TNNI2

Three homologous genes have evolved in vertebrates, encoding three muscle type-specific isoforms of TnI. Sequence analysis, immunological distance, and examination of evolutionarily suppressed conformational states showed that the TnI genes have evolved in close linkage with the genes encoding troponin T (TnT), another subunit of the troponin complex. The phylogenetic tree in Fig. 2 summarizes the evolutionary lineage of fsTnI isoforms in vertebrate species. Phylogenetic analysis of vertebrate TnI isoforms demonstrated that each of the muscle type-specific isoforms is more conserved across species than the three isoforms in one given species, indicating early diverged functions of the muscle fiber type-specific isoforms as well as the conservation of functions for each muscle fiber type. == Tissue distribution ==

Fast skeletal muscle TnI was first cloned from a skeletal muscle cDNA library. It is generally observed that fsTnI is exclusively expressed in fast twitch skeletal muscle fibers. More recent studies reported that subunits of fast skeletal muscle troponin (fsTnI, fsTnT, fsTnC) were expressed at significant levels in smooth muscle cells of mouse blood vessels, bladder and bronchi. Expression of fsTnI was also found in non-muscle cells, such as human corneal epithelial cells and cartilage. The function of fsTnI expressed in smooth muscle and non-muscle cells is unclear. == Protein structure and function ==

Crystallographic structure of fsTnI in troponin complex from chicken fast skeletal muscle showed an overall structure similar to that of cardiac troponin. The inhibitory region of fsTnI was resolved in skeletal troponin whereas it was invisible in the cardiac troponin crystal structure. Based on the crystal structure, a schematic illustration (Fig. 3) was proposed to show the conformational changes in troponin during muscle activation and relaxation. Posttranslational modifications Phosphorylation: Ser118 of fsTnI, equivalent to Ser150 in cTnI, was reported as a phosphorylation substrate of AMPK. As AMPK is a key regulator of cellular energetics, phosphorylation of this site may provide an adaptive mechanism during energy deprivation in both skeletal and cardiac muscles. S-glutathionylation: fsTnI was found to be S-glutathionylated at Cys133 in rodent fast-twitch skeletal muscle and in human type II muscle fibers after exercise, which increased Ca2+ sensitivity of the contractile apparatus. == Clinical significance ==

A missense mutation R174Q, a nonsense mutation R156X, and three single residue deletions DE167, DK175 and DK176, all in the C-terminal actin-tropomyosin interacting domain, have been found in patients with distal arthrogryposis. Skeletal muscle TnI has been proposed as a sensitive and fast fiber-specific serum marker of skeletal muscle injury. fsTnI concentration in increased peripheral blood when fast twitch fibers were damaged. ==Notes==