Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q13461 (FOXE3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein E3
Alternative name(s):
Forkhead-related protein FKHL12
Forkhead-related transcription factor 8
Short name=FREAC-8
Gene names
Name:FOXE3
Synonyms:FKHL12, FREAC8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length319 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Subcellular location

Nucleus.

Developmental stage

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. Ref.7

Involvement in disease

Anterior segment mesenchymal dysgenesis (ASMD) [MIM:107250]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.6

Congenital primary aphakia (CPA) [MIM:610256]: Aphakia 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseasePeters anomaly
   LigandDNA-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell development

Inferred from electronic annotation. Source: Ensembl

embryonic organ morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

hair follicle morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

hard palate development

Inferred from Biological aspect of Ancestor. Source: RefGenome

lens morphogenesis in camera-type eye

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

soft palate development

Inferred from Biological aspect of Ancestor. Source: RefGenome

thyroid gland development

Inferred from Biological aspect of Ancestor. Source: RefGenome

thyroid hormone generation

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10652278. Source: MGI

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

transcription factor complex

Inferred from direct assay PubMed 10652278. Source: MGI

   Molecular_functionDNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.4. Source: UniProtKB

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 319319Forkhead box protein E3
PRO_0000091829

Regions

DNA binding70 – 16192Fork-head
Compositional bias61 – 655Poly-Arg
Compositional bias174 – 1796Poly-Ala
Compositional bias245 – 2495Poly-Ala
Compositional bias254 – 2574Poly-Ala

Natural variations

Natural variant491G → A in a family with eye development anomalies. Ref.7
VAR_062582
Natural variant821M → V in a family with eye development anomalies. Ref.7
VAR_062583
Natural variant901R → L in ASMD; a patient with Peters anomaly. Ref.6
VAR_062584
Natural variant1961G → A. Ref.2
VAR_026234
Natural variant3001S → G. Ref.2
VAR_026235

Experimental info

Sequence conflict1621R → P in AAB48856. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q13461 [UniParc].

Last modified January 11, 2001. Version 2.
Checksum: E25A64457B7ECDF8

FASTA31933,234
        10         20         30         40         50         60 
MAGRSDMDPP AAFSGFPALP AVAPSGPPPS PLAGAEPGRE PEEAAAGRGE AAPTPAPGPG 

        70         80         90        100        110        120 
RRRRRPLQRG KPPYSYIALI AMALAHAPGR RLTLAAIYRF ITERFAFYRD SPRKWQNSIR 

       130        140        150        160        170        180 
HNLTLNDCFV KVPREPGNPG KGNYWTLDPA AADMFDNGSF LRRRKRFKRA ELPAHAAAAP 

       190        200        210        220        230        240 
GPPLPFPYAP YAPAPGPALL VPPPSAGPGP SPPARLFSVD SLVNLQPELA GLGAPEPPCC 

       250        260        270        280        290        300 
AAPDAAAAAF PPCAAAASPP LYSQVPDRLV LPATRPGPGP LPAEPLLALA GPAAALGPLS 

       310 
PGEAYLRQPG FASGLERYL 

« Hide

References

« Hide 'large scale' references
[1]"Forkhead transcription factor FOXE3 is expressed in lens epithelium."
Carlsson P.
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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.
[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. expand/collapse author list , 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]"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.
[6]"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: VARIANT ASMD LEU-90.
[7]"Seeing clearly: the dominant and recessive nature of FOXE3 in eye developmental anomalies."
Iseri S.U., Osborne R.J., Farrall M., Wyatt A.W., Mirza G., Nurnberg G., Kluck C., Herbert H., Martin A., Hussain M.S., Collin J.R., Lathrop M., Nurnberg P., Ragoussis J., Ragge N.K.
Hum. Mutat. 30:1378-1386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-49 AND VAL-82, DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF275722 mRNA. Translation: AAF82793.1.
AL607122 Genomic DNA. Translation: CAI14973.1.
U42990 Genomic DNA. Translation: AAB48856.1.
CCDSCCDS550.1.
PIRG02311.
RefSeqNP_036318.1. NM_012186.2.
UniGeneHs.112968.

3D structure databases

ProteinModelPortalQ13461.
SMRQ13461. Positions 71-166.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000334472.

PTM databases

PhosphoSiteQ13461.

Polymorphism databases

DMDM12644406.

Proteomic databases

PRIDEQ13461.

Protocols and materials databases

DNASU2301.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335071; ENSP00000334472; ENSG00000186790.
GeneID2301.
KEGGhsa:2301.
UCSCuc001crk.3. human.

Organism-specific databases

CTD2301.
GeneCardsGC01P047881.
HGNCHGNC:3808. FOXE3.
MIM107250. phenotype.
601094. gene.
610256. phenotype.
neXtProtNX_Q13461.
Orphanet83461. Congenital primary aphakia.
88632. Familial ocular anterior segment mesenchymal dysgenesis.
PharmGKBPA28225.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000231286.
HOVERGENHBG051642.
InParanoidQ13461.
KOK09398.
OMAYRDNPRK.
OrthoDBEOG7KWSK8.
PhylomeDBQ13461.
TreeFamTF316127.

Gene expression databases

BgeeQ13461.
CleanExHS_FOXE3.
GenevestigatorQ13461.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFOXE3.
GenomeRNAi2301.
NextBio9341.
PROQ13461.
SOURCESearch...

Entry information

Entry nameFOXE3_HUMAN
AccessionPrimary (citable) accession number: Q13461
Secondary accession number(s): Q5SVY9, Q9NQV9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 11, 2001
Last modified: July 9, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM