TNNT2

Cardiac Troponin T (TnT), is a is_associated_with::protein which in humans is encoded by the TNNT2 is_associated_with::gene. Cardiac TnT is the is_associated_with::tropomyosin-binding subunit of the is_associated_with::troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

Structure
Cardiac TnT is a 35.9 kDa protein composed of 298 amino acids. Cardiac TnT is the largest of the three troponin subunits (cTnT, troponin I (TnI), troponin C (TnC)) on the actin thin filament of cardiac muscle. The structure of TnT is asymmetric; the globular C-terminal domain interacts with tropomyosin (Tm), TnI and TnC, and the N-terminal tether which strongly binds Tm. The N-terminal region of TnT is alternatively spliced, accounting for multiple isoforms observed in cardiac muscle.

Function
As part of the Troponin complex, the function of cTnT is to regulate muscle contraction. The N-terminal region of TnT that strongly binds actin most likely moves with Tm and actin during strong myosin crossbridge binding and force generation. This region is likely involved in the transduction of cooperativity down the thin filament. The C-terminal region of TnT constitutes part of the globular troponin complex domain, and participates in employing the calcium sensitivity of strong myosin crossbridge binding to the thin filament.

Clinical significance
Mutations in this gene have been associated with familial is_associated_with::hypertrophic cardiomyopathy as well as with restrictive and is_associated_with::dilated cardiomyopathy. Transcripts for this gene undergo is_associated_with::alternative splicing that results in many tissue-specific isoforms, however, the full-length nature of some of these variants has not yet been determined. Mutations of this gene may be associated with mild or absent is_associated_with::hypertrophy and predominant restrictive disease, with a high risk of is_associated_with::sudden cardiac death. Advancement to dilated cardiomyopathy may be more rapid in patients with TNNT2 mutations than in those with is_associated_with::myosin heavy chain mutations.