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Q99JB6

- FOXP3_MOUSE

UniProt

Q99JB6 - FOXP3_MOUSE

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Protein

Forkhead box protein P3

Gene

Foxp3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Probable transcription factor. Plays a critical role in the control of immune response.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri196 – 22126C2H2-typeAdd
BLAST
DNA bindingi337 – 42387Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. NFAT protein binding Source: UniProtKB
  3. protein homodimerization activity Source: UniProtKB
  4. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
  5. sequence-specific DNA binding Source: UniProtKB
  6. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  7. transcription corepressor activity Source: MGI

GO - Biological processi

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

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein P3
Alternative name(s):
Scurfin
Gene namesi
Name:Foxp3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome X

Organism-specific databases

MGIiMGI:1891436. Foxp3.

Subcellular locationi

Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. intracellular Source: MGI
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 429429Forkhead box protein P3PRO_0000091888Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei31 – 311N6-acetyllysine1 Publication
Modified residuei262 – 2621N6-acetyllysine1 Publication
Modified residuei267 – 2671N6-acetyllysine1 Publication

Post-translational modificationi

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

Keywords - PTMi

Acetylation

Proteomic databases

PRIDEiQ99JB6.

PTM databases

PhosphoSiteiQ99JB6.

Expressioni

Tissue specificityi

High level of expression in thymus and spleen.

Gene expression databases

BgeeiQ99JB6.
CleanExiMM_FOXP3.
ExpressionAtlasiQ99JB6. baseline and differential.
GenevestigatoriQ99JB6.

Interactioni

Subunit structurei

Interacts with IKZF3.By similarity

Protein-protein interaction databases

BioGridi203183. 369 interactions.
DIPiDIP-59739N.

Structurei

Secondary structure

1
429
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni204 – 2074
Helixi208 – 25750

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4I1LX-ray2.10A189-276[»]
ProteinModelPortaliQ99JB6.
SMRiQ99JB6. Positions 201-262, 336-417.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni238 – 25922Leucine-zipperAdd
BLAST

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 fingeri196 – 22126C2H2-typeAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00750000117475.
HOGENOMiHOG000082490.
HOVERGENiHBG051656.
InParanoidiQ99JB6.
KOiK10163.
OMAiKHCQADH.
OrthoDBiEOG7M6D7G.
PhylomeDBiQ99JB6.
TreeFamiTF326978.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
3.30.160.60. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
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]

Sequencei

Sequence statusi: Complete.

Q99JB6-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPNPRPAKPM APSLALGPSP GVLPSWKTAP KGSELLGTRG SGGPFQGRDL
60 70 80 90 100
RSGAHTSSSL NPLPPSQLQL PTVPLVMVAP SGARLGPSPH LQALLQDRPH
110 120 130 140 150
FMHQLSTVDA HAQTPVLQVR PLDNPAMISL PPPSAATGVF SLKARPGLPP
160 170 180 190 200
GINVASLEWV SREPALLCTF PRSGTPRKDS NLLAAPQGSY PLLANGVCKW
210 220 230 240 250
PGCEKVFEEP EEFLKHCQAD HLLDEKGKAQ CLLQREVVQS LEQQLELEKE
260 270 280 290 300
KLGAMQAHLA GKMALAKAPS VASMDKSSCC IVATSTQGSV LPAWSAPREA
310 320 330 340 350
PDGGLFAVRR HLWGSHGNSS FPEFFHNMDY FKYHNMRPPF TYATLIRWAI
360 370 380 390 400
LEAPERQRTL NEIYHWFTRM FAYFRNHPAT WKNAIRHNLS LHKCFVRVES
410 420
EKGAVWTVDE FEFRKKRSQR PNKCSNPCP
Length:429
Mass (Da):47,346
Last modified:June 1, 2001 - v1
Checksum:i28D5B8E67891840C
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF277994 Genomic DNA. Translation: AAG53608.1.
AF277991 mRNA. Translation: AAG53605.1.
AF277992 mRNA. Translation: AAG53606.1.
CCDSiCCDS29965.1.
RefSeqiNP_001186276.1. NM_001199347.1.
NP_001186277.1. NM_001199348.1.
NP_473380.1. NM_054039.2.
UniGeneiMm.182291.
Mm.288192.

Genome annotation databases

EnsembliENSMUST00000045566; ENSMUSP00000041953; ENSMUSG00000039521.
ENSMUST00000115738; ENSMUSP00000111403; ENSMUSG00000039521.
ENSMUST00000115739; ENSMUSP00000111404; ENSMUSG00000039521.
ENSMUST00000115740; ENSMUSP00000111405; ENSMUSG00000039521.
GeneIDi20371.
KEGGimmu:20371.
UCSCiuc009sll.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF277994 Genomic DNA. Translation: AAG53608.1 .
AF277991 mRNA. Translation: AAG53605.1 .
AF277992 mRNA. Translation: AAG53606.1 .
CCDSi CCDS29965.1.
RefSeqi NP_001186276.1. NM_001199347.1.
NP_001186277.1. NM_001199348.1.
NP_473380.1. NM_054039.2.
UniGenei Mm.182291.
Mm.288192.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4I1L X-ray 2.10 A 189-276 [» ]
ProteinModelPortali Q99JB6.
SMRi Q99JB6. Positions 201-262, 336-417.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 203183. 369 interactions.
DIPi DIP-59739N.

PTM databases

PhosphoSitei Q99JB6.

Proteomic databases

PRIDEi Q99JB6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000045566 ; ENSMUSP00000041953 ; ENSMUSG00000039521 .
ENSMUST00000115738 ; ENSMUSP00000111403 ; ENSMUSG00000039521 .
ENSMUST00000115739 ; ENSMUSP00000111404 ; ENSMUSG00000039521 .
ENSMUST00000115740 ; ENSMUSP00000111405 ; ENSMUSG00000039521 .
GeneIDi 20371.
KEGGi mmu:20371.
UCSCi uc009sll.2. mouse.

Organism-specific databases

CTDi 50943.
MGIi MGI:1891436. Foxp3.

Phylogenomic databases

eggNOGi COG5025.
GeneTreei ENSGT00750000117475.
HOGENOMi HOG000082490.
HOVERGENi HBG051656.
InParanoidi Q99JB6.
KOi K10163.
OMAi KHCQADH.
OrthoDBi EOG7M6D7G.
PhylomeDBi Q99JB6.
TreeFami TF326978.

Miscellaneous databases

NextBioi 298278.
PROi Q99JB6.
SOURCEi Search...

Gene expression databases

Bgeei Q99JB6.
CleanExi MM_FOXP3.
ExpressionAtlasi Q99JB6. baseline and differential.
Genevestigatori Q99JB6.

Family and domain databases

Gene3Di 1.10.10.10. 1 hit.
3.30.160.60. 1 hit.
InterProi IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view ]
Pfami PF00250. Fork_head. 1 hit.
[Graphical view ]
PRINTSi PR00053. FORKHEAD.
SMARTi SM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view ]
PROSITEi PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  2. "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(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-31; LYS-262 AND LYS-267, DEACETYLATION BY SIRT1.

Entry informationi

Entry nameiFOXP3_MOUSE
AccessioniPrimary (citable) accession number: Q99JB6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: June 1, 2001
Last modified: October 29, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3