PITX3
Description
The PITX3 (paired like homeodomain 3) is a protein-coding gene located on chromosome 10.
Pituitary homeobox 3 is a protein that in humans is encoded by the PITX3 gene. This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family act as transcription factors. This protein is involved in lens formation during eye development, and the specification and terminal differentiation of mesencephalic dopamine neurons in the substantia nigra compacta that are lost in Parkinson's disease. Mutations of this gene have been associated with anterior segment mesenchymal dysgenesis (ASMD) and congenital cataracts.
PITX3 acts as a transcription factor, playing a crucial role in the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. This includes contributing to their long-term survival and maintenance. PITX3 activates NR4A2/NURR1-mediated transcription of genes such as SLC6A3, SLC18A2, TH and DRD2, which are essential for mdDA neuron development. It achieves this by decreasing the interaction of NR4A2/NURR1 with the corepressor NCOR2/SMRT, which would normally repress transcription through histone deacetylases (HDACs). PITX3 is also essential for normal lens development and differentiation. It maintains the mitotic activity of lens epithelial cells, promotes fiber cell differentiation, and controls the temporal and spatial activation of fiber cell-specific crystallins. Furthermore, it positively regulates FOXE3 expression and negatively regulates PROX1 in the anterior lens epithelium, preventing the activation of CDKN1B/P27Kip1 and CDKN1C/P57Kip2, thus maintaining lens epithelial cells in the cell cycle.
PITX3 is also known as ASGD1, ASMD, ASOD, CTPP4, CTRCT11, PTX3.
