Reviewed, UniProtKB/Swiss-Prot Q9UJU5 (FOXD3_HUMAN)

Names and origin

Protein names

Recommended name:
    Forkhead box protein D3
Alternative name(s):
    HNF3/FH transcription factor genesis

Gene names

Name:	FOXD3
Synonyms:	HFH2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	478 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3' and acts as a transcriptional repressor. Also acts as a transcriptional activator. Promotes development of neural crest cells from neural tube progenitors. Restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation. Required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis. Ref.4
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in chronic myeloid leukemia, Jurkat T-cell leukemia and teratocarcinoma cell lines, but not in any other cell lines or normal tissues examined. Ref.3
Involvement in disease	Defects in FOXD3 are associated with susceptibility to autoimmune disease type 1 (AIS1) [MIM:607836]; also called vitiligo-associated multiple autoimmune disease susceptibility type 2 (VAMAS2). Generalized vitiligo is an acquired disorder in which white patches of skin and hair result from autoimmune loss of melanocytes, often associated with other autoimmune disorders. Most cases occur in a sporadic family pattern suggesting polygenic, multifactorial inheritance. However, a striking family in which a somewhat unusual vitiligo phenotype has been described, characterized by progressively coalescent diffuse depigmentation and relatively early disease onset, segregated as an apparent autosomal dominant with incomplete penetrance. Ref.5
Sequence similarities	Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator Developmental protein Repressor
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Ref.4 Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.4 Inferred from physical interaction. Source: IntAct sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
POU5F1	Q01860	2	EBI-475674,EBI-475687

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 478	478	Forkhead box protein D3		PRO_0000091817
Regions
	DNA binding	141 – 235	95	Fork-head
	Compositional bias	262 – 268	7	Poly-Ala
	Compositional bias	280 – 285	6	Poly-Ala
	Compositional bias	290 – 300	11	Poly-Ala
	Compositional bias	350 – 355	6	Poly-Ala
	Compositional bias	460 – 473	14	Poly-Ala
Experimental info
	Sequence conflict	200	1	V → D in AAK13574. Ref.3
	Sequence conflict	207 – 210	4	GNPG → ATRP in AAK13574. Ref.3
	Sequence conflict	239	1	R → A in AAK13574. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9UJU5-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 06163F6318FB13CB	FASTA	478	47,630
	10 20 30 40 50 60 MTLSGGGSAS DMSGQTVLTA EDVDIDVVGE GDDGLEEKDS DAGCDSPAGP PELRLDEADE 70 80 90 100 110 120 VPPAAPHHGQ PQPPHQQPLT LPKEAAGAGA GPGGDVGAPE ADGCKGGVGG EEGGASGGGP 130 140 150 160 170 180 GAGSGSAGGL APSKPKNSLV KPPYSYIALI TMAILQSPQK KLTLSGICEF ISNRFPYYRE 190 200 210 220 230 240 KFPAWQNSIR HNLSLNDCFV KIPREPGNPG KGNYWTLDPQ SEDMFDNGSF LRRRKRFKRH 250 260 270 280 290 300 QQEHLREQTA LMMQSFGAYS LAAAAGAAGP YGRPYGLHPA AAAGAYSHPA AAAAAAAAAA 310 320 330 340 350 360 LQYPYALPPV APVLPPAVPL LPSGELGRKA AAFGSQLGPG LQLQLNSLGA AAAAAGTAGA 370 380 390 400 410 420 AGTTASLIKS EPSARPSFSI ENIIGGGPAA PGGSAVGAGV AGGTGGSGGG STAQSFLRPP 430 440 450 460 470 GTVQSAALMA THQPLSLSRT TATIAPILSV PLSGQFLQPA ASAAAAAAAA AQAKWPAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The winged helix transcriptional regulator Genesis/HFH2/FoxD3 is located at human chromosome 1p31-32 in PAC dj792g4 as a single exon." Ramsey H.C., Hromas R. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Drosophila forkhead homologues are expressed in a lineage-restricted manner in human hematopoietic cells." Hromas R., Moore J., Johnston T., Socha C., Klemsz M. Blood 81:2854-2859(1993) [PubMed: 8499623] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 133-244, TISSUE SPECIFICITY. Tissue: Chronic myeloid leukemia cell.
[4]	"The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression." Guo Y., Costa R., Ramsey H., Starnes T., Vance G., Robertson K., Kelley M., Reinbold R., Scholer H., Hromas R. Proc. Natl. Acad. Sci. U.S.A. 99:3663-3667(2002) [PubMed: 11891324] [Abstract] Cited for: FUNCTION, INTERACTION WITH POU5F1.
[5]	"Candidate functional promoter variant in the FOXD3 melanoblast developmental regulator gene in autosomal dominant vitiligo." Alkhateeb A., Fain P.R., Spritz R.A. J. Invest. Dermatol. 125:388-391(2005) [PubMed: 16098053] [Abstract] Cited for: INVOLVEMENT IN AIS1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF197560 Genomic DNA. Translation: AAF05844.1. AL049636 Genomic DNA. Translation: CAC19431.1. L12142 mRNA. Translation: AAK13574.1.
IPI	IPI00007164.
RefSeq	NP_036315.1.
UniGene	Hs.546573
3D structure databases
SMR	Q9UJU5. Positions 140-236.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UJU5. 1 interaction.
STRING	Q9UJU5.
Proteomic databases
PRIDE	Q9UJU5.
Genome annotation databases
Ensembl	ENST00000371116; ENSP00000360157; ENSG00000187140; Homo sapiens. [Genome view]
GeneID	27022.
KEGG	hsa:27022.
UCSC	uc001dax.2. human.
Organism-specific databases
CTD	27022.
GeneCards	GC01P063561.
HGNC	HGNC:3804. FOXD3.
HPA	CAB022455.
MIM	607836. phenotype. 611539. gene.
PharmGKB	PA28221.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19624.
HOGENOM	HBG714715.
HOVERGEN	Q9UJU5.
InParanoid	Q9UJU5.
OMA	PYGLHPA.
PhylomeDB	Q9UJU5.
Gene expression databases
ArrayExpress	Q9UJU5.
Bgee	Q9UJU5.
CleanEx	HS_FOXD3.
Genevestigator	Q9UJU5.
GermOnline	ENSG00000187140. Homo sapiens.
Family and domain databases
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
PANTHER	PTHR11829. Fork_box_protein. 1 hit.
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 Resources
NextBio	49550.
SOURCE	Search...

Entry information

Entry name

FOXD3_HUMAN

Accession

Primary (citable) accession number: Q9UJU5
Secondary accession number(s): Q9BYM2, Q9UDD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 2000
Last modified:	February 9, 2010
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.