MYOM1

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MYOM1
2y23.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MYOM1, SKELEMIN, myomesin 1
External IDs MGI: 1341430 HomoloGene: 31196 GeneCards: MYOM1
RNA expression pattern
PBB GE MYOM1 205610 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003803
NM_019856

NM_001083934
NM_010867

RefSeq (protein)

NP_003794
NP_062830

NP_001077403.1
NP_034997.2
NP_001077403
NP_034997

Location (UCSC) Chr 18: 3.07 – 3.22 Mb Chr 17: 71.02 – 71.13 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Myomesin-1 is a protein that in humans is encoded by the MYOM1 gene.[3][4] 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[edit]

Alternatively spliced variants of MYOM1, including EH-myomesin,[5] Skelemin[6] and Myomesin-1[6][7][8] have been identified; with Skelemin having an additional 96 amino acids rich in serine and proline residues.[6] 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 is has intermediate filament core-like motifs, one near each terminus.[9] 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.[10] Myomesin-1 can dimerize in an anti-parallel fashion via its C-terminal region.[11]

Function[edit]

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.[9] Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression.[12] Myomesin-1 functions to mediate stretch-induced signaling,[13] and the EH-myomesin splice variant, expressed in embryonic hearts and in dilated cardiomyopathy, can modulate its elasticity.[14]

Clinical Significance[edit]

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.[15]

MYOM1 has also been shown to be abnormally spliced in patients with myotonic dystrophy type I; specifically, exon 17a.[16]

Interactions[edit]

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

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. 
  4. ^ "Entrez Gene: MYOM1 myomesin 1 (skelemin) 185kDa". 
  5. ^ 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. 
  6. ^ a b c 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. 
  7. ^ "Protein sequence of human MYOM1 (Uniprot ID: P52179)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 24 June 2015. 
  8. ^ "Protein sequence of human MYOM1 (Uniprot ID: P52179-2)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 24 June 2015. 
  9. ^ a b 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. PMID 8408035. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. doi:10.1016/j.tcb.2005.07.001. PMID 16061384. 
  14. ^ 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. 
  15. ^ 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. PMID 21069531. 
  16. ^ 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. 
  17. ^ a b 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. 
  18. ^ a b 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. 
  19. ^ 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. PMID 9029142. 
  20. ^ 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 25310Freely accessible. PMID 9529381. 
  21. ^ 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 25262Freely accessible. PMID 10233145. 
  22. ^ 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. PMID 9029142. 
  23. ^ 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". Acta Biochimica et Biophysica Sinica. 36 (6): 412–8. doi:10.1093/abbs/36.6.412. PMID 15188056. 

Further reading[edit]

  • 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 2113097Freely accessible. 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. 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 / FEBS. 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. 
  • 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.