Affinage

MYOM1

Myomesin-1 · UniProt P52179

Length
1685 aa
Mass
187.6 kDa
Annotated
2026-06-10
40 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYOM1 encodes myomesin-1, a structural M-band component of the sarcomere that is required for sarcomere assembly, contractile function, and calcium homeostasis in human cardiomyocytes, where its loss recapitulates a myocardial atrophy phenotype (PMID:33452765). Myomesin-1 localizes to both the sarcomere M-band and the nuclear envelope together with the α-kinase ALPK3, which is required for correct myomesin localization and for regulating M-band protein turnover (PMID:36321451). Expression of MYOM1 depends on the transcription factor SRF, whose cardiac loss blocks myofibril formation and rhythmic beating (PMID:19004760), while developmental embryonic-to-adult isoform switching is governed by alternative splicing controlled antagonistically by MBNL1–3 versus CELF1/CELF2 at exon 17a (PMID:21794030) and by SRSF5, whose loss prevents completion of the isoform switch and causes ventricular noncompaction (PMID:34622152). Myomesin-1 protein abundance is set by regulated degradation: the E3 ubiquitin ligase MuRF1 binds MYOM1 and mediates its ubiquitination in catabolic muscle, an interaction reduced by H2S-driven S-sulfhydration of MuRF1 at Cys44 (PMID:32633463). Layer-specific MYOM1/MYOM2 M-band composition in extraocular muscle correlates with altered mechanical properties (PMID:17325154).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2007 Medium

    Established that muscle-type-specific M-band composition, including MYOM1 expression levels, tracks with distinct mechanical properties, linking myomesin content to sarcomere biomechanics.

    Evidence PCR, qPCR, immunohistochemistry, confocal and electron microscopy across rat extraocular muscle layers

    PMID:17325154

    Open questions at the time
    • Mechanical predictions modeled, not directly measured
    • No causal manipulation of MYOM1 levels
  2. 2008 Medium

    Identified SRF as a transcriptional requirement for Myom1 expression, placing myomesin-1 downstream of the core cardiac myofibrillar gene program.

    Evidence Conditional cardiac SRF knockout mouse with cofactor-mutant and viral rescue experiments

    PMID:19004760

    Open questions at the time
    • Direct SRF binding to the MYOM1 promoter not demonstrated
    • Myom1 is one of many affected myofibrillar genes
  3. 2011 Medium

    Defined MYOM1 exon 17a as an alternative-splicing target controlled by competing MBNL and CELF factors, explaining aberrant splicing in myotonic dystrophy via MBNL sequestration.

    Evidence Exon array of DM1 patient muscle plus MYOM1 minigene splicing assays in HEK293T with MBNL1-3/CELF1/CELF2

    PMID:21794030

    Open questions at the time
    • Functional consequence of exon 17a inclusion on myomesin-1 protein not established
    • Minigene context may not reflect endogenous regulation
  4. 2015 Low

    Showed that loss of Mbnl1 in vivo causes persistence of embryonic Myom1 isoforms in heart, linking splicing dysregulation to cardiac pathology.

    Evidence Mbnl1 deletion mouse with cardiac RNA splicing analysis and phenotyping

    PMID:25761764

    Open questions at the time
    • Myom1 splicing change is one of many in a broad regulator KO; no MYOM1-specific rescue
    • Causal contribution of Myom1 mis-splicing to phenotype unresolved
  5. 2020 Medium

    Identified MuRF1-mediated ubiquitination as a degradation pathway controlling MYOM1 abundance and showed it is reversible by H2S-driven S-sulfhydration of MuRF1.

    Evidence Reciprocal Co-IP, ubiquitination assay, and S-sulfhydration site mapping in db/db mice and C2C12 cells

    PMID:32633463

    Open questions at the time
    • MYOM1 ubiquitination site not mapped
    • Established in skeletal/diabetic muscle; cardiac relevance untested
  6. 2021 Medium

    Demonstrated by loss-of-function that myomesin-1 is required for sarcomere assembly, contractility, and calcium homeostasis in human cardiomyocytes, giving the gene a defined cellular phenotype.

    Evidence CRISPR/Cas9 MYOM1 knockout in hESC-derived cardiomyocytes with structural and functional readouts

    PMID:33452765

    Open questions at the time
    • Molecular mechanism of contractility and calcium defect not dissected
    • Single-lab in vitro model
  7. 2021 Medium

    Established SRSF5 as the splicing factor driving the embryonic-to-adult Myom1 isoform switch, connecting incomplete switching to ventricular noncompaction.

    Evidence CRISPR-Cas9 Srsf5 knockout mice with Myom1 isoform and cardiac phenotype analysis

    PMID:34622152

    Open questions at the time
    • Whether arrested Myom1 switching alone drives noncompaction not isolated
    • Other SRSF5 targets contribute
  8. 2022 Medium

    Placed myomesin proteins downstream of ALPK3, showing ALPK3 co-localizes with MYOM1 at M-band and nuclear envelope and is required for its correct localization and M-band protein turnover.

    Evidence Co-localization in hiPSC-derived cardiomyocytes and patient tissue, ALPK3 LOF iPSC model, proteomics

    PMID:36321451

    Open questions at the time
    • Direct ALPK3-MYOM1 physical interaction vs. indirect effect not resolved
    • Kinase substrate relationship undefined
  9. 2022 Low

    Reported miR-135a as a direct negative regulator of MYOM1 in an immune-cell injury context, an uncharacterized setting for this sarcomeric protein.

    Evidence Dual-luciferase 3'UTR reporter, qRT-PCR/western, and rescue in LPS-treated THP-1 cells

    PMID:35977075

    Open questions at the time
    • Biological role of MYOM1 in non-muscle immune cells unexplained
    • Single-lab reporter and rescue without orthogonal validation
  10. 2023 Low

    Showed in vitro that SARS-CoV-2 PLpro can cleave a predicted MYOM1 sequence, raising a candidate host-protein target during infection.

    Evidence In vitro protease cleavage assay on a predicted MYOM1 cleavage site

    PMID:36851756

    Open questions at the time
    • No functional consequence of cleavage established
    • Cleavage not demonstrated in cells
  11. 2026 Low

    Defined a calpain-mediated degradation axis controlling MYOM1 protein levels in drug-induced cardiotoxicity, with calpain inhibition preserving myofilament structure.

    Evidence Calpain inhibitor and calpain1 gain/loss-of-function in vandetanib-treated cardiomyocytes with western blot and calcium imaging

    PMID:41765115

    Open questions at the time
    • No in vitro cleavage reconstitution or site identification
    • Direct vs. indirect calpain action not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How myomesin-1's M-band cross-linking activity mechanistically integrates with its transcriptional, splicing, and degradation control to determine sarcomere mechanics in human disease remains unresolved.
  • No structural model of MYOM1 in the human M-band lattice in the corpus
  • No timeline-documented Mendelian disease mutation in MYOM1 itself
  • Integration of regulatory inputs (SRF, splicing, MuRF1, calpain, ALPK3) into a unified control model untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005856 cytoskeleton 3 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-397014 Muscle contraction 2
Partners
ALPK3MURF1MYOM2
Complex memberships
sarcomere M-band

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 CRISPR/Cas9 knockout of MYOM1 in human embryonic stem cell-derived cardiomyocytes demonstrated that myomesin-1 is required for sarcomere assembly, contractility regulation, and cardiomyocyte development; loss of myomesin-1 recapitulates a myocardial atrophy phenotype in vitro and impairs calcium homeostasis. CRISPR/Cas9 knockout of MYOM1 in hESCs, differentiation to cardiomyocytes, phenotypic analysis of sarcomere structure and contractility Journal of cellular and molecular medicine Medium 33452765
2022 ALPK3 (α-kinase 3) colocalized with MYOM1 and MYOM2 at both the nuclear envelope and the sarcomere M-band; loss-of-function variants in ALPK3 caused mislocalization of myomesin proteins (including MYOM1) and dysregulated additional M-band proteins involved in sarcomere protein turnover, impairing cardiomyocyte structure and function. Co-localization in hiPSC-derived cardiomyocytes and patient tissues, ALPK3 loss-of-function iPSC model, proteomic analysis Circulation Medium 36321451
2011 Alternative splicing of MYOM1 exon 17a is regulated by MBNL1-3, CELF1, and CELF2 (which decrease exon 17a inclusion), and is aberrantly increased in DM1 muscle due to sequestration of MBNL proteins by expanded CUG repeats; CELF1 activity on MYOM1 splicing was not affected by expanded CUG repeats. Exon array to detect aberrant splicing in DM1 patient muscle; MYOM1 minigene splicing assay in HEK293T cells with MBNL1-3, CELF1, CELF2 overexpression or CUG repeat expression Genes to cells Medium 21794030
2021 SRSF5 (splicing factor) promotes the alternative splicing of Myom1 in the heart, facilitating the switch from embryonic to adult isoforms; loss of Srsf5 in mice prevented completion of this isoform switch and caused noncompaction of the ventricular myocardium with cardiac dysfunction. CRISPR-Cas9 Srsf5 knockout mice; RNA splicing analysis of Myom1 isoforms; cardiac phenotype characterization iScience Medium 34622152
2020 MuRF1 (E3 ubiquitin ligase) interacts with MYOM1 and mediates its ubiquitination in diabetic skeletal muscle; exogenous hydrogen sulphide reduces the interaction between MuRF1 and MYOM1 via MuRF1 S-sulfhydration at Cys44, thereby decreasing MYOM1 ubiquitination and degradation. Co-immunoprecipitation of MuRF1 with MYOM1, ubiquitination assay in db/db mice, S-sulfhydration analysis, H2S treatment in vivo and in C2C12 cells Journal of cellular and molecular medicine Medium 32633463
2007 MYOM1 (myomesin-1) and MYOM2 (M-protein) show layer-specific differential expression at the structural, mRNA, and protein levels in extraocular muscle orbital vs. global layers, with the differential M-band composition predicting increased elasticity but reduced force and eccentric contraction-mediated damage in EOMs, providing a potential mechanism for EOM sparing in Duchenne muscular dystrophy. Semiquantitative PCR, qPCR, immunohistochemistry, confocal microscopy, electron microscopy on rat EOM layers Investigative ophthalmology & visual science Medium 17325154
2008 Serum response factor (SRF) is required for expression of Myom1 in the heart; conditional cardiac SRF knockout powerfully attenuated Myom1 expression along with other myofibril proteins, blocking sarcomere formation and rhythmic beating. Conditional cardiac-specific SRF knockout mouse, SRF point mutants blocking cofactor interactions, viral rescue of SRF-null ES cells Proceedings of the National Academy of Sciences of the United States of America Medium 19004760
2015 Loss of muscleblind-like 1 (Mbnl1) in mice results in persistence of embryonic splice isoforms of Myom1 in cardiac tissue, associated with cardiac pathology including hypertrophy, fibrosis, and sudden death. Mbnl1 deletion mouse model (Mbnl1ΔE2/ΔE2), splicing analysis of cardiac RNAs including Myom1, cardiac phenotype characterization Scientific reports Low 25761764
2023 The SARS-CoV-2 papain-like protease (PLpro) was shown to cleave a predicted sequence in MYOM1 in an in vitro cleavage assay. In vitro protease cleavage assay using SARS-CoV-2 PLpro on predicted MYOM1 cleavage sequence Viruses Low 36851756
2022 miR-135a directly targets MYOM1 (confirmed by dual-luciferase assay), negatively regulating its expression in LPS-treated THP-1 cells; MYOM1 depletion reversed the protective effect of miR-135a inhibition on LPS-induced cell injury. Dual-luciferase reporter assay confirming miR-135a binding to MYOM1 3'UTR; qRT-PCR and western blot for MYOM1 expression; rescue experiments in LPS-treated THP-1 cells Acta biochimica Polonica Low 35977075
2026 Calpain activation mediates degradation of MYOM1 in vandetanib-treated cardiomyocytes; calpain inhibition rescued MYOM1 protein levels and preserved myofilament structure, while calpain1 overexpression aggravated loss of contractile proteins. Calpain inhibitor treatment and calpain1 overexpression/knockdown in cardiomyocytes treated with vandetanib; western blot quantification of MYOM1 protein levels; calcium imaging European journal of pharmaceutical sciences Low 41765115

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. PLoS genetics 165 23236287
2008 Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart. Proceedings of the National Academy of Sciences of the United States of America 93 19004760
2015 Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families. Genome biology 89 26036949
2015 OBSCN Mutations Associated with Dilated Cardiomyopathy and Haploinsufficiency. PloS one 72 26406308
2015 Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms. Scientific reports 69 25761764
2017 Transcriptional landscape of human cancers. Oncotarget 68 28427185
2022 Pathogenesis of Cardiomyopathy Caused by Variants in ALPK3, an Essential Pseudokinase in the Cardiomyocyte Nucleus and Sarcomere. Circulation 38 36321451
2011 Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1. Genes to cells : devoted to molecular & cellular mechanisms 31 21794030
2017 Comparative analysis on genome-wide DNA methylation in longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep. Asian-Australasian journal of animal sciences 29 28728367
2020 Hydrogen sulphide ameliorating skeletal muscle atrophy in db/db mice via Muscle RING finger 1 S-sulfhydration. Journal of cellular and molecular medicine 26 32633463
2021 Knockout of MYOM1 in human cardiomyocytes leads to myocardial atrophy via impairing calcium homeostasis. Journal of cellular and molecular medicine 24 33452765
2006 Unbalanced whole arm translocation resulting in loss of 18p in dystonia. Movement disorders : official journal of the Movement Disorder Society 23 16541453
2005 Genomic structure and organization of the high grade Myopia-2 locus (MYP2) critical region: mutation screening of 9 positional candidate genes. Molecular vision 21 15723005
2023 Loss of Cardiac Splicing Regulator RBM20 Is Associated With Early-Onset Atrial Fibrillation. JACC. Basic to translational science 18 38510713
2020 Population structure, genetic diversity, and selective signature of Chaka sheep revealed by whole genome sequencing. BMC genomics 18 32727368
2017 Dissection of Z-disc myopalladin gene network involved in the development of restrictive cardiomyopathy using system genetics approach. World journal of cardiology 17 28515850
2007 Identification and characterization of layer-specific differences in extraocular muscle m-bands. Investigative ophthalmology & visual science 17 17325154
2022 Analysis of characteristic genes and ceRNA regulation mechanism of endometriosis based on full transcriptional sequencing. Frontiers in genetics 13 35938015
2021 Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium. iScience 13 34622152
2022 Gill and Liver Transcript Expression Changes Associated With Gill Damage in Atlantic Salmon (Salmo salar). Frontiers in immunology 12 35418993
2021 The miR-223/nuclear factor I-A axis regulates inflammation and cellular functions in intestinal tissues with necrotizing enterocolitis. FEBS open bio 12 33932136
2018 Detection of genetic variants between different Polish Landrace and Puławska pigs by means of RNA-seq analysis. Animal genetics 11 29635698
2013 Identification of an interstitial 18p11.32-p11.31 duplication including the EMILIN2 gene in a family with porokeratosis of Mibelli. PloS one 10 23593459
2017 The effect of high fat diet on daily rhythm of the core clock genes and muscle functional genes in the skeletal muscle of Chinese soft-shelled turtle (Trionyx sinensis). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 9 28729066
2023 Automated SSHHPS Analysis Predicts a Potential Host Protein Target Common to Several Neuroinvasive (+)ssRNA Viruses. Viruses 7 36851756
2018 Mutant myocilin impacts sarcomere ultrastructure in mouse gastrocnemius muscle. PloS one 7 30395621
2024 Transcriptome networks and physiology related to cardiac function and motor activity are perturbed in larval zebrafish (Danio rerio) following exposure to the antidepressant citalopram. Environmental pollution (Barking, Essex : 1987) 5 39168440
2010 Mouse chromosome 17 candidate modifier genes for thrombosis. Mammalian genome : official journal of the International Mammalian Genome Society 5 20700597
2023 Chemical hazard of robotic hull in-water cleaning discharge on coastal embryonic fish. Ecotoxicology and environmental safety 4 36812868
2022 FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis. International journal of general medicine 4 35082523
2025 Genome-wide detection of runs of homozygosity in Ding'an pigs revealed candidate genes relating to meat quality traits. BMC genomics 3 40165050
2024 Identification of the cytoplasmic DNA-Sensing cGAS-STING pathway-mediated gene signatures and molecular subtypes in prostate cancer. BMC cancer 3 38877472
2024 Proteomic analysis of the serum in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease: the preliminary study. Frontiers in veterinary science 2 38596466
2021 MYP2 locus genes: Sequence variations, genetic association studies and haplotypic association in patients with High Myopia. International journal of biochemistry and molecular biology 2 33824778
2025 Reproductive tract microbiota dysbiosis in ovarian endometrioma and adenomyosis: multi-site 16S rRNA profiling and functional impact of key bacterial species on human endometrial stromal cells. BMC microbiology 1 41193989
2024 Ventricular fibrillation during football training as a consequence of kratom and caffeine use in an adolescent: case report. European heart journal. Case reports 1 39139851
2022 MiR-135a is highly expressed and aggravates inflammatory response in sepsis by targeting MYOM1. Acta biochimica Polonica 1 35977075
2026 Calpain inhibition preserves myofilament integrity and prevents vandetanib-induced cardiac dysfunction. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 0 41765115
2025 Comprehensive analysis of aberrant alternative splicing and RNA binding proteins associated with age-related sensorineural hearing loss. Scientific reports 0 41125741
2024 Dilatative fetal cardiomyopathy followed by a mirror syndrome. Wiener medizinische Wochenschrift (1946) 0 38836950

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