InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Pitx3

Summary

InnateDB Protein

IDBP-172276.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Pitx3

Protein Name

paired-like homeodomain transcription factor 3

Synonyms

ak; Ptx3;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000026259

InnateDB Gene

IDBG-172274 (Pitx3)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:15950611, ECO:0000269PubMed:17184956, ECO:0000269PubMed:19007884, ECO:0000269PubMed:19144721, ECO:0000269PubMed:19334279}.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00108, ECO:0000255PROSITE-ProRule:PRU00138, ECO:0000269PubMed:17184956}.

Disease Associations

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. {ECO:0000269PubMed:19334279}.

Tissue Specificity

Highly expressed in developing eye lens. Expression is restricted to the substantia nigra and ventral tegmental area in the midbrain. {ECO:0000269PubMed:15950611, ECO:0000269PubMed:19007884}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	1 [view]
Protein-Protein	1 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
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:0007626	locomotory behavior
GO:0010468	regulation of gene expression
GO:0030901	midbrain development
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048666	neuron development
GO:0070306	lens fiber cell differentiation
GO:0071542	dopaminergic neuron differentiation