TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure-function relationships

Gene. 2016 May 10;582(1):1-13. doi: 10.1016/j.gene.2016.01.006. Epub 2016 Jan 13.


Troponin T (TnT) is a central player in the calcium regulation of actin thin filament function and is essential for the contraction of striated muscles. Three homologous genes have evolved in vertebrates to encode three muscle type-specific TnT isoforms: TNNT1 for slow skeletal muscle TnT, TNNT2 for cardiac muscle TnT, and TNNT3 for fast skeletal muscle TnT. Alternative splicing and posttranslational modifications confer additional structural and functional variations of TnT during development and muscle adaptation to various physiological and pathological conditions. This review focuses on the TnT isoform genes and their molecular evolution, alternative splicing, developmental regulation, structure-function relationships of TnT proteins, posttranslational modifications, and myopathic mutations and abnormal splicing. The goal is to provide a concise summary of the current knowledge and some perspectives for future research and translational applications.

Keywords: Alternative splicing; Cardiac function; Evolution; Isoform; Myopathy; Restrictive proteolysis; Striated muscle; Troponin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Alternative Splicing / genetics
  • Calcium / metabolism
  • Evolution, Molecular*
  • Gene Expression Regulation, Developmental
  • Humans
  • Muscle Contraction / genetics
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • Muscle, Striated / growth & development
  • Muscle, Striated / metabolism
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Structure-Activity Relationship
  • Troponin T / biosynthesis
  • Troponin T / chemistry
  • Troponin T / genetics*
  • Troponin T / metabolism


  • Protein Isoforms
  • TNNT2 protein, human
  • TNNT3 protein, human
  • Troponin T
  • Calcium