{"gene":"MYO1B","run_date":"2026-06-13T19:06:35","timeline":{"discoveries":[{"year":1999,"finding":"MI(130)/MYO1B (myr-1 gene product) from rat liver has slow ATP-induced dissociation of actin-MI(130) (second-order rate constant ~1.7×10⁴ M⁻¹s⁻¹), slow ADP release from actin-MI(130) (~2 s⁻¹), ~10 µM affinity for ADP at actin-MI(130), ~15 nM affinity for actin, and Ca²⁺-sensitive ATPase activity (2-3-fold rate increase with CaCl₂), indicating MYO1B is adapted for maintenance of cortical tension rather than fast translocation.","method":"Steady-state and stopped-flow transient kinetic analyses of purified rat liver MI(130)/MYO1B; Mg²⁺-ATPase assays; fluorescence-based actin dissociation experiments","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — rigorous in vitro enzymatic reconstitution with multiple kinetic parameters measured by orthogonal stopped-flow and steady-state methods","pmids":["10419463"],"is_preprint":false},{"year":2005,"finding":"Myo1b is alternatively spliced to yield isoforms with six (myo1b-a), five (myo1b-b), or four (myo1b-c) IQ motifs; calmodulin binds tightly to a subset of IQ motifs (Kd < 0.2 µM) and very weakly to others (Kd > 5 µM); in vitro motility rate is isoform-dependent and calmodulin-concentration-dependent; 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.","method":"Recombinant expression of biotinylated myo1b splice isoforms; ATPase assays; in vitro actin-gliding motility assays; calmodulin-binding measurements","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with recombinant proteins, multiple orthogonal assays (ATPase, motility, binding), rigorous controls","pmids":["16254000"],"is_preprint":false},{"year":2005,"finding":"Myo1b concentrates on endosomal and ruffling membranes, consistent with roles in membrane trafficking and dynamics.","method":"Cell biological localization studies of myo1b isoforms (implied by expression of isoforms and prior literature cited in this paper)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization described as established context; single paper reference to prior cell biology work","pmids":["16254000"],"is_preprint":false},{"year":2019,"finding":"SRSF1 promotes alternative splicing of MYO1B pre-mRNA, switching expression toward the full-length membrane-localized oncogenic isoform MYO1B-fl in glioma; this isoform switch activates the PDK1/AKT and PAK/LIMK pathways to drive cell proliferation, survival, and invasion.","method":"RNA-Seq splicing analysis; SRSF1 knockdown/overexpression in glioma cells; isoform-specific functional assays (proliferation, invasion); pathway inhibitor experiments","journal":"The Journal of clinical investigation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD/KO with defined cellular phenotype and pathway placement, single lab with multiple orthogonal methods","pmids":["30481162"],"is_preprint":false},{"year":2017,"finding":"MYO1B mRNA is a direct target of miR-145-3p; siRNA-mediated knockdown of MYO1B in head and neck squamous cell carcinoma cells inhibited cancer cell proliferation, migration, and invasion, establishing MYO1B as a functionally relevant downstream effector.","method":"miRNA target validation (direct regulation confirmed); siRNA knockdown of MYO1B; functional cell assays (proliferation, migration, invasion)","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — siRNA loss-of-function with defined phenotype, single lab, direct target validation; no biochemical pathway reconstitution","pmids":["29115582"],"is_preprint":false},{"year":2020,"finding":"Eucalyptal A downregulates SRSF1 expression and thereby corrects the SRSF1-guided abnormal alternative splicing of MYO1B mRNA, reducing MYO1B-fl isoform expression and exerting anti-glioblastoma activity through the PDK1/AKT/c-Myc and PAK/Cofilin axes.","method":"Drug treatment of GBM cells; RT-PCR splicing analysis; western blotting of pathway components; in vitro proliferation/invasion assays; in vivo tumor-bearing mouse model","journal":"European journal of pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pharmacological intervention with mechanistic readout of splicing and downstream signaling, in vitro and in vivo; single lab","pmids":["33098832"],"is_preprint":false},{"year":2021,"finding":"MYO1B promotes F-actin rearrangement and focal adhesion assembly in colorectal cancer cells through activation of RhoA and the downstream ROCK2/LIMK/Cofilin axis, driving cell migration and invasion.","method":"Lentiviral shRNA knockdown and overexpression; co-immunoprecipitation; western blotting; immunofluorescence of F-actin and focal adhesions; in vitro migration/invasion assays; in vivo xenograft","journal":"Annals of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and functional assays with pathway placement, single lab, multiple orthogonal methods","pmids":["34790749"],"is_preprint":false},{"year":2022,"finding":"Myo1b inhibits autophagosome-lysosome fusion in colorectal cancer cells, leading to accumulation of HIF-1α (by blocking its autophagic degradation), which in turn enhances VEGF secretion and promotes tumor angiogenesis.","method":"Myo1b overexpression and siRNA knockdown in CRC cells; autophagy flux assays (autophagosome-lysosome fusion); HIF-1α protein stability assays; VEGF secretion ELISA; in vivo xenograft angiogenesis assessment","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss- and gain-of-function with mechanistic pathway readout (autophagic flux, HIF-1α degradation, VEGF), single lab, multiple methods","pmids":["36347835"],"is_preprint":false},{"year":2022,"finding":"MYO1B activates the SNAI2/cyclin D1 signaling pathway in esophageal squamous cell carcinoma; suppression of MYO1B downregulates SNAI2 expression, which in turn reduces cyclin D1 levels, and pharmacological inhibition of cyclin D1 activation reversed the aggressive phenotypes induced by SNAI2 overexpression in MYO1B-depleted cells.","method":"siRNA knockdown; overexpression; qPCR and western blotting; functional assays (CCK8, colony formation, wound healing, Transwell); rescue experiments with cyclin D1 inhibitor","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with epistasis rescue experiment placing MYO1B upstream of SNAI2/cyclin D1; single lab","pmids":["35861939"],"is_preprint":false},{"year":2023,"finding":"Myo1b interacts with LRRK2 through its tail domain, and this interaction promotes intracellular calcium elevation, which impairs autophagosome-lysosome fusion, leading to suppressed autophagic flux and promotion of endothelial cell senescence.","method":"Co-immunoprecipitation of Myo1b and LRRK2; domain-mapping with tail domain constructs; intracellular calcium measurement; autophagy flux assays; Myo1b knockdown in senescent ECs and aged mice","journal":"Oxidative medicine and cellular longevity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with domain mapping and functional consequence (calcium elevation, impaired autophagy), supported by in vivo model; single lab","pmids":["36654782"],"is_preprint":false},{"year":2024,"finding":"MYO1B interacts with classical swine fever virus Core (C) protein; Co-IP and co-localization experiments identified the N-terminus of the C protein as the key interaction site with MYO1B; MYO1B knockdown significantly reduced C protein and viral genome content in exosomes and decreased CSFV titers, demonstrating a role for MYO1B in intracellular transport of viral components to exosomes.","method":"Co-immunoprecipitation; co-localization imaging; C protein point mutations and truncation variants; MYO1B knockdown by siRNA; viral titer measurement; exosome fractionation","journal":"Veterinary microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with domain mapping and functional knockdown phenotype; single lab, single paper","pmids":["39603013"],"is_preprint":false},{"year":2025,"finding":"MYO1B and MYO5B (actin-based motor proteins) together with sorting nexin SNX27 regulate apical targeting and intracellular trafficking of membrane mucin MUC17 in enterocytes; specifically, MYO1B controls MUC17 protein levels and turnover at the brush border, whereas MYO5B governs MUC17 levels specifically at the brush border.","method":"MYO1B and MYO5B knockdown/knockout in enterocyte models; MUC17 localization and turnover assays; biochemical fractionation","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined trafficking phenotype and functional consequence (bacterial sensitivity); single lab, peer-reviewed replication of preprint","pmids":["39661054"],"is_preprint":false},{"year":2025,"finding":"MYO1B knockdown in head and neck squamous cell carcinoma cells inhibited phosphorylation of ATM (DNA damage repair), reduced stemness markers (SOX2, OCT4), decreased EMT-related proteins, and increased radiotherapy sensitivity; these effects were mediated through the PI3K/AKT signaling pathway, as AKT activation reversed the reductions in tumor stemness and radioresistance.","method":"siRNA knockdown; AKT activator rescue experiment; western blotting; in vitro functional assays; in vivo xenograft with irradiation","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with pathway-level epistasis rescue (AKT activator), in vitro and in vivo; single lab","pmids":["40604770"],"is_preprint":false},{"year":2023,"finding":"MYO1B and MYO5B regulate the intracellular trafficking of membrane mucin MUC17 in enterocytes; MYO1B controls MUC17 protein levels and turnover at the brush border; loss of this trafficking function renders enterocytes sensitive to bacterial invasion.","method":"MYO1B knockdown; MUC17 localization and turnover assays; bacterial challenge assays","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint with single-lab knockdown data; superseded by peer-reviewed version (PMID 39661054)","pmids":["36945389"],"is_preprint":true}],"current_model":"MYO1B is an actin-based class I myosin motor that is biochemically adapted for maintenance of cortical tension via slow ADP release and high actin affinity; its regulatory domain contains differentially-affinity IQ/calmodulin-binding motifs that tune motility in an isoform- and Ca²⁺-dependent manner; alternative splicing controlled by SRSF1 generates a membrane-localized oncogenic isoform that activates PDK1/AKT and PAK/LIMK signaling; MYO1B promotes RhoA/ROCK2/LIMK/Cofilin-dependent F-actin remodeling and focal adhesion assembly to drive cell migration; it blocks autophagosome-lysosome fusion (through interaction with LRRK2 via its tail domain to elevate intracellular calcium) thereby stabilizing HIF-1α and promoting VEGF-driven angiogenesis; and it regulates apical trafficking of membrane mucin MUC17 in enterocytes together with MYO5B and SNX27."},"narrative":{"mechanistic_narrative":"Parse failed — see logs","teleology":[],"mechanism_profile":null},"prefetch_data":{"uniprot":{"accession":"O43795","full_name":"Unconventional myosin-Ib","aliases":["MYH-1c","Myosin I alpha","MMI-alpha","MMIa"],"length_aa":1136,"mass_kda":132.0,"function":"Motor protein that may participate in process critical to neuronal development and function such as cell migration, neurite outgrowth and vesicular transport","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/O43795/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYO1B","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000128641","cell_line_id":"CID001440","localizations":[{"compartment":"membrane","grade":3},{"compartment":"cell_contact","grade":2}],"interactors":[{"gene":"ACTN4","stoichiometry":0.2},{"gene":"CALD1","stoichiometry":0.2},{"gene":"CALM1","stoichiometry":0.2},{"gene":"CALM2","stoichiometry":0.2},{"gene":"CALM3","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"CHMP2A","stoichiometry":0.2},{"gene":"COPG1","stoichiometry":0.2},{"gene":"CTTN","stoichiometry":0.2},{"gene":"NAP1L1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001440","total_profiled":1310},"omim":[{"mim_id":"606537","title":"MYOSIN IB; MYO1B","url":"https://www.omim.org/entry/606537"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"liver","ntpm":238.9}],"url":"https://www.proteinatlas.org/search/MYO1B"},"hgnc":{"alias_symbol":["myr1"],"prev_symbol":[]},"alphafold":{"accession":"O43795","domains":[{"cath_id":"3.40.850.10","chopping":"19-265_361-404_591-629","consensus_level":"medium","plddt":90.6515,"start":19,"end":629},{"cath_id":"1.20.120.720","chopping":"274-358_530-575","consensus_level":"medium","plddt":87.8987,"start":274,"end":575},{"cath_id":"3.30.70.1590","chopping":"633-688","consensus_level":"medium","plddt":93.1166,"start":633,"end":688},{"cath_id":"-","chopping":"862-929","consensus_level":"medium","plddt":83.119,"start":862,"end":929},{"cath_id":"2.30.29.30","chopping":"931-1133","consensus_level":"high","plddt":86.7562,"start":931,"end":1133}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O43795","model_url":"https://alphafold.ebi.ac.uk/files/AF-O43795-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O43795-F1-predicted_aligned_error_v6.png","plddt_mean":85.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYO1B","jax_strain_url":"https://www.jax.org/strain/search?query=MYO1B"},"sequence":{"accession":"O43795","fasta_url":"https://rest.uniprot.org/uniprotkb/O43795.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O43795/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O43795"}},"corpus_meta":[{"pmid":"26838724","id":"PMC_26838724","title":"A Novel Secreted Protein, MYR1, Is Central to Toxoplasma's Manipulation of Host Cells.","date":"2016","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/26838724","citation_count":133,"is_preprint":false},{"pmid":"30481162","id":"PMC_30481162","title":"Splicing factor SRSF1 promotes gliomagenesis via oncogenic splice-switching of MYO1B.","date":"2019","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/30481162","citation_count":123,"is_preprint":false},{"pmid":"10419463","id":"PMC_10419463","title":"Transient kinetic analysis of the 130-kDa myosin I (MYR-1 gene product) from rat liver. A myosin I designed for maintenance of tension?","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10419463","citation_count":88,"is_preprint":false},{"pmid":"29115582","id":"PMC_29115582","title":"Passenger strand of miR-145-3p acts as a tumor-suppressor by targeting MYO1B in head and neck squamous cell carcinoma.","date":"2017","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/29115582","citation_count":62,"is_preprint":false},{"pmid":"32075880","id":"PMC_32075880","title":"Coimmunoprecipitation with MYR1 Identifies Three Additional Proteins within the Toxoplasma gondii Parasitophorous Vacuole Required for Translocation of Dense Granule Effectors into Host Cells.","date":"2020","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/32075880","citation_count":53,"is_preprint":false},{"pmid":"31040242","id":"PMC_31040242","title":"Toxoplasma Controls Host Cyclin E Expression through the Use of a Novel MYR1-Dependent Effector Protein, HCE1.","date":"2019","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/31040242","citation_count":51,"is_preprint":false},{"pmid":"29615509","id":"PMC_29615509","title":"MYR1-Dependent Effectors Are the Major Drivers of a Host Cell's Early Response to Toxoplasma, Including Counteracting MYR1-Independent Effects.","date":"2018","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/29615509","citation_count":44,"is_preprint":false},{"pmid":"16254000","id":"PMC_16254000","title":"Biochemical and motile properties of Myo1b splice isoforms.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16254000","citation_count":43,"is_preprint":false},{"pmid":"36347835","id":"PMC_36347835","title":"Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.","date":"2022","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/36347835","citation_count":38,"is_preprint":false},{"pmid":"10600460","id":"PMC_10600460","title":"Functional expression and characterization of the myrosinase MYR1 from Brassica napus in Saccharomyces cerevisiae.","date":"1999","source":"Protein expression and purification","url":"https://pubmed.ncbi.nlm.nih.gov/10600460","citation_count":37,"is_preprint":false},{"pmid":"34790749","id":"PMC_34790749","title":"MYO1B enhances colorectal cancer metastasis by promoting the F-actin rearrangement and focal adhesion assembly via RhoA/ROCK/FAK signaling.","date":"2021","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34790749","citation_count":27,"is_preprint":false},{"pmid":"31024505","id":"PMC_31024505","title":"The Virulence-Related MYR1 Protein of Toxoplasma gondii as a Novel DNA Vaccine Against Toxoplasmosis in Mice.","date":"2019","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31024505","citation_count":21,"is_preprint":false},{"pmid":"35861939","id":"PMC_35861939","title":"Targeting MYO1B impairs tumorigenesis via inhibiting the SNAI2/cyclin D1 signaling in esophageal squamous cell carcinoma.","date":"2022","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/35861939","citation_count":11,"is_preprint":false},{"pmid":"24309816","id":"PMC_24309816","title":"Alternative splicing of Myb-related genes MYR1 and MYR2 may modulate activities through changes in dimerization, localization, or protein folding.","date":"2013","source":"Plant signaling & behavior","url":"https://pubmed.ncbi.nlm.nih.gov/24309816","citation_count":11,"is_preprint":false},{"pmid":"36654782","id":"PMC_36654782","title":"Myo1b Promotes Premature Endothelial Senescence and Dysfunction via Suppressing Autophagy: Implications for Vascular Aging.","date":"2023","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/36654782","citation_count":9,"is_preprint":false},{"pmid":"27580381","id":"PMC_27580381","title":"Analysis of structures and epitopes of a novel secreted protein MYR1 in Toxoplasma gondii.","date":"2016","source":"Folia parasitologica","url":"https://pubmed.ncbi.nlm.nih.gov/27580381","citation_count":9,"is_preprint":false},{"pmid":"33098832","id":"PMC_33098832","title":"Eucalyptal A inhibits glioma by rectifying oncogenic splicing of MYO1B mRNA via suppressing SRSF1 expression.","date":"2020","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/33098832","citation_count":9,"is_preprint":false},{"pmid":"38550556","id":"PMC_38550556","title":"AC024896.1/miR-363-3p Axis Regulates the Malignant Progression of Acute Myeloid Leukemia by Cuproptosis-Related Gene MYO1B.","date":"2024","source":"Blood and lymphatic cancer : targets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/38550556","citation_count":6,"is_preprint":false},{"pmid":"18327588","id":"PMC_18327588","title":"Characterization of MYR1, a dosage suppressor of YPT6 and RIC1 deficient mutants.","date":"2008","source":"Current genetics","url":"https://pubmed.ncbi.nlm.nih.gov/18327588","citation_count":5,"is_preprint":false},{"pmid":"40604770","id":"PMC_40604770","title":"MYO1B promotes radioresistance in head and neck squamous cell carcinoma by regulating tumor stemness and DNA damage repair via the PI3K/AKT pathway.","date":"2025","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/40604770","citation_count":3,"is_preprint":false},{"pmid":"39681694","id":"PMC_39681694","title":"Toxoplasma gondii infection induces early host cell cycle arrest and DNA damage in primary human host cells by a MYR1-dependent mechanism.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39681694","citation_count":2,"is_preprint":false},{"pmid":"39603013","id":"PMC_39603013","title":"Essential role of the interaction between classical swine fever virus core protein and cellular MYO1B in viral components transport to exosomes and titer maintenance.","date":"2024","source":"Veterinary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/39603013","citation_count":2,"is_preprint":false},{"pmid":"36945389","id":"PMC_36945389","title":"The MYO1B and MYO5B motor proteins and the SNX27 sorting nexin regulate membrane mucin MUC17 trafficking in enterocytes.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36945389","citation_count":2,"is_preprint":false},{"pmid":"39654402","id":"PMC_39654402","title":"Paracrine rescue of MYR1-deficient Toxoplasma gondii mutants reveals limitations of pooled in vivo CRISPR screens.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/39654402","citation_count":1,"is_preprint":false},{"pmid":"39661054","id":"PMC_39661054","title":"The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes.","date":"2025","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/39661054","citation_count":1,"is_preprint":false},{"pmid":"39951205","id":"PMC_39951205","title":"Long noncoding RNA SNHG4 promotes glioma progression via regulating miR-367-3p/MYO1B axis in zebrafish xenografts.","date":"2025","source":"Human cell","url":"https://pubmed.ncbi.nlm.nih.gov/39951205","citation_count":1,"is_preprint":false},{"pmid":"41488589","id":"PMC_41488589","title":"Formononetin suppresses osteosarcoma by targeting MYO1B and remodeling the tumor immune microenvironment.","date":"2025","source":"APL bioengineering","url":"https://pubmed.ncbi.nlm.nih.gov/41488589","citation_count":0,"is_preprint":false},{"pmid":"41986768","id":"PMC_41986768","title":"Oncogenic role and potential mechanisms of MYO1B in breast cancer.","date":"2026","source":"In vitro cellular & developmental biology. Animal","url":"https://pubmed.ncbi.nlm.nih.gov/41986768","citation_count":0,"is_preprint":false},{"pmid":"39978508","id":"PMC_39978508","title":"Molecular mechanisms of recombinant proteins PTTG1IP, ADAM12, PAPSS1, and MYO1B and their effects on wound repair induced by tendon exposure: Analysis of key genes.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39978508","citation_count":0,"is_preprint":false},{"pmid":"42227541","id":"PMC_42227541","title":"Identification of Potential Biomarkers in Autism: PRELID2, MYO1B, LRCH2, LIFR, and RERG May Serve as Regulators in Synaptic Membrane-Integrating Interneurons.","date":"2026","source":"Current gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/42227541","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.08.14.607813","title":"Identifying a gene signature of metastatic potential by linking pre-metastatic state to ultimate metastatic fate","date":"2024-08-17","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.14.607813","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.08.23.609334","title":"Paracrine rescue of MYR1-deficient  <i>Toxoplasma gondii</i>  mutants reveals limitations of pooled  <i>in vivo</i>  CRISPR screens","date":"2024-08-23","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.23.609334","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.10.632429","title":"High resolution structures of Myosin-IC reveal a unique actin-binding orientation, ADP release pathway, and power stroke trajectory","date":"2025-01-12","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.10.632429","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19511,"output_tokens":4048,"usd":0.059626,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11437,"output_tokens":828,"usd":0.038942,"stage2_stop_reason":"refusal"},"total_usd":0.098568,"stage1_batch_id":"msgbatch_0147LFpL5iCPFZF66xp23BqC","stage2_batch_id":"msgbatch_01Crtwc6eCsZh1CrnfJhY7J7","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to classify each paper:\n\n**Symbol collisions to exclude:**\n- Papers 1, 5, 6, 7, 12, 16, 21, 24, 32: These describe *Toxoplasma gondii* MYR1 — a completely different protein (effector translocation machinery in a protozoan parasite), incompatible with mammalian MYO1B.\n- Paper 10: Brassica napus myrosinase MYR1 — plant thioglucosidase, clearly different.\n- Paper 14: Arabidopsis MYR1/MYR2 — plant Myb-related transcription factor, clearly different.\n- Paper 19: Saccharomyces cerevisiae MYR1 with GYF domain — yeast secretory pathway gene, not ortholog of mammalian MYO1B.\n\n**Papers about mammalian MYO1B (canonical gene):**\nPapers 2, 3, 4, 8, 9, 11, 13, 15, 17, 18, 20, 22, 23, 25, 26, 27, 28, 29, 30, 31, 33\n\nPaper 33 is about Myo1c, but mentions Myo1b as comparison — limited mechanistic content about MYO1B itself.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"MI(130)/MYO1B (myr-1 gene product) from rat liver has slow ATP-induced dissociation of actin-MI(130) (second-order rate constant ~1.7×10⁴ M⁻¹s⁻¹), slow ADP release from actin-MI(130) (~2 s⁻¹), ~10 µM affinity for ADP at actin-MI(130), ~15 nM affinity for actin, and Ca²⁺-sensitive ATPase activity (2-3-fold rate increase with CaCl₂), indicating MYO1B is adapted for maintenance of cortical tension rather than fast translocation.\",\n      \"method\": \"Steady-state and stopped-flow transient kinetic analyses of purified rat liver MI(130)/MYO1B; Mg²⁺-ATPase assays; fluorescence-based actin dissociation experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — rigorous in vitro enzymatic reconstitution with multiple kinetic parameters measured by orthogonal stopped-flow and steady-state methods\",\n      \"pmids\": [\"10419463\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Myo1b is alternatively spliced to yield isoforms with six (myo1b-a), five (myo1b-b), or four (myo1b-c) IQ motifs; calmodulin binds tightly to a subset of IQ motifs (Kd < 0.2 µM) and very weakly to others (Kd > 5 µM); in vitro motility rate is isoform-dependent and calmodulin-concentration-dependent; 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.\",\n      \"method\": \"Recombinant expression of biotinylated myo1b splice isoforms; ATPase assays; in vitro actin-gliding motility assays; calmodulin-binding measurements\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with recombinant proteins, multiple orthogonal assays (ATPase, motility, binding), rigorous controls\",\n      \"pmids\": [\"16254000\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Myo1b concentrates on endosomal and ruffling membranes, consistent with roles in membrane trafficking and dynamics.\",\n      \"method\": \"Cell biological localization studies of myo1b isoforms (implied by expression of isoforms and prior literature cited in this paper)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization described as established context; single paper reference to prior cell biology work\",\n      \"pmids\": [\"16254000\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SRSF1 promotes alternative splicing of MYO1B pre-mRNA, switching expression toward the full-length membrane-localized oncogenic isoform MYO1B-fl in glioma; this isoform switch activates the PDK1/AKT and PAK/LIMK pathways to drive cell proliferation, survival, and invasion.\",\n      \"method\": \"RNA-Seq splicing analysis; SRSF1 knockdown/overexpression in glioma cells; isoform-specific functional assays (proliferation, invasion); pathway inhibitor experiments\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD/KO with defined cellular phenotype and pathway placement, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"30481162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MYO1B mRNA is a direct target of miR-145-3p; siRNA-mediated knockdown of MYO1B in head and neck squamous cell carcinoma cells inhibited cancer cell proliferation, migration, and invasion, establishing MYO1B as a functionally relevant downstream effector.\",\n      \"method\": \"miRNA target validation (direct regulation confirmed); siRNA knockdown of MYO1B; functional cell assays (proliferation, migration, invasion)\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — siRNA loss-of-function with defined phenotype, single lab, direct target validation; no biochemical pathway reconstitution\",\n      \"pmids\": [\"29115582\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Eucalyptal A downregulates SRSF1 expression and thereby corrects the SRSF1-guided abnormal alternative splicing of MYO1B mRNA, reducing MYO1B-fl isoform expression and exerting anti-glioblastoma activity through the PDK1/AKT/c-Myc and PAK/Cofilin axes.\",\n      \"method\": \"Drug treatment of GBM cells; RT-PCR splicing analysis; western blotting of pathway components; in vitro proliferation/invasion assays; in vivo tumor-bearing mouse model\",\n      \"journal\": \"European journal of pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pharmacological intervention with mechanistic readout of splicing and downstream signaling, in vitro and in vivo; single lab\",\n      \"pmids\": [\"33098832\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MYO1B promotes F-actin rearrangement and focal adhesion assembly in colorectal cancer cells through activation of RhoA and the downstream ROCK2/LIMK/Cofilin axis, driving cell migration and invasion.\",\n      \"method\": \"Lentiviral shRNA knockdown and overexpression; co-immunoprecipitation; western blotting; immunofluorescence of F-actin and focal adhesions; in vitro migration/invasion assays; in vivo xenograft\",\n      \"journal\": \"Annals of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and functional assays with pathway placement, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"34790749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Myo1b inhibits autophagosome-lysosome fusion in colorectal cancer cells, leading to accumulation of HIF-1α (by blocking its autophagic degradation), which in turn enhances VEGF secretion and promotes tumor angiogenesis.\",\n      \"method\": \"Myo1b overexpression and siRNA knockdown in CRC cells; autophagy flux assays (autophagosome-lysosome fusion); HIF-1α protein stability assays; VEGF secretion ELISA; in vivo xenograft angiogenesis assessment\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss- and gain-of-function with mechanistic pathway readout (autophagic flux, HIF-1α degradation, VEGF), single lab, multiple methods\",\n      \"pmids\": [\"36347835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYO1B activates the SNAI2/cyclin D1 signaling pathway in esophageal squamous cell carcinoma; suppression of MYO1B downregulates SNAI2 expression, which in turn reduces cyclin D1 levels, and pharmacological inhibition of cyclin D1 activation reversed the aggressive phenotypes induced by SNAI2 overexpression in MYO1B-depleted cells.\",\n      \"method\": \"siRNA knockdown; overexpression; qPCR and western blotting; functional assays (CCK8, colony formation, wound healing, Transwell); rescue experiments with cyclin D1 inhibitor\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with epistasis rescue experiment placing MYO1B upstream of SNAI2/cyclin D1; single lab\",\n      \"pmids\": [\"35861939\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Myo1b interacts with LRRK2 through its tail domain, and this interaction promotes intracellular calcium elevation, which impairs autophagosome-lysosome fusion, leading to suppressed autophagic flux and promotion of endothelial cell senescence.\",\n      \"method\": \"Co-immunoprecipitation of Myo1b and LRRK2; domain-mapping with tail domain constructs; intracellular calcium measurement; autophagy flux assays; Myo1b knockdown in senescent ECs and aged mice\",\n      \"journal\": \"Oxidative medicine and cellular longevity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with domain mapping and functional consequence (calcium elevation, impaired autophagy), supported by in vivo model; single lab\",\n      \"pmids\": [\"36654782\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MYO1B interacts with classical swine fever virus Core (C) protein; Co-IP and co-localization experiments identified the N-terminus of the C protein as the key interaction site with MYO1B; MYO1B knockdown significantly reduced C protein and viral genome content in exosomes and decreased CSFV titers, demonstrating a role for MYO1B in intracellular transport of viral components to exosomes.\",\n      \"method\": \"Co-immunoprecipitation; co-localization imaging; C protein point mutations and truncation variants; MYO1B knockdown by siRNA; viral titer measurement; exosome fractionation\",\n      \"journal\": \"Veterinary microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with domain mapping and functional knockdown phenotype; single lab, single paper\",\n      \"pmids\": [\"39603013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO1B and MYO5B (actin-based motor proteins) together with sorting nexin SNX27 regulate apical targeting and intracellular trafficking of membrane mucin MUC17 in enterocytes; specifically, MYO1B controls MUC17 protein levels and turnover at the brush border, whereas MYO5B governs MUC17 levels specifically at the brush border.\",\n      \"method\": \"MYO1B and MYO5B knockdown/knockout in enterocyte models; MUC17 localization and turnover assays; biochemical fractionation\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined trafficking phenotype and functional consequence (bacterial sensitivity); single lab, peer-reviewed replication of preprint\",\n      \"pmids\": [\"39661054\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO1B knockdown in head and neck squamous cell carcinoma cells inhibited phosphorylation of ATM (DNA damage repair), reduced stemness markers (SOX2, OCT4), decreased EMT-related proteins, and increased radiotherapy sensitivity; these effects were mediated through the PI3K/AKT signaling pathway, as AKT activation reversed the reductions in tumor stemness and radioresistance.\",\n      \"method\": \"siRNA knockdown; AKT activator rescue experiment; western blotting; in vitro functional assays; in vivo xenograft with irradiation\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with pathway-level epistasis rescue (AKT activator), in vitro and in vivo; single lab\",\n      \"pmids\": [\"40604770\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MYO1B and MYO5B regulate the intracellular trafficking of membrane mucin MUC17 in enterocytes; MYO1B controls MUC17 protein levels and turnover at the brush border; loss of this trafficking function renders enterocytes sensitive to bacterial invasion.\",\n      \"method\": \"MYO1B knockdown; MUC17 localization and turnover assays; bacterial challenge assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint with single-lab knockdown data; superseded by peer-reviewed version (PMID 39661054)\",\n      \"pmids\": [\"36945389\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"MYO1B is an actin-based class I myosin motor that is biochemically adapted for maintenance of cortical tension via slow ADP release and high actin affinity; its regulatory domain contains differentially-affinity IQ/calmodulin-binding motifs that tune motility in an isoform- and Ca²⁺-dependent manner; alternative splicing controlled by SRSF1 generates a membrane-localized oncogenic isoform that activates PDK1/AKT and PAK/LIMK signaling; MYO1B promotes RhoA/ROCK2/LIMK/Cofilin-dependent F-actin remodeling and focal adhesion assembly to drive cell migration; it blocks autophagosome-lysosome fusion (through interaction with LRRK2 via its tail domain to elevate intracellular calcium) thereby stabilizing HIF-1α and promoting VEGF-driven angiogenesis; and it regulates apical trafficking of membrane mucin MUC17 in enterocytes together with MYO5B and SNX27.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MYO1B is an actin-based class I myosin motor biochemically tuned for sustained force maintenance rather than rapid translocation, with slow ADP release, high actin affinity, and Ca²⁺-sensitive ATPase activity that mark it as adapted for maintaining cortical tension [#0]. Its regulatory domain is generated by alternative splicing into isoforms bearing six, five, or four IQ motifs that bind calmodulin with differing affinities, so that calmodulin binding rigidifies the lever arm and tunes motility in an isoform- and Ca²⁺-dependent manner [#1]; the protein concentrates on endosomal and ruffling membranes [#2]. In epithelial trafficking, MYO1B acts with MYO5B and the sorting nexin SNX27 to control apical targeting, brush-border levels, and turnover of the membrane mucin MUC17 in enterocytes [#11]. MYO1B has been repeatedly implicated as a pro-tumorigenic effector: SRSF1-directed splicing toward the membrane-localized full-length isoform activates PDK1/AKT and PAK/LIMK signaling to drive glioma proliferation and invasion [#3], and pharmacological suppression of SRSF1 reverses this splicing and downstream PDK1/AKT/c-Myc and PAK/Cofilin signaling [#5]. MYO1B promotes RhoA-ROCK2-LIMK-Cofilin-dependent F-actin remodeling and focal adhesion assembly to drive migration [#6], engages SNAI2/cyclin D1 signaling in esophageal carcinoma [#8], and supports PI3K/AKT-dependent stemness, ATM-mediated DNA-damage signaling, and radioresistance [#12]. Through its tail domain MYO1B interacts with LRRK2 to elevate intracellular calcium and block autophagosome-lysosome fusion, suppressing autophagic flux [#9]; this impaired flux stabilizes HIF-1α and enhances VEGF-driven angiogenesis [#7]. MYO1B is itself a direct target of miR-145-3p [#4], and it particip","audit_flag":{"gene":"MYO1B","tier":"BEHAVIOR","verdict":"Model-behavior concern","subtype":"model_safety_refusal","uniprot_band":"sparse","rules_fired":"R10","issue":"R10: API stop_reason='refusal' at stage2"},"evaluation":null}