ID   FOXF2_HUMAN             Reviewed;         444 AA.
AC   Q12947; Q5TGJ1; Q9UQ85;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   24-JAN-2024, entry version 180.
DE   RecName: Full=Forkhead box protein F2;
DE   AltName: Full=Forkhead-related activator 2;
DE            Short=FREAC-2;
DE   AltName: Full=Forkhead-related protein FKHL6;
DE   AltName: Full=Forkhead-related transcription factor 2;
GN   Name=FOXF2; Synonyms=FKHL6, FREAC2;
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], AND SUBCELLULAR LOCATION.
RX   PubMed=9799607; DOI=10.1006/geno.1998.5451;
RA   Blixt A., Mahlapuu M., Bjursell C., Darnfors C., Johannesson T.,
RA   Enerbaeck S., Carlsson P.;
RT   "The two-exon gene of the human forkhead transcription factor FREAC-2
RT   (FKHL6) is located at 6p25.3.";
RL   Genomics 53:387-390(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 37-444, AND TISSUE SPECIFICITY.
RC   TISSUE=Lung;
RX   PubMed=8626802; DOI=10.1074/jbc.271.8.4482;
RA   Hellqvist M., Mahlapuu M., Samuelsson L., Enerbaeck S., Carlsson P.;
RT   "Differential activation of lung-specific genes by two forkhead proteins,
RT   FREAC-1 and FREAC-2.";
RL   J. Biol. Chem. 271:4482-4490(1996).
RN   [5]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7957066; DOI=10.1002/j.1460-2075.1994.tb06827.x;
RA   Pierrou S., Hellqvist M., Samuelsson L., Enerbaeck S., Carlsson P.;
RT   "Cloning and characterization of seven human forkhead proteins: binding
RT   site specificity and DNA bending.";
RL   EMBO J. 13:5002-5012(1994).
RN   [6]
RP   DOMAIN, AND INTERACTION WITH TBP AND TFIIB.
RX   PubMed=9722567; DOI=10.1074/jbc.273.36.23335;
RA   Hellqvist M., Mahlapuu M., Blixt A., Enerbaeck S., Carlsson P.;
RT   "The human forkhead protein FREAC-2 contains two functionally redundant
RT   activation domains and interacts with TBP and TFIIB.";
RL   J. Biol. Chem. 273:23335-23343(1998).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=29374064; DOI=10.1158/0008-5472.can-17-2403;
RA   Higashimori A., Dong Y., Zhang Y., Kang W., Nakatsu G., Ng S.S.M.,
RA   Arakawa T., Sung J.J.Y., Chan F.K.L., Yu J.;
RT   "Forkhead Box F2 Suppresses Gastric Cancer through a Novel FOXF2-IRF2BPL-
RT   beta-Catenin Signaling Axis.";
RL   Cancer Res. 78:1643-1656(2018).
CC   -!- FUNCTION: Probable transcription activator for a number of lung-
CC       specific genes (PubMed:8626802). Mediates up-regulation of the E3
CC       ligase IRF2BPL and drives ubiquitination and degradation of CTNNB1
CC       (PubMed:29374064). {ECO:0000269|PubMed:29374064,
CC       ECO:0000269|PubMed:8626802}.
CC   -!- SUBUNIT: Interacts with the transcription factors TBP and TFIIB.
CC       {ECO:0000269|PubMed:9722567}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29374064,
CC       ECO:0000269|PubMed:9799607}.
CC   -!- TISSUE SPECIFICITY: Lung and placenta (PubMed:8626802). Predominantly
CC       expressed in gastrointestinal tract including stomach
CC       (PubMed:29374064). {ECO:0000269|PubMed:29374064,
CC       ECO:0000269|PubMed:8626802}.
CC   -!- DOMAIN: Two activation domains, AD1 and AD2, C-terminal of (and
CC       distinct from) the forkhead domains are necessary for transcriptional
CC       activation. {ECO:0000269|PubMed:9722567}.
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DR   EMBL; AF084939; AAD19875.1; -; Genomic_DNA.
DR   EMBL; AF084938; AAD19875.1; JOINED; Genomic_DNA.
DR   EMBL; AL034346; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471087; EAW55072.1; -; Genomic_DNA.
DR   EMBL; U13220; AAC32226.1; -; mRNA.
DR   CCDS; CCDS4472.1; -.
DR   PIR; S51625; S51625.
DR   PIR; T09474; T09474.
DR   RefSeq; NP_001443.1; NM_001452.1.
DR   AlphaFoldDB; Q12947; -.
DR   SMR; Q12947; -.
DR   BioGRID; 108584; 54.
DR   IntAct; Q12947; 14.
DR   MINT; Q12947; -.
DR   STRING; 9606.ENSP00000496415; -.
DR   iPTMnet; Q12947; -.
DR   PhosphoSitePlus; Q12947; -.
DR   BioMuta; FOXF2; -.
DR   DMDM; 8247925; -.
DR   jPOST; Q12947; -.
DR   MassIVE; Q12947; -.
DR   MaxQB; Q12947; -.
DR   PaxDb; 9606-ENSP00000259806; -.
DR   PeptideAtlas; Q12947; -.
DR   ProteomicsDB; 59042; -.
DR   Pumba; Q12947; -.
DR   Antibodypedia; 9203; 256 antibodies from 23 providers.
DR   DNASU; 2295; -.
DR   Ensembl; ENST00000645481.2; ENSP00000496415.1; ENSG00000137273.6.
DR   GeneID; 2295; -.
DR   KEGG; hsa:2295; -.
DR   MANE-Select; ENST00000645481.2; ENSP00000496415.1; NM_001452.2; NP_001443.1.
DR   UCSC; uc003mtm.3; human.
DR   AGR; HGNC:3810; -.
DR   CTD; 2295; -.
DR   DisGeNET; 2295; -.
DR   GeneCards; FOXF2; -.
DR   HGNC; HGNC:3810; FOXF2.
DR   HPA; ENSG00000137273; Tissue enhanced (intestine).
DR   MIM; 603250; gene.
DR   neXtProt; NX_Q12947; -.
DR   OpenTargets; ENSG00000137273; -.
DR   PharmGKB; PA28227; -.
DR   VEuPathDB; HostDB:ENSG00000137273; -.
DR   eggNOG; KOG2294; Eukaryota.
DR   GeneTree; ENSGT00940000162527; -.
DR   HOGENOM; CLU_039845_1_0_1; -.
DR   InParanoid; Q12947; -.
DR   OMA; SNSGMRR; -.
DR   OrthoDB; 5385885at2759; -.
DR   PhylomeDB; Q12947; -.
DR   TreeFam; TF351598; -.
DR   PathwayCommons; Q12947; -.
DR   SignaLink; Q12947; -.
DR   SIGNOR; Q12947; -.
DR   BioGRID-ORCS; 2295; 17 hits in 1180 CRISPR screens.
DR   GenomeRNAi; 2295; -.
DR   Pharos; Q12947; Tbio.
DR   PRO; PR:Q12947; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q12947; Protein.
DR   Bgee; ENSG00000137273; Expressed in periodontal ligament and 129 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0016604; C:nuclear body; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0140296; F:general transcription initiation factor binding; IPI:UniProtKB.
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:NTNU_SB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0001093; F:TFIIB-class transcription factor binding; IPI:UniProtKB.
DR   GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR   GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl.
DR   GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl.
DR   GO; GO:0001837; P:epithelial to mesenchymal transition; NAS:UniProtKB.
DR   GO; GO:0042249; P:establishment of planar polarity of embryonic epithelium; IEA:Ensembl.
DR   GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR   GO; GO:0048806; P:genitalia development; IMP:UniProtKB.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:Ensembl.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR   GO; GO:1902914; P:regulation of protein polyubiquitination; IDA:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0060021; P:roof of mouth development; IMP:UniProtKB.
DR   CDD; cd20049; FH_FOXF1; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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   PANTHER; PTHR46262; FORKHEAD BOX PROTEIN BINIOU; 1.
DR   PANTHER; PTHR46262:SF3; FORKHEAD BOX PROTEIN F2; 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; Q12947; HS.
PE   1: Evidence at protein level;
KW   Activator; DNA-binding; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..444
FT                   /note="Forkhead box protein F2"
FT                   /id="PRO_0000091834"
FT   DNA_BIND        99..190
FT                   /note="Fork-head"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT   REGION          32..98
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          256..323
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          338..367
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        41..71
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        352..367
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   444 AA;  45993 MW;  32BDC5F373CFB147 CRC64;
     MTTEGGPPPA PLRRACSPVP GALQAALMSP PPAAAAAAAA APETTSSSSS SSSASCASSS
     SSSNSASAPS AACKSAGGGG AGAGSGGAKK ASSGLRRPEK PPYSYIALIV MAIQSSPSKR
     LTLSEIYQFL QARFPFFRGA YQGWKNSVRH NLSLNECFIK LPKGLGRPGK GHYWTIDPAS
     EFMFEEGSFR RRPRGFRRKC QALKPMYHRV VSGLGFGASL LPQGFDFQAP PSAPLGCHSQ
     GGYGGLDMMP AGYDAGAGAP SHAHPHHHHH HHVPHMSPNP GSTYMASCPV PAGPGGVGAA
     GGGGGGDYGP DSSSSPVPSS PAMASAIECH SPYTSPAAHW SSPGASPYLK QPPALTPSSN
     PAASAGLHSS MSSYSLEQSY LHQNAREDLS VGLPRYQHHS TPVCDRKDFV LNFNGISSFH
     PSASGSYYHH HHQSVCQDIK PCVM
//