FOXP3

GeneName

FOXP3

Summary

FOXP3, also known as IPEX, JM2, or forkhead box protein P3, is a 47 kDa transcription factor that plays a critical role in the development and function of regulatory T cells (Tregs). It is primarily expressed in the nucleus and cytoplasm of CD4-positive T cells and is essential for maintaining immune tolerance. FOXP3 binds to DNA and regulates the transcription of genes involved in T cell proliferation and differentiation, particularly in the context of immune responses. It is also implicated in chromatin remodelling and interacts with various proteins, including histone deacetylases and NF-kappaB, to modulate gene expression. Mutations in FOXP3 are associated with autoimmune disorders, such as IPEX syndrome, highlighting its importance in immune regulation.

Importance

FOXP3 is relevant to: - Regulatory T cell function and the maintenance of immune tolerance, which is crucial for preventing autoimmune diseases - The modulation of inflammatory responses, impacting conditions such as allergies and chronic inflammation - Cancer immunology, as it influences T cell responses within the tumour microenvironment - The establishment of the blood-brain barrier, which is important for neuroinflammatory conditions and central nervous system immunity - Research into T cell anergy and memory, contributing to our understanding of immune memory and potential therapeutic strategies.

Top Products

For researchers investigating FOXP3, we highly recommend the top-selling recombinant antibody, Anti-FOXP3 antibody [236A/E7] (ab20034). This well-cited antibody has garnered 691 citations, underscoring its reliability and trust within the scientific community. It has been validated for use in immunohistochemistry (IHC) and western blotting (WB), making it an excellent choice for those requiring robust detection of FOXP3 in various experimental settings. The recombinant nature of this antibody ensures batch-to-batch consistency, providing researchers with confidence in their results. The Anti-FOXP3 antibody [236A/E7] ELISA Kit (ab20034), with an impressive 691 citations, is an excellent option for researchers looking to accurately measure FOXP3 levels in their samples.

Abcam Product Citation Summary

The data indicates a significant focus on the role of FOXP3 in various human and mouse tissues, particularly in the context of immune responses, cancer, and inflammatory conditions. The use of multiple applications such as immunohistochemistry (IHC) and western blotting (WB) highlights the versatility of Abcam antibodies in studying FOXP3 across different biological contexts, including liver disease, tumoral infiltration, and immune cell dynamics.

Abcam Product Citation Table

Domain

The fork-head DNA-binding domain is essential for its dimerization and interaction with NFATC2.

Function

The protein expressed by the FOXP3 gene is a transcriptional regulator critical for the development and inhibitory function of regulatory T-cells (Treg). It plays an essential role in immune system homeostasis by ensuring the suppressive function and stability of Treg cells and directly influencing conventional T-cells' expansion and function. FOXP3 can function as either a transcriptional repressor or activator, depending on its interactions with other factors, such as transcription factors, histone acetylases, and deacetylases. It co-activates genes like CTLA4 and TNFRSF18 and represses cytokine genes, including interleukin-2 (IL2) and interferon-gamma (IFNG), and inhibits cytokine production by repressing the activity of transcription factors RELA and NFATC2. FOXP3's association with histone acetylase KAT5 and deacetylase HDAC7 mediates IL2 repression, while its interaction with transcription factor RUNX1 modulates the expression of TNFRSF18, IL2RA, CTLA4, IL2, and IFNG. It also antagonizes RORC to inhibit the differentiation of IL17 producing helper T-cells (Th17), leading to reduced IL17 expression and promoting Treg development, while inhibiting the transcriptional activator activity of RORA. This supplementary information is collated from multiple sources and compiled automatically.

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Polyubiquitinated, leading to its proteasomal degradation in regulatory T-cells (Treg) which is mediated by STUB1 in a HSPA1A/B-dependent manner. Deubiquitinated by USP7 and USP44; leading to increase in protein stability.

Phosphorylation at Ser-418 regulates its transcriptional repressor activity and consequently, regulatory T-cells (Treg) suppressive function. Dephosphorylated at Ser-418 by protein phosphatase 1 (PP1) in Treg cells derived from patients with rheumatoid arthritis. Phosphorylation by CDK2 negatively regulates its transcriptional activity and protein stability (By similarity).

Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions (PubMed:17360565, PubMed:24835996). Acetylation is mediated by a coordinated action of KAT5 and EP300/p300 acetyltransferases: EP300/p300 is required to enhance KAT5 autoacetylation, promoting acetylation of FOXP3 by KAT5 (PubMed:24835996). Deacetylated by SIRT1 (PubMed:22312127).

Undergoes proteolytic cleavage in activated regulatory T-cells (Treg), and can be cleaved at either the N- or C-terminal site, or at both sites.

Cellular localization

• Nucleus
• Cytoplasm
• Predominantly expressed in the cytoplasm in activated conventional T-cells whereas predominantly expressed in the nucleus in regulatory T-cells (Treg). The 41 kDa form derived by proteolytic processing is found exclusively in the chromatin fraction of activated Treg cells (By similarity).

Alternative names

IPEX, JM2, FOXP3, Forkhead box protein P3, Scurfin

Database links

swissprot:Q9BZS1 entrezGene:50943 omim:300292

Other research areas

• Immunology & Infectious Disease