Gene Details: HK2
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General Information
Gene Name: HK2 (Hexokinase-2)
Synonym:
Short Names:
Alternative Names: Hexokinase type II;Hexokinase-B;Muscle form hexokinase;
Notes:
- HK2 transfers phosphate to glucose to create glucose-6-phosphate. This is the first step of glycolysis, and necessary to form nucleotide-sugars.
Description from Dr.Glyco-GPT:
Write a 100-350 word essay about the enzyme human HK2. Provide information related to enzyme: i) function, ii) reaction pathways, ii) Location, and iv) diseases. In writing include these four subheadings ### Function Human HK2, or hexokinase 2, is a critical enzyme in glucose metabolism, specifically catalyzing the phosphorylation of glucose to glucose-6-phosphate, the first and rate-limiting step of glycolysis. This reaction is vital for trapping glucose within the cell and committing it to metabolic pathways that produce energy, synthesize glycogen, or generate intermediates for biosynthetic processes. HK2 is particularly important in tissues with high metabolic demands, such as muscle and adipose tissue. ### Reaction Pathways HK2 functions within the glycolysis pathway by converting glucose into glucose-6-phosphate, using ATP as a phosphate donor. This step is essential for glycolysis to proceed, leading to the production of pyruvate and ATP. Glucose-6-phosphate also serves as a precursor for other metabolic pathways, including the pentose phosphate pathway, which generates NADPH and ribose-5-phosphate, and glycogen synthesis, where glucose is stored for future energy needs. HK2’s activity is crucial for maintaining the energy balance and metabolic flexibility of cells. ### Location HK2 is predominantly localized in the cytoplasm but is also associated with the outer mitochondrial membrane. This mitochondrial association allows HK2 to directly channel glucose-6-phosphate into glycolysis while linking it to mitochondrial ATP production. This dual localization is particularly important in energy-intensive tissues, such as the heart and skeletal muscles, where efficient glucose utilization is critical for maintaining cellular energy levels. ### Diseases HK2 is often overexpressed in various cancers, including breast, lung, and liver cancers. Its overexpression is associated with the Warburg effect, where cancer cells rely heavily on glycolysis for energy production, even in the presence of oxygen. This metabolic reprogramming supports rapid cell growth and proliferation, making HK2 a potential target for cancer therapies. Additionally, dysregulation of HK2 has been implicated in metabolic disorders such as type 2 diabetes, where impaired glucose metabolism leads to hyperglycemia and insulin resistance. Understanding the role of HK2 in these diseases is crucial for developing strategies to target aberrant glucose metabolism in cancer and metabolic conditions.
Catalytic Activity

Reaction and Disease Links
Brenda:
2.7.1.1
OMIM:
601125
KEGG: 3099
Reactome :
R-HSA-70171
Transcript levels (Cell lines and Single cell data) URL
CRISPR-knockout

CRISPR-activation

CRISPR-inactivation

Top 10 TFs
TF | Score |
---|---|
TCF25 | 0.404176 |
UBE2I | 0.399213 |
ZNF207 | 0.399075 |
NCOR1 | 0.391142 |
SSU72 | 0.390995 |
BRD4 | 0.390264 |
YY1 | 0.390042 |
SNRNP70 | 0.383657 |
SRSF4 | 0.383021 |
RBM25 | 0.380830 |
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