UCK2

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Description

The UCK2 (uridine-cytidine kinase 2) is a protein-coding gene located on chromosome 1.

UCK2 (Uridine-cytidine kinase 2) is an enzyme encoded by the UCK2 gene in humans. It catalyzes the phosphorylation of uridine and cytidine to UMP (uridine monophosphate) and CMP (cytidine monophosphate), respectively. This is the initial step in producing pyrimidine nucleoside triphosphates, crucial for RNA and DNA synthesis. An allele of this gene might contribute to nonhumoral immunity against Hemophilus influenzae type B. UCK2 is a tetramer with a molecular mass of about 112 kDa. Its active site, present in each monomer, comprises a five-stranded β-sheet surrounded by five α-helices and a β-hairpin loop. The β-hairpin loop forms a deep binding pocket for uridine/cytidine substrates, regulating binding and release of substrates and products. Specificity for nucleosides is determined by His-117 and Tyr-112 residues, which hydrogen bond with the 4-amino group or the 6-oxo group of cytidine and uridine, respectively. A magnesium ion is coordinated in the active site by Glu-135, Ser-34, and Asp-62. Asp-62 is responsible for catalytic activity, where its acidic side chain deprotonates the 5’-hydroxyl group on the substrate, activating it to attack the γ-phosphorus of ATP. Structural analyses suggest that Asp-62 undergoes a conformational change following phosphorylation, moving away from the newly attached 5’-phosphate of the UMP/CMP product.

UCK2 phosphorylates uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP), respectively. It does not phosphorylate deoxyribonucleosides or purine ribonucleosides. UCK2 can utilize ATP or GTP as a phosphate donor. Additionally, UCK2 can phosphorylate cytidine and uridine nucleoside analogs such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5-bromouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, and N(4)-anisoylcytidine.

UCK2 is also known as TSA903, UK, UMPK.

Associated Diseases

• glaucoma
• breast cancer
• lung cancer
• cancer
• hemoglobin D disease
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
• alpha thalassemia-intellectual disability syndrome type 1
• delta-beta-thalassemia
• hemoglobin E-beta-thalassemia syndrome
• hemoglobin E disease
• dominant beta-thalassemia
• alpha-thalassemia-myelodysplastic syndrome
• hemoglobin C-beta-thalassemia syndrome