Summary
Specificity
Human, Monkey, Mouse
Basic Information
Immunogen
Recombinant human full-length FOXP3 protein
Specificity
Human, Monkey, Mouse
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.
Target
Introduction
The protein encoded by this gene is a member of the forkhead/winged-helix family of transcriptional regulators. Defects in this gene are the cause of immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), also known as X-linked autoimmunity-immunodeficiency syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Alternative Names
Forkhead Box P3; Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked; Scurfin; IPEX; Immunodeficiency, Polyendocrinopathy, Enteropathy, X-Linked; Forkhead Box Protein P3; FOXP3delta7;
Function
Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:30513302, PubMed:23947341, PubMed:24354325, PubMed:24722479).
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).
Biological Process
B cell homeostasis Source: Ensembl
CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment Source: UniProtKB
Chromatin remodeling Source: UniProtKB
Establishment of endothelial blood-brain barrier Source: Ensembl
Gene expression Source: Ensembl
Myeloid cell homeostasis Source: Ensembl
Negative regulation of activated T cell proliferation Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of chronic inflammatory response Source: Ensembl
Negative regulation of CREB transcription factor activity Source: UniProtKB
Negative regulation of cytokine production Source: UniProtKB
Negative regulation of defense response to virus Source: Ensembl
Negative regulation of DNA-binding transcription factor activity Source: UniProtKB
Negative regulation of histone acetylation Source: Ensembl
Negative regulation of histone deacetylation Source: BHF-UCL
Negative regulation of immune response Source: UniProtKB
Negative regulation of interferon-gamma production Source: UniProtKB
Negative regulation of interleukin-10 production Source: UniProtKB
Negative regulation of interleukin-17 production Source: UniProtKB
Negative regulation of interleukin-2 production Source: UniProtKB
Negative regulation of interleukin-4 production Source: UniProtKB
Negative regulation of interleukin-5 production Source: Ensembl
Negative regulation of interleukin-6 production Source: Ensembl
Negative regulation of isotype switching to IgE isotypes Source: Ensembl
Negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
Negative regulation of T cell cytokine production Source: UniProtKB
Negative regulation of T cell proliferation Source: UniProtKB
Negative regulation of T-helper 17 cell differentiation Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: GO_Central
Negative regulation of tumor necrosis factor production Source: Ensembl
Positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation Source: UniProtKB
Positive regulation of histone acetylation Source: BHF-UCL
Positive regulation of immature T cell proliferation in thymus Source: Ensembl
Positive regulation of interleukin-4 production Source: Ensembl
Positive regulation of peripheral T cell tolerance induction Source: Ensembl
Positive regulation of T cell anergy Source: Ensembl
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of transforming growth factor beta1 production Source: Ensembl
Regulation of isotype switching to IgG isotypes Source: Ensembl
Regulation of T cell anergy Source: UniProtKB
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to lipopolysaccharide Source: Ensembl
Response to radiation Source: Ensembl
Response to rapamycin Source: Ensembl
Response to virus Source: UniProtKB
T cell activation Source: UniProtKB
T cell homeostasis Source: UniProtKB
T cell mediated immunity Source: Ensembl
T cell receptor signaling pathway Source: Ensembl
Tolerance induction to self antigen Source: Ensembl
Cellular Location
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).
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.
PTM
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 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. Deacetylated by SIRT1.
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.