MYOM1

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
View/Edit Human View/Edit Mouse

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.

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]

References

1. GRCh38: Ensembl release 89: ENSG00000101605 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024049 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Speel EJ, van der Ven PF, Albrechts JC, Ramaekers FC, Fürst DO, Hopman AH (Nov 1998). "Assignment of the human gene for the sarcomeric M-band protein myomesin (MYOM1) to 18p11.31-p11.32". Genomics. 54 (1): 184–6. doi:10.1006/geno.1998.5503. PMID   9806852.
6. "Entrez Gene: MYOM1 myomesin 1 (skelemin) 185kDa".
7. Agarkova I, Auerbach D, Ehler E, Perriard JC (Apr 2000). "A novel marker for vertebrate embryonic heart, the EH-myomesin isoform". The Journal of Biological Chemistry. 275 (14): 10256–64. doi: 10.1074/jbc.275.14.10256 . PMID   10744711.
8. Steiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89. doi:10.1006/geno.1998.5682. PMID   10036188.
9. "Protein sequence of human MYOM1 (Uniprot ID: P52179)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 24 June 2015. Retrieved 24 June 2015.
10. "Protein sequence of human MYOM1 (Uniprot ID: P52179-2)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 24 June 2015. Retrieved 24 June 2015.
11. Price MG, Gomer RH (Oct 1993). "Skelemin, a cytoskeletal M-disc periphery protein, contains motifs of adhesion/recognition and intermediate filament proteins". The Journal of Biological Chemistry. 268 (29): 21800–10. doi: 10.1016/S0021-9258(20)80613-9 . PMID   8408035.
12. Bantle S, Keller S, Haussmann I, Auerbach D, Perriard E, Mühlebach S, Perriard JC (Aug 1996). "Tissue-specific isoforms of chicken myomesin are generated by alternative splicing". The Journal of Biological Chemistry. 271 (32): 19042–52. doi: 10.1074/jbc.271.32.19042 . PMID   8702575.
13. Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98. doi:10.1016/j.jmb.2004.10.040. PMID   15571722.
14. Reddy KB, Fox JE, Price MG, Kulkarni S, Gupta S, Das B, Smith DM (2008). "Nuclear localization of Myomesin-1: possible functions". Journal of Muscle Research and Cell Motility. 29 (1): 1–8. doi:10.1007/s10974-008-9137-x. PMID   18521710. S2CID   12298270.
15. Agarkova I, Perriard JC (Sep 2005). "The M-band: an elastic web that crosslinks thick filaments in the center of the sarcomere". Trends in Cell Biology. 15 (9): 477–85. CiteSeerX   10.1.1.384.2007 . doi:10.1016/j.tcb.2005.07.001. PMID   16061384.
16. Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79. doi:10.1016/j.jmb.2005.03.055. PMID   15890201.
17. Schoenauer R, Emmert MY, Felley A, Ehler E, Brokopp C, Weber B, Nemir M, Faggian GG, Pedrazzini T, Falk V, Hoerstrup SP, Agarkova I (Mar 2011). "EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy". Basic Research in Cardiology. 106 (2): 233–47. doi:10.1007/s00395-010-0131-2. PMC   3032906 . PMID   21069531.
18. Koebis M, Ohsawa N, Kino Y, Sasagawa N, Nishino I, Ishiura S (Sep 2011). "Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1". Genes to Cells. 16 (9): 961–72. doi:10.1111/j.1365-2443.2011.01542.x. PMID   21794030. S2CID   3272510.
19. Reddy KB, Gascard P, Price MG, Negrescu EV, Fox JE (Dec 1998). "Identification of an interaction between the m-band protein skelemin and beta-integrin subunits. Colocalization of a skelemin-like protein with beta1- and beta3-integrins in non-muscle cells". The Journal of Biological Chemistry. 273 (52): 35039–47. doi: 10.1074/jbc.273.52.35039 . PMID   9857037.
20. Deshmukh L, Tyukhtenko S, Liu J, Fox JE, Qin J, Vinogradova O (Nov 2007). "Structural insight into the interaction between platelet integrin alphaIIbbeta3 and cytoskeletal protein skelemin". The Journal of Biological Chemistry. 282 (44): 32349–56. doi: 10.1074/jbc.M704666200 . PMID   17804417.
21. Obermann WM, Gautel M, Weber K, Fürst DO (Jan 1997). "Molecular structure of the sarcomeric M band: mapping of titin and myosin binding domains in myomesin and the identification of a potential regulatory phosphorylation site in myomesin". The EMBO Journal. 16 (2): 211–20. doi:10.1093/emboj/16.2.211. PMC   1169628 . PMID   9029142.
22. Obermann WM, van der Ven PF, Steiner F, Weber K, Fürst DO (Apr 1998). "Mapping of a myosin-binding domain and a regulatory phosphorylation site in M-protein, a structural protein of the sarcomeric M band". Molecular Biology of the Cell. 9 (4): 829–40. doi:10.1091/mbc.9.4.829. PMC   25310 . PMID   9529381.
23. Auerbach D, Bantle S, Keller S, Hinderling V, Leu M, Ehler E, Perriard JC (May 1999). "Different domains of the M-band protein myomesin are involved in myosin binding and M-band targeting". Molecular Biology of the Cell. 10 (5): 1297–308. doi:10.1091/mbc.10.5.1297. PMC   25262 . PMID   10233145.
24. Li TB, Liu XH, Feng S, Hu Y, Yang WX, Han Y, Wang YG, Gong LM (Jun 2004). "Characterization of MR-1, a novel myofibrillogenesis regulator in human muscle" (PDF). Acta Biochimica et Biophysica Sinica. 36 (6): 412–8. doi:10.1093/abbs/36.6.412. PMID   15188056. S2CID   18331104. Archived from the original (PDF) on 2019-02-22.

Further reading

• Grove BK, Kurer V, Lehner C, Doetschman TC, Perriard JC, Eppenberger HM (Feb 1984). "A new 185,000-dalton skeletal muscle protein detected by monoclonal antibodies". The Journal of Cell Biology. 98 (2): 518–24. doi:10.1083/jcb.98.2.518. PMC   2113097 . PMID   6537951.
• Vinkemeier U, Obermann W, Weber K, Fürst DO (Sep 1993). "The globular head domain of titin extends into the center of the sarcomeric M band. cDNA cloning, epitope mapping and immunoelectron microscopy of two titin-associated proteins". Journal of Cell Science. 106 (1): 319–30. doi:10.1242/jcs.106.1.319. PMID   7505783.
• Obermann WM, Plessmann U, Weber K, Fürst DO (Oct 1995). "Purification and biochemical characterization of myomesin, a myosin-binding and titin-binding protein, from bovine skeletal muscle". European Journal of Biochemistry. 233 (1): 110–5. doi:10.1111/j.1432-1033.1995.110_1.x. PMID   7588733.
• Steiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89. doi:10.1006/geno.1998.5682. PMID   10036188.
• Agarkova I, Auerbach D, Ehler E, Perriard JC (Apr 2000). "A novel marker for vertebrate embryonic heart, the EH-myomesin isoform". The Journal of Biological Chemistry. 275 (14): 10256–64. doi: 10.1074/jbc.275.14.10256 . PMID   10744711.
• Porter JD, Merriam AP, Gong B, Kasturi S, Zhou X, Hauser KF, Andrade FH, Cheng G (Sep 2003). "Postnatal suppression of myomesin, muscle creatine kinase and the M-line in rat extraocular muscle". The Journal of Experimental Biology. 206 (Pt 17): 3101–12. doi:10.1242/jeb.00511. PMID   12878677. S2CID   21867785.
• Hornemann T, Kempa S, Himmel M, Hayess K, Fürst DO, Wallimann T (Sep 2003). "Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein". Journal of Molecular Biology. 332 (4): 877–87. doi:10.1016/S0022-2836(03)00921-5. PMID   12972258.
• Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98. doi:10.1016/j.jmb.2004.10.040. PMID   15571722.
• Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79. doi:10.1016/j.jmb.2005.03.055. PMID   15890201.