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Reviewed, UniProtKB/Swiss-Prot Q9BZS1 (FOXP3_HUMAN)

Last modified June 16, 2009. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Forkhead box protein P3
Alternative name(s):
    Scurfin
Gene names
Name: FOXP3
Synonyms: IPEX
ORF Names: JM2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length431 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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

Subcellular location

Nucleus Potential.

Involvement in disease

Defects in FOXP3 are the cause of immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) [MIM:304790]; also known as X-linked autoimmunity-immunodeficiency syndrome. IPEX is characterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, trombocytopenia, anemia and eczema. It is usually lethal in infancy. Ref.7 Ref.8 Ref.9 Ref.10

Sequence similarities

Contains 1 C2H2-type zinc finger.

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDiabetes mellitus
Disease mutation
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
Gene Ontology (GO)
   Biological processT cell activation

Inferred from direct assay. Source: UniProtKB

T cell homeostasis

Non-traceable author statement. Source: UniProtKB

chromatin remodeling

Non-traceable author statement. Source: UniProtKB

negative regulation of CREB transcription factor activity

Inferred from direct assay. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay. Source: UniProtKB

negative regulation of T cell cytokine production

Inferred from direct assay. Source: UniProtKB

negative regulation of activated T cell proliferation

Non-traceable author statement. Source: UniProtKB

negative regulation of cytokine secretion

Inferred from direct assay. Source: UniProtKB

negative regulation of interferon-gamma production

Inferred from direct assay. Source: UniProtKB

negative regulation of interleukin-10 production

Inferred from direct assay. Source: UniProtKB

negative regulation of interleukin-2 biosynthetic process

Inferred from mutant phenotype. Source: UniProtKB

negative regulation of interleukin-2 production

Inferred from direct assay. Source: UniProtKB

negative regulation of interleukin-4 production

Inferred from direct assay. Source: UniProtKB

negative regulation of transcription, DNA-dependent

Inferred from direct assay. Source: UniProtKB

positive regulation of transcription

Inferred from direct assay. Source: UniProtKB

transcription

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentnucleus

Inferred from direct assay. Source: UniProtKB

protein complex

Non-traceable author statement. Source: UniProtKB

   Molecular functionNF-kappaB binding

Non-traceable author statement. Source: UniProtKB

NFAT protein binding

Inferred from physical interaction. Source: UniProtKB

general transcriptional repressor activity

Inferred from direct assay. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay. Source: UniProtKB

transcription factor activity Ref.1

Inferred from direct assay. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BZS1-1)

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.
Isoform 2 (identifier: Q9BZS1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     72-106: Missing.
Isoform 3 (identifier: Q9BZS1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     72-106: Missing.
     382-382: K → KVSSSEVAVTGMASSAIAAQSGQAWVWAHRHIGEERDVGCWWWLLASEVDAHLLPVPGLPQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 431431Forkhead box protein P3
PRO_0000091886

Regions

Domain239 – 26022Leucine-zipper
Zinc finger197 – 22226C2H2-type
DNA binding337 – 42387Fork-head

Natural variations

Alternative sequence72 – 10635Missing in isoform 2 and isoform 3.
VSP_015796
Alternative sequence3821K → KVSSSEVAVTGMASSAIAAQ SGQAWVWAHRHIGEERDVGC WWWLLASEVDAHLLPVPGLP Q in isoform 3.
VSP_036418
Natural variant2511Missing in IPEX. Ref.7
VAR_011330
Natural variant3631I → V in IPEX. Ref.8
VAR_023569
Natural variant3711F → C in IPEX. Ref.9
VAR_011331
Natural variant3841A → T in IPEX. Ref.9 Ref.10
VAR_011332
Natural variant3971R → W in IPEX. Ref.9
VAR_011333

Experimental info

Sequence conflict16 – 205LGPSP → MSPIS in CAA06748. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 91737C3CEA665A15

FASTA43147,244
        10         20         30         40         50         60 
MPNPRPGKPS APSLALGPSP GASPSWRAAP KASDLLGARG PGGTFQGRDL RGGAHASSSS 

        70         80         90        100        110        120 
LNPMPPSQLQ LPTLPLVMVA PSGARLGPLP HLQALLQDRP HFMHQLSTVD AHARTPVLQV 

       130        140        150        160        170        180 
HPLESPAMIS LTPPTTATGV FSLKARPGLP PGINVASLEW VSREPALLCT FPNPSAPRKD 

       190        200        210        220        230        240 
STLSAVPQSS YPLLANGVCK WPGCEKVFEE PEDFLKHCQA DHLLDEKGRA QCLLQREMVQ 

       250        260        270        280        290        300 
SLEQQLVLEK EKLSAMQAHL AGKMALTKAS SVASSDKGSC CIVAAGSQGP VVPAWSGPRE 

       310        320        330        340        350        360 
APDSLFAVRR HLWGSHGNST FPEFLHNMDY FKFHNMRPPF TYATLIRWAI LEAPEKQRTL 

       370        380        390        400        410        420 
NEIYHWFTRM FAFFRNHPAT WKNAIRHNLS LHKCFVRVES EKGAVWTVDE LEFRKKRSQR 

       430 
PSRCSNPTPG P 

« Hide

Isoform 2.

Checksum: BF4DF0DD83D61CD5
Show »

FASTA39643,410
Isoform 3.

Checksum: 39E7483703031335
Show »

FASTA45649,843

References

« Hide 'large scale' 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: 11138001] [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 (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]Lin L., Nong W., Li H., Ke R., Shen C., Zhong G., Zheng Z., Liang M., Huang B., Zhou G., Yang S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]"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. expand/collapse author list , 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(2005) [PubMed: 15772651] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"Transcription map in Xp11.23."
Strom T.M., Nyakatura G., Hellebrand H., Drescher B., Rosenthal A., Meindl A.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 16-431 (ISOFORM 3).
[7]"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(2000) [PubMed: 11120765] [Abstract]
Cited for: VARIANT IPEX GLU-251 DEL.
[8]"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(2001) [PubMed: 11768393] [Abstract]
Cited for: VARIANT IPEX VAL-363.
[9]"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(2001) [PubMed: 11137992] [Abstract]
Cited for: VARIANTS IPEX CYS-371; THR-384 AND TRP-397.
[10]"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(2001) [PubMed: 11137993] [Abstract]
Cited for: VARIANT IPEX THR-384.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF277993 mRNA. Translation: AAG53607.1.
EF534714 mRNA. Translation: ABQ15210.1.
DQ010327 mRNA. Translation: AAY27088.1.
AF235097 Genomic DNA. No translation available.
BC113401 mRNA. Translation: AAI13402.1.
BC113403 mRNA. Translation: AAI13404.1.
AJ005891 mRNA. Translation: CAA06748.1.
IPIIPI00328094.
IPI00604500.
IPI00644203.
RefSeqNP_001107849.1.
NP_054728.2.
UniGeneHs.247700

3D structure databases

HSSPHSSP built from PDB template 1D5V based on UniProtKB Q99958.
SMRQ9BZS1. Positions 336-417.
ModBaseSearch...

Proteomic databases

PRIDEQ9BZS1.

Genome annotation databases

EnsemblENSG00000049768. Homo sapiens. [Contig view]
GeneID50943.
KEGGhsa:50943.

Organism-specific databases

GeneCardsGC0XM048993.
H-InvDBHIX0056162.
HGNCHGNC:6106. FOXP3.
HPACAB008383.
HPA003191.
MIM300292. gene.
304790. phenotype.
Orphanet37042. Immune dysregulation - polyendocrinopathy - enteropathy, X-linked.
PharmGKBPA201094.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ9BZS1.
OMAQ9BZS1. GPSPHLQ.

Enzyme and pathway databases

Pathway_Interaction_DBnfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
il2_stat5pathway. IL2 signaling events mediated by STAT5.

Gene expression databases

BgeeQ9BZS1.
CleanExHS_FOXP3.
GermOnlineENSG00000049768. Homo sapiens.

Family and domain databases

InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. Wing_hlx_DNA_bd.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
[Graphical view]
Gene3DG3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
PANTHERPTHR11829. Fork_box_protein. 1 hit.
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
ProDomPD000425. TF_Fork_head. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. False negative.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
PS50157. ZINC_FINGER_C2H2_2. False negative.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio53405.
SOURCESearch...

Entry information

Entry nameFOXP3_HUMAN
AccessionPrimary (citable) accession number: Q9BZS1
Secondary accession number(s): A5HJT1 expand/collapse secondary AC list , O60827, Q14DD8, Q4ZH51
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: June 1, 2001
Last modified: June 16, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents