Mybpc3

Summary

Gene Symbol: Mybpc3
Description: myosin binding protein C, cardiac
Alias: myosin-binding protein C, cardiac-type, C-protein, cardiac muscle isoform, cardiac MyBP-C
Species: rat
Products:     Mybpc3

Top Publications

  1. Wang P, Zou Y, Fu C, Zhou X, Hui R. MYBPC3 polymorphism is a modifier for expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2005;329:796-9 pubmed
    ..To test if MYBPC3 polymorphism could modify the expression of cardiac hypertrophy, 226 patients with hypertrophic cardiomyopathy and ..
  2. Garcia Castro M, Reguero J, Alvarez V, Batalla A, Soto M, Albaladejo V, et al. Hypertrophic cardiomyopathy linked to homozygosity for a new mutation in the myosin-binding protein C gene (A627V) suggests a dosage effect. Int J Cardiol. 2005;102:501-7 pubmed
    Mutations in the cardiac myosin-binding protein C gene (MYBPC3) are responsible for up to 50% of familial cases with hypertrophic cardiomyopathy (HC)...
  3. Peddy S, Vricella L, Crosson J, Oswald G, Cohn R, Cameron D, et al. Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene. Pediatrics. 2006;117:1830-3 pubmed
    ..She successfully received an orthotopic heart transplant 172 days after VAD implantation. ..
  4. Sadayappan S, Osinska H, Klevitsky R, Lorenz J, Sargent M, Molkentin J, et al. Cardiac myosin binding protein C phosphorylation is cardioprotective. Proc Natl Acad Sci U S A. 2006;103:16918-23 pubmed
    ..These data demonstrate that cMyBP-C phosphorylation functions in maintaining thick filament spacing and structure and can help protect the myocardium from ischemic injury. ..
  5. Kuster D, Govindan S, Springer T, Martin J, Finley N, Sadayappan S. A hypertrophic cardiomyopathy-associated MYBPC3 mutation common in populations of South Asian descent causes contractile dysfunction. J Biol Chem. 2015;290:5855-67 pubmed publisher
    Hypertrophic cardiomyopathy (HCM) results from mutations in genes encoding sarcomeric proteins, most often MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C)...
  6. Kampourakis T, Yan Z, Gautel M, Sun Y, Irving M. Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells. Proc Natl Acad Sci U S A. 2014;111:18763-8 pubmed publisher
    Myosin binding protein-C (MyBP-C) is a key regulatory protein in heart muscle, and mutations in the MYBPC3 gene are frequently associated with cardiomyopathy...
  7. Mohamed A, Dignam J, Schlender K. Cardiac myosin-binding protein C (MyBP-C): identification of protein kinase A and protein kinase C phosphorylation sites. Arch Biochem Biophys. 1998;358:313-9 pubmed
    ..Only chicken cardiac MyBP-C had a phosphorylatable residue at the position corresponding to S1169. All of the cardiac MyBP-C phosphorylation sites are absent in known sequences of skeletal muscle MyBP-C isoforms. ..
  8. Cazorla O, Szilagyi S, Vignier N, Salazar G, Kramer E, Vassort G, et al. Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice. Cardiovasc Res. 2006;69:370-80 pubmed
  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. ..

More Information

Publications35

  1. Bhuiyan M, Gulick J, Osinska H, Gupta M, Robbins J. Determination of the critical residues responsible for cardiac myosin binding protein C's interactions. J Mol Cell Cardiol. 2012;53:838-47 pubmed publisher
  2. Govindan S, McElligott A, Muthusamy S, Nair N, Barefield D, Martin J, et al. Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction. J Mol Cell Cardiol. 2012;52:154-64 pubmed publisher
    ..The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease...
  3. Harris S, Rostkova E, Gautel M, Moss R. Binding of myosin binding protein-C to myosin subfragment S2 affects contractility independent of a tether mechanism. Circ Res. 2004;95:930-6 pubmed
  4. Toepfer C, Sikkel M, Caorsi V, Vydyanath A, Torre I, Copeland O, et al. A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation. Am J Physiol Heart Circ Physiol. 2016;311:H465-75 pubmed publisher
    ..These sensitivities to CMI are in accordance with phosphorylation-dependent regulatory roles for RLC and MyBP-C in crossbridge function and with compensatory adaptation in force and power that we observed in post-CMI trabeculae. ..
  5. Wang L, Lai G, Chu G, Liang X, Zhao Y. cMyBP-C was decreased via KLHL3-mediated proteasomal degradation in congenital heart diseases. Exp Cell Res. 2017;355:18-25 pubmed publisher
    ..These results demonstrate that Hcy decreases the expression of cMyBP-C through a KLHL3-mediated ubiquitin-proteasome pathway, and thereby influences heart development. ..
  6. Mearini G, Gedicke C, Schlossarek S, Witt C, Kramer E, Cao P, et al. Atrogin-1 and MuRF1 regulate cardiac MyBP-C levels via different mechanisms. Cardiovasc Res. 2010;85:357-66 pubmed publisher
    ..These data suggest that atrogin-1 specifically targets truncated M7t-cMyBP-C, but not WT-cMyBP-C, for proteasomal degradation and that MuRF1 indirectly reduces cMyBP-C levels by regulating the transcription of MHC. ..
  7. Brown L, Singh L, Sale K, Yu B, Trent R, Fajer P, et al. Functional and spectroscopic studies of a familial hypertrophic cardiomyopathy mutation in Motif X of cardiac myosin binding protein-C. Eur Biophys J. 2002;31:400-8 pubmed
    ..Taken together, these data suggest that the Motif X mutation may interfere with other, as yet unidentified, functional interactions. ..
  8. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371-423 pubmed
    ..Both myosin and troponin isoforms contribute to the differences in the resistance to fatigue of muscle fibers...
  9. Palmer B, Georgakopoulos D, Janssen P, Wang Y, Alpert N, Belardi D, et al. Role of cardiac myosin binding protein C in sustaining left ventricular systolic stiffening. Circ Res. 2004;94:1249-55 pubmed
    ..Abnormal sarcomere shortening velocity and abbreviated muscle stiffening may underlie development of cardiac dysfunction associated with deficient incorporation of cMyBP-C. ..
  10. Sadayappan S, Gulick J, Osinska H, Martin L, Hahn H, Dorn G, et al. Cardiac myosin-binding protein-C phosphorylation and cardiac function. Circ Res. 2005;97:1156-63 pubmed
    ..In contrast, when the MyBP-C(t/t) mice were bred to a TG line expressing normal MyBP-C (MyBP-CWT), the MyBP-C(t/t) phenotype was rescued. These data suggest that cMyBP-C phosphorylation is essential for normal cardiac function. ..
  11. Jääskeläinen P, Kuusisto J, Miettinen R, Kärkkäinen P, Kärkkäinen S, Heikkinen S, et al. Mutations in the cardiac myosin-binding protein C gene are the predominant cause of familial hypertrophic cardiomyopathy in eastern Finland. J Mol Med (Berl). 2002;80:412-22 pubmed
    ..Kuopio University Hospital region in eastern Finland for variants in the cardiac myosin-binding protein C gene ( MYBPC3)...
  12. Yang Q, Sanbe A, Osinska H, Hewett T, Klevitsky R, Robbins J. In vivo modeling of myosin binding protein C familial hypertrophic cardiomyopathy. Circ Res. 1999;85:841-7 pubmed
    ..Fiber mechanics showed decreased unloading shortening velocity, maximum shortening velocity, and relative maximal power output. ..
  13. Govindan S, Sarkey J, Ji X, Sundaresan N, Gupta M, de Tombe P, et al. Pathogenic properties of the N-terminal region of cardiac myosin binding protein-C in vitro. J Muscle Res Cell Motil. 2012;33:17-30 pubmed publisher
    ..By elucidating the deleterious effects of endogenously expressed cMyBP-C N-terminal fragments on sarcomere function, these data contribute to the understanding of contractile dysfunction following myocardial injury. ..
  14. Morita H, Larson M, Barr S, Vasan R, O Donnell C, Hirschhorn J, et al. Single-gene mutations and increased left ventricular wall thickness in the community: the Framingham Heart Study. Circulation. 2006;113:2697-705 pubmed
    ..We detected 8 mutations in 9 individuals (2 women); 7 mutations in 5 sarcomere protein genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL3), and 1 GLA mutation...
  15. Niimura H, Patton K, McKenna W, Soults J, Maron B, Seidman J, et al. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation. 2002;105:446-51 pubmed
    ..Rather, mutations in cardiac myosin binding protein-C, troponin I, and alpha-cardiac myosin heavy chain caused elderly-onset hypertrophic cardiomyopathy. ..
  16. Ababou A, Gautel M, Pfuhl M. Dissecting the N-terminal myosin binding site of human cardiac myosin-binding protein C. Structure and myosin binding of domain C2. J Biol Chem. 2007;282:9204-15 pubmed
    ..We expect that this model will stimulate future research to further refine the details of this interaction and their importance for cardiomyopathy. ..
  17. Weisberg A, Winegrad S. Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle. Proc Natl Acad Sci U S A. 1996;93:8999-9003 pubmed
    ..These changes could alter rate constants for attachment to and detachment from the thin filament and thereby modify force production in activated cardiac muscle. ..
  18. Watkins H, Conner D, Thierfelder L, Jarcho J, MacRae C, McKenna W, et al. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet. 1995;11:434-7 pubmed
    ..These findings define cardiac MyBP-C mutations as the cause of FHC on chromosome 11p and reaffirm that FHC is a disease of the sarcomere. ..
  19. Van Driest S, Vasile V, Ommen S, Will M, Tajik A, Gersh B, et al. Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004;44:1903-10 pubmed
    We sought to determine the frequency and phenotype of mutations in myosin binding protein C (MYBPC3) in a large outpatient cohort of patients with hypertrophic cardiomyopathy (HCM) seen at our tertiary referral center...
  20. Carrier L, Bonne G, Bährend E, Yu B, Richard P, Niel F, et al. Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy. Circ Res. 1997;80:427-34 pubmed
    ..The gene encoding cardiac MyBP-C (MYBPC3) in humans is located on chromosome 11p11...
  21. Gruen M, Gautel M. Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C. J Mol Biol. 1999;286:933-49 pubmed
    ..We suggest that the regulatory function of MyBP-C is mediated by the interaction with S2, and that mutations in beta-myosin S2 may act by altering the interactions with MyBP-C. ..
  22. McConnell B, Jones K, Fatkin D, Arroyo L, Lee R, Aristizabal O, et al. Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice. J Clin Invest. 1999;104:1235-44 pubmed
    ..We also propose that mice bearing homozygous familial hypertrophic cardiomyopathy-causing mutations may provide useful tools for predicting the severity of disease that these mutations will cause in humans. ..
  23. Korte F, McDonald K, Harris S, Moss R. Loaded shortening, power output, and rate of force redevelopment are increased with knockout of cardiac myosin binding protein-C. Circ Res. 2003;93:752-8 pubmed
    ..8+/-0.9 s(-1) versus MyBP-C-/-=7.7+/-1.7 s(-1)). These results suggest that cMyBP-C is an important regulator of myocardial work capacity whereby MyBP-C acts to limit power output. ..
  24. Niimura H, Bachinski L, Sangwatanaroj S, Watkins H, Chudley A, McKenna W, et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med. 1998;338:1248-57 pubmed
    ..Clinical screening in adult life may be warranted for members of families characterized by hypertrophic cardiomyopathy. ..
  25. Flashman E, Korkie L, Watkins H, Redwood C, Moolman Smook J. Support for a trimeric collar of myosin binding protein C in cardiac and fast skeletal muscle, but not in slow skeletal muscle. FEBS Lett. 2008;582:434-8 pubmed publisher
    ..These data have implications for the role and quaternary structure of MyBPC in skeletal muscle. ..
  26. Colson B, Bekyarova T, Fitzsimons D, Irving T, Moss R. Radial displacement of myosin cross-bridges in mouse myocardium due to ablation of myosin binding protein-C. J Mol Biol. 2007;367:36-41 pubmed