Biology:MYOM1

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Short description: Protein-coding gene in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Myomesin-1 is a protein that in humans is encoded by the MYOM1 gene.[1][2] 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,[3] Skelemin[4] and Myomesin-1[4][5][6] have been identified; with Skelemin having an additional 96 amino acids rich in serine and proline residues.[4] 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.[7] 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.[8] Myomesin-1 can dimerize in an anti-parallel fashion via its C-terminal region.[9]

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.[7] Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression.[10] Myomesin-1 functions to mediate stretch-induced signaling,[11] and the EH-myomesin splice variant, expressed in embryonic hearts and in dilated cardiomyopathy, can modulate its elasticity.[12]

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.[13]

MYOM1 has also been shown to be abnormally spliced in patients with myotonic dystrophy type I; specifically, exon 17a.[14]

Interactions

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

References

  1. ↑ "Assignment of the human gene for the sarcomeric M-band protein myomesin (MYOM1) to 18p11.31-p11.32". Genomics 54 (1): 184–6. Nov 1998. doi:10.1006/geno.1998.5503. PMID 9806852. 
  2. ↑ "Entrez Gene: MYOM1 myomesin 1 (skelemin) 185kDa". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8736. 
  3. ↑ "A novel marker for vertebrate embryonic heart, the EH-myomesin isoform". The Journal of Biological Chemistry 275 (14): 10256–64. Apr 2000. doi:10.1074/jbc.275.14.10256. PMID 10744711. 
  4. ↑ 4.0 4.1 4.2 "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics 56 (1): 78–89. Feb 1999. doi:10.1006/geno.1998.5682. PMID 10036188. 
  5. ↑ "Protein sequence of human MYOM1 (Uniprot ID: P52179)". http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P52179. 
  6. ↑ "Protein sequence of human MYOM1 (Uniprot ID: P52179-2)". http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P52179-2. 
  7. ↑ 7.0 7.1 "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. Oct 1993. doi:10.1016/S0021-9258(20)80613-9. PMID 8408035. 
  8. ↑ "Tissue-specific isoforms of chicken myomesin are generated by alternative splicing". The Journal of Biological Chemistry 271 (32): 19042–52. Aug 1996. doi:10.1074/jbc.271.32.19042. PMID 8702575. 
  9. ↑ "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology 345 (2): 289–98. Jan 2005. doi:10.1016/j.jmb.2004.10.040. PMID 15571722. 
  10. ↑ "Nuclear localization of Myomesin-1: possible functions". Journal of Muscle Research and Cell Motility 29 (1): 1–8. 2008. doi:10.1007/s10974-008-9137-x. PMID 18521710. 
  11. ↑ "The M-band: an elastic web that crosslinks thick filaments in the center of the sarcomere". Trends in Cell Biology 15 (9): 477–85. Sep 2005. doi:10.1016/j.tcb.2005.07.001. PMID 16061384. 
  12. ↑ "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology 349 (2): 367–79. Jun 2005. doi:10.1016/j.jmb.2005.03.055. PMID 15890201. 
  13. ↑ "EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy". Basic Research in Cardiology 106 (2): 233–47. Mar 2011. doi:10.1007/s00395-010-0131-2. PMID 21069531. 
  14. ↑ "Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1". Genes to Cells 16 (9): 961–72. Sep 2011. doi:10.1111/j.1365-2443.2011.01542.x. PMID 21794030. 
  15. ↑ 15.0 15.1 "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. Dec 1998. doi:10.1074/jbc.273.52.35039. PMID 9857037. 
  16. ↑ 16.0 16.1 "Structural insight into the interaction between platelet integrin alphaIIbbeta3 and cytoskeletal protein skelemin". The Journal of Biological Chemistry 282 (44): 32349–56. Nov 2007. doi:10.1074/jbc.M704666200. PMID 17804417. 
  17. ↑ 17.0 17.1 "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. Jan 1997. doi:10.1093/emboj/16.2.211. PMID 9029142. 
  18. ↑ "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. Apr 1998. doi:10.1091/mbc.9.4.829. PMID 9529381. 
  19. ↑ "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. May 1999. doi:10.1091/mbc.10.5.1297. PMID 10233145. 
  20. ↑ "Characterization of MR-1, a novel myofibrillogenesis regulator in human muscle". Acta Biochimica et Biophysica Sinica 36 (6): 412–8. Jun 2004. doi:10.1093/abbs/36.6.412. PMID 15188056. http://pdfs.semanticscholar.org/3c46/643d9f9d7feea345ea96d51843e35ce830fe.pdf. 

Further reading




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