Affinage

MYO1B

Unconventional myosin-Ib · UniProt O43795

Round 2 corrected
Length
1136 aa
Mass
132.0 kDa
Annotated
2026-04-29
60 papers in source corpus 14 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYO1B is a widely expressed class I unconventional myosin that functions as a molecular force sensor and tension-maintenance motor, with kinetics characterized by very slow ATP-induced actin dissociation, slow ADP release, and high actin affinity (~15 nM Kd), and whose actin-detachment rate decreases >75-fold under piconewton loads, transitioning it from low to high duty ratio (PMID:10419463, PMID:18599791). Its regulatory domain is alternatively spliced to yield isoforms with four to six calmodulin-binding IQ motifs, and differential calmodulin occupancy and Ca²⁺ sensitivity tune lever-arm rigidity, ATPase activity, and motility rate in an isoform-dependent manner (PMID:16254000). In cells, MYO1B regulates membrane trafficking—including apical targeting of MUC17 in enterocytes and exosomal cargo transport—and drives cytoskeletal remodeling through RhoA/ROCK2/LIMK/Cofilin signaling, while also suppressing autophagosome–lysosome fusion via a LRRK2-tail-domain interaction that elevates intracellular Ca²⁺, thereby stabilizing HIF-1α and promoting VEGF-driven angiogenesis (PMID:39661054, PMID:34790749, PMID:36347835, PMID:36654782). Oncogenic alternative splicing driven by SRSF1 produces a membrane-localized full-length isoform that activates PDK1/AKT signaling and contributes to glioma progression (PMID:30481162).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1994 Medium

    Establishing MYO1B as a widely expressed unconventional myosin resolved whether this class I myosin was tissue-restricted or ubiquitous, setting the stage for functional studies across cell types.

    Evidence PCR, hybridization screening, RNase protection, and immunoblot across human cell types

    PMID:8022818

    Open questions at the time
    • No functional characterization beyond expression profiling
    • Subcellular localization not resolved
  2. 1999 High

    Detailed transient kinetic analysis revealed that MYO1B is kinetically tuned for tension maintenance rather than rapid motility, establishing a biochemical framework for its cellular role as a cortical force-bearing motor.

    Evidence Steady-state and stopped-flow kinetic analysis of purified MI(130) ATPase activity with actin

    PMID:10419463

    Open questions at the time
    • Force-dependent kinetic behavior not yet measured
    • In vivo relevance of slow kinetics not demonstrated
  3. 2005 High

    Characterization of alternatively spliced IQ-motif isoforms and their differential calmodulin binding explained how MYO1B lever-arm mechanics and Ca²⁺ sensitivity are diversified post-transcriptionally.

    Evidence Recombinant isoform expression, calmodulin-binding Kd measurements, ATPase assays, and in vitro motility assays

    PMID:16254000

    Open questions at the time
    • Physiological consequences of isoform-specific motility differences unknown
    • Identity of the light chain at weakly bound IQ motifs unresolved
  4. 2008 High

    Single-molecule force measurements demonstrated that myosin I transitions from low to high duty ratio under piconewton loads, establishing MYO1B-class motors as bona fide molecular force sensors capable of detecting membrane tension.

    Evidence Single-molecule optical trap with force-clamp on individual myosin I molecules

    PMID:18599791

    Open questions at the time
    • Direct demonstration of force-sensing in a cellular membrane-tension context not provided
    • Structural basis of force-dependent ADP release not resolved
  5. 2019 High

    Discovery that SRSF1 drives oncogenic alternative splicing of MYO1B to produce a membrane-localized full-length isoform that activates PDK1/AKT and PAK/LIMK signaling linked MYO1B isoform regulation to glioma progression.

    Evidence RNA-seq, splice-switching, siRNA knockdown and overexpression in glioma cells with pathway readouts

    PMID:30481162

    Open questions at the time
    • Direct structural or biochemical basis for isoform-specific PDK1/AKT activation not defined
    • Whether the splicing switch operates in non-glioma tumors not established
  6. 2020 Medium

    Pharmacological correction of SRSF1-driven MYO1B splicing by Eucalyptal A validated the MYO1B splice isoform as a druggable effector in glioblastoma, confirming the PDK1/AKT and PAK/Cofilin axes in vivo.

    Evidence RT-PCR splicing analysis, cell assays, and xenograft tumor model with survival analysis

    PMID:33098832

    Open questions at the time
    • Eucalyptal A target specificity not fully characterized; off-target effects possible
    • No direct binding assay between compound and SRSF1/MYO1B mRNA
  7. 2021 Medium

    Identification of MYO1B as an activator of RhoA/ROCK2/LIMK/Cofilin signaling in colorectal cancer connected its motor function to cytoskeletal remodeling and focal adhesion dynamics in metastasis.

    Evidence Co-immunoprecipitation, shRNA knockdown, immunofluorescence, in vitro and in vivo migration/invasion assays

    PMID:34790749

    Open questions at the time
    • Reciprocal IP or direct binding assay for MYO1B–RhoA interaction not shown
    • Mechanism by which a myosin I activates RhoA not elucidated
  8. 2022 Medium

    Demonstration that MYO1B inhibits autophagosome–lysosome fusion, stabilizing HIF-1α and promoting VEGF-dependent angiogenesis, revealed a non-canonical trafficking function with direct consequences for tumor vascularization.

    Evidence siRNA/overexpression with autophagy flux, HIF-1α stability, and VEGF secretion assays in colorectal cancer models

    PMID:36347835

    Open questions at the time
    • Molecular mechanism by which MYO1B blocks autophagosome–lysosome fusion not defined
    • Whether HIF-1α stabilization requires the motor domain or tail domain unclear
  9. 2023 Medium

    The finding that MYO1B interacts with LRRK2 via its tail domain and elevates intracellular Ca²⁺ to suppress autophagy provided a molecular mechanism for the autophagy-inhibitory activity and extended its relevance to endothelial senescence and vascular aging.

    Evidence Co-immunoprecipitation, calcium imaging, autophagy flux assay, senescence markers, aged mouse model

    PMID:36654782

    Open questions at the time
    • Whether LRRK2 kinase activity is required for the MYO1B-dependent Ca²⁺ elevation unknown
    • Source of Ca²⁺ (ER release vs. channel opening) not identified
  10. 2023 Medium

    Functional trafficking studies showed MYO1B controls MUC17 protein levels and apical brush-border targeting in enterocytes, establishing a direct physiological role in intestinal barrier defense against bacterial invasion.

    Evidence Live imaging, knockdown/knockout, brush border fractionation, bacterial challenge in enterocytes

    PMID:36945389 PMID:39661054

    Open questions at the time
    • Cargo-recognition mechanism between MYO1B and MUC17-containing vesicles not defined
    • Whether other brush-border cargoes depend on MYO1B trafficking unclear
  11. 2024 Medium

    MYO1B was shown to interact with CSFV Core protein and to be required for nucleocapsid loading into exosomes, extending its trafficking roles to viral exploitation of the exosomal pathway.

    Evidence Co-immunoprecipitation with C-protein truncation/point mutants, siRNA knockdown, exosome isolation, viral titer assays

    PMID:39603013

    Open questions at the time
    • Generalizability to other viruses not tested
    • Whether MYO1B motor activity or tail-mediated binding is the critical determinant not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for MYO1B force-dependent gating, the mechanism by which the tail domain inhibits autophagosome–lysosome fusion, and whether distinct isoforms have non-overlapping trafficking versus signaling roles in vivo.
  • No high-resolution structure of MYO1B in a force-bearing state
  • No genetic model cleanly separating isoform-specific functions
  • Tail-domain interaction network beyond LRRK2 largely unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0140657 ATP-dependent activity 2 GO:0140299 molecular sensor activity 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9612973 Autophagy 2
Partners
CALM1LRRK2MUC17MYO5BRHOASNX27SRSF1

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The 130-kDa myosin I (MI(130)), product of the myr-1 gene (MYO1B), was characterized biochemically and found to have very slow ATP-induced dissociation of the actin-MI complex (second-order rate constant of ATP binding ~1.7×10⁴ M⁻¹s⁻¹; maximal rate ~32 s⁻¹), slow ADP release from actin-MI (~2 s⁻¹), and high actin affinity (~15 nM), indicating it is kinetically adapted for maintenance of cortical tension rather than rapid motility. Ca²⁺ increased the rates of ATP-induced dissociation and ADP release 2–3-fold, indicating Ca²⁺-sensitivity of motor activity. Steady-state and stopped-flow kinetic analysis (transient kinetics) of purified MI(130) ATPase activity with actin The Journal of biological chemistry High 10419463
2005 Myo1b is alternatively spliced within the regulatory domain, yielding isoforms with six (myo1b-a), five (myo1b-b), or four (myo1b-c) IQ motifs. Calmodulin binds tightly (Kd <0.2 µM) to a subset of IQ motifs and very weakly (Kd >5 µM) to others, suggesting not all IQ motifs are calmodulin-bound under physiological conditions. In vitro motility rate depends on the isoform and calmodulin concentration, and Ca²⁺-dependent changes in ATPase activity are due to Ca²⁺ binding to the calmodulin closest to the motor domain. The regulatory domain acts as a rigid lever arm upon calmodulin binding. Recombinant expression with site-specific biotinylation, ATPase assays, in vitro motility assay, calmodulin-binding measurements The Journal of biological chemistry High 16254000
2008 Myosin I (including Myo1b-class motors) acts as a molecular force sensor: single-molecule optical trap measurements showed that the rate of actin detachment decreases >75-fold under loads of ≤2 pN, causing the motor to transition from a low duty ratio (<0.2) to a high duty ratio (>0.9). This force-dependent gating supports a role for myosin I in sensing membrane tension. Single-molecule optical trap measurements of displacement and actin-attachment kinetics under defined mechanical loads Science High 18599791
1994 MYO1B (myr-1 gene product) was identified as one of at least 11 unconventional myosin genes expressed in overlapping fashion across human cell types including epithelial cells, leukocytes, and liver, establishing it as a widely expressed class I myosin. PCR amplification from cDNA, hybridization screening, RNase protection assay, immunoblot Proceedings of the National Academy of Sciences of the United States of America Medium 8022818
2019 Splicing factor SRSF1 promotes gliomagenesis by switching alternative splicing of MYO1B to favor the full-length, membrane-localized oncogenic isoform (MYO1B-fl). This isoform switch increases tumorigenic potential of glioma cells through the PDK1/AKT and PAK/LIMK signaling pathways. Knockdown of MYO1B or reversal of the splice switch suppressed cell proliferation, survival, and invasion. RNA-seq, motif analysis, siRNA knockdown, overexpression, cell proliferation/invasion assays, pathway analysis (PDK1/AKT, PAK/LIMK) The Journal of clinical investigation High 30481162
2021 MYO1B promotes colorectal cancer metastasis by activating RhoA, which drives F-actin rearrangement through the ROCK2/LIMK/Cofilin axis and promotes assembly of focal adhesions. Co-immunoprecipitation confirmed MYO1B interaction with RhoA pathway components. Co-immunoprecipitation, western blotting, immunofluorescence, shRNA knockdown, in vitro and in vivo migration/invasion assays Annals of translational medicine Medium 34790749
2022 Myo1b inhibits autophagosome-lysosome fusion, thereby blocking autophagic degradation of HIF-1α and leading to HIF-1α accumulation, enhanced VEGF secretion, and tumor angiogenesis in colorectal cancer. Silencing Myo1b restored autophagy flux and reduced VEGF/HIF-1α levels. siRNA knockdown, overexpression, autophagy flux assays, HIF-1α protein stability assays, VEGF secretion measurements, in vitro and in vivo tumor models Cell death & disease Medium 36347835
2023 Myo1b interacts with LRRK2 via its tail domain, and this interaction promotes intracellular calcium elevation that impairs autophagosome-lysosome fusion, thereby suppressing autophagic flux and promoting endothelial cell senescence and vascular aging. Knockdown of Myo1b in senescent endothelial cells and in aged mice enhanced autophagy and ameliorated endothelial dysfunction. Co-immunoprecipitation, overexpression/knockdown, calcium imaging, autophagy flux assay, senescence markers (SA-β-gal, p21), in vivo aged mouse model Oxidative medicine and cellular longevity Medium 36654782
2023 MYO1B and MYO5B motor proteins, together with sorting nexin SNX27, regulate intracellular trafficking and apical targeting of membrane mucin MUC17 in enterocytes. MYO1B specifically controls MUC17 protein levels and its slow turnover at the brush border, while MYO5B governs MUC17 levels at the brush border. Loss of MYO1B-mediated trafficking renders enterocytes sensitive to bacterial invasion. Live imaging, knockdown/knockout, protein level quantification, brush border fractionation, bacterial challenge assays in enterocytes bioRxiv / The Biochemical journal Medium 36945389 39661054
2022 MYO1B activates the SNAI2/cyclin D1 signaling pathway in esophageal squamous cell carcinoma: MYO1B depletion downregulates SNAI2, which in turn inhibits cyclin D1, reducing tumorigenesis and increasing chemosensitivity to cisplatin. siRNA knockdown, overexpression, qPCR, western blot, CCK8/colony formation/Transwell assays, selective cyclin D1 inhibitor rescue experiment Journal of cellular physiology Medium 35861939
2020 Eucalyptal A, a phloroglucinol-terpene natural product, inhibits glioblastoma by downregulating SRSF1 expression, thereby rectifying SRSF1-driven oncogenic alternative splicing of MYO1B mRNA. This correction of MYO1B splicing suppresses GBM cell proliferation, invasion, and tumor growth in vivo through the PDK1/AKT/c-Myc and PAK/Cofilin axes. RT-PCR splicing analysis, western blot, cell proliferation/invasion assays, xenograft tumor model, survival analysis European journal of pharmacology Medium 33098832
2024 MYO1B was functionally validated as a mediator of pancreatic ductal adenocarcinoma (PDAC) metastasis in a functional screen linking pre-metastatic cell state to in vivo metastatic potential. Myo1b knockdown reduced metastatic capacity of PDAC subclones with high metastatic potential. DNA barcode lineage tracing, ATAC-seq, RNA-seq, functional metastasis screen (in vivo) bioRxivpreprint Low bio_10.1101_2024.08.14.607813
2024 MYO1B interacts with the classical swine fever virus (CSFV) Core (C) protein, and this interaction is mediated by specific N-terminal sites on the C protein. MYO1B knockdown significantly reduced C protein and viral genome content in exosomes and decreased CSFV titers, establishing MYO1B as required for transport of the viral nucleocapsid into exosomes during CSFV infection. Co-immunoprecipitation, co-localization, C protein point mutations and truncation variants, siRNA knockdown, exosome isolation and quantification, viral titer assays Veterinary microbiology Medium 39603013

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2011 Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nature genetics 456 22001757
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2013 PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry. Molecular cell 204 24332808
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2008 Myosin I can act as a molecular force sensor. Science (New York, N.Y.) 192 18599791
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2019 MET Inhibitors Promote Liver Tumor Evasion of the Immune Response by Stabilizing PDL1. Gastroenterology 165 30711629
2022 USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma. Nature communications 162 35449157
2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Science signaling 162 25468996
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
1994 Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types. Proceedings of the National Academy of Sciences of the United States of America 149 8022818
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2022 A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nature biotechnology 140 36217030
2016 A Novel Secreted Protein, MYR1, Is Central to Toxoplasma's Manipulation of Host Cells. mBio 130 26838724
2019 Splicing factor SRSF1 promotes gliomagenesis via oncogenic splice-switching of MYO1B. The Journal of clinical investigation 121 30481162
1999 Transient kinetic analysis of the 130-kDa myosin I (MYR-1 gene product) from rat liver. A myosin I designed for maintenance of tension? The Journal of biological chemistry 86 10419463
2017 Passenger strand of miR-145-3p acts as a tumor-suppressor by targeting MYO1B in head and neck squamous cell carcinoma. International journal of oncology 61 29115582
2020 Coimmunoprecipitation with MYR1 Identifies Three Additional Proteins within the Toxoplasma gondii Parasitophorous Vacuole Required for Translocation of Dense Granule Effectors into Host Cells. mSphere 51 32075880
2019 Toxoplasma Controls Host Cyclin E Expression through the Use of a Novel MYR1-Dependent Effector Protein, HCE1. mBio 49 31040242
2018 MYR1-Dependent Effectors Are the Major Drivers of a Host Cell's Early Response to Toxoplasma, Including Counteracting MYR1-Independent Effects. mBio 43 29615509
2005 Biochemical and motile properties of Myo1b splice isoforms. The Journal of biological chemistry 42 16254000
2022 Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer. Cell death & disease 36 36347835
1999 Functional expression and characterization of the myrosinase MYR1 from Brassica napus in Saccharomyces cerevisiae. Protein expression and purification 36 10600460
2011 The Arabidopsis Myb genes MYR1 and MYR2 are redundant negative regulators of flowering time under decreased light intensity. The Plant journal : for cell and molecular biology 35 21255164
2021 MYO1B enhances colorectal cancer metastasis by promoting the F-actin rearrangement and focal adhesion assembly via RhoA/ROCK/FAK signaling. Annals of translational medicine 24 34790749
2019 The Virulence-Related MYR1 Protein of Toxoplasma gondii as a Novel DNA Vaccine Against Toxoplasmosis in Mice. Frontiers in microbiology 21 31024505
2013 Alternative splicing of Myb-related genes MYR1 and MYR2 may modulate activities through changes in dimerization, localization, or protein folding. Plant signaling & behavior 11 24309816
2022 Targeting MYO1B impairs tumorigenesis via inhibiting the SNAI2/cyclin D1 signaling in esophageal squamous cell carcinoma. Journal of cellular physiology 9 35861939
2020 Eucalyptal A inhibits glioma by rectifying oncogenic splicing of MYO1B mRNA via suppressing SRSF1 expression. European journal of pharmacology 9 33098832
2016 Analysis of structures and epitopes of a novel secreted protein MYR1 in Toxoplasma gondii. Folia parasitologica 9 27580381
2023 Myo1b Promotes Premature Endothelial Senescence and Dysfunction via Suppressing Autophagy: Implications for Vascular Aging. Oxidative medicine and cellular longevity 8 36654782
2024 AC024896.1/miR-363-3p Axis Regulates the Malignant Progression of Acute Myeloid Leukemia by Cuproptosis-Related Gene MYO1B. Blood and lymphatic cancer : targets and therapy 5 38550556
2008 Characterization of MYR1, a dosage suppressor of YPT6 and RIC1 deficient mutants. Current genetics 5 18327588
2025 MYO1B promotes radioresistance in head and neck squamous cell carcinoma by regulating tumor stemness and DNA damage repair via the PI3K/AKT pathway. Cancer cell international 2 40604770
2025 Long noncoding RNA SNHG4 promotes glioma progression via regulating miR-367-3p/MYO1B axis in zebrafish xenografts. Human cell 1 39951205
2024 Paracrine rescue of MYR1-deficient Toxoplasma gondii mutants reveals limitations of pooled in vivo CRISPR screens. eLife 1 39654402
2024 Toxoplasma gondii infection induces early host cell cycle arrest and DNA damage in primary human host cells by a MYR1-dependent mechanism. Communications biology 1 39681694
2023 The MYO1B and MYO5B motor proteins and the SNX27 sorting nexin regulate membrane mucin MUC17 trafficking in enterocytes. bioRxiv : the preprint server for biology 1 36945389
2026 Oncogenic role and potential mechanisms of MYO1B in breast cancer. In vitro cellular & developmental biology. Animal 0 41986768
2025 The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes. The Biochemical journal 0 39661054
2025 Molecular mechanisms of recombinant proteins PTTG1IP, ADAM12, PAPSS1, and MYO1B and their effects on wound repair induced by tendon exposure: Analysis of key genes. International journal of biological macromolecules 0 39978508
2025 Formononetin suppresses osteosarcoma by targeting MYO1B and remodeling the tumor immune microenvironment. APL bioengineering 0 41488589
2024 Essential role of the interaction between classical swine fever virus core protein and cellular MYO1B in viral components transport to exosomes and titer maintenance. Veterinary microbiology 0 39603013