ID:PITX3_HUMAN 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 (By similarity). SUBUNIT: Interacts with SFPQ (By similarity). SUBCELLULAR LOCATION: Nucleus (By similarity). TISSUE SPECIFICITY: Highly expressed in developing eye lens. DISEASE: Defects in PITX3 are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract is the most common treatable cause of visual disability in childhood. DISEASE: Defects in PITX3 are a cause of anterior segment mesenchymal dysgenesis (ASMD) [MIM:107250]; also known as anterior segment ocular dysgenesis (ASOD). ASMD consists of a range of developmental defects in structures at the front of the eye, resulting from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to the cornea, iris, and other components of the anterior chamber during eye development. Mature anterior segment anomalies are associated with an increased risk of glaucoma and corneal opacity. Conditions falling within the phenotypic spectrum include aniridia, posterior embryotoxon, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. DISEASE: Defects in PITX3 are the cause of cataract posterior polar type 4 (CTPP4) [MIM:610623]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity. Some patients affected by cataract posterior polar type 4 can present a severe phenotype including microphthalmia and neurological dysfunction. SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily. SIMILARITY: Contains 1 homeobox DNA-binding domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PITX3";
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 O75364
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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:0000981 RNA polymerase II transcription factor activity, 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: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:0009887 animal organ morphogenesis 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
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
