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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)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

  • cell development Source: Ensembl
  • 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
  • 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

Enzyme and pathway databases

BioCyciZFISH:G66-33771-MONOMER.

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

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06258490R → L in ASMD and CPA; a patient with Peters anomaly; significant reduction of sequence-specific DNA binding transcription factor activity. 2 PublicationsCorresponds to variant rs371048362dbSNPEnsembl.1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06258490R → L in ASMD and CPA; a patient with Peters anomaly; significant reduction of sequence-specific DNA binding transcription factor activity. 2 PublicationsCorresponds to variant rs371048362dbSNPEnsembl.1
Natural variantiVAR_072783120R → G in CPA; complete loss of DNA binding; significant reduction of sequence-specific DNA binding transcription factor activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Peters anomaly

Organism-specific databases

DisGeNETi2301.
MalaCardsiFOXE3.
MIMi107250. phenotype.
610256. 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.
PeptideAtlasiQ13461.
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.

Organism-specific databases

HPAiCAB022645.

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

Sequence similaritiesi

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

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.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
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)DescriptionActionsGraphical viewLength
Sequence conflicti162R → P in AAB48856 (PubMed:8825632).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06258249G → A in a family with eye development anomalies. 1 PublicationCorresponds to variant rs566961335dbSNPEnsembl.1
Natural variantiVAR_06258382M → V in a family with eye development anomalies. 1 PublicationCorresponds to variant rs746531116dbSNPEnsembl.1
Natural variantiVAR_06258490R → L in ASMD and CPA; a patient with Peters anomaly; significant reduction of sequence-specific DNA binding transcription factor activity. 2 PublicationsCorresponds to variant rs371048362dbSNPEnsembl.1
Natural variantiVAR_072783120R → G in CPA; complete loss of DNA binding; significant reduction of sequence-specific DNA binding transcription factor activity. 1 Publication1
Natural variantiVAR_026234196G → A.1 PublicationCorresponds to variant rs281865461dbSNPEnsembl.1
Natural variantiVAR_026235300S → G.1 PublicationCorresponds to variant rs552420470dbSNPEnsembl.1

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000334472.

PTM databases

iPTMnetiQ13461.
PhosphoSitePlusiQ13461.

Polymorphism and mutation databases

BioMutaiFOXE3.
DMDMi12644406.

Proteomic databases

PaxDbiQ13461.
PeptideAtlasiQ13461.
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.
DisGeNETi2301.
GeneCardsiFOXE3.
HGNCiHGNC:3808. FOXE3.
HPAiCAB022645.
MalaCardsiFOXE3.
MIMi107250. phenotype.
601094. gene.
610256. phenotype.
neXtProtiNX_Q13461.
OpenTargetsiENSG00000186790.
Orphaneti83461. Congenital primary aphakia.
88632. Familial ocular anterior segment mesenchymal dysgenesis.
PharmGKBiPA28225.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:G66-33771-MONOMER.

Miscellaneous databases

GeneWikiiFOXE3.
GenomeRNAii2301.
PROiQ13461.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 143 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

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 one 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.