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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). Controls the expression of DNAJB1 in a pathway that is crucial for the development of the anterior segment of the eye (PubMed:27218149).By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi71 – 165Fork-headPROSITE-ProRule annotationAdd BLAST95

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: GO_Central
  • sequence-specific DNA binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding 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
  • eye development Source: UniProtKB
  • iris morphogenesis Source: UniProtKB
  • lens development in camera-type eye Source: UniProtKB
  • mRNA transcription from RNA polymerase II promoter 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
  • trabecular meshwork development Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: MGI

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation

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
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000186790.5.
HGNCiHGNC:3808. FOXE3.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Anterior segment dysgenesis 2 (ASGD2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. Some ASGD2 patients show congenital primary aphakia, a defect caused by eye development arrest around the 4th-5th week of gestation. This prevents the formation of any lens structure and leads to severe secondary ocular anomalies, 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. ASGD2 inheritance is autosomal recessive.
See also OMIM:610256
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06258382M → V in ASGD2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs746531116Ensembl.1
Natural variantiVAR_06258490R → L in ASGD2; significant reduction of sequence-specific DNA binding transcription factor activity. 2 PublicationsCorresponds to variant dbSNP:rs371048362Ensembl.1
Natural variantiVAR_072783120R → G in ASGD2; complete loss of DNA binding; significant reduction of sequence-specific DNA binding transcription factor activity. 1 Publication1
Cataract 34, multiple types (CTRCT34)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function.
See also OMIM:612968
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078112103E → K in CTRCT34; decreases DNAJB1 expression. 1 Publication1
Natural variantiVAR_078113117N → K in CTRCT34; decreases DNAJB1 expression. 1 Publication1
Aortic aneurysm, familial thoracic 11 (AAT11)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of thoracic aortic aneurysm, a disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.
See also OMIM:617349
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078114137G → D in AAT11. 1 PublicationCorresponds to variant dbSNP:rs749960549Ensembl.1
Natural variantiVAR_078115153D → H in AAT11. 1 PublicationCorresponds to variant dbSNP:rs367943249Ensembl.1

Keywords - Diseasei

Aortic aneurysm, Cataract, Disease mutation, Peters anomaly

Organism-specific databases

DisGeNETi2301.
MalaCardsiFOXE3.
MIMi610256. phenotype.
612968. phenotype.
617349. phenotype.
OpenTargetsiENSG00000186790.
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)DescriptionActionsGraphical viewLength
ChainiPRO_00000918291 – 319Forkhead box protein E3Add BLAST319

Proteomic databases

PaxDbiQ13461.
PRIDEiQ13461.

PTM databases

iPTMnetiQ13461.
PhosphoSitePlusiQ13461.

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

BgeeiENSG00000186790.
CleanExiHS_FOXE3.
ExpressionAtlasiQ13461. baseline and differential.
GenevisibleiQ13461. HS.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000334472.

Structurei

3D structure databases

ProteinModelPortaliQ13461.
SMRiQ13461.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi180 – 301Pro-richPROSITE-ProRule annotationAdd BLAST122

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231286.
HOVERGENiHBG051642.
InParanoidiQ13461.
KOiK09398.
OMAiPEPPCCA.
OrthoDBiEOG091G0TOA.
PhylomeDBiQ13461.
TreeFamiTF316127.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiView protein in InterPro
IPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
PfamiView protein in Pfam
PF00250. Forkhead. 1 hit.
PRINTSiPR00053. FORKHEAD.
SMARTiView protein in SMART
SM00339. FH. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiView protein in PROSITE
PS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti162R → P in AAB48856 (PubMed:8825632).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06258249G → A1 PublicationCorresponds to variant dbSNP:rs566961335Ensembl.1
Natural variantiVAR_06258382M → V in ASGD2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs746531116Ensembl.1
Natural variantiVAR_06258490R → L in ASGD2; significant reduction of sequence-specific DNA binding transcription factor activity. 2 PublicationsCorresponds to variant dbSNP:rs371048362Ensembl.1
Natural variantiVAR_078112103E → K in CTRCT34; decreases DNAJB1 expression. 1 Publication1
Natural variantiVAR_078113117N → K in CTRCT34; decreases DNAJB1 expression. 1 Publication1
Natural variantiVAR_072783120R → G in ASGD2; complete loss of DNA binding; significant reduction of sequence-specific DNA binding transcription factor activity. 1 Publication1
Natural variantiVAR_078114137G → D in AAT11. 1 PublicationCorresponds to variant dbSNP:rs749960549Ensembl.1
Natural variantiVAR_078115153D → H in AAT11. 1 PublicationCorresponds to variant dbSNP:rs367943249Ensembl.1
Natural variantiVAR_026234196G → A1 PublicationCorresponds to variant dbSNP:rs281865461Ensembl.1
Natural variantiVAR_026235300S → G1 PublicationCorresponds to variant dbSNP:rs552420470Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF275722 mRNA. Translation: AAF82793.1.
AL607122 Genomic DNA. No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiFOXE3_HUMAN
AccessioniPrimary (citable) accession number: Q13461
Secondary accession number(s): Q5SVY9, Q9NQV9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 11, 2001
Last modified: September 27, 2017
This is version 151 of the entry and version 2 of the sequence. See 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