Reviewed, UniProtKB/Swiss-Prot Q9BZS1 (FOXP3_HUMAN)

Names and origin

Protein names

Recommended name:
    Forkhead box protein P3
Alternative name(s):
    Scurfin

Gene names

Name:	FOXP3
Synonyms:	IPEX
ORF Names:	JM2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	431 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Diabetes mellitus Disease mutation
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Gene Ontology (GO)
Biological process	T 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 component	nucleus Inferred from direct assay. Source: UniProtKB protein complex Non-traceable author statement. Source: UniProtKB
Molecular function	NF-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 431	431	Forkhead box protein P3		PRO_0000091886
Regions
	Domain	239 – 260	22	Leucine-zipper
	Zinc finger	197 – 222	26	C2H2-type
	DNA binding	337 – 423	87	Fork-head
Natural variations
	Alternative sequence	72 – 106	35	Missing in isoform 2 and isoform 3.		VSP_015796
	Alternative sequence	382	1	K → KVSSSEVAVTGMASSAIAAQ SGQAWVWAHRHIGEERDVGC WWWLLASEVDAHLLPVPGLP Q in isoform 3.		VSP_036418
	Natural variant	251	1	Missing in IPEX. Ref.7		VAR_011330
	Natural variant	363	1	I → V in IPEX. Ref.8		VAR_023569
	Natural variant	371	1	F → C in IPEX. Ref.9		VAR_011331
	Natural variant	384	1	A → T in IPEX. Ref.9 Ref.10		VAR_011332
	Natural variant	397	1	R → W in IPEX. Ref.9		VAR_011333
Experimental info
	Sequence conflict	16 – 20	5	LGPSP → MSPIS in CAA06748. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 91737C3CEA665A15	FASTA	431	47,244
	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
	Isoform 2. Checksum: BF4DF0DD83D61CD5	FASTA	396	43,410
	10 20 30 40 50 60 MPNPRPGKPS APSLALGPSP GASPSWRAAP KASDLLGARG PGGTFQGRDL RGGAHASSSS 70 80 90 100 110 120 LNPMPPSQLQ LSTVDAHART PVLQVHPLES PAMISLTPPT TATGVFSLKA RPGLPPGINV 130 140 150 160 170 180 ASLEWVSREP ALLCTFPNPS APRKDSTLSA VPQSSYPLLA NGVCKWPGCE KVFEEPEDFL 190 200 210 220 230 240 KHCQADHLLD EKGRAQCLLQ REMVQSLEQQ LVLEKEKLSA MQAHLAGKMA LTKASSVASS 250 260 270 280 290 300 DKGSCCIVAA GSQGPVVPAW SGPREAPDSL FAVRRHLWGS HGNSTFPEFL HNMDYFKFHN 310 320 330 340 350 360 MRPPFTYATL IRWAILEAPE KQRTLNEIYH WFTRMFAFFR NHPATWKNAI RHNLSLHKCF 370 380 390 VRVESEKGAV WTVDELEFRK KRSQRPSRCS NPTPGP
	Isoform 3. Checksum: 39E7483703031335	FASTA	456	49,843
	10 20 30 40 50 60 MPNPRPGKPS APSLALGPSP GASPSWRAAP KASDLLGARG PGGTFQGRDL RGGAHASSSS 70 80 90 100 110 120 LNPMPPSQLQ LSTVDAHART PVLQVHPLES PAMISLTPPT TATGVFSLKA RPGLPPGINV 130 140 150 160 170 180 ASLEWVSREP ALLCTFPNPS APRKDSTLSA VPQSSYPLLA NGVCKWPGCE KVFEEPEDFL 190 200 210 220 230 240 KHCQADHLLD EKGRAQCLLQ REMVQSLEQQ LVLEKEKLSA MQAHLAGKMA LTKASSVASS 250 260 270 280 290 300 DKGSCCIVAA GSQGPVVPAW SGPREAPDSL FAVRRHLWGS HGNSTFPEFL HNMDYFKFHN 310 320 330 340 350 360 MRPPFTYATL IRWAILEAPE KQRTLNEIYH WFTRMFAFFR NHPATWKVSS SEVAVTGMAS 370 380 390 400 410 420 SAIAAQSGQA WVWAHRHIGE ERDVGCWWWL LASEVDAHLL PVPGLPQNAI RHNLSLHKCF 430 440 450 VRVESEKGAV WTVDELEFRK KRSQRPSRCS NPTPGP

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

FOXP3base

FOXP3 mutation db

GeneReviews

Wikipedia

FOXP3 entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00328094. IPI00604500. IPI00644203.
RefSeq	NP_001107849.1. NP_054728.2.
UniGene	Hs.247700
3D structure databases
HSSP	HSSP built from PDB template 1D5V based on UniProtKB Q99958.
SMR	Q9BZS1. Positions 336-417.
ModBase	Search...
Proteomic databases
PRIDE	Q9BZS1.
Genome annotation databases
Ensembl	ENSG00000049768. Homo sapiens. [Contig view]
GeneID	50943.
KEGG	hsa:50943.
Organism-specific databases
GeneCards	GC0XM048993.
H-InvDB	HIX0056162.
HGNC	HGNC:6106. FOXP3.
HPA	CAB008383. HPA003191.
MIM	300292. gene. 304790. phenotype.
Orphanet	37042. Immune dysregulation - polyendocrinopathy - enteropathy, X-linked.
PharmGKB	PA201094.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9BZS1.
OMA	Q9BZS1. GPSPHLQ.
Enzyme and pathway databases
Pathway_Interaction_DB	nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes. il2_stat5pathway. IL2 signaling events mediated by STAT5.
Gene expression databases
Bgee	Q9BZS1.
CleanEx	HS_FOXP3.
GermOnline	ENSG00000049768. Homo sapiens.
Family and domain databases
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. Wing_hlx_DNA_bd. IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
PANTHER	PTHR11829. Fork_box_protein. 1 hit.
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
ProDom	PD000425. TF_Fork_head. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00339. FH. 1 hit. SM00355. ZnF_C2H2. 1 hit. [Graphical view]
PROSITE	PS00657. 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]
ProtoNet	Search...
Other Resources
NextBio	53405.
SOURCE	Search...

Entry information

Entry name

FOXP3_HUMAN

Accession

Primary (citable) accession number: Q9BZS1
Secondary accession number(s): A5HJT1 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)