Tnnc1

Summary

Gene Symbol: Tnnc1
Description: troponin C1, slow skeletal and cardiac type
Alias: Tncc, troponin C, slow skeletal and cardiac muscles, troponin C type 1 (slow), troponin C, cardiac/slow skeletal
Species: rat
Products:     Tnnc1

Top Publications

  1. Davis J, Metzger J. Combinatorial effects of double cardiomyopathy mutant alleles in rodent myocytes: a predictive cellular model of myofilament dysregulation in disease. PLoS ONE. 2010;5:e9140 pubmed publisher
  2. Redwood C, Lohmann K, Bing W, Esposito G, Elliott K, Abdulrazzak H, et al. Investigation of a truncated cardiac troponin T that causes familial hypertrophic cardiomyopathy: Ca(2+) regulatory properties of reconstituted thin filaments depend on the ratio of mutant to wild-type protein. Circ Res. 2000;86:1146-52 pubmed
    ..Further, these findings underscore the importance of studying mixed mutant:wild-type preparations to faithfully model this autosomal-dominant disease. ..
  3. al Hillawi E, Minchin S, Trayer I. Overexpression of human cardiac troponin-I and troponin-C in Escherichia coli and their purification and characterisation. Two point mutations allow high-level expression of troponin-I. Eur J Biochem. 1994;225:1195-201 pubmed
    ..Biological activity was also demonstrated in vivo in that the recombinant proteins were able to restore the calcium-dependent force generation to calcium-insensitive skinned muscle fibres. ..
  4. Pineda Sanabria S, Robertson I, Sun Y, Irving M, Sykes B. Probing the mechanism of cardiovascular drugs using a covalent levosimendan analog. J Mol Cell Cardiol. 2016;92:174-84 pubmed publisher
    ..These findings provide new insights into the in vivo mechanism of Ca(2+) sensitization and demonstrate that directly targeting cTnC has significant potential in cardiovascular therapy. ..
  5. Fuchs F, Grabarek Z. The Ca2+/Mg2+ sites of troponin C modulate crossbridge-mediated thin filament activation in cardiac myofibrils. Biochem Biophys Res Commun. 2011;408:697-700 pubmed publisher
  6. Asumda F, Chase P. Nuclear cardiac troponin and tropomyosin are expressed early in cardiac differentiation of rat mesenchymal stem cells. Differentiation. 2012;83:106-15 pubmed publisher
  7. O Connell B, Nguyen L, Stephenson G. A single-fibre study of the relationship between MHC and TnC isoform composition in rat skeletal muscle. Biochem J. 2004;378:269-74 pubmed
    ..Our results suggest a close relationship between MHC and TnC isoform composition in non-transforming skeletal muscles of adult rat. ..
  8. Homsher E, Lee D, Morris C, Pavlov D, Tobacman L. Regulation of force and unloaded sliding speed in single thin filaments: effects of regulatory proteins and calcium. J Physiol. 2000;524 Pt 1:233-43 pubmed
  9. Dong W, Rosenfeld S, Wang C, Gordon A, Cheung H. Kinetic studies of calcium binding to the regulatory site of troponin C from cardiac muscle. J Biol Chem. 1996;271:688-94 pubmed
    ..These transitions provide the first information on the rates of Ca(2+)-induced conformational changes involving helix movements in the regulatory domain. ..

More Information

Publications30

  1. 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 pubmed
  2. Julien O, Sun Y, Wang X, Lindhout D, Thiessen A, Irving M, et al. Tryptophan mutants of cardiac troponin C: 3D structure, troponin I affinity, and in situ activity. Biochemistry. 2008;47:597-606 pubmed
  3. Davis J, Norman C, Kobayashi T, Solaro R, Swartz D, Tikunova S. Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C. Biophys J. 2007;92:3195-206 pubmed
    ..These results imply that both cross-bridge kinetics and Ca(2+) dissociation from troponin C work together to modulate the rate of cardiac muscle relaxation. ..
  4. Gomes A, Guzman G, Zhao J, Potter J. Cardiac troponin T isoforms affect the Ca2+ sensitivity and inhibition of force development. Insights into the role of troponin T isoforms in the heart. J Biol Chem. 2002;277:35341-9 pubmed
    ..These results suggest that the different N-terminal TnT isoforms would produce different functional properties in the heart that would directly affect myocardial contraction. ..
  5. Cordina N, Liew C, Gell D, Fajer P, Mackay J, Brown L. Effects of calcium binding and the hypertrophic cardiomyopathy A8V mutation on the dynamic equilibrium between closed and open conformations of the regulatory N-domain of isolated cardiac troponin C. Biochemistry. 2013;52:1950-62 pubmed publisher
    ..The PRE data show that the Ca(2+) switch mechanism is perturbed by the A8V mutation, resulting in a more open N-domain conformation in both the apo and holo states. ..
  6. Schaub M, Heizmann C. Calcium, troponin, calmodulin, S100 proteins: from myocardial basics to new therapeutic strategies. Biochem Biophys Res Commun. 2008;369:247-64 pubmed
    ..Some of these sensor proteins are critically involved in certain diseases and are now used in clinical diagnostics. ..
  7. Cordina N, Liew C, Gell D, Fajer P, Mackay J, Brown L. Interdomain orientation of cardiac troponin C characterized by paramagnetic relaxation enhancement NMR reveals a compact state. Protein Sci. 2012;21:1376-87 pubmed publisher
    ..Ensemble fitting of our interdomain PRE measurements reveals that isolated cTnC has considerable interdomain flexibility and preferentially adopts a bent conformation in solution, with a defined range of relative domain orientations. ..
  8. Potluri P, Chamoun J, Cooke J, Badr M, Guse J, Rayes R, et al. The concerted movement of the switch region of Troponin I in cardiac muscle thin filaments as tracked by conventional and pulsed (DEER) EPR. J Struct Biol. 2017;200:376-387 pubmed publisher
  9. Wijnker P, Li Y, Zhang P, Foster D, dos Remedios C, Van Eyk J, et al. A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis. J Mol Cell Cardiol. 2015;82:93-103 pubmed publisher
    ..In addition, cTnI-Ser199 pseudo-phosphorylation or mutation regulates calpain I mediated proteolysis of cTnI. ..
  10. Rossmanith G, Hoh J, Turnbull L, Ludowyke R. Mechanism of action of endothelin in rat cardiac muscle: cross-bridge kinetics and myosin light chain phosphorylation. J Physiol. 1997;505 ( Pt 1):217-27 pubmed
  11. O Connell B, Stephenson D, Blazev R, Stephenson G. Troponin C isoform composition determines differences in Sr(2+)-activation characteristics between rat diaphragm fibers. Am J Physiol Cell Physiol. 2004;287:C79-87 pubmed
  12. Li K, Ghashghaee N, Solaro R, Dong W. Sarcomere length dependent effects on the interaction between cTnC and cTnI in skinned papillary muscle strips. Arch Biochem Biophys. 2016;601:69-79 pubmed publisher
    ..These novel observations suggest the importance of the C-domain of cTnI and the dynamic and complex interplay between various components of myofilament in the LDA mechanism. ..
  13. Mogensen J, Murphy R, Shaw T, Bahl A, Redwood C, Watkins H, et al. Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2004;44:2033-40 pubmed
    We performed genetic investigations of cardiac troponin T (TNNT2) and troponin C (TNNC1) in 235 consecutive patients with idiopathic dilated cardiomyopathy (DCM) to evaluate prevalence of mutations and associated disease expression in ..
  14. Takahashi Yanaga F, Morimoto S, Harada K, Minakami R, Shiraishi F, Ohta M, et al. Functional consequences of the mutations in human cardiac troponin I gene found in familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001;33:2095-107 pubmed
  15. Heller W, Abusamhadneh E, Finley N, Rosevear P, Trewhella J. The solution structure of a cardiac troponin C-troponin I-troponin T complex shows a somewhat compact troponin C interacting with an extended troponin I-troponin T component. Biochemistry. 2002;41:15654-63 pubmed
    ..A., and Trewhella, J. (1994) Biochemistry 33, 12800-12806]. ..
  16. Fuchs F, Grabarek Z. The green tea polyphenol (-)-epigallocatechin-3-gallate inhibits magnesium binding to the C-domain of cardiac troponin C. J Muscle Res Cell Motil. 2013;34:107-13 pubmed publisher
  17. Rieck D, Li K, Ouyang Y, Solaro R, Dong W. Structural basis for the in situ Ca(2+) sensitization of cardiac troponin C by positive feedback from force-generating myosin cross-bridges. Arch Biochem Biophys. 2013;537:198-209 pubmed publisher
  18. Huynh Q, Butters C, Leiden J, Tobacman L. Effects of cardiac thin filament Ca2+: statistical mechanical analysis of a troponin C site II mutant. Biophys J. 1996;70:1447-55 pubmed
    ..However, these indirect TnC-TnC interactions are weak, indicating that the cooperativity of muscle activation by Ca2+ requires other sources of cooperativity. ..
  19. Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg H, et al. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994;77:701-12 pubmed
    ..Further, because the splice site mutation is predicted to function as a null allele, we suggest that abnormal stoichiometry of sarcomeric proteins can cause cardiac hypertrophy. ..
  20. Berlin J, Bassani J, Bers D. Intrinsic cytosolic calcium buffering properties of single rat cardiac myocytes. Biophys J. 1994;67:1775-87 pubmed
    ..The present data indicate that a rapid rise of [Ca2+]i from 0.1 to 1 microM during a contraction requires approximately 50 microM Ca2+ to be added to the cytosol. ..
  21. Hoffmann B, Schmidt Traub H, Perrot A, Osterziel K, Gessner R. First mutation in cardiac troponin C, L29Q, in a patient with hypertrophic cardiomyopathy. Hum Mutat. 2001;17:524 pubmed