MYOM1

Myomesin-1 is a protein that in humans is encoded by the MYOM1 gene.^[5][6] 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 dilated cardiomyopathy.

MYOM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2R15, 2Y23, 2Y25, 3RBS
Identifiers
Aliases	MYOM1, SKELEMIN, myomesin 1
External IDs	OMIM: 603508; MGI: 1341430; HomoloGene: 31196; GeneCards: MYOM1; OMA:MYOM1 - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18p11.31 Start 3,066,807 bp[1] End 3,219,968 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 E1.3 Start 71,309,628 bp[2] End 71,433,851 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle of thigh Skeletal muscle tissue of rectus abdominis Skeletal muscle tissue of biceps brachii glutes apex of heart gastrocnemius muscle triceps brachii muscle left ventricle vastus lateralis muscle right auricle of heart Top expressed in triceps brachii muscle temporal muscle muscle of thigh sternocleidomastoid muscle digastric muscle triceps surae gastrocnemius muscle medial head of gastrocnemius muscle vastus lateralis muscle tibialis anterior muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function structural constituent of muscle protein binding protein homodimerization activity identical protein binding actin filament binding muscle alpha-actinin binding structural molecule activity conferring elasticity kinase binding Cellular component cytoplasm myosin filament sarcomere striated muscle myosin thick filament Z discdkac M band striated muscle thin filament Biological process muscle contraction extraocular skeletal muscle development striated muscle contraction actin filament organization sarcomere organization striated muscle myosin thick filament assembly positive regulation of gene expression protein kinase A signaling positive regulation of protein secretion skeletal muscle thin filament assembly skeletal muscle myosin thick filament assembly cardiac myofibril assembly cardiac muscle tissue morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8736 17929 Ensembl ENSG00000101605 ENSMUSG00000024049 UniProt P52179 Q62234 RefSeq (mRNA) NM_003803 NM_019856 NM_001083934 NM_010867 RefSeq (protein) NP_003794 NP_062830 NP_001077403 NP_034997 Location (UCSC) Chr 18: 3.07 – 3.22 Mb Chr 17: 71.31 – 71.43 Mb PubMed search [3] [4]
Wikidata
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Structure

Alternatively spliced variants of MYOM1, including EH-myomesin,^[7] Skelemin^[8] and Myomesin-1^[8][9][10] have been identified; with Skelemin having an additional 96 amino acids rich in serine and proline residues.^[8] Myomesin-1, like myomesin 2 and titin, is a member of a family of 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 it has intermediate filament core-like motifs, one near each terminus.^[11] 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 titin string extends into the center of the M band. Alternatively spliced, tissue-specific transcript variants encoding different isoforms have been identified.^[12] Myomesin-1 can dimerize in an anti-parallel fashion via its C-terminal region.^[13]

Function

Titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the 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 myofibrils with the intermediate filament cytoskeleton.^[11] Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression.^[14] Myomesin-1 functions to mediate stretch-induced signaling,^[15] and the EH-myomesin splice variant, expressed in embryonic hearts and in dilated cardiomyopathy, can modulate its elasticity.^[16]

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 dilated cardiomyopathy, coincident with isoform switches in titin.^[17]

MYOM1 has also been shown to be abnormally spliced in patients with myotonic dystrophy type I; specifically, exon 17a.^[18]

Interactions

Skelemin/Myomesin-1 has been shown to interact with:

• ITGB1^[19]
• ITGB3^[19][20]
• ITGA2B^[20]
• MYH7^[21][22][23]
• Titin^[21]
• PNKD^[24]