Q13461 (FOXE3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	319 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Peters anomaly
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell development Inferred from electronic annotation. Source: Compara cell migration Inferred from Biological aspect of Ancestor. Source: RefGenome embryonic organ morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome enteric nervous system development 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 pattern specification process Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of epithelial cell proliferation Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome 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
Cellular_component	transcription factor complex Inferred from direct assay PubMed 10652278. Source: MGI
Molecular_function	DNA 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 transcription factor binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 319	319	Forkhead box protein E3		PRO_0000091829
Regions
	DNA binding	70 – 161	92	Fork-head
	Compositional bias	61 – 65	5	Poly-Arg
	Compositional bias	174 – 179	6	Poly-Ala
	Compositional bias	245 – 249	5	Poly-Ala
	Compositional bias	254 – 257	4	Poly-Ala
Natural variations
	Natural variant	49	1	G → A in a family with eye development anomalies. Ref.7		VAR_062582
	Natural variant	82	1	M → V in a family with eye development anomalies. Ref.7		VAR_062583
	Natural variant	90	1	R → L in ASMD; a patient with Peters anomaly. Ref.6		VAR_062584
	Natural variant	196	1	G → A. Ref.2		VAR_026234
	Natural variant	300	1	S → G. Ref.2		VAR_026235
Experimental info
	Sequence conflict	162	1	R → P in AAB48856. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q13461 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: E25A64457B7ECDF8	FASTA	319	33,234
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF275722 mRNA. Translation: AAF82793.1. AL607122 Genomic DNA. Translation: CAI14973.1. U42990 Genomic DNA. Translation: AAB48856.1.
IPI	IPI00013354.
PIR	G02311.
RefSeq	NP_036318.1. NM_012186.2.
UniGene	Hs.112968.
3D structure databases
ProteinModelPortal	Q13461.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000334472.
PTM databases
PhosphoSite	Q13461.
Polymorphism databases
DMDM	12644406.
Proteomic databases
PRIDE	Q13461.
Protocols and materials databases
DNASU	2301.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000335071; ENSP00000334472; ENSG00000186790.
GeneID	2301.
KEGG	hsa:2301.
UCSC	uc001crk.3. human.
Organism-specific databases
CTD	2301.
GeneCards	GC01P047881.
HGNC	HGNC:3808. FOXE3.
MIM	107250. phenotype. 601094. gene. 610256. phenotype.
neXtProt	NX_Q13461.
Orphanet	83461. Congenital primary aphakia. 88632. Familial ocular anterior segment mesenchymal dysgenesis.
PharmGKB	PA28225.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5025.
HOGENOM	HOG000231286.
HOVERGEN	HBG051642.
InParanoid	Q13461.
KO	K09398.
OMA	FPYAPFP.
OrthoDB	EOG4001JR.
PhylomeDB	Q13461.
Gene expression databases
Bgee	Q13461.
CleanEx	HS_FOXE3.
Genevestigator	Q13461.
GermOnline	ENSG00000186790. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
SMART	SM00339. FH. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2301.
NextBio	9341.
SOURCE	Search...

Entry information

Entry name

FOXE3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.