This guide distinguishes original annotation sources from auxiliary corroboration. Selected Methods/Results or captions are identified below; availability of an article is not a claim that every section, supplementary assay or figure image was examined. The source assessments apply to specific claims, so an UNVERIFIED source may also contain verified experiments for other annotations. Original reference identifiers are preserved.
No new publication quotations were added. Supported generic interactions remain non-core when their source does not justify a specific functional refinement; unresolved evidence remains undecided. A partner’s activity, location or tissue role is not automatically transferred to FOXC2.
Selected publisher-indexed Results, Figure 2 caption, transgene and oxygen-consumption Methods were read; direct full-page access failed. Human FOXC2 was expressed in transgenic mice. Increased white-adipose oxidative metabolism and the 4 °C/24-hour brown-adipose lipid endpoint do not resolve the exact negative cold-induced thermogenesis assertion. The direction-specific uncertainty remains; it is not evidence that the paper is irrelevant.
Locators: Publisher-indexed original Results, Figure 2 caption, cloning/transgenic and oxygen-consumption Methods and selected Discussion. Direct opening was forbidden; preserved search extraction contains the actual sections.
Selected original Results, Figures 1 and 5–6 captions, and Methods were read. Figure 1G–H reports nuclear Foxc1/Foxc2 staining in cultured human aortic smooth-muscle cells. The developmental experiments are separate mouse compound-genotype studies: complete compound loss disrupts somite formation, while individual-null and other compound genotypes still form somites. Neither the complete compound phenotype nor exclusive nuclear localization is assigned to human FOXC2 alone. Image pixels and the separate antibody-generation paper were not inspected.
Locators: Read original PMC Methods for mutant breeding/histology and Results/Figures 5–6 on somite segmentation and marker expression; indexed lines 151–190,239–245. The reused local HTML was a CAPTCHA, not the primary body; later web-index extraction recovered the original. Original Results: Expression of Foxc1 and Foxc2; Figure 1G–H; Figures 5–6; Methods (indexed lines 111–120, 151–190, 239–254).
PubMed; Original source 1; Original source 2
Selected original reprint Methods, Results, Figure 5 caption and Discussion were read. The 74-person human series includes mutation-positive cases and a linkage-supported family. Imaging supports lymphatic reflux/dysfunction despite normal or increased channel numbers. It does not establish absence of vessels, a direct endothelial-cell mechanism or molecular lymphangiogenesis. Image pixels and all individual patient-table entries were not adjudicated.
Locators: Original journal reprint selected Methods lines 72–80/133–153, Results 165–182/235–250, Figure 5 caption and Discussion 539–563. No imaging pixels or complete patient-table adjudication.
Selected indexed original PDF Results, Figures 2–4 captions and Methods were read. Sequence-checked full-length human FOXC2 was tested by COS-7 lysate EMSA and a FOX-site reporter in HeLa. Xpress-tagged WT was predominantly nuclear; disease variants were compared separately. This is cell-extract binding, not purified equilibrium affinity. Human insert identity is distinct from the monkey host, and mutant effects do not establish natural-product differences. No PDF pixels or supplements were read.
Locators: Publisher PDF extracted by the web index: Results, Figures 2–4 captions and Methods at indexed lines 21–182, particularly 170–178. No PDF pixels or supplements read.
Selected original Methods, Results and Figures 1–6 captions were read. Endogenous human HMEC-1 anti-FOXC2 ChIP recovers PAI-1 promoter chromatin, increasing after insulin/TGF-β. Nearby sites are not individually resolved by the chromatin fragments. Separate bovine/mouse reporter and mouse physiological experiments retain their species limits; the inspected expression-plasmid paragraph does not independently establish its insert species. Expanded online Methods were not inspected.
Locators: Original Circulation Research PDF Methods and Results, Figures 1–6 text/captions; indexed lines 31–45, 47–97, 156–180 and 224–236. Online expanded Methods not inspected.
Original PMC Methods, selected Results and Figures 2F/3/4 captions were read. Actual FOXC2 reporter activation and mammary-cell migration experiments are present. The inspected ChIP concerns FOXM1, so it does not verify the exact FOXC2 DNA-binding assertion. The supplied FOXC2 plasmid is named without an independently established insert sequence/species. The original two-atom part_of conjunction remains intact. Figure pixels and supplements were not inspected.
Locators: Original PMC3001014 Methods and Results, including Fig 2F and Figures 3–4 captions; paragraph indices 31,33,35,36,42,44,46,47,59,60,62,63,65,67,68,89 in the pinned local extraction. No figure-pixel or supplement inspection.
Only the authentic abstract and identifier metadata were recovered; the bounded publisher route failed. FOXC2 was included among sequenced candidate genes and rare inherited variants were reported. The precise FOXC2 IMP functional basis remains unresolved. No wrong-gene attribution, variant-function assay or opposing biological conclusion is inferred from the abstract.
Locators: Read authentic PubMed abstract and identifier metadata. The bounded publisher full-text route remained inaccessible.
The retained extraction contains Introduction/Discussion, despite full-text metadata; original Methods, Results and supplementary Table 2G were not directly inspected. Four exact accession-specific FOXC2 pairs are supported by positive IntAct screen/array/retest records. This is the 2014 human interaction study, not the 2020 HuRI study. Repeated stages are not independent native-cell confirmations; partner classification does not establish a physiological pathway.
Locators: Cached Introduction and Discussion, lines 188–275; authentic PubMed identity/title metadata. Retained source lines 188–275; IntAct supplementary-table-2G record locators.
Selected source-wide Results/Figure 1 workflow and Methods were read. SFB-tagged human transcription factors in HEK293T undergo soluble/chromatin fractionation and tandem-affinity MS. The exact FOXC2 self-pair and fraction entry remain unrecovered; no matching self-pair was found in the retained response. This is an access limitation, not negative interaction evidence. Soluble does not mean cytosolic, and co-complex detection does not establish homodimer stoichiometry.
Locators: Read source-wide Results/Fig 1 workflow and Methods in the exact-main cache, including lines 88,117,119,417,429,433,439. The exact FOXC2 self-association table row has not been recovered.
PubMed; Original source 1; Original source 2; Original source 3
The authentic journal abstract and selected first-author Osaka dissertation were read; journal full-text access failed. Dissertation Figure 35 and Methods describe FOXC2 nuclear staining in human dermal lymphatic endothelial cells after Ang1/Ang2 exposure. The thesis lists the journal publication on printed page 72, but is not a byte-identical reprint or independent replication. Mouse Polydom-loss outcomes remain separate. No figure-pixel inspection or exact journal figure-number equivalence is claimed.
Locators: Author thesis printed pages 19, 23–24, 51–52 and 72; indexed lines 625–644, 755–766, 1481–1516 and 2254–2259
PubMed; Original source 1; Original source 2
Selected original Methods and authentic supplementary workbook entries were read. The assayed human FOXC2 extended DNA-binding domain maps exactly to residues 55–186. Tagged E. coli-expressed purified-domain HT-SELEX produces methylated/unmethylated DNA-selection motifs. Workbook S1 row 255 and S2 rows 5028/5033/5038/5043/9121 identify the construct/results. Domain enrichment and PWMs are not full-length cellular regulation or equilibrium-affinity measurements.
Locators: Exact-main full-text cache lines 106–108 and 184–208; actual supplementary workbook S1 row 255, S2 rows 5028/5033/5038/5043 and 9121, independently extracted in the companion receipt.
Selected original cached Results and Extended Data Figures 1/3 captions were read. Three exact FOXC2 pairs are supported by positive HuRI IntAct screen/retest records; Supplementary Table 9 is a curator locator, not a directly inspected table. Sequence confirmation and yeast retesting do not establish pair-specific MAPPIT/GPCA or native interaction. The 13–1002 feature belongs to GOLGA2, not the 501-aa FOXC2 protein.
Locators: Selected cached Results lines 255–269, Discussion line 317, and Extended Data Fig. 1/3 captions at lines 331/339. Retained source Results lines 255–269; Discussion 317; Extended Data captions 331/339.
PubMed; Original source 1; Original source 2
Selected original Development reprint Methods, Results and Figures 4–7 captions were read. Mouse MFH-1 expression was mapped during mesoderm development; human work concerns genomic organization/chromosome mapping. The amputated-mutation relationship was a candidate hypothesis. These data are not human mesoderm perturbation or established causation. The historical human NAS assertion remains distinct from later mouse genetics; no figure-pixel inspection is claimed.
Locators: Read original Development reprint selected Methods (RNA/in-situ/genomic methods), Results and Figures 4–7 captions; indexed lines 182–195,245–345,350–425,431–478. No figure-pixel inspection.
The authentic abstract explicitly describes mouse MFH-1 and human FKHL14 transcriptional activation. Publisher access failed with HTTP 429; full Methods and figures remain unread. Construct, host and promoter details are not supplied from inference. Independent human activation/localization evidence corroborates the function while leaving this older source-specific access gap explicit.
Locators: Read the authentic PubMed abstract in the pinned 14-paper metadata batch. Bounded publisher access failed with HTTP 429; no full Methods or figures inspected.
Selected original PMC Methods, Results and Discussion were read. Mouse Foxc2 promoter occupancy and Itgb3 activation accompany endothelial adhesion, migration and ex vivo sprouting. Mouse inserts/functional assays are distinct from human 293T virus production; HUVEC induction is data-not-shown. Scratch closure measures cultured-cell migration, not repair of an injured vessel. Downregulated microarray probes alone do not establish direct DNA-bound repression. This auxiliary donor source does not replace the original human transfer reference.
Locators: Read original PMC2527100 Methods paragraphs 19–32 and Results/Discussion 37,40,41,44,48,49,52,53,56–58,62,63,65 in the pinned extraction.
The retained selected-primary consultation identifies original Methods and Results/captions supporting mouse Foxc2 Cxcr4 activation and Foxc2-specific promoter ChIP. The selected-primary consultation does not constitute a complete-paper read. Foxc1 conditional knockout/migration experiments remain separate. The auxiliary donor paper supplements the original human transfer context without converting the experiment into human FOXC2 perturbation.
Locators: Retained selected-primary consultation; no new independent primary-body read is claimed here. The note identifies original Methods and three Results subsections/captions.
PubMed; Original source 1; Original source 2
Selected original 2026 Methods, Results and captions were read. Purified human FOXC2/NFAT1 domains support interaction; tagged full-length human proteins in HEK293T suppress NFAT1-driven transcription, with interface-mutant tests. This does not establish native T-cell physiology, universal repression, full-length purified kinetics or a separate DNA-binding repressor core. It corroborates a mechanism without becoming the original evidence behind older mouse transfers. Supplementary figures and structural coordinates were not inspected.
Locators: Read original publisher Methods paragraphs 10–12,30,32,34,36,38,40 and Results/captions 45–72. Supplemental figures and raw structural coordinates were not inspected.
Selected original cached Results/Figure 3 caption, plasmid description and denaturing ubiquitination Methods were read. Human TRIM27 WT versus RING-mutant cellular NOD2 assays support its E3 partner class. This is auxiliary classification evidence, not evidence that FOXC2 catalyses ubiquitination or is a TRIM27 substrate. No image pixels or supplements were inspected.
Locators: Retained source Results 120–125/Figure 3 caption; plasmids 192/194; Methods 210–222.
UniProt Q99958 identifies the reviewed human 501-aa protein. Its displayed sequence was matched to the family alignment; no alternative-product block was reported. Full-length constructs, residues 55–186 used for extended-domain selection, and the separate 72–172 interaction construct remain distinct.
HPA FOXC2 and its official XML report HPA056302 Supported ICC/IF nucleoplasm and nuclear bodies in BJ and HeLa. Standard support is not enhanced genetic validation. The 72-aa antigen matches FOXC2 residues 429–500; WB support is uncertain. No image-pixel, specific nuclear-body subtype or universal-localization claim is made.
The PTHR11829 tree and alignment contain 1,182 matched entries; target PTN002483621 exactly matches Q99958. Six incoming IBA rows trace to positive IBD node PTN000930906 on the target path. Two incoming support lists additionally contain RGD:621723 relative to the inspected current IBD rows; their original assertions and dates remain preserved. Target self-evidence is not circular, and donor count is not used as evidence strength. The source evidence retains exact IBD fields and source-list differences. General transfer/domain mapping references are preserved without claiming every historical pipeline execution was reconstructed.
The genuine fetch produced 62 annotations from 62 original QuickGO contexts. All source fields and their fresh ordering are retained, including the two-atom conjunction. The source evidence embeds every original object and its genuine raw/TSV/stored mapping. All 23 normal sources are present: 12 were reused exactly from main and 11 were acquired through repository tooling, including the two follow-up auxiliary papers. Original cache bytes are unchanged. Metadata declaring full-text availability does not expand the selected reading scopes above.
The configured Falcon attempt and perplexity-lite fallback failed authentication/access and produced no research document. The review uses the manual selected-primary research described here. The original UniProt text and GOA snapshot remain unedited.
Original phosphorylation study (PMID:23878394) was genuinely fetched as an abstract-only normal cache. Separately recovered original HTML supplied the selected Methods, Results, Discussion and Figures 1–5 captions. Myc-tagged human wild-type and eight-site mutant FOXC2 were compared in primary human lymphatic endothelial cells. Anti-Myc ChIP-chip and ChIP-qPCR were restricted to sites previously occupied by endogenous FOXC2; the current experiment does not independently remeasure that endogenous baseline. The mutant showed selective loss of occupancy and altered transcription, while nuclear localization and extract binding to naked DNA were preserved. Exact phosphosites were mapped on overexpressed protein. The animal experiment induced FOXC2 in embryonic mouse blood endothelial cells, because the driver did not target lymphatic endothelium. No FOXC2 kinase activity or lymphatic in-vivo phosphosite mechanism is inferred. Figure pixels and supplements were not inspected.
Original NFAT1 study (PMID:42023653), Materials and methods (Plasmids, purification, pull-down, ITC, SPR, cellular reporter and RNA assays), Results/Figures 1–5 captions and selected Discussion establish a distinct corepressor activity. Purified human FOXC2 residues 72–172 directly bind human NFAT1 residues 392–678; DNA enhances this binding rather than making all contact possible. Full-length proteins and interface mutants were tested separately in transfected HEK293T cells. Repression requires the NFAT-responsive element, while a cognate forkhead element is dispensable. The supported molecular activity is transcription corepressor activity; a second new generic/specific binding assertion or new process assertion would add little here. These assays do not establish native immune-cell function. NFAT1 means NFATC2; background discussion of lymphatic cooperation with NFATC1 does not establish that the same repression mechanism operates in valves.
The broader Pol II binding terms are now assessed consistently at gene level. The actual FOXM1 ChIP in PMID20956529 remains distinct from FOXC2 reporter experiments, and the original two-part extension is retained without claiming that its exact source assay was recovered. The cold-induced thermogenesis direction remains undecided. Locating the original direction-specific endpoint is a curation task retained in the notes and source questions, not a structured biological knowledge gap; increased basal oxidative metabolism is not converted to an opposite cold-response annotation.
Selected original Results, Methods, Discussion and Figures 3 and 7–10 captions were read. Mouse Foxc2 loss, Nfatc1 loss and calcineurin inhibition support collecting-vessel maturation and valve regulation; drug treatment is not a protein-specific genetic perturbation. The human experiments use endogenous FOXC2 ChIP-chip in primary intestinal lymphatic endothelial cells, identifying 2,350 non-mitochondrial sites, with separate extract-EMSA validation. NFATc1 binds selected fragments, and overexpressed factors yield fragment-dependent reporter responses in 293T cells: fragment 8 is coactivated, while FOXC2 partially represses the NFATc1 response of fragment 3. Reported overexpression co-IP is supported by inspected Methods/Results text; its supplementary image was not read. These are not purified binary-affinity measurements. The paper leaves the exact effector genes connecting this regulatory network to collecting-vessel identity unresolved. NFATc1 is distinct from NFAT1/NFATC2 in the 2026 corepressor study. No new developmental annotation or natural-product assignment follows from these experiments.
The official is_a-only ancestry of GO:0000978 includes GO:1990837. The broader sequence-specific dsDNA-binding row is therefore TOO_GENERAL, with its positive domain HT-SELEX evidence preserved. The original assay remains distinct from independent gene-level promoter-specific evidence.
The corepressor core now records the unresolved endogenous human cell and target range as a BIOLOGY knowledge gap, paired with the existing targeted perturbation/rescue experiment. The direct biochemical and transfected-cell mechanism remains supported; no native immune-cell or lymphatic-valve repression is inferred.