FOXK2_HUMAN
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 03-AUG-2022, entry version 222.
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};
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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; 224.
DR IntAct; Q01167; 136.
DR MINT; Q01167; -.
DR STRING; 9606.ENSP00000335677; -.
DR GlyGen; Q01167; 4 sites, 1 O-linked glycan (4 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; Q01167; -.
DR PeptideAtlas; Q01167; -.
DR PRIDE; Q01167; -.
DR ProteomicsDB; 57924; -. [Q01167-1]
DR ProteomicsDB; 57925; -. [Q01167-2]
DR ProteomicsDB; 57926; -. [Q01167-3]
DR Antibodypedia; 33026; 241 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 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; LMTDNSQ; -.
DR OrthoDB; 1270467at2759; -.
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; 22 hits in 1098 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 198 other tissues.
DR ExpressionAtlas; Q01167; baseline and differential.
DR Genevisible; Q01167; HS.
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:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA: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:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR CDD; cd00059; FH; 1.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR IDEAL; IID00065; -.
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; 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 R-
FT 633."
FT /evidence="ECO:0000269|PubMed:29540677"
FT MUTAGEN 633
FT /note="K->R: Abolished SUMOylation; when associated with R-
FT 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
