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Protein

Forkhead box protein E3

Gene

FOXE3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor that controls lens epithelial cell growth through regulation of proliferation, apoptosis and cell cycle (PubMed:22527307, PubMed:25504734). During lens development, controls the ratio of the lens fiber cells to the cells of the anterior lens epithelium by regulating the rate of proliferation and differentiation (By similarity). Controls lens vesicle closure and subsequent separation of the lens vesicle from ectoderm (By similarity). Is required for morphogenesis and differentiation of the anterior segment of the eye (By similarity).By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi71 – 16595Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • sequence-specific DNA binding Source: UniProtKB
  • sequence-specific DNA binding RNA polymerase II transcription factor activity Source: GO_Central
  • sequence-specific DNA binding transcription factor activity Source: UniProtKB

GO - Biological processi

  • anatomical structure morphogenesis Source: GO_Central
  • cell development Source: Ensembl
  • cell differentiation Source: GO_Central
  • ciliary body morphogenesis Source: UniProtKB
  • cornea development in camera-type eye Source: UniProtKB
  • iris morphogenesis Source: UniProtKB
  • lens development in camera-type eye Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell cycle arrest Source: UniProtKB
  • negative regulation of lens fiber cell differentiation Source: UniProtKB
  • positive regulation of lens epithelial cell proliferation Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: GO_Central
  • trabecular meshwork development Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: MGI
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein E3
Alternative name(s):
Forkhead-related protein FKHL12
Forkhead-related transcription factor 8
Short name:
FREAC-8
Gene namesi
Name:FOXE3
Synonyms:FKHL12, FREAC8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:3808. FOXE3.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Anterior segment mesenchymal dysgenesis (ASMD)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA range of developmental defects in structures at the front of the eye, resulting from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to the cornea, iris, and other components of the anterior chamber during eye development. Different mature anterior segment anomalies may exist alone or in combination, and are associated with an increased risk of glaucoma and corneal opacity. Conditions falling within the phenotypic spectrum of anterior segment anomalies include aniridia, posterior embryotoxon, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis.

See also OMIM:107250
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti90 – 901R → L in ASMD and CPA; a patient with Peters anomaly; significant reduction of sequence-specific DNA binding transcription factor activity. 2 Publications
VAR_062584
Congenital primary aphakia (CPA)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAphakia is a rare congenital eye disorder in which the lens is missing. It has been histologically subdivided into primary and secondary forms, in accordance with the severity of defects of the ocular tissues, whose development requires the initial presence of a lens. CPA results from an early developmental arrest, around the 4th-5th week of gestation in humans, that prevents the formation of any lens structure and leads to severe secondary ocular defects, including a complete aplasia of the anterior segment of the eye. In contrast, in secondary aphakic eyes, lens induction has occurred, and the lens vesicle has developed to some degree but finally has progressively resorbed perinatally, leading, therefore, to less-severe ocular defects.

See also OMIM:610256
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti90 – 901R → L in ASMD and CPA; a patient with Peters anomaly; significant reduction of sequence-specific DNA binding transcription factor activity. 2 Publications
VAR_062584
Natural varianti120 – 1201R → G in CPA; complete loss of DNA binding; significant reduction of sequence-specific DNA binding transcription factor activity. 1 Publication
VAR_072783

Keywords - Diseasei

Disease mutation, Peters anomaly

Organism-specific databases

MIMi107250. phenotype.
610256. phenotype.
Orphaneti83461. Congenital primary aphakia.
88632. Familial ocular anterior segment mesenchymal dysgenesis.
PharmGKBiPA28225.

Polymorphism and mutation databases

BioMutaiFOXE3.
DMDMi12644406.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 319319Forkhead box protein E3PRO_0000091829Add
BLAST

Proteomic databases

PRIDEiQ13461.

PTM databases

PhosphoSiteiQ13461.

Expressioni

Developmental stagei

Expressed in the lens during embryonic development. Predominantly expressed in the anterior lens epithelium but with some expression posteriorly. Not expressed in brain in embryos.1 Publication

Gene expression databases

BgeeiQ13461.
CleanExiHS_FOXE3.
GenevisibleiQ13461. HS.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000334472.

Structurei

3D structure databases

ProteinModelPortaliQ13461.
SMRiQ13461. Positions 71-166.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi180 – 301122Pro-richPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231286.
HOVERGENiHBG051642.
InParanoidiQ13461.
KOiK09398.
OMAiPEPPCCA.
OrthoDBiEOG7KWSK8.
PhylomeDBiQ13461.
TreeFamiTF316127.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS_1.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q13461-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGRSDMDPP AAFSGFPALP AVAPSGPPPS PLAGAEPGRE PEEAAAGRGE
60 70 80 90 100
AAPTPAPGPG RRRRRPLQRG KPPYSYIALI AMALAHAPGR RLTLAAIYRF
110 120 130 140 150
ITERFAFYRD SPRKWQNSIR HNLTLNDCFV KVPREPGNPG KGNYWTLDPA
160 170 180 190 200
AADMFDNGSF LRRRKRFKRA ELPAHAAAAP GPPLPFPYAP YAPAPGPALL
210 220 230 240 250
VPPPSAGPGP SPPARLFSVD SLVNLQPELA GLGAPEPPCC AAPDAAAAAF
260 270 280 290 300
PPCAAAASPP LYSQVPDRLV LPATRPGPGP LPAEPLLALA GPAAALGPLS
310
PGEAYLRQPG FASGLERYL
Length:319
Mass (Da):33,234
Last modified:January 11, 2001 - v2
Checksum:iE25A64457B7ECDF8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti162 – 1621R → P in AAB48856 (PubMed:8825632).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti49 – 491G → A in a family with eye development anomalies. 1 Publication
VAR_062582
Natural varianti82 – 821M → V in a family with eye development anomalies. 1 Publication
VAR_062583
Natural varianti90 – 901R → L in ASMD and CPA; a patient with Peters anomaly; significant reduction of sequence-specific DNA binding transcription factor activity. 2 Publications
VAR_062584
Natural varianti120 – 1201R → G in CPA; complete loss of DNA binding; significant reduction of sequence-specific DNA binding transcription factor activity. 1 Publication
VAR_072783
Natural varianti196 – 1961G → A.1 Publication
VAR_026234
Natural varianti300 – 3001S → G.1 Publication
VAR_026235

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF275722 mRNA. Translation: AAF82793.1.
AL607122 Genomic DNA. Translation: CAI14973.1.
U42990 Genomic DNA. Translation: AAB48856.1.
CCDSiCCDS550.1.
PIRiG02311.
RefSeqiNP_036318.1. NM_012186.2.
UniGeneiHs.112968.

Genome annotation databases

EnsembliENST00000335071; ENSP00000334472; ENSG00000186790.
GeneIDi2301.
KEGGihsa:2301.
UCSCiuc001crk.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF275722 mRNA. Translation: AAF82793.1.
AL607122 Genomic DNA. Translation: CAI14973.1.
U42990 Genomic DNA. Translation: AAB48856.1.
CCDSiCCDS550.1.
PIRiG02311.
RefSeqiNP_036318.1. NM_012186.2.
UniGeneiHs.112968.

3D structure databases

ProteinModelPortaliQ13461.
SMRiQ13461. Positions 71-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000334472.

PTM databases

PhosphoSiteiQ13461.

Polymorphism and mutation databases

BioMutaiFOXE3.
DMDMi12644406.

Proteomic databases

PRIDEiQ13461.

Protocols and materials databases

DNASUi2301.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000335071; ENSP00000334472; ENSG00000186790.
GeneIDi2301.
KEGGihsa:2301.
UCSCiuc001crk.3. human.

Organism-specific databases

CTDi2301.
GeneCardsiGC01P047881.
HGNCiHGNC:3808. FOXE3.
MIMi107250. phenotype.
601094. gene.
610256. phenotype.
neXtProtiNX_Q13461.
Orphaneti83461. Congenital primary aphakia.
88632. Familial ocular anterior segment mesenchymal dysgenesis.
PharmGKBiPA28225.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231286.
HOVERGENiHBG051642.
InParanoidiQ13461.
KOiK09398.
OMAiPEPPCCA.
OrthoDBiEOG7KWSK8.
PhylomeDBiQ13461.
TreeFamiTF316127.

Miscellaneous databases

GeneWikiiFOXE3.
GenomeRNAii2301.
NextBioi9341.
PROiQ13461.
SOURCEiSearch...

Gene expression databases

BgeeiQ13461.
CleanExiHS_FOXE3.
GenevisibleiQ13461. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS_1.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mutations in the human forkhead transcription factor FOXE3 associated with anterior segment ocular dysgenesis and cataracts."
    Semina E.V., Brownell I., Mintz-Hittner H.A., Murray J.C., Jamrich M.
    Hum. Mol. Genet. 10:231-236(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-196 AND GLY-300, INVOLVEMENT IN ASMD.
  2. "Foxe3 haploinsufficiency in mice: a model for Peters' anomaly."
    Ormestad M., Blixt A., Churchill A., Martinsson T., Enerback S., Carlsson P.
    Invest. Ophthalmol. Vis. Sci. 43:1350-1357(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASMD LEU-90.
    Tissue: Lens epithelium.
  3. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12)."
    Larsson C., Hellqvist M., Pierrou S., White I., Enerbaeck S., Carlsson P.
    Genomics 30:464-469(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 66-171.
  5. "Growth inhibition of human lens epithelial cells by short hairpin RNA in transcription factor forkhead box E3 (FOXE3)."
    Wang Y., Li W., Wang Y., Huang Y.
    Graefes Arch. Clin. Exp. Ophthalmol. 250:999-1007(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Functional analysis of FOXE3 mutations causing dominant and recessive ocular anterior segment disease."
    Islam L., Kelberman D., Williamson L., Lewis N., Glindzicz M.B., Nischal K.K., Sowden J.C.
    Hum. Mutat. 36:296-300(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANTS CPA LEU-90 AND GLY-120, CHARACTERIZATION OF VARIANTS CPA LEU-90 AND GLY-120.
  7. "Homozygous nonsense mutation in the FOXE3 gene as a cause of congenital primary aphakia in humans."
    Valleix S., Niel F., Nedelec B., Algros M.-P., Schwartz C., Delbosc B., Delpech M., Kantelip B.
    Am. J. Hum. Genet. 79:358-364(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CPA.
  8. Cited for: VARIANTS ALA-49 AND VAL-82, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiFOXE3_HUMAN
AccessioniPrimary (citable) accession number: Q13461
Secondary accession number(s): Q5SVY9, Q9NQV9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 11, 2001
Last modified: July 22, 2015
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.