Synonyms
Cardiac troponin C : Tncc; Tnnc1; Troponin C, cardiac; Troponin C, cardiac/slow skeletal
Cardiac troponin I : cTnI, the inhibitory subunit of troponin (Tn); Tn1; TNNC1; Tnni3; Troponin I, cardiac
Cardiac troponin T : cTnT, the tropomyosin-binding subunit of troponin (Tn); Ctt; CTTG; RATCTTG; Tnnt2; TnT; Troponin T, cardiac; Troponin T2; Troponin T2, cardiac
Historical Background
The modern molecular understanding of muscle contraction took shape in the 1950s and 1960s. The sliding filament model was proposed in 1954, and it was known that muscle contraction was driven by myosin ATPase in the presence of actin. In the early 1960s, it was suspected, though not widely accepted, that muscle contraction is triggered by calcium. The idea was controversial, because while native preparations of actomyosin could be induced to relax by calcium-chelating agents, highly purified and reconstituted actomyosin did not display this behavior. In 1963, Ebashi demonstrated that the calcium...
This is a preview of subscription content, log in via an institution.
References
de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304:2503–12. doi:10.1001/jama.2010.1768.
Ebashi S. Third component participating in the superprecipitation of ‘Natural Actomyosin’. Nature. 1963;200:1010.
Ebashi S, Kodama A. A new protein factor promoting aggregation of tropomyosin. J Biochem. 1965;58:107–8.
Franklin AJ, Baxley T, Kobayashi T, Chalovich JM. The C-terminus of troponin T is essential for maintaining the inactive state of regulated actin. Biophys J. 2012;102:2536–44. doi:10.1016/j.bpj.2012.04.037.
Gaponenko V, Abusamhadneh E, Abbott MB, Finley N, Gasmi-Seabrook G, Solaro RJ, et al. Effects of troponin I phosphorylation on conformational exchange in the regulatory domain of cardiac troponin C. J Biol Chem. 1999;274:16681–4.
Gomes AV, Harada K, Potter JD. A mutation in the N-terminus of troponin I that is associated with hypertrophic cardiomyopathy affects the Ca(2+)-sensitivity, phosphorylation kinetics and proteolytic susceptibility of troponin. J Mol Cell Cardiol. 2005a;39:754–65. doi:10.1016/j.yjmcc.2005.05.013.
Gomes AV, Liang J, Potter JD. Mutations in human cardiac troponin I that are associated with restrictive cardiomyopathy affect basal ATPase activity and the calcium sensitivity of force development. J Biol Chem. 2005b;280:30909–15. doi:10.1074/jbc.M500287200.
Greaser ML, Gergely J. Reconstitution of troponin activity from three protein components. J Biol Chem. 1971;246:4226–33.
Hwang PM, Cai F, Pineda-Sanabria SE, Corson DC, Sykes BD. The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C. Proc Natl Acad Sci USA. 2014;111:14412–7. doi:10.1073/pnas.1410775111.
Ishii Y, Lehrer SS. Two-site attachment of troponin to pyrene-labeled tropomyosin. J Biol Chem. 1991;266:6894–903.
Li MX, Hwang PM. Structure and function of cardiac troponin C (TNNC1): implications for heart failure, cardiomyopathies, and troponin modulating drugs. Gene. 2015;571:153–66. doi:10.1016/j.gene.2015.07.074.
Li MX, Spyracopoulos L, Sykes BD. Binding of cardiac troponin-I147-163 induces a structural opening in human cardiac troponin-C. Biochemistry. 1999;38:8289–98. doi:10.1021/bi9901679.
Lu QW, Wu XY, Morimoto S. Inherited cardiomyopathies caused by troponin mutations. J Geriatr Cardiol. 2013;10:91–101. doi:10.3969/j.issn.1671-5411.2013.01.014.
Morimoto S, Lu QW, Harada K, Takahashi-Yanaga F, Minakami R, Ohta M, et al. Ca(2+)-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy. Proc Natl Acad Sci USA. 2002;99:913–8. doi:10.1073/pnas.022628899.
Murakami K, Stewart M, Nozawa K, Tomii K, Kudou N, Igarashi N, et al. Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T. Proc Natl Acad Sci USA. 2008;105:7200–5. doi:10.1073/pnas.0801950105.
Parvatiyar MS, Pinto JR, Dweck D, Potter JD. Cardiac troponin mutations and restrictive cardiomyopathy. J Biomed Biotechnol. 2010;2010:350706. doi:10.1155/2010/350706.
Pinto JR, Yang SW, Hitz MP, Parvatiyar MS, Jones MA, Liang J, et al. Fetal cardiac troponin isoforms rescue the increased Ca2+ sensitivity produced by a novel double deletion in cardiac troponin T linked to restrictive cardiomyopathy: a clinical, genetic, and functional approach. J Biol Chem. 2011;286:20901–12. doi:10.1074/jbc.M111.234336.
Sheng JJ, Jin JP. TNNI1, TNNI2 and TNNI3: evolution, regulation, and protein structure-function relationships. Gene. 2016;576:385–94. doi:10.1016/j.gene.2015.10.052.
Sia SK, Li MX, Spyracopoulos L, Gagne SM, Liu W, Putkey JA, et al. Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain. J Biol Chem. 1997;272:18216–21.
Solaro RJ, Henze M, Kobayashi T. Integration of troponin I phosphorylation with cardiac regulatory networks. Circ Res. 2013;112:355–66. doi:10.1161/CIRCRESAHA.112.268672.
Sommese RF, Nag S, Sutton S, Miller SM, Spudich JA, Ruppel KM. Effects of troponin T cardiomyopathy mutations on the calcium sensitivity of the regulated thin filament and the actomyosin cross-bridge kinetics of human beta-cardiac myosin. PloS one. 2013;8:e83403. doi:10.1371/journal.pone.0083403.
Sumandea MP, Pyle WG, Kobayashi T, de Tombe PP, Solaro RJ. Identification of a functionally critical protein kinase C phosphorylation residue of cardiac troponin T. J Biol Chem. 2003;278:35135–44. doi:10.1074/jbc.M306325200.
Takeda S, Yamashita A, Maeda K, Maeda Y. Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form. Nature. 2003;424:35–41. doi:10.1038/nature01780.
Tripet B, Van Eyk JE, Hodges RS. Mapping of a second actin-tropomyosin and a second troponin C binding site within the C terminus of troponin I, and their importance in the Ca2+-dependent regulation of muscle contraction. J Mol Biol. 1997;271:728–50. doi:10.1006/jmbi.1997.1200.
Wei B, Jin JP. TNNT1, TNNT2, and TNNT3: isoform genes, regulation, and structure-function relationships. Gene. 2016;582:1–13. doi:10.1016/j.gene.2016.01.006.
Wijnker PJ, Murphy AM, Stienen GJ, van der Velden J. Troponin I phosphorylation in human myocardium in health and disease. Neth Heart J. 2014;22:463–9. doi:10.1007/s12471-014-0590-4.
Zhang R, Zhao J, Mandveno A, Potter JD. Cardiac troponin I phosphorylation increases the rate of cardiac muscle relaxation. Circ Res. 1995;76:1028–35.
Zhang P, Kirk JA, Ji W, dos Remedios CG, Kass DA, Van Eyk JE, et al. Multiple reaction monitoring to identify site-specific troponin I phosphorylated residues in the failing human heart. Circulation. 2012;126:1828–37. doi:10.1161/CIRCULATIONAHA.112.096388.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media LLC
About this entry
Cite this entry
Mahmud, Z., Hwang, P.M. (2016). Cardiac Troponin Complex: Cardiac Troponin C (TNNC1), Cardiac Troponin I (TNNI3), and Cardiac Troponin T (TNNT2). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101901-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101901-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-6438-9
Online ISBN: 978-1-4614-6438-9
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences