Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I

Abstract

Cardiac-restricted genes play important roles in cardiovascular system. In an effort to identify such novel genes we identified a novel cardiac-specific kinase gene TNNI3K localized on 1p31.1 based on bioinformatics analyses. Sequence analysis suggested that TNNI3K is a distant family member of integrin-linked kinase. Northern blot and 76-tissue array analyses showed that TNNI3K is highly expressed in heart, but is undetectable in other tissues. Immunohistochemical analysis predominantly localized TNNI3K in the nucleus of cardiac myocytes. In vitro kinase assay showed that TNNI3K is a functional kinase. The yeast two-hybrid system showed that TNNI3K could directly interact with cardiac troponin I, results that were further confirmed by coimmunoprecipitation in vivo. Our data suggest that TNNI3K is a cardiac-specific kinase and play important roles in cardiac system.

Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

“…TNNI3K is a novel cardiac troponin I-interacting kinase gene (23), but its role in body weight and obesity is unclear. The lack of association observed in the adolescent/young adult period for SH2B1 is supported by the published literature.…”

“…The purpose of the current study was to conduct a two-stage GWAS for genetic loci influencing BMI during late adolescence and early adulthood (aged [16][17][18][19][20][21][22][23][24][25]. Furthermore, we sought to compare estimates of effect sizes on BMI for the 32 BMI loci previously identified in European middle-aged adults (4) to effect sizes observed in adolescent and young adults of European descent.…”

Quantitative Trait Locus Analysis, Pathway Analysis, and Consomic Mapping Show Genetic Variants of Tnni3k, Fpgt, or H28 Control Susceptibility to Viral Myocarditis

“…Indeed, the SNP rs49812611 was recently identified as leading to nonsense mediated decay of Tnni3k transcripts (28). Tnni3k was identified as a cardiac specific tropinininteracting kinase in 2003 (47). Although the normal function of Tnni3k is still obscure, some recent results have somewhat clarified the situation.…”

Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis

“…43 A proposed candidate gene for hrtfm2 was Tnni3k, a cardiac troponin-interacting kinase. 44 The significance of this overlap is conjectural, but may indicate a role for altered function of basic house-keeping genes that modify myocardium function or structure, possibly similar to the role of dystrophin and CVB3 susceptibility in the mdx mouse. The peak of Vms1 also coincides with If1, a locus that has been reported to regulate the production of type I interferons in strains closely related to those used in this study.…”