Affinage

MYO1E

Unconventional myosin-Ie · UniProt Q12965

Length
1108 aa
Mass
127.1 kDa
Annotated
2026-06-10
21 papers in source corpus 13 papers cited in narrative 13 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

MYO1E encodes a single-headed class I myosin motor that couples the plasma membrane to the actin cytoskeleton to regulate endocytosis, adhesion, and migration across podocytes and immune cells (PMID:23977349, PMID:36316095). Its motor domain has a defined ATPase cycle in which actin activates ADP release as the primary regulatory step, with ADP release more than tenfold faster than other vertebrate myosin-I isoforms, kinetically tuning Myo1e for rapid actin sliding (PMID:11940582). The C-terminal tail anchors the motor to membranes by binding anionic phospholipids (PtdIns(4,5)P2 and phosphatidylserine) through nonspecific electrostatic interactions of its basic region rather than a stereospecific PH-domain contact, and this basic region directs localization to clathrin-coated vesicles (PMID:20860408). Through this membrane-actin linkage Myo1e promotes clathrin-mediated and dynamin-dependent endocytosis, cell adhesion, and migration in podocytes (PMID:23977349, PMID:24339252, PMID:32211226), and is recruited to clathrin-mediated endocytosis sites stalled by elevated membrane tension where it promotes Arp2/3-dependent branched actin assembly to rescue them [PMID:bio_10.1101_2025.11.12.688091]. In immune cells Myo1e localizes to the podosome base via its TH2 domain to control podosome size, turnover, and macrophage migration [PMID:bio_10.1101_2025.04.28.651090], is required for phagocytic cup closure during Fc-receptor phagocytosis (PMID:42094351), and acts upstream of the FAK–PI3K–RAC-1 pathway to govern B-cell adhesion and migration while also directing intracellular transport of CCL2 and MHC-II (PMID:25263281, PMID:31964710). Biallelic MYO1E mutations cause autosomal recessive focal segmental glomerulosclerosis and steroid-resistant nephrotic syndrome, with pathogenic variants clustered in the motor and neck domains that disrupt subcellular localization and/or ATPase and actin-translocation activity (PMID:21756023, PMID:36316095, PMID:35723736).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Established the kinetic identity of the motor, answering whether Myo1e is built for force-holding or for fast movement along actin.

    Evidence In vitro stopped-flow and ATPase analysis of a truncated motor+IQ construct with calmodulin

    PMID:11940582

    Open questions at the time
    • Kinetics measured on a truncated construct, not full-length protein
    • Does not address how the tail or membrane binding modulates motor output
  2. 2010 High

    Defined how the motor is tethered to membranes, showing the tail uses electrostatic phospholipid binding rather than a stereospecific PH-domain interaction.

    Evidence Sedimentation and stopped-flow lipid-binding assays plus PH-domain mutagenesis and in vivo localization of recombinant tail constructs

    PMID:20860408

    Open questions at the time
    • Does not identify the protein partners at clathrin-coated vesicles
    • Binding studied on tail fragments outside the context of the intact motor
  3. 2011 High

    Linked MYO1E to human disease, establishing it as required for glomerular filtration barrier integrity via two functionally distinct FSGS mutations.

    Evidence Linkage analysis, sequencing, and expression/localization studies in two autosomal-recessive FSGS pedigrees

    PMID:21756023

    Open questions at the time
    • Cellular mechanism connecting mislocalization to podocyte failure not resolved here
    • Motor-domain mutation effect on ATPase activity not measured
  4. 2013 Medium

    Connected the genetic disease phenotype to defined cellular roles, showing Myo1e is needed for podocyte actin organization, migration, endocytosis, and adhesion.

    Evidence Morpholino knockdown in zebrafish and knockdown in conditionally immortalized podocytes with actin, migration, endocytosis, and adhesion assays

    PMID:23977349

    Open questions at the time
    • Single lab
    • Does not separate direct motor function from indirect actin reorganization effects
  5. 2014 Medium

    Showed Myo1e is a positive, dose-sensitive regulator of podocyte endocytosis, migration, and adhesion through gain-of-function.

    Evidence Overexpression in MPC5 podocytes with transferrin endocytosis, transwell migration, and detachment assays

    PMID:24339252

    Open questions at the time
    • Overexpression may not reflect physiological stoichiometry
    • No in vitro reconstitution
  6. 2014 Medium

    Extended Myo1e function to immune cells, implicating it in intracellular transport of CCL2 and MHC-II and in antigen presentation independent of transcription.

    Evidence Knockout bone marrow-derived macrophages and DCs with spreading, chemokine ELISA, surface MHC-II flow cytometry, T-cell proliferation, and antigen proteolysis assays

    PMID:25263281

    Open questions at the time
    • Direct cargo/transport mechanism not defined
    • Redundancy with Myo1f not fully separated
  7. 2020 Medium

    Placed Myo1e in a dynamin-dependent albumin internalization pathway in podocytes.

    Evidence Gain/loss-of-function in MPC5 podocytes with FITC-BSA endocytosis and Dynasore epistasis

    PMID:32211226

    Open questions at the time
    • Pharmacological dynamin inhibition lacks genetic confirmation
    • Direct Myo1e-dynamin physical link not shown
  8. 2020 Medium

    Positioned Myo1e upstream of FAK–PI3K–RAC-1 signaling to drive B-cell adhesion and migration in vivo.

    Evidence Intravital microscopy in Myo1e-deficient mice plus in vitro adhesion/migration and FAK/AKT/RAC-1 phosphorylation assays

    PMID:31964710

    Open questions at the time
    • Whether Myo1e acts directly or via altered actin/integrin geometry on the pathway is unresolved
    • Single lab
  9. 2022 High

    Resolved how disease mutations act mechanistically, distinguishing localization defects from ATPase/translocation defects within the motor domain.

    Evidence EGFP-Myo1e localization and FRAP in Myo1e-KO podocytes plus in vitro ATPase and actin-gliding assays of mutant constructs

    PMID:36316095

    Open questions at the time
    • The altered binding partners implied by D388H FRAP behavior not identified
    • Effects measured on truncated motor constructs
  10. 2022 Medium

    Confirmed across additional patients that pathogenic variants cluster in motor and neck domains and cause Myo1e protein mislocalization in kidney.

    Evidence Sequencing, immunolocalization in patient kidney sections, and computational variant modeling

    PMID:35723736

    Open questions at the time
    • Functional consequences inferred computationally for most variants
    • Single lab
  11. 2025 Medium

    Defined the sub-podosome localization and its determinant, showing Myo1e/f attach core actin filaments to the membrane at the podosome base to control podosome dynamics and migration.

    Evidence TIRF/fluorescence imaging of Myo1e/f-GFP, siRNA/CRISPR depletion, and TH2 domain-deletion constructs in macrophages (preprint)

    PMID:bio_10.1101_2025.04.28.651090

    Open questions at the time
    • Preprint, single lab
    • Myo1e versus Myo1f individual contributions not fully separated
  12. 2025 Medium

    Identified Myo1e as a membrane-tension-sensing rescue factor at clathrin-mediated endocytosis sites acting through Arp2/3-dependent branched actin.

    Evidence Live-cell and super-resolution imaging of genome-edited hiPSCs with endogenous tagging, Myo1e knockout, and membrane tension manipulation (preprint)

    PMID:bio_10.1101_2025.11.12.688091

    Open questions at the time
    • Preprint, single lab
    • Direct Myo1e-Arp2/3 interaction versus indirect recruitment not distinguished
  13. 2026 Medium

    Established a role in phagocytic cup closure, showing Myo1e/f organize actin teeth and the contractile ring during Fc-receptor phagocytosis to prevent premature ring constriction and trogocytosis.

    Evidence CRISPR double-KO RAW 264.7 macrophages with bead uptake, lattice-light-sheet imaging, rescue, and trogocytosis assays (preprint)

    PMID:42094351

    Open questions at the time
    • Preprint, single lab
    • Mechanism coupling Myo1e/f to NM2 ring organization not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Myo1e's fast-sliding motor kinetics, electrostatic membrane tethering, and Arp2/3-based actin assembly are integrated and which physical partners recruit it to distinct sites (CCVs, podosomes, phagocytic cup) remains unresolved.
  • No identified direct protein partner explaining junction/CCV recruitment
  • No structure of full-length motor on membrane
  • Relationship between motor activity and tension sensing not mechanistically reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 2 GO:0008092 cytoskeletal protein binding 2 GO:0016787 hydrolase activity 2 GO:0140657 ATP-dependent activity 2 GO:0008289 lipid binding 1
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
CALM1DNM1MYO1F

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Myo1e (human myosin-IC) has a defined ATPase kinetic mechanism: it has low K(ATPase) (~1 µM) for actin, weak actin affinity in the presence of ATP, rapid phosphate release while dissociated from actin, and actin activation of ADP release as the primary mechanism of actin-stimulated ATPase activation. ADP release from actomyo1e is >10-fold faster than other vertebrate myosin-I isoforms, suggesting subclass-1 myosin-Is are tuned for rapid sliding. In vitro kinetic analysis (stopped-flow, ATPase assays) of truncated myo1e motor+IQ construct with bound calmodulin The Journal of biological chemistry High 11940582
2010 The myo1e C-terminal tail domain binds anionic phospholipids (PtdIns(4,5)P2 and phosphatidylserine) with high affinity through nonspecific electrostatic interactions rather than stereospecific protein-phosphoinositide interaction. The rate of attachment to lipid vesicles nears the diffusion limit, and the calculated dissociation rate is slow (≤0.4 s⁻¹). Mutation of conserved PH-domain residues has little effect on lipid binding in vitro or membrane localization in vivo. The basic region of the tail (not the PH domain per se) is required for localization to clathrin-coated vesicles. Sedimentation assays, stopped-flow fluorescence, fluorescence microscopy with recombinant myo1e-tail constructs and site-directed mutagenesis of PH domain residues Biochemistry High 20860408
2011 Two MYO1E mutations identified in familial FSGS have distinct functional consequences: the A159P motor-domain mutation causes abnormal subcellular localization of Myo1e in transfected cells, while the Y695X mutation causes loss of calmodulin binding and loss of the tail domains of Myo1e. Both mutations segregate with autosomal recessive FSGS, establishing Myo1e as required for podocyte function and glomerular filtration barrier integrity. Whole-genome linkage analysis, high-throughput sequencing, transfection/expression studies in cultured cells, immunohistochemistry on kidney biopsies, electron microscopy The New England journal of medicine High 21756023
2013 Knockdown of Myo1e in cultured podocytes induces actin cytoskeleton rearrangement, morphological changes, and defects in cell proliferation, migration, endocytosis, and adhesion to the glomerular basement membrane. In zebrafish, Myo1e knockdown causes pericardial edema and pronephric cysts consistent with proteinuria, establishing Myo1e as a key component of podocyte cytoskeletal organization. Myo1e-specific knockdown in zebrafish (morpholino) and conditionally immortalized podocyte cell line; actin staining, migration assay, endocytosis assay, adhesion assay PloS one Medium 23977349
2014 Myo1e overexpression in mouse podocytes enhances endocytosis (FITC-transferrin internalization), cell migration, and cell adhesion to substrate, and inhibits puromycin aminonucleoside-induced podocyte detachment, establishing Myo1e as a positive regulator of these cellular processes in podocytes. Overexpression of Myo1e in MPC5 podocyte cell line; transwell migration assay, FITC-transferrin endocytosis assay, detachment assay Journal of cellular biochemistry Medium 24339252
2014 Myo1e (and Myo1f) are required for LPS-triggered macrophage spreading. Loss of Myo1e leads to selectively increased CCL2 chemokine secretion and reduced MHC class II surface expression without transcriptional changes in these genes, indicating Myo1e regulates intracellular transport of CCL2 and MHC-II. Myo1e-deficient macrophages and DCs have impaired capacity to stimulate antigen-specific CD4+ T-cell proliferation, and Myo1e-deficient DCs show increased proteolytic cleavage of endocytosed antigen. Bone marrow-derived macrophages and DCs from Myo1e knockout mice; spreading assay, ELISA for chemokines, flow cytometry for surface MHC-II, T-cell proliferation assay, antigen proteolysis assay European journal of immunology Medium 25263281
2020 Myo1e overexpression promotes albumin endocytosis in podocytes via a Dynamin-dependent mechanism: inhibition of Dynamin GTPase activity (Dynasore) attenuates the Myo1e-overexpression-induced increase in FITC-BSA endocytosis, suggesting a Myo1e–Dynamin–Albumin pathway for podocyte albumin internalization. Myo1e overexpression and knockdown in MPC5 podocytes; FITC-BSA endocytosis measured by flow cytometry; Dynasore pharmacological inhibition PeerJ Medium 32211226
2020 Myo1e is required for efficient adhesion and inclusion of activated B cells into high endothelial venules in vivo, and for B-cell migration in vitro. Myo1e-deficient B cells show reduced integrin and F-actin levels in membrane protrusions, reduced phosphorylation of FAK, AKT, and RAC-1, indicating Myo1e acts upstream of the FAK–PI3K–RAC-1 signaling pathway to regulate B-cell adhesion and migration. Intravital microscopy in Myo1e-deficient mice; in vitro adhesion and migration assays; flow cytometry for integrin expression; phosphorylation assays for FAK, AKT, RAC-1 Journal of cell science Medium 31964710
2022 Two SRNS-associated MYO1E motor domain mutations, T119I and D388H, have distinct functional consequences: T119I disrupts Myo1e enrichment at cell junctions and clathrin-coated vesicles (CCVs); D388H localizes similarly to WT but shows decreased rate of dissociation from junctions and CCVs (suggesting altered interaction with binding partners) and has drastically reduced ATPase activity and actin filament translocation ability in vitro. EGFP-Myo1e expression in Myo1e-KO mouse podocyte cells; localization and FRAP analysis; clathrin-dependent endocytosis assay; in vitro ATPase assay and actin gliding assay using baculovirus-expressed truncated constructs Journal of the American Society of Nephrology : JASN High 36316095
2022 Pathogenic MYO1E variants (including compound heterozygous variants and exon 19 deletion) cause mislocalization of Myo1e protein in kidney sections. Pathogenic variants predominantly map to the motor and neck domains, consistent with disruption of Myo1e function in regulating podocyte actin cytoskeleton dynamics and cell adhesion. DNA/RNA sequencing; immunolocalization of Myo1e in kidney sections; computer modeling of variant effects Pediatric nephrology (Berlin, Germany) Medium 35723736
2025 Myo1e (and Myo1f) localize to a specific region underneath the podosome core near the ventral plasma membrane (the podosome 'base'), with localization primarily mediated by the Myo1e/f TH2 domains. Knockout/knockdown of Myo1e/f increases podosome size, alters podosome turnover and lateral mobility, and reduces 3D and 2D macrophage migration, indicating that Myo1e/f regulate attachment of core actin filaments to the plasma membrane at podosomes. Fluorescence microscopy and TIRF of Myo1e/f-GFP fusions; siRNA knockdown and CRISPR knockout in macrophages; podosome size/turnover/mobility measurements; 3D and 2D migration assays; domain deletion constructs for TH2 domain localization bioRxivpreprint Medium bio_10.1101_2025.04.28.651090
2026 Myo1e and Myo1f are required for efficient phagocytic cup closure in macrophages via Fc-receptor-mediated phagocytosis. In double-KO macrophages, podosome formation during phagocytosis is diminished, actin 'teeth' structures are absent, the contractile phagocytic ring forms prematurely, cup progression stalls, and trogocytosis (partial target ingestion) increases. Myo1e/f localize to phagocytic podosomes and the inner surface of the phagocytic ring; their absence correlates with diffuse distribution of non-muscle myosin II (NM2) at the ring outer surface. CRISPR-edited Myo1e/f double-KO RAW 264.7 macrophages; bead uptake assay; lattice-light-sheet and confocal imaging of F-actin architectures; rescue by re-expression; trogocytosis assay bioRxivpreprint Medium 42094351
2025 In human iPSCs, Myo1e is recruited to clathrin-mediated endocytosis (CME) sites that stall due to increased membrane tension. Under normal tension, Myo1e recruitment is rare; as membrane tension increases, Myo1e is recruited to more CME sites. Loss of Myo1e results in increased Arp2/3 complex lifetime at CME sites under normal conditions and failure to recruit sufficient Arp2/3 at high membrane tension, indicating Myo1e promotes branched actin network assembly via Arp2/3 to rescue stalled CME sites. Live-cell imaging and super-resolution microscopy of genome-edited hiPSCs expressing endogenous tagged proteins; Myo1e knockout; manipulation of membrane tension; measurement of CME dynamics and Arp2/3 lifetime bioRxivpreprint Medium bio_10.1101_2025.11.12.688091

Source papers

Stage 0 corpus · 21 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 MYO1E mutations and childhood familial focal segmental glomerulosclerosis. The New England journal of medicine 195 21756023
2002 The kinetic mechanism of Myo1e (human myosin-IC). The Journal of biological chemistry 60 11940582
2011 Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome. Kidney international 54 21697813
2010 Myo1e binds anionic phospholipids with high affinity. Biochemistry 51 20860408
2015 Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease. Pediatric nephrology (Berlin, Germany) 37 25739341
2005 Differential expression and molecular characterisation of Lmo7, Myo1e, Sash1, and Mcoln2 genes in Btk-defective B-cells. Cellular immunology 36 16137664
2014 Class I myosin Myo1e regulates TLR4-triggered macrophage spreading, chemokine release, and antigen presentation via MHC class II. European journal of immunology 28 25263281
2014 Overexpression of Myo1e in mouse podocytes enhances cellular endocytosis, migration, and adhesion. Journal of cellular biochemistry 23 24339252
2020 Myo1e modulates the recruitment of activated B cells to inguinal lymph nodes. Journal of cell science 19 31964710
2013 Myo1e impairment results in actin reorganization, podocyte dysfunction, and proteinuria in zebrafish and cultured podocytes. PloS one 16 23977349
2022 Focal segmental glomerulosclerosis and proteinuria associated with Myo1E mutations: novel variants and histological phenotype analysis. Pediatric nephrology (Berlin, Germany) 12 35723736
2023 Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality. Scientific reports 8 36914720
2022 Steroid-Resistant Nephrotic Syndrome-Associated MYO1E Mutations Have Differential Effects on Myosin 1e Localization, Dynamics, and Activity. Journal of the American Society of Nephrology : JASN 4 36316095
2020 Overexpression of Myo1e promotes albumin endocytosis by mouse glomerular podocytes mediated by Dynamin. PeerJ 4 32211226
2023 Effect of cyclosporine A on focal segmental glomerulosclerosis caused by MYO1E mutation in a Chinese adult patient: A case report. Medicine 3 36705362
2023 Analysis and validation of the potential of the MYO1E gene in pancreatic adenocarcinoma based on a bioinformatics approach. Oncology letters 3 37274465
2022 Concordant nephrotic syndrome in twins with PAX2 and MYO1E mutations. Clinical nephrology. Case studies 2 35574290
2014 [Mutational analysis of MYO1E in children with sporadic steroid-resistant nephrotic syndrome in Chinese Han ethnic group]. Zhonghua er ke za zhi = Chinese journal of pediatrics 1 25224051
2026 Steroid-Resistant Focal Segmental Glomerulosclerosis with Alport-like Glomerular Basement Membrane Lesions Due to a MYO1E Mutation: A Pediatric Case Report. International journal of molecular sciences 0 41898697
2026 Myo1e/f regulate phagocytic podosomes to promote efficient cup closure in macrophages. bioRxiv : the preprint server for biology 0 42094351
2014 [Mutational analysis of MYO1E in Chinese children with familial steroid-resistant nephrotic syndrome]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 24750828

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