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Protein

Forkhead box protein P3

Gene

FOXP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity6 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei51 – 522Cleavage1 Publication
Sitei417 – 4182Cleavage; by PCSK1 or PCSK21 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri197 – 22226C2H2-typeAdd
BLAST
DNA bindingi337 – 42387Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. core promoter binding Source: UniProtKB
  2. histone acetyltransferase binding Source: BHF-UCL
  3. histone deacetylase binding Source: BHF-UCL
  4. metal ion binding Source: UniProtKB-KW
  5. NFAT protein binding Source: UniProtKB
  6. NF-kappaB binding Source: UniProtKB
  7. protein homodimerization activity Source: UniProtKB
  8. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
  9. sequence-specific DNA binding Source: UniProtKB
  10. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: GO_Central
  11. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  12. transcription corepressor activity Source: Ensembl

GO - Biological processi

  1. B cell homeostasis Source: Ensembl
  2. CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment Source: UniProtKB
  3. chromatin remodeling Source: UniProtKB
  4. cytokine production Source: Ensembl
  5. myeloid cell homeostasis Source: Ensembl
  6. negative regulation of activated T cell proliferation Source: UniProtKB
  7. negative regulation of cell proliferation Source: UniProtKB
  8. negative regulation of chronic inflammatory response Source: Ensembl
  9. negative regulation of CREB transcription factor activity Source: UniProtKB
  10. negative regulation of cytokine biosynthetic process Source: UniProtKB
  11. negative regulation of cytokine secretion Source: UniProtKB
  12. negative regulation of histone acetylation Source: Ensembl
  13. negative regulation of histone deacetylation Source: BHF-UCL
  14. negative regulation of immune response Source: UniProtKB
  15. negative regulation of interferon-gamma biosynthetic process Source: Ensembl
  16. negative regulation of interferon-gamma production Source: UniProtKB
  17. negative regulation of interleukin-10 production Source: UniProtKB
  18. negative regulation of interleukin-17 production Source: UniProtKB
  19. negative regulation of interleukin-2 biosynthetic process Source: UniProtKB
  20. negative regulation of interleukin-2 production Source: UniProtKB
  21. negative regulation of interleukin-4 production Source: UniProtKB
  22. negative regulation of interleukin-5 production Source: Ensembl
  23. negative regulation of interleukin-6 production Source: Ensembl
  24. negative regulation of isotype switching to IgE isotypes Source: Ensembl
  25. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  26. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  27. negative regulation of T cell cytokine production Source: UniProtKB
  28. negative regulation of T cell proliferation Source: UniProtKB
  29. negative regulation of T-helper 17 cell differentiation Source: UniProtKB
  30. negative regulation of transcription, DNA-templated Source: UniProtKB
  31. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  32. negative regulation of tumor necrosis factor production Source: Ensembl
  33. positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation Source: UniProtKB
  34. positive regulation of histone acetylation Source: BHF-UCL
  35. positive regulation of immature T cell proliferation in thymus Source: Ensembl
  36. positive regulation of interleukin-4 production Source: Ensembl
  37. positive regulation of peripheral T cell tolerance induction Source: Ensembl
  38. positive regulation of T cell anergy Source: Ensembl
  39. positive regulation of transcription, DNA-templated Source: UniProtKB
  40. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  41. positive regulation of transforming growth factor beta1 production Source: Ensembl
  42. regulation of isotype switching to IgG isotypes Source: Ensembl
  43. regulation of T cell anergy Source: UniProtKB
  44. regulation of transcription, DNA-templated Source: UniProtKB
  45. response to virus Source: UniProtKB
  46. T cell activation Source: UniProtKB
  47. T cell homeostasis Source: UniProtKB
  48. T cell mediated immunity Source: Ensembl
  49. T cell receptor signaling pathway Source: Ensembl
  50. tolerance induction to self antigen Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ9BZS1.

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein P3
Alternative name(s):
Scurfin
Cleaved into the following 2 chains:
Gene namesi
Name:FOXP3
Synonyms:IPEX
ORF Names:JM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:6106. FOXP3.

Subcellular locationi

Nucleus PROSITE-ProRule annotation6 Publications. Cytoplasm 1 Publication
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).By similarity1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
  3. protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)4 Publications

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

Disease descriptionCharacterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, thrombocytopenia, anemia and eczema. It is usually lethal in infancy.

See also OMIM:304790
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti251 – 2511Missing in IPEX. 1 Publication
VAR_011330
Natural varianti363 – 3631I → V in IPEX. 1 Publication
VAR_023569
Natural varianti371 – 3711F → C in IPEX. 1 Publication
VAR_011331
Natural varianti384 – 3841A → T in IPEX. 2 Publications
VAR_011332
Natural varianti397 – 3971R → W in IPEX. 1 Publication
Corresponds to variant rs28935477 [ dbSNP | Ensembl ].
VAR_011333

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi69 – 691L → A: Decrease in nuclear export; when associated with A-71, A-74 and A-76. 1 Publication
Mutagenesisi71 – 711L → A: Decrease in nuclear export; when associated with A-69, A-74 and A-76. 1 Publication
Mutagenesisi74 – 741L → A: Decrease in nuclear export; when associated with A-69, A-71 and A-76. 1 Publication
Mutagenesisi76 – 761L → A: Decrease in nuclear export; when associated with A-69, A-71 and A-74. 1 Publication
Mutagenesisi95 – 962LL → AA: Loss of interaction with RORA. 1 Publication
Mutagenesisi242 – 2421L → A: Decrease in nuclear export; when associated with A-246 and A-248. 1 Publication
Mutagenesisi246 – 2461L → A: Decrease in nuclear export; when associated with A-242 and A-248. 1 Publication
Mutagenesisi248 – 2481L → A: Decrease in nuclear export; when associated with A-242 and A-246. 1 Publication
Mutagenesisi415 – 4162KK → EE: Loss of nuclear localization. 1 Publication
Mutagenesisi418 – 4181S → 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. 1 Publication
Mutagenesisi418 – 4181S → E: Slight increase in transcriptional repressor activity. 1 Publication
Mutagenesisi422 – 4221S → A: Significant decrease in phosphorylation and transcriptional repressor activity; when associated with A-418. 1 Publication

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

MIMi304790. phenotype.
Orphaneti37042. Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.
PharmGKBiPA201094.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 431431Forkhead box protein P3PRO_0000091886Add
BLAST
Chaini1 – 417417Forkhead box protein P3, C-terminally processed1 PublicationPRO_0000432430Add
BLAST
Chaini52 – 417366Forkhead box protein P3 41 kDa form1 PublicationPRO_0000432431Add
BLAST
Propeptidei418 – 431141 PublicationPRO_0000432432Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Phosphoserine; by CDK2By similarity
Modified residuei31 – 311N6-acetyllysine1 Publication
Cross-linki250 – 250Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki252 – 252Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei263 – 2631N6-acetyllysine1 Publication
Cross-linki263 – 263Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei268 – 2681N6-acetyllysine1 Publication
Cross-linki268 – 268Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki393 – 393Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei418 – 4181Phosphoserine1 Publication

Post-translational modificationi

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.2 Publications
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).By similarity1 Publication
Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions. Deacetylated by SIRT1.2 Publications
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.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9BZS1.
PRIDEiQ9BZS1.

PTM databases

PhosphoSiteiQ9BZS1.

Expressioni

Inductioni

Down-regulated in regulatory T-cells (Treg) during inflammation.1 Publication

Gene expression databases

BgeeiQ9BZS1.
CleanExiHS_FOXP3.
ExpressionAtlasiQ9BZS1. baseline and differential.
GenevestigatoriQ9BZS1.

Organism-specific databases

HPAiCAB026301.
HPA045943.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with IKZF3. Isoform 1 (via LXXLL motif), but not isoform 2, interacts with isoform 4 of RORA (via AF-2 motif). Interacts with STUB1, HSPA8 and HSPA1A/B. Interacts with PPP1CA, PPP1CB and PPP1CG. Interacts with KAT5 and HDAC7. Interacts with HDAC9 in the absence of T-cell stimulation. Interacts with USP7. Interacts with isoform 2 of ZFP90 and can form a complex with TRIM28 in the presence of isoform 2 of ZFP90. Interacts with RUNX1. Interacts with RORC. Interacts with RELA and NFATC2. Interacts with RUNX2, RUNX3 and IKZF4 (By similarity).By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HDAC7Q8WUI42EBI-9695448,EBI-1048378
IKZF3Q9UKT92EBI-983719,EBI-747204
KAT5Q929932EBI-9695448,EBI-399080

Protein-protein interaction databases

BioGridi119170. 24 interactions.
DIPiDIP-36584N.
IntActiQ9BZS1. 4 interactions.
STRINGi9606.ENSP00000365380.

Structurei

Secondary structure

1
431
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi342 – 35110Combined sources
Helixi360 – 37112Combined sources
Turni372 – 3754Combined sources
Helixi381 – 39111Combined sources
Beta strandi395 – 3984Combined sources
Beta strandi401 – 4033Combined sources
Beta strandi405 – 4084Combined sources
Helixi410 – 4167Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QRFX-ray2.80F/G/H/I336-417[»]
ProteinModelPortaliQ9BZS1.
SMRiQ9BZS1. Positions 202-263, 336-417.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BZS1.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni106 – 19893Interaction with ZFP901 PublicationAdd
BLAST
Regioni106 – 19085Essential for transcriptional repressor activity and for interaction with KAT5 and HDAC71 PublicationAdd
BLAST
Regioni149 – 19951Interaction with IKZF4By similarityAdd
BLAST
Regioni239 – 26022Leucine-zipperAdd
BLAST
Regioni278 – 33659Interaction with RUNX11 PublicationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi68 – 769Nuclear export signal1 Publication
Motifi92 – 965LXXLL motif1 Publication
Motifi239 – 24810Nuclear export signal1 Publication
Motifi414 – 4174Nuclear localization signal1 Publication

Sequence similaritiesi

Contains 1 C2H2-type zinc finger.Curated
Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri197 – 22226C2H2-typeAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00780000121840.
HOGENOMiHOG000082490.
HOVERGENiHBG051656.
InParanoidiQ9BZS1.
KOiK10163.
OMAiKHCQADH.
OrthoDBiEOG7M6D7G.
PhylomeDBiQ9BZS1.
TreeFamiTF326978.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
3.30.160.60. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR011991. WHTH_DNA-bd_dom.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BZS1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPNPRPGKPS APSLALGPSP GASPSWRAAP KASDLLGARG PGGTFQGRDL
60 70 80 90 100
RGGAHASSSS LNPMPPSQLQ LPTLPLVMVA PSGARLGPLP HLQALLQDRP
110 120 130 140 150
HFMHQLSTVD AHARTPVLQV HPLESPAMIS LTPPTTATGV FSLKARPGLP
160 170 180 190 200
PGINVASLEW VSREPALLCT FPNPSAPRKD STLSAVPQSS YPLLANGVCK
210 220 230 240 250
WPGCEKVFEE PEDFLKHCQA DHLLDEKGRA QCLLQREMVQ SLEQQLVLEK
260 270 280 290 300
EKLSAMQAHL AGKMALTKAS SVASSDKGSC CIVAAGSQGP VVPAWSGPRE
310 320 330 340 350
APDSLFAVRR HLWGSHGNST FPEFLHNMDY FKFHNMRPPF TYATLIRWAI
360 370 380 390 400
LEAPEKQRTL NEIYHWFTRM FAFFRNHPAT WKNAIRHNLS LHKCFVRVES
410 420 430
EKGAVWTVDE LEFRKKRSQR PSRCSNPTPG P
Length:431
Mass (Da):47,244
Last modified:June 1, 2001 - v1
Checksum:i91737C3CEA665A15
GO
Isoform 2 (identifier: Q9BZS1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     72-106: Missing.

Show »
Length:396
Mass (Da):43,410
Checksum:iBF4DF0DD83D61CD5
GO
Isoform 3 (identifier: Q9BZS1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     72-106: Missing.
     382-382: K → KVSSSEVAVTGMASSAIAAQSGQAWVWAHRHIGEERDVGCWWWLLASEVDAHLLPVPGLPQ

Note: No experimental confirmation available.

Show »
Length:456
Mass (Da):49,843
Checksum:i39E7483703031335
GO
Isoform 4 (identifier: Q9BZS1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     246-272: Missing.

Show »
Length:404
Mass (Da):44,407
Checksum:i4D164C39EF069DBB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti16 – 205LGPSP → MSPIS in CAA06748 (Ref. 7) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti251 – 2511Missing in IPEX. 1 Publication
VAR_011330
Natural varianti363 – 3631I → V in IPEX. 1 Publication
VAR_023569
Natural varianti371 – 3711F → C in IPEX. 1 Publication
VAR_011331
Natural varianti384 – 3841A → T in IPEX. 2 Publications
VAR_011332
Natural varianti397 – 3971R → W in IPEX. 1 Publication
Corresponds to variant rs28935477 [ dbSNP | Ensembl ].
VAR_011333

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei72 – 10635Missing in isoform 2 and isoform 3. 3 PublicationsVSP_015796Add
BLAST
Alternative sequencei246 – 27227Missing in isoform 4. 1 PublicationVSP_047859Add
BLAST
Alternative sequencei382 – 3821K → KVSSSEVAVTGMASSAIAAQ SGQAWVWAHRHIGEERDVGC WWWLLASEVDAHLLPVPGLP Q in isoform 3. 1 PublicationVSP_036418

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF277993 mRNA. Translation: AAG53607.1.
EF534714 mRNA. Translation: ABQ15210.1.
EU855812 mRNA. Translation: ACJ46653.1.
DQ010327 mRNA. Translation: AAY27088.1.
AF235097 Genomic DNA. No translation available.
BC113401 mRNA. Translation: AAI13402.1.
BC113403 mRNA. Translation: AAI13404.1.
BC143785 mRNA. Translation: AAI43786.1.
AJ005891 mRNA. Translation: CAA06748.1.
CCDSiCCDS14323.1. [Q9BZS1-1]
CCDS48109.1. [Q9BZS1-2]
RefSeqiNP_001107849.1. NM_001114377.1. [Q9BZS1-2]
NP_054728.2. NM_014009.3. [Q9BZS1-1]
UniGeneiHs.247700.

Genome annotation databases

EnsembliENST00000376199; ENSP00000365372; ENSG00000049768. [Q9BZS1-2]
ENST00000376207; ENSP00000365380; ENSG00000049768. [Q9BZS1-1]
ENST00000518685; ENSP00000428952; ENSG00000049768. [Q9BZS1-2]
ENST00000557224; ENSP00000451208; ENSG00000049768. [Q9BZS1-3]
GeneIDi50943.
KEGGihsa:50943.
UCSCiuc004dne.4. human. [Q9BZS1-2]
uc004dnf.4. human. [Q9BZS1-1]
uc022bwa.1. human. [Q9BZS1-3]

Polymorphism databases

DMDMi14548061.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
FOXP3base

FOXP3 mutation db

Wikipedia

FOXP3 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF277993 mRNA. Translation: AAG53607.1.
EF534714 mRNA. Translation: ABQ15210.1.
EU855812 mRNA. Translation: ACJ46653.1.
DQ010327 mRNA. Translation: AAY27088.1.
AF235097 Genomic DNA. No translation available.
BC113401 mRNA. Translation: AAI13402.1.
BC113403 mRNA. Translation: AAI13404.1.
BC143785 mRNA. Translation: AAI43786.1.
AJ005891 mRNA. Translation: CAA06748.1.
CCDSiCCDS14323.1. [Q9BZS1-1]
CCDS48109.1. [Q9BZS1-2]
RefSeqiNP_001107849.1. NM_001114377.1. [Q9BZS1-2]
NP_054728.2. NM_014009.3. [Q9BZS1-1]
UniGeneiHs.247700.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QRFX-ray2.80F/G/H/I336-417[»]
ProteinModelPortaliQ9BZS1.
SMRiQ9BZS1. Positions 202-263, 336-417.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119170. 24 interactions.
DIPiDIP-36584N.
IntActiQ9BZS1. 4 interactions.
STRINGi9606.ENSP00000365380.

PTM databases

PhosphoSiteiQ9BZS1.

Polymorphism databases

DMDMi14548061.

Proteomic databases

PaxDbiQ9BZS1.
PRIDEiQ9BZS1.

Protocols and materials databases

DNASUi50943.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376199; ENSP00000365372; ENSG00000049768. [Q9BZS1-2]
ENST00000376207; ENSP00000365380; ENSG00000049768. [Q9BZS1-1]
ENST00000518685; ENSP00000428952; ENSG00000049768. [Q9BZS1-2]
ENST00000557224; ENSP00000451208; ENSG00000049768. [Q9BZS1-3]
GeneIDi50943.
KEGGihsa:50943.
UCSCiuc004dne.4. human. [Q9BZS1-2]
uc004dnf.4. human. [Q9BZS1-1]
uc022bwa.1. human. [Q9BZS1-3]

Organism-specific databases

CTDi50943.
GeneCardsiGC0XM049106.
GeneReviewsiFOXP3.
HGNCiHGNC:6106. FOXP3.
HPAiCAB026301.
HPA045943.
MIMi300292. gene.
304790. phenotype.
neXtProtiNX_Q9BZS1.
Orphaneti37042. Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.
PharmGKBiPA201094.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00780000121840.
HOGENOMiHOG000082490.
HOVERGENiHBG051656.
InParanoidiQ9BZS1.
KOiK10163.
OMAiKHCQADH.
OrthoDBiEOG7M6D7G.
PhylomeDBiQ9BZS1.
TreeFamiTF326978.

Enzyme and pathway databases

SignaLinkiQ9BZS1.

Miscellaneous databases

EvolutionaryTraceiQ9BZS1.
GeneWikiiFOXP3.
GenomeRNAii50943.
NextBioi35482169.
PROiQ9BZS1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BZS1.
CleanExiHS_FOXP3.
ExpressionAtlasiQ9BZS1. baseline and differential.
GenevestigatoriQ9BZS1.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
3.30.160.60. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR011991. WHTH_DNA-bd_dom.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse."
    Brunkow M.E., Jeffery E.W., Hjerrild K.A., Paeper B., Clark L.B., Yasayko S.-A., Wilkinson J.E., Galas D., Ziegler S.F., Ramsdell F.
    Nat. Genet. 27:68-73(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Cloning and expression of the cDNA for FOXP3."
    Wang J., Liu Q., Zhang Y., Xu Z., Huang C.
    Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Functional characterization of FOXP3 splice variants in human regulatory T cells."
    Kaur G., Goodall J.C., Jarvis L.B., Gaston J.S.H.
    Submitted (MAY-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
  4. Lin L., Nong W., Li H., Ke R., Shen C., Zhong G., Zheng Z., Liang M., Huang B., Zhou G., Yang S.
    Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  5. "The DNA sequence of the human X chromosome."
    Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.
    , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
    Nature 434:325-337(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
  7. "Transcription map in Xp11.23."
    Strom T.M., Nyakatura G., Hellebrand H., Drescher B., Rosenthal A., Meindl A.
    Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 16-431 (ISOFORM 3).
  8. "Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells."
    Bettelli E., Dastrange M., Oukka M.
    Proc. Natl. Acad. Sci. U.S.A. 102:5138-5143(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RELA AND NFATC2.
  9. "Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1."
    Ono M., Yaguchi H., Ohkura N., Kitabayashi I., Nagamura Y., Nomura T., Miyachi Y., Tsukada T., Sakaguchi S.
    Nature 446:685-689(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RUNX1.
  10. "FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression."
    Li B., Samanta A., Song X., Iacono K.T., Bembas K., Tao R., Basu S., Riley J.L., Hancock W.W., Shen Y., Saouaf S.J., Greene M.I.
    Proc. Natl. Acad. Sci. U.S.A. 104:4571-4576(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ACETYLATION, INTERACTION WITH KAT5; HDAC7 AND HDAC9, SUBCELLULAR LOCATION.
  11. "Isoform-specific inhibition of ROR alpha-mediated transcriptional activation by human FOXP3."
    Du J., Huang C., Zhou B., Ziegler S.F.
    J. Immunol. 180:4785-4792(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RORA, SUBCELLULAR LOCATION, MUTAGENESIS OF 95-LEU-LEU-96.
  12. "TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function."
    Zhou L., Lopes J.E., Chong M.M., Ivanov I.I., Min R., Victora G.D., Shen Y., Du J., Rubtsov Y.P., Rudensky A.Y., Ziegler S.F., Littman D.R.
    Nature 453:236-240(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RORC.
  13. "Foxp3 processing by proprotein convertases and control of regulatory T cell function."
    de Zoeten E.F., Lee I., Wang L., Chen C., Ge G., Wells A.D., Hancock W.W., Ozkaynak E.
    J. Biol. Chem. 284:5709-5716(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING.
  14. "Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells."
    Gandhi R., Kumar D., Burns E.J., Nadeau M., Dake B., Laroni A., Kozoriz D., Weiner H.L., Quintana F.J.
    Nat. Immunol. 11:846-853(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IKZF3.
  15. "Subcellular localization of FOXP3 in human regulatory and nonregulatory T cells."
    Magg T., Mannert J., Ellwart J.W., Schmid I., Albert M.H.
    Eur. J. Immunol. 42:1627-1638(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF LEU-69; LEU-71; LEU-74; LEU-76; 415-LYS-LYS-416; LEU-242; LEU-246 AND LEU-248.
  16. "Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells."
    Kwon H.S., Lim H.W., Wu J., Schnolzer M., Verdin E., Ott M.
    J. Immunol. 188:2712-2721(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-31; LYS-263 AND LYS-268, DEACETYLATION BY SIRT1.
  17. Cited for: FUNCTION.
  18. "Searching for the Achilles Heel of FOXP3."
    Lozano T., Casares N., Lasarte J.J.
    Front. Oncol. 3:294-294(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  19. "Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7 increases Treg-cell-suppressive capacity."
    van Loosdregt J., Fleskens V., Fu J., Brenkman A.B., Bekker C.P., Pals C.E., Meerding J., Berkers C.R., Barbi J., Grone A., Sijts A.J., Maurice M.M., Kalkhoven E., Prakken B.J., Ovaa H., Pan F., Zaiss D.M., Coffer P.J.
    Immunity 39:259-271(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, DEUBIQUITINATION, SUBCELLULAR LOCATION, INTERACTION WITH USP7.
  20. "The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3."
    Chen Z., Barbi J., Bu S., Yang H.Y., Li Z., Gao Y., Jinasena D., Fu J., Lin F., Chen C., Zhang J., Yu N., Li X., Shan Z., Nie J., Gao Z., Tian H., Li Y.
    , Yao Z., Zheng Y., Park B.V., Pan Z., Zhang J., Dang E., Li Z., Wang H., Luo W., Li L., Semenza G.L., Zheng S.G., Loser K., Tsun A., Greene M.I., Pardoll D.M., Pan F., Li B.
    Immunity 39:272-285(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH STUB1; HSPA8 AND HSPA1A/B, SUBCELLULAR LOCATION, UBIQUITINATION, INDUCTION.
  21. "Cutting Edge: a novel, human-specific interacting protein couples FOXP3 to a chromatin-remodeling complex that contains KAP1/TRIM28."
    Huang C., Martin S., Pfleger C., Du J., Buckner J.H., Bluestone J.A., Riley J.L., Ziegler S.F.
    J. Immunol. 190:4470-4473(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ZFP90.
  22. "Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-alpha in rheumatoid arthritis."
    Nie H., Zheng Y., Li R., Guo T.B., He D., Fang L., Liu X., Xiao L., Chen X., Wan B., Chin Y.E., Zhang J.Z.
    Nat. Med. 19:322-328(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-418, SUBCELLULAR LOCATION, INTERACTION WITH PPP1CA; PPP1CB AND PPP1CG, MUTAGENESIS OF SER-418 AND SER-422, DEPHOSPHORYLATION.
  23. Cited for: REVIEW ON FUNCTION.
  24. Cited for: REVIEW ON FUNCTION.
  25. Cited for: REVIEW.
  26. "Post-translational modification networks regulating FOXP3 function."
    van Loosdregt J., Coffer P.J.
    Trends Immunol. 35:368-378(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON PTM.
  27. "JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome."
    Chatila T.A., Blaeser F., Ho N., Lederman H.M., Voulgaropoulos C., Helms C., Bowcock A.M.
    J. Clin. Invest. 106:R75-R81(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT IPEX GLU-251 DEL.
  28. "Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX)."
    Kobayashi I., Shiari R., Yamada M., Kawamura N., Okano M., Yara A., Iguchi A., Ishikawa N., Ariga T., Sakiyama Y., Ochs H.D., Kobayashi K.
    J. Med. Genet. 38:874-876(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT IPEX VAL-363.
  29. "X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy."
    Wildin R.S., Ramsdell F., Peake J., Faravelli F., Casanova J.-L., Buist N., Levy-Lahad E., Mazzella M., Goulet O., Perroni L., Bricarelli F.D., Byrne G., McEuen M., Proll S., Appleby M., Brunkow M.E.
    Nat. Genet. 27:18-20(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS IPEX CYS-371; THR-384 AND TRP-397.
  30. "The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3."
    Bennett C.L., Christie J., Ramsdell F., Brunkow M.E., Ferguson P.J., Whitesell L., Kelly T.E., Saulsbury F.T., Chance P.F., Ochs H.D.
    Nat. Genet. 27:20-21(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT IPEX THR-384.

Entry informationi

Entry nameiFOXP3_HUMAN
AccessioniPrimary (citable) accession number: Q9BZS1
Secondary accession number(s): A5HJT1
, B7ZLG0, B9UN80, O60827, Q14DD8, Q4ZH51
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: June 1, 2001
Last modified: April 1, 2015
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.