Troponin C, fast skeletal muscle (sTnC) is a protein that in humans is encoded by the TNNC2 gene. It is the troponin C paralog expressed in fast-twitching fibers of skeletal muscle.[5][6]
Troponin (Tn), is a key protein complex in the regulation of striated muscle contraction, composed of three subunits. The TnI subunit inhibits actomyosin ATPase, the TnT subunit binds tropomyosin and TnC, while the TnC subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin thin filaments. The protein encoded by the TNNC2 gene is the TnC subunit.[6]
There are already multiple troponin activators that bind to fast skeletal troponin C (TNNC2), of which tirasemtiv[7] has been tested in multiple clinical trials.[8][9][10]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000101470 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017300 – Ensembl, May 2017
- ^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Gahlmann R, Kedes L (Aug 1990). “Cloning, structural analysis, and expression of the human fast twitch skeletal muscle troponin C gene”. J Biol Chem. 265 (21): 12520–8. doi:10.1016/S0021-9258(19)38376-0. PMID 2373703.
- ^ a b “Entrez Gene: TNNC2 troponin C type 2 (fast)”.
- ^ Russell AJ, Hartman JJ, Hinken AC, Muci AR, Kawas R, Driscoll L, Godinez G, Lee KH, Marquez D, Browne WF, Chen MM, Clarke D, Collibee SE, Garard M, Hansen R, Jia Z, Lu PP, Rodriguez H, Saikali KG, Schaletzky J, Vijayakumar V, Albertus DL, Claflin DR, Morgans DJ, Morgan BP, Malik FI (Mar 2012). “Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases”. Nature Medicine. 18 (3): 452–455. doi:10.1038/nm.2618. PMC 3296825. PMID 22344294.
- ^ Shefner JM, Wolff AA, Meng L (Dec 2013). “The relationship between tirasemtiv serum concentration and functional outcomes in patients with ALS”. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration. 14 (7–8): 582–5. doi:10.3109/21678421.2013.817587. PMID 23952600. S2CID 25563161.
- ^ Bauer TA, Wolff AA, Hirsch AT, Meng LL, Rogers K, Malik FI, Hiatt WR (May 2014). “Effect of tirasemtiv, a selective activator of the fast skeletal muscle troponin complex, in patients with peripheral artery disease”. Vascular Medicine. 19 (4): 297–306. doi:10.1177/1358863X14534516. PMID 24872402. S2CID 25185883.
- ^ Sanders DB, Rosenfeld J, Dimachkie MM, Meng L, Malik FI, Andrews J, Barohn R, Corse A, Deboo A, Felice K, Harati Y, Heiman-Patterson T, Howard JF, Jackson C, Juel V, Katz J, Lee J, Massey J, McVey A, Mozaffar T, Pasnoor M, Small G, So Y, Wang AK, Weinberg D, Wolff AA (Apr 2015). “A double-blinded, randomized, placebo-controlled trial to evaluate efficacy, safety, and tolerability of single doses of tirasemtiv in patients with acetylcholine receptor-binding antibody-positive myasthenia gravis”. Neurotherapeutics. 12 (2): 455–60. doi:10.1007/s13311-015-0345-y. PMC 4404445. PMID 25742919.
Further reading
- Romero-Herrera AE, Castillo O, Lehmann H (1977). “Human skeletal muscle proteins. The primary structure of troponin C.”. J. Mol. Evol. 8 (3): 251–70. doi:10.1007/bf01730999. PMID 978749. S2CID 12057790.
- Tomasselli AG, Hui JO, Adams L, et al. (1991). “Actin, troponin C, Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus”. J. Biol. Chem. 266 (22): 14548–53. doi:10.1016/S0021-9258(18)98721-1. PMID 1907279.
- Gahlmann R, Wade R, Gunning P, Kedes L (1988). “Differential expression of slow and fast skeletal muscle troponin C. Slow skeletal muscle troponin C is expressed in human fibroblasts”. J. Mol. Biol. 201 (2): 379–91. doi:10.1016/0022-2836(88)90145-3. PMID 3166492.
- Prentice H, Kloner RA, Prigozy T, et al. (1995). “Tissue restricted gene expression assayed by direct DNA injection into cardiac and skeletal muscle”. J. Mol. Cell. Cardiol. 26 (10): 1393–401. doi:10.1006/jmcc.1994.1157. PMID 7869399.
- Tiso N, Rampoldi L, Pallavicini A, et al. (1997). “Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast”. Biochem. Biophys. Res. Commun. 230 (2): 347–50. doi:10.1006/bbrc.1996.5958. hdl:11577/2466889. PMID 9016781.
- Townsend PJ, Yacoub MH, Barton PJ (1998). “Assignment of the human fast skeletal muscle troponin C gene (TNNC2) between D20S721 and GCT10F11 on chromosome 20 by somatic cell hybrid analysis”. Ann. Hum. Genet. 61 (Pt 5): 457–9. doi:10.1046/j.1469-1809.1997.6150457.x. PMID 9459007. S2CID 1450195.
- Vassylyev DG, Takeda S, Wakatsuki S, et al. (1998). “Crystal structure of troponin C in complex with troponin I fragment at 2.3-A resolution”. Proc. Natl. Acad. Sci. U.S.A. 95 (9): 4847–52. doi:10.1073/pnas.95.9.4847. PMC 20176. PMID 9560191.
- Deloukas P, Matthews LH, Ashurst J, et al. (2002). “The DNA sequence and comparative analysis of human chromosome 20”. Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi:10.1038/414865a. PMID 11780052.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). “Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS…9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)”. Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
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