FOXC1 is a forkhead-family nuclear transcription factor that recognizes defined regulatory DNA sequences and activates transcription through regions flanking its winged-helix DNA-binding domain. An internal inhibitory region attenuates activation-domain-driven output in engineered reporter assays. Its demonstrated targets include FOXO1 in human ocular cells. Protein partners and growth-factor signaling can alter its transcriptional output or stability. FOXC1 contributes to eye, cardiovascular, renal, skeletal and mesenchymal developmental programs; in some settings it acts through signals produced by surrounding mesenchyme rather than within the responding tissue. Pathogenic variants cause anterior segment dysgenesis, including Axenfeld-Rieger syndrome, and increase glaucoma susceptibility. Proliferation, migration and differentiation effects vary with cellular context. In selected cancer models, FOXC1 associates with GLI2 and enhances GLI2 DNA-binding activity and transcriptional output.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | UNDECIDED | Summary: The transferred negative transcription-regulation direction remains source-specific unresolved. Reason: The original mouse Foxc1 Q61572 donor trace points to PMID:28223138. Its authentic abstract and section previews support dose-dependent Foxc1/Foxc2 podocyte integrity, but the precise negative Pol-II regulatory assay was not accessible. Human PMID:11782474 independently establishes an internal inhibitory region: residues 215–366 attenuated activation by FOXC1 and by an engineered GAL4 activation-domain fusion. In the original Results and Figure 5E, the same segment fused to the GAL4 DNA-binding domain did not reduce constitutive SV40 reporter output without an activation domain; the Discussion explicitly describes activation-domain-dependent inhibition. This positive modular inhibition is acknowledged alongside UniProt’s activator-or-repressor summary. It does not resolve the particular mouse donor assay or establish a separate full-length DNA-binding repressor mechanism. The original transfer therefore remains source-specific UNDECIDED, without denying FOXC1’s inhibitory region or transferring inhibition of FOXC1 by a partner onto FOXC1 itself. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | UNDECIDED | Summary: The transferred negative transcription-regulation direction remains source-specific unresolved. Reason: The original mouse Foxc1 Q61572 donor trace points to PMID:28223138. Its authentic abstract and section previews support dose-dependent Foxc1/Foxc2 podocyte integrity, but the precise negative Pol-II regulatory assay was not accessible. Human PMID:11782474 independently establishes an internal inhibitory region: residues 215–366 attenuated activation by FOXC1 and by an engineered GAL4 activation-domain fusion. In the original Results and Figure 5E, the same segment fused to the GAL4 DNA-binding domain did not reduce constitutive SV40 reporter output without an activation domain; the Discussion explicitly describes activation-domain-dependent inhibition. This positive modular inhibition is acknowledged alongside UniProt’s activator-or-repressor summary. It does not resolve the particular mouse donor assay or establish a separate full-length DNA-binding repressor mechanism. The original transfer therefore remains source-specific UNDECIDED, without denying FOXC1’s inhibitory region or transferring inhibition of FOXC1 by a partner onto FOXC1 itself. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: FOXC1 associates with chromatin while regulating selected genes. Reason: The inherited TFClass assignment is consistent with endogenous FOXC1 promoter ChIP in PMID:17993506. This supports transient regulatory chromatin association, not constitutive incorporation into every nucleosome or a general chromatin-assembly function. The classification and primary target assay remain distinct evidence sources. |
| GO:0000792 heterochromatin | IDA PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | KEEP AS NON CORE | Summary: FOXC1 can accumulate in HP1alpha-rich nuclear regions under partner-dependent inhibition. Reason: PMID:15684392 separates retained FOXC1 DNA binding from partner-dependent inhibition of its reporter output. FOXC1 remains nuclear in FLNA-deficient M2 and FLNA-restored A7 cells, while A7 cells show increased HP1alpha-region overlap. FLNA/PBX1-dependent attenuation is inhibition of FOXC1, not evidence that FOXC1 itself represses the partner. The heterochromatin-associated localization is conditional on the studied melanoma-cell/FLNA setting. Retain that pool without presenting it as the universal location of active FOXC1 or evidence that FOXC1 catalyzes heterochromatin assembly. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:17210863 Analyses of a novel L130F missense mutation in FOXC1. | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: PMID:17210863 compares human WT and patient L130F constructs using COS-7 immunofluorescence and normalized extract EMSA, and a HeLa six-site reporter. WT is nuclear, binds the tested site and activates the reporter; mutant defects are not WT absences. Structural interpretation used a homology model. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:19279310 Severe molecular defects of a novel FOXC1 W152G mutation res... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The authentic abstract of PMID:19279310 reports W152G construct defects in localization, folding, DNA binding and reporter activity. Exact hosts and full controls were unavailable. Independent original WT experiments support the gene-level function; mutant cytoplasmic aggregation must not be assigned to normal FOXC1. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:25786029 Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma:... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: PMID:25786029 assays human FOXC1 constructs in HEK293T cells, including a human CXCR4 promoter reporter containing a FOX element, nuclear-extract EMSA with competitor and nuclear imaging. WT activity is distinguished from I126S defects; these readouts do not establish every endogenous target. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:27804176 Comparison of Bioinformatics Prediction, Molecular Modeling,... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The authentic abstract of PMID:27804176 reports functional testing of human H128R, C135Y, M161V and T368N variants against WT, with different effects on binding, activity, localization and stability. Full Methods/hosts/controls were unavailable. Established WT functions can be retained without claiming source-specific assay replay or equivalent effects of every variant. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0000976 transcription cis-regulatory region binding | ISS GO_REF:0000024 | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IDA PMID:7957066 Cloning and characterization of seven human forkhead protein... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The selected original Methods/Results of PMID:7957066 assay human FREAC3/FOXC1 forkhead-domain GST fusions expressed in bacteria, using site selection, footprinting and circular permutation with controls. These establish selective DNA binding and bending for the tested domain. Full-length activation was described as work in preparation, and nuclear localization was not directly assayed. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: FOXC1 binds defined cis-regulatory DNA recognition sites. Reason: The actual PAINT target path and original IBD record support this ancestral assertion, with an exact 553-aa human sequence match. The source is a curator-placed ancestral node, not a pairwise donor-count argument. The original donor/date snapshot is preserved even where the current tree projection differs. Sequence-selective regulatory DNA recognition is part of its core transcriptional mechanism, independently supported by the human construct and promoter studies. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: FOXC1 binds defined cis-regulatory DNA recognition sites. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. Sequence-selective regulatory DNA recognition is part of its core transcriptional mechanism, independently supported by the human construct and promoter studies. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The actual PAINT target path and original IBD record support this ancestral assertion, with an exact 553-aa human sequence match. The source is a curator-placed ancestral node, not a pairwise donor-count argument. The original donor/date snapshot is preserved even where the current tree projection differs. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The original ISA GO_REF:0000113 assertion is a TFClass3.3.1 classification; it does not list mouse Foxc1 as its source. Independent human motif-binding and reporter studies support the TF activity. GO:0000981 is a valid general class but broader than the retained GO:0001228 activator activity in the well-established human activation setting. This specificity distinction does not assert absence of every possible repressive context. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:17993506 FOXC1 is required for cell viability and resistance to oxida... | ACCEPT | Summary: FOXC1 activates transcription from selected Pol-II promoters. Reason: PMID:17993506 combines an engineered inducible fusion for discovery with endogenous FOXC1 ChIP at the human FOXO1 promoter, promoter-responsive luciferase and FOXC1-knockdown effects on FOXO1 in human ocular cells. A promoter deletion removes a region containing three candidate sites; it is not a single-site point-mutation test. The fusion is not a natural product. This direction is supported by WT reporter activation and target-promoter experiments. Where present, the original FOXO1 input extension identifies the target gene and does not assert a protein interaction. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: FOXC1 activates transcription from selected Pol-II promoters. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. This direction is supported by WT reporter activation and target-promoter experiments. Where present, the original FOXO1 input extension identifies the target gene and does not assert a protein interaction. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: FOXC1 activates transcription from selected Pol-II promoters. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. This direction is supported by WT reporter activation and target-promoter experiments. Where present, the original FOXO1 input extension identifies the target gene and does not assert a protein interaction. |
| GO:0001654 eye development | IDA PMID:9792859 Mutations of the forkhead/winged-helix gene, FKHL7, in patie... | KEEP AS NON CORE | Summary: FOXC1 variation is associated with abnormal anterior-eye development. Reason: PMID:9792859 reports human family and sporadic anterior-segment cases carrying FKHL7/FOXC1 variants, with murine expression as corroboration. The accessible original abstract supports the developmental association but does not expose every clinical or functional assay. Eye development is an important physiological context of transcriptional regulation, not a separate molecular activity; no all-product or cell-autonomous mechanism is inferred. |
| GO:0001657 ureteric bud development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc factors support ureteric-bud developmental organization. Reason: The donor identities are mouse Foxc1 Q61572 and Foxc2 Q61850. PMID:10704385 explicitly reports Foxc1-null kidney/ureteric-bud abnormalities and altered Gdnf distribution, as well as a Foxc1/Foxc2 compound-dosage phenotype. This provides a relevant renal developmental context even for the paralog-derived row; it is not a wrong-paralog conclusion. Exact Methods were unavailable, so no direct Gdnf-promoter mechanism or isolated human assay is claimed. |
| GO:0001657 ureteric bud development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc factors support ureteric-bud developmental organization. Reason: The donor identities are mouse Foxc1 Q61572 and Foxc2 Q61850. PMID:10704385 explicitly reports Foxc1-null kidney/ureteric-bud abnormalities and altered Gdnf distribution, as well as a Foxc1/Foxc2 compound-dosage phenotype. This provides a relevant renal developmental context even for the paralog-derived row; it is not a wrong-paralog conclusion. Exact Methods were unavailable, so no direct Gdnf-promoter mechanism or isolated human assay is claimed. |
| GO:0001756 somitogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: FOXC1 is associated with somite developmental patterning. Reason: The mouse Foxc1 transfer is consistent with the actual compound Foxc1/Foxc2 developmental study in PMID:11562355, which shows dosage-dependent somitogenesis phenotypes. It remains a developmental application of a transcription factor, not an independently assayed human somite activity. Combined-mutant and possible secondary vascular effects are not generalized to every FOXC1 context. |
| GO:0001822 kidney development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc factors contribute to renal development. Reason: The original source is mouse Foxc1 Q61572. PMID:10704385 explicitly reports renal abnormalities in Foxc1 homozygous mutants and combined Foxc1/Foxc2 dosage effects. Retain this renal developmental context with original-abstract access limits, without inventing direct target occupancy or a human construct assay. The distinct Foxc2 Q61850 transfer is preserved in its own source row. |
| GO:0001822 kidney development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc factors contribute to renal development. Reason: PMID:10704385 directly reports renal abnormalities of mouse Foxc1 mutants and combined Foxc1/Foxc2 dosage effects. Thus the Q61850 Foxc2 donor row is not dismissed merely because the donor is a paralog; the same source includes Foxc1. Preserve the renal process as a contextual transfer, with original-abstract access limits and no invented direct target or human construct assay. |
| GO:0001958 endochondral ossification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 supports endochondral bone formation in the studied developmental setting. Reason: The authentic PMID:25808752 abstract reports delayed endochondral ossification after mouse Foxc1 loss and functional cooperation with Gli2/Ihh transcription. Full original Methods were not recovered. This supports a skeletal developmental context, without importing purified interaction or promoter-assay details from the separate human cancer study or treating dominant-negative reagents as natural products. |
| GO:0001958 endochondral ossification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 supports endochondral bone formation in the studied developmental setting. Reason: The authentic PMID:25808752 abstract reports delayed endochondral ossification after mouse Foxc1 loss and functional cooperation with Gli2/Ihh transcription. Full original Methods were not recovered. This supports a skeletal developmental context, without importing purified interaction or promoter-assay details from the separate human cancer study or treating dominant-negative reagents as natural products. |
| GO:0003677 DNA binding | IDA PMID:11179011 Analyses of the effects that disease-causing missense mutati... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: PMID:11179011 tested human FOXC1 expression constructs in COS-7 cells for nuclear localization and cell-extract DNA binding, and in HeLa cells with a six-site thymidine-kinase reporter. WT activity was separated from patient-variant defects; the EMSA was not a purified-protein affinity measurement. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0003677 DNA binding | IDA PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: PMID:15684392 separates retained FOXC1 DNA binding from partner-dependent inhibition of its reporter output. FOXC1 remains nuclear in FLNA-deficient M2 and FLNA-restored A7 cells, while A7 cells show increased HP1alpha-region overlap. FLNA/PBX1-dependent attenuation is inhibition of FOXC1, not evidence that FOXC1 itself represses the partner. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0003677 DNA binding | IDA PMID:7957066 Cloning and characterization of seven human forkhead protein... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The selected original Methods/Results of PMID:7957066 assay human FREAC3/FOXC1 forkhead-domain GST fusions expressed in bacteria, using site selection, footprinting and circular permutation with controls. These establish selective DNA binding and bending for the tested domain. Full-length activation was described as work in preparation, and nuclear localization was not directly assayed. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:11179011 Analyses of the effects that disease-causing missense mutati... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: PMID:11179011 tested human FOXC1 expression constructs in COS-7 cells for nuclear localization and cell-extract DNA binding, and in HeLa cells with a six-site thymidine-kinase reporter. WT activity was separated from patient-variant defects; the EMSA was not a purified-protein affinity measurement. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:11782474 FOXC1 transcriptional regulation is mediated by N- and C-ter... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: PMID:11782474 tested the human 553-aa protein and engineered deletions. WT activated a six-site reporter in HeLa cells; deleting N- or C-terminal activation regions reduced output while DNA binding could remain. COS-7 fragment/localization experiments identified nuclear-targeting contributions. Engineered fragments are not natural products. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:14506133 Structural and functional analyses of disease-causing missen... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The authentic abstract of PMID:14506133 reports functional characterization of five human patient variants, including localization, DNA-binding and transactivation defects. Exact assay hosts, controls and bending measurements were not recovered; independent original WT studies provide corroboration without converting that corroboration into a full read of this source. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:14578375 Identification and analysis of a novel mutation in the FOXC1... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: Selected original Methods/Results of PMID:14578375 compare human WT, patient L86F and engineered L86P constructs. WT was nuclear in COS-7 cells and bound the selected site in normalized cell extracts; WT strongly activated a six-site reporter. Mutant loss or mislocalization does not negate WT function or identify a natural isoform. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:15277473 The wing 2 region of the FOXC1 forkhead domain is necessary ... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: PMID:15277473 compares WT human FOXC1 with G165R, R169P and M161K constructs. WT and all tested mutants were predominantly nuclear in COS-7 cells; normalized cell-extract DNA binding and six-site reporter activation were separable, with G165R retaining WT-like binding despite reduced activation. These are construct assays, not all-endogenous-target measurements. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:15299087 Essential structural and functional determinants within the ... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The selected original Methods/Results of PMID:15299087 separate COS-7 localization and normalized extract EMSA from HeLa six-site reporter assays. WT binds and activates; engineered charge variants distinguish sequence recognition, localization and activation. The paper explicitly leaves native higher-order chromatin mechanisms unresolved. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: PMID:15684392 separates retained FOXC1 DNA binding from partner-dependent inhibition of its reporter output. FOXC1 remains nuclear in FLNA-deficient M2 and FLNA-restored A7 cells, while A7 cells show increased HP1alpha-region overlap. FLNA/PBX1-dependent attenuation is inhibition of FOXC1, not evidence that FOXC1 itself represses the partner. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:27804176 Comparison of Bioinformatics Prediction, Molecular Modeling,... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The authentic abstract of PMID:27804176 reports functional testing of human H128R, C135Y, M161V and T368N variants against WT, with different effects on binding, activity, localization and stability. Full Methods/hosts/controls were unavailable. Established WT functions can be retained without claiming source-specific assay replay or equivalent effects of every variant. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:14578375 Identification and analysis of a novel mutation in the FOXC1... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: Selected original Methods/Results of PMID:14578375 compare human WT, patient L86F and engineered L86P constructs. WT was nuclear in COS-7 cells and bound the selected site in normalized cell extracts; WT strongly activated a six-site reporter. Mutant loss or mislocalization does not negate WT function or identify a natural isoform. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:16449236 Functional interactions between FOXC1 and PITX2 underlie the... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: PMID:16449236 uses transfected FOXC1 and PITX2A, with co-immunoprecipitation, nuclear colocalization and a HeLa transcription reporter. PITX2A attenuates FOXC1 activation; the reverse effect was small. Bacterial bait plus mammalian extract is not a two-purified-protein affinity assay, and PITX2A is the partner product. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:17210863 Analyses of a novel L130F missense mutation in FOXC1. | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: PMID:17210863 compares human WT and patient L130F constructs using COS-7 immunofluorescence and normalized extract EMSA, and a HeLa six-site reporter. WT is nuclear, binds the tested site and activates the reporter; mutant defects are not WT absences. Structural interpretation used a homology model. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:19279310 Severe molecular defects of a novel FOXC1 W152G mutation res... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: The authentic abstract of PMID:19279310 reports W152G construct defects in localization, folding, DNA binding and reporter activity. Exact hosts and full controls were unavailable. Independent original WT experiments support the gene-level function; mutant cytoplasmic aggregation must not be assigned to normal FOXC1. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:19793056 Characterization of a novel FOXC1 mutation, P297S, identifie... | UNDECIDED | Summary: The source-specific functional assay remains unresolved. Reason: FOXC1’s nuclear location, DNA-binding transcription-factor activity and positive transcriptional regulation are established by other retained studies and accepted elsewhere in this review. The reviewed UniProt record also attributes relevant function and nuclear localization to PMID:19793056. These curated attributions are acknowledged as corroboration. However, only the verified title and identifier of the P297S letter were recovered; its abstract and functional Methods/Results remain inaccessible. UNDECIDED records that source-specific limit and does not negate the established gene-level function, allege misattribution or convert missing access into contrary experimental evidence. |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:25786029 Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma:... | TOO GENERAL | Summary: FOXC1 functions as a sequence-selective transcription factor. Reason: PMID:25786029 assays human FOXC1 constructs in HEK293T cells, including a human CXCR4 promoter reporter containing a FOX element, nuclear-extract EMSA with competitor and nuclear imaging. WT activity is distinguished from I126S defects; these readouts do not establish every endogenous target. The general TF class is valid but less precise than the retained GO:0001228 transcription-activator activity for the well-established human activation function. This specificity decision does not reinterpret partner-mediated inhibition as intrinsic FOXC1 repression or assert that no repressive context can exist. |
| GO:0005515 protein binding | IPI PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | MODIFY | Summary: FOXC1 associates with filamin A in human cell extracts; filamin binding is the supported specific class. Reason: PMID:15684392 identified FLNA after recombinant full-length FOXC1 affinity capture from human nonpigmented ciliary epithelial cell lysate and confirmed association by co-immunoprecipitation in transfected HeLa cells. Endogenous co-immunoprecipitation in mouse C2C12 cells is separate corroboration. The official definition of GO:0031005 includes filamin A, so filamin binding is more informative than generic protein binding for this source and partner. These lysate-based assays and deletion mapping do not establish a two-purified-protein equilibrium interaction or equivalent binding by every engineered fragment. Proposed replacements: filamin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | MODIFY | Summary: FOXC1 associates with the DNA-binding transcription factor PBX1 in the tested nuclear context. Reason: PMID:15684392 first detected PBX1 in a FOXC1-associated transcription-factor screen, then confirmed FOXC1-PBX1 co-immunoprecipitation in transfected HeLa cells and at endogenous levels in A7 nuclear extracts. PBX1 is an established sequence-specific RNA polymerase II transcription factor, supporting GO:0061629 as the specific binding class. The reporter experiments identify PBX1a-mediated inhibition of FOXC1 activity; they do not establish FOXC1 as the transcriptional inhibitor or demonstrate identical interactions for all PBX1 products. Co-immunoprecipitation establishes association in these conditions without requiring a claim of purified binary contact. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | MODIFY | Summary: The positive FOXC1–NFIA screen association supports a transcription-factor-binding refinement at the reported assay scope. Reason: PMID:15684392 identifies NF1-A, corresponding to the verified human NFIA protein Q12857, as a positive candidate in the transcription-factor interaction array. The assay combined recombinant His-tagged FOXC1, M2/A7 nuclear extracts and transcription-factor DNA probes, followed by nickel capture and probe detection. NFIA is a sequence-specific RNA polymerase II DNA-binding transcription factor, so GO:0061629 describes the established partner class more informatively than generic protein binding. This refinement retains the curated association at the screen’s scope: it does not claim isolated two-protein contact, the separate PBX1 co-immunoprecipitation result, a native stoichiometric complex or transcriptional inhibition by NFIA. The original paper explicitly reports that NF1-A did not impair FOXC1 transcriptional activity. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16449236 Functional interactions between FOXC1 and PITX2 underlie the... | MODIFY | Summary: FOXC1 associates with the tested PITX2A partner in the nucleus. Reason: PMID:16449236 reports reciprocal co-immunoprecipitation of FOXC1 and PITX2A in COS-7 cells and pulldowns combining a bacterially produced bait with mammalian extracts. Exact positive IntAct records retain both the co-immunoprecipitation and pulldown experiments; the colocalization records are separate observations. PITX2 is an established RNA polymerase II DNA-binding transcription factor, so GO:0061629 is an evidence-backed refinement. The tested partner PITX2A is the original Q99697-3 record, not a FOXC1 isoform; retain the original nuclear extension. The assays do not establish two-purified-protein binding or equivalent behavior of every PITX2 product. PITX2A attenuation of a FOXC1-responsive reporter must not be inverted into a FOXC1 transcriptional-repressor claim. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18676636 Human p32 is a novel FOXC1-interacting protein that regulate... | KEEP AS NON CORE | Summary: The source reports FOXC1 interaction with p32/C1QBP and modulation of FOXC1 reporter activity. Reason: The authentic abstract of PMID:18676636 explicitly identifies human p32/C1QBP in a FOXC1 yeast two-hybrid screen and reports confirmation by Ni-pulldown and immunoprecipitation, forkhead-domain mapping, partial nuclear colocalization and dose-dependent suppression of a FOXC1 reporter without altered FOXC1 DNA-binding affinity. These target-specific observations support retaining the curated association as non-core. The full Methods and Results were not inspected, so exact constructs and an isolated two-protein mechanism remain unverified. The context does not establish a more specific receptor-binding or catalytic function of FOXC1, and p32-mediated reporter suppression is not evidence that FOXC1 is the inhibitory entity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | KEEP AS NON CORE | Summary: Exact curated records support FOXC1 association with the HIV-1 retropepsin fragment. Reason: For PMID:22190034, IntAct contains three exact positive Q12948-Q9Q2G4 records: two expanded affinity-associated records and a separate pulldown record EBI-6178677/IM-17346-96 linked to Figure S11a in HEK293T cells. The original partner Q9Q2G4 is an HIV-1 retropepsin fragment. This supports retaining the source-specific association as non-core while preserving the viral partner and assay context. The primary study Methods were inspected through a retained source consultation, but the supplementary figure and workbook were not inspected. The records do not establish direct molecular contact, FOXC1 cleavage, protease inhibition or a distinct FOXC1 viral-process function; none is inferred from the partner name. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | UNDECIDED | Summary: The FOXC1-PBX1 pair is plausible, but this proteomics source remains unverified at the pair level. Reason: PMID:25609649 profiled SFB-tagged transcription-factor complexes from soluble and nuclease-released chromatin fractions in HEK293T cells. Its exact FOXC1-PBX1 high-confidence interacting-protein row in Supplementary Table S6 was not recovered: attempted spreadsheet access returned an HTML challenge, and the queried IntAct responses did not supply an exact source-specific pair. Independent FOXC1-PBX1 experiments in PMID:15684392 corroborate that the proteins can associate but do not verify this distinct proteomics context. Retain UNDECIDED for this source without declaring the curated interaction false or transferring another paper's validation. |
| GO:0005515 protein binding | IPI PMID:26565916 FOXC1 Activates Smoothened-Independent Hedgehog Signaling in... | MODIFY | Summary: FOXC1 binds the DNA-binding transcription factor GLI2 in cellular and purified-protein assays. Reason: PMID:26565916 reports FOXC1-GLI2 co-immunoprecipitation in human cell models, including endogenous proteins in BT549 cells, and reciprocal pulldown with bacterially produced His-FOXC1 and GST-GLI2. These source-specific assays and the established RNA polymerase II DNA-binding transcription-factor role of GLI2 support refinement to GO:0061629. Human GLI2 fragment mapping and mouse Gli2 deletion experiments are distinct constructs; the findings should not be generalized to every natural GLI2 product or processed form. Proximity measurements and computational modeling do not constitute a resolved complex structure. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005634 nucleus | EXP PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:15684392 separates retained FOXC1 DNA binding from partner-dependent inhibition of its reporter output. FOXC1 remains nuclear in FLNA-deficient M2 and FLNA-restored A7 cells, while A7 cells show increased HP1alpha-region overlap. FLNA/PBX1-dependent attenuation is inhibition of FOXC1, not evidence that FOXC1 itself represses the partner. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: FOXC1 is a nuclear transcription factor. Reason: The positive PAINT nuclear-localization assertion is on the verified human target path with the exact 553-aa sequence. Independent human-cell immunolocalization and endogenous tissue studies support nuclear residence. The original IBA source list is preserved without interpreting self donors as circular evidence. |
| GO:0005634 nucleus | IC PMID:7957066 Cloning and characterization of seven human forkhead protein... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: The selected original Methods/Results of PMID:7957066 assay human FREAC3/FOXC1 forkhead-domain GST fusions expressed in bacteria, using site selection, footprinting and circular permutation with controls. These establish selective DNA binding and bending for the tested domain. Full-length activation was described as work in preparation, and nuclear localization was not directly assayed. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. The inherited IC assertion is supported holistically by these independent localization studies, without claiming immunolocalization in the domain-binding paper. |
| GO:0005634 nucleus | IDA PMID:11179011 Analyses of the effects that disease-causing missense mutati... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:11179011 tested human FOXC1 expression constructs in COS-7 cells for nuclear localization and cell-extract DNA binding, and in HeLa cells with a six-site thymidine-kinase reporter. WT activity was separated from patient-variant defects; the EMSA was not a purified-protein affinity measurement. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:11562355 The murine winged helix transcription factors, Foxc1 and Fox... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: The selected original Results of PMID:11562355 directly show nuclear immunostaining in cultured human aortic smooth-muscle cells, separately from mouse tissue and compound-mutant developmental experiments. Antibody-generation details were delegated to an accompanying paper and were not independently replayed. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:11782474 FOXC1 transcriptional regulation is mediated by N- and C-ter... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:11782474 tested the human 553-aa protein and engineered deletions. WT activated a six-site reporter in HeLa cells; deleting N- or C-terminal activation regions reduced output while DNA binding could remain. COS-7 fragment/localization experiments identified nuclear-targeting contributions. Engineered fragments are not natural products. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:14506133 Structural and functional analyses of disease-causing missen... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: The authentic abstract of PMID:14506133 reports functional characterization of five human patient variants, including localization, DNA-binding and transactivation defects. Exact assay hosts, controls and bending measurements were not recovered; independent original WT studies provide corroboration without converting that corroboration into a full read of this source. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:14578375 Identification and analysis of a novel mutation in the FOXC1... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: Selected original Methods/Results of PMID:14578375 compare human WT, patient L86F and engineered L86P constructs. WT was nuclear in COS-7 cells and bound the selected site in normalized cell extracts; WT strongly activated a six-site reporter. Mutant loss or mislocalization does not negate WT function or identify a natural isoform. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:15277473 The wing 2 region of the FOXC1 forkhead domain is necessary ... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:15277473 compares WT human FOXC1 with G165R, R169P and M161K constructs. WT and all tested mutants were predominantly nuclear in COS-7 cells; normalized cell-extract DNA binding and six-site reporter activation were separable, with G165R retaining WT-like binding despite reduced activation. These are construct assays, not all-endogenous-target measurements. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:15299087 Essential structural and functional determinants within the ... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: The selected original Methods/Results of PMID:15299087 separate COS-7 localization and normalized extract EMSA from HeLa six-site reporter assays. WT binds and activates; engineered charge variants distinguish sequence recognition, localization and activation. The paper explicitly leaves native higher-order chromatin mechanisms unresolved. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:16449236 Functional interactions between FOXC1 and PITX2 underlie the... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:16449236 uses transfected FOXC1 and PITX2A, with co-immunoprecipitation, nuclear colocalization and a HeLa transcription reporter. PITX2A attenuates FOXC1 activation; the reverse effect was small. Bacterial bait plus mammalian extract is not a two-purified-protein affinity assay, and PITX2A is the partner product. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:17210863 Analyses of a novel L130F missense mutation in FOXC1. | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:17210863 compares human WT and patient L130F constructs using COS-7 immunofluorescence and normalized extract EMSA, and a HeLa six-site reporter. WT is nuclear, binds the tested site and activates the reporter; mutant defects are not WT absences. Structural interpretation used a homology model. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:19279310 Severe molecular defects of a novel FOXC1 W152G mutation res... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: The authentic abstract of PMID:19279310 reports W152G construct defects in localization, folding, DNA binding and reporter activity. Exact hosts and full controls were unavailable. Independent original WT experiments support the gene-level function; mutant cytoplasmic aggregation must not be assigned to normal FOXC1. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:19793056 Characterization of a novel FOXC1 mutation, P297S, identifie... | UNDECIDED | Summary: The source-specific functional assay remains unresolved. Reason: FOXC1’s nuclear location, DNA-binding transcription-factor activity and positive transcriptional regulation are established by other retained studies and accepted elsewhere in this review. The reviewed UniProt record also attributes relevant function and nuclear localization to PMID:19793056. These curated attributions are acknowledged as corroboration. However, only the verified title and identifier of the P297S letter were recovered; its abstract and functional Methods/Results remain inaccessible. UNDECIDED records that source-specific limit and does not negate the established gene-level function, allege misattribution or convert missing access into contrary experimental evidence. |
| GO:0005634 nucleus | IDA PMID:20406990 FOXC1 is a potential prognostic biomarker with functional si... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: Selected indexed original Methods/Results of PMID:20406990 distinguish full-length human FOXC1 expression in human breast-cancer cells, mouse 4T1 knockdown and human nuclear immunohistochemistry. Endogenous nuclear staining was independently assessed in human tumors. Behavioral assays and marker changes do not establish direct target-promoter occupancy. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IDA PMID:25786029 Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma:... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:25786029 assays human FOXC1 constructs in HEK293T cells, including a human CXCR4 promoter reporter containing a FOX element, nuclear-extract EMSA with competitor and nuclear imaging. WT activity is distinguished from I126S defects; these readouts do not establish every endogenous target. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:26565916 FOXC1 Activates Smoothened-Independent Hedgehog Signaling in... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: PMID:26565916 supports human FOXC1–GLI2 association with reciprocal bacterially purified pull-downs and endogenous BT549 co-immunoprecipitation. GLI2 promoter occupancy and reporter output rise with FOXC1 in cancer-cell assays. The proposed allosteric opening is a model; it is not a solved structure or a universal partner mechanism. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:27804176 Comparison of Bioinformatics Prediction, Molecular Modeling,... | ACCEPT | Summary: FOXC1 is localized to the nucleus. Reason: The authentic abstract of PMID:27804176 reports functional testing of human H128R, C135Y, M161V and T368N variants against WT, with different effects on binding, activity, localization and stability. Full Methods/hosts/controls were unavailable. Established WT functions can be retained without claiming source-specific assay replay or equivalent effects of every variant. Nuclear localization is concordant with the transcriptional function. WT localization is distinguished from disease-variant mislocalization and from context-dependent heterochromatin sequestration. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: FOXC1 has a conserved nuclear localization. Reason: The original UniProt/Ensembl mouse mapping and subcellular-location source are retained. Independent human nuclear staining and WT construct experiments establish the target localization, without transferring disease-mutant aggregates or assuming identical localization of every engineered truncation. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: A nucleoplasmic FOXC1 pool is reported by curated cell-localization evidence. Reason: Current official HPA textual metadata reports supported main nucleoplasm localization with antibody HPA040670: A-431 and U2OS are listed with nucleoplasm, and U-251MG with nucleoplasm plus cytosol. This positively corroborates the inherited nucleoplasm assertion as a contextual subnuclear pool. The antibody images, specificity controls and historical GOA-version assignment were not independently replayed. The nucleoplasmic pool is compatible with the separately observed chromatin-associated and conditional heterochromatin pools. |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:11782474 FOXC1 transcriptional regulation is mediated by N- and C-ter... | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: PMID:11782474 tested the human 553-aa protein and engineered deletions. WT activated a six-site reporter in HeLa cells; deleting N- or C-terminal activation regions reduced output while DNA binding could remain. COS-7 fragment/localization experiments identified nuclear-targeting contributions. Engineered fragments are not natural products. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:14506133 Structural and functional analyses of disease-causing missen... | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: The authentic abstract of PMID:14506133 reports functional characterization of five human patient variants, including localization, DNA-binding and transactivation defects. Exact assay hosts, controls and bending measurements were not recovered; independent original WT studies provide corroboration without converting that corroboration into a full read of this source. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:15299087 Essential structural and functional determinants within the ... | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: The selected original Methods/Results of PMID:15299087 separate COS-7 localization and normalized extract EMSA from HeLa six-site reporter assays. WT binds and activates; engineered charge variants distinguish sequence recognition, localization and activation. The paper explicitly leaves native higher-order chromatin mechanisms unresolved. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: PMID:15684392 separates retained FOXC1 DNA binding from partner-dependent inhibition of its reporter output. FOXC1 remains nuclear in FLNA-deficient M2 and FLNA-restored A7 cells, while A7 cells show increased HP1alpha-region overlap. FLNA/PBX1-dependent attenuation is inhibition of FOXC1, not evidence that FOXC1 itself represses the partner. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: The inherited domain/family classification is consistent with the human FOXC1 protein and independently demonstrated transcriptional function. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: The actual PAINT target path and original IBD record support this ancestral assertion, with an exact 553-aa human sequence match. The source is a curator-placed ancestral node, not a pairwise donor-count argument. The original donor/date snapshot is preserved even where the current tree projection differs. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0007507 heart development | IDA PMID:10474162 Expression of the Mf1 gene in developing mouse hearts: impli... | KEEP AS NON CORE | Summary: FOXC1 contributes to cardiac developmental contexts. Reason: PMID:10474162 combines spatial Mf1 expression in mouse embryonic valves and atrial-septal territories with human FOXC1-associated atrial-septal or mitral-valve defects. Only the authentic abstract and indexed original first page were accessible. Expression is not itself a perturbation assay, and the study explicitly distinguishes the interventricular septum. Retain the existing developmental assertion with those limits rather than extrapolating a direct downstream cardiac mechanism. |
| GO:0008283 cell population proliferation | IDA PMID:20406990 FOXC1 is a potential prognostic biomarker with functional si... | KEEP AS NON CORE | Summary: FOXC1 can promote proliferation in the studied breast-cancer cells. Reason: Selected indexed original Methods/Results of PMID:20406990 distinguish full-length human FOXC1 expression in human breast-cancer cells, mouse 4T1 knockdown and human nuclear immunohistochemistry. Endogenous nuclear staining was independently assessed in human tumors. Behavioral assays and marker changes do not establish direct target-promoter occupancy. Increased proliferation is a context-specific output of the transcriptional program. The opposite growth-regulatory setting in PMID:12408963 is not erased; neither study establishes a universal direction across cell types. |
| GO:0008283 cell population proliferation | IMP PMID:22991501 FOXC1 contributes to microvascular invasion in primary hepat... | KEEP AS NON CORE | Summary: FOXC1 supports proliferation in the tested liver-cancer cell models. Reason: Selected original Methods/Results of PMID:22991501 report FOXC1 perturbation in the paper-described cancer lines, with knockdown-associated G1 arrest rather than an apoptosis increase. The proliferation effect is specific to the tested cellular setting; its direction need not be universal across tissues. |
| GO:0008301 DNA binding, bending | IDA PMID:14506133 Structural and functional analyses of disease-causing missen... | UNDECIDED | Summary: The DNA-bending assay attributed to PMID:14506133 remains unverified. Reason: The reviewed UniProt record explicitly attributes FOXC1 DNA bending to PMID:14506133 and PMID:7957066. This curated attribution is positive corroboration, and the independently read PMID:7957066 experiment establishes bending by a human FREAC3/FOXC1 forkhead-domain fusion. The authentic PMID:14506133 abstract describes patient-variant effects on DNA binding, localization and transactivation, but the original bending Results, constructs and controls for that paper were not recovered. Retain source-specific UNDECIDED for this row without disputing FOXC1 bending, treating ordinary DNA binding as a bending assay, or claiming that the curator’s experimental assertion is false. |
| GO:0008301 DNA binding, bending | IDA PMID:7957066 Cloning and characterization of seven human forkhead protein... | KEEP AS NON CORE | Summary: The FOXC1 forkhead domain can bend bound DNA. Reason: The selected original Methods/Results of PMID:7957066 assay human FREAC3/FOXC1 forkhead-domain GST fusions expressed in bacteria, using site selection, footprinting and circular permutation with controls. These establish selective DNA binding and bending for the tested domain. Full-length activation was described as work in preparation, and nuclear localization was not directly assayed. The circular-permutation assay supports the additional bending property for the tested GST-domain construct. Retain this distinct biochemical observation without promoting a measured fragment angle into an all-full-length or in-vivo chromatin claim. |
| GO:0009653 anatomical structure morphogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FOXC1 has broad morphogenetic roles across tissues. Reason: The six-IBA target/path replay supports the inherited PAINT assertion without a donor-count penalty. Eye, cardiac, renal and skeletal contexts provide independent biological concordance. This broad developmental description is retained as non-core because it summarizes tissue applications of the transcription factor, rather than defining a second molecular function. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: FOXC1 can increase expression of selected target genes. Reason: The original mouse mapping is consistent with human FOXC1-dependent FOXO1 protein expression and promoter activation in PMID:17993506. The official GO:0010628 definition concerns mature gene-product output and is not a formal ancestor of GO:0045944 in the inspected ontology. Retain the expression-output assertion with target and cell-type limits; do not claim control of every post-transcriptional step. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IMP PMID:22991501 FOXC1 contributes to microvascular invasion in primary hepat... | KEEP AS NON CORE | Summary: FOXC1 promotes parts of an EMT-associated program in the tested cancer cells. Reason: PMID:22991501 supports perturbation-dependent changes in EMT-associated markers and behavior in the studied liver-cancer models. The response is partial rather than a uniform marker switch. Snail, Twist and TGF-beta are described upstream of FOXC1 in this setting; this does not establish the reverse regulatory direction or direct occupancy of each marker promoter. |
| GO:0014031 mesenchymal cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 supports mesenchymal niche-cell development and maintenance. Reason: The authentic PMID:24590069 abstract places Foxc1 in mesenchymal CAR niche cells: embryonic deletion decreases CAR cells and hematopoietic support while promoting marrow adipocytes. Adult-deletion findings differ. Retain the mesenchymal developmental context without assigning a hematopoietic-cell-intrinsic mechanism or claiming that inaccessible full assays were replayed. |
| GO:0014031 mesenchymal cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 supports mesenchymal niche-cell development and maintenance. Reason: The authentic PMID:24590069 abstract places Foxc1 in mesenchymal CAR niche cells: embryonic deletion decreases CAR cells and hematopoietic support while promoting marrow adipocytes. Adult-deletion findings differ. Retain the mesenchymal developmental context without assigning a hematopoietic-cell-intrinsic mechanism or claiming that inaccessible full assays were replayed. |
| GO:0016477 cell migration | IDA PMID:20406990 FOXC1 is a potential prognostic biomarker with functional si... | KEEP AS NON CORE | Summary: FOXC1 can enhance migration in the studied breast-cancer models. Reason: Selected indexed original Methods/Results of PMID:20406990 distinguish full-length human FOXC1 expression in human breast-cancer cells, mouse 4T1 knockdown and human nuclear immunohistochemistry. Endogenous nuclear staining was independently assessed in human tumors. Behavioral assays and marker changes do not establish direct target-promoter occupancy. |
| GO:0016477 cell migration | IMP PMID:22991501 FOXC1 contributes to microvascular invasion in primary hepat... | KEEP AS NON CORE | Summary: FOXC1 affects migration in the studied liver-cancer models. Reason: Selected original PMID:22991501 Results support altered migration after FOXC1 perturbation, alongside a partial EMT-associated response. This is a cellular context of transcriptional regulation, not evidence that FOXC1 directly performs the mechanical motility step or binds every implicated promoter. |
| GO:0016525 negative regulation of angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 restrains blood-vessel growth in the corneal stromal context. Reason: Actual original PMID:22171010 Results show blood-vessel growth after global or neural-crest/stromal Foxc1 loss, while endothelial deletion alone does not reproduce that corneal phenotype. Human pedigrees provide separate corroboration. Retain this context-dependent antiangiogenic role without generalizing it to all vascular or cancer settings. |
| GO:0016525 negative regulation of angiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 restrains blood-vessel growth in the corneal stromal context. Reason: Actual original PMID:22171010 Results show blood-vessel growth after global or neural-crest/stromal Foxc1 loss, while endothelial deletion alone does not reproduce that corneal phenotype. Human pedigrees provide separate corroboration. Retain this context-dependent antiangiogenic role without generalizing it to all vascular or cancer settings. |
| GO:0021549 cerebellum development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 supports cerebellar development through surrounding mesenchyme. Reason: Actual original PMID:19668217 Results place Foxc1 in mesenchyme around the cerebellum, with null/hypomorphic mouse defects and human variation corroboration. Altered mesenchymal signals and rhombic-lip/granule-layer outcomes support a non-cell-autonomous developmental role. Do not infer neuron-intrinsic FOXC1 activity or direct Atoh1 promoter binding. |
| GO:0021549 cerebellum development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 supports cerebellar development through surrounding mesenchyme. Reason: Actual original PMID:19668217 Results place Foxc1 in mesenchyme around the cerebellum, with null/hypomorphic mouse defects and human variation corroboration. Altered mesenchymal signals and rhombic-lip/granule-layer outcomes support a non-cell-autonomous developmental role. Do not infer neuron-intrinsic FOXC1 activity or direct Atoh1 promoter binding. |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FOXC1 contributes to differentiation programs in several developmental contexts. Reason: The positive PAINT ancestral placement is on the verified human target path. Human keratinocyte and mouse mesenchymal contexts support a differentiation role, but the process describes tissue-specific applications rather than an additional molecular function. It is not rejected because the IBA includes distant or self donors. |
| GO:0036438 maintenance of lens transparency | IEA GO_REF:0000107 | UNDECIDED | Summary: The transferred lens-transparency assertion is not resolved by corneal evidence. Reason: The exact mouse donor points to PMID:22171010, whose inspected original experiments concern corneal stromal avascularity and transparency. Official GO:0036438 specifically describes the ocular lens, an anatomically distinct structure. Retain the original transfer as source-specific UNDECIDED while recording the probable anatomical source defect for curator checking. The corneal findings remain supported. A corneal-development term is not selected automatically as a replacement for a transparency-maintenance assertion; the appropriate correction and any independent lens evidence require source-level adjudication. |
| GO:0036438 maintenance of lens transparency | ISS GO_REF:0000024 | UNDECIDED | Summary: The transferred lens-transparency assertion is not resolved by corneal evidence. Reason: The exact mouse donor points to PMID:22171010, whose inspected original experiments concern corneal stromal avascularity and transparency. Official GO:0036438 specifically describes the ocular lens, an anatomically distinct structure. Retain the original transfer as source-specific UNDECIDED while recording the probable anatomical source defect for curator checking. The corneal findings remain supported. A corneal-development term is not selected automatically as a replacement for a transparency-maintenance assertion; the appropriate correction and any independent lens evidence require source-level adjudication. |
| GO:0038084 vascular endothelial growth factor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 influences a VEGF-dependent corneal vascular response. Reason: In actual PMID:22171010 Results, VEGFR2 inhibition reduces injury-associated blood-vessel growth and removes the Foxc1-genotype difference, whereas the tested lymphatic effect is not significant. Matrix/MMP changes suggest altered VEGF availability. Retain the contextual pathway association without assigning receptor activity, direct MMP-promoter occupancy or a measured increase in VEGF-A abundance to FOXC1. |
| GO:0038084 vascular endothelial growth factor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 influences a VEGF-dependent corneal vascular response. Reason: In actual PMID:22171010 Results, VEGFR2 inhibition reduces injury-associated blood-vessel growth and removes the Foxc1-genotype difference, whereas the tested lymphatic effect is not significant. Matrix/MMP changes suggest altered VEGF availability. Retain the contextual pathway association without assigning receptor activity, direct MMP-promoter occupancy or a measured increase in VEGF-A abundance to FOXC1. |
| GO:0042475 odontogenesis of dentin-containing tooth | IMP PMID:12614756 A family with Axenfeld-Rieger syndrome and Peters Anomaly ca... | KEEP AS NON CORE | Summary: FOXC1 variation is linked to dental developmental abnormalities. Reason: The original PMID:12614756 abstract and section previews describe a human Phe112Ser family with Rieger-syndrome ocular/dental/facial findings and segregation analysis. The full clinical table was inaccessible. Retain the existing developmental association with that limit; it does not establish an autonomous odontoblast mechanism or a natural-product-specific function. |
| GO:0043388 positive regulation of DNA binding | IMP PMID:26565916 FOXC1 Activates Smoothened-Independent Hedgehog Signaling in... | ACCEPT | Summary: FOXC1 promotes GLI2 DNA-binding activity in the tested human breast-cancer cell models. Reason: PMID:26565916 supports FOXC1–GLI2 association with reciprocal bacterially purified pulldowns and endogenous BT549 co-immunoprecipitation. In MDA-MB-231 cells, FOXC1 increases GLI2 occupancy of the FAM38B promoter, oligonucleotide-binding readouts and GLI-site reporter output, with GLI2-dependence demonstrated by knockdown. These findings support a distinct GLI2-binding regulatory mechanism. The experimentally supported increase in GLI2 DNA binding is retained as core to that mechanism; modeled allosteric opening is not a solved structure, and these data do not establish equivalent effects on every transcription factor. Supporting Evidence: |
| GO:0043565 sequence-specific DNA binding | IDA PMID:15277473 The wing 2 region of the FOXC1 forkhead domain is necessary ... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: PMID:15277473 compares WT human FOXC1 with G165R, R169P and M161K constructs. WT and all tested mutants were predominantly nuclear in COS-7 cells; normalized cell-extract DNA binding and six-site reporter activation were separable, with G165R retaining WT-like binding despite reduced activation. These are construct assays, not all-endogenous-target measurements. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:7957066 Cloning and characterization of seven human forkhead protein... | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The selected original Methods/Results of PMID:7957066 assay human FREAC3/FOXC1 forkhead-domain GST fusions expressed in bacteria, using site selection, footprinting and circular permutation with controls. These establish selective DNA binding and bending for the tested domain. Full-length activation was described as work in preparation, and nuclear localization was not directly assayed. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: FOXC1 recognizes transcriptional cis-regulatory DNA. Reason: The inherited domain/family classification is consistent with the human FOXC1 protein and independently demonstrated transcriptional function. The underlying binding activity is valid, but this term is broader than the retained GO:0000978 cis-regulatory sequence-specific binding assertion. Official ancestry supports the specificity distinction; the original source and its experimental limits remain preserved. |
| GO:0045618 positive regulation of keratinocyte differentiation | IMP PMID:27907090 Forkhead Box C1 Regulates Human Primary Keratinocyte Termina... | KEEP AS NON CORE | Summary: FOXC1 supports late keratinocyte differentiation. Reason: Actual PMID:27907090 Methods/Results show that FOXC1 knockdown in primary human keratinocytes reduces late FLG, IVL and LOR output, with overexpression increasing corresponding mRNAs; early keratins and cell-cycle outcomes are not similarly changed. Retain this differentiation context without inferring a universal epithelial effect or direct FOXC1 occupancy at every differentiation gene. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:11237714 DSCAM, a highly conserved gene in mammals, expressed in diff... | UNDECIDED | Summary: The activation assertion cannot be verified against the cited source. Reason: The authentic PMID:11237714 metadata and abstract identify a DSCAM study in differentiating mouse brain. The original full text was inaccessible, so the precise FOXC1 experiment or source attribution cannot be checked. The independently established FOXC1 activator function does not identify the intended source for this row. Preserve the original experimental assertion and identifier with source-specific uncertainty; do not infer a wrong gene, a replacement PMID or removal from the abstract alone. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:15277473 The wing 2 region of the FOXC1 forkhead domain is necessary ... | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: PMID:15277473 compares WT human FOXC1 with G165R, R169P and M161K constructs. WT and all tested mutants were predominantly nuclear in COS-7 cells; normalized cell-extract DNA binding and six-site reporter activation were separable, with G165R retaining WT-like binding despite reduced activation. These are construct assays, not all-endogenous-target measurements. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0045893 positive regulation of DNA-templated transcription | NAS PMID:8499623 Drosophila forkhead homologues are expressed in a lineage-re... | TOO GENERAL | Summary: FOXC1 regulates transcription, with positive Pol-II output directly supported. Reason: The original PMID:8499623 identifies the human 5-3 clone, linked through accession L12143 to FOXC1, and reports cloning/expression/homology. Its Discussion treats transcriptional activation as an inference for future experiments, consistent with the inherited NAS evidence. Modern direct activation evidence is separate corroboration, not an assay in this paper. The inherited process is broader than retained GO:0045944 positive regulation of transcription by RNA polymerase II in the supported activation setting. The official hierarchy establishes this relationship; the source record is retained rather than replaced by another assay. |
| GO:0045930 negative regulation of mitotic cell cycle | IDA PMID:12408963 Identification of FOXC1 as a TGF-beta1 responsive gene and i... | KEEP AS NON CORE | Summary: FOXC1 can restrain cell-cycle progression in a TGF-beta-responsive setting. Reason: The authentic PMID:12408963 abstract describes ectopic FOXC1 restoring TGF-beta1-dependent growth inhibition and G0/G1 arrest in HeLa cells reported to lack both FOXC1 alleles. Exact Methods and controls were inaccessible. This supports a contextual negative regulation claim without contradicting distinct pro-proliferative cancer contexts or establishing a universal tumor-suppressor role. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16449236 Functional interactions between FOXC1 and PITX2 underlie the... | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: PMID:16449236 uses transfected FOXC1 and PITX2A, with co-immunoprecipitation, nuclear colocalization and a HeLa transcription reporter. PITX2A attenuates FOXC1 activation; the reverse effect was small. Bacterial bait plus mammalian extract is not a two-purified-protein affinity assay, and PITX2A is the partner product. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:17993506 FOXC1 is required for cell viability and resistance to oxida... | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: PMID:17993506 combines an engineered inducible fusion for discovery with endogenous FOXC1 ChIP at the human FOXO1 promoter, promoter-responsive luciferase and FOXC1-knockdown effects on FOXO1 in human ocular cells. A promoter deletion removes a region containing three candidate sites; it is not a single-site point-mutation test. The fusion is not a natural product. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:14578375 Identification and analysis of a novel mutation in the FOXC1... | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: Selected original Methods/Results of PMID:14578375 compare human WT, patient L86F and engineered L86P constructs. WT was nuclear in COS-7 cells and bound the selected site in normalized cell extracts; WT strongly activated a six-site reporter. Mutant loss or mislocalization does not negate WT function or identify a natural isoform. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:16492674 Regulation of FOXC1 stability and transcriptional activity b... | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: Selected original Methods/Results of PMID:16492674 show EGF-dependent stabilization and reporter activation of FOXC1 in HeLa cells, with S272A and MAPK-inhibitor comparisons. Endogenous protein decay was measured separately. This is EGF/MAPK regulation of FOXC1 abundance and output, not FOXC1 kinase activity or proof that FOXC1 activates MAPK. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17210863 Analyses of a novel L130F missense mutation in FOXC1. | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: PMID:17210863 compares human WT and patient L130F constructs using COS-7 immunofluorescence and normalized extract EMSA, and a HeLa six-site reporter. WT is nuclear, binds the tested site and activates the reporter; mutant defects are not WT absences. Structural interpretation used a homology model. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:19279310 Severe molecular defects of a novel FOXC1 W152G mutation res... | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: The authentic abstract of PMID:19279310 reports W152G construct defects in localization, folding, DNA binding and reporter activity. Exact hosts and full controls were unavailable. Independent original WT experiments support the gene-level function; mutant cytoplasmic aggregation must not be assigned to normal FOXC1. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:19793056 Characterization of a novel FOXC1 mutation, P297S, identifie... | UNDECIDED | Summary: The source-specific functional assay remains unresolved. Reason: FOXC1’s nuclear location, DNA-binding transcription-factor activity and positive transcriptional regulation are established by other retained studies and accepted elsewhere in this review. The reviewed UniProt record also attributes relevant function and nuclear localization to PMID:19793056. These curated attributions are acknowledged as corroboration. However, only the verified title and identifier of the P297S letter were recovered; its abstract and functional Methods/Results remain inaccessible. UNDECIDED records that source-specific limit and does not negate the established gene-level function, allege misattribution or convert missing access into contrary experimental evidence. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:25786029 Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma:... | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: PMID:25786029 assays human FOXC1 constructs in HEK293T cells, including a human CXCR4 promoter reporter containing a FOX element, nuclear-extract EMSA with competitor and nuclear imaging. WT activity is distinguished from I126S defects; these readouts do not establish every endogenous target. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:27804176 Comparison of Bioinformatics Prediction, Molecular Modeling,... | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: The authentic abstract of PMID:27804176 reports functional testing of human H128R, C135Y, M161V and T368N variants against WT, with different effects on binding, activity, localization and stability. Full Methods/hosts/controls were unavailable. Established WT functions can be retained without claiming source-specific assay replay or equivalent effects of every variant. The positive transcriptional output is consistent with the core activator function. Construct, cell-type and source-access limitations remain explicit; this does not assign every downstream cellular phenotype to direct promoter binding. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:27907090 Forkhead Box C1 Regulates Human Primary Keratinocyte Termina... | ACCEPT | Summary: FOXC1 positively regulates transcriptional output during late keratinocyte differentiation. Reason: Actual PMID:27907090 perturbation experiments in primary human keratinocytes support increased target-gene output downstream of FOXC1. The reported ChIP examines KLF4/ZNF750 on the FOXC1 promoter, not FOXC1 occupancy at GRHL3. Retain positive transcriptional regulation as part of the activator function while explicitly distinguishing output evidence from direct target-occupancy proof. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: FOXC1 positively regulates Pol-II transcription in the tested cellular setting. Reason: The original ISS GO_REF:0000024 assertion is a sequence-similarity transfer from mouse Foxc1 Q61572. Independent human FOXC1 WT reporter and target-promoter experiments corroborate positive Pol-II transcriptional regulation. Retain the core activation function while distinguishing this human corroboration from exact replay of the original mouse donor assay. |
| GO:0048341 paraxial mesoderm formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: FOXC1 participates in paraxial-mesoderm developmental patterning. Reason: The original mouse Foxc1 mapping is biologically consistent with the Foxc1/Foxc2 mesoderm/somite phenotypes in PMID:11562355. Retain the developmental context rather than a separate molecular function. Compound-mutant tissue phenotypes are not treated as an autonomous human assay or evidence for a specific untested promoter. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:16449236 Functional interactions between FOXC1 and PITX2 underlie the... | KEEP AS NON CORE | Summary: FOXC1 associates with the Pol-II transcription factor PITX2A. Reason: PMID:16449236 uses transfected FOXC1 and PITX2A, with co-immunoprecipitation, nuclear colocalization and a HeLa transcription reporter. PITX2A attenuates FOXC1 activation; the reverse effect was small. Bacterial bait plus mammalian extract is not a two-purified-protein affinity assay, and PITX2A is the partner product. The specific TF-binding class is appropriate for this partner. The original PITX2 product identifier remains intact. This source row has no original extension; the nuclear extension belongs to the separate generic-binding context from the same paper. Neither the tested partner product nor the colocalization assay establishes a FOXC1 natural-product restriction. |
| GO:0070098 chemokine-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 modulates a chemokine-responsive endothelial program. Reason: Actual PMID:18187037 Methods/Results show Foxc1-dependent Cxcr4 expression and reduced CXCL12-directed migration in endothelial cells from conditional Foxc1-knockout mice. Reporter experiments support promoter regulation, but the ChIP in that paper is Foxc2-specific. This supports contextual chemokine signaling through receptor expression; direct endogenous Foxc1 occupancy was not established by that assay. |
| GO:0070098 chemokine-mediated signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 modulates a chemokine-responsive endothelial program. Reason: Actual PMID:18187037 Methods/Results show Foxc1-dependent Cxcr4 expression and reduced CXCL12-directed migration in endothelial cells from conditional Foxc1-knockout mice. Reporter experiments support promoter regulation, but the ChIP in that paper is Foxc2-specific. This supports contextual chemokine signaling through receptor expression; direct endogenous Foxc1 occupancy was not established by that assay. |
| GO:0071364 cellular response to epidermal growth factor stimulus | IMP PMID:16492674 Regulation of FOXC1 stability and transcriptional activity b... | KEEP AS NON CORE | Summary: FOXC1 transcriptional output responds to epidermal growth factor. Reason: Selected original Methods/Results of PMID:16492674 show EGF-dependent stabilization and reporter activation of FOXC1 in HeLa cells, with S272A and MAPK-inhibitor comparisons. Endogenous protein decay was measured separately. EGF/MAPK signaling regulates FOXC1 abundance and transcriptional output in these experiments, preserving the direction of the cellular response. |
| GO:0072010 glomerular epithelium development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 contributes to glomerular epithelial development and integrity. Reason: The authentic PMID:28223138 abstract and previews describe dose-dependent Foxc1/Foxc2 podocyte phenotypes and maintained podocin/Cxcl12 expression, with a stronger Foxc2 contribution. This supports the existing glomerular epithelial context. Do not infer an independently verified Foxc1 repression assay, equal paralog effects or a particular human construct mechanism from the limited access. |
| GO:0072010 glomerular epithelium development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 contributes to glomerular epithelial development and integrity. Reason: The authentic PMID:28223138 abstract and previews describe dose-dependent Foxc1/Foxc2 podocyte phenotypes and maintained podocin/Cxcl12 expression, with a stronger Foxc2 contribution. This supports the existing glomerular epithelial context. Do not infer an independently verified Foxc1 repression assay, equal paralog effects or a particular human construct mechanism from the limited access. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX... | MODIFY | Summary: FOXC1 associates with the tested RNA polymerase II DNA-binding transcription factor PBX1a. Reason: PMID:15684392 supports FOXC1–PBX1 association by co-immunoprecipitation in transfected human cells and endogenous A7 nuclear extracts, with PBX1a-mediated attenuation of FOXC1 reporter output. PBX1 is an established RNA polymerase II-specific DNA-binding transcription factor, so GO:0061629 refines the broader GO:0140297 using this row’s own source and identified partner. The original P40424-1 PBX1a context is retained; association in nuclear extracts does not establish purified binary affinity or equivalent binding by all PBX1 products. The reporter direction is PBX1a acting on FOXC1. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0160108 animal gross anatomical part developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FOXC1 has established roles in development of several anatomical structures. Reason: The original ARBA-derived assertion is concordant with human eye and cardiac clinical evidence and experimentally studied mouse developmental contexts. It remains a broad non-core developmental description of the transcription factor; no new autonomous structural activity, all-tissue expression or individual ARBA-rule experimental replay is claimed. |
| GO:1901491 negative regulation of lymphangiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 restrains corneal lymphatic-vessel growth in a stromal setting. Reason: Actual PMID:22171010 Results show lymphatic growth after corneal stromal/global Foxc1 loss. This supports a contextual negative-lymphangiogenesis role. The VEGFR2 inhibitor did not significantly rescue the lymphatic phenotype in the tested regimen, so blood-vessel rescue must not be transferred to lymphatic vessels. |
| GO:1901491 negative regulation of lymphangiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 restrains corneal lymphatic-vessel growth in a stromal setting. Reason: Actual PMID:22171010 Results show lymphatic growth after corneal stromal/global Foxc1 loss. This supports a contextual negative-lymphangiogenesis role. The VEGFR2 inhibitor did not significantly rescue the lymphatic phenotype in the tested regimen, so blood-vessel rescue must not be transferred to lymphatic vessels. |
| GO:1901534 positive regulation of hematopoietic progenitor cell differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact positive hematopoietic differentiation assertion remains unresolved. Reason: The mouse Foxc1 source trace points to PMID:24590069. Its authentic abstract establishes mesenchymal CAR niche maintenance, altered CXCL12/SCF and changes in hematopoietic stem/progenitor abundance after deletion. Those observations do not alone specify lineage-commitment direction, and the full differentiation assays were inaccessible. Preserve the transfer with source-specific uncertainty rather than claiming an HSC-intrinsic mechanism or a confirmed donor error. |
| GO:1901534 positive regulation of hematopoietic progenitor cell differentiation | ISS GO_REF:0000024 | UNDECIDED | Summary: The exact positive hematopoietic differentiation assertion remains unresolved. Reason: The mouse Foxc1 source trace points to PMID:24590069. Its authentic abstract establishes mesenchymal CAR niche maintenance, altered CXCL12/SCF and changes in hematopoietic stem/progenitor abundance after deletion. Those observations do not alone specify lineage-commitment direction, and the full differentiation assays were inaccessible. Preserve the transfer with source-specific uncertainty rather than claiming an HSC-intrinsic mechanism or a confirmed donor error. |
| GO:1902038 positive regulation of hematopoietic stem cell differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact positive hematopoietic differentiation assertion remains unresolved. Reason: The mouse Foxc1 source trace points to PMID:24590069. Its authentic abstract establishes mesenchymal CAR niche maintenance, altered CXCL12/SCF and changes in hematopoietic stem/progenitor abundance after deletion. Those observations do not alone specify lineage-commitment direction, and the full differentiation assays were inaccessible. Preserve the transfer with source-specific uncertainty rather than claiming an HSC-intrinsic mechanism or a confirmed donor error. |
| GO:1902038 positive regulation of hematopoietic stem cell differentiation | ISS GO_REF:0000024 | UNDECIDED | Summary: The exact positive hematopoietic differentiation assertion remains unresolved. Reason: The mouse Foxc1 source trace points to PMID:24590069. Its authentic abstract establishes mesenchymal CAR niche maintenance, altered CXCL12/SCF and changes in hematopoietic stem/progenitor abundance after deletion. Those observations do not alone specify lineage-commitment direction, and the full differentiation assays were inaccessible. Preserve the transfer with source-specific uncertainty rather than claiming an HSC-intrinsic mechanism or a confirmed donor error. |
| GO:1904798 positive regulation of core promoter binding | ISS GO_REF:0000024 | UNDECIDED | Summary: The precise positive regulation of core-promoter binding needs source-specific verification. Reason: The mouse donor cites PMID:25808752. Its authentic abstract supports Foxc1–Gli2 cooperation and Ihh transcription, but exact binding-assay details were unavailable because purported original PDF access returned challenge HTML. The separately read human PMID:26565916 provides relevant GLI2-binding/occupancy evidence in another setting; it does not automatically verify this source or the precise core-promoter scope. |
| GO:1990841 promoter-specific chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: FOXC1 associates with promoter-containing chromatin. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. Human endogenous FOXC1 ChIP at the FOXO1 promoter supplies target-specific chromatin evidence. This supports transient regulatory occupancy, not a constitutive structural chromatin subunit or universal promoter binding. |
| GO:1990841 promoter-specific chromatin binding | ISS GO_REF:0000024 | ACCEPT | Summary: FOXC1 associates with promoter-containing chromatin. Reason: The original electronic or similarity source is retained, including mouse Foxc1 and the listed mapping identifiers. Independent human FOXC1 motif-binding, reporter and endogenous-promoter experiments support the biological activity; these are corroboration rather than a replay of every donor experiment. Human endogenous FOXC1 ChIP at the FOXO1 promoter supplies target-specific chromatin evidence. This supports transient regulatory occupancy, not a constitutive structural chromatin subunit or universal promoter binding. |
| GO:1990869 cellular response to chemokine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Foxc1 supports endothelial cellular responses to CXCL12. Reason: Actual PMID:18187037 Results show reduced CXCL12-directed migration and Cxcr4 expression in endothelial cells from Foxc1 conditional-knockout mice. These readouts support a chemokine-responsive endothelial context. ChIP in the paper tests Foxc2, so it is not imported as direct Foxc1 occupancy evidence. |
| GO:1990869 cellular response to chemokine | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Foxc1 supports endothelial cellular responses to CXCL12. Reason: Actual PMID:18187037 Results show reduced CXCL12-directed migration and Cxcr4 expression in endothelial cells from Foxc1 conditional-knockout mice. These readouts support a chemokine-responsive endothelial context. ChIP in the paper tests Foxc2, so it is not imported as direct Foxc1 occupancy evidence. |
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Download this section (compressed HTML)Q: Under what endogenous promoter and cellular conditions does the central inhibitory region tune FOXC1 output, and can full-length FOXC1 repress transcription independently of attenuation of an activation domain?
Q: Which molecular partners couple the phosphorylation state of the central inhibitory region to FOXC1 transcriptional output?
Q: How much of the hematopoietic phenotype follows altered mesenchymal niche maintenance, survival or retention, and how much reflects a change in stem or progenitor differentiation?
Q: Which endogenous complexes account for the NFIA-associated FOXC1 screen signal, and does that association alter transcription in contexts beyond the tested M2/A7 cells?
Experiment: Compare matched-expression full-length FOXC1 and targeted inhibitory-region mutants in a human ocular-cell model, measuring nascent transcription and FOXC1 occupancy at established target promoters. Include protein abundance, nuclear localization and DNA-binding controls, and distinguish reduced activation from output below the appropriate basal condition.
Hypothesis: The central inhibitory region changes activation strength at endogenous FOXC1 targets without necessarily establishing independent basal repression.
Type: Endogenous target transcription and chromatin-occupancy analysis
Experiment: In a controlled mesenchymal–hematopoietic coculture, perturb Foxc1 in the support compartment and measure niche signals, cell survival, retention and lineage commitment separately. Use lineage-resolved time courses and restoration of specific niche signals to distinguish these outcomes.
Hypothesis: The hematopoietic phenotype can arise from altered mesenchymal support rather than a stem-cell-intrinsic differentiation program.
Type: Compartment-specific perturbation and lineage-resolved coculture
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