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Protein

Forkhead box protein E1

Gene

FOXE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. Involved in proper palate formation, most probably through the expression of MSX1 and TGFB3 genes which are direct targets of this transcription factor. Also implicated in thyroid gland morphogenesis. May indirectly play a role in cell growth and migration through the regulation of WNT5A expression.8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi53 – 147Fork-headPROSITE-ProRule annotationAdd BLAST95

GO - Molecular functioni

  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • 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 differentiation Source: GO_Central
  • cell migration Source: UniProtKB
  • cranial skeletal system development Source: Ensembl
  • embryonic organ morphogenesis Source: UniProtKB
  • hair follicle morphogenesis Source: UniProtKB
  • hard palate development Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • pharynx development Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • soft palate development Source: UniProtKB
  • thymus development Source: UniProtKB
  • thyroid gland development Source: UniProtKB
  • thyroid hormone generation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein E1
Alternative name(s):
Forkhead box protein E2
Forkhead-related protein FKHL15
HFKH4
HNF-3/fork head-like protein 5
Short name:
HFKL5
Thyroid transcription factor 2
Short name:
TTF-2
Gene namesi
Name:FOXE1
Synonyms:FKHL15, FOXE2, TITF2, TTF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000178919.8.
HGNCiHGNC:3806. FOXE1.

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

Bamforth-Lazarus syndrome (BLS)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by thyroid agenesis, cleft palate and choanal atresia.
See also OMIM:241850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01688257S → N in BLS; without choanal atresia; no effect on protein abundance; no effect on localization to the nucleus; decreased sequence-specific DNA binding; decreased transcriptional activity. 2 PublicationsCorresponds to variant dbSNP:rs28937575Ensembl.1
Natural variantiVAR_00885765A → V in BLS; loss of sequence-specific DNA binding; loss of transcriptional activity. 3 PublicationsCorresponds to variant dbSNP:rs104894110Ensembl.1
Natural variantiVAR_07597873R → S in BLS; no effect on protein abundance; no effect on sequence-specific DNA binding; enhances transcriptional activity toward TG and TPO genes. 1 Publication1
Thyroid cancer, non-medullary, 4 (NMTC4)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
See also OMIM:616534
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075981248A → G in NMTC4; increased cell growth; increased cell migration; associated with increased expression of the WNT5A gene. 1 PublicationCorresponds to variant dbSNP:rs538912281Ensembl.1

Keywords - Diseasei

Congenital hypothyroidism, Disease mutation

Organism-specific databases

DisGeNETi2304.
MalaCardsiFOXE1.
MIMi241850. phenotype.
616534. phenotype.
OpenTargetsiENSG00000178919.
Orphaneti95713. Athyreosis.
1226. Bamforth-Lazarus syndrome.
146. Papillary or follicular thyroid carcinoma.
95720. Thyroid hypoplasia.
PharmGKBiPA28223.

Polymorphism and mutation databases

BioMutaiFOXE1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000918261 – 373Forkhead box protein E1Add BLAST373

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO00358.
PRIDEiO00358.

PTM databases

iPTMnetiO00358.
PhosphoSitePlusiO00358.

Expressioni

Tissue specificityi

Detected in adult brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, heart, colon, small intestine testis and thymus. Expression was strongest in heart and pancreas.

Gene expression databases

BgeeiENSG00000178919.
CleanExiHS_FOXE1.
HS_TTF2.
GenevisibleiO00358. HS.

Interactioni

Protein-protein interaction databases

BioGridi108593. 77 interactors.
IntActiO00358. 74 interactors.
STRINGi9606.ENSP00000364265.

Structurei

3D structure databases

ProteinModelPortaliO00358.
SMRiO00358.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi164 – 309Ala-richAdd BLAST146
Compositional biasi164 – 177Poly-AlaAdd BLAST14
Compositional biasi180 – 241Pro-richAdd BLAST62

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231286.
HOVERGENiHBG051642.
InParanoidiO00358.
KOiK09398.
OMAiMTAESGP.
OrthoDBiEOG091G0HW9.
PhylomeDBiO00358.
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.

O00358-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAESGPPPP QPEVLATVKE ERGETAAGAG VPGEATGRGA GGRRRKRPLQ
60 70 80 90 100
RGKPPYSYIA LIAMAIAHAP ERRLTLGGIY KFITERFPFY RDNPKKWQNS
110 120 130 140 150
IRHNLTLNDC FLKIPREAGR PGKGNYWALD PNAEDMFESG SFLRRRKRFK
160 170 180 190 200
RSDLSTYPAY MHDAAAAAAA AAAAAAAAAI FPGAVPAARP PYPGAVYAGY
210 220 230 240 250
APPSLAAPPP VYYPAASPGP CRVFGLVPER PLSPELGPAP SGPGGSCAFA
260 270 280 290 300
SAGAPATTTG YQPAGCTGAR PANPSAYAAA YAGPDGAYPQ GAGSAIFAAA
310 320 330 340 350
GRLAGPASPP AGGSSGGVET TVDFYGRTSP GQFGALGACY NPGGQLGGAS
360 370
AGAYHARHAA AYPGGIDRFV SAM
Length:373
Mass (Da):38,076
Last modified:September 23, 2008 - v3
Checksum:iD201EAF05572FCF0
GO

Sequence cautioni

The sequence CAA64246 differs from that shown. Several conflicts.Curated

Polymorphismi

An alanine stretch that varies from 12 to 19 residues is present. This polymorphisms can be used as a marker to study the role of FOXE1 in other cases of thyroid dysgenesis, especially in familial cases.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01688257S → N in BLS; without choanal atresia; no effect on protein abundance; no effect on localization to the nucleus; decreased sequence-specific DNA binding; decreased transcriptional activity. 2 PublicationsCorresponds to variant dbSNP:rs28937575Ensembl.1
Natural variantiVAR_00885765A → V in BLS; loss of sequence-specific DNA binding; loss of transcriptional activity. 3 PublicationsCorresponds to variant dbSNP:rs104894110Ensembl.1
Natural variantiVAR_07597873R → S in BLS; no effect on protein abundance; no effect on sequence-specific DNA binding; enhances transcriptional activity toward TG and TPO genes. 1 Publication1
Natural variantiVAR_027508102R → C in congenital hypothyroidism; with absence of thyroid agenesis; loss of sequence-specific DNA binding; loss of transcriptional activity. 2 PublicationsCorresponds to variant dbSNP:rs104894111Ensembl.1
Natural variantiVAR_075979132N → D in congenital hypothyroidism; slightly decreased sequence-specific DNA binding to the TPO promoter; 0.5 fold decreased transcriptional activity. 1 PublicationCorresponds to variant dbSNP:rs762041111Ensembl.1
Natural variantiVAR_075980137F → S in congenital hypothyroidism; loss of sequence-specific DNA binding; loss of transcriptional activity. 2 Publications1
Natural variantiVAR_037643179A → AAA. 1
Natural variantiVAR_075981248A → G in NMTC4; increased cell growth; increased cell migration; associated with increased expression of the WNT5A gene. 1 PublicationCorresponds to variant dbSNP:rs538912281Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94553 mRNA. Translation: CAA64246.1. Sequence problems.
U89995 mRNA. Translation: AAC51294.1.
Y13386 Genomic DNA. Translation: CAA73816.1.
AL499604 Genomic DNA. No translation available.
CH471105 Genomic DNA. Translation: EAW58856.1.
CCDSiCCDS35078.1.
RefSeqiNP_004464.2. NM_004473.3.
UniGeneiHs.159234.

Genome annotation databases

EnsembliENST00000375123; ENSP00000364265; ENSG00000178919.
GeneIDi2304.
KEGGihsa:2304.
UCSCiuc004axu.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFOXE1_HUMAN
AccessioniPrimary (citable) accession number: O00358
Secondary accession number(s): O75765, Q5T109, Q99526
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 23, 2008
Last modified: September 27, 2017
This is version 161 of the entry and version 3 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 9
    Human chromosome 9: 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