1. Abnormal TnI phosphorylation observed in cardiac failure may explain exacerbated relaxation delay in response to increased afterload and contribute to blunted chronotropic reserve. PMID: 16936010
2. The cTnI-G203S mutation disrupts interactions with partner proteins, and results in intracellular Ca2+ dysregulation early in life, suggesting a pathogenic role in development of familial hypertrophic cardiomyopathy. PMID: 16950368
3. TnI deficiency impairs left ventricular relaxation, which leads to diastolic heart failure. PMID: 17526646
4. cTnI-Cre mice have delayed onset of Cre activity during early heart development PMID: 17540338
5. key role of cTnI in myocyte relaxation PMID: 17615373
6. The primary effect of protein kinase A phosphorylation of cardiac troponin I is reduced Ca(2+) sensitivity of force, whereas phosphorylation of cardiac myosin-binding protein C accelerates the kinetics of force development. PMID: 17641226
7. Changes in Ca(2+) affinity also support the idea that the equilibrium between states of actin-tropomyosin-troponin was shifted to the inactive state by mutations that mimic troponin I phosphorylation. PMID: 17872964
8. Thr144 in cardiac TnI modulates cardiac myofilament length-dependent activation. PMID: 17975107
9. Lys184 deletion in troponin I impairs relaxation kinetics and induces hypercontractility in murine cardiac myofibrils. PMID: 18096573
10. Simultaneous defects in MHC7 & TnI accelerate onset & progression of familial hypertrophic cardiomyopathy. Compared with single-mutant models, double-mutant mice develop severe disease & premature death, progressing directly to a dilated phenotype. PMID: 18362229
11. Impaired relaxation is the main manifestation in transgenic mice expressing a restrictive cardiomyopathy mutation, R193H, in cardiac TnI. PMID: 18408133
12. Removal of the N-terminal extension of cardiac troponin I as a functional compensation for impaired myocardial beta-adrenergic signaling PMID: 18815135
13. Transfer of troponin I-specific T cells can induce inflammation and fibrosis in wild-type mice, leading to deterioration of contractile function. Two sequence motifs of cTnI that induce inflammation and fibrosis in myocardium are characterized. PMID: 18955666
14. These results indicate that YY1 is a novel regulator of fetal TnI transcription in the heart. PMID: 19013134
15. the nNOS-PMCA4b complex regulates contractility via cAMP and phosphorylation of both PLB and cTnI. PMID: 19278978
16. Studies indicate that that immunization of genetically susceptible mice with troponin I but not troponin T induced a robust autoimmune response leading to marked inflammation and fibrosis in the myocardium. PMID: 19446498
17. Ca(2+) binding to thin filaments reconstituted with either cTnI(wild-type) or pseudo-phosphorylated cTnI(S23D/S24D), cTnI(T144E), and cTnI(S23D/S24D/T144E) was determined. PMID: 20164197
18. the functional effect of cTnI mutation and its potential value in compensating for the cTnT abnormality PMID: 20551314
19. Loss of troponin I leads to myofibril hypersensitivity to Ca(2+) causing impaired relaxation in restrictive cardiomyopathy. PMID: 20580639
20. Data suggest that AMPK emerges as a possibly important regulator of cardiac and skeletal contractility via phosphorylation of a preferred site adjacent to the inhibitory loop of the thin filament protein TnI. PMID: 21416543
21. Generation and functional characterization of knock-in mice harboring the cardiac troponin I-R21C mutation associated with hypertrophic cardiomyopathy. PMID: 22086914
22. Conclude that cTnI phosphorylation by AMPK may represent a novel mechanism of regulation of cardiac function. PMID: 22456184
23. A new functional and pathological role of amino acid modifications in the N-terminal acidic domain of cardiac TnI has been found that is modified by phosphorylations at TnI(S23/S24). PMID: 22940544
24. Data show that cardiac TnI gene transition and the alternatively spliced cardiac TnT isoform switching occur in postnatal pulmonary vein. PMID: 23176202
25. The pattern of cTnI post-translational modification depends on sex and hypertrophic cardiomyopathy genotype. PMID: 23352598
26. Conclude that dilated cardiomyopathy-causing mutations in thin filament proteins abolish the relationship between myofilament Ca(2+) sensitivity and troponin I phosphorylation by PKA. PMID: 23539503
27. R193H and R205H mutation increase the binding affinity of Troponin I for Troponin T and Troponin C. PMID: 24326031
28. Combined troponin I Ser-150 and Ser-23/24 phosphorylation sustains thin filament Ca(2+) sensitivity playing an adaptive role to preserve contraction during acidic ischemia. PMID: 24657721
29. Dominant negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, causes early ventricular remodeling, and blunts the beta-adrenergic response of cardiac myocytes. PMID: 24898585
30. these results indicate that the inability to enhance myofilament relaxation through cTnI phosphorylation predisposes the heart to abnormal diastolic function, reduced accessibility of cardiac reserves, dysautonomia, and hypertrophy. PMID: 24973218
31. troponin I phosphorylation specifically alters the Ca(2+) sensitivity of isometric tension and the time course of relaxation in cardiac muscle myofibrils PMID: 25418306
32. The difference in myosin regulatory light chain phosphorylation between the ventricles of R21C(+/+) in cardiac troponin I mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice PMID: 25961037
33. The contributions of cardiac myosin binding protein C and troponin I phosphorylation to beta-adrenergic enhancement of in vivo cardiac function PMID: 26635197
34. Hyperphosphorylation of this serine199 in cTnI C terminus impacts heart function by depressing diastolic function at baseline and limiting systolic reserve under physiological stresses. Paradoxically, it preserves heart function after ischemia/reperfusion injury, potentially by decreasing proteolysis of cTnI. PMID: 28899987
35. Pim-1 is a novel kinase that phosphorylates cTnI primarily at Ser23/24 and Ser150 in cardiomyocytes, which in turn may modulate myofilament function under a variety of physiological and pathophysiological conditions. PMID: 29544221

KEGG: mmu:21954

STRING: 10090.ENSMUSP00000096458

UniGene: Mm.27674