Homeobox protein Nkx-2.5

3RKQ, 4S0H148218091ENSG00000183072ENSMUSG00000015579P52952P42582NM_004387NM_001166175NM_001166176NM_008700NP_001159647NP_001159648NP_004378NP_032726Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2.5 gene. Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2.5 gene. Homeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as determining the temporal and spatial patterns of development (Shiojima et al., 1995). It has been demonstrated that a Drosophila homeobox-containing gene called 'tinman' is expressed in the developing dorsal vessel and in the equivalent of the vertebrate heart. Mutations in tinman result in loss of heart formation in the embryo, suggesting that tinman is essential for Drosophila heart formation. Furthermore, abundant expression of Csx, the presumptive mouse homolog of tinman, is observed only in the heart from the time of cardiac differentiation. CSX, the human homolog of murine Csx, has a homeodomain sequence identical to that of Csx and is expressed only in the heart, again suggesting that CSX plays an important role in human heart formation.In humans, proper NKX2-5 expression is essential for the development of atrial, ventricular, and conotruncal septation, atrioventricular (AV) valve formation, and maintenance of AV conduction. Mutations in expression are associated with congenital heart disease (CHD) and related ailments. Patients with NKX2-5 mutations commonly present AV conduction block and atrial septal defects (ASD). Recently, postnatal roles of cardiac transcription factors have been extensively investigated. Consistent with the direct transactivation of numerous cardiac genes reactivated in response to hypertrophic stimulation, cardiac transcription factors are profoundly involved in the generation of cardiac hypertrophy or in cardioprotection from cytotoxic stress in the adult heart. Nkx-2.5 transcription factor may help myocytes endure cytotoxic stress, however further exploration in this field is required. NK-2 homeobox genes are a family of genes that encode for numerous transcription factors that go on to aid in the development of many structures including the thyroid, colon, and heart. Of the NK-2 genes, Nkx-2.5 transcription factor is mostly involved in cardiac development and defects with this gene can lead to congenital heart defects including, but not limited to atrial septal defects. Nkx-2.5 is expressed in precursor cardiac cells and this expression is necessary in order to lead to proper cardiac development. In Nkx-2.5 gene knock out mice, subjects were found to have induced congenital heart defects by leading to differentially expressed genes. In the case of loss of function of Nkx-2.5, test subjects developed increased heart rate and decreased variability in heart rate. This discovery indicates that Nkx-2.5 is necessary for proper cardiac formatting as well as proper cardiac function after formatting. Nkx-2.5 has also been shown to bind to the promoter of FGF-16 and regulate its expression. This finding suggests that Nkx-2.5 is implicated in cardiac injury via cytotoxic effects.