MYBPC3

MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. MYBPC3, the cardiac isoform, is expressed exclussively in heart muscle. Regulatory phosphorylation of the cardiac isoform in vivo by cAMP-dependent protein kinase (PKA) upon adrenergic stimulation may be linked to modulation of cardiac contraction. Mutations in MYBPC3 are one cause of familial hypertrophic cardiomyopathy.

Full Name

MYOSIN BINDING PROTEIN C, CARDIAC

Function

Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.

Biological Process

Cardiac muscle contraction Source: BHF-UCL
Cell adhesion Source: UniProtKB-KW
Heart morphogenesis Source: BHF-UCL
Positive regulation of ATP-dependent activity Source: BHF-UCL
Regulation of muscle filament sliding Source: BHF-UCL
Regulation of striated muscle contraction Source: BHF-UCL
Ventricular cardiac muscle tissue morphogenesis Source: HGNC-UCL

Cellular Location

Cytosol
Other locations
A band
C zone
cardiac myofibril
sarcomere
striated muscle myosin thick filament

Involvement in disease

Cardiomyopathy, familial hypertrophic 4 (CMH4):
A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Cardiomyopathy, dilated 1MM (CMD1MM):
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. MYBPC3 mutations may be involved in restrictive cardiomyopathy (RCM), a rare non-ischemic myocardial disease. RCM is characterized by restrictive ventricular-filling physiology in the presence of normal or reduced diastolic and/or systolic volumes (of 1 or both ventricles), biatrial enlargement, and normal ventricular wall thickness.
Left ventricular non-compaction 10 (LVNC10):
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC10 is an autosomal dominant condition.

PTM

Substrate for phosphorylation by PKA and PKC. Reversible phosphorylation appears to modulate contraction (By similarity).
Polyubiquitinated.