Affinage

MYO5C

Unconventional myosin-Vc · UniProt Q9NQX4

Length
1742 aa
Mass
202.8 kDa
Annotated
2026-06-10
20 papers in source corpus 7 papers cited in narrative 7 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

MYO5C encodes myosin Vc, a class V actin-based motor that drives membrane trafficking and regulated exocytosis in epithelial and glandular cells (PMID:19741097). The motor associates with two distinct membrane compartments: chromogranin A/Rab27b-positive secretory granules, which it moves slowly (~30 nm/s) in a microtubule-independent fashion, and Rab8a-positive tubular carriers, which move rapidly (~440 nm/s) along microtubules (PMID:19741097). Through its Rab8-associated trafficking activity it controls transferrin/transferrin-receptor recycling compartments, and dominant-negative tail expression perturbs these compartments and granule distribution, establishing a requirement for Myo5c in secretory granule transport and apical exocytosis (PMID:11870218, PMID:19741097). In lacrimal acinar cells Myo5c localizes to mature secretory vesicles and is required for carbachol-stimulated content release and compound vesicle fusion (PMID:18434623). Biophysically, a single Myo5c dimer is a low duty-ratio, non-processive motor, but coupling of two dimers confers processive stepping in 30–36 nm increments, reflecting inter-head cooperativity, and its actin-activated ATPase and motility are tuned by tropomyosin isoforms and inhibited by pentabromopseudilin (PMID:24809456, PMID:38606007). The protein comprises a motor domain, a neck with six IQ motifs binding calmodulin/EF-hand light chains, a coiled-coil dimerization region, and a C-terminal globular tail (PMID:38606007).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2002 Medium

    Established that Myo5c participates in membrane trafficking by linking it to a Rab8/transferrin-receptor recycling compartment, the first functional clue to its cellular role.

    Evidence GFP-Myo5c tail dominant-negative expression and immunolocalization in HeLa cells

    PMID:11870218

    Open questions at the time
    • Dominant-negative approach does not prove direct motor transport
    • No demonstration of direct Rab8 binding
    • Cargo specificity not defined
  2. 2008 High

    Showed Myo5c functions in regulated apical exocytosis by demonstrating it localizes to mature secretory vesicles and is required for stimulated content release and compound fusion.

    Evidence Confocal/immunogold EM and adenoviral dominant-negative tail expression with secretory readouts in lacrimal acinar cells

    PMID:18434623

    Open questions at the time
    • Mechanism of vesicle fusion coupling unresolved
    • Light-chain/calcium regulation in this context not addressed
  3. 2009 High

    Resolved that Myo5c operates on two functionally distinct compartments with different motility regimes, distinguishing microtubule-independent granule movement from microtubule-dependent tubule transport.

    Evidence Live-cell GFP/TIRF imaging, colocalization with chromogranin A/Rab27b and Rab8a, and dominant-negative tail in MCF-7 cells

    PMID:19741097

    Open questions at the time
    • Molecular basis of cargo selection between granules and tubules unknown
    • Direct Rab27b/Rab8a binding not biochemically established
  4. 2009 Medium

    Extended Myo5c/Rab8 trafficking to a pathophysiological readout by showing it is required for dengue virus egress without affecting intracellular replication.

    Evidence Colocalization, dominant-negative tail stable transfection, plaque assay and Rab8 flow cytometry in HepG2 cells

    PMID:19641326

    Open questions at the time
    • Does not establish direct interaction with viral components
    • Step of egress pathway controlled by Myo5c undefined
  5. 2014 High

    Defined the motor mechanochemistry, showing single dimers are non-processive but paired dimers move processively with inter-head cooperativity.

    Evidence Steady-state ATPase, ADP dissociation kinetics, and single-molecule tracking of DNA-scaffold-linked Myo5c-HMM dimers

    PMID:24809456

    Open questions at the time
    • Physiological mechanism for in vivo dimer coupling unknown
    • Cargo-induced activation not addressed
  6. 2024 High

    Characterized regulation of human Myo5c motor output by tropomyosin isoforms and identified a small-molecule inhibitor, plus its domain architecture and light-chain binding.

    Evidence Recombinant human Myo5c-HMM reconstitution, actin-activated ATPase with tropomyosin cofilaments, motility assays, PBP docking, and tissue immunohistochemistry

    PMID:38606007

    Open questions at the time
    • In vivo relevance of specific tropomyosin isoforms not tested
    • Light-chain composition under physiological conditions undefined
  7. 2025 Low

    Implicated Myo5c as a negative regulator of neutrophil activation, expanding its role beyond epithelial trafficking.

    Evidence myo5c knockout in HL60 cells with NET formation assay and RNA-seq correlation in patient neutrophils

    PMID:40495980

    Open questions at the time
    • No mechanistic pathway linking Myo5c to NET formation established
    • Single cell-line knockout without rescue
    • Correlative patient data only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Myo5c selectively recognizes and is activated by its distinct membrane cargoes (Rab8a tubules versus Rab27b/chromogranin granules) at the molecular level remains unresolved.
  • No direct biochemical mapping of tail-Rab interactions
  • Mechanism of cargo-dependent motor activation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 2
Partners
CALM1RAB27BRAB8A

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Myo5c tail domain (dominant-negative) colocalizes with and perturbs a membrane compartment containing the transferrin receptor and Rab8, and causes transferrin accumulation in that compartment, indicating Myo5c functions in transferrin/Rab8-associated membrane trafficking in epithelial cells. GFP-Myo5c tail dominant-negative expression in HeLa cells with immunolocalization Journal of cell science Medium 11870218
2008 Myo5c associates with mature secretory vesicles (by confocal and immunogold EM) in lacrimal acinar cells; dominant-negative Myo5c tail expression reduces carbachol-stimulated secretion of vesicle content markers (secretory component, syncollin-GFP) and impairs compound vesicle fusion, indicating Myo5c facilitates apical exocytosis of secretory vesicles. Confocal fluorescence and immunogold EM; adenovirus-mediated dominant-negative GFP-Myo5c-tail expression; measurement of secretory vesicle content release and vesicle diameter American journal of physiology. Cell physiology High 18434623
2009 Endogenous Myo5c localizes to two distinct compartments in MCF-7 cells: small puncta that colocalize with secretory granule markers (chromogranin A, Rab27b) and slender tubules labeled by Rab8a. Myo5c puncta move slowly (~30 nm/s) in a microtubule-independent manner while tubules move rapidly (~440 nm/s) in a microtubule-dependent manner. Dominant-negative Myo5c tail dramatically perturbs the distribution of granule markers, establishing a functional role in secretory granule trafficking. Live-cell GFP imaging, TIRF microscopy, immunofluorescence colocalization, dominant-negative tail expression, microtubule depolymerization experiments Molecular biology of the cell High 19741097
2009 Myo5c colocalizes with Rab8 in HepG2 cells; expression of dominant-negative Myo5c tail reduces release of dengue virus 2 (DV2) from cells without affecting intracellular viral production, and is accompanied by increased Rab8 expression, indicating Myo5c/Rab8-mediated membrane trafficking is required for DV2 egress. Fluorescent immunostaining/colocalization, dominant-negative Myo5c tail stable transfection, plaque assay for viral titer, flow cytometry for Rab8 expression Intervirology Medium 19641326
2014 Myo5c is a low duty ratio, non-processive motor as a single dimer, but coupling of two Myo5c-HMM dimers via a DNA scaffold enables processive movement along actin filaments in 30–36 nm steps. Steady-state ATPase and ADP dissociation kinetics show that the Myo5c-HMM dimer has 6-fold lower Km for actin than the single-headed S1, indicating inter-head cooperativity. Steady-state ATPase assay, ADP dissociation kinetics, nanometer-precision single-molecule tracking of DNA-scaffold-linked Myo5c dimers Scientific reports High 24809456
2024 Human Myo5c-HMM motor activity is modulated by tropomyosin isoforms (Tpm1.6, Tpm1.8, Tpm3.1 alter maximum actin-activated ATPase and motile activity) and inhibited by pentabromopseudilin (PBP) with IC50 ~280 nM, predicted to bind near the actin and nucleotide binding site. Myo5c is composed of a motor domain, neck with six IQ motifs binding calmodulin or EF-hand light chains, coiled-coil dimerization region, and C-terminal globular tail domain. Recombinant human Myo5c-HMM purification and reconstitution with CaM/light chains; actin-activated ATPase assay with tropomyosin cofilaments; in vitro motility assay; computational docking of PBP; immunohistochemical localization in rat and human tissue Frontiers in physiology High 38606007
2025 myo5c knockdown in HL60 cells enhanced neutrophil extracellular trap (NET) formation upon stimulation, suggesting Myo5c negatively regulates neutrophil activation. In vivo, neutrophil Myo5c expression was inversely correlated with IL-6 levels and markers of neutrophil and platelet activation after cardiopulmonary bypass. myo5c knockout in HL60 cells (neutrophil cell line) with NET formation assay; RNA sequencing of patient neutrophils; correlation analyses Frontiers in cardiovascular medicine Low 40495980

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Human myosin-Vc is a novel class V myosin expressed in epithelial cells. Journal of cell science 149 11870218
2018 Characteristics and Outcome of ROS1-Positive Non-Small Cell Lung Cancer Patients in Routine Clinical Practice. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 87 29883837
2009 Myosin Vc is a molecular motor that functions in secretory granule trafficking. Molecular biology of the cell 58 19741097
2014 Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease. Translational psychiatry 54 26126179
2018 Deep molecular phenotypes link complex disorders and physiological insult to CpG methylation. Human molecular genetics 30 29325019
2008 The class V myosin motor, myosin 5c, localizes to mature secretory vesicles and facilitates exocytosis in lacrimal acini. American journal of physiology. Cell physiology 27 18434623
2010 A multi-gene transcriptional profiling approach to the discovery of cell signature markers. Cytotechnology 20 20972619
2021 Comparative Genomics and Integrated Network Approach Unveiled Undirected Phylogeny Patterns, Co-mutational Hot Spots, Functional Cross Talk, and Regulatory Interactions in SARS-CoV-2. mSystems 17 33622851
2014 Coupling of two non-processive myosin 5c dimers enables processive stepping along actin filaments. Scientific reports 15 24809456
2009 Myosin Vc, a member of the actin motor family associated with Rab8, is involved in the release of DV2 from HepG2 cells. Intervirology 14 19641326
2021 Pendred Syndrome, or Not Pendred Syndrome? That Is the Question. Genes 10 34680964
2019 Replicating associations between DNA methylation and body mass index in a longitudinal sample of older twins. International journal of obesity (2005) 10 31801962
2020 Severe Phenotype in a Patient With Homozygous 15q21.2 Microdeletion Involving BCL2L10, GNB5, and MYO5C Genes, Resembling Infantile Developmental Disorder With Cardiac Arrhythmias (IDDCA). Frontiers in genetics 8 32477400
2025 Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon. Cell genomics 3 40961947
2024 Motor properties of Myosin 5c are modulated by tropomyosin isoforms and inhibited by pentabromopseudilin. Frontiers in physiology 3 38606007
2018 Predicting miRNA targets for head and neck squamous cell carcinoma using an ensemble method. The International journal of biological markers 3 28665450
2012 Chromosome 15q21-22-related polymorphisms and haplotypes are associated with susceptibility to type-2 diabetic nonproliferative retinopathy. Genetic testing and molecular biomarkers 3 22409602
2026 Research note: Integration of GWAS and RNA-seq identifies mutations linked to within feather patterning in domestic chickens. Poultry science 0 41722227
2025 Neutrophil Myo5c gene downregulation is associated with postoperative organ dysfunction following pediatric cardiac surgery with cardiopulmonary bypass. Frontiers in cardiovascular medicine 0 40495980
2019 Duplicated Myosin V Genes in Teleosts Show Evolutionary Rate Variations among the Motor and Cargo-Binding Domains. Genome biology and evolution 0 30496538

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