin homology (PH) domain; MYO1F and the CASS complex co-localize at actin-rich podosomes and phagocytic cups in macrophages and microglia; MYO1F recruitment to the phagocytic cup requires motor activity and intact PH and SH3 domains. In situ proximity labelling proteomics, structural modelling, mutagenesis of SH3/PH domains, immunofluorescence co-localization, functional phagocytosis assays Journal of cell science High 41208482
2025 Myo1e and Myo1f localize specifically to the base of podosomes (between podosome core and ventral plasma membrane) in macrophages, primarily via their TH2 domains; knockdown or knockout of Myo1e/f increases podosome size and alters turnover and lateral mobility, indicating a role in attaching core actin filaments to the plasma membrane; Myo1e/f double KO macrophages show reduced 2D and 3D migration despite increased ECM degradation. Knockout/knockdown macrophages, live-cell imaging, TIRF microscopy, podosome turnover/mobility assays, 2D/3D migration assays, ECM degradation assay, domain truncation experiments bioRxivpreprint Medium bio_10.1101_2025.04.28.651090
2025 MYO1F normally inhibits neutrophil immunosuppression and proliferation by restraining STAT3 activity; tumor-derived TGF-β1 suppresses Myo1f transcription via SPI1 binding disruption through DNA methylation of intron 8, reducing MYO1F and reprogramming neutrophils into an immunosuppressive state through STAT3-dependent signaling. KO/knockdown neutrophil models, STAT3 activity assays, chromatin/methylation analysis, tumor microenvironment functional assays, ICB therapy mouse models The Journal of experimental medicine Medium 40202509
2026 Myo1f promotes actin polymerization in monocytes by recruiting EPLINα, which stabilizes F-actin and drives depolymerization of G-actin/MRTFA, causing MRTFA nuclear translocation and transcriptional upregulation of ITGB2 (integrin β2); this mechanism promotes monocyte adhesion to vascular endothelial cells and contributes to atherosclerosis. Myo1f KO mice crossed to Apoe-/- atherosclerosis model, bone marrow transplantation, co-immunoprecipitation mass spectrometry, actin polymerization assays, MRTFA nuclear localization imaging, ITGB2 expression assays, MRTFA inhibitor (CCG-1423) treatment Redox biology Medium 41610517
2018 A MYO1F p.Gly134Ser mutation (in the motor/ATP-binding domain) causes altered mitochondrial network morphology with increased mitochondrial mass and elevated ROS in thyroid cells; mutant MYO1F confers increased colony formation, invasion, and anchorage-independent growth compared to wild-type MYO1F, and induces proliferation when overexpressed in zebrafish embryos. Stable cell line expression of mutant vs. wild-type MYO1F, mitochondrial staining, ROS measurement, colony/invasion assays, zebrafish overexpression model International journal of cancer Medium 29672841

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Modulation of cell adhesion and motility in the immune system by Myo1f. Science (New York, N.Y.) 98 17023661
2018 Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer. International journal of cancer 36 29672841
2005 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. Oncogene 35 15897884
2008 Are MYO1C and MYO1F associated with hearing loss? Biochimica et biophysica acta 29 19027848
2021 MYO1F regulates antifungal immunity by regulating acetylation of microtubules. Proceedings of the National Academy of Sciences of the United States of America 25 34301894
2001 MYO1F as a candidate gene for nonsyndromic deafness, DFNB15. Archives of otolaryngology--head & neck surgery 22 11493199
2022 Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T cell lymphoma. Cell reports 21 35443168
2021 MYO1F Regulates IgE and MRGPRX2-Dependent Mast Cell Exocytosis. Journal of immunology (Baltimore, Md. : 1950) 14 33941653
2019 Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration. Frontiers in immunology 13 31143189
2024 MYO1F positions cGAS on the plasma membrane to ensure full and functional signaling. Molecular cell 12 39694035
2023 Myo1f has an essential role in γδT intraepithelial lymphocyte adhesion and migration. Frontiers in immunology 6 37207213
2024 Role of MYO1F in neutrophil and macrophage recruitment and pro-inflammatory cytokine production in Aspergillus fumigatus keratitis. International immunopharmacology 3 39276460
2024 MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH. Cellular & molecular immunology 3 39668163
2023 The fusion oncogene VAV1-MYO1F triggers aberrant T-cell receptor signaling in vivo and drives peripheral T-cell lymphoma in mice. European journal of immunology 3 36541400
2025 MYO1F in neutrophils is required for the response to immune checkpoint blockade therapy. The Journal of experimental medicine 2 40202509
2025 The MYO1F interactome reveals ASAP1, CD2AP and SH3KBP1 as novel adaptor proteins in podosomes and phagosomes. Journal of cell science 2 41208482
2026 Myo1f regulates monocyte adhesion and contributes to atherosclerosis via MRTFA-dependent ITGB2 expression. Redox biology 0 41610517

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