General Information of Target

Target ID LDTP05282
Target Name Forkhead box protein K2 (FOXK2)
Gene Name FOXK2
Gene ID 3607
Synonyms
ILF; ILF1; Forkhead box protein K2; G/T-mismatch specific binding protein; nGTBP; Interleukin enhancer-binding factor 1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAAAAAALSGAGTPPAGGGAGGGGAGGGGSPPGGWAVARLEGREFEYLMKKRSVTIGRNS
SQGSVDVSMGHSSFISRRHLEIFTPPGGGGHGGAAPELPPAQPRPDAGGDFYLRCLGKNG
VFVDGVFQRRGAPPLQLPRVCTFRFPSTNIKITFTALSSEKREKQEASESPVKAVQPHIS
PLTINIPDTMAHLISPLPSPTGTISAANSCPSSPRGAGSSGYKVGRVMPSDLNLMADNSQ
PENEKEASGGDSPKDDSKPPYSYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYRTADK
GWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRIDPASESKLIEQAFRKRRPRGVPCFRT
PLGPLSSRSAPASPNHAGVLSAHSSGAQTPESLSREGSPAPLEPEPGAAQPKLAVIQEAR
FAQSAPGSPLSSQPVLITVQRQLPQAIKPVTYTVATPVTTSTSQPPVVQTVHVVHQIPAV
SVTSVAGLAPANTYTVSGQAVVTPAAVLAPPKAEAQENGDHREVKVKVEPIPAIGHATLG
TASRIIQTAQTTPVQTVTIVQQAPLGQHQLPIKTVTQNGTHVASVPTAVHGQVNNAAASP
LHMLATHASASASLPTKRHNGDQPEQPELKRIKTEDGEGIVIALSVDTPPAAVREKGVQN
Target Bioclass
Transcription factor
Subcellular location
Nucleus
Function
Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy. Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context. Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen. Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4. Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate. Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins. In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription. Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence. Binds to NFAT-like motifs (purine-rich) in the IL2 promoter. Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus. Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements.
Uniprot ID
Q01167
Ensemble ID
ENST00000335255.10
HGNC ID
HGNC:6036

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
COLO679 SNV: p.H287Q .
HCT15 SNV: p.K173N .
HSC3 SNV: p.P133Q DBIA    Probe Info 
HT115 SNV: p.A608T .
KNS42 SNV: p.R114L DBIA    Probe Info 
MDAMB468 SNV: p.S30A DBIA    Probe Info 
MFE319 SNV: p.A387S DBIA    Probe Info 
MOLT4 SNV: p.S159N .
SKMEL28 SNV: p.G397C .
SW1116 SNV: p.L443V DBIA    Probe Info 
WM2664 Insertion: p.E625GfsTer45 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
15.00  LDD0402  [1]
DBIA
 Probe Info 
C357(2,661.27)  LDD0209  [2]
Acrolein
 Probe Info 
N.A.  LDD0221  [3]
IPM
 Probe Info 
N.A.  LDD0147  [4]
Phosphinate-6
 Probe Info 
N.A.  LDD0018  [5]
AOyne
 Probe Info 
12.30  LDD0443  [6]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0156  Aniline NCI-H1299 11.63  LDD0403  [1]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [3]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C357(1.87)  LDD1702  [7]
 LDCM0107  IAA HeLa N.A.  LDD0221  [3]
 LDCM0022  KB02 42-MG-BA C357(2.45)  LDD2244  [8]
 LDCM0023  KB03 Jurkat C357(2,661.27)  LDD0209  [2]
 LDCM0024  KB05 MKN-1 C357(2.85)  LDD3331  [8]
 LDCM0109  NEM HeLa N.A.  LDD0223  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transcription factor
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Interferon regulatory factor 2 (IRF2) IRF family P14316
Protein max (MAX) MAX family P61244

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
3 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
4 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
5 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
6 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
7 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
8 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840