FOXE3_MOUSE
ID FOXE3_MOUSE Reviewed; 288 AA.
AC Q9QY14;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Forkhead box protein E3;
GN Name=Foxe3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DEVELOPMENTAL STAGE, FUNCTION,
RP INVOLVEMENT IN DYL, VARIANTS DYL LEU-93 AND SER-98, AND CHARACTERIZATION OF
RP VARIANTS DYL LEU-93 AND SER-98.
RC STRAIN=129/Sv; TISSUE=Lens;
RX PubMed=10652278;
RA Blixt A., Mahlapuu M., Aitola M., Pelto-Huikko M., Enerbaeck S.,
RA Carlsson P.;
RT "A forkhead gene, FoxE3, is essential for lens epithelial proliferation and
RT closure of the lens vesicle.";
RL Genes Dev. 14:245-254(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION, DEVELOPMENTAL
RP STAGE, AND VARIANTS DYL LEU-93 AND SER-98.
RX PubMed=10890982;
RX DOI=10.1002/1526-968x(200006)27:2<81::aid-gene50>3.0.co;2-n;
RA Brownell I., Dirksen M., Jamrich M.;
RT "Forkhead Foxe3 maps to the dysgenetic lens locus and is critical in lens
RT development and differentiation.";
RL Genesis 27:81-93(2000).
RN [3]
RP CHARACTERIZATION OF VARIANTS DYL LEU-93 AND SER-98.
RX PubMed=11980846;
RA Ormestad M., Blixt A., Churchill A., Martinsson T., Enerback S.,
RA Carlsson P.;
RT "Foxe3 haploinsufficiency in mice: a model for Peters' anomaly.";
RL Invest. Ophthalmol. Vis. Sci. 43:1350-1357(2002).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16199865; DOI=10.1128/mcb.25.20.8854-8863.2005;
RA Medina-Martinez O., Brownell I., Amaya-Manzanares F., Hu Q.,
RA Behringer R.R., Jamrich M.;
RT "Severe defects in proliferation and differentiation of lens cells in Foxe3
RT null mice.";
RL Mol. Cell. Biol. 25:8854-8863(2005).
RN [5]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=17064680; DOI=10.1016/j.ydbio.2006.09.021;
RA Blixt A., Landgren H., Johansson B.R., Carlsson P.;
RT "Foxe3 is required for morphogenesis and differentiation of the anterior
RT segment of the eye and is sensitive to Pax6 gene dosage.";
RL Dev. Biol. 302:218-229(2007).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=26854927; DOI=10.1172/jci83778;
RA Kuang S.Q., Medina-Martinez O., Guo D.C., Gong L., Regalado E.S.,
RA Reynolds C.L., Boileau C., Jondeau G., Prakash S.K., Kwartler C.S.,
RA Zhu L.Y., Peters A.M., Duan X.Y., Bamshad M.J., Shendure J.,
RA Nickerson D.A., Santos-Cortez R.L., Dong X., Leal S.M., Majesky M.W.,
RA Swindell E.C., Jamrich M., Milewicz D.M.;
RT "FOXE3 mutations predispose to thoracic aortic aneurysms and dissections.";
RL J. Clin. Invest. 126:948-961(2016).
RN [7]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=27218149; DOI=10.1038/ncomms10953;
RA Khan S.Y., Vasanth S., Kabir F., Gottsch J.D., Khan A.O., Chaerkady R.,
RA Lee M.C., Leitch C.C., Ma Z., Laux J., Villasmil R., Khan S.N.,
RA Riazuddin S., Akram J., Cole R.N., Talbot C.C., Pourmand N., Zaghloul N.A.,
RA Hejtmancik J.F., Riazuddin S.A.;
RT "FOXE3 contributes to Peters anomaly through transcriptional regulation of
RT an autophagy-associated protein termed DNAJB1.";
RL Nat. Commun. 7:10953-10953(2016).
CC -!- FUNCTION: Transcription factor that controls lens epithelial cell
CC growth through regulation of proliferation, apoptosis and cell cycle
CC (PubMed:10652278, PubMed:10890982). During lens development, controls
CC the ratio of the lens fiber cells to the cells of the anterior lens
CC epithelium by regulating the rate of proliferation and differentiation
CC (PubMed:16199865). Controls lens vesicle closure and subsequent
CC separation of the lens vesicle from ectoderm (PubMed:10652278). Is
CC required for morphogenesis and differentiation of the anterior segment
CC of the eye (PubMed:17064680). Controls the expression of DNAJB1 in a
CC pathway that is crucial for the development of the anterior segment of
CC the eye (By similarity). {ECO:0000250|UniProtKB:Q13461,
CC ECO:0000269|PubMed:10652278, ECO:0000269|PubMed:10890982,
CC ECO:0000269|PubMed:16199865, ECO:0000269|PubMed:17064680}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17064680}.
CC -!- TISSUE SPECIFICITY: Expressed in the embryonic lens.
CC {ECO:0000269|PubMed:10652278, ECO:0000269|PubMed:10890982,
CC ECO:0000269|PubMed:27218149}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing lens from the start of
CC lens placode induction and becomes restricted to the anterior
CC proliferating cells when lens fiber differentiation begins.
CC {ECO:0000269|PubMed:10652278, ECO:0000269|PubMed:10890982,
CC ECO:0000269|PubMed:27218149}.
CC -!- INDUCTION: Head ectoderm expression is induced by RAX and lens
CC expression is induced by PAX6. {ECO:0000269|PubMed:10890982}.
CC -!- DISEASE: Note=Defects in Foxe3 are the cause of the dysgenetic lens
CC (dyl) phenotype. In mouse mutant dyl the lens vesicle fails to separate
CC from the ectoderm, causing a fusion between the lens and the cornea.
CC Lack of a proliferating anterior lens epithelium leads to absence of
CC secondary lens fibers and a dysplastic, cataractous lens.
CC {ECO:0000269|PubMed:10652278, ECO:0000269|PubMed:10890982}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are viable and fertile but show eye
CC abnormalities; in some cases the eyes never open. Eyes are much
CC smaller, the anterior chamber is not formed, and the pupil is markedly
CC smaller. There are no abnormalities in brain development
CC (PubMed:16199865). Mice show reduced smooth muscle cell (SMC) density
CC and impaired SMC differentiation that is limited to the ascending aorta
CC (PubMed:26854927). {ECO:0000269|PubMed:16199865,
CC ECO:0000269|PubMed:26854927}.
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DR EMBL; AF142647; AAF15997.1; -; Genomic_DNA.
DR CCDS; CCDS18483.1; -.
DR RefSeq; NP_056573.1; NM_015758.2.
DR AlphaFoldDB; Q9QY14; -.
DR SMR; Q9QY14; -.
DR BioGRID; 206001; 2.
DR IntAct; Q9QY14; 2.
DR STRING; 10090.ENSMUSP00000050445; -.
DR PhosphoSitePlus; Q9QY14; -.
DR PaxDb; Q9QY14; -.
DR PRIDE; Q9QY14; -.
DR ProteomicsDB; 267495; -.
DR Antibodypedia; 18909; 223 antibodies from 28 providers.
DR DNASU; 30923; -.
DR Ensembl; ENSMUST00000050940; ENSMUSP00000050445; ENSMUSG00000044518.
DR GeneID; 30923; -.
DR KEGG; mmu:30923; -.
DR UCSC; uc008uef.1; mouse.
DR CTD; 2301; -.
DR MGI; MGI:1353569; Foxe3.
DR VEuPathDB; HostDB:ENSMUSG00000044518; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000163987; -.
DR HOGENOM; CLU_023357_0_1_1; -.
DR InParanoid; Q9QY14; -.
DR OMA; MAGRSDM; -.
DR OrthoDB; 1270467at2759; -.
DR PhylomeDB; Q9QY14; -.
DR TreeFam; TF316127; -.
DR BioGRID-ORCS; 30923; 4 hits in 73 CRISPR screens.
DR PRO; PR:Q9QY14; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9QY14; protein.
DR Bgee; ENSMUSG00000044518; Expressed in lens placode and 34 other tissues.
DR Genevisible; Q9QY14; MM.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0048468; P:cell development; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0061073; P:ciliary body morphogenesis; IMP:UniProtKB.
DR GO; GO:0061303; P:cornea development in camera-type eye; IMP:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0001654; P:eye development; IMP:MGI.
DR GO; GO:0061072; P:iris morphogenesis; IMP:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IMP:UniProtKB.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1902747; P:negative regulation of lens fiber cell differentiation; IMP:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:2001111; P:positive regulation of lens epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0002930; P:trabecular meshwork development; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR018122; TF_fork_head_CS_1.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Disease variant; DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..288
FT /note="Forkhead box protein E3"
FT /id="PRO_0000091830"
FT DNA_BIND 64..158
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..189
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 93
FT /note="F -> L (in dyl; negative regulation of lens
FT epithelial cell proliferation; positive regulation of lens
FT fiber cell differentiation; positive regulation of
FT epithelial cell apoptotic process; loss of sequence-
FT specific DNA binding)"
FT /evidence="ECO:0000269|PubMed:10652278,
FT ECO:0000269|PubMed:10890982, ECO:0000269|PubMed:11980846"
FT VARIANT 98
FT /note="F -> S (in dyl; negative regulation of lens
FT epithelial cell proliferation; positive regulation of lens
FT fiber cell differentiation; positive regulation of
FT epithelial cell apoptotic process; loss of sequence-
FT specific DNA binding)"
FT /evidence="ECO:0000269|PubMed:10652278,
FT ECO:0000269|PubMed:10890982, ECO:0000269|PubMed:11980846"
SQ SEQUENCE 288 AA; 30541 MW; 16425926F3E466C5 CRC64;
MDAQVAFSGF PALPSLTPSG PQLPTLAGAE PGREPEEVVG GGDAEPTAVP GPGKRRRRPL
QRGKPPYSYI ALIAMALAHA PGRRLTLAAI YRFITERFAF YRDSPRKWQN SIRHNLTLND
CFVKVPREPG NPGKGNYWTL DPAAADMFDN GSFLRRRKRF KRAELPAPPP PPPPFPYAPF
PPPPAPASAP PARLFRLDSL LGLQPEPPGP VAPEPPCCAA PDAAFPPCAA AASPPLYSPA
SERLGLPAPL PAQPLLALAG SAGALGPLGA GEAYLRQPGF APGLERYL
