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Protein TNNI2 PDB 1a2x.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases TNNI2, AMCD2B, DA2B, FSSV, fsTnI, troponin I2, fast skeletal type
External IDs MGI: 105070 HomoloGene: 37752 GeneCards: 7136
RNA expression pattern
PBB GE TNNI2 206393 at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 11: 1.84 – 1.84 Mb Chr 7: 142.44 – 142.44 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

Troponin I, fast skeletal muscle is a protein that in humans is encoded by the TNNI2 gene.[3][4]

The TNNI2 gene is located at 11p15.5 in the human chromosomal genome, encoding the fast twitch skeletal muscle troponin I (fsTnI). fsTnI is a 21.3 kDa protein consisting of 182 amino acids including the first methionine with an isoelectric point (pI) of 8.74. It is the inhibitory subunit of the troponin complex in fast twitch skeletal muscle fibers.[5]

Gene evolution[edit]

Figure 1: Evolutionary lineages of TnI-TnT gene pairs
Figure 2: Evolutionary lineage of vertebrate fsTnI isoforms deduced from alignment of amino acid sequences.

Three homologous genes have evolved in vertebrates, encoding three muscle type-specific isoforms of TnI.[6][7][8] 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.[8] The fast TnI-fast TnT gene pair represents the original TnI and TnT genes (Fig. 1). The three muscle fiber type-specific TnI-TnT gene pairs were likely originated from a TnI-like ancestor gene that presumably duplicated to form a closely linked fast TnI-like and fast TnT-like gene pair. A later duplication events resulted in emergences of a slow TnI-like and cardiac TnT-like gene pair that was further duplicated to give rise of the present-day slow TnI-cardiac TnT and cardiac TnI-slow TnT gene pairs. The seemingly scrambled ssTnI and cTnI gene pair is actually functionally related as they co-express and form troponin complex in the embryonic heart. The overlapping of enhancer elements of the TnT gene promoter with the upstream TnI gene structure may be a critical factor in the preservation of the close linkage of TnI and TnT gene pairs[9]

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.[10]

Tissue distribution[edit]

Fast skeletal muscle TnI was first cloned from a skeletal muscle cDNA library.[11] 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,[12] bladder and bronchi.[13] Expression of fsTnI was also found in non-muscle cells, such as human corneal epithelial cells[14] and cartilage.[15][16] The function of fsTnI expressed in smooth muscle and non-muscle cells is unclear.

Protein structure and function[edit]

Figure 3: Conformational changes occurring in the troponin complex during muscle contraction and relaxation (modified from the model proposed by Vinogradova et al.

Crystallographic structure of fsTnI in troponin complex from chicken fast skeletal muscle showed an overall structure[17] similar to that of cardiac troponin.[18] 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[edit]

Phosphorylation: Ser118 of fsTnI, equivalent to Ser150 in cTnI, was reported as a phosphorylation substrate of AMPK.[19] 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.[20]

Clinical significance[edit]

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.[21][22][23][24]

Skeletal muscle TnI has been proposed as a sensitive and fast fiber-specific serum marker of skeletal muscle injury.[25][26] fsTnI concentration in increased peripheral blood when fast twitch fibers were damaged.[26]


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  2. ^ "Mouse PubMed Reference:". 
  3. ^ Tiso N, Rampoldi L, Pallavicini A, Zimbello R, Pandolfo D, Valle G, Lanfranchi G, Danieli GA (Jan 1997). "Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast". Biochemical and Biophysical Research Communications. 230 (2): 347–50. doi:10.1006/bbrc.1996.5958. PMID 9016781. 
  4. ^ "Entrez Gene: TNNI2 troponin I type 2 (skeletal, fast)". 
  5. ^ Jin JP, Zhang Z, Bautista JA (2008-01-01). "Isoform diversity, regulation, and functional adaptation of troponin and calponin". Critical Reviews in Eukaryotic Gene Expression. 18 (2): 93–124. doi:10.1615/critreveukargeneexpr.v18.i2.10. PMID 18304026. 
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  7. ^ Perry SV (Jan 1999). "Troponin I: inhibitor or facilitator". Molecular and Cellular Biochemistry. 190 (1-2): 9–32. doi:10.1023/A:1006939307715. PMID 10098965. 
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  10. ^ Jin JP, Chen A, Huang QQ (Jul 1998). "Three alternatively spliced mouse slow skeletal muscle troponin T isoforms: conserved primary structure and regulated expression during postnatal development". Gene. 214 (1-2): 121–9. doi:10.1016/s0378-1119(98)00214-5. PMID 9651500. 
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  15. ^ Moses MA, Wiederschain D, Wu I, Fernandez CA, Ghazizadeh V, Lane WS, Flynn E, Sytkowski A, Tao T, Langer R (Mar 1999). "Troponin I is present in human cartilage and inhibits angiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 96 (6): 2645–50. doi:10.1073/pnas.96.6.2645. PMC 15822free to read. PMID 10077564. 
  16. ^ Li Q, Shen PY, Wu G, Chen XZ (Jan 2003). "Polycystin-2 interacts with troponin I, an angiogenesis inhibitor". Biochemistry. 42 (2): 450–7. doi:10.1021/bi0267792. PMID 12525172. 
  17. ^ PDB: 1YTZ​; Vinogradova MV, Stone DB, Malanina GG, Karatzaferi C, Cooke R, Mendelson RA, Fletterick RJ (Apr 2005). "Ca(2+)-regulated structural changes in troponin". Proceedings of the National Academy of Sciences of the United States of America. 102 (14): 5038–43. doi:10.1073/pnas.0408882102. PMC 555973free to read. PMID 15784741. 
  18. ^ Takeda S, Yamashita A, Maeda K, Maéda Y (Jul 2003). "Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form". Nature. 424 (6944): 35–41. doi:10.1038/nature01780. PMID 12840750. 
  19. ^ Sancho Solis R, Ge Y, Walker JW (May 2011). "A preferred AMPK phosphorylation site adjacent to the inhibitory loop of cardiac and skeletal troponin I". Protein Science. 20 (5): 894–907. doi:10.1002/pro.623. PMC 3125873free to read. PMID 21416543. 
  20. ^ Mollica JP, Dutka TL, Merry TL, Lamboley CR, McConell GK, McKenna MJ, Murphy RM, Lamb GD (Mar 2012). "S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans". The Journal of Physiology. 590 (Pt 6): 1443–63. doi:10.1113/jphysiol.2011.224535. PMC 3382333free to read. PMID 22250211. 
  21. ^ Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, Jorde LB, Carey JC, Bamshad M (Mar 2003). "Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes". American Journal of Human Genetics. 72 (3): 681–90. doi:10.1086/368294. PMC 1180243free to read. PMID 12592607. 
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Further reading[edit]