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Titin, or Connectin, is the largest protein that has so far been discovered, undertaking the role of a structural and mechanical molecule, and it is commonly found in the myofibrils of skeletal muscle fibres. Within each sarcomere it acts as a stable, long, elastic filament that run from the Z disc to the M line region [1]. Its main function is to help stop muscles from over-stretching, or over-relaxing, by acting as a flexible and dynamic shock absorber [2]. They can contract, tighten or even shrink to redirect the energy output whenever muscles stretch.

The titin protein is encoded by a single gene, and in humans is known to have 363 exons that code for around 38,000 amino acids [3]. Skeletal muscle titin is 3,700 kDa and measures 2 µm in length in vivo [4].

In the myofibril, Titin helps place and align the thick myosin filaments between the Z discs within the middle of the sarcomere. It contains long chains of specific domains that resemble immunoglobulins – it is these domains that give the protein its characteristic spring-like elasticity. They can fold and unfold to maintain the structural arrangement of the thick filaments over the M line when the protein is undergoing stress or compression [5], thus acting as an entropic spring [6].

In recent experiments, it has been implied that titin shows traits of its function as a molecular ruler – where the sarcomere is longer, for example in the vertebrate C. elegans, the titin filaments are also longer, showing a relationship between the length of titin and the length of the sarcomeres [7].

Mutations in the titin gene have been associated with tibial muscular dystrophy (TMD), an autosomal dominant distal myopathy [8], with a late-onset of 35-45 years of age, or later [9]. The official symbol of Titin is TTN [10].


  1. Nunes J.M., Hensen U, Ge L, Lipinsky M, Helenius J, Grubmüller H, Muller D.J. (2010) Angewandte Chemie International Edition, Volume 49 Issue 20, pp.3528-3531 [Peer Reviewed Journal]. [ONLINE] Available at http://onlinelibrary.wiley.com.libproxy.ncl.ac.uk/doi/10.1002/anie.200906388/full [Accessed 29 November 2012].
  2. Benichou I, Givli S (2011) Applied Physics Letters 98, 091904: The Hidden Ingenuity in Titin Structure [Peer Reviewed Journal] The American Institue of Physics. [ONLINE] Available at http://apl.aip.org.libproxy.ncl.ac.uk/resource/1/applab/v98/i9/p091904_s1 [Accessed 29 November 2012].
  3. Granzier H.L., Labeit S (2004) Circulation Research 94: page 284-295: The Giant Protein Titin, American Heart Association. [ONLINE] Available at http://circres.ahajournals.org/content/94/3/284.full [Accessed 29 November 2012].
  4. The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system.Bang ML et al. http://www.ncbi.nlm.nih.gov/pubmed/11717165
  5. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular Biology of The Cell, page 1028, 5th edition, New York: Garland Science.
  6. Erickson, H.P. (1997) Science, Volume 276 No 5315, page 1090-1092 Stretching Single Protein Molecules: Titin is a Weird Spring [Peer Reviewed Journal]. [ONLINE] Available at http://www.sciencemag.org.libproxy.ncl.ac.uk/content/276/5315/1090 [Accessed 29 November 2012].
  7. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular Biology of The Cell, page 1028, 5th edition, New York: Garland Science.
  8. TIBIAL MUSCULAR DYSTROPHY, TARDIVE. http://omim.org/entry/600334
  9. Muscular dystrophy with separate clinical phenotypes in a large family. Udd B et al. http://www.ncbi.nlm.nih.gov/pubmed/1745277
  10. https://www.ncbi.nlm.nih.gov/gene/7273
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