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TNNI1

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TNNI1
Identifiers
AliasesTNNI1, SSTNI, TNN1, troponin I1, slow skeletal type
External IDsOMIM: 191042 MGI: 105073 HomoloGene: 2462 GeneCards: TNNI1
Orthologs
SpeciesHumanMouse
Entrez

7135

21952

Ensembl

ENSG00000159173

ENSMUSG00000026418

UniProt

P19237

Q9WUZ5

RefSeq (mRNA)

NM_003281

NM_001112702
NM_021467

RefSeq (protein)

NP_003272

NP_001106173
NP_067442

Location (UCSC)Chr 1: 201.4 – 201.43 MbChr 1: 135.78 – 135.81 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Troponin I, slow skeletal muscle is a protein that in humans is encoded by the TNNI1 gene.[5][6][7] It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

Gene TNNI1, troponin I type 1 (skeletal muscle, slow), also known as TNN1 and SSTNI, is located at 1q31.3 in the human chromosomal genome, encoding the slow twitch skeletal muscle isoform of troponin I (ssTnI), the inhibitory subunit of the troponin complex in striated muscle myofilaments.[8][9] Human TNNI1 spans 12.5 kilobases in the genomic DNA and contains 9 exons and 8 introns.[10] Exon 2 to exon 8 contain the coding sequences, encoding a protein of 21.7 kDa consisting of 187 amino acids including the first methionine with an isoelectric point (pI) of 9.59.

Gene evolution[]

Figure 1: Evolutionary lineage of vertebrate TNNI1 deduced from alignment of ssTnI amino acid sequences.

Three homologous genes have evolved in vertebrates, encoding three muscle type-specific isoforms of TnI.[8][11][12] In mammals, the amino acid sequence of ssTnI is highly conserved. Mouse and bovine ssTnI each differs from human ssTnI in only four amino acids, and rhesus monkey ssTnI is identical to human in the amino acid sequences. In lower vertebrates, the divergence of ssTnI between species is larger than that in the higher vertebrates (Fig1).

Tissue distribution[]

Comparing with the fast twitch skeletal muscle and cardiac TnI isoform genes (TNNT2 and TNNT3), TNNI1 has a broader range of expression in avian and mammalian striated muscles. It is the predominant TnI isoform expressed in both slow skeletal muscle and cardiac muscle in early embryonic stage.[13] An isoform switch from ssTnI to cTnI occurs during perinatal heart development.[13][14][15] ssTnI is not expressed in the embryonic hearts of Xenopus and zebrafish, while it is expressed in the somites and skeletal muscles.[16][17]

Structure-function relationships[]

The function of TnI is to control striated muscle contraction and relaxation. Troponin I interacts with all major regulatory proteins in the sarcomeric thin filaments of cardiac and skeletal muscles: troponin C, troponin T, tropomyosin and actin. When cytosolic Ca2+ is low, TnI binds the thin filament to block the myosin binding sites on actin. The rise of cytosolic Ca2+ results in binding to the N-terminal domain of troponin C and induces conformational changes in troponin C and the troponin complex, which releases the inhibition of myosin-actin interaction and activates myosin ATPase and cross bridge cycling to generate myosin power strokes and muscle contraction.

To date, no high resolution structure of ssTnI has been solved. As homologous proteins, ssTnI, fast skeletal muscle TnI and cardiac TnI have highly conserved structures and crystallographic high resolution structure of partial cardiac and fast skeletal troponin complex are both available. Therefore, the structure-function relationship of ssTnI would rely on the information from studies performed on fast skeletal muscle and cardiac TnI.

Posttranslational modifications[]

To date, no posttranslational modification of ssTnI has been identified.

Mutations[]

To date, no human disease has been reported with mutations in TNNI1.

Clinical significance[]

Slow to fast skeletal TnI isoform switch occurs as an indicator for slow to fast fiber type transition in muscle adaptations.[18] Slow skeletal TnI has been proposed as a sensitive and muscle fiber type-specific marker for skeletal muscle injuries.[19][20] In patients with skeletal muscle disorders, intact ssTnI or its degraded products may be detected in peripheral blood as a diagnostic indicator for slow fiber damages.

Notes[]

References[]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000159173 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026418 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Wade R, Eddy R, Shows TB, Kedes L (Jul 1990). "cDNA sequence, tissue-specific expression, and chromosomal mapping of the human slow-twitch skeletal muscle isoform of troponin I". Genomics. 7 (3): 346–57. doi:10.1016/0888-7543(90)90168-T. PMID 2365354.
  6. ^ Corin SJ, Juhasz O, Zhu L, Conley P, Kedes L, Wade R (Apr 1994). "Structure and expression of the human slow twitch skeletal muscle troponin I gene". The Journal of Biological Chemistry. 269 (14): 10651–9. doi:10.1016/S0021-9258(17)34109-1. PMID 8144655.
  7. ^ "Entrez Gene: TNNI1 troponin I type 1 (skeletal, slow)".
  8. ^ a b 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. S2CID 23721684.
  9. ^ Jin JP, Zhang Z, Bautista JA (2008). "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.
  10. ^ Corin SJ, Juhasz O, Zhu L, Conley P, Kedes L, Wade R (Apr 1994). "Structure and expression of the human slow twitch skeletal muscle troponin I gene". The Journal of Biological Chemistry. 269 (14): 10651–9. doi:10.1016/S0021-9258(17)34109-1. PMID 8144655.
  11. ^ Hastings KE (Feb 1997). "Molecular evolution of the vertebrate troponin I gene family". Cell Structure and Function. 22 (1): 205–11. doi:10.1247/csf.22.205. PMID 9113408.
  12. ^ Chong SM, Jin JP (May 2009). "To investigate protein evolution by detecting suppressed epitope structures". Journal of Molecular Evolution. 68 (5): 448–60. doi:10.1007/s00239-009-9202-0. PMC 2752406. PMID 19365646.
  13. ^ a b Sasse S, Brand NJ, Kyprianou P, Dhoot GK, Wade R, Arai M, Periasamy M, Yacoub MH, Barton PJ (May 1993). "Troponin I gene expression during human cardiac development and in end-stage heart failure". Circulation Research. 72 (5): 932–8. doi:10.1161/01.res.72.5.932. PMID 8477526.
  14. ^ Saggin L, Gorza L, Ausoni S, Schiaffino S (Sep 1989). "Troponin I switching in the developing heart". The Journal of Biological Chemistry. 264 (27): 16299–302. doi:10.1016/S0021-9258(18)71621-9. PMID 2777792.
  15. ^ Jin JP (Aug 1996). "Alternative RNA splicing-generated cardiac troponin T isoform switching: a non-heart-restricted genetic programming synchronized in developing cardiac and skeletal muscles". Biochemical and Biophysical Research Communications. 225 (3): 883–9. doi:10.1006/bbrc.1996.1267. PMID 8780706.
  16. ^ Warkman AS, Atkinson BG (Jul 2002). "The slow isoform of Xenopus troponin I is expressed in developing skeletal muscle but not in the heart". Mechanisms of Development. 115 (1–2): 143–6. doi:10.1016/s0925-4773(02)00096-5. PMID 12049779. S2CID 12461520.
  17. ^ Fu CY, Lee HC, Tsai HJ (Jun 2009). "The molecular structures and expression patterns of zebrafish troponin I genes". Gene Expression Patterns. 9 (5): 348–56. doi:10.1016/j.gep.2009.02.001. PMID 19602390.
  18. ^ Stevens L, Bastide B, Kischel P, Pette D, Mounier Y (May 2002). "Time-dependent changes in expression of troponin subunit isoforms in unloaded rat soleus muscle". American Journal of Physiology. Cell Physiology. 282 (5): C1025–30. doi:10.1152/ajpcell.00252.2001. PMID 11940518. S2CID 11767406.
  19. ^ Simpson JA, Labugger R, Collier C, Brison RJ, Iscoe S, Van Eyk JE (Jun 2005). "Fast and slow skeletal troponin I in serum from patients with various skeletal muscle disorders: a pilot study". Clinical Chemistry. 51 (6): 966–72. doi:10.1373/clinchem.2004.042671. PMID 15833785.
  20. ^ Chapman DW, Simpson JA, Iscoe S, Robins T, Nosaka K (Jan 2013). "Changes in serum fast and slow skeletal troponin I concentration following maximal eccentric contractions". Journal of Science and Medicine in Sport / Sports Medicine Australia. 16 (1): 82–5. doi:10.1016/j.jsams.2012.05.006. PMID 22795680.

Further reading[]

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