FOXK2

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. [provided by RefSeq]

forkhead box K2

Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (By similarity).

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 (PubMed:22083952, PubMed:25451922).

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 (By similarity).

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 (By similarity).

Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity).

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 (By similarity).

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 (PubMed:22083952).

Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901).

Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390).

Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136).

Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027).

Canonical glycolysis Source: UniProtKB
Cellular glucose homeostasis Source: UniProtKB
Negative regulation of autophagy Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: NTNU_SB
Regulation of glucose metabolic process Source: UniProtKB
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to starvation Source: UniProtKB

Cytoplasm; Nucleus

Hyperphosphorylated during mitosis by CDK1 and, to a lower extent, CDK2 (PubMed:20810654). Phosphorylation at Ser-373 and Ser-428 affects stability by promoting degradation (PubMed:20810654).