Foxp3
entrez
20371
canonical
uniprot
Q99JB6
canonical
ensembl
ENSMUSG00000039521
resolver
ensp
ENSMUSP00000041953
resolver
ensp
ENSMUSP00000111403
resolver
ensp
ENSMUSP00000111404
resolver
ensp
ENSMUSP00000111405
resolver
ensp
ENSMUSP00000157059
resolver
ensp
ENSMUSP00000157093
resolver
enst
ENSMUST00000045566
resolver
enst
ENSMUST00000115738
resolver
enst
ENSMUST00000115739
resolver
enst
ENSMUST00000115740
resolver
enst
ENSMUST00000234363
resolver
enst
ENSMUST00000235116
resolver
genesymbol
Foxp3
resolver
uniprot
Q53Z59
resolver
uniprot_entry
FOXP3_MOUSE
resolver
uniprot_entry
Q53Z59_MOUSE
resolver
amino_acid_sequence
MPNPRPAKPMAPSLALGPSPGVLPSWKTAPKGSELLGTRGSGGPFQGRDLRSGAHTSSSLNPLPPSQLQLPTVPLVMVAPSGARLGPSPHLQALLQDRPHFMHQLSTVDAHAQTPVLQVRPLDNPAMISLPPPSAATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPRSGTPRKDSNLLAAPQGSYPLLANGVCKWPGCEKVFEEPEEFLKHCQADHLLDEKGKAQCLLQREVVQSLEQQLELEKEKLGAMQAHLAGKMALAKAPSVASMDKSSCCIVATSTQGSVLPAWSAPREAPDGGLFAVRRHLWGSHGNSSFPEFFHNMDYFKYHNMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRKKRSQRPNKCSNPCP
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Foxp3 are the cause of the scurfy phenotype (sf). It results in a lethal disorder of immunoregulation, characterized by infections, diarrhea, anemia, thrombocytopenia, hypogonadism, gastrointestinal bleeding, lymphadenopathy and leukocytosis.
uniprot
proteins
function
FUNCTION: Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:22813742). 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 (By similarity). 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 (By similarity). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (PubMed:19696312). {ECO:0000250|UniProtKB:Q9BZS1, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:18368049, ECO:0000269|PubMed:19696312, ECO:0000269|PubMed:22813742}.
uniprot
proteins
mass_dalton
47346
uniprot
proteins
mutagenesis
MUTAGEN 19; /note="S->A: Loss of phosphorylation. Increase in protein stability, transcriptional activity and the ability to suppress the proliferation of conventional T-cells in vitro; when associated with A-88; A-114 and A-175."; /evidence="ECO:0000269|PubMed:23853094"; MUTAGEN 48..51; /note="RDLR->HDLH: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:19117830"; MUTAGEN 88; /note="S->A: Increase in protein stability, transcriptional activity and the ability to suppress the proliferation of conventional T-cells in vitro; when associated with A-19; A-114 and A-175."; /evidence="ECO:0000269|PubMed:23853094"; MUTAGEN 114; /note="T->A: Increase in protein stability, transcriptional activity and the ability to suppress the proliferation of conventional T-cells in vitro; when associated with A-19; A-88 and A-175."; /evidence="ECO:0000269|PubMed:23853094"; MUTAGEN 175; /note="T->A: Increase in protein stability, transcriptional activity and the ability to suppress the proliferation of conventional T-cells in vitro; when associated with A-19; A-88 and A-114."; /evidence="ECO:0000269|PubMed:23853094"; MUTAGEN 250; /note="Missing: Loss of homodimerization, decrease in transcriptional repressor activity, elimination of its Treg suppressor activity, defects in Th1 and Th2 cytokine secretion and down-regulation of cell surface markers on regulatory T-cells."; /evidence="ECO:0000269|PubMed:16769892"; MUTAGEN 329..330; /note="DY->VH: Reduced interaction with RUNX1, decrease in its ability to regulate the expression of IL2, TNFRSF18, IL2RA and CTLA4 in a RUNX1-dependent manner. Loss of interaction with RUNX1 but no effect on interaction with NFATC2 and loss of its ability to regulate the expression of IL2, TNFRSF18, IL2RA and CTLA4 in a RUNX1-dependent manner; when associated with L-332."; /evidence="ECO:0000269|PubMed:17377532"; MUTAGEN 332; /note="K->L: Loss of interaction with RUNX1 but no effect on interaction with NFATC2 and loss of its ability to regulate the expression of IL2, TNFRSF18, IL2RA and CTLA4 in a RUNX1-dependent manner; when associated with 329-VH-330."; /evidence="ECO:0000269|PubMed:17377532"; MUTAGEN 414..417; /note="RKKR->PNNW: Loss of ability to suppress the proliferation of effector T-cells."; /evidence="ECO:0000269|PubMed:19117830"; MUTAGEN 414..417; /note="RKKR->QNKS: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:19117830
uniprot
proteins
post_translational_modification
PTM: Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions (PubMed:22312127). 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 (By similarity). Deacetylated by SIRT1 (PubMed:22312127). {ECO:0000250|UniProtKB:Q9BZS1, ECO:0000269|PubMed:22312127}.; 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 and USP44 leading to increase in protein stability. {ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:23973223}.; PTM: Phosphorylation at Ser-418 regulates its transcriptional repressor activity and consequently, regulatory T-cells (Treg) suppressive function (By similarity). Phosphorylation by CDK2 negatively regulates its transcriptional activity and protein stability. {ECO:0000250|UniProtKB:Q9BZS1, ECO:0000269|PubMed:23853094}.; PTM: 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. Treg expressing the form cleaved at C-terminal site or both N- and C-terminal sites exhibit an increased induction of IL10 and an increased capacity to suppress proliferation of conventional T-cells in vitro. Treg expressing the form cleaved at only the C-terminal site are highly effective at preventing experimental colitis in an in vivo model of inflammatory bowel disease. {ECO:0000269|PubMed:19117830}.
uniprot
proteins
pubmed
11138001
uniprot
proteins
pubmed
15790681
uniprot
proteins
pubmed
16769892
uniprot
proteins
pubmed
17377532
uniprot
proteins
pubmed
18368049
uniprot
proteins
pubmed
19117830
uniprot
proteins
pubmed
19696312
uniprot
proteins
pubmed
22312127
uniprot
proteins
pubmed
22813742
uniprot
proteins
pubmed
23853094
uniprot
proteins
pubmed
23973222
uniprot
proteins
pubmed
23973223
uniprot
proteins
pubmed
24722479
uniprot
proteins
sequence_length
429
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:18368049}. Cytoplasm {ECO:0000250|UniProtKB:Q9BZS1}. Note=Predominantly expressed in the cytoplasm in activated conventional T-cells whereas predominantly expressed in the nucleus in regulatory T-cells (Treg) (By similarity). The 41 kDa form derived by proteolytic processing is found exclusively in the chromatin fraction of activated Treg cells. {ECO:0000250|UniProtKB:Q9BZS1, ECO:0000269|PubMed:19117830}.
uniprot
proteins