FOXD3_HUMAN
ID FOXD3_HUMAN Reviewed; 478 AA.
AC Q9UJU5; Q9BYM2; Q9UDD1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Forkhead box protein D3;
DE AltName: Full=HNF3/FH transcription factor genesis;
GN Name=FOXD3; Synonyms=HFH2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Ramsey H.C., Hromas R.;
RT "The winged helix transcriptional regulator Genesis/HFH2/FoxD3 is located
RT at human chromosome 1p31-32 in PAC dj792g4 as a single exon.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 133-244, AND TISSUE SPECIFICITY.
RC TISSUE=Chronic myeloid leukemia cell;
RX PubMed=8499623;
RA Hromas R., Moore J., Johnston T., Socha C., Klemsz M.;
RT "Drosophila forkhead homologues are expressed in a lineage-restricted
RT manner in human hematopoietic cells.";
RL Blood 81:2854-2859(1993).
RN [4]
RP FUNCTION, AND INTERACTION WITH POU5F1.
RX PubMed=11891324; DOI=10.1073/pnas.062041099;
RA Guo Y., Costa R., Ramsey H., Starnes T., Vance G., Robertson K., Kelley M.,
RA Reinbold R., Scholer H., Hromas R.;
RT "The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to
RT regulate endodermal-specific promoter expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:3663-3667(2002).
RN [5]
RP INVOLVEMENT IN AIS1.
RX PubMed=16098053; DOI=10.1111/j.0022-202x.2005.23822.x;
RA Alkhateeb A., Fain P.R., Spritz R.A.;
RT "Candidate functional promoter variant in the FOXD3 melanoblast
RT developmental regulator gene in autosomal dominant vitiligo.";
RL J. Invest. Dermatol. 125:388-391(2005).
CC -!- FUNCTION: Binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3' and
CC acts as a transcriptional repressor. Also acts as a transcriptional
CC activator. Promotes development of neural crest cells from neural tube
CC progenitors. Restricts neural progenitor cells to the neural crest
CC lineage while suppressing interneuron differentiation. Required for
CC maintenance of pluripotent cells in the pre-implantation and peri-
CC implantation stages of embryogenesis. {ECO:0000269|PubMed:11891324}.
CC -!- SUBUNIT: Interacts with POU5F1. {ECO:0000269|PubMed:11891324}.
CC -!- INTERACTION:
CC Q9UJU5; Q01860: POU5F1; NbExp=2; IntAct=EBI-475674, EBI-475687;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in chronic myeloid leukemia, Jurkat T-
CC cell leukemia and teratocarcinoma cell lines, but not in any other cell
CC lines or normal tissues examined. {ECO:0000269|PubMed:8499623}.
CC -!- DISEASE: Autoimmune disease 1 (AIS1) [MIM:607836]: An autoimmune
CC disorder characterized by the association of vitiligo with autoimmune
CC thyroiditis (Hashimoto thyroiditis). {ECO:0000269|PubMed:16098053}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
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DR EMBL; AF197560; AAF05844.1; -; Genomic_DNA.
DR EMBL; AL049636; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L12142; AAK13574.1; -; mRNA.
DR CCDS; CCDS624.1; -.
DR RefSeq; NP_036315.1; NM_012183.2.
DR AlphaFoldDB; Q9UJU5; -.
DR SMR; Q9UJU5; -.
DR BioGRID; 117959; 38.
DR IntAct; Q9UJU5; 17.
DR MINT; Q9UJU5; -.
DR STRING; 9606.ENSP00000360157; -.
DR iPTMnet; Q9UJU5; -.
DR PhosphoSitePlus; Q9UJU5; -.
DR BioMuta; FOXD3; -.
DR DMDM; 8134475; -.
DR EPD; Q9UJU5; -.
DR MassIVE; Q9UJU5; -.
DR PaxDb; Q9UJU5; -.
DR PeptideAtlas; Q9UJU5; -.
DR PRIDE; Q9UJU5; -.
DR ProteomicsDB; 84658; -.
DR ABCD; Q9UJU5; 1 sequenced antibody.
DR Antibodypedia; 19495; 305 antibodies from 36 providers.
DR DNASU; 27022; -.
DR Ensembl; ENST00000371116.4; ENSP00000360157.2; ENSG00000187140.6.
DR GeneID; 27022; -.
DR KEGG; hsa:27022; -.
DR MANE-Select; ENST00000371116.4; ENSP00000360157.2; NM_012183.3; NP_036315.1.
DR UCSC; uc001dax.3; human.
DR CTD; 27022; -.
DR DisGeNET; 27022; -.
DR GeneCards; FOXD3; -.
DR HGNC; HGNC:3804; FOXD3.
DR HPA; ENSG00000187140; Tissue enhanced (intestine).
DR MalaCards; FOXD3; -.
DR MIM; 607836; phenotype.
DR MIM; 611539; gene.
DR neXtProt; NX_Q9UJU5; -.
DR OpenTargets; ENSG00000187140; -.
DR Orphanet; 3435; NON RARE IN EUROPE: Vitiligo.
DR PharmGKB; PA28221; -.
DR VEuPathDB; HostDB:ENSG00000187140; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000161645; -.
DR HOGENOM; CLU_040357_0_0_1; -.
DR InParanoid; Q9UJU5; -.
DR OMA; EGHDQST; -.
DR OrthoDB; 1270467at2759; -.
DR PhylomeDB; Q9UJU5; -.
DR TreeFam; TF316127; -.
DR PathwayCommons; Q9UJU5; -.
DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
DR SignaLink; Q9UJU5; -.
DR BioGRID-ORCS; 27022; 26 hits in 1092 CRISPR screens.
DR GeneWiki; FOXD3; -.
DR GenomeRNAi; 27022; -.
DR Pharos; Q9UJU5; Tbio.
DR PRO; PR:Q9UJU5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UJU5; protein.
DR Bgee; ENSG00000187140; Expressed in sural nerve and 69 other tissues.
DR Genevisible; Q9UJU5; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR018122; TF_fork_head_CS_1.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..478
FT /note="Forkhead box protein D3"
FT /id="PRO_0000091817"
FT DNA_BIND 141..235
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..39
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 200
FT /note="V -> D (in Ref. 3; AAK13574)"
FT /evidence="ECO:0000305"
FT CONFLICT 207..210
FT /note="GNPG -> ATRP (in Ref. 3; AAK13574)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="R -> A (in Ref. 3; AAK13574)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 478 AA; 47630 MW; 06163F6318FB13CB CRC64;
MTLSGGGSAS DMSGQTVLTA EDVDIDVVGE GDDGLEEKDS DAGCDSPAGP PELRLDEADE
VPPAAPHHGQ PQPPHQQPLT LPKEAAGAGA GPGGDVGAPE ADGCKGGVGG EEGGASGGGP
GAGSGSAGGL APSKPKNSLV KPPYSYIALI TMAILQSPQK KLTLSGICEF ISNRFPYYRE
KFPAWQNSIR HNLSLNDCFV KIPREPGNPG KGNYWTLDPQ SEDMFDNGSF LRRRKRFKRH
QQEHLREQTA LMMQSFGAYS LAAAAGAAGP YGRPYGLHPA AAAGAYSHPA AAAAAAAAAA
LQYPYALPPV APVLPPAVPL LPSGELGRKA AAFGSQLGPG LQLQLNSLGA AAAAAGTAGA
AGTTASLIKS EPSARPSFSI ENIIGGGPAA PGGSAVGAGV AGGTGGSGGG STAQSFLRPP
GTVQSAALMA THQPLSLSRT TATIAPILSV PLSGQFLQPA ASAAAAAAAA AQAKWPAQ
