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Q99JB6 (FOXP3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein P3
Alternative name(s):
Scurfin
Gene names
Name:Foxp3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length429 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

Interacts with IKZF3 By similarity.

Subcellular location

Nucleus Potential.

Tissue specificity

High level of expression in thymus and spleen.

Post-translational modification

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. Ref.2

Involvement in disease

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.

Sequence similarities

Contains 1 C2H2-type zinc finger.

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell homeostasis

Inferred from mutant phenotype PubMed 10072494. Source: MGI

CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation

Inferred from mutant phenotype PubMed 12612578PubMed 18573908. Source: MGI

T cell activation

Inferred from sequence or structural similarity. Source: UniProtKB

T cell mediated immunity

Inferred from mutant phenotype PubMed 11714795. Source: MGI

T cell receptor signaling pathway

Inferred from mutant phenotype PubMed 10072494PubMed 11265635. Source: MGI

cardiac muscle cell differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytokine production

Inferred from direct assay PubMed 15790681. Source: MGI

immunoglobulin V(D)J recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

lung development

Inferred from Biological aspect of Ancestor. Source: RefGenome

myeloid cell homeostasis

Inferred from mutant phenotype PubMed 10072494. Source: MGI

negative regulation of CREB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of T cell cytokine production

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of T cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of chronic inflammatory response

Inferred from direct assay PubMed 16769892. Source: MGI

negative regulation of cytokine biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cytokine secretion

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of histone acetylation

Inferred from direct assay PubMed 17028180. Source: MGI

negative regulation of histone deacetylation

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of immune response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of inflammatory response

Inferred from mutant phenotype PubMed 16203996. Source: MGI

negative regulation of interferon-gamma biosynthetic process

Inferred from direct assay PubMed 17028180. Source: MGI

negative regulation of interferon-gamma production

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-10 production

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-2 biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-2 production

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-4 production

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of interleukin-5 production

Inferred from direct assay PubMed 16769892. Source: MGI

negative regulation of interleukin-6 production

Inferred from mutant phenotype PubMed 16275384. Source: MGI

negative regulation of isotype switching to IgE isotypes

Inferred from mutant phenotype PubMed 16275384. Source: MGI

negative regulation of lymphocyte proliferation

Inferred from mutant phenotype PubMed 16227984PubMed 16275384. Source: MGI

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16230479PubMed 16769892PubMed 17028180. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of tumor necrosis factor production

Inferred from mutant phenotype PubMed 16275384. Source: MGI

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation

Inferred from mutant phenotype PubMed 16275384PubMed 16301745. Source: MGI

positive regulation of T cell anergy

Inferred from mutant phenotype PubMed 16945588. Source: MGI

positive regulation of T cell tolerance induction

Inferred from mutant phenotype PubMed 16945588. Source: MGI

positive regulation of epithelial cell proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of gene expression

Inferred from direct assay PubMed 20706986. Source: MGI

positive regulation of histone acetylation

Inferred from direct assay PubMed 17028180. Source: MGI

positive regulation of immature T cell proliferation in thymus

Inferred from mutant phenotype PubMed 16230479. Source: MGI

positive regulation of immunoglobulin production

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of interleukin-4 production

Inferred from mutant phenotype PubMed 20944002. Source: MGI

positive regulation of peripheral T cell tolerance induction

Inferred from mutant phenotype PubMed 16532000. Source: MGI

positive regulation of regulatory T cell differentiation

Inferred from direct assay PubMed 16769892PubMed 17028180. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17028180. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transforming growth factor beta1 production

Inferred from direct assay PubMed 17028180. Source: MGI

pre-B cell differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of immunoglobulin production

Inferred from mutant phenotype PubMed 16275384. Source: MGI

regulation of isotype switching to IgG isotypes

Inferred from mutant phenotype PubMed 16275384. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 18997793. Source: MGI

regulatory T cell differentiation

Inferred from direct assay PubMed 12522256PubMed 15100250. Source: MGI

response to virus

Inferred from electronic annotation. Source: Ensembl

tolerance induction

Inferred from direct assay PubMed 15809349. Source: MGI

tolerance induction to self antigen

Inferred from mutant phenotype PubMed 15780990. Source: MGI

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17028180. Source: GOC

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 17028180. Source: MGI

intracellular

Inferred from direct assay PubMed 19015308. Source: MGI

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionDNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

NFAT protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 17028180. Source: MGI

chromatin binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

histone acetyltransferase binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

histone deacetylase binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein heterodimerization activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription corepressor activity

Inferred from direct assay PubMed 15790681. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 429429Forkhead box protein P3
PRO_0000091888

Regions

Zinc finger196 – 22126C2H2-type
DNA binding337 – 42387Fork-head
Region238 – 25922Leucine-zipper

Amino acid modifications

Modified residue311N6-acetyllysine Ref.2
Modified residue2621N6-acetyllysine Ref.2
Modified residue2671N6-acetyllysine Ref.2

Secondary structure

.... 429
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q99JB6 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 28D5B8E67891840C

FASTA42947,346
        10         20         30         40         50         60 
MPNPRPAKPM APSLALGPSP GVLPSWKTAP KGSELLGTRG SGGPFQGRDL RSGAHTSSSL 

        70         80         90        100        110        120 
NPLPPSQLQL PTVPLVMVAP SGARLGPSPH LQALLQDRPH FMHQLSTVDA HAQTPVLQVR 

       130        140        150        160        170        180 
PLDNPAMISL PPPSAATGVF SLKARPGLPP GINVASLEWV SREPALLCTF PRSGTPRKDS 

       190        200        210        220        230        240 
NLLAAPQGSY PLLANGVCKW PGCEKVFEEP EEFLKHCQAD HLLDEKGKAQ CLLQREVVQS 

       250        260        270        280        290        300 
LEQQLELEKE KLGAMQAHLA GKMALAKAPS VASMDKSSCC IVATSTQGSV LPAWSAPREA 

       310        320        330        340        350        360 
PDGGLFAVRR HLWGSHGNSS FPEFFHNMDY FKYHNMRPPF TYATLIRWAI LEAPERQRTL 

       370        380        390        400        410        420 
NEIYHWFTRM FAYFRNHPAT WKNAIRHNLS LHKCFVRVES EKGAVWTVDE FEFRKKRSQR 


PNKCSNPCP 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF277994 Genomic DNA. Translation: AAG53608.1.
AF277991 mRNA. Translation: AAG53605.1.
AF277992 mRNA. Translation: AAG53606.1.
CCDSCCDS29965.1.
RefSeqNP_001186276.1. NM_001199347.1.
NP_001186277.1. NM_001199348.1.
NP_473380.1. NM_054039.2.
UniGeneMm.182291.
Mm.288192.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4I1LX-ray2.10A189-276[»]
ProteinModelPortalQ99JB6.
SMRQ99JB6. Positions 201-262, 336-417.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203183. 369 interactions.
DIPDIP-59739N.

PTM databases

PhosphoSiteQ99JB6.

Proteomic databases

PRIDEQ99JB6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000045566; ENSMUSP00000041953; ENSMUSG00000039521.
ENSMUST00000115738; ENSMUSP00000111403; ENSMUSG00000039521.
ENSMUST00000115739; ENSMUSP00000111404; ENSMUSG00000039521.
ENSMUST00000115740; ENSMUSP00000111405; ENSMUSG00000039521.
GeneID20371.
KEGGmmu:20371.
UCSCuc009sll.2. mouse.

Organism-specific databases

CTD50943.
MGIMGI:1891436. Foxp3.

Phylogenomic databases

eggNOGCOG5025.
GeneTreeENSGT00750000117475.
HOGENOMHOG000082490.
HOVERGENHBG051656.
InParanoidQ99JB6.
KOK10163.
OMAKHCQADH.
OrthoDBEOG7M6D7G.
PhylomeDBQ99JB6.
TreeFamTF326978.

Gene expression databases

ArrayExpressQ99JB6.
BgeeQ99JB6.
CleanExMM_FOXP3.
GenevestigatorQ99JB6.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
3.30.160.60. 1 hit.
InterProIPR001766. 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]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio298278.
PROQ99JB6.
SOURCESearch...

Entry information

Entry nameFOXP3_MOUSE
AccessionPrimary (citable) accession number: Q99JB6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot