FOXC1

This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it has been shown to play a role in the regulation of embryonic and ocular development. Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld-Rieger anomaly. [provided by RefSeq, Jul 2008]

Forkhead Box C1

DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development (PubMed:11782474, PubMed:15299087, PubMed:15684392, PubMed:16492674, PubMed:27907090, PubMed:14506133, PubMed:14578375, PubMed:15277473, PubMed:16449236, PubMed:17210863, PubMed:19793056, PubMed:19279310, PubMed:25786029, PubMed:27804176).

Acts either as a transcriptional activator or repressor (PubMed:11782474).

Binds to the consensus binding site 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes (PubMed:7957066, PubMed:11782474, PubMed:12533514, PubMed:14506133, PubMed:19793056, PubMed:27804176).

Upon DNA-binding, promotes DNA bending (PubMed:7957066, PubMed:14506133).

Acts as a transcriptional coactivator (PubMed:26565916).

Stimulates Indian hedgehog (Ihh)-induced target gene expression mediated by the transcription factor GLI2, and hence regulates endochondral ossification (By similarity).

Acts also as a transcriptional coregulator by increasing DNA-binding capacity of GLI2 in breast cancer cells (PubMed:26565916).

Regulates FOXO1 through binding to a conserved element, 5'-GTAAACAAA-3' in its promoter region, implicating FOXC1 as an important regulator of cell viability and resistance to oxidative stress in the eye (PubMed:17993506).

Cooperates with transcription factor FOXC2 in regulating expression of genes that maintain podocyte integrity (By similarity).

Promotes cell growth inhibition by stopping the cell cycle in the G1 phase through TGFB1-mediated signals (PubMed:12408963).

Involved in epithelial-mesenchymal transition (EMT) induction by increasing cell proliferation, migration and invasion (PubMed:20406990, PubMed:22991501).

Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (By similarity).

Plays a role in the gene regulatory network essential for epidermal keratinocyte terminal differentiation (PubMed:27907090).

Essential developmental transcriptional factor required for mesoderm-derived tissues, such as the somites, skin, bone and cartilage. Positively regulates CXCL12 and stem cell factor expression in bone marrow mesenchymal progenitor cells, and hence plays a role in the development and maintenance of mesenchymal niches for haematopoietic stem and progenitor cells (HSPC). Plays a role in corneal transparency by preventing both blood vessel and lymphatic vessel growth during embryonic development in a VEGF-dependent manner. Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (By similarity).

May function as a tumor suppressor (PubMed:12408963).

Anatomical structure morphogenesis Source: GO_Central
Angiogenesis Source: UniProtKB-KW
Artery morphogenesis Source: Ensembl
Blood vessel diameter maintenance Source: Ensembl
Blood vessel remodeling Source: Ensembl
Camera-type eye development Source: Ensembl
Cardiac muscle cell proliferation Source: Ensembl
Cell differentiation Source: GO_Central
Cell migration Source: UniProtKB
Cell population proliferation Source: UniProtKB
Cellular response to chemokine Source: UniProtKB
Cellular response to epidermal growth factor stimulus Source: UniProtKB
Cerebellum development Source: UniProtKB
Chemokine-mediated signaling pathway Source: UniProtKB
Collagen fibril organization Source: Ensembl
Embryonic heart tube development Source: Ensembl
Endochondral ossification Source: UniProtKB
Eye development Source: MGI
Germ cell migration Source: Ensembl
Glomerular epithelium development Source: UniProtKB
Glycosaminoglycan metabolic process Source: Ensembl
Heart development Source: MGI
In utero embryonic development Source: Ensembl
Kidney development Source: UniProtKB
Lacrimal gland development Source: Ensembl
Lymph vessel development Source: Ensembl
Maintenance of lens transparency Source: UniProtKB
Mesenchymal cell development Source: UniProtKB
Negative regulation of angiogenesis Source: UniProtKB
Negative regulation of apoptotic process involved in outflow tract morphogenesis Source: Ensembl
Negative regulation of lymphangiogenesis Source: UniProtKB
Negative regulation of mitotic cell cycle Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Neural crest cell development Source: Ensembl
Notch signaling pathway Source: Ensembl
Odontogenesis of dentin-containing tooth Source: UniProtKB
Ovarian follicle development Source: Ensembl
Paraxial mesoderm formation Source: Ensembl
Positive regulation of core promoter binding Source: UniProtKB
Positive regulation of DNA binding Source: UniProtKB
Positive regulation of epithelial to mesenchymal transition Source: UniProtKB
Positive regulation of gene expression Source: Ensembl
Positive regulation of hematopoietic progenitor cell differentiation Source: UniProtKB
Positive regulation of hematopoietic stem cell differentiation Source: UniProtKB
Positive regulation of keratinocyte differentiation Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Regulation of organ growth Source: Ensembl
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Somitogenesis Source: Ensembl
Ureteric bud development Source: UniProtKB
Vascular endothelial growth factor receptor signaling pathway Source: Ensembl
Vascular endothelial growth factor signaling pathway Source: UniProtKB
Ventricular cardiac muscle tissue morphogenesis Source: Ensembl

Nucleus. Colocalizes with PITX2 isoform 3 in the nucleus at subnuclear chromatine regions (PubMed:16449236). Colocalizes with CBX5 to a heterochromatin-rich region of the nucleus (PubMed:15684392). Colocalizes with GLI2 in the nucleus (By similarity).

Axenfeld-Rieger syndrome 3 (RIEG3):
An autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Features include posterior corneal embryotoxon, prominent Schwalbe line and iris adhesion to the Schwalbe line, hypertelorism, hypodontia, sensorineural deafness, redundant periumbilical skin, and cardiovascular defects such as patent ductus arteriosus and atrial septal defect. When associated with tooth anomalies, the disorder is known as Rieger syndrome.
Anterior segment dysgenesis 3 (ASGD3):
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD3 inheritance is autosomal dominant.

Phosphorylated (PubMed:11782474, PubMed:19279310, PubMed:25786029). Phosphorylated on Ser-272 in response to epidermal growth factor (EGF) in a ERK1/2 MAPK-dependent signaling pathway; phosphorylation contributes to its protein stability and transcriptional activity (PubMed:16492674).
Sumoylated preferentially with SUMO2 or SUMO3 (PubMed:22493429). Desumoylated by SENP2 (PubMed:22493429).
Ubiquitinated, leading to its proteasomal degradation (PubMed:16492674).