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]

Full Name

forkhead box K2

Function

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).

Biological Process

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

Cellular Location

Cytoplasm; Nucleus

PTM

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).