ID FOXK2_HUMAN Reviewed; 660 AA. AC Q01167; A6NEP5; Q13622; Q13623; Q13624; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2006, sequence version 3. DT 27-MAR-2024, entry version 231. DE RecName: Full=Forkhead box protein K2 {ECO:0000305}; DE AltName: Full=G/T-mismatch specific binding protein {ECO:0000303|PubMed:20097901}; DE Short=nGTBP {ECO:0000303|PubMed:20097901}; DE AltName: Full=Interleukin enhancer-binding factor 1 {ECO:0000303|PubMed:12402362, ECO:0000303|PubMed:1909027}; GN Name=FOXK2; GN Synonyms=ILF {ECO:0000303|PubMed:1339390, ECO:0000303|PubMed:1909027}, GN ILF1 {ECO:0000303|PubMed:12402362}; 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 [MRNA] (ISOFORM 1), AND FUNCTION. RC TISSUE=Cervix carcinoma; RX PubMed=1909027; DOI=10.1073/pnas.88.17.7739; RA Li C., Lai C., Sigman D.S., Gaynor R.B.; RT "Cloning of a cellular factor, interleukin binding factor, that binds to RT NFAT-like motifs in the human immunodeficiency virus long terminal RT repeat."; RL Proc. Natl. Acad. Sci. U.S.A. 88:7739-7743(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Cervix carcinoma, and Lymphoid tissue; RX PubMed=1339390; DOI=10.1016/0888-7543(92)90139-j; RA Li C., Lusis A.J., Sparkes R., Nirula A., Gaynor R.B.; RT "Characterization and chromosomal mapping of the gene encoding the cellular RT DNA binding protein ILF."; RL Genomics 13:665-671(1992). RN [3] RP SEQUENCE REVISION (ISOFORMS 1; 2 AND 3). RA Nirula A., Moore D.J., Li C., Gaynor R.B.; RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [7] RP IDENTIFICATION BY 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 [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398 AND SER-428, AND 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 [10] RP FUNCTION, AND DNA-BINDING. RX PubMed=20097901; DOI=10.1093/jb/mvq004; RA Fujii Y., Nakamura M.; RT "FOXK2 transcription factor is a novel G/T-mismatch DNA binding protein."; RL J. Biochem. 147:705-709(2010). RN [11] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-373 AND SER-428, AND RP MUTAGENESIS OF SER-373 AND SER-428. RX PubMed=20810654; DOI=10.1074/jbc.m110.154005; RA Marais A., Ji Z., Child E.S., Krause E., Mann D.J., Sharrocks A.D.; RT "Cell cycle-dependent regulation of the forkhead transcription factor FOXK2 RT by CDK.cyclin complexes."; RL J. Biol. Chem. 285:35728-35739(2010). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-30; SER-398; SER-424 AND SER-428, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [13] RP FUNCTION, AND DNA-BINDING. RX PubMed=22083952; DOI=10.1128/mcb.05504-11; RA Ji Z., Donaldson I.J., Liu J., Hayes A., Zeef L.A., Sharrocks A.D.; RT "The forkhead transcription factor FOXK2 promotes AP-1-mediated RT transcriptional regulation."; RL Mol. Cell. Biol. 32:385-398(2012). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239; SER-398; SER-424 AND RP SER-428, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-144, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; 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 [18] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-527, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [19] RP INTERACTION WITH BAP1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-58. RX PubMed=24748658; DOI=10.1093/nar/gku274; RA Ji Z., Mohammed H., Webber A., Ridsdale J., Han N., Carroll J.S., RA Sharrocks A.D.; RT "The forkhead transcription factor FOXK2 acts as a chromatin targeting RT factor for the BAP1-containing histone deubiquitinase complex."; RL Nucleic Acids Res. 42:6232-6242(2014). RN [20] RP FUNCTION, INTERACTION WITH DVL1; DVL2; DVL3 AND SUDS3, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF ARG-129; ARG-130; GLY-131; PRO-133; GLN-136; RP LEU-137; PRO-138; CYS-141; THR-142; PHE-145; PRO-146; SER-147; THR-148; RP ILE-150; LYS-151; ILE-152; PHE-154; THR-155; LEU-157 AND HIS-308. RX PubMed=25805136; DOI=10.1016/j.devcel.2015.01.031; RA Wang W., Li X., Lee M., Jun S., Aziz K.E., Feng L., Tran M.K., Li N., RA McCrea P.D., Park J.I., Chen J.; RT "FOXKs promote Wnt/beta-catenin signaling by translocating DVL into the RT nucleus."; RL Dev. Cell 32:707-718(2015). RN [21] RP FUNCTION, AND INTERACTION WITH BAP1. RX PubMed=25451922; DOI=10.1074/jbc.m114.609834; RA Okino Y., Machida Y., Frankland-Searby S., Machida Y.J.; RT "BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes the RT ubiquitin-mediated activation of FoxK2 target genes."; RL J. Biol. Chem. 290:1580-1591(2015). RN [22] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-161; LYS-164; LYS-527 AND RP LYS-633, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [23] RP SUMOYLATION AT LYS-527 AND LYS-633, AND MUTAGENESIS OF LYS-527 AND LYS-633. RX PubMed=29540677; DOI=10.1038/s41389-018-0038-6; RA Nestal de Moraes G., Ji Z., Fan L.Y., Yao S., Zona S., Sharrocks A.D., RA Lam E.W.; RT "SUMOylation modulates FOXK2-mediated paclitaxel sensitivity in breast RT cancer cells."; RL Oncogenesis 7:29-29(2018). RN [24] RP STRUCTURE BY NMR OF 256-353 (ISOFORM 1), AND DNA-BINDING. RX PubMed=12402362; DOI=10.1002/prot.10227; RA Liu P.-P., Chen Y.-C., Li C., Hsieh Y.-H., Chen S.-W., Chen S.-H., RA Jeng W.-Y., Chuang W.-J.; RT "Solution structure of the DNA-binding domain of interleukin enhancer RT binding factor 1 (FOXK1a)."; RL Proteins 49:543-553(2002). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 256-353 (ISOFORM 1) IN COMPLEX RP WITH MAGNESIUM AND DUPLEX DNA, DNA-BINDING, DOMAIN, AND MUTAGENESIS OF RP LYS-258; LYS-300; SER-305; ARG-307 AND LYS-328. RX PubMed=16624804; DOI=10.1074/jbc.m600478200; RA Tsai K.-L., Huang C.-Y., Chang C.-H., Sun Y.-J., Chuang W.-J., Hsiao C.-D.; RT "Crystal structure of the human FOXK1a-DNA complex and its implications on RT the diverse binding specificity of winged helix/forkhead proteins."; RL J. Biol. Chem. 281:17400-17409(2006). CC -!- FUNCTION: Transcriptional regulator involved in different processes CC such as glucose metabolism, aerobic glycolysis and autophagy (By CC similarity). Recognizes and binds the forkhead DNA sequence motif (5'- CC GTAAACA-3') and can both act as a transcription activator or repressor, CC depending on the context (PubMed:22083952, PubMed:25451922). Together CC with FOXK1, acts as a key regulator of metabolic reprogramming towards CC aerobic glycolysis, a process in which glucose is converted to lactate CC in the presence of oxygen (By similarity). Acts by promoting expression CC of enzymes for glycolysis (such as hexokinase-2 (HK2), CC phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), CC while suppressing further oxidation of pyruvate in the mitochondria by CC up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By CC similarity). Probably plays a role in gluconeogenesis during overnight CC fasting, when lactate from white adipose tissue and muscle is the main CC substrate (By similarity). Together with FOXK1, 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 (By similarity). In addition to the 5'-GTAAACA-3' DNA motif, CC also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates CC with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to CC bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'- CC TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs CC (purine-rich) in the IL2 promoter (PubMed:1339390). Positively CC regulates WNT/beta-catenin signaling by translocating DVL proteins into CC the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal CC repeat. May be involved in both positive and negative regulation of CC important viral and cellular promoter elements (PubMed:1909027). CC {ECO:0000250|UniProtKB:Q3UCQ1, ECO:0000269|PubMed:1339390, CC ECO:0000269|PubMed:1909027, ECO:0000269|PubMed:20097901, CC ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:25451922, CC ECO:0000269|PubMed:25805136}. CC -!- SUBUNIT: Component of SIN3A-, but not SIN3B-, containing multiprotein CC complexes (By similarity). Interacts with DVL1, DVL2 (when CC phosphorylated) and DVL3; the interaction induces DVL2 nuclear CC translocation (PubMed:25805136). Interacts with SUDS3 CC (PubMed:25805136). Interacts with BAP1 (when phosphorylated); leading CC to recruit the PR-DUB complex and repress FOXK2 target genes CC (PubMed:24748658, PubMed:25451922). {ECO:0000250|UniProtKB:Q3UCQ1, CC ECO:0000269|PubMed:24748658, ECO:0000269|PubMed:25451922, CC ECO:0000269|PubMed:25805136}. CC -!- INTERACTION: CC Q01167; P14316: IRF2; NbExp=4; IntAct=EBI-2509991, EBI-2866589; CC Q01167; P61244: MAX; NbExp=4; IntAct=EBI-2509991, EBI-751711; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20810654, CC ECO:0000269|PubMed:24748658, ECO:0000269|PubMed:25805136}. Cytoplasm CC {ECO:0000250|UniProtKB:Q3UCQ1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q01167-1; Sequence=Displayed; CC Name=2; CC IsoId=Q01167-2; Sequence=VSP_001559; CC Name=3; CC IsoId=Q01167-3; Sequence=VSP_001560, VSP_001561; CC -!- TISSUE SPECIFICITY: Expressed in both lymphoid and non-lymphoid cells. CC {ECO:0000269|PubMed:1339390}. CC -!- DOMAIN: The C-terminal part of the DNA-binding domain may contribute to CC DNA recognition specificity. {ECO:0000269|PubMed:16624804}. CC -!- PTM: Hyperphosphorylated during mitosis by CDK1 and, to a lower extent, CC CDK2 (PubMed:20810654). Phosphorylation at Ser-373 and Ser-428 affects CC stability by promoting degradation (PubMed:20810654). CC {ECO:0000269|PubMed:20810654}. CC -!- CAUTION: Was initially named FOXK1a by some reports (PubMed:12402362, CC PubMed:16624804). It should not be confused with FOXK1 (AC P85037) CC paralog. {ECO:0000303|PubMed:12402362, ECO:0000303|PubMed:16624804, CC ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB02820.1; Type=Miscellaneous discrepancy; Note=The N-terminal sequence differs due to frameshifts and sequencing errors.; Evidence={ECO:0000305}; CC Sequence=AAB02821.1; Type=Miscellaneous discrepancy; Note=The N-terminal sequence differs due to frameshifts and sequencing errors.; Evidence={ECO:0000305}; CC Sequence=AAB02822.1; Type=Miscellaneous discrepancy; Note=The N-terminal sequence differs due to frameshifts and sequencing errors.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X60787; CAA43200.1; -; mRNA. DR EMBL; U58196; AAB02820.1; ALT_SEQ; mRNA. DR EMBL; U58197; AAB02821.1; ALT_SEQ; mRNA. DR EMBL; U58198; AAB02822.1; ALT_SEQ; mRNA. DR EMBL; AC124287; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS11813.1; -. [Q01167-1] DR PIR; A41285; A41285. DR RefSeq; NP_004505.2; NM_004514.3. [Q01167-1] DR PDB; 1JXS; NMR; -; A=256-353. DR PDB; 2C6Y; X-ray; 2.40 A; A/B=256-353. DR PDBsum; 1JXS; -. DR PDBsum; 2C6Y; -. DR AlphaFoldDB; Q01167; -. DR BMRB; Q01167; -. DR SMR; Q01167; -. DR BioGRID; 109820; 241. DR IntAct; Q01167; 136. DR MINT; Q01167; -. DR STRING; 9606.ENSP00000335677; -. DR GlyCosmos; Q01167; 4 sites, 1 glycan. DR GlyGen; Q01167; 7 sites, 1 O-linked glycan (7 sites). DR iPTMnet; Q01167; -. DR PhosphoSitePlus; Q01167; -. DR BioMuta; FOXK2; -. DR DMDM; 118572648; -. DR EPD; Q01167; -. DR jPOST; Q01167; -. DR MassIVE; Q01167; -. DR MaxQB; Q01167; -. DR PaxDb; 9606-ENSP00000335677; -. DR PeptideAtlas; Q01167; -. DR ProteomicsDB; 57924; -. [Q01167-1] DR ProteomicsDB; 57925; -. [Q01167-2] DR ProteomicsDB; 57926; -. [Q01167-3] DR Pumba; Q01167; -. DR Antibodypedia; 33026; 279 antibodies from 30 providers. DR DNASU; 3607; -. DR Ensembl; ENST00000335255.10; ENSP00000335677.5; ENSG00000141568.21. [Q01167-1] DR Ensembl; ENST00000473637.6; ENSP00000436108.2; ENSG00000141568.21. [Q01167-2] DR GeneID; 3607; -. DR KEGG; hsa:3607; -. DR MANE-Select; ENST00000335255.10; ENSP00000335677.5; NM_004514.4; NP_004505.2. DR UCSC; uc002kfm.2; human. [Q01167-1] DR AGR; HGNC:6036; -. DR CTD; 3607; -. DR DisGeNET; 3607; -. DR GeneCards; FOXK2; -. DR HGNC; HGNC:6036; FOXK2. DR HPA; ENSG00000141568; Low tissue specificity. DR MIM; 147685; gene. DR neXtProt; NX_Q01167; -. DR OpenTargets; ENSG00000141568; -. DR PharmGKB; PA29851; -. DR VEuPathDB; HostDB:ENSG00000141568; -. DR eggNOG; KOG2294; Eukaryota. DR GeneTree; ENSGT00940000155709; -. DR HOGENOM; CLU_022344_0_0_1; -. DR InParanoid; Q01167; -. DR OMA; PKGEPQE; -. DR OrthoDB; 5385885at2759; -. DR PhylomeDB; Q01167; -. DR TreeFam; TF325718; -. DR PathwayCommons; Q01167; -. DR Reactome; R-HSA-5689603; UCH proteinases. DR SignaLink; Q01167; -. DR SIGNOR; Q01167; -. DR BioGRID-ORCS; 3607; 25 hits in 1176 CRISPR screens. DR ChiTaRS; FOXK2; human. DR EvolutionaryTrace; Q01167; -. DR GeneWiki; FOXK2; -. DR GenomeRNAi; 3607; -. DR Pharos; Q01167; Tbio. DR PRO; PR:Q01167; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q01167; Protein. DR Bgee; ENSG00000141568; Expressed in adrenal tissue and 200 other cell types or tissues. DR ExpressionAtlas; Q01167; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; 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; ISS:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. 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:0061621; P:canonical glycolysis; ISS:UniProtKB. DR GO; GO:0001678; P:intracellular glucose homeostasis; ISS:UniProtKB. DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; NAS:UniProtKB. DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB. DR CDD; cd20055; FH_FOXK2; 1. DR CDD; cd22723; FHA_FOXK2; 1. DR Gene3D; 2.60.200.20; -; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR IDEAL; IID00065; -. DR InterPro; IPR047397; FH_FOXK2. DR InterPro; IPR000253; FHA_dom. DR InterPro; IPR047398; FHA_FOXK2. 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 PANTHER; PTHR45881; CHECKPOINT SUPPRESSOR 1-LIKE, ISOFORM A-RELATED; 1. DR PANTHER; PTHR45881:SF3; FORKHEAD BOX PROTEIN K2; 1. 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; SSF49879; SMAD/FHA domain; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 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. DR Genevisible; Q01167; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Cytoplasm; KW DNA-binding; Isopeptide bond; Magnesium; Metal-binding; Methylation; KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription; KW Transcription regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231" FT CHAIN 2..660 FT /note="Forkhead box protein K2" FT /id="PRO_0000091858" FT DOMAIN 54..128 FT /note="FHA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086" FT DNA_BIND 258..353 FT /note="Fork-head" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089" FT REGION 1..36 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 85..104 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 129..171 FT /note="Required for interaction with DVL2 and SUDS3" FT /evidence="ECO:0000269|PubMed:25805136" FT REGION 203..260 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 300..318 FT /note="DNA-binding; major groove" FT /evidence="ECO:0000269|PubMed:16624804" FT REGION 328..332 FT /note="DNA-binding; minor groove" FT /evidence="ECO:0000269|PubMed:16624804" FT REGION 348..353 FT /note="DNA-binding; minor groove" FT /evidence="ECO:0000269|PubMed:16624804" FT REGION 359..407 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 610..632 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 366..395 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 310 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:16624804" FT BINDING 311 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:16624804" FT BINDING 313 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:16624804" FT BINDING 316 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:16624804" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231" FT MOD_RES 30 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 144 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 239 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 373 FT /note="Phosphoserine; by CDK1 and CDK2" FT /evidence="ECO:0000269|PubMed:20810654" FT MOD_RES 398 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 424 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 428 FT /note="Phosphoserine; by CDK1 and CDK2" FT /evidence="ECO:0000269|PubMed:20810654, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 599 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3UCQ1" FT CROSSLNK 161 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 164 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 527 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000269|PubMed:29540677, FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:28112733" FT CROSSLNK 633 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000269|PubMed:29540677, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 304..328 FT /note="NSIRHNLSLNRYFIKVPRSQEEPGK -> RGESFAHVGNTRIRIGLPAHKAP FT QR (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_001560" FT VAR_SEQ 329..660 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_001561" FT VAR_SEQ 596..660 FT /note="AAASPLHMLATHASASASLPTKRHNGDQPEQPELKRIKTEDGEGIVIALSVD FT TPPAAVREKGVQN -> GPLGLRRPPCASSDWSCLS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1339390" FT /id="VSP_001559" FT MUTAGEN 58 FT /note="R->A: Reduced interaction with BAP1." FT /evidence="ECO:0000269|PubMed:24748658" FT MUTAGEN 129 FT /note="R->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 130 FT /note="R->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 131 FT /note="G->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 133 FT /note="P->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 136 FT /note="Q->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 137 FT /note="L->A: Abolishes interaction with DVL2 and SUDS3 as FT well as DVL2 nuclear translocation." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 138 FT /note="P->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 141 FT /note="C->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 142 FT /note="T->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 145 FT /note="F->A: Abolishes interaction with DVL2 and SUDS3 as FT well as DVL2 nuclear translocation." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 146 FT /note="P->A: Highly reduces interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 147 FT /note="S->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 148 FT /note="T->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 150 FT /note="I->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 151 FT /note="K->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 152 FT /note="I->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 154 FT /note="F->A: Abolishes interaction with DVL2 and SUDS3 as FT well as DVL2 nuclear translocation." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 155 FT /note="T->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 157 FT /note="L->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 258 FT /note="K->A: Decreases DNA-binding to 40%." FT /evidence="ECO:0000269|PubMed:16624804" FT MUTAGEN 300 FT /note="K->A: Decreases DNA-binding to 20%." FT /evidence="ECO:0000269|PubMed:16624804" FT MUTAGEN 305 FT /note="S->A: Decreases DNA-binding to 70%." FT /evidence="ECO:0000269|PubMed:16624804" FT MUTAGEN 307 FT /note="R->A: Abolishes DNA-binding." FT /evidence="ECO:0000269|PubMed:16624804" FT MUTAGEN 308 FT /note="H->A: No effect on interaction with DVL2." FT /evidence="ECO:0000269|PubMed:25805136" FT MUTAGEN 328 FT /note="K->A: Decreases DNA-binding to 25%." FT /evidence="ECO:0000269|PubMed:16624804" FT MUTAGEN 373 FT /note="S->A: Decreased phosphorylation leading to increased FT stability of the protein; when associated with A-428." FT /evidence="ECO:0000269|PubMed:20810654" FT MUTAGEN 373 FT /note="S->D: Phosphomimetic mutant; decreased FT phosphorylation leading to decreased stability of the FT protein; when associated with D-428." FT /evidence="ECO:0000269|PubMed:20810654" FT MUTAGEN 428 FT /note="S->A: Decreased phosphorylation leading to increased FT stability of the protein; when associated with A-373." FT /evidence="ECO:0000269|PubMed:20810654" FT MUTAGEN 428 FT /note="S->D: Phosphomimetic mutant; decreased FT phosphorylation leading to decreased stability of the FT protein; when associated with D-373." FT /evidence="ECO:0000269|PubMed:20810654" FT MUTAGEN 527 FT /note="K->R: Abolished SUMOylation; when associated with FT R-633." FT /evidence="ECO:0000269|PubMed:29540677" FT MUTAGEN 633 FT /note="K->R: Abolished SUMOylation; when associated with FT R-527." FT /evidence="ECO:0000269|PubMed:29540677" FT CONFLICT 3..120 FT /note="AAAAALSGAGTPPAGGGAGGGGAGGGGSPPGGWAVARLEGREFEYLMKKRSV FT TIGRNSSQGSVDVSMGHSSFISRRHLEIFTPPGGGGHGGAAPELPPAQPRPDAGGDFYL FT RCLGKNG -> Q (in Ref. 1; CAA43200)" FT /evidence="ECO:0000305" FT HELIX 263..272 FT /evidence="ECO:0007829|PDB:2C6Y" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:1JXS" FT HELIX 281..291 FT /evidence="ECO:0007829|PDB:2C6Y" FT STRAND 295..298 FT /evidence="ECO:0007829|PDB:1JXS" FT HELIX 300..312 FT /evidence="ECO:0007829|PDB:2C6Y" FT STRAND 316..319 FT /evidence="ECO:0007829|PDB:2C6Y" FT STRAND 324..329 FT /evidence="ECO:0007829|PDB:1JXS" FT STRAND 331..334 FT /evidence="ECO:0007829|PDB:2C6Y" FT HELIX 336..346 FT /evidence="ECO:0007829|PDB:2C6Y" SQ SEQUENCE 660 AA; 69062 MW; E11C0B24370F1260 CRC64; MAAAAAALSG AGTPPAGGGA GGGGAGGGGS PPGGWAVARL EGREFEYLMK KRSVTIGRNS SQGSVDVSMG HSSFISRRHL EIFTPPGGGG HGGAAPELPP AQPRPDAGGD FYLRCLGKNG VFVDGVFQRR GAPPLQLPRV CTFRFPSTNI KITFTALSSE KREKQEASES PVKAVQPHIS PLTINIPDTM AHLISPLPSP TGTISAANSC PSSPRGAGSS GYKVGRVMPS DLNLMADNSQ PENEKEASGG DSPKDDSKPP YSYAQLIVQA ITMAPDKQLT LNGIYTHITK NYPYYRTADK GWQNSIRHNL SLNRYFIKVP RSQEEPGKGS FWRIDPASES KLIEQAFRKR RPRGVPCFRT PLGPLSSRSA PASPNHAGVL SAHSSGAQTP ESLSREGSPA PLEPEPGAAQ PKLAVIQEAR FAQSAPGSPL SSQPVLITVQ RQLPQAIKPV TYTVATPVTT STSQPPVVQT VHVVHQIPAV SVTSVAGLAP ANTYTVSGQA VVTPAAVLAP PKAEAQENGD HREVKVKVEP IPAIGHATLG TASRIIQTAQ TTPVQTVTIV QQAPLGQHQL PIKTVTQNGT HVASVPTAVH GQVNNAAASP LHMLATHASA SASLPTKRHN GDQPEQPELK RIKTEDGEGI VIALSVDTPP AAVREKGVQN //