FOXC1_HUMAN
ID FOXC1_HUMAN Reviewed; 553 AA.
AC Q12948; Q86UP7; Q9BYM1; Q9NUE5; Q9UDD0; Q9UP06;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 3.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Forkhead box protein C1;
DE AltName: Full=Forkhead-related protein FKHL7;
DE AltName: Full=Forkhead-related transcription factor 3;
DE Short=FREAC-3;
GN Name=FOXC1; Synonyms=FKHL7, FREAC3;
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], VARIANTS ASGD3 SER-112; MET-126 AND
RP LEU-131, AND INVOLVEMENT IN ASGD3.
RX PubMed=9620769; DOI=10.1038/493;
RA Nishimura D.Y., Swiderski R.E., Alward W.L.M., Searby C.C., Patil S.R.,
RA Bennet S.R., Kanis A.B., Gastier J.M., Stone E.M., Sheffield V.C.;
RT "The forkhead transcription factor gene FKHL7 is responsible for glaucoma
RT phenotypes which map to 6p25.";
RL Nat. Genet. 19:140-147(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS RIEG3 THR-82 AND MET-87, AND
RP INVOLVEMENT IN RIEG3.
RX PubMed=9792859; DOI=10.1086/302109;
RA Mears A.J., Jordan T., Mirzayans F., Dubois S., Kume T., Parlee M.,
RA Ritch R., Koop B., Kuo W.-L., Collins C., Marshall J., Gould D.B.,
RA Pearce W., Carlsson P., Enerbaeck S., Morissette J., Bhattacharya S.,
RA Hogan B., Raymond V., Walter M.A.;
RT "Mutations of the forkhead/winged-helix gene, FKHL7, in patients with
RT Axenfeld-Rieger anomaly.";
RL Am. J. Hum. Genet. 63:1316-1328(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT RIEG3 LYS-161.
RX PubMed=12592227;
RA Komatireddy S., Chakrabarti S., Mandal A.K., Reddy A.B.M., Sampath S.,
RA Panicker S.G., Balasubramanian D.;
RT "Mutation spectrum of FOXC1 and clinical genetic heterogeneity of Axenfeld-
RT Rieger anomaly in India.";
RL Mol. Vis. 9:43-48(2003).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 68-177, AND TISSUE SPECIFICITY.
RC TISSUE=Erythroleukemia;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 73-178, FUNCTION, AND DNA-BENDING.
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 [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=12408963; DOI=10.1006/geno.2002.6860;
RA Zhou Y., Kato H., Asanoma K., Kondo H., Arima T., Kato K., Matsuda T.,
RA Wake N.;
RT "Identification of FOXC1 as a TGF-beta1 responsive gene and its involvement
RT in negative regulation of cell growth.";
RL Genomics 80:465-472(2002).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL,
RP TRANSCRIPTIONAL ACTIVATION/REPRESSION DOMAINS, AND PHOSPHORYLATION.
RX PubMed=11782474; DOI=10.1074/jbc.m110266200;
RA Berry F.B., Saleem R.A., Walter M.A.;
RT "FOXC1 transcriptional regulation is mediated by N- and C-terminal
RT activation domains and contains a phosphorylated transcriptional inhibitory
RT domain.";
RL J. Biol. Chem. 277:10292-10297(2002).
RN [9]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=12533514; DOI=10.1101/gad.1048903;
RA Yamagishi H., Maeda J., Hu T., McAnally J., Conway S.J., Kume T.,
RA Meyers E.N., Yamagishi C., Srivastava D.;
RT "Tbx1 is regulated by tissue-specific forkhead proteins through a common
RT Sonic hedgehog-responsive enhancer.";
RL Genes Dev. 17:269-281(2003).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PRO-79; LEU-86; ILE-87;
RP ILE-91; ILE-126 AND ARG-127.
RX PubMed=15299087; DOI=10.1093/nar/gkh742;
RA Saleem R.A., Banerjee-Basu S., Murphy T.C., Baxevanis A., Walter M.A.;
RT "Essential structural and functional determinants within the forkhead
RT domain of FOXC1.";
RL Nucleic Acids Res. 32:4182-4193(2004).
RN [11]
RP FUNCTION, DNA-BINDING, INTERACTION WITH FLNA AND PBX1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15684392; DOI=10.1128/mcb.25.4.1415-1424.2005;
RA Berry F.B., O'Neill M.A., Coca-Prados M., Walter M.A.;
RT "FOXC1 transcriptional regulatory activity is impaired by PBX1 in a filamin
RT A-mediated manner.";
RL Mol. Cell. Biol. 25:1415-1424(2005).
RN [12]
RP FUNCTION, UBIQUITINATION, PHOSPHORYLATION AT SER-272, AND MUTAGENESIS OF
RP THR-68; SER-241; SER-259 AND SER-272.
RX PubMed=16492674; DOI=10.1074/jbc.m513629200;
RA Berry F.B., Mirzayans F., Walter M.A.;
RT "Regulation of FOXC1 stability and transcriptional activity by an epidermal
RT growth factor-activated mitogen-activated protein kinase signaling
RT cascade.";
RL J. Biol. Chem. 281:10098-10104(2006).
RN [13]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=17993506; DOI=10.1093/hmg/ddm326;
RA Berry F.B., Skarie J.M., Mirzayans F., Fortin Y., Hudson T.J., Raymond V.,
RA Link B.A., Walter M.A.;
RT "FOXC1 is required for cell viability and resistance to oxidative stress in
RT the eye through the transcriptional regulation of FOXO1A.";
RL Hum. Mol. Genet. 17:490-505(2008).
RN [14]
RP INTERACTION WITH C1QBP.
RX PubMed=18676636; DOI=10.1167/iovs.07-1625;
RA Huang L., Chi J., Berry F.B., Footz T.K., Sharp M.W., Walter M.A.;
RT "Human p32 is a novel FOXC1-interacting protein that regulates FOXC1
RT transcriptional activity in ocular cells.";
RL Invest. Ophthalmol. Vis. Sci. 49:5243-5249(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-235; SER-241 AND SER-320, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-235, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20406990; DOI=10.1158/0008-5472.can-09-4120;
RA Ray P.S., Wang J., Qu Y., Sim M.S., Shamonki J., Bagaria S.P., Ye X.,
RA Liu B., Elashoff D., Hoon D.S., Walter M.A., Martens J.W., Richardson A.L.,
RA Giuliano A.E., Cui X.;
RT "FOXC1 is a potential prognostic biomarker with functional significance in
RT basal-like breast cancer.";
RL Cancer Res. 70:3870-3876(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320 AND SER-521, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22991501; DOI=10.7150/ijbs.4769;
RA Xu Z.Y., Ding S.M., Zhou L., Xie H.Y., Chen K.J., Zhang W., Xing C.Y.,
RA Guo H.J., Zheng S.S.;
RT "FOXC1 contributes to microvascular invasion in primary hepatocellular
RT carcinoma via regulating epithelial-mesenchymal transition.";
RL Int. J. Biol. Sci. 8:1130-1141(2012).
RN [22]
RP SUMOYLATION.
RX PubMed=22493429; DOI=10.1074/jbc.m112.339424;
RA Danciu T.E., Chupreta S., Cruz O., Fox J.E., Whitman M.,
RA Iniguez-Lluhi J.A.;
RT "Small ubiquitin-like modifier (SUMO) modification mediates function of the
RT inhibitory domains of developmental regulators FOXC1 and FOXC2.";
RL J. Biol. Chem. 287:18318-18329(2012).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP FUNCTION, INTERACTION WITH GLI2, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=26565916; DOI=10.1016/j.celrep.2015.09.063;
RA Han B., Qu Y., Jin Y., Yu Y., Deng N., Wawrowsky K., Zhang X., Li N.,
RA Bose S., Wang Q., Sakkiah S., Abrol R., Jensen T.W., Berman B.P.,
RA Tanaka H., Johnson J., Gao B., Hao J., Liu Z., Buttyan R., Ray P.S.,
RA Hung M.C., Giuliano A.E., Cui X.;
RT "FOXC1 activates smoothened-independent Hedgehog signaling in basal-like
RT breast cancer.";
RL Cell Rep. 13:1046-1058(2015).
RN [25]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=27907090; DOI=10.1371/journal.pone.0167392;
RA Bin L., Deng L., Yang H., Zhu L., Wang X., Edwards M.G., Richers B.,
RA Leung D.Y.;
RT "Forkhead Box C1 regulates human primary keratinocyte terminal
RT differentiation.";
RL PLoS ONE 11:E0167392-E0167392(2016).
RN [26]
RP VARIANTS RIEG3 LEU-79 AND LEU-131.
RX PubMed=11170889; DOI=10.1086/318183;
RA Nishimura D.Y., Searby C.C., Alward W.L., Walton D., Craig J.E.,
RA Mackey D.A., Kawase K., Kanis A.B., Patil S.R., Stone E.M., Sheffield V.C.;
RT "A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for
RT developmental defects of the anterior chamber of the eye.";
RL Am. J. Hum. Genet. 68:364-372(2001).
RN [27]
RP VARIANTS RIEG3 THR-82; MET-87; SER-112; MET-126 AND LEU-131, AND
RP CHARACTERIZATION OF VARIANTS RIEG3 THR-82; MET-87; SER-112; MET-126 AND
RP LEU-131.
RX PubMed=11179011; DOI=10.1086/318792;
RA Saleem R.A., Banerjee-Basu S., Berry F.B., Baxevanis A.D., Walter M.A.;
RT "Analyses of the effects that disease-causing missense mutations have and
RT function of the winged-helix protein FOXC1.";
RL Am. J. Hum. Genet. 68:627-641(2001).
RN [28]
RP VARIANT RIEG3 THR-79.
RX PubMed=11589884; DOI=10.1016/s0002-9394(01)01059-5;
RA Suzuki T., Takahashi K., Kuwahara S., Wada Y., Abe T., Tamai M.;
RT "A novel (Pro79Thr) mutation in the FKHL7 gene in a Japanese family with
RT Axenfeld-Rieger syndrome.";
RL Am. J. Ophthalmol. 132:572-575(2001).
RN [29]
RP VARIANTS RIEG3 SER-91 AND HIS-127.
RX PubMed=11740218; DOI=10.1097/00061198-200112000-00007;
RA Kawase C., Kawase K., Taniguchi T., Sugiyama K., Yamamoto T., Kitazawa Y.,
RA Alward W.L., Stone E.M., Nishimura D.Y., Sheffield V.C.;
RT "Screening for mutations of Axenfeld-Rieger syndrome caused by FOXC1 gene
RT in Japanese patients.";
RL J. Glaucoma 10:477-482(2001).
RN [30]
RP VARIANT RIEG3 LYS-161.
RX PubMed=12454026;
RA Panicker S.G., Sampath S., Mandal A.K., Reddy A.B.M., Ahmed N.,
RA Hasnain S.E.;
RT "Novel mutation in FOXC1 wing region causing Axenfeld-Rieger anomaly.";
RL Invest. Ophthalmol. Vis. Sci. 43:3613-3616(2002).
RN [31]
RP VARIANT ASGD3 SER-112.
RX PubMed=12614756; DOI=10.1016/s0002-9394(02)02061-5;
RA Honkanen R.A., Nishimura D.Y., Swiderski R.E., Bennett S.R., Hong S.,
RA Kwon Y.H., Stone E.M., Sheffield V.C., Alward W.L.M.;
RT "A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a
RT point mutation (Phe112Ser) in the FOXC1 gene.";
RL Am. J. Ophthalmol. 135:368-375(2003).
RN [32]
RP CHARACTERIZATION OF VARIANTS RIEG3 LEU-79; THR-79; THR-82; SER-91; THR-91;
RP SER-112; MET-126; HIS-127 AND LEU-131, FUNCTION, AND DNA-BENDING.
RX PubMed=14506133; DOI=10.1093/hmg/ddg324;
RA Saleem R.A., Banerjee-Basu S., Berry F.B., Baxevanis A.D., Walter M.A.;
RT "Structural and functional analyses of disease-causing missense mutations
RT in the forkhead domain of FOXC1.";
RL Hum. Mol. Genet. 12:2993-3005(2003).
RN [33]
RP VARIANT RIEG3 PHE-86, MUTAGENESIS OF LEU-86, CHARACTERIZATION OF VARIANT
RP RIEG3 PHE-86, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14578375; DOI=10.1167/iovs.03-0090;
RA Saleem R.A., Murphy T.C., Liebmann J.M., Walter M.A.;
RT "Identification and analysis of a novel mutation in the FOXC1 forkhead
RT domain.";
RL Invest. Ophthalmol. Vis. Sci. 44:4608-4612(2003).
RN [34]
RP VARIANT RIEG3 THR-91.
RX PubMed=15477465; DOI=10.1001/archopht.122.10.1527;
RA Mortemousque B., Amati-Bonneau P., Couture F., Graffan R., Dubois S.,
RA Colin J., Bonneau D., Morissette J., Lacombe D., Raymond V.;
RT "Axenfeld-Rieger anomaly: a novel mutation in the forkhead box C1 (FOXC1)
RT gene in a 4-generation family.";
RL Arch. Ophthalmol. 122:1527-1533(2004).
RN [35]
RP VARIANTS RIEG3 ARG-165 AND PRO-169, CHARACTERIZATION OF VARIANTS RIEG3
RP LYS-161; ARG-165 AND PRO-169, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15277473; DOI=10.1167/iovs.04-0167;
RA Murphy T.C., Saleem R.A., Footz T., Ritch R., McGillivray B., Walter M.A.;
RT "The wing 2 region of the FOXC1 forkhead domain is necessary for normal
RT DNA-binding and transactivation functions.";
RL Invest. Ophthalmol. Vis. Sci. 45:2531-2538(2004).
RN [36]
RP CHARACTERIZATION OF VARIANTS RIEG3 HIS-127 AND LEU-131, FUNCTION,
RP INTERACTION WITH PITX2, AND SUBCELLULAR LOCATION.
RX PubMed=16449236; DOI=10.1093/hmg/ddl008;
RA Berry F.B., Lines M.A., Oas J.M., Footz T., Underhill D.A., Gage P.J.,
RA Walter M.A.;
RT "Functional interactions between FOXC1 and PITX2 underlie the sensitivity
RT to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment
RT dysgenesis.";
RL Hum. Mol. Genet. 15:905-919(2006).
RN [37]
RP VARIANTS RIEG3 ARG-79; SER-115; ASP-149 AND VAL-161.
RX PubMed=16936096; DOI=10.1167/iovs.06-0343;
RA Weisschuh N., Dressler P., Schuettauf F., Wolf C., Wissinger B., Gramer E.;
RT "Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger
RT malformations.";
RL Invest. Ophthalmol. Vis. Sci. 47:3846-3852(2006).
RN [38]
RP ERRATUM OF PUBMED:16936096.
RA Weisschuh N., Dressler P., Schuettauf F., Wolf C., Wissinger B., Gramer E.;
RL Invest. Ophthalmol. Vis. Sci. 47:5162-5162(2006).
RN [39]
RP VARIANT RIEG3 PHE-130, CHARACTERIZATION OF VARIANT RIEG3 PHE-130, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=17210863; DOI=10.1001/archopht.125.1.128;
RA Ito Y.A., Footz T.K., Murphy T.C., Courtens W., Walter M.A.;
RT "Analyses of a novel L130F missense mutation in FOXC1.";
RL Arch. Ophthalmol. 125:128-135(2007).
RN [40]
RP VARIANT RIEG3 PRO-85.
RX PubMed=17653043;
RA Fuse N., Takahashi K., Yokokura S., Nishida K.;
RT "Novel mutations in the FOXC1 gene in Japanese patients with Axenfeld-
RT Rieger syndrome.";
RL Mol. Vis. 13:1005-1009(2007).
RN [41]
RP VARIANT ASGD3 LYS-161.
RX PubMed=18484311; DOI=10.1080/13816810801908152;
RA Khan A.O., Aldahmesh M.A., Al-Amri A.;
RT "Heterozygous FOXC1 mutation (M161K) associated with congenital glaucoma
RT and aniridia in an infant and a milder phenotype in her mother.";
RL Ophthalmic Genet. 29:67-71(2008).
RN [42]
RP VARIANT ASGD3 SER-297, CHARACTERIZATION OF VARIANT ASGD3 SER-297, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=19793056; DOI=10.1111/j.1399-0004.2009.01210.x;
RA Fetterman C.D., Mirzayans F., Walter M.A.;
RT "Characterization of a novel FOXC1 mutation, P297S, identified in two
RT individuals with anterior segment dysgenesis.";
RL Clin. Genet. 76:296-299(2009).
RN [43]
RP VARIANT ASGD3 GLY-152, CHARACTERIZATION OF VARIANT ASGD3 GLY-152, FUNCTION,
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND CHARACTERIZATION OF VARIANT
RP RIEG3 PHE-130.
RX PubMed=19279310; DOI=10.1167/iovs.08-3032;
RA Ito Y.A., Footz T.K., Berry F.B., Mirzayans F., Yu M., Khan A.O.,
RA Walter M.A.;
RT "Severe molecular defects of a novel FOXC1 W152G mutation result in
RT aniridia.";
RL Invest. Ophthalmol. Vis. Sci. 50:3573-3579(2009).
RN [44]
RP VARIANTS ASGD3 VAL-109; TRP-131 AND GLU-138.
RX PubMed=20881294; DOI=10.1167/iovs.10-5309;
RA D'haene B., Meire F., Claerhout I., Kroes H.Y., Plomp A., Arens Y.H.,
RA de Ravel T., Casteels I., De Jaegere S., Hooghe S., Wuyts W.,
RA van den Ende J., Roulez F., Veenstra-Knol H.E., Oldenburg R.A., Giltay J.,
RA Verheij J.B., de Faber J.T., Menten B., De Paepe A., Kestelyn P.,
RA Leroy B.P., De Baere E.;
RT "Expanding the spectrum of FOXC1 and PITX2 mutations and copy number
RT changes in patients with anterior segment malformations.";
RL Invest. Ophthalmol. Vis. Sci. 52:324-333(2011).
RN [45]
RP VARIANT RIEG3 TRP-170.
RX PubMed=23239455; DOI=10.1002/ajmg.a.35697;
RA Gripp K.W., Hopkins E., Jenny K., Thacker D., Salvin J.;
RT "Cardiac anomalies in Axenfeld-Rieger syndrome due to a novel FOXC1
RT mutation.";
RL Am. J. Med. Genet. A 161A:114-119(2013).
RN [46]
RP VARIANT RIEG3 SER-126, CHARACTERIZATION OF VARIANT RIEG3 SER-126, FUNCTION,
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=25786029; DOI=10.1371/journal.pone.0119272;
RA Medina-Trillo C., Sanchez-Sanchez F., Aroca-Aguilar J.D.,
RA Ferre-Fernandez J.J., Morales L., Mendez-Hernandez C.D., Blanco-Kelly F.,
RA Ayuso C., Garcia-Feijoo J., Escribano J.;
RT "Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma:
RT transactivation and phenotypic variability.";
RL PLoS ONE 10:E0119272-E0119272(2015).
RN [47]
RP VARIANT RIEG3 LEU-127.
RX PubMed=24914578; DOI=10.3109/13816810.2014.924016;
RA Du R.F., Huang H., Fan L.L., Li X.P., Xia K., Xiang R.;
RT "A novel mutation of FOXC1 (R127L) in an Axenfeld-Rieger syndrome family
RT with glaucoma and multiple congenital heart diseases.";
RL Ophthalmic Genet. 37:111-115(2016).
RN [48]
RP VARIANTS RIEG3 ARG-128; TYR-135 AND VAL-161, VARIANT ASN-368,
RP CHARACTERIZATION OF VARIANTS RIEG3 ARG-128; TYR-135 AND VAL-161,
RP CHARACTERIZATION OF VARIANT ASN-368, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27804176; DOI=10.1002/humu.23141;
RA Seifi M., Footz T., Taylor S.A., Walter M.A.;
RT "Comparison of bioinformatics prediction, molecular modeling, and
RT functional analyses of FOXC1 mutations in patients with Axenfeld-Rieger
RT syndrome.";
RL Hum. Mutat. 38:169-179(2017).
CC -!- FUNCTION: DNA-binding transcriptional factor that plays a role in a
CC broad range of cellular and developmental processes such as eye, bones,
CC cardiovascular, kidney and skin development (PubMed:11782474,
CC PubMed:15299087, PubMed:15684392, PubMed:16492674, PubMed:27907090,
CC PubMed:14506133, PubMed:14578375, PubMed:15277473, PubMed:16449236,
CC PubMed:17210863, PubMed:19793056, PubMed:19279310, PubMed:25786029,
CC PubMed:27804176). Acts either as a transcriptional activator or
CC repressor (PubMed:11782474). Binds to the consensus binding site 5'-
CC [G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes
CC (PubMed:7957066, PubMed:11782474, PubMed:12533514, PubMed:14506133,
CC PubMed:19793056, PubMed:27804176). Upon DNA-binding, promotes DNA
CC bending (PubMed:7957066, PubMed:14506133). Acts as a transcriptional
CC coactivator (PubMed:26565916). Stimulates Indian hedgehog (Ihh)-induced
CC target gene expression mediated by the transcription factor GLI2, and
CC hence regulates endochondral ossification (By similarity). Acts also as
CC a transcriptional coregulator by increasing DNA-binding capacity of
CC GLI2 in breast cancer cells (PubMed:26565916). Regulates FOXO1 through
CC binding to a conserved element, 5'-GTAAACAAA-3' in its promoter region,
CC implicating FOXC1 as an important regulator of cell viability and
CC resistance to oxidative stress in the eye (PubMed:17993506). Cooperates
CC with transcription factor FOXC2 in regulating expression of genes that
CC maintain podocyte integrity (By similarity). Promotes cell growth
CC inhibition by stopping the cell cycle in the G1 phase through TGFB1-
CC mediated signals (PubMed:12408963). Involved in epithelial-mesenchymal
CC transition (EMT) induction by increasing cell proliferation, migration
CC and invasion (PubMed:20406990, PubMed:22991501). Involved in chemokine
CC CXCL12-induced endothelial cell migration through the control of CXCR4
CC expression (By similarity). Plays a role in the gene regulatory network
CC essential for epidermal keratinocyte terminal differentiation
CC (PubMed:27907090). Essential developmental transcriptional factor
CC required for mesoderm-derived tissues, such as the somites, skin, bone
CC and cartilage. Positively regulates CXCL12 and stem cell factor
CC expression in bone marrow mesenchymal progenitor cells, and hence plays
CC a role in the development and maintenance of mesenchymal niches for
CC haematopoietic stem and progenitor cells (HSPC). Plays a role in
CC corneal transparency by preventing both blood vessel and lymphatic
CC vessel growth during embryonic development in a VEGF-dependent manner.
CC Involved in chemokine CXCL12-induced endothelial cell migration through
CC the control of CXCR4 expression (By similarity). May function as a
CC tumor suppressor (PubMed:12408963). {ECO:0000250|UniProtKB:Q61572,
CC ECO:0000269|PubMed:11782474, ECO:0000269|PubMed:12408963,
CC ECO:0000269|PubMed:12533514, ECO:0000269|PubMed:14506133,
CC ECO:0000269|PubMed:14578375, ECO:0000269|PubMed:15277473,
CC ECO:0000269|PubMed:15299087, ECO:0000269|PubMed:15684392,
CC ECO:0000269|PubMed:16449236, ECO:0000269|PubMed:16492674,
CC ECO:0000269|PubMed:17210863, ECO:0000269|PubMed:17993506,
CC ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:19793056,
CC ECO:0000269|PubMed:20406990, ECO:0000269|PubMed:22991501,
CC ECO:0000269|PubMed:25786029, ECO:0000269|PubMed:26565916,
CC ECO:0000269|PubMed:27804176, ECO:0000269|PubMed:27907090,
CC ECO:0000269|PubMed:7957066}.
CC -!- SUBUNIT: Monomer. Interacts with C1QBP (PubMed:18676636). Interacts
CC (via N-terminus) with GLI2 (via C-terminal internal region); this
CC interaction is direct and increases GLI2 DNA-binding and
CC transcriptional activity through a smoothened (SMO)-independent
CC Hedgehog (Hh) signaling pathway (PubMed:26565916). Interacts (via C-
CC terminus domain) with PITX2 isoform 3 (via homeobox domain)
CC (PubMed:16449236). Interacts with FLNA and PBX1 (PubMed:15684392).
CC {ECO:0000269|PubMed:15684392, ECO:0000269|PubMed:16449236,
CC ECO:0000269|PubMed:18676636, ECO:0000269|PubMed:26565916}.
CC -!- INTERACTION:
CC Q12948; Q07021: C1QBP; NbExp=6; IntAct=EBI-1175253, EBI-347528;
CC Q12948; P21333: FLNA; NbExp=8; IntAct=EBI-1175253, EBI-350432;
CC Q12948; P40424: PBX1; NbExp=5; IntAct=EBI-1175253, EBI-301611;
CC Q12948; Q99697-3: PITX2; NbExp=6; IntAct=EBI-1175253, EBI-1175243;
CC Q12948; Q9Q2G4: ORF; Xeno; NbExp=3; IntAct=EBI-1175253, EBI-6248094;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11782474,
CC ECO:0000269|PubMed:14578375, ECO:0000269|PubMed:15277473,
CC ECO:0000269|PubMed:15299087, ECO:0000269|PubMed:15684392,
CC ECO:0000269|PubMed:16449236, ECO:0000269|PubMed:17210863,
CC ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:19793056,
CC ECO:0000269|PubMed:20406990, ECO:0000269|PubMed:25786029,
CC ECO:0000269|PubMed:26565916, ECO:0000269|PubMed:27804176}.
CC Note=Colocalizes with PITX2 isoform 3 in the nucleus at subnuclear
CC chromatine regions (PubMed:16449236). Colocalizes with CBX5 to a
CC heterochromatin-rich region of the nucleus (PubMed:15684392).
CC Colocalizes with GLI2 in the nucleus (By similarity).
CC {ECO:0000250|UniProtKB:Q61572, ECO:0000269|PubMed:15684392,
CC ECO:0000269|PubMed:16449236}.
CC -!- TISSUE SPECIFICITY: Expressed in keratinocytes of epidermis and hair
CC follicle (PubMed:27907090). Expressed strongly in microvascular
CC invasion (MVI) formation, basal-like breast cancer (BLBC) and
CC hepatocellular tumors (PubMed:20406990, PubMed:22991501). Expressed in
CC breast cancers (at protein level) (PubMed:26565916). Expressed in
CC hematopoietic cells (PubMed:8499623). {ECO:0000269|PubMed:20406990,
CC ECO:0000269|PubMed:22991501, ECO:0000269|PubMed:26565916,
CC ECO:0000269|PubMed:27907090, ECO:0000269|PubMed:8499623}.
CC -!- INDUCTION: Up-regulated during the progression of epidermal
CC keratinocyte differentiation (at protein level) (PubMed:27907090). Up-
CC regulated upon calcium-mediated keratinocyte differentiation
CC (PubMed:27907090). Up-regulated by transforming growth factor TGFB1
CC (PubMed:12408963). {ECO:0000269|PubMed:12408963,
CC ECO:0000269|PubMed:27907090}.
CC -!- PTM: Phosphorylated (PubMed:11782474, PubMed:19279310,
CC PubMed:25786029). Phosphorylated on Ser-272 in response to epidermal
CC growth factor (EGF) in a ERK1/2 MAPK-dependent signaling pathway;
CC phosphorylation contributes to its protein stability and
CC transcriptional activity (PubMed:16492674).
CC {ECO:0000269|PubMed:11782474, ECO:0000269|PubMed:16492674,
CC ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:25786029}.
CC -!- PTM: Sumoylated preferentially with SUMO2 or SUMO3 (PubMed:22493429).
CC Desumoylated by SENP2 (PubMed:22493429). {ECO:0000269|PubMed:22493429}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation
CC (PubMed:16492674). {ECO:0000269|PubMed:16492674}.
CC -!- DISEASE: Axenfeld-Rieger syndrome 3 (RIEG3) [MIM:602482]: An autosomal
CC dominant disorder of morphogenesis that results in abnormal development
CC of the anterior segment of the eye, and results in blindness from
CC glaucoma in approximately 50% of affected individuals. Features include
CC posterior corneal embryotoxon, prominent Schwalbe line and iris
CC adhesion to the Schwalbe line, hypertelorism, hypodontia, sensorineural
CC deafness, redundant periumbilical skin, and cardiovascular defects such
CC as patent ductus arteriosus and atrial septal defect. When associated
CC with tooth anomalies, the disorder is known as Rieger syndrome.
CC {ECO:0000269|PubMed:11170889, ECO:0000269|PubMed:11179011,
CC ECO:0000269|PubMed:11589884, ECO:0000269|PubMed:11740218,
CC ECO:0000269|PubMed:12454026, ECO:0000269|PubMed:12592227,
CC ECO:0000269|PubMed:14506133, ECO:0000269|PubMed:14578375,
CC ECO:0000269|PubMed:15277473, ECO:0000269|PubMed:15477465,
CC ECO:0000269|PubMed:16449236, ECO:0000269|PubMed:16936096,
CC ECO:0000269|PubMed:17210863, ECO:0000269|PubMed:17653043,
CC ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:23239455,
CC ECO:0000269|PubMed:24914578, ECO:0000269|PubMed:25786029,
CC ECO:0000269|PubMed:27804176, ECO:0000269|PubMed:9792859}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Anterior segment dysgenesis 3 (ASGD3) [MIM:601631]: A form of
CC anterior segment dysgenesis, a group of defects affecting anterior
CC structures of the eye including cornea, iris, lens, trabecular
CC meshwork, and Schlemm canal. Anterior segment dysgeneses result from
CC abnormal migration or differentiation of the neural crest derived
CC mesenchymal cells that give rise to components of the anterior chamber
CC during eye development. Different anterior segment anomalies may exist
CC alone or in combination, including iris hypoplasia, enlarged or reduced
CC corneal diameter, corneal vascularization and opacity, posterior
CC embryotoxon, corectopia, polycoria, abnormal iridocorneal angle,
CC ectopia lentis, and anterior synechiae between the iris and posterior
CC corneal surface. Clinical conditions falling within the phenotypic
CC spectrum of anterior segment dysgeneses include aniridia, Axenfeld
CC anomaly, Reiger anomaly/syndrome, Peters anomaly, and
CC iridogoniodysgenesis. ASGD3 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:12614756, ECO:0000269|PubMed:18484311,
CC ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:19793056,
CC ECO:0000269|PubMed:20881294, ECO:0000269|PubMed:9620769}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FOXC1ID40624ch6p25.html";
CC ---------------------------------------------------------------------------
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DR EMBL; AF048693; AAC18081.1; -; Genomic_DNA.
DR EMBL; AF078096; AAC72915.1; -; Genomic_DNA.
DR EMBL; AY228704; AAP15181.1; -; Genomic_DNA.
DR EMBL; AL034344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L12143; AAK13575.1; -; mRNA.
DR EMBL; U13221; AAA92038.1; -; mRNA.
DR CCDS; CCDS4473.1; -.
DR PIR; S51626; S51626.
DR RefSeq; NP_001444.2; NM_001453.2.
DR AlphaFoldDB; Q12948; -.
DR SMR; Q12948; -.
DR BioGRID; 108585; 95.
DR IntAct; Q12948; 76.
DR MINT; Q12948; -.
DR STRING; 9606.ENSP00000370256; -.
DR GlyGen; Q12948; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q12948; -.
DR PhosphoSitePlus; Q12948; -.
DR BioMuta; FOXC1; -.
DR DMDM; 13638267; -.
DR EPD; Q12948; -.
DR jPOST; Q12948; -.
DR MassIVE; Q12948; -.
DR PaxDb; Q12948; -.
DR PeptideAtlas; Q12948; -.
DR PRIDE; Q12948; -.
DR ProteomicsDB; 59043; -.
DR Antibodypedia; 9213; 436 antibodies from 41 providers.
DR DNASU; 2296; -.
DR Ensembl; ENST00000645831.2; ENSP00000493906.1; ENSG00000054598.9.
DR GeneID; 2296; -.
DR KEGG; hsa:2296; -.
DR MANE-Select; ENST00000645831.2; ENSP00000493906.1; NM_001453.3; NP_001444.2.
DR CTD; 2296; -.
DR DisGeNET; 2296; -.
DR GeneCards; FOXC1; -.
DR HGNC; HGNC:3800; FOXC1.
DR HPA; ENSG00000054598; Tissue enriched (salivary).
DR MalaCards; FOXC1; -.
DR MIM; 601090; gene.
DR MIM; 601631; phenotype.
DR MIM; 602482; phenotype.
DR neXtProt; NX_Q12948; -.
DR OpenTargets; ENSG00000054598; -.
DR Orphanet; 98978; Axenfeld anomaly.
DR Orphanet; 782; Axenfeld-Rieger syndrome.
DR Orphanet; 250923; Isolated aniridia.
DR Orphanet; 708; Peters anomaly.
DR Orphanet; 91483; Rieger anomaly.
DR PharmGKB; PA28217; -.
DR VEuPathDB; HostDB:ENSG00000054598; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000162303; -.
DR HOGENOM; CLU_035722_3_0_1; -.
DR InParanoid; Q12948; -.
DR OMA; HCNLQAM; -.
DR OrthoDB; 1270467at2759; -.
DR PhylomeDB; Q12948; -.
DR TreeFam; TF316127; -.
DR PathwayCommons; Q12948; -.
DR SignaLink; Q12948; -.
DR SIGNOR; Q12948; -.
DR BioGRID-ORCS; 2296; 26 hits in 1092 CRISPR screens.
DR ChiTaRS; FOXC1; human.
DR GeneWiki; Forkhead_box_C1; -.
DR GenomeRNAi; 2296; -.
DR Pharos; Q12948; Tbio.
DR PRO; PR:Q12948; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q12948; protein.
DR Bgee; ENSG00000054598; Expressed in parotid gland and 196 other tissues.
DR ExpressionAtlas; Q12948; baseline and differential.
DR Genevisible; Q12948; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0008301; F:DNA binding, bending; IDA:UniProtKB.
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:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS: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:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0003275; P:apoptotic process involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IDA:UniProtKB.
DR GO; GO:1990869; P:cellular response to chemokine; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; ISS:UniProtKB.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0035050; P:embryonic heart tube development; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
DR GO; GO:0001654; P:eye development; IDA:MGI.
DR GO; GO:0008354; P:germ cell migration; IEA:Ensembl.
DR GO; GO:0072010; P:glomerular epithelium development; ISS:UniProtKB.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IDA:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0032808; P:lacrimal gland development; IEA:Ensembl.
DR GO; GO:0001945; P:lymph vessel development; IEA:Ensembl.
DR GO; GO:0036438; P:maintenance of lens transparency; ISS:UniProtKB.
DR GO; GO:0014031; P:mesenchymal cell development; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:1902257; P:negative regulation of apoptotic process involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:1901491; P:negative regulation of lymphangiogenesis; ISS:UniProtKB.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0014032; P:neural crest cell development; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0048341; P:paraxial mesoderm formation; IEA:Ensembl.
DR GO; GO:1904798; P:positive regulation of core promoter binding; ISS:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; IMP:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1901534; P:positive regulation of hematopoietic progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:1902038; P:positive regulation of hematopoietic stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0046620; P:regulation of organ growth; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR GO; GO:0001657; P:ureteric bud development; ISS:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IEA:Ensembl.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR033067; FoxC1.
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:SF68; PTHR11829:SF68; 1.
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; Angiogenesis; Deafness; Developmental protein; Disease variant;
KW DNA-binding; Nucleus; Peters anomaly; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..553
FT /note="Forkhead box protein C1"
FT /id="PRO_0000091806"
FT DNA_BIND 77..168
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..51
FT /note="Required for transcriptional activation"
FT /evidence="ECO:0000269|PubMed:11782474"
FT REGION 173..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 215..366
FT /note="Required for transcriptional inhibition"
FT /evidence="ECO:0000269|PubMed:11782474"
FT REGION 356..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 414..465
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 466..553
FT /note="Required for transcriptional activation"
FT /evidence="ECO:0000269|PubMed:11782474"
FT MOTIF 78..93
FT /note="Nuclear localization signal 1 (NLS 1)"
FT /evidence="ECO:0000269|PubMed:11782474"
FT MOTIF 168..176
FT /note="Nuclear localization signal 2 (NLS 2)"
FT /evidence="ECO:0000269|PubMed:11782474"
FT COMPBIAS 178..194
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..221
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..278
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..302
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 356..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16492674"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VARIANT 79
FT /note="P -> L (in RIEG3; decreased location at the nucleus;
FT decreased transcription regulatory region DNA binding;
FT decreased sequence-specific DNA binding transcription
FT factor activity; no change on DNA bending activity)"
FT /evidence="ECO:0000269|PubMed:11170889,
FT ECO:0000269|PubMed:14506133"
FT /id="VAR_058722"
FT VARIANT 79
FT /note="P -> R (in RIEG3)"
FT /evidence="ECO:0000269|PubMed:16936096"
FT /id="VAR_058723"
FT VARIANT 79
FT /note="P -> T (in RIEG3; decreased location at the nucleus;
FT decreased transcription regulatory region DNA binding;
FT decreased sequence-specific DNA binding transcription
FT factor activity; no change on DNA bending activity)"
FT /evidence="ECO:0000269|PubMed:11589884,
FT ECO:0000269|PubMed:14506133"
FT /id="VAR_058724"
FT VARIANT 82
FT /note="S -> T (in RIEG3; decreased location at the nucleus;
FT decreased transcription regulatory region DNA binding;
FT decreased sequence-specific DNA binding transcription
FT factor activity; dbSNP:rs104893953)"
FT /evidence="ECO:0000269|PubMed:11179011,
FT ECO:0000269|PubMed:14506133, ECO:0000269|PubMed:9792859"
FT /id="VAR_007944"
FT VARIANT 85
FT /note="A -> P (in RIEG3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:17653043"
FT /id="VAR_078501"
FT VARIANT 86
FT /note="L -> F (in RIEG3; no change in location at the
FT nucleus; decreased transcription regulatory region DNA
FT binding; decreased sequence-specific DNA binding
FT transcription factor activity; dbSNP:rs886039568)"
FT /evidence="ECO:0000269|PubMed:14578375"
FT /id="VAR_058725"
FT VARIANT 87
FT /note="I -> M (in RIEG3; loss of protein stability;
FT dbSNP:rs104893954)"
FT /evidence="ECO:0000269|PubMed:11179011,
FT ECO:0000269|PubMed:9792859"
FT /id="VAR_007945"
FT VARIANT 91
FT /note="I -> S (in RIEG3; decreased location at the nucleus;
FT decreased transcription regulatory region DNA binding;
FT decreased sequence-specific DNA binding transcription
FT factor activity; no change on DNA bending activity)"
FT /evidence="ECO:0000269|PubMed:11740218,
FT ECO:0000269|PubMed:14506133"
FT /id="VAR_058726"
FT VARIANT 91
FT /note="I -> T (in RIEG3; decreased location at the nucleus;
FT decreased transcription regulatory region DNA binding;
FT decreased sequence-specific DNA binding transcription
FT factor activity; no change on DNA bending activity)"
FT /evidence="ECO:0000269|PubMed:14506133,
FT ECO:0000269|PubMed:15477465"
FT /id="VAR_058727"
FT VARIANT 109
FT /note="M -> V (in ASGD3; dbSNP:rs917382067)"
FT /evidence="ECO:0000269|PubMed:20881294"
FT /id="VAR_078502"
FT VARIANT 112
FT /note="F -> S (in ASGD3 and RIEG3; decreased location at
FT the nucleus; decreased transcription regulatory region DNA
FT binding; decreased sequence-specific DNA binding
FT transcription factor activity; dbSNP:rs104893951)"
FT /evidence="ECO:0000269|PubMed:11179011,
FT ECO:0000269|PubMed:12614756, ECO:0000269|PubMed:14506133,
FT ECO:0000269|PubMed:9620769"
FT /id="VAR_007815"
FT VARIANT 115
FT /note="Y -> S (in RIEG3)"
FT /evidence="ECO:0000269|PubMed:16936096"
FT /id="VAR_058728"
FT VARIANT 126
FT /note="I -> M (in ASGD3 and RIEG3; with glaucoma; decreased
FT location at the nucleus; decreased transcription regulatory
FT region DNA binding; decreased sequence-specific DNA binding
FT transcription factor activity; dbSNP:rs104893958)"
FT /evidence="ECO:0000269|PubMed:11179011,
FT ECO:0000269|PubMed:14506133, ECO:0000269|PubMed:9620769"
FT /id="VAR_007816"
FT VARIANT 126
FT /note="I -> S (in RIEG3; hypomorphic mutation; decreased
FT protein abundance; decreased protein stability; changed
FT post-translational phosphorylation; decreased location at
FT the nucleus; novel location at the cytoplasm; decreased
FT transcription regulatory region DNA binding; decreased
FT sequence-specific DNA binding transcription factor
FT activity; dbSNP:rs483352810)"
FT /evidence="ECO:0000269|PubMed:25786029"
FT /id="VAR_078503"
FT VARIANT 127
FT /note="R -> H (in RIEG3; decreased location at the nucleus;
FT decreased transcription regulatory region DNA binding;
FT decreased sequence-specific DNA binding transcription
FT factor activity; dbSNP:rs1085307884)"
FT /evidence="ECO:0000269|PubMed:11740218,
FT ECO:0000269|PubMed:14506133, ECO:0000269|PubMed:16449236"
FT /id="VAR_058729"
FT VARIANT 127
FT /note="R -> L (in RIEG3; dbSNP:rs1085307884)"
FT /evidence="ECO:0000269|PubMed:24914578"
FT /id="VAR_078504"
FT VARIANT 128
FT /note="H -> R (in RIEG3; no effect on protein abundance;
FT increased protein stability; decreased location at nucleus;
FT loss of transcription regulatory region DNA binding; loss
FT of sequence-specific DNA binding transcription factor
FT activity)"
FT /evidence="ECO:0000269|PubMed:27804176"
FT /id="VAR_078505"
FT VARIANT 130
FT /note="L -> F (in RIEG3; no effect on protein abundance;
FT changed post-translational phosphorylation; novel location
FT at aggresome, aggregation correspond to microtubule-
FT dependent inclusion bodies; decreased location at the
FT nucleus; decreased transcription regulatory region DNA
FT binding; decreased sequence-specific DNA binding
FT transcription factor activity; dbSNP:rs121909338)"
FT /evidence="ECO:0000269|PubMed:17210863,
FT ECO:0000269|PubMed:19279310"
FT /id="VAR_058730"
FT VARIANT 131
FT /note="S -> L (in RIEG3 and ASGD3; with glaucoma; decreased
FT location at the nucleus; decreased transcription regulatory
FT region DNA binding; decreased sequence-specific DNA binding
FT transcription factor activity; dbSNP:rs104893957)"
FT /evidence="ECO:0000269|PubMed:11170889,
FT ECO:0000269|PubMed:11179011, ECO:0000269|PubMed:14506133,
FT ECO:0000269|PubMed:16449236, ECO:0000269|PubMed:9620769"
FT /id="VAR_007817"
FT VARIANT 131
FT /note="S -> W (in ASGD3)"
FT /evidence="ECO:0000269|PubMed:20881294"
FT /id="VAR_078506"
FT VARIANT 135
FT /note="C -> Y (in RIEG3; decreased protein abundance;
FT decreased protein stability; decreased location at nucleus;
FT loss of transcription regulatory region DNA binding; loss
FT of sequence-specific DNA binding transcription factor
FT activity)"
FT /evidence="ECO:0000269|PubMed:27804176"
FT /id="VAR_078507"
FT VARIANT 138
FT /note="K -> E (in ASGD3)"
FT /evidence="ECO:0000269|PubMed:20881294"
FT /id="VAR_078508"
FT VARIANT 149
FT /note="G -> D (in RIEG3)"
FT /evidence="ECO:0000269|PubMed:16936096"
FT /id="VAR_058731"
FT VARIANT 152
FT /note="W -> G (in ASGD3; no change in protein abundance;
FT changed post-translational phosphorylation; changed protein
FT structure; decreased location at the nucleus; novel
FT location at the cytoplasm; increased protein aggregation,
FT aggregation do not correspond to microtubule-dependent
FT inclusion bodies; loss of transcription regulatory region
FT DNA binding; loss of sequence-specific DNA binding
FT transcription factor activity)"
FT /evidence="ECO:0000269|PubMed:19279310"
FT /id="VAR_078509"
FT VARIANT 161
FT /note="M -> K (in RIEG3 and ASGD3; no change in location at
FT the nucleus; decreased transcription regulatory region DNA
FT binding; decreased sequence-specific DNA binding
FT transcription factor activity)"
FT /evidence="ECO:0000269|PubMed:12454026,
FT ECO:0000269|PubMed:12592227, ECO:0000269|PubMed:15277473,
FT ECO:0000269|PubMed:18484311"
FT /id="VAR_018150"
FT VARIANT 161
FT /note="M -> V (in RIEG3; no effect on protein abundance; no
FT effect on protein stability; no effect on location at
FT nucleus; no effect on transcription regulatory region DNA
FT binding; decreased sequence-specific DNA binding
FT transcription factor activity)"
FT /evidence="ECO:0000269|PubMed:16936096,
FT ECO:0000269|PubMed:27804176"
FT /id="VAR_058732"
FT VARIANT 165
FT /note="G -> R (in RIEG3; no change in location at the
FT nucleus; no effect on transcription regulatory region DNA
FT binding; decreased sequence-specific DNA binding
FT transcription factor activity)"
FT /evidence="ECO:0000269|PubMed:15277473"
FT /id="VAR_058733"
FT VARIANT 169
FT /note="R -> P (in RIEG3; no change in location at the
FT nucleus; decreased transcription regulatory region DNA
FT binding; decreased sequence-specific DNA binding
FT transcription factor activity)"
FT /evidence="ECO:0000269|PubMed:15277473"
FT /id="VAR_058734"
FT VARIANT 170
FT /note="R -> W (in RIEG3; unknown pathological significance;
FT dbSNP:rs1581373890)"
FT /evidence="ECO:0000269|PubMed:23239455"
FT /id="VAR_078510"
FT VARIANT 297
FT /note="P -> S (in ASGD3; no effect on protein abundance;
FT increased protein stability; no effect on nuclear location;
FT no effect on transcription regulatory region DNA binding;
FT decreased sequence-specific DNA binding transcription
FT factor activity; dbSNP:rs79691946)"
FT /evidence="ECO:0000269|PubMed:19793056"
FT /id="VAR_078511"
FT VARIANT 368
FT /note="T -> N (no effect on protein abundance; no effect on
FT protein stability; no effect on nuclear location; no effect
FT on transcription regulatory region DNA binding; no effect
FT on sequence-specific DNA binding transcription factor
FT activity)"
FT /evidence="ECO:0000269|PubMed:27804176"
FT /id="VAR_078512"
FT MUTAGEN 68
FT /note="T->A: No effect on protein stability. No effect on
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:16492674"
FT MUTAGEN 79
FT /note="P->A: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 79
FT /note="P->E: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 79
FT /note="P->K: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 86
FT /note="L->A: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 86
FT /note="L->E: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 86
FT /note="L->K: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 86
FT /note="L->P: Severely disrupts the protein function."
FT /evidence="ECO:0000269|PubMed:14578375"
FT MUTAGEN 87
FT /note="I->A,E,K: Loss of protein stability."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 91
FT /note="I->A: Decreased nuclear localization. Decreased DNA-
FT binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 91
FT /note="I->E: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 91
FT /note="I->K: Decreased nuclear localization. No effect on
FT DNA-binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 126
FT /note="I->A: Decreased nuclear localization. Decreased DNA-
FT binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 126
FT /note="I->E: Decreased nuclear localization. Decreased DNA-
FT binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 126
FT /note="I->K: Decreased nuclear localization. Decreased DNA-
FT binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 127
FT /note="R->A: Decreased nuclear localization. Decreased DNA-
FT binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 127
FT /note="R->E: Decreased nuclear localization. Decreased DNA-
FT binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 127
FT /note="R->K: Decreased nuclear localization. Decreased DNA-
FT binding activity. Decreased transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15299087"
FT MUTAGEN 241
FT /note="S->A: Decreased protein stability. No effect on
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:16492674"
FT MUTAGEN 259
FT /note="S->A: No effect on protein stability. No effect on
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:16492674"
FT MUTAGEN 272
FT /note="S->A: Decreased protein stability. Decreased
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:16492674"
FT CONFLICT 70..77
FT /note="QPQPKDMV -> RSRSPRHG (in Ref. 5; AAK13575)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="L -> Q (in Ref. 5; AAK13575)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="V -> L (in Ref. 2; AAC72915)"
FT /evidence="ECO:0000305"
FT CONFLICT 199..202
FT /note="RQPP -> ASPR (in Ref. 2; AAC72915)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="D -> N (in Ref. 1; AAC18081 and 3; AAP15181)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 56789 MW; 59C6FB94303ED59A CRC64;
MQARYSVSSP NSLGVVPYLG GEQSYYRAAA AAAGGGYTAM PAPMSVYSHP AHAEQYPGGM
ARAYGPYTPQ PQPKDMVKPP YSYIALITMA IQNAPDKKIT LNGIYQFIMD RFPFYRDNKQ
GWQNSIRHNL SLNECFVKVP RDDKKPGKGS YWTLDPDSYN MFENGSFLRR RRRFKKKDAV
KDKEEKDRLH LKEPPPPGRQ PPPAPPEQAD GNAPGPQPPP VRIQDIKTEN GTCPSPPQPL
SPAAALGSGS AAAVPKIESP DSSSSSLSSG SSPPGSLPSA RPLSLDGADS APPPPAPSAP
PPHHSQGFSV DNIMTSLRGS PQSAAAELSS GLLASAAASS RAGIAPPLAL GAYSPGQSSL
YSSPCSQTSS AGSSGGGGGG AGAAGGAGGA GTYHCNLQAM SLYAAGERGG HLQGAPGGAG
GSAVDDPLPD YSLPPVTSSS SSSLSHGGGG GGGGGGQEAG HHPAAHQGRL TSWYLNQAGG
DLGHLASAAA AAAAAGYPGQ QQNFHSVREM FESQRIGLNN SPVNGNSSCQ MAFPSSQSLY
RTSGAFVYDC SKF
