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   27-MAR-2024, entry version 216.
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=10.1016/s0888-7543(02)96860-6;
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="https://atlasgeneticsoncology.org/gene/40624/FOXC1";
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; 225.
DR   IntAct; Q12948; 75.
DR   MINT; Q12948; -.
DR   STRING; 9606.ENSP00000493906; -.
DR   GlyGen; Q12948; 5 sites, 1 O-linked glycan (5 sites).
DR   iPTMnet; Q12948; -.
DR   PhosphoSitePlus; Q12948; -.
DR   BioMuta; FOXC1; -.
DR   DMDM; 13638267; -.
DR   EPD; Q12948; -.
DR   jPOST; Q12948; -.
DR   MassIVE; Q12948; -.
DR   PaxDb; 9606-ENSP00000370256; -.
DR   PeptideAtlas; Q12948; -.
DR   ProteomicsDB; 59043; -.
DR   Pumba; Q12948; -.
DR   Antibodypedia; 9213; 499 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   AGR; HGNC:3800; -.
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; TSWYLNQ; -.
DR   OrthoDB; 5385885at2759; -.
DR   PhylomeDB; Q12948; -.
DR   TreeFam; TF316127; -.
DR   PathwayCommons; Q12948; -.
DR   Reactome; R-HSA-9761174; Formation of intermediate mesoderm.
DR   SignaLink; Q12948; -.
DR   SIGNOR; Q12948; -.
DR   BioGRID-ORCS; 2296; 31 hits in 1171 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 198 other cell types or tissues.
DR   ExpressionAtlas; Q12948; baseline and differential.
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:0045893; P:positive regulation of DNA-templated transcription; IDA: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:0006355; P:regulation of DNA-templated transcription; 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: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; cd20044; FH_FOXC1; 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; IPR047391; FOXC1/C2-like_FH.
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:SF68; FORKHEAD BOX PROTEIN C1; 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; Q12948; HS.
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; uncertain 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
FT                   microtubule-dependent inclusion bodies; decreased location
FT                   at the nucleus; decreased transcription regulatory region
FT                   DNA 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; uncertain 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
FT                   DNA-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
FT                   DNA-binding activity. Decreased transcriptional activity."
FT                   /evidence="ECO:0000269|PubMed:15299087"
FT   MUTAGEN         126
FT                   /note="I->E: Decreased nuclear localization. Decreased
FT                   DNA-binding activity. Decreased transcriptional activity."
FT                   /evidence="ECO:0000269|PubMed:15299087"
FT   MUTAGEN         126
FT                   /note="I->K: Decreased nuclear localization. Decreased
FT                   DNA-binding activity. Decreased transcriptional activity."
FT                   /evidence="ECO:0000269|PubMed:15299087"
FT   MUTAGEN         127
FT                   /note="R->A: Decreased nuclear localization. Decreased
FT                   DNA-binding activity. Decreased transcriptional activity."
FT                   /evidence="ECO:0000269|PubMed:15299087"
FT   MUTAGEN         127
FT                   /note="R->E: Decreased nuclear localization. Decreased
FT                   DNA-binding activity. Decreased transcriptional activity."
FT                   /evidence="ECO:0000269|PubMed:15299087"
FT   MUTAGEN         127
FT                   /note="R->K: Decreased nuclear localization. Decreased
FT                   DNA-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
//