Nkx2-5
Developmental stage
Expression preceeds the onset of myogenic differentiation, and continues in cardiomyocytes of embryonic, fetal and adult hearts. It is also expressed laterally in future pharyngeal endoderm which is believed to produce the heart inducer. After foregut closure expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid primordium a derivative of the pharyngeal floor continues to express the protein after its levels diminish in the rest of the pharynx.
Domain
The homeobox domain binds to double-stranded DNA.
Function
Transcription factor required for the development of the heart and the spleen (PubMed:16556915, PubMed:19483677, PubMed:22560297, PubMed:9584153). During heart development, acts as a transcriptional activator of NPPA/ANF in cooperation with GATA4 (PubMed:9584153). May cooperate with TBX2 to negatively modulate expression of NPPA/ANF in the atrioventricular canal (PubMed:12023302). Binds to the core DNA motif of NPPA promoter (PubMed:19483677). Together with PBX1, required for spleen development through a mechanism that involves CDKN2B repression (PubMed:22560297). Positively regulates transcription of genes such as COL3A1 and MMP2, resulting in increased pulmonary endothelial fibrosis in response to hypoxia (By similarity).
Sequence Similarities
Belongs to the NK-2 homeobox family.
Tissue Specificity
Predominantly in the adult and embryonic heart, and to a lesser extent in lingual muscle, spleen and stomach.
Cellular localization
- Nucleus
Alternative names
Csx, Nkx-2.5, Nkx2e, Nkx2-5, Homeobox protein Nkx-2.5, Cardiac-specific homeobox, Homeobox protein CSX, Homeobox protein NK-2 homolog E