FOXP3
entrez
50943
canonical
uniprot
Q9BZS1
canonical
ensembl
ENSG00000049768
resolver
ensp
ENSP00000365372
resolver
ensp
ENSP00000365380
resolver
genesymbol
FOXP3
resolver
genesymbol_syn
IPEX
resolver
hgnc
HGNC:6106
resolver
uniprot
A5HJT1
resolver
uniprot
B7ZLG0
resolver
uniprot
B9UN80
resolver
uniprot
O60827
resolver
uniprot
Q14DD8
resolver
uniprot
Q4ZH51
resolver
uniprot_entry
FOXP3_HUMAN
resolver
uniprot_sec
A5HJT1
resolver
uniprot_sec
B7ZLG0
resolver
uniprot_sec
B9UN80
resolver
uniprot_sec
O60827
resolver
uniprot_sec
Q14DD8
resolver
uniprot_sec
Q4ZH51
resolver
amino_acid_sequence
MPNPRPGKPSAPSLALGPSPGASPSWRAAPKASDLLGARGPGGTFQGRDLRGGAHASSSSLNPMPPSQLQLPTLPLVMVAPSGARLGPLPHLQALLQDRPHFMHQLSTVDAHARTPVLQVHPLESPAMISLTPPTTATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPNPSAPRKDSTLSAVPQSSYPLLANGVCKWPGCEKVFEEPEDFLKHCQADHLLDEKGRAQCLLQREMVQSLEQQLVLEKEKLSAMQAHLAGKMALTKASSVASSDKGSCCIVAAGSQGPVVPAWSGPREAPDSLFAVRRHLWGSHGNSTFPEFLHNMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTLNEIYHWFTRMFAFFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDELEFRKKRSQRPSRCSNPTPGP
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) [MIM:304790]: Characterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, thrombocytopenia, anemia and eczema. It is usually lethal in infancy. {ECO:0000269|PubMed:11120765, ECO:0000269|PubMed:11137992, ECO:0000269|PubMed:11137993, ECO:0000269|PubMed:11768393, ECO:0000269|PubMed:18951619, ECO:0000269|PubMed:21458306}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {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, ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:30513302, ECO:0000269|PubMed:32644293, ECO:0000303|PubMed:23947341, ECO:0000303|PubMed:24354325, ECO:0000303|PubMed:24722479}.
uniprot
proteins
mass_dalton
47244
uniprot
proteins
mutagenesis
MUTAGEN 69; /note="L->A: Decrease in nuclear export; when associated with A-71, A-74 and A-76."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 71; /note="L->A: Decrease in nuclear export; when associated with A-69, A-74 and A-76."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 74; /note="L->A: Decrease in nuclear export; when associated with A-69, A-71 and A-76."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 76; /note="L->A: Decrease in nuclear export; when associated with A-69, A-71 and A-74."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 95..96; /note="LL->AA: Loss of interaction with RORA."; /evidence="ECO:0000269|PubMed:18354202"; MUTAGEN 242; /note="L->A: Decrease in nuclear export; when associated with A-246 and A-248."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 246; /note="L->A: Decrease in nuclear export; when associated with A-242 and A-248."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 248; /note="L->A: Decrease in nuclear export; when associated with A-242 and A-246."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 348; /note="W->Q: No loss of DNA-binding. Disrupts dimerization but does not affect DNA-binding; when associated with T-370. Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with T-370 and P-372."; /evidence="ECO:0000269|PubMed:21458306"; MUTAGEN 370; /note="M->T: Disrupts dimerization but does not affect DNA-binding; when associated with Q-348. Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with Q-348 and P-372."; /evidence="ECO:0000269|PubMed:21458306"; MUTAGEN 372; /note="A->P: Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with Q-348 and T-370."; /evidence="ECO:0000269|PubMed:21458306"; MUTAGEN 415..416; /note="KK->EE: Loss of nuclear localization."; /evidence="ECO:0000269|PubMed:22678915"; MUTAGEN 418; /note="S->A: Decrease in phosphorylation, significant decrease in transcriptional repressor activity and reduced interaction with PP1CA, PP1CB and PP1CG. Significant decrease in phosphorylation and transcriptional repressor activity; when associated with A-422."; /evidence="ECO:0000269|PubMed:23396208"; MUTAGEN 418; /note="S->E: Slight increase in transcriptional repressor activity."; /evidence="ECO:0000269|PubMed:23396208"; MUTAGEN 422; /note="S->A: Significant decrease in phosphorylation and transcriptional repressor activity; when associated with A-418."; /evidence="ECO:0000269|PubMed:23396208
uniprot
proteins
post_translational_modification
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, ECO:0000269|PubMed:32644293}.; PTM: 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). {ECO:0000250|UniProtKB:Q99JB6, ECO:0000269|PubMed:23396208}.; PTM: 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). {ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:22312127, ECO:0000269|PubMed:24835996}.; 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. {ECO:0000269|PubMed:19117830}.
uniprot
proteins
pubmed
11120765
uniprot
proteins
pubmed
11137992
uniprot
proteins
pubmed
11137993
uniprot
proteins
pubmed
11138001
uniprot
proteins
pubmed
11768393
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
15790681
uniprot
proteins
pubmed
17360565
uniprot
proteins
pubmed
17377532
uniprot
proteins
pubmed
18354202
uniprot
proteins
pubmed
18368049
uniprot
proteins
pubmed
18951619
uniprot
proteins
pubmed
19117830
uniprot
proteins
pubmed
20676092
uniprot
proteins
pubmed
21458306
uniprot
proteins
pubmed
22312127
uniprot
proteins
pubmed
22678915
uniprot
proteins
pubmed
23169781
uniprot
proteins
pubmed
23396208
uniprot
proteins
pubmed
23543754
uniprot
proteins
pubmed
23947341
uniprot
proteins
pubmed
23973222
uniprot
proteins
pubmed
23973223
uniprot
proteins
pubmed
24350059
uniprot
proteins
pubmed
24354325
uniprot
proteins
pubmed
24722479
uniprot
proteins
pubmed
24835996
uniprot
proteins
pubmed
25047417
uniprot
proteins
pubmed
25567984
uniprot
proteins
pubmed
30513302
uniprot
proteins
pubmed
32644293
uniprot
proteins
sequence_length
431
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:18354202, ECO:0000269|PubMed:22678915, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:32644293}. Cytoplasm {ECO:0000269|PubMed:22678915}. Note=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). {ECO:0000250|UniProtKB:Q99JB6, ECO:0000269|PubMed:22678915}.
uniprot
proteins