FOXP3
Gene Information
- Official Symbol: FOXP3
- Official Name: forkhead box P3
- Aliases and Previous Symbols: N/A
- Entrez ID: 50943
- UniProt: Q9BZS1
- Interactions: BioGRID
- PubMed articles: Open PubMed
- OMIM: Open OMIM
Function Summary
- Entrez Summary: 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].
- UniProt Summary: Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). 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. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. 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). 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). {ECO:0000250|UniProtKB:Q99JB6, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:18354202, ECO:0000269|PubMed:18368049, ECO:0000269|PubMed:21458306, ECO:0000269|PubMed:23169781}.
Pfam Domains GO Terms
Pfam Domains
| Fork head |
GO Terms
| regulation of peripheral T cell tolerance induction |
| CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment |
| positive regulation of peripheral T cell tolerance induction |
| positive regulation of T cell anergy |
| positive regulation of immature T cell proliferation in thymus |
| positive regulation of tolerance induction dependent upon immune response |
| negative regulation of isotype switching to IgE isotypes |
| positive regulation of lymphocyte anergy |
| positive regulation of peripheral tolerance induction |
| regulation of peripheral tolerance induction |
| CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation |
| regulation of tolerance induction dependent upon immune response |
| positive regulation of immature T cell proliferation |
| regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation |
| positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation |
| negative regulation of isotype switching |
| negative regulation of chronic inflammatory response |
| negative regulation of interferon-gamma biosynthetic process |
| regulation of T cell anergy |
| regulation of lymphocyte anergy |
| tolerance induction to self antigen |
| NFAT protein binding |
| negative regulation of interleukin-4 production |
| regulatory T cell differentiation |
| negative regulation of interleukin-2 biosynthetic process |
| regulation of immature T cell proliferation in thymus |
| negative regulation of histone deacetylation |
| regulation of isotype switching to IgE isotypes |
| positive regulation of T cell tolerance induction |
| negative regulation of CREB transcription factor activity |
| negative regulation of interleukin-5 production |
| positive regulation of transforming growth factor beta1 production |
| regulation of immature T cell proliferation |
| negative regulation of T cell cytokine production |
| positive regulation of tolerance induction |
| regulation of T cell tolerance induction |
| negative regulation of T-helper 17 cell differentiation |
| regulation of chronic inflammatory response |
| negative regulation of T-helper 17 type immune response |
| negative regulation of immunoglobulin mediated immune response |
| negative regulation of B cell mediated immunity |
| negative regulation of activated T cell proliferation |
| CD4-positive, alpha-beta T cell lineage commitment |
| regulation of transforming growth factor beta1 production |
| negative regulation of immunoglobulin production |
| positive regulation of T cell differentiation in thymus |
| regulation of isotype switching to IgG isotypes |
| alpha-beta T cell lineage commitment |
| tolerance induction |
| positive regulation of regulatory T cell differentiation |
| negative regulation of interleukin-17 production |
| CD4-positive or CD8-positive, alpha-beta T cell lineage commitment |
| negative regulation of histone acetylation |
| negative regulation of T-helper cell differentiation |
| regulation of tolerance induction |
| regulation of T-helper 17 cell differentiation |
| regulation of interferon-gamma biosynthetic process |
| negative regulation of interleukin-10 production |
| negative regulation of peptidyl-lysine acetylation |
| positive regulation of transforming growth factor beta production |
| regulation of interleukin-2 biosynthetic process |
| negative regulation of T cell mediated immunity |
| T cell lineage commitment |
| regulation of T-helper 17 type immune response |
| negative regulation of CD4-positive, alpha-beta T cell differentiation |
| negative regulation of protein acetylation |
| regulation of interleukin-5 production |
| negative regulation of interleukin-2 production |
| positive regulation of interleukin-4 production |
| negative regulation of alpha-beta T cell differentiation |
| regulation of T cell differentiation in thymus |
| negative regulation of cytokine production involved in immune response |
| B cell homeostasis |
| positive T cell selection |
| regulation of interleukin-4 production |
| regulation of histone deacetylation |
| NF-kappaB binding |
| regulation of interleukin-17 production |
| positive regulation of CD4-positive, alpha-beta T cell differentiation |
| negative regulation of CD4-positive, alpha-beta T cell activation |
| histone acetyltransferase binding |
| positive regulation of histone acetylation |
| negative regulation of B cell activation |
| regulation of regulatory T cell differentiation |
| negative regulation of cytokine biosynthetic process |
| regulation of T cell cytokine production |
| positive regulation of peptidyl-lysine acetylation |
| negative regulation of interferon-gamma production |
| T cell homeostasis |
| regulation of isotype switching |
| positive regulation of CD4-positive, alpha-beta T cell activation |
| regulation of T-helper cell differentiation |
| CD4-positive, alpha-beta T cell differentiation |
| regulation of transforming growth factor beta production |
| negative regulation of production of molecular mediator of immune response |
| regulation of activated T cell proliferation |
| negative regulation of alpha-beta T cell activation |
| negative regulation of lymphocyte mediated immunity |
| T cell selection |
| CD4-positive, alpha-beta T cell activation |
| negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains |
| positive regulation of protein acetylation |
| negative regulation of histone modification |
| T cell mediated immunity |
| regulation of protein deacetylation |
| negative regulation of interleukin-6 production |
| negative regulation of T cell differentiation |
| negative regulation of adaptive immune response |
| negative regulation of DNA recombination |
| regulation of CD4-positive, alpha-beta T cell differentiation |
| positive regulation of alpha-beta T cell differentiation |
| positive regulation of T cell mediated immunity |
| negative regulation of leukocyte mediated immunity |
| alpha-beta T cell differentiation |
| regulation of immunoglobulin mediated immune response |
| regulation of B cell mediated immunity |
| regulation of interleukin-10 production |
| negative regulation of lymphocyte differentiation |
| lymphocyte homeostasis |
| regulation of interleukin-2 production |
| regulation of histone acetylation |
| negative regulation of tumor necrosis factor production |
| positive regulation of alpha-beta T cell activation |
| negative regulation of T cell proliferation |
| regulation of CD4-positive, alpha-beta T cell activation |
| alpha-beta T cell activation |
| negative regulation of chromatin organization |
| negative regulation of tumor necrosis factor superfamily cytokine production |
| regulation of peptidyl-lysine acetylation |
| regulation of alpha-beta T cell differentiation |
| regulation of immunoglobulin production |
| negative regulation of cytokine secretion |
| leukocyte homeostasis |
| regulation of T cell mediated immunity |
| regulation of protein acetylation |
| negative regulation of lymphocyte proliferation |
| negative regulation of mononuclear cell proliferation |
| negative regulation of leukocyte proliferation |
| positive regulation of T cell differentiation |
| negative regulation of NF-kappaB transcription factor activity |
| regulation of cytokine production involved in immune response |
| positive regulation of histone modification |
| regulation of alpha-beta T cell activation |
| positive regulation of lymphocyte differentiation |
| positive regulation of T cell proliferation |
| regulation of interferon-gamma production |
| positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains |
| negative regulation of leukocyte differentiation |
| regulation of DNA recombination |
| positive regulation of chromatin organization |
| positive regulation of adaptive immune response |
| positive regulation of lymphocyte mediated immunity |
| regulation of cytokine biosynthetic process |
| myeloid cell homeostasis |
| negative regulation of T cell activation |
| histone deacetylase binding |
| negative regulation of immune effector process |
| negative regulation of leukocyte cell-cell adhesion |
| negative regulation of DNA metabolic process |
| positive regulation of lymphocyte proliferation |
| positive regulation of mononuclear cell proliferation |
| negative regulation of protein secretion |
| positive regulation of leukocyte mediated immunity |
| negative regulation of chromosome organization |
| T cell differentiation |
| negative regulation of hemopoiesis |
| negative regulation of inflammatory response |
| positive regulation of leukocyte proliferation |
| regulation of T cell differentiation |
| negative regulation of peptide secretion |
| regulation of interleukin-6 production |
| regulation of production of molecular mediator of immune response |
| regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains |
| negative regulation of lymphocyte activation |
| regulation of histone modification |
| positive regulation of leukocyte differentiation |
| negative regulation of immune response |
| regulation of tumor necrosis factor production |
| cytokine production |
| regulation of lymphocyte mediated immunity |
| regulation of tumor necrosis factor superfamily cytokine production |
| regulation of T cell proliferation |
| negative regulation of DNA-binding transcription factor activity |
| regulation of adaptive immune response |
| chromatin remodeling |
| regulation of lymphocyte differentiation |
| negative regulation of cell-cell adhesion |
| positive regulation of chromosome organization |
| negative regulation of leukocyte activation |
| T cell receptor signaling pathway |
| negative regulation of protein transport |
| negative regulation of establishment of protein localization |
| positive regulation of hemopoiesis |
| regulation of chromatin organization |
| negative regulation of cell activation |
| homeostasis of number of cells |
| positive regulation of T cell activation |
| negative regulation of secretion by cell |
| regulation of cytokine secretion |
| regulation of leukocyte mediated immunity |
| negative regulation of defense response |
| regulation of B cell activation |
| regulation of lymphocyte proliferation |
| regulation of mononuclear cell proliferation |
| positive regulation of leukocyte cell-cell adhesion |
| positive regulation of immune effector process |
| regulation of leukocyte proliferation |
| negative regulation of secretion |
| T cell activation |
| lymphocyte differentiation |
| transcription corepressor activity |
| cell fate commitment |
| positive regulation of cell-cell adhesion |
| lymphocyte mediated immunity |
| negative regulation of cell adhesion |
| regulation of leukocyte differentiation |
| negative regulation of cytokine production |
| adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains |
| response to virus |
| antigen receptor-mediated signaling pathway |
| regulation of leukocyte cell-cell adhesion |
| regulation of T cell activation |
| leukocyte differentiation |
| regulation of inflammatory response |
| regulation of chromosome organization |
| regulation of DNA metabolic process |
| positive regulation of lymphocyte activation |
| regulation of Wnt signaling pathway |
| negative regulation of response to external stimulus |
| negative regulation of organelle organization |
| lymphocyte activation |
| regulation of cell-cell adhesion |
| positive regulation of cell adhesion |
| positive regulation of leukocyte activation |
| positive regulation of cell activation |
| sequence-specific DNA binding |
| regulation of DNA-binding transcription factor activity |
| negative regulation of immune system process |
| immune response-activating cell surface receptor signaling pathway |
| positive regulation of cytokine production |
| regulation of hemopoiesis |
| regulation of protein secretion |
| regulation of immune effector process |
| immune response-regulating cell surface receptor signaling pathway |
| negative regulation of transport |
| regulation of peptide secretion |
| RNA polymerase II proximal promoter sequence-specific DNA binding |
| regulation of lymphocyte activation |
| hemopoiesis |
| immune response-activating signal transduction |
| negative regulation of protein modification process |
| protein-containing complex |
| immune response-regulating signaling pathway |
| regulation of leukocyte activation |
| hematopoietic or lymphoid organ development |
| adaptive immune response |
| positive regulation of organelle organization |
| activation of immune response |
| regulation of cell activation |
| immune system development |
| DNA-binding transcription factor activity |
| negative regulation of cell population proliferation |
| regulation of cell adhesion |
| regulation of cytokine production |
| chromatin organization |
| negative regulation of cellular component organization |
| regulation of protein transport |
| negative regulation of cell differentiation |
| regulation of peptide transport |
| regulation of establishment of protein localization |
| regulation of secretion by cell |
| regulation of defense response |
| leukocyte mediated immunity |
| regulation of secretion |
| negative regulation of transcription by RNA polymerase II |
| positive regulation of immune response |
| protein homodimerization activity |
| positive regulation of cell population proliferation |
| leukocyte activation |
| negative regulation of developmental process |
| positive regulation of cell differentiation |
| regulation of protein localization |
| negative regulation of cellular protein metabolic process |
| chromosome organization |
| cell activation |
| immune effector process |
| regulation of response to external stimulus |
| negative regulation of protein metabolic process |
| negative regulation of molecular function |
| positive regulation of immune system process |
| regulation of immune response |
| negative regulation of transcription, DNA-templated |
| negative regulation of multicellular organismal process |
| positive regulation of cellular component organization |
| positive regulation of transcription by RNA polymerase II |
| positive regulation of protein modification process |
| negative regulation of nucleic acid-templated transcription |
| negative regulation of RNA biosynthetic process |
| regulation of organelle organization |
| response to other organism |
| response to external biotic stimulus |
| response to biotic stimulus |
| negative regulation of RNA metabolic process |
| positive regulation of developmental process |
| negative regulation of cellular macromolecule biosynthetic process |
| negative regulation of nucleobase-containing compound metabolic process |
| DNA binding |
| negative regulation of macromolecule biosynthetic process |
| regulation of response to stress |
| negative regulation of cellular biosynthetic process |
| positive regulation of transcription, DNA-templated |
| negative regulation of biosynthetic process |
| DNA-binding transcription factor activity, RNA polymerase II-specific |
| positive regulation of cellular protein metabolic process |
| regulation of cell population proliferation |
| negative regulation of response to stimulus |
| positive regulation of nucleic acid-templated transcription |
| positive regulation of RNA biosynthetic process |
| homeostatic process |
| regulation of immune system process |
| positive regulation of protein metabolic process |
| negative regulation of gene expression |
| positive regulation of RNA metabolic process |
| positive regulation of multicellular organismal process |
| regulation of cell differentiation |
| regulation of protein modification process |
| regulation of transport |
| immune response |
| positive regulation of nucleobase-containing compound metabolic process |
| positive regulation of macromolecule biosynthetic process |
| positive regulation of cellular biosynthetic process |
| positive regulation of gene expression |
| positive regulation of biosynthetic process |
CRISPR Data
Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Compound Hit
| Screen | Score |
|---|---|
| Tunicamycin 0.04 to 0.075μM on day4 R07 exp419 | -2.15 |
| 35°C R06 exp302 | -1.92 |
| CI-1040 9.5μM R08 exp472 | -1.79 |
| NFN1 0.1μM R01 exp49 | 1.89 |
Most Correlated Genes in Chemogenomics
No correlation found to any other genes in chemogenomics.
Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Global Fraction of Cell Lines Where Essential: 0/694
| Tissue | Fraction Of Cell Lines Where Essential |
|---|---|
| 1290807.0 | 0/1 |
| 909776.0 | 0/1 |
| bile duct | 0/28 |
| blood | 0/26 |
| bone | 0/26 |
| breast | 0/30 |
| central nervous system | 0/49 |
| cervix | 0/4 |
| colorectal | 0/17 |
| esophagus | 0/11 |
| fibroblast | 0/1 |
| gastric | 0/14 |
| kidney | 0/18 |
| liver | 0/19 |
| lung | 0/72 |
| lymphocyte | 0/16 |
| ovary | 0/25 |
| pancreas | 0/22 |
| peripheral nervous system | 0/15 |
| plasma cell | 0/12 |
| prostate | 0/1 |
| skin | 0/20 |
| soft tissue | 0/9 |
| thyroid | 0/2 |
| upper aerodigestive | 0/22 |
| urinary tract | 0/28 |
| uterus | 0/5 |
Essentiality in NALM6
- Essentiality Rank: 7511
- Expression level (log2 read counts): -0.93
Expression Distribution
FOXP3 Expression in NALM6 Cells: -0.93
