TNNI1

Last updated
TNNI1
Identifiers
Aliases TNNI1 , SSTNI, TNN1, troponin I1, slow skeletal type
External IDs OMIM: 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 Mb Chr 1: 135.71 – 135.74 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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.

Contents

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. [6] 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. SsTnI align.jpg
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] [10] [11] 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. [12] An isoform switch from ssTnI to cTnI occurs during perinatal heart development. [12] [13] [14] ssTnI is not expressed in the embryonic hearts of Xenopus and zebrafish, while it is expressed in the somites and skeletal muscles. [15] [16]

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. [17] Slow skeletal TnI has been proposed as a sensitive and muscle fiber type-specific marker for skeletal muscle injuries. [18] [19] 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

Related Research Articles

<span class="mw-page-title-main">Troponin</span> Protein complex

Troponin, or the troponin complex, is a complex of three regulatory proteins that are integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Measurements of cardiac-specific troponins I and T are extensively used as diagnostic and prognostic indicators in the management of myocardial infarction and acute coronary syndrome. Blood troponin levels may be used as a diagnostic marker for stroke or other myocardial injury that is ongoing, although the sensitivity of this measurement is low.

<span class="mw-page-title-main">Muscle contraction</span> Activation of tension-generating sites in muscle

Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as when holding something heavy in the same position. The termination of muscle contraction is followed by muscle relaxation, which is a return of the muscle fibers to their low tension-generating state.

<span class="mw-page-title-main">Tropomyosin</span> Protein

Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in many animal and fungal cells. In animals, it is an important component of the muscular system which works in conjunction with troponin to regulate muscle contraction. It is present in smooth and striated muscle tissues, which can be found in various organs and body systems, including the heart, blood vessels, respiratory system, and digestive system. In fungi, tropomyosin is found in cell walls and helps maintain the structural integrity of cells.

<span class="mw-page-title-main">MYH7</span> Protein-coding gene in the species Homo sapiens

MYH7 is a gene encoding a myosin heavy chain beta (MHC-β) isoform expressed primarily in the heart, but also in skeletal muscles. This isoform is distinct from the fast isoform of cardiac myosin heavy chain, MYH6, referred to as MHC-α. MHC-β is the major protein comprising the thick filament that forms the sarcomeres in cardiac muscle and plays a major role in cardiac muscle contraction.

<span class="mw-page-title-main">Troponin I</span> Muscle protein

Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack. It occurs in different plasma concentration but the same circumstances as troponin T - either test can be performed for confirmation of cardiac muscle damage and laboratories usually offer one test or the other.

<span class="mw-page-title-main">TNNI3</span> Protein-coding gene in the species Homo sapiens

Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

<span class="mw-page-title-main">TNNT2</span> Protein-coding gene in the species Homo sapiens

Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

<span class="mw-page-title-main">TPM1</span> Protein-coding gene in the species Homo sapiens

Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene. This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells.

<span class="mw-page-title-main">Troponin C type 1</span> Protein-coding gene in the species Homo sapiens

Troponin C, also known as TN-C or TnC, is a protein that resides in the troponin complex on actin thin filaments of striated muscle and is responsible for binding calcium to activate muscle contraction. Troponin C is encoded by the TNNC1 gene in humans for both cardiac and slow skeletal muscle.

<span class="mw-page-title-main">TPM2</span> Protein-coding gene in the species Homo sapiens

β-Tropomyosin, also known as tropomyosin beta chain is a protein that in humans is encoded by the TPM2 gene. β-tropomyosin is striated muscle-specific coiled coil dimer that functions to stabilize actin filaments and regulate muscle contraction.

<span class="mw-page-title-main">MYH10</span> Protein-coding gene in the species Homo sapiens

Myosin-10 also known as myosin heavy chain 10 or non-muscle myosin IIB (NM-IIB) is a protein that in humans is encoded by the MYH10 gene. Non-muscle myosins are expressed in a wide variety of tissues, but NM-IIB is the only non-muscle myosin II isoform expressed in cardiac muscle, where it localizes to adherens junctions within intercalated discs. NM-IIB is essential for normal development of cardiac muscle and for integrity of intercalated discs. Mutations in MYH10 have been identified in patients with left atrial enlargement.

<span class="mw-page-title-main">TNNI2</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">TNNT1</span> Protein-coding gene in the species Homo sapiens

Slow skeletal muscle troponin T (sTnT) is a protein that in humans is encoded by the TNNT1 gene.

<span class="mw-page-title-main">MYBPC1</span> Protein-coding gene in the species Homo sapiens

Myosin-binding protein C, slow-type is a protein that in humans is encoded by the MYBPC1 gene.

<span class="mw-page-title-main">MYL3</span> Protein-coding gene in the species Homo sapiens

Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene. This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (MYL1) and cardiac atrial muscle (MYL4). Ventricular ELC is part of the myosin molecule and is important in modulating cardiac muscle contraction.

<span class="mw-page-title-main">MYL4</span> Protein-coding gene in the species Homo sapiens

Atrial Light Chain-1 (ALC-1), also known as Essential Light Chain, Atrial is a protein that in humans is encoded by the MYL4 gene. ALC-1 is expressed in fetal cardiac ventricular and fetal skeletal muscle, as well as fetal and adult cardiac atrial tissue. ALC-1 expression is reactivated in human ventricular myocardium in various cardiac muscle diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and congenital heart diseases.

<span class="mw-page-title-main">TNNT3</span> Protein-coding gene in the species Homo sapiens

Fast skeletal muscle troponin T (fTnT) is a protein that in humans is encoded by the TNNT3 gene.

<span class="mw-page-title-main">Troponin C, skeletal muscle</span> Protein-coding gene in the species Homo sapiens

Troponin C, skeletal muscle is a protein that in humans is encoded by the TNNC2 gene.

<span class="mw-page-title-main">MYLPF</span> Protein-coding gene in the species Homo sapiens

Myosin light chain, phosphorylatable, fast skeletal muscle is a protein that in humans is encoded by the MYLPF gene. It is located on chromosome 16 in humans. Myosin light chain, phosphorylatable

<span class="mw-page-title-main">MYBPC2</span> Protein-coding gene in the species Homo sapiens

Myosin binding protein C, fast type is a protein that in humans is encoded by the MYBPC2 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000159173 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 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. ↑ 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.
  11. ↑ Chong SM, Jin JP (May 2009). "To investigate protein evolution by detecting suppressed epitope structures". Journal of Molecular Evolution. 68 (5): 448–60. Bibcode:2009JMolE..68..448C. doi:10.1007/s00239-009-9202-0. PMC   2752406 . PMID   19365646.
  12. 1 2 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ Fu CY, Lee HC, Tsai HJ (Jun 2009). "The molecular structures and expression patterns of zebrafish troponin I genes" (PDF). Gene Expression Patterns. 9 (5): 348–56. doi:10.1016/j.gep.2009.02.001. PMID   19602390.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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. 16 (1): 82–5. doi: 10.1016/j.jsams.2012.05.006 . PMID   22795680.

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