FOXK2
Description
The FOXK2 (forkhead box K2) is a protein-coding gene located on chromosome 17.
Forkhead box protein K2 is a protein that in humans is encoded by the FOXK2 gene. The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements.
FOXK2 is a transcriptional regulator involved in various cellular processes including glucose metabolism, aerobic glycolysis and autophagy. It binds to the forkhead DNA sequence motif (5'-GTAAACA-3') and can act as both a transcription activator and repressor depending on the context. Together with FOXK1, it plays a key role in metabolic reprogramming towards aerobic glycolysis by promoting expression of glycolytic enzymes such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase, while suppressing further oxidation of pyruvate in the mitochondria. FOXK2 also likely plays a role in gluconeogenesis during overnight fasting. In skeletal muscle, FOXK2, along with FOXK1, negatively regulates autophagy by repressing expression of autophagy genes in response to starvation. In addition to the forkhead motif, FOXK2 binds to the 5'-TGANTCA-3' palindromic DNA motif and cooperates with JUN/AP-1 to activate transcription. It can also bind to a minimal DNA heteroduplex containing a G/T-mismatch with the sequence 5'-TRT[G/T]NB-3'. FOXK2 binds to NFAT-like motifs (purine-rich) in the IL2 promoter and positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus. FOXK2 also binds to the HIV-1 long terminal repeat and may be involved in regulating both viral and cellular promoter elements. It is an accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex, recruiting it to specific FOXK2-bound genes. FOXK2 is part of SIN3A-containing multiprotein complexes but not SIN3B-containing complexes. It interacts with DVL1, DVL2 (when phosphorylated) and DVL3, promoting DVL2 nuclear translocation. It also interacts with SUDS3 and BAP1 (when phosphorylated), leading to the recruitment of the PR-DUB complex and repression of FOXK2 target genes. FOXK2 is part of the PR-DUB complex, which also includes BAP1, one of ASXL1, ASXL2 or ASXL3 and one of MBD5 or MBD6. The PR-DUB core associates with a number of accessory proteins, including FOXK1, FOXK2, KDM1B, HCFC1 and OGT.
FOXK2 is also known as ILF, ILF-1, ILF1, nGTBP.
