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Details on Person UniProt:Q61572 Foxc1
| Class:Id | ReferenceGeneProduct:90699 |
|---|---|
| _chainChangeLog | chain:1-553 added on Sat February 7 2015 |
| _displayName | UniProt:Q61572 Foxc1 |
| _timestamp | 2025-05-21 21:11:50 |
| chain | chain:1-553 |
| checksum | 3CDB14F69AA2F217 |
| comment | FUNCTION 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:10395790, PubMed:10479458, PubMed:11562355, PubMed:18187037, PubMed:19668217, PubMed:22493429, PubMed:24590069, PubMed:25808752, PubMed:28223138, PubMed:9106663, PubMed:9635428). Acts either as a transcriptional activator or repressor (PubMed:28223138). Binds to the consensus binding site 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes (PubMed:25808752). Upon DNA-binding, promotes DNA bending. Acts as a transcriptional coactivator (PubMed:25808752). Stimulates Indian hedgehog (Ihh)-induced target gene expression mediated by the transcription factor GLI2, and hence regulates endochondral ossification (PubMed:25808752). Also acts as a transcriptional coregulator by increasing DNA-binding capacity of GLI2 in breast cancer cells. 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 (By similarity). Cooperates with transcription factor FOXC2 in regulating expression of genes that maintain podocyte integrity (PubMed:28223138). Promotes cell growth inhibition by stopping the cell cycle in the G1 phase through TGFB1-mediated signals. Involved in epithelial-mesenchymal transition (EMT) induction by increasing cell proliferation, migration and invasion (By similarity). Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (PubMed:18187037). Plays a role in the gene regulatory network essential for epidermal keratinocyte terminal differentiation (By similarity). Essential developmental transcriptional factor required for mesoderm-derived tissues formation, such as the somites, skin, bone and cartilage (PubMed:10395790, PubMed:10479458, PubMed:10704385, PubMed:11562355, PubMed:15196959, PubMed:9106663). 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) (PubMed:24590069). Plays a role in corneal transparency by preventing both blood vessel and lymphatic vessel growth during embryonic development in a VEGF-dependent manner (PubMed:22171010). May function as a tumor suppressor (By similarity).SUBUNIT Monomer. Interacts with C1QBP (By similarity). Interacts (via N-terminus) with GLI2 (via C-terminal internal region); this interaction is direct and increases GLI2 DNA-binding and transcriptional activity through a smoothened (SMO)-independent Hedgehog (Hh) signaling pathway (PubMed:25808752, PubMed:26565916). Interacts (via C-terminus domain) with PITX2 (via homeobox domain) (By similarity). Interacts with FLNA and PBX1 (By similarity).SUBCELLULAR LOCATION Colocalizes with PITX2 in the nucleus at subnuclear chromatin regions. Colocalizes with CBX5 to a heterochromatin-rich region of the nucleus (By similarity). Colocalizes with GLI2 in the nucleus (PubMed:25808752).TISSUE SPECIFICITY Expressed in glomerular epithelial cells, the podocytes (PubMed:28223138). Expressed in a population of adipo-osteogenic progenitor cells, termed CXCL12-abundant reticular (CAR) cells (at protein level) (PubMed:24590069). Expressed in many embryonic tissues, including prechondrogenic mesenchyme, periocular mesenchyme, meninges, endothelial cells and kidney (PubMed:9767123). Detected in adult brain, heart, kidney, adrenal gland, lung and testis, with lower levels in stomach, spleen and thymus (PubMed:9767123). Expressed in endothelial cells (PubMed:18187037). Expressed in the mesenchyme adjacent to the developing cerebellum (PubMed:19668217). Expressed in the sternum and rib cartilage (PubMed:25808752). Expressed in growth plate chondrocytes (PubMed:25808752).DEVELOPMENTAL STAGE Expressed in the anterior presomitic mesoderm (PSM) and somites at 9.5 dpc. Expressed in endothelial and smooth muscle cells of blood vessels at 9.5 dpc (PubMed:11562355). Expressed in growth plate chondrocytes and perichondrial cells at 13.5 dpc (at protein level) (PubMed:25808752). Expressed in non-notochordal mesoderm surrounding the node and notochord at 7.5 dpc (PubMed:9106663). Expressed in anterior presomitic mesoderm adjacent to somites, in the somites, and in the cephalic mesoderm at 8.5 and 9.5 dpc (PubMed:9106663). Detected weakly in yolk sac at 9.5 dpc (PubMed:11562355). Expressed in presumptive intermediate mesoderm, as well as in the presomitic mesoderm and somites at 8.5 and 9.5 dpc (PubMed:10704385). Expressed in the metanephric mesenchyme of the kidney at 10.5 and 12.5 dpc (PubMed:10704385). Expressed during the developing cardiovascular system (PubMed:10479458). Expressed in the branchial arches and mesenchymal cells surrounding the eye at 10.5 dpc (PubMed:9106663). Expressed in nasal processes, corneal mesenchyme cells, branchial arches, blood vessels and endocardium at 11.5 dpc (PubMed:10395790, PubMed:9106663). Expressed in cells located in the presumptive anterior segment that are fated to contribute to the corneal endothelium or stroma, as well as within cells located at the periphery of the optic cup at 11.5 dpc (PubMed:16449236). Expressed in periocular mesenchyme cells at 11.5, 12.5 and 16.5 dpc (PubMed:10395790, PubMed:16449236). Expressed in developing limb buds at 12.5 dpc (PubMed:25808752). Expressed in chondrocytes at 15 dpc (PubMed:25808752). Expressed in the trabecular meshwork cells, the sclera, the conjunctival epithelium and the corneal epithelium at 16.5 dpc (PubMed:10395790). Strongly expressed in adipo-osteogenic progenitor cells (CXCL12-abundant reticular (CAR) cells) at 16.5 dpc and at birth (PubMed:24590069).PTM Phosphorylated (PubMed:22493429). Phosphorylated on Ser-274 in response to epidermal growth factor (EGF) in a ERK1/2 MAPK-dependent signaling pathway; phosphorylation contributes to its protein stability and transcriptional regulatory activity (By similarity).PTM Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP2.PTM Ubiquitinated, leading to its proteasomal degradation.DISRUPTION PHENOTYPE Embryos die pre- and perinatally with haemorrhagic hydrocephalus and calvarial defects, beginning at 13.5 dpc (PubMed:10479458, PubMed:19668217, PubMed:9635428). Mutants that survive to later stages exhibit multiple craniofacial and vertebral defects characterized by disorganized rib fusion, absence of chondrocytes proliferation and ossification (PubMed:25808752, PubMed:9106663). Show abnormal cerebellar development with an enlarged fourth ventricle roof plate at 12.5 dpc and a disorganized cerebellar rhombic lip (PubMed:19668217). Show eye formation abnormalities: the lens remains attached to the cornea, both the anterior chamber and the corneal endothelium are absent, the corneal stroma is thicker, the arrangement of mesenchyme cells are disorganized and the corneal endothelial cells do not differentiate (PubMed:10395790). Show cardiovascular defects including persistent truncus arteriosus, ventricular septal defect, coarctation of the aortic arch, and aortic and pulmonary valve dysplasia (PubMed:10479458). Show abnormal kidney and ureter development, including duplex kidneys connecting to double ureters (PubMed:10704385). Show a decrease in hedgehog-induced genes expression levels involved in endochondral ossification (PubMed:25808752). Double knockout of FOXC1 and FOXC2 genes in mice embryos die around 8-9.5 dpc and show profound abnormalities in the first and second branchial arches, the early remodeling of blood vessels, a complete absence of segmented paraxial mesoderm, and the presence of ectopic and disorganized mesonephric kidney tubules (PubMed:11562355, PubMed:15196959). Mice with conditional knockout of both FOXC1 and FOXC2 genes in adult mice show renal tubular damage with protein reabsorption droplets, tubular dilation and proteinaceous casts and show also altered expression levels for several genes involved in the differentiation of podocytes (PubMed:28223138). Display also podocyte degeneration characterized with microvillous transformation, podocyte foot process effacement and irregular thickness of the glomerular basement membrane (PubMed:28223138). Podocyte-cell-specific conditional knockout of both FOXC1 and FOXC2 genes in adult mice show reabsorption droplets, tubular dilation and proteinaceous casts (PubMed:28223138). Endothelial-specific conditional knockout mice show a significant reduction in CXCR4 expression as well as in chemokine CXCL12-induced endothelial cell migration (PubMed:18187037). Limb bud mesenchymal-specific conditional knockout mice display strong reduction in haematopoietic stem and progenitor cells, the presence of adipocytes in marrow cavities (yellow adipose marrow) instead of CXCL12-abundant reticular (CAR) cells and die around 6 weeks of age with haemorrhagic hydrocephalus and calvarial defects (PubMed:24590069). CAR cell-specific conditional knockout mice are viable and die without hydrocephalus defects, but show a reduction in haematopoietic stem and progenitor cells (HSPCs) and most marrow cavities are filled with adipocytes (PubMed:24590069). Adult widespread cell-specific conditional knockout mice show a reduction in haematopoietic stem and progenitor cells (HSPCs), with only occasional adipocytes present in marrow cavities (PubMed:24590069). Neural crest (NC)-specific conditional knockout mice die postnatally with hydrocephalus and craniofacial abnormalities comparable to those seen in conventional knockout mice; embryos display pupillary abnormalities, with impaired collagen formation in the corneal stroma and aberrant vessel growth in the normally avascular corneas (PubMed:22171010). |
| description | recommendedName: Forkhead box protein C1 alternativeName: Forkhead-related protein FKHL7 alternativeName: Forkhead-related transcription factor 3 shortName: FREAC-3 alternativeName: Mesoderm/mesenchyme forkhead 1 shortName: MF-1 alternativeName: Transcription factor FKH-1 |
| geneName | Foxc1 Fkh1 Fkhl7 Freac3 Mf1 |
| identifier | Q61572 |
| isSequenceChanged | FALSE |
| keyword | Activator Angiogenesis Developmental protein DNA-binding Nucleus Phosphoprotein Reference proteome Repressor Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 |
| name | Foxc1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | FOXC1_MOUSE O88409 Q61582 Q9QWR9 |
| sequenceLength | 553 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:3927820] polySumo2,3-K229-Foxc1 [nucleoplasm] [Mus musculus] [EntityWithAccessionedSequence:3927823] Foxc1 [nucleoplasm] [Mus musculus] |
| (referenceSequence) | [GroupModifiedResidue:3927957] sumoylated lysine (polySumo2,3 [nucleoplasm]) at 229 |
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No pathways have been reviewed or authored by UniProt:Q61572 Foxc1 (90699)
