UniProtKB - O00358 (FOXE1_HUMAN)
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Protein
Forkhead box protein E1
Gene
FOXE1
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 53 – 147 | Fork-headPROSITE-ProRule annotationAdd BLAST | 95 |
GO - Molecular functioni
- DNA binding transcription factor activity Source: UniProtKB
- RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: UniProtKB
- 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 by RNA polymerase II Source: UniProtKB
- pharynx development Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II 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 function | DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
SIGNORi | O00358. |
Names & Taxonomyi
Protein namesi | Recommended name: Forkhead box protein E1Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000178919.8. |
HGNCi | HGNC:3806. FOXE1. |
MIMi | 602617. gene. |
neXtProti | NX_O00358. |
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:241850Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_016882 | 57 | S → 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_008857 | 65 | A → V in BLS; loss of sequence-specific DNA binding; loss of transcriptional activity. 3 PublicationsCorresponds to variant dbSNP:rs104894110Ensembl. | 1 | |
Natural variantiVAR_075978 | 73 | R → S in BLS; no effect on protein abundance; no effect on sequence-specific DNA binding; enhances transcriptional activity toward TG and TPO genes. 1 Publication | 1 |
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:616534Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075981 | 248 | A → 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 mutationOrganism-specific databases
DisGeNETi | 2304. |
MalaCardsi | FOXE1. |
MIMi | 241850. phenotype. 616534. phenotype. |
OpenTargetsi | ENSG00000178919. |
Orphaneti | 95713. Athyreosis. 1226. Bamforth-Lazarus syndrome. 146. Papillary or follicular thyroid carcinoma. 95720. Thyroid hypoplasia. |
PharmGKBi | PA28223. |
Polymorphism and mutation databases
BioMutai | FOXE1. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000091826 | 1 – 373 | Forkhead box protein E1Add BLAST | 373 |
Post-translational modificationi
Phosphorylated.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | O00358. |
PeptideAtlasi | O00358. |
PRIDEi | O00358. |
PTM databases
iPTMneti | O00358. |
PhosphoSitePlusi | O00358. |
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
Bgeei | ENSG00000178919. |
CleanExi | HS_FOXE1. HS_TTF2. |
Genevisiblei | O00358. HS. |
Interactioni
Protein-protein interaction databases
BioGridi | 108593. 77 interactors. |
IntActi | O00358. 74 interactors. |
MINTi | O00358. |
STRINGi | 9606.ENSP00000364265. |
Structurei
3D structure databases
ProteinModelPortali | O00358. |
SMRi | O00358. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 164 – 309 | Ala-richAdd BLAST | 146 | |
Compositional biasi | 164 – 177 | Poly-AlaAdd BLAST | 14 | |
Compositional biasi | 180 – 241 | Pro-richAdd BLAST | 62 |
Phylogenomic databases
eggNOGi | KOG2294. Eukaryota. COG5025. LUCA. |
GeneTreei | ENSGT00900000140781. |
HOGENOMi | HOG000231286. |
HOVERGENi | HBG051642. |
InParanoidi | O00358. |
KOi | K09398. |
OMAi | MTAESGP. |
OrthoDBi | EOG091G0HW9. |
PhylomeDBi | O00358. |
TreeFami | TF316127. |
Family and domain databases
CDDi | cd00059. FH. 1 hit. |
Gene3Di | 1.10.10.10. 1 hit. |
InterProi | View protein in InterPro IPR001766. Fork_head_dom. IPR018122. TF_fork_head_CS_1. IPR030456. TF_fork_head_CS_2. IPR036388. WH-like_DNA-bd_sf. IPR036390. WH_DNA-bd_sf. |
Pfami | View protein in Pfam PF00250. Forkhead. 1 hit. |
PRINTSi | PR00053. FORKHEAD. |
SMARTi | View protein in SMART SM00339. FH. 1 hit. |
SUPFAMi | SSF46785. SSF46785. 1 hit. |
PROSITEi | View protein in PROSITE PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. |
i Sequence
Sequence statusi: Complete.
O00358-1 [UniParc]FASTAAdd to basket
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
Sequence cautioni
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_016882 | 57 | S → 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_008857 | 65 | A → V in BLS; loss of sequence-specific DNA binding; loss of transcriptional activity. 3 PublicationsCorresponds to variant dbSNP:rs104894110Ensembl. | 1 | |
Natural variantiVAR_075978 | 73 | R → S in BLS; no effect on protein abundance; no effect on sequence-specific DNA binding; enhances transcriptional activity toward TG and TPO genes. 1 Publication | 1 | |
Natural variantiVAR_027508 | 102 | R → 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_075979 | 132 | N → 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_075980 | 137 | F → S in congenital hypothyroidism; loss of sequence-specific DNA binding; loss of transcriptional activity. 2 Publications | 1 | |
Natural variantiVAR_037643 | 179 | A → AAA. | 1 | |
Natural variantiVAR_075981 | 248 | A → 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. |
CCDSi | CCDS35078.1. |
RefSeqi | NP_004464.2. NM_004473.3. |
UniGenei | Hs.159234. |
Genome annotation databases
Ensembli | ENST00000375123; ENSP00000364265; ENSG00000178919. |
GeneIDi | 2304. |
KEGGi | hsa:2304. |
UCSCi | uc004axu.4. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Entry informationi
Entry namei | FOXE1_HUMAN | |
Accessioni | O00358Primary (citable) accession number: O00358 Secondary accession number(s): O75765, Q5T109, Q99526 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | September 23, 2008 | |
Last modified: | March 28, 2018 | |
This is version 165 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |