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O00358 (FOXE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FOXE1
Synonyms:FKHL15, FOXE2, TITF2, TTF2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length373 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable transcription factor. Could be involved in thyroid gland organogenesis.

Subcellular location

Nucleus Potential.

Tissue specificity

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.

Post-translational modification

Phosphorylated By similarity.

Polymorphism

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.

Involvement in disease

Bamforth-Lazarus syndrome (BLS) [MIM:241850]: A disease characterized by thyroid agenesis, cleft palate and choanal atresia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Sequence caution

The sequence CAA64246.1 differs from that shown. Reason: Several conflicts.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandDNA-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Non-traceable author statement Ref.2. Source: UniProtKB

cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic organ morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

hair follicle morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

hard palate development

Inferred from mutant phenotype Ref.7. Source: UniProtKB

lens morphogenesis in camera-type eye

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

pharynx development

Inferred from expression pattern PubMed 15494458. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.6. Source: UniProtKB

regulation of sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

soft palate development

Inferred from mutant phenotype Ref.7. Source: UniProtKB

thymus development

Inferred from expression pattern PubMed 15494458. Source: UniProtKB

thyroid gland development

Inferred from mutant phenotype Ref.6. Source: UniProtKB

thyroid hormone generation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentnucleus

Inferred from direct assay Ref.6. Source: UniProtKB

transcription factor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding

Inferred from direct assay Ref.6. Source: UniProtKB

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: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.6. Source: UniProtKB

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 373373Forkhead box protein E1
PRO_0000091826

Regions

DNA binding53 – 14795Fork-head
Compositional bias164 – 309146Ala-rich
Compositional bias164 – 17714Poly-Ala
Compositional bias180 – 24162Pro-rich

Natural variations

Natural variant571S → N in BLS; without choanal atresia. Ref.7
Corresponds to variant rs28937575 [ dbSNP | Ensembl ].
VAR_016882
Natural variant651A → V in BLS. Ref.6
VAR_008857
Natural variant1021R → C in congenital hypothyroidism; with absence of thyroid agenesis; complete loss of DNA binding and transcriptionally inactive. Ref.8
VAR_027508
Natural variant1791A → AAA.
VAR_037643

Sequences

Sequence LengthMass (Da)Tools
O00358 [UniParc].

Last modified September 23, 2008. Version 3.
Checksum: D201EAF05572FCF0

FASTA37338,076
        10         20         30         40         50         60 
MTAESGPPPP QPEVLATVKE ERGETAAGAG VPGEATGRGA GGRRRKRPLQ RGKPPYSYIA 

        70         80         90        100        110        120 
LIAMAIAHAP ERRLTLGGIY KFITERFPFY RDNPKKWQNS IRHNLTLNDC FLKIPREAGR 

       130        140        150        160        170        180 
PGKGNYWALD PNAEDMFESG SFLRRRKRFK RSDLSTYPAY MHDAAAAAAA AAAAAAAAAI 

       190        200        210        220        230        240 
FPGAVPAARP PYPGAVYAGY APPSLAAPPP VYYPAASPGP CRVFGLVPER PLSPELGPAP 

       250        260        270        280        290        300 
SGPGGSCAFA SAGAPATTTG YQPAGCTGAR PANPSAYAAA YAGPDGAYPQ GAGSAIFAAA 

       310        320        330        340        350        360 
GRLAGPASPP AGGSSGGVET TVDFYGRTSP GQFGALGACY NPGGQLGGAS AGAYHARHAA 

       370 
AYPGGIDRFV SAM 

« Hide

References

« Hide 'large scale' references
[1]"The novel human HNF-3/fork head-like 5 gene: chromosomal localization and expression pattern."
Wiese S., Emmerich D., Schroeder B., Murphy D.B., Grzeschik K.H., Van Kessel A.G., Thies U.
DNA Cell Biol. 16:165-171(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"FKHL15, a new human member of the forkhead gene family located on chromosome 9q22."
Chadwick B.P., Obermayr F., Frischauf A.-M.
Genomics 41:390-396(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], POLYMORPHISM OF POLY-ALA REGION.
Tissue: Keratinocyte.
[3]"Cloning, chromosomal localization and identification of polymorphisms in the human thyroid transcription factor 2 gene (TITF2)."
Macchia P.E., Mattei M.-G., Lapi P., Fenzi G., Di Lauro R.
Biochimie 81:433-440(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM.
[4]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia."
Clifton-Bligh R.J., Wentworth J.M., Heinz P., Crisp M.S., John R., Lazarus J.H., Ludgate M., Chatterjee V.K.
Nat. Genet. 19:399-401(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BLS VAL-65.
[7]"A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate."
Castanet M., Park S.M., Smith A., Bost M., Leger J., Lyonnet S., Pelet A., Czernichow P., Chatterjee K., Polak M.
Hum. Mol. Genet. 11:2051-2059(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BLS ASN-57.
[8]"A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis."
Baris I., Arisoy A.E., Smith A., Agostini M., Mitchell C.S., Park S.M., Halefoglu A.M., Zengin E., Chatterjee V.K., Battaloglu E.
J. Clin. Endocrinol. Metab. 91:4183-4187(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CONGENITAL HYPOTHYROIDISM CYS-102, CHARACTERIZATION OF VARIANT CONGENITAL HYPOTHYROIDISM CYS-102.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X94553 mRNA. Translation: CAA64246.1. Sequence problems.
U89995 mRNA. Translation: AAC51294.1.
Y13386 Genomic DNA. Translation: CAA73816.1.
AL499604 Genomic DNA. Translation: CAI12803.1.
CH471105 Genomic DNA. Translation: EAW58856.1.
CCDSCCDS35078.1.
RefSeqNP_004464.2. NM_004473.3.
UniGeneHs.159234.

3D structure databases

ProteinModelPortalO00358.
SMRO00358. Positions 53-148.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000364265.

PTM databases

PhosphoSiteO00358.

Proteomic databases

PaxDbO00358.
PRIDEO00358.

Protocols and materials databases

DNASU2304.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375123; ENSP00000364265; ENSG00000178919.
GeneID2304.
KEGGhsa:2304.
UCSCuc004axu.3. human.

Organism-specific databases

CTD2304.
GeneCardsGC09P100615.
H-InvDBHIX0034929.
HGNCHGNC:3806. FOXE1.
MIM241850. phenotype.
602617. gene.
neXtProtNX_O00358.
Orphanet95713. Athyreosis.
1226. Bamforth syndrome.
146. Papillary or follicular thyroid carcinoma.
95720. Thyroid hypoplasia.
PharmGKBPA28223.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000231286.
HOVERGENHBG051642.
InParanoidO00358.
KOK09398.
OMAMTAESGP.
OrthoDBEOG7C8GHD.
PhylomeDBO00358.
TreeFamTF316127.

Gene expression databases

BgeeO00358.
CleanExHS_FOXE1.
HS_TTF2.
GenevestigatorO00358.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFOXE1.
GenomeRNAi2304.
NextBio9355.
PROO00358.
SOURCESearch...

Entry information

Entry nameFOXE1_HUMAN
AccessionPrimary (citable) accession number: O00358
Secondary accession number(s): O75765, Q5T109, Q99526
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 23, 2008
Last modified: July 9, 2014
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM