# MYOM2

## Overview
MYOM2 is a gene that encodes the protein myomesin 2, a structural component of the M-band in sarcomeres, which are the fundamental units of muscle fibers in both skeletal and cardiac muscles. Myomesin 2 plays a pivotal role in the structural integrity and biomechanical function of muscle tissues by anchoring and cross-linking thick filaments of myosin and interacting with other sarcomeric proteins such as titin and MYH7. This interaction is crucial for maintaining the alignment and stability of the thick filaments during muscle contraction and relaxation cycles. The protein is predominantly expressed in the adult heart and fast skeletal muscle fibers, where it contributes to the contractile performance and structural organization of the sarcomere. Despite its critical role in muscle function, the detailed molecular structure of myomesin 2 remains less understood, highlighting the need for further research to elucidate its structural and functional mechanisms in muscle and cardiac tissues (Auxerre-Plantié2020Identification; Lamber2022The).

## Structure
The MYOM2 protein, encoded by the MYOM2 gene, is characterized by a complex domain structure that includes immunoglobulin-like (Ig) and fibronectin type III (FN3) domains. These domains are crucial for the protein's function as a cross-linker in the sarcomere's M-band, facilitating interactions with neighboring thick filaments of myosin and other sarcomere proteins such as titin (TTN) and MYH7 (Auxerre-Plantié2020Identification). The C-terminal part of MYOM2 comprises five Ig domains, which likely form Ig-helix patterns similar to those found in myomesin-1, although MYOM2 does not exhibit dimerization at domain Mp13, suggesting a unique aspect of the C-terminus that might be involved in unknown interactions (Lamber2022The).

Despite the detailed description of domain interactions, specific information on the primary, secondary, tertiary, and quaternary structures of MYOM2 is not provided in the available literature. Additionally, the texts do not detail common post-translational modifications or splice variant isoforms of MYOM2, indicating gaps in the current understanding of the molecular structure of this protein. This lack of detailed structural information underscores the need for further research to fully elucidate the molecular architecture and functional mechanisms of MYOM2 in muscle and cardiac tissues.

## Function
MYOM2 encodes the myomesin 2 protein, which is a crucial component of the M-band in sarcomeres, the basic units of muscle fibers in both skeletal and cardiac muscles. This protein plays a significant role in anchoring the thick (myosin) and thin (actin) filaments within the sarcomere, influencing the contractile performance of the heart and skeletal muscle (Auxerre-Plantié2020Identification). Myomesin 2 is specifically expressed in the adult heart and fast fibers, where it acts as a cross-linker for neighboring thick filaments of myosin and interacts with titin, contributing to the structural organization of the sarcomere (Auxerre-Plantié2020Identification). This interaction is essential for maintaining the alignment and stability of the thick filaments, which is crucial for the biomechanical properties of muscle tissue during contraction and relaxation cycles.

The expression of MYOM2 varies, being weaker in the embryonic human heart compared to skeletal muscle, and it is not expressed in smooth muscle. In cardiomyocytes derived from induced pluripotent stem cells, MYOM2 is expressed during cardiac differentiation, suggesting its involvement in the developmental processes of the heart (Auxerre-Plantié2020Identification). Additionally, MYOM2 interacts with other sarcomere proteins such as MYH7, which is known to be involved in hypertrophic cardiomyopathy and other congenital heart diseases, underscoring its critical role in cardiac structural integrity and function (Auxerre-Plantié2020Identification).

## Clinical Significance
MYOM2 mutations have been identified as significant contributors to hypertrophic cardiomyopathy (HCM) and Tetralogy of Fallot (TOF), two serious heart conditions. In HCM, characterized by left ventricular hypertrophy, mutations in MYOM2 are particularly notable in patients who do not have mutations in the most commonly associated HCM genes. These mutations can lead to severe arrhythmias and sudden cardiac death (Auxerre-Plantié2020Identification). In the context of TOF, a congenital heart defect involving four cardiac malformations, approximately 31% of a studied cohort of isolated TOF patients exhibited MYOM2 mutations. These mutations were associated with disturbances in gene expression networks and up-regulated MYOM2 mRNA levels, suggesting a disruption in normal cardiac developmental processes (Auxerre-Plantié2020Identification).

The clinical impact of MYOM2 mutations extends to various cardiac phenotypes, ranging from dilated to restrictive cardiomyopathy, similar to effects observed with mutations in other sarcomere-related genes like MYH7. This indicates a broad spectrum of potential cardiac dysfunctions arising from MYOM2 mutations (Auxerre-Plantié2020Identification). Moreover, these genetic alterations have been linked to an increased arrhythmic burden in adult TOF patients, highlighting the long-term effects of MYOM2 mutations on heart function (Auxerre-Plantié2020Identification).

## Interactions
MYOM2 interacts with a variety of proteins within the sarcomere, particularly in the M-band, which is crucial for muscle contraction and stability. It forms interactions with titin (TTN) and myosin, which are essential for the structural integrity of the sarcomere. MYOM2's interaction with titin is noted, although the specific domains involved are not fully confirmed, suggesting a complex interaction that may vary across different studies (Lamber2022The). Additionally, MYOM2 interacts with the muscle isoform of creatine kinase and the light meromyosin part of the beta-myosin heavy chain, which are critical for muscle function and energy processes (Auxerre-Plantié2020Identification).

MYOM2 also plays a role in cardiac muscle function through its interaction with the ryanodine receptors RYR1 and potentially RYR2, which are involved in calcium signaling pathways crucial for cardiac function and possibly cardiac arrhythmias (Lamber2022The). Furthermore, MYOM2 is part of a dense network of proteins associated with limb-girdle muscular dystrophies (LGMD), indicating its involvement in broader muscular and neuromuscular disorders (Blandin2013A).

These interactions highlight MYOM2's role not only in maintaining sarcomere structure but also in regulating muscle and cardiac function, making it a significant protein in understanding muscle integrity and related diseases.


## References


[1. (Auxerre-Plantié2020Identification) Identification ofMYOM2as a candidate gene in hypertrophic cardiomyopathy and Tetralogy of Fallot and its functional evaluation in theDrosophilaheart (30 citations) 10.1101/2020.08.18.255760](https://doi.org/10.1101/2020.08.18.255760)

[2. (Blandin2013A) Gaëlle Blandin, Sylvie Marchand, Karine Charton, Nathalie Danièle, Evelyne Gicquel, Jean-Baptiste Boucheteil, Azéddine Bentaib, Laetitia Barrault, Daniel Stockholm, Marc Bartoli, and Isabelle Richard. A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: lgmd interactome. Skeletal Muscle, February 2013. URL: http://dx.doi.org/10.1186/2044-5040-3-3, doi:10.1186/2044-5040-3-3. (47 citations) 10.1186/2044-5040-3-3](https://doi.org/10.1186/2044-5040-3-3)

[3. (Lamber2022The) Ekaterina P. Lamber, Pascale Guicheney, and Nikos Pinotsis. The role of the m-band myomesin proteins in muscle integrity and cardiac disease. Journal of Biomedical Science, March 2022. URL: http://dx.doi.org/10.1186/s12929-022-00801-6, doi:10.1186/s12929-022-00801-6. (19 citations) 10.1186/s12929-022-00801-6](https://doi.org/10.1186/s12929-022-00801-6)