ID:PITX3_MOUSE DESCRIPTION: RecName: Full=Pituitary homeobox 3; AltName: Full=Homeobox protein PITX3; AltName: Full=Paired-like homeodomain transcription factor 3; FUNCTION: Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. In addition to its importance during development, it also has roles in the long-term survival and maintenance of the mdDA neurons. Activates NR4A2/NURR1- mediated transcription of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons. Acts by decreasing the interaction of NR4A2/NURR1 with the corepressor NCOR2/SMRT which acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state. Essential for the normal lens development and differentiation. Plays a critical role in the maintenance of mitotic activity of lens epithelial cells, fiber cell differentiation and in the control of the temporal and spatial activation of fiber cell-specific crystallins. Positively regulates FOXE3 expression and negatively regulates PROX1 in the anterior lens epithelium, preventing activation of CDKN1B/P27Kip1 and CDKN1C/P57Kip2 and thus maintains lens epithelial cells in cell cycle. SUBUNIT: Interacts with SFPQ. SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Highly expressed in developing eye lens. Expression is restricted to the substantia nigra and ventral tegmental area in the midbrain. DEVELOPMENTAL STAGE: First visible in E10.5 embryos where expression is confined to the lens vesicles. Between E11.5 and E12.5, expressed in both the lens epithelium and differentiating primary fiber cells. In the late fetal stage after the lens is formed, primarily found in the lens epithelium and the lens equator region where lens epithelial cells exit from the cell cycle and differentiate into fiber cells (at protein level). First expressed in the eye at 10 dpc embryos. Throughout eye development, expressed in the lens placode and forming lens pit. From 12 dpc, also detected in the midbrain region, tongue, incisor primordia, condensing mesenchyme around the sternum and vertebrae and in the head muscles. DISEASE: Note=Mutations in Pitx3 appear to be the cause of the aphakia (ak) phenotype, a recessive homozygous disease characterized by small eyes and closed eyelids. DISRUPTION PHENOTYPE: Mice show loss of nascent substantia nigra dopaminergic neurons at the beginning of their final differentiation and a loss of tyrosine hydroxylase (TH) expression specifically in the substantia nigra neurons. SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily. SIMILARITY: Contains 1 homeobox DNA-binding domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 46689 - Homeodomain-like 88659 - Sigma3 and sigma4 domains of RNA polymerase sigma factors
ModBase Predicted Comparative 3D Structure on O35160
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0043565 sequence-specific DNA binding
Biological Process: GO:0002088 lens development in camera-type eye GO:0002089 lens morphogenesis in camera-type eye GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0007275 multicellular organism development GO:0007568 aging GO:0007626 locomotory behavior GO:0010468 regulation of gene expression GO:0014014 negative regulation of gliogenesis GO:0030901 midbrain development GO:0035902 response to immobilization stress GO:0042220 response to cocaine GO:0043278 response to morphine GO:0043525 positive regulation of neuron apoptotic process GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048666 neuron development GO:0050768 negative regulation of neurogenesis GO:0070306 lens fiber cell differentiation GO:0071542 dopaminergic neuron differentiation GO:1904313 response to methamphetamine hydrochloride GO:1904935 positive regulation of cell proliferation in midbrain GO:1990792 cellular response to glial cell derived neurotrophic factor
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