[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. DOI=10.1006/geno.1997.4695; PubMed=9169153 [NCBI, ExPASy, EBI, Israel, Japan] Miura N., Iida K., Kakinuma H., Yang X.-L., Sugiyama T.; "Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures."; Genomics 41:489-492(1997).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[3]	INVOLVEMENT IN LYH2. DOI=10.1086/316915; PubMed=11078474 [NCBI, ExPASy, EBI, Israel, Japan] Fang J., Dagenais S.L., Erickson R.P., Arlt M.F., Glynn M.W., Gorski J.L., Seaver L.H., Glover T.W.; "Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome."; Am. J. Hum. Genet. 67:1382-1388(2000).
[4]	INVOLVEMENT IN LYMPHEDEMA SYNDROMES. DOI=10.1093/hmg/10.11.1185; PubMed=11371511 [NCBI, ExPASy, EBI, Israel, Japan] Finegold D.N., Kimak M.A., Lawrence E.C., Levinson K.L., Cherniske E.M., Pober B.R., Dunlap J.W., Ferrell R.E.; "Truncating mutations in FOXC2 cause multiple lymphedema syndromes."; Hum. Mol. Genet. 10:1185-1189(2001).
[5]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232 AND SER-240, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan] Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."; Cell 127:635-648(2006).
[6]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1021/pr070152u; PubMed=17924679 [NCBI, ExPASy, EBI, Israel, Japan] Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."; J. Proteome Res. 6:4150-4162(2007).
[7]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-235; SER-240 AND SER-281, AND MASS SPECTROMETRY. DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan] Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."; J. Proteome Res. 7:1346-1351(2008).
[8]	STRUCTURE BY NMR OF 70-162. DOI=10.1006/jmbi.1999.3476; PubMed=10669593 [NCBI, ExPASy, EBI, Israel, Japan] van Dongen M.J., Cederberg A., Carlsson P., Enerback S., Wikstrom M.; "Solution structure and dynamics of the DNA-binding domain of the adipocyte-transcription factor FREAC-11."; J. Mol. Biol. 296:351-359(2000).
[9]	VARIANT LYD LEU-125. DOI=10.1007/s004390100528; PubMed=11499682 [NCBI, ExPASy, EBI, Israel, Japan] Bell R., Brice G., Child A.H., Murday V.A., Mansour S., Sandy C.J., Collin J.R.O., Brady A.F., Callen D.F., Burnand K., Mortimer P., Jeffery S.; "Analysis of lymphoedema-distichiasis families for FOXC2 mutations reveals small insertions and deletions throughout the gene."; Hum. Genet. 108:546-551(2001).

Comments

FUNCTION: Transcriptional activator. Might be involved in the formation of special mesenchymal tissues.
SUBCELLULAR LOCATION: Nucleus (Probable).
DISEASE: Defects in FOXC2 are the cause of lymphedema hereditary type 2 (LYH2) [MIM:153200]; also known as Meige lymphedema. Hereditary lymphedema is a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment.
DISEASE: Defects in FOXC2 are a cause of lymphedema-yellow nails (LYYN) [MIM:153300]. LYYN is characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities.
DISEASE: Defects in FOXC2 are a cause of lymphedema-distichiasis syndrome (LYD) [MIM:153400]. LYD is characterized by primary limb lymphedema usually starting at puberty (but in some cases later or at birth) and associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices).
SIMILARITY: Contains 1 fork-head DNA-binding domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=FOXC2";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

Y08223; CAA69400.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC113437; AAI13438.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC113439; AAI13440.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_005242.1; -.

UniGene

Hs.436448

3D structure databases

PDB

1D5V; NMR; -; A=70-162.

[ExPASy / RCSB / EBI]

PDBsum

1D5V; -.

ModBase

Q99958.

Organism-specific databases

HIX0038664; -.

HGNC:3801; FOXC2.

153200; phenotype. [NCBI / EBI]
153300; phenotype. [NCBI / EBI]
153400; phenotype. [NCBI / EBI]
602402; gene+phenotype. [NCBI / EBI]

Orphanet

86917; Lymphoedema - cleft palate.
33001; Lymphoedema - distichiasis.
2419; Lymphoedema - ptosis.
77242; Lymphoedema tarda.
2416; Lymphoedema, congenital.
662; Yellow nail syndrome.

PharmGKB

PA28218; -.

GeneCards

Q99958.

Gene expression databases

ArrayExpress

Q99958; -.

CleanEx

HS_FOXC2; -.

GermOnline

ENSG00000176692; Homo sapiens.

Ontologies

GO:0005634;	Cellular component: nucleus (inferred from direct assay from UniProtKB).
GO:0031490;	Molecular function: chromatin DNA binding (inferred from direct assay from UniProtKB).
GO:0043565;	Molecular function: sequence-specific DNA binding (inferred from direct assay from UniProtKB).
GO:0016563;	Molecular function: transcription activator activity (inferred from direct assay from UniProtKB).
GO:0003700;	Molecular function: transcription factor activity (inferred from direct assay from UniProtKB).
GO:0008286;	Biological process: insulin receptor signaling pathway (inferred from direct assay from UniProtKB).
GO:0001946;	Biological process: lymphangiogenesis (inferred from mutant phenotype from UniProtKB).
GO:0007498;	Biological process: mesoderm development (non-traceable author statement from UniProtKB).
GO:0045893;	Biological process: positive regulation of transcription, DNA-dependent (inferred from direct assay from UniProtKB).
GO:0009725;	Biological process: response to hormone stimulus (inferred from direct assay from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR001766; TF_Fork_head.
IPR011991; Wing_hlx_DNA_bd.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 1.

PANTHER

PTHR11829; Fork_box_protein; 1.

Pfam

PF00250; Fork_head; 1.
Pfam graphical view of domain structure.

PRINTS

PR00053; FORKHEAD.

ProDom

PD000425; TF_Fork_head; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00339; FH; 1.
SMART graphical view of domain structure.

PROSITE

PS00657; FORK_HEAD_1; 1.
PS00658; FORK_HEAD_2; 1.
PS50039; FORK_HEAD_3; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

Q99958.

Genome annotation databases

Ensembl

ENSG00000176692; Homo sapiens. [Contig view]

GeneID

2303; -.

KEGG

hsa:2303; -.

Phylogenomic databases

HOGENOM

Q99958; -.

HOVERGEN

Q99958; -.

Other

FOXC2; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Activator; Developmental protein; Disease mutation; DNA-binding; Nucleus; Phosphoprotein; Transcription; Transcription regulation.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 501`	`501`	`Forkhead box protein C2.`	`PRO_0000091808`
`DNA_BIND`	`71 162`	`92`	`Fork-head.`
`COMPBIAS`	`163 167`	`5`	`Poly-Arg.`
`COMPBIAS`	`387 396`	`10`	`His-rich.`
`COMPBIAS`	`397 421`	`25`	`Ala/Pro-rich.`
`COMPBIAS`	`400 408`	`9`	`Poly-Pro.`
`COMPBIAS`	`416 422`	`7`	`Poly-Ala.`
`MOD_RES`	`219 219`		`Phosphoserine.`
`MOD_RES`	`232 232`		`Phosphoserine.`
`MOD_RES`	`235 235`		`Phosphoserine.`
`MOD_RES`	`240 240`		`Phosphoserine.`
`MOD_RES`	`281 281`		`Phosphoserine.`
`VARIANT`	`125 125`	`1`	`S -> L (in LYD).`	`VAR_018418`
`HELIX`	`77 86`	`10`
`STRAND`	`89 93`	`5`
`HELIX`	`95 105`	`11`
`HELIX`	`108 111`	`4`
`HELIX`	`116 126`	`11`
`STRAND`	`128 132`	`5`
`STRAND`	`146 148`	`3`

Sequence information

Length: 501 AA [This is the length of the unprocessed precursor]

Molecular weight: 53719 Da [This is the MW of the unprocessed precursor]

CRC64: F66513878EDC3A87 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MQARYSVSDP NALGVVPYLS EQNYYRAAGS YGGMASPMGV YSGHPEQYSA GMGRSYAPYH 

        70         80         90        100        110        120 
HHQPAAPKDL VKPPYSYIAL ITMAIQNAPE KKITLNGIYQ FIMDRFPFYR ENKQGWQNSI 

       130        140        150        160        170        180 
RHNLSLNECF VKVPRDDKKP GKGSYWTLDP DSYNMFENGS FLRRRRRFKK KDVSKEKEER 

       190        200        210        220        230        240 
AHLKEPPPAA SKGAPATPHL ADAPKEAEKK VVIKSEAASP ALPVITKVET LSPESALQGS 

       250        260        270        280        290        300 
PRSAASTPAG SPDGSLPEHH AAAPNGLPGF SVENIMTLRT SPPGGELSPG AGRAGLVVPP 

       310        320        330        340        350        360 
LALPYAAAPP AAYGQPCAQG LEAGAAGGYQ CSMRAMSLYT GAERPAHMCV PPALDEALSD 

       370        380        390        400        410        420 
HPSGPTSPLS ALNLAAGQEG ALAATGHHHQ HHGHHHPQAP PPPPAPQPQP TPQPGAAAAQ 

       430        440        450        460        470        480 
AASWYLNHSG DLNHLPGHTF AAQQQTFPNV REMFNSHRLG IENSTLGESQ VSGNASCQLP 

       490        500 
YRSTPPLYRH AAPYSYDCTK Y

Q99958 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools