cDNA clones encoding human hexokinase have been isolated from an adult kidney library. Analysis of this 917 amino acid protein (Mr = 102,519) indicates that the sequences of the NH2- and COOH-terminal halves, corresponding to the regulatory and catalytic domains, respectively, are homologous; and that eukaryotic hexokinases evolved by duplication of a gene encoding a protein of 450 amino acids. The COOH-terminal half of the protein created by this gene duplication retained the glucose binding site and glucose phosphorylating activity while the substrate binding sites of the NH2-terminal half evolved into a new allosteric effector site.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionIntAct
The transcription factor ATF2 elicits oncogenic activities in melanoma and tumor suppressor activities in nonmalignant skin cancer. Here, we identify that ATF2 tumor suppressor function is determined by its ability to localize at the mitochondria, where it alters membrane permeability following genotoxic stress. The ability of ATF2 to reach the mitochondria is determined by PKCε, which directs ATF2 nuclear localization. Genotoxic stress attenuates PKCε effect on ATF2; enables ATF2 nuclear export and localization at the mitochondria, where it perturbs the HK1-VDAC1 complex; increases mitochondrial permeability; and promotes apoptosis. Significantly, high levels of PKCε, as seen in melanoma cells, block ATF2 nuclear export and function at the mitochondria, thereby attenuating apoptosis following exposure to genotoxic stress. In melanoma tumor samples, high PKCε levels associate with poor prognosis. Overall, our findings provide the framework for understanding how subcellular localization enables ATF2 oncogenic or tumor suppressor functions.
A cellular homeostatic process involved in the maintenance of an internal steady state of glucose within a cell or between a cell and its external environment.
The chemical reactions and pathways involving glucose 6-phosphate, a monophosphorylated derivative of glucose with the phosphate group attached to C-6.
The chemical reactions and pathways resulting in the breakdown of a monosaccharide (generally glucose) into pyruvate, with the concomitant production of a small amount of ATP. Glycolysis begins with phosphorylation of a monosaccharide (generally glucose) on the sixth carbon by a hexokinase, and ends with the production of pyruvate. Pyruvate may be converted to ethanol, lactate, or other small molecules, or fed into the TCA cycle.
IBARefGenome
Enzymatic activity
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.1.1: ATP + D-hexose ⇄ ADP + D-hexose 6-phosphate.
CuratedUniProtKB
It is regulated in the following manner
Hexokinase is an allosteric enzyme inhibited by its product Glc-6-P.
Protein involved in the anaerobic enzymatic conversion of glucose to lactate or pyruvate, resulting in energy stored in the form of adenosine triphosphate (ATP), as occurs in skeletal muscle and in embryonic tissue.
Enzyme whose activity is modified by the noncovalent binding of an allosteric effector at a site other than the active site. This binding mediates conformational changes, altering its catalytic or binding properties.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.