ReviewTNNI1, TNNI2 and TNNI3: Evolution, regulation, and protein structure-function relationships

•Higher vertebrate genomes contain three troponin I genes, TNNI1, TNNI2 and TNNI3.•The muscle fiber type-specific troponin I isoforms are evolutionarily diverged.•Each of the isoform genes is conserved across species.•The N-terminal extension of cardiac troponin I is an adult heart-specific regulator.•Mutations of troponin I cause myopathies.

Troponin I (TnI) is the inhibitory subunit of the troponin complex in the sarcomeric thin filament of striated muscle and plays a central role in the calcium regulation of contraction and relaxation. Vertebrate TnI has evolved into three isoforms encoded by three homologous genes: TNNI1 for slow skeletal muscle TnI, TNNI2 for fast skeletal muscle TnI and TNNI3 for cardiac TnI, which are expressed under muscle type-specific and developmental regulations. To summarize the current knowledge on the TnI isoform genes and products, this review focuses on the evolution, gene regulation, posttranslational modifications, and structure-function relationship of TnI isoform proteins. Their physiological and medical significances are also discussed.

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