O00358 (FOXE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	FOXE1
Synonyms:	FKHL15, FOXE2, TITF2, TTF2

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	373 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anatomical 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_component	nucleus Inferred from direct assay Ref.6. Source: UniProtKB transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	DNA 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 373	373	Forkhead box protein E1		PRO_0000091826
Regions
	DNA binding	53 – 147	95	Fork-head
	Compositional bias	164 – 309	146	Ala-rich
	Compositional bias	164 – 177	14	Poly-Ala
	Compositional bias	180 – 241	62	Pro-rich
Natural variations
	Natural variant	57	1	S → N in BLS; without choanal atresia. Ref.7 Corresponds to variant rs28937575 [ dbSNP | Ensembl ].		VAR_016882
	Natural variant	65	1	A → V in BLS. Ref.6		VAR_008857
	Natural variant	102	1	R → C in congenital hypothyroidism; with absence of thyroid agenesis; complete loss of DNA binding and transcriptionally inactive. Ref.8		VAR_027508
	Natural variant	179	1	A → AAA.		VAR_037643

Sequences

	Sequence		Length	Mass (Da)
	O00358 [UniParc]. Last modified September 23, 2008. Version 3. Checksum: D201EAF05572FCF0	FASTA	373	38,076
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

Web resources

GeneReviews

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
RefSeq	NP_004464.2. NM_004473.3.
UniGene	Hs.159234.
3D structure databases
ProteinModelPortal	O00358.
SMR	O00358. Positions 53-148.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000364265.
PTM databases
PhosphoSite	O00358.
Proteomic databases
PaxDb	O00358.
PRIDE	O00358.
Protocols and materials databases
DNASU	2304.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375123; ENSP00000364265; ENSG00000178919.
GeneID	2304.
KEGG	hsa:2304.
UCSC	uc004axu.3. human.
Organism-specific databases
CTD	2304.
GeneCards	GC09P100615.
H-InvDB	HIX0034929.
HGNC	HGNC:3806. FOXE1.
MIM	241850. phenotype. 602617. gene.
neXtProt	NX_O00358.
Orphanet	95713. Athyreosis. 1226. Bamforth syndrome. 146. Papillary or follicular thyroid carcinoma. 95720. Thyroid hypoplasia.
PharmGKB	PA28223.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5025.
HOGENOM	HOG000231286.
HOVERGEN	HBG051642.
InParanoid	O00358.
KO	K09398.
OMA	MTAESGP.
OrthoDB	EOG7C8GHD.
PhylomeDB	O00358.
TreeFam	TF316127.
Gene expression databases
Bgee	O00358.
CleanEx	HS_FOXE1. HS_TTF2.
Genevestigator	O00358.
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
GeneWiki	FOXE1.
GenomeRNAi	2304.
NextBio	9355.
PRO	O00358.
SOURCE	Search...

Entry information

Entry name

FOXE1_HUMAN

Accession

Primary (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:	April 16, 2014
This is version 133 of the entry and version 3 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.