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Q99JB6

- FOXP3_MOUSE

UniProt

Q99JB6 - FOXP3_MOUSE

Protein

Forkhead box protein P3

Gene

Foxp3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiQ99JB6.
    BgeeiQ99JB6.
    CleanExiMM_FOXP3.
    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

    MPNPRPAKPM APSLALGPSP GVLPSWKTAP KGSELLGTRG SGGPFQGRDL    50
    RSGAHTSSSL NPLPPSQLQL PTVPLVMVAP SGARLGPSPH LQALLQDRPH 100
    FMHQLSTVDA HAQTPVLQVR PLDNPAMISL PPPSAATGVF SLKARPGLPP 150
    GINVASLEWV SREPALLCTF PRSGTPRKDS NLLAAPQGSY PLLANGVCKW 200
    PGCEKVFEEP EEFLKHCQAD HLLDEKGKAQ CLLQREVVQS LEQQLELEKE 250
    KLGAMQAHLA GKMALAKAPS VASMDKSSCC IVATSTQGSV LPAWSAPREA 300
    PDGGLFAVRR HLWGSHGNSS FPEFFHNMDY FKYHNMRPPF TYATLIRWAI 350
    LEAPERQRTL NEIYHWFTRM FAYFRNHPAT WKNAIRHNLS LHKCFVRVES 400
    EKGAVWTVDE FEFRKKRSQR PNKCSNPCP 429
    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

    ArrayExpressi Q99JB6.
    Bgeei Q99JB6.
    CleanExi MM_FOXP3.
    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 1, 2014
    This is version 119 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