MYOM1

Myomesin-1 is a is_associated_with::protein that in humans is encoded by the MYOM1 is_associated_with::gene. Myomesin-1 is expressed in muscle cells and functions to stabilize the three-dimensional conformation of the thick filament. Embryonic forms of Myomesin-1 have been detected in is_associated_with::dilated cardiomyopathy.

Structure
Alternatively spliced variants of MYOM1, including EH-myomesin, Skelemin and Myomesin-1  have been identified; with Skelemin having an additional 96 amino acids rich in is_associated_with::serine and is_associated_with::proline residues. Myomesin-1, like myomesin 2 and is_associated_with::titin, is a member of a family of is_associated_with::myosin-associated proteins containing structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin-1 bears uniqueness within this family in that is has is_associated_with::intermediate filament core-like motifs, one near each terminus. Myomesin-1 and Myomesin-2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the is_associated_with::titin string extends into the center of the M band. Alternatively spliced, tissue-specific transcript variants encoding different is_associated_with::isoforms have been identified. Myomesin-1 can dimerize in an anti-parallel fashion via its C-terminal region.

Function
is_associated_with::Titin, together with its associated proteins, interconnects the major structure of is_associated_with::sarcomeres, the M bands and Z discs. The C-terminal end of the is_associated_with::titin string extends into the M line, where it binds tightly to Myomesin-1 and myomesin 2. Skelemin/Myomesin-1 is concentrated at peripheral regions of M-bands, and is postulated to link is_associated_with::myofibrils with the is_associated_with::intermediate filament is_associated_with::cytoskeleton. Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression. Myomesin-1 functions to mediate stretch-induced signaling, and the EH-myomesin splice variant, expressed in embyronic hearts and in is_associated_with::dilated cardiomyopathy, can modulate its elasticity.

Clinical Significance
The fetal EH-myomesin alternatively spliced form of MYOM1 has been shown to be reexpressed at an early timepoint in the progression of is_associated_with::dilated cardiomyopathy, coincident with isoform switches in is_associated_with::titin.

MYOM1 has also been shown to be abnormally spliced in patients with is_associated_with::myotonic dystrophy type I; specifically, exon 17a.

Interactions
Skelemin/Myomesin-1 has been shown to interact with:
 * is_associated_with::ITGB1
 * is_associated_with::ITGB3
 * is_associated_with::ITGA2B
 * is_associated_with::MYH7
 * is_associated_with::Titin
 * is_associated_with::PNKD