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   27-MAR-2024, entry version 186.
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).
RN   [6] {ECO:0000305}
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=22306510; DOI=10.1016/j.freeradbiomed.2012.01.003;
RA   Iida R., Ueki M., Yasuda T.;
RT   "Identification of Rhit as a novel transcriptional repressor of human
RT   Mpv17-like protein with a mitigating effect on mitochondrial dysfunction,
RT   and its transcriptional regulation by FOXD3 and GABP.";
RL   Free Radic. Biol. Med. 52:1413-1422(2012).
CC   -!- FUNCTION: Binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3' and
CC       acts as a transcriptional repressor (PubMed:11891324). Also acts as a
CC       transcriptional activator (PubMed:11891324). Negatively regulates
CC       transcription of transcriptional repressor RHIT/ZNF205
CC       (PubMed:22306510). Promotes development of neural crest cells from
CC       neural tube progenitors (PubMed:11891324). Restricts neural progenitor
CC       cells to the neural crest lineage while suppressing interneuron
CC       differentiation (PubMed:11891324). Required for maintenance of
CC       pluripotent cells in the pre-implantation and peri-implantation stages
CC       of embryogenesis (PubMed:11891324). {ECO:0000269|PubMed:11891324,
CC       ECO:0000269|PubMed:22306510}.
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   -!- DEVELOPMENTAL STAGE: In spleen levels are higher in adult than in fetal
CC       tissue. {ECO:0000269|PubMed:22306510}.
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.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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   GlyGen; Q9UJU5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9UJU5; -.
DR   PhosphoSitePlus; Q9UJU5; -.
DR   BioMuta; FOXD3; -.
DR   DMDM; 8134475; -.
DR   EPD; Q9UJU5; -.
DR   MassIVE; Q9UJU5; -.
DR   PaxDb; 9606-ENSP00000360157; -.
DR   PeptideAtlas; Q9UJU5; -.
DR   ProteomicsDB; 84658; -.
DR   ABCD; Q9UJU5; 1 sequenced antibody.
DR   Antibodypedia; 19495; 321 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   AGR; HGNC:3804; -.
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; 5385885at2759; -.
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; 27 hits in 1170 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 70 other cell types or tissues.
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; cd20047; FH_FOXD3; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR047392; FH_FOXD3.
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   PANTHER; PTHR11829; FORKHEAD BOX PROTEIN; 1.
DR   PANTHER; PTHR11829:SF361; FORKHEAD BOX PROTEIN D3; 1.
DR   Pfam; PF00250; Forkhead; 1.
DR   PRINTS; PR00053; FORKHEAD.
DR   SMART; SM00339; FH; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS00657; FORK_HEAD_1; 1.
DR   PROSITE; PS00658; FORK_HEAD_2; 1.
DR   PROSITE; PS50039; FORK_HEAD_3; 1.
DR   Genevisible; Q9UJU5; HS.
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
//