FOXC2

Forkhead box C2
PDB rendering based on 1d5v.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1D5V
Identifiers
Symbols	FOXC2 ; FKHL14; LD; MFH-1; MFH1
External IDs	OMIM: 602402 MGI: 1347481 HomoloGene: 21091 GeneCards: FOXC2 Gene
Gene ontology Molecular function • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcription factor activity, sequence-specific DNA binding • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • protein binding • chromatin DNA binding • sequence-specific DNA binding • transcription regulatory region DNA binding Cellular component • nucleus Biological process • negative regulation of transcription from RNA polymerase II promoter • ossification • patterning of blood vessels • metanephros development • ureteric bud development • somitogenesis • lymphangiogenesis • blood vessel remodeling • regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • Notch signaling pathway • mesoderm development • heart development • insulin receptor signaling pathway • response to hormone • positive regulation of endothelial cell migration • neural crest cell development • cell differentiation • collagen fibril organization • positive regulation of cell adhesion mediated by integrin • embryonic heart tube development • positive regulation of vascular wound healing • camera-type eye development • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • regulation of organ growth • vascular endothelial growth factor receptor signaling pathway • paraxial mesodermal cell fate commitment • embryonic viscerocranium morphogenesis • artery morphogenesis • regulation of blood vessel size • ventricular cardiac muscle tissue morphogenesis • cardiac muscle cell proliferation • glomerular endothelium development • glomerular visceral epithelial cell differentiation • glomerular mesangial cell development • positive regulation of cell migration involved in sprouting angiogenesis • negative regulation of apoptotic process involved in outflow tract morphogenesis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2303	14234
Ensembl	ENSG00000176692	ENSMUSG00000046714
UniProt	Q99958	Q61850
RefSeq (mRNA)	NM_005251	NM_013519
RefSeq (protein)	NP_005242	NP_038547
Location (UCSC)	Chr 16: 86.57 – 86.57 Mb	Chr 8: 121.12 – 121.12 Mb
PubMed search	[1]	[2]

Forkhead box protein C2 (FOXC2) also known as forkhead-related protein FKHL14 (FKHL14), transcription factor FKH-14, or mesenchyme fork head protein 1 (MFH1) is a protein that in humans is encoded by the FOXC2 gene. FOXC2 is a member of the fork head box (FOX) family of transcription factors.

Structure and function

The protein is 501 amino acids in length. The gene has no introns; the single exon is approximately 1.5kb is size.

FOX transcription factors are expressed during development and are associated with a number of cellular and developmental differentiation processes. FOXC2 is required during early development of the kidneys, including differentiation of podocytes and maturation of the glomerular basement membrane. It is also involved in the early development of the heart.

An increased expression of FOXC2 in adipocytes can increase the amount of brown adipose tissue leading to lower weight and an increased sensitivity to insulin.

Role in disease

Absence of FOXC2 has been shown to lead to the failure of lymphatic valves to form and problems with lymphatic remodelling. A number of mutations in the FOXC2 gene have been associated with Lymphedema–distichiasis syndrome, It has also been suggested that there may be a link between polymorphisms in FOXC2 and varicose veins.

FOXC2 is also involved in cancer metastases. In particular, expression of FOXC2 is induced when epithelial cells undergo an epithelial-mesenchymal transition (EMT) and become mesenchymal looking cells. EMT can be induced by a number of genes including Snail, Twist, Goosecoid, and TGF-beta 1. Overexpression of FOXC2 has been noted in subtypes of breast cancer which are highly metastatic. Suppression of FOXC2 expression using shRNA in a highly metastatic breast cancer model blocks their metastatic ability.

External links

• GeneReviews/NCBI/NIH/UW entry on Lymphedema-Distichiasis Syndrome