FOXK1_MOUSE
ID FOXK1_MOUSE Reviewed; 719 AA.
AC P42128; O35939; Q3UHI6; Q3UN67;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Forkhead box protein K1 {ECO:0000303|PubMed:12446708};
DE AltName: Full=Myocyte nuclear factor {ECO:0000303|PubMed:10792059, ECO:0000303|PubMed:8007964};
DE Short=MNF {ECO:0000303|PubMed:10792059, ECO:0000303|PubMed:8007964};
GN Name=Foxk1 {ECO:0000303|PubMed:12446708, ECO:0000312|MGI:MGI:1347488};
GN Synonyms=Mnf {ECO:0000303|PubMed:10792059};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RC TISSUE=Pancreatic acinar cell;
RX PubMed=8007964; DOI=10.1128/mcb.14.7.4596-4605.1994;
RA Bassel-Duby R., Hernandez M.D., Yang Q., Rochelle J.M., Seldin M.F.,
RA Williams R.S.;
RT "Myocyte nuclear factor, a novel winged-helix transcription factor under
RT both developmental and neural regulation in striated myocytes.";
RL Mol. Cell. Biol. 14:4596-4605(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Diencephalon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-411, FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=9271401; DOI=10.1128/mcb.17.9.5236;
RA Yang Q., Bassel-Duby R., Williams R.S.;
RT "Transient expression of a winged-helix protein, MNF-beta, during
RT myogenesis.";
RL Mol. Cell. Biol. 17:5236-5243(1997).
RN [4]
RP INTERACTION WITH SIN3B.
RC TISSUE=Heart;
RX PubMed=10620510; DOI=10.1042/bj3450335;
RA Yang Q., Kong Y., Rothermel B., Garry D.J., Bassel-Duby R., Williams R.S.;
RT "The winged-helix/forkhead protein myocyte nuclear factor beta (MNF-beta)
RT forms a co-repressor complex with mammalian Sin3B.";
RL Biochem. J. 345:335-343(2000).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10792059; DOI=10.1073/pnas.100501197;
RA Garry D.J., Meeson A., Elterman J., Zhao Y., Yang P., Bassel-Duby R.,
RA Williams R.S.;
RT "Myogenic stem cell function is impaired in mice lacking the
RT forkhead/winged helix protein MNF.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5416-5421(2000).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12446708; DOI=10.1074/jbc.m209200200;
RA Hawke T.J., Jiang N., Garry D.J.;
RT "Absence of p21CIP rescues myogenic progenitor cell proliferative and
RT regenerative capacity in Foxk1 null mice.";
RL J. Biol. Chem. 278:4015-4020(2003).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=16376864; DOI=10.1016/j.brainres.2005.11.022;
RA Wijchers P.J.E.C., Hoekman M.F.M., Burbach J.P.H., Smidt M.P.;
RT "Identification of forkhead transcription factors in cortical and
RT dopaminergic areas of the adult murine brain.";
RL Brain Res. 1068:23-33(2006).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=17363903; DOI=10.1038/sj.emboj.7601635;
RA Meeson A.P., Shi X., Alexander M.S., Williams R.S., Allen R.E., Jiang N.,
RA Adham I.M., Goetsch S.C., Hammer R.E., Garry D.J.;
RT "Sox15 and Fhl3 transcriptionally coactivate Foxk1 and regulate myogenic
RT progenitor cells.";
RL EMBO J. 26:1902-1912(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-422, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199; SER-209; SER-225;
RP SER-229; THR-231; THR-233; SER-239; SER-243; SER-281; SER-285; THR-422;
RP SER-427 AND SER-431, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH FHL2.
RX PubMed=20013826; DOI=10.1002/stem.274;
RA Shi X., Bowlin K.M., Garry D.J.;
RT "Fhl2 interacts with Foxk1 and corepresses Foxo4 activity in myogenic
RT progenitors.";
RL Stem Cells 28:462-469(2010).
RN [12]
RP FUNCTION, INTERACTION WITH FOXO4 AND MEF2C, MUTAGENESIS OF LYS-333 AND
RP ARG-340, AND DNA-BINDING.
RX PubMed=22956541; DOI=10.1242/jcs.105239;
RA Shi X., Wallis A.M., Gerard R.D., Voelker K.A., Grange R.W., DePinho R.A.,
RA Garry M.G., Garry D.J.;
RT "Foxk1 promotes cell proliferation and represses myogenic differentiation
RT by regulating Foxo4 and Mef2.";
RL J. Cell Sci. 125:5329-5337(2012).
RN [13]
RP INTERACTION WITH SIN3A AND SIN3B.
RX PubMed=22476904; DOI=10.1007/s11010-012-1302-2;
RA Shi X., Garry D.J.;
RT "Sin3 interacts with Foxk1 and regulates myogenic progenitors.";
RL Mol. Cell. Biochem. 366:251-258(2012).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=23714736; DOI=10.1016/j.gep.2013.05.003;
RA Sel S., Muenzenberg C., Nass N., Kalinski T., Datan M., Auffarth G.U.,
RA Toeteberg-Harms M., Zenkel M., Kruse F.E., Paulsen F., Schicht M.;
RT "The transcription factor Foxk1 is expressed in developing and adult mouse
RT neuroretina.";
RL Gene Expr. Patterns 13:280-286(2013).
RN [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-147, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SIN3A.
RX PubMed=25402684; DOI=10.1038/ncb3062;
RA Bowman C.J., Ayer D.E., Dynlacht B.D.;
RT "Foxk proteins repress the initiation of starvation-induced atrophy and
RT autophagy programs.";
RL Nat. Cell Biol. 16:1202-1214(2014).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH YWHAE, PHOSPHORYLATION AT
RP SER-402; SER-406; SER-427 AND SER-431, AND MUTAGENESIS OF 402-SER--SER-406
RP AND 417-SER--SER-431.
RX PubMed=29861159; DOI=10.1016/j.molcel.2018.04.024;
RA He L., Gomes A.P., Wang X., Yoon S.O., Lee G., Nagiec M.J., Cho S.,
RA Chavez A., Islam T., Yu Y., Asara J.M., Kim B.Y., Blenis J.;
RT "mTORC1 promotes metabolic reprogramming by the suppression of GSK3-
RT dependent foxk1 phosphorylation.";
RL Mol. Cell 70:949-960(2018).
RN [18]
RP FUNCTION.
RX PubMed=30700909; DOI=10.1038/s41586-019-0900-5;
RA Sukonina V., Ma H., Zhang W., Bartesaghi S., Subhash S., Heglind M.,
RA Foyn H., Betz M.J., Nilsson D., Lidell M.E., Naumann J., Haufs-Brusberg S.,
RA Palmgren H., Mondal T., Beg M., Jedrychowski M.P., Tasken K., Pfeifer A.,
RA Peng X.R., Kanduri C., Enerbaeck S.;
RT "FOXK1 and FOXK2 regulate aerobic glycolysis.";
RL Nature 566:279-283(2019).
RN [19]
RP STRUCTURE BY NMR OF 289-389.
RX PubMed=12449423; DOI=10.1023/a:1020616926152;
RA Chuang W.J., Yeh I.J., Hsieh Y.H., Liu P.P., Chen S.W., Jeng W.Y.;
RT "1H, 15N and 13C resonance assignments for the DNA-binding domain of
RT myocyte nuclear factor (Foxk1).";
RL J. Biomol. NMR 24:75-76(2002).
CC -!- FUNCTION: Transcriptional regulator involved in different processes
CC such as glucose metabolism, aerobic glycolysis, muscle cell
CC differentiation and autophagy (PubMed:25402684, PubMed:29861159,
CC PubMed:30700909). Recognizes and binds the forkhead DNA sequence motif
CC (5'-GTAAACA-3') and can both act as a transcription activator or
CC repressor, depending on the context (PubMed:25402684, PubMed:29861159,
CC PubMed:30700909). Together with FOXK2, acts as a key regulator of
CC metabolic reprogramming towards aerobic glycolysis, a process in which
CC glucose is converted to lactate in the presence of oxygen
CC (PubMed:30700909). Acts by promoting expression of enzymes for
CC glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate
CC kinase (PKLR) and lactate dehydrogenase), while suppressing further
CC oxidation of pyruvate in the mitochondria by up-regulating pyruvate
CC dehydrogenase kinases PDK1 and PDK4 (PubMed:30700909). Probably plays a
CC role in gluconeogenesis during overnight fasting, when lactate from
CC white adipose tissue and muscle is the main substrate
CC (PubMed:30700909). Involved in mTORC1-mediated metabolic reprogramming:
CC in response to mTORC1 signaling, translocates into the nucleus and
CC regulates the expression of genes associated with glycolysis and
CC downstream anabolic pathways, such as HIF1A, thereby regulating glucose
CC metabolism (PubMed:29861159). Together with FOXK2, acts as a negative
CC regulator of autophagy in skeletal muscle: in response to starvation,
CC enters the nucleus, binds the promoters of autophagy genes and
CC represses their expression, preventing proteolysis of skeletal muscle
CC proteins (PubMed:25402684). Acts as a transcriptional regulator of the
CC myogenic progenitor cell population in skeletal muscle (PubMed:8007964,
CC PubMed:9271401, PubMed:12446708, PubMed:22956541). Binds to the
CC upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating
CC the myogenic progenitor cell population (PubMed:8007964,
CC PubMed:9271401). Promotes muscle progenitor cell proliferation by
CC repressing the transcriptional activity of FOXO4, thereby inhibiting
CC myogenic differentiation (PubMed:12446708, PubMed:22956541). Involved
CC in remodeling processes of adult muscles that occur in response to
CC physiological stimuli (PubMed:9271401, PubMed:22956541). Required to
CC correct temporal orchestration of molecular and cellular events
CC necessary for muscle repair (PubMed:10792059). Represses myogenic
CC differentiation by inhibiting MEFC activity (PubMed:22956541).
CC Positively regulates Wnt/beta-catenin signaling by translocating DVL
CC into the nucleus (By similarity). Reduces virus replication, probably
CC by binding the interferon stimulated response element (ISRE) to promote
CC antiviral gene expression (By similarity).
CC {ECO:0000250|UniProtKB:P85037, ECO:0000269|PubMed:10792059,
CC ECO:0000269|PubMed:12446708, ECO:0000269|PubMed:22956541,
CC ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:29861159,
CC ECO:0000269|PubMed:30700909, ECO:0000269|PubMed:8007964,
CC ECO:0000269|PubMed:9271401}.
CC -!- SUBUNIT: Interacts with SIN3A and SIN3B (via PAH2) to form a complex
CC which represses transcription (PubMed:10620510). Component of SIN3A-,
CC but not SIN3B-, containing multiprotein complexes (PubMed:25402684).
CC Interacts with FOXO4 and MEF2C; both interactions inhibit FOXO4 and
CC MEF2C transactivation activity (PubMed:22956541). Interacts (when
CC phosphorylated) with YWHAE/14-3-3-epsilon; promotes sequestration in
CC the cytoplasm and leads to impaired ability to bind DNA
CC (PubMed:29861159). Interacts with FHL2 (PubMed:20013826). Interacts
CC with SRF (By similarity). Interacts with DVL2 and DVL3; the interaction
CC induces DVL2 nuclear translocation (By similarity). Interacts with BAP1
CC (when phosphorylated) (By similarity). {ECO:0000250|UniProtKB:P85037,
CC ECO:0000269|PubMed:10620510, ECO:0000269|PubMed:20013826,
CC ECO:0000269|PubMed:22956541, ECO:0000269|PubMed:25402684,
CC ECO:0000269|PubMed:29861159}.
CC -!- INTERACTION:
CC P42128; Q62141-2: Sin3b; NbExp=11; IntAct=EBI-878270, EBI-591466;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20013826,
CC ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:29861159}. Cytoplasm
CC {ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:29861159}.
CC Note=Translocation to the nucleus is regulated by phosphorylation:
CC phosphorylation by GSK3 (GSK3A or GSK3B) promotes interaction with 14-
CC 3-3 proteins and sequestration in the cytoplasm (PubMed:29861159).
CC Dephosphorylation promotes translocation to the nucleus
CC (PubMed:29861159). {ECO:0000269|PubMed:29861159}.
CC -!- TISSUE SPECIFICITY: Expressed in tissues and cells in which the
CC myoglobin gene is transcriptionally active including cardiac and
CC skeletal myocytes, brain and kidney (PubMed:8007964, PubMed:9271401).
CC In the adult brain, expressed in the piriform cortex and the indusium
CC griseum. In the hippocampus, expression is localized to the dentate
CC gyrus and CA3 area (PubMed:16376864). In the cerebellum, expression is
CC confined to the Purkinje cell layer (PubMed:16376864). Present in
CC neuroretinal cells: expressed in rod bipolar cells, amacrine cells and
CC ganglion cells (at protein level) (PubMed:23714736).
CC {ECO:0000269|PubMed:16376864, ECO:0000269|PubMed:23714736,
CC ECO:0000269|PubMed:8007964, ECO:0000269|PubMed:9271401}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 13.5 dpc in developing muscle, limbs,
CC trunk, and heart. {ECO:0000269|PubMed:17363903}.
CC -!- PTM: Phosphorylation by GSK3 (GSK3A or GSK3B) promotes interaction with
CC YWHAE/14-3-3-epsilon and retention in the cytoplasm (PubMed:29861159).
CC In response to mTORC1 signaling, phosphorylation by GSK3 is prevented,
CC leading to translocation to the nucleus (PubMed:29861159).
CC {ECO:0000269|PubMed:29861159}.
CC -!- DISRUPTION PHENOTYPE: Mutants exhibit a growth deficiency and a severe
CC impairment in skeletal muscle regeneration following injury
CC (PubMed:12446708, PubMed:10792059). They show atrophic skeletal muscles
CC and their satellite cell function is impaired (PubMed:10792059). Double
CC knockouts of CDKN1A and FOXK1 don't show significant differences
CC compared to wild-type (PubMed:12446708). {ECO:0000269|PubMed:10792059,
CC ECO:0000269|PubMed:12446708}.
CC -!- CAUTION: The mode of regulation of FOXK1 by mTORC1 is controversial.
CC According to a first report, mTORC1 signaling promotes phosphorylation
CC of FOXK1 and nuclear exclusion (PubMed:25402684). According to a second
CC report, mTORC1 signaling prevents phosphorylation by GSK3 (GSK3A or
CC GSK3B), thereby promoting translocation to the nucleus
CC (PubMed:29861159). {ECO:0000269|PubMed:25402684,
CC ECO:0000269|PubMed:29861159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA37529.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB69641.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE25880.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L26507; AAA37529.1; ALT_FRAME; mRNA.
DR EMBL; AK144418; BAE25880.1; ALT_INIT; mRNA.
DR EMBL; AK147375; BAE27871.1; -; mRNA.
DR EMBL; U95016; AAB69641.1; ALT_FRAME; mRNA.
DR CCDS; CCDS19826.1; -.
DR PIR; A56051; A56051.
DR RefSeq; NP_951031.2; NM_199068.2.
DR PDB; 2A3S; NMR; -; A=289-389.
DR PDB; 2D2W; NMR; -; A=289-389.
DR PDBsum; 2A3S; -.
DR PDBsum; 2D2W; -.
DR AlphaFoldDB; P42128; -.
DR BMRB; P42128; -.
DR SMR; P42128; -.
DR BioGRID; 201459; 5.
DR IntAct; P42128; 2.
DR MINT; P42128; -.
DR STRING; 10090.ENSMUSP00000072616; -.
DR iPTMnet; P42128; -.
DR PhosphoSitePlus; P42128; -.
DR EPD; P42128; -.
DR jPOST; P42128; -.
DR MaxQB; P42128; -.
DR PaxDb; P42128; -.
DR PeptideAtlas; P42128; -.
DR PRIDE; P42128; -.
DR ProteomicsDB; 271796; -.
DR Antibodypedia; 11250; 230 antibodies from 30 providers.
DR DNASU; 17425; -.
DR Ensembl; ENSMUST00000072837; ENSMUSP00000072616; ENSMUSG00000056493.
DR GeneID; 17425; -.
DR KEGG; mmu:17425; -.
DR UCSC; uc009aio.1; mouse.
DR CTD; 221937; -.
DR MGI; MGI:1347488; Foxk1.
DR VEuPathDB; HostDB:ENSMUSG00000056493; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000159507; -.
DR HOGENOM; CLU_022344_0_0_1; -.
DR InParanoid; P42128; -.
DR OMA; VTIGQHH; -.
DR OrthoDB; 1270467at2759; -.
DR PhylomeDB; P42128; -.
DR TreeFam; TF325718; -.
DR Reactome; R-MMU-5689603; UCH proteinases.
DR BioGRID-ORCS; 17425; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Foxk1; mouse.
DR EvolutionaryTrace; P42128; -.
DR PRO; PR:P42128; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P42128; protein.
DR Bgee; ENSMUSG00000056493; Expressed in ascending aorta and 231 other tissues.
DR ExpressionAtlas; P42128; baseline and differential.
DR Genevisible; P42128; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0061621; P:canonical glycolysis; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISO:MGI.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0010507; P:negative regulation of autophagy; ISO:MGI.
DR GO; GO:0045786; P:negative regulation of cell cycle; TAS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0042594; P:response to starvation; ISO:MGI.
DR CDD; cd00059; FH; 1.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR018122; TF_fork_head_CS_1.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SMART; SM00240; FHA; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 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 3D-structure; Acetylation; Activator; Cytoplasm; Developmental protein;
KW Differentiation; DNA-binding; Methylation; Myogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P85037"
FT CHAIN 2..719
FT /note="Forkhead box protein K1"
FT /id="PRO_0000091857"
FT DOMAIN 109..161
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DNA_BIND 291..386
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 2..40
FT /note="Interaction with SIN3A and SIN3B"
FT /evidence="ECO:0000269|PubMed:10620510,
FT ECO:0000269|PubMed:22476904"
FT REGION 35..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..406
FT /note="Required for interaction with FOXO4 and MEF2C"
FT /evidence="ECO:0000269|PubMed:22956541"
FT REGION 399..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 665..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..61
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 399..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 669..686
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 696..710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P85037"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P85037"
FT MOD_RES 147
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 177
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P85037"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 231
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 233
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 402
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29861159"
FT MOD_RES 406
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29861159"
FT MOD_RES 408
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P85037"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P85037"
FT MOD_RES 422
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29861159,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29861159,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P85037"
FT MUTAGEN 333
FT /note="K->A: Decreases DNA-binding. No effect on
FT transcriptional repression."
FT /evidence="ECO:0000269|PubMed:22956541"
FT MUTAGEN 340
FT /note="R->A: Abolishes DNA-binding. No effect on
FT transcriptional repression."
FT /evidence="ECO:0000269|PubMed:22956541"
FT MUTAGEN 402..406
FT /note="SAPAS->AAPAA: Decreased phosphorylation by GSK3A and
FT interaction with 14-3-3 proteins."
FT /evidence="ECO:0000269|PubMed:29861159"
FT MUTAGEN 427..431
FT /note="SREGS->AREGA: Decreased phosphorylation by GSK3A and
FT interaction with 14-3-3 proteins."
FT /evidence="ECO:0000269|PubMed:29861159"
FT CONFLICT 43
FT /note="Missing (in Ref. 1; AAA37529 and 3; AAB69641)"
FT /evidence="ECO:0000305"
FT CONFLICT 402..403
FT /note="SA -> RS (in Ref. 1; AAA37529)"
FT /evidence="ECO:0000305"
FT CONFLICT 407..411
FT /note="PTHPG -> HTSHA (in Ref. 3; AAB69641)"
FT /evidence="ECO:0000305"
FT CONFLICT 551
FT /note="R -> A (in Ref. 1; AAA37529)"
FT /evidence="ECO:0000305"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:2A3S"
FT HELIX 298..304
FT /evidence="ECO:0007829|PDB:2A3S"
FT STRAND 307..312
FT /evidence="ECO:0007829|PDB:2A3S"
FT HELIX 314..324
FT /evidence="ECO:0007829|PDB:2A3S"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:2A3S"
FT HELIX 335..345
FT /evidence="ECO:0007829|PDB:2A3S"
FT STRAND 347..356
FT /evidence="ECO:0007829|PDB:2A3S"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:2A3S"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:2A3S"
FT HELIX 372..380
FT /evidence="ECO:0007829|PDB:2A3S"
SQ SEQUENCE 719 AA; 74920 MW; 0A0D3049B7846328 CRC64;
MAEVGEDSGA RALLALRSAP CSPVLCAAAA AAAFPATTSP PPPAQPPPGP PALPAEPGPG
PVPSTVATAT TTAPALVAAA AASVRQSPGP ALARLEGREF EFLMRQPSVT IGRNSSQGSV
DLSMGLSSFI SRRHLQLSFQ EPHFYLRCLG KNGVFVDGAF QRRGAPALQL PQQCTFRFPS
TAIKIQFTSL YHKEEAPASP LRPLYPQISP LKIHIPEPDL RSLVSPIPSP TGTISVPNSC
PASPRGAGSS SYRFVQNVTS DLQLAAEFAA KAASEQQADA SGGDSPKDES KPPYSYAQLI
VQAISSAQDR QLTLSGIYAH ITKHYPYYRT ADKGWQNSIR HNLSLNRYFI KVPRSQEEPG
KGSFWRIDPA SEAKLVEQAF RKRRQRGVSC FRTPFGPLSS RSAPASPTHP GLMSPRSSGL
QTPECLSREG SPIPHDPDLG SKLASVPEYR YSQSAPGSPV SAQPVIMAVP PRPSNLVAKP
VAYMPASIVT SQQPSGHAIH VVQQAPTVTM VRVVTTSANS ANGYILASQG STGTSHDTAG
TAVLDLGNEA RGLEEKPTIA FATIPAASRV IQTVASQMAP GVPGHTVTIL QPATPVTIGQ
HHLPVRAVTQ NGKHAVPTNS LTGNAYALSS PLQLLAAQAS SSTPVVITRV CEVGPEEPAA
AVSVAANAAP TPAASTTTSA SSSGEPEVKR SRVEEPGGTA TTQPTAMAAT GPQGPGTGE
