Recombinant Human Forkhead box protein P3 (FOXP3), partial

Function

Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479, PubMed:24835996, PubMed:30513302, PubMed:32644293). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells (PubMed:23169781). Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479). The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (PubMed:17360565). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (PubMed:18354202). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (By similarity)

Subcellular Location

Nucleus; Cytoplasm

Disease Association

Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) : Characterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, thrombocytopenia, anemia and eczema. It is usually lethal in infancy. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Homodimer (PubMed:21458306, PubMed:25567984). Dimerization is essential for its transcriptional regulator activity (PubMed:21458306). Interacts with IKZF3. Isoform 1 (via LXXLL motif), but not isoform 2, interacts with isoform 4 of RORA (via AF-2 motif). Interacts with STUB1, HSPA8 and HSPA1A/B. Interacts with PPP1CA, PPP1CB and PPP1CG. Interacts with KAT5 and HDAC7. Interacts with HDAC9 in the absence of T-cell stimulation. Interacts with USP7. Interacts with isoform 2 of ZFP90 and can form a complex with TRIM28 in the presence of isoform 2 of ZFP90. Interacts with RUNX1. Interacts with RORC. Interacts with RELA and NFATC2. Interacts with RUNX2, RUNX3 and IKZF4 (By similarity)

• Brunkow M.E. et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. — Nat. Genet. (2001)
• Wang J. et al. Cloning and expression of the cDNA for FOXP3. (APR-)
• Kaur G. et al. Functional characterization of FOXP3 splice variants in human regulatory T cells. (JUN-)
• Lin L. et al. PubMed: CI-BS4K6O98PAPN3 (APR-)
• Ross M.T. et al. The DNA sequence of the human X chromosome. — Nature (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Strom T.M. et al. Transcription map in Xp11.23. (APR-)
• Bettelli E. et al. Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. — Proc. Natl. Acad. Sci. U.S.A. (2005)