Disease relevance of UCK2

• All UMPK 3-3 homozygotes in this study were Hib cases, and we found that in cases and controls, there was no difference between UMPK phenotype and serum levels of total Hib antibody as measured by radioimmunoassay [1].
• The quantitative correlation of thymidine kinase (TK), uridine kinase (UK), and phosphoserine phosphatase to mitotic frequency was highly significant for mesotheliomas, as well as for carcinomas [2].
• Comparison of the capsid amino acid sequences of the 3 UK strains together with the antigenically distinct SRSV/Nor/68/US revealed a hypervariable region that could be surface-exposed and contain the SRSV antigenic determinants [3].
• Mel/89/UK RNA was isolated from a 1989 school outbreak of gastroenteritis [3].
• The DTs of the 16 neoplasms ranged from 24 days in an oat cell carcinoma to over 500 in a pulmonary carcinoid tumor, and showed a statistically significant, inverse correlation to the TK (thymidine kinase) and the UK (uridine kinase) concentration of the biopsy samples per g wet weight or mg DNA [4].

High impact information on UCK2

• Red cell uridine monophosphate kinase: effects of red cell aging on the activity of two UMPK gene products [5].
• Human pyrimidine nucleoside monophosphate kinase is a polymorphic enzyme having two allelic gene products, UMPK 1 and UMPK 2, in several populations [6].
• A procedure is described for the partial purification of this enzyme from human red blood cells resulting in a 1500-fold purification of the enzyme for UMPK 1 and 583-fold for UMPK 2 [6].
• Isolation of three testis-specific genes (TSA303, TSA806, TSA903) by a differential mRNA display method [7].
• The third gene, TSA903, encodes a protein homologous to the C-terminal region of murine uridine monophosphate kinase [7].

Biological context of UCK2

• These results suggest that UCK2 is responsible for the phosphorylation and activation of the antitumor 3'-ethynyl nucleosides [8].
• This mutation was confirmed by genome sequence analysis of the UCK2 gene [8].
• As a result of cDNA sequence analysis, we found that UCK2 mRNA expressed in EUrd-resistant HT-1080 cells has a 98-base pair deletion of exon 5, whereas EUrd-resistant NUGC-3 cells were harboring the point mutation at nucleotide position 484 (C to T) within exon 4 of UCK2 mRNA [8].
• Two of the four major samarium sites are located in the active sites of the two UCK2 molecules that form the asymmetric unit and appear to displace the magnesium ions present in the native crystals [9].
• The fact that no gene dosage effect exists, although the tendency for del(1p) coexists with the relative decrease of UMPK activity in cancerous by comparison to non-cancerous cells, suggests that either mutation or disregulation of UMPK gene occurred early [10].

Anatomical context of UCK2

• In addition, the mRNA or protein expression level of UCK2 was closely correlated with UCK activity in these cell lines, but neither the level of expression of UCK1 mRNA nor that of protein was correlated with enzyme activity [11].
• CMP and UMP kinase activities were increased in high reticulocyte (4.4 +/- 2.1 and 8.5 +/- 3.3 mumol/ml RBC per minute) compared to normal RBC (2.8 +/- 1.0 and 6.0 +/- 2.5 mumol/ml RBC per minute) [12].

Associations of UCK2 with chemical compounds

• Thus, expression of UCK2 appeared to be correlated with cellular sensitivity to TAS-106, and it may contribute to the tumor-selective cytotoxicity of TAS-106 [11].
• Diffraction data were collected on a copper rotating-anode X-ray generator from one native UCK2 crystal and a single samarium-derivative crystal [9].
• Uridine-cytidine nucleoside kinase 2 (UCK2) is the rate-limiting enzyme in the pyrimidine-nucleotide salvage pathway [9].
• The present contribution reports the rapid crystal structure determination of human UCK2 complexed with a magnesium ion and the reaction products adenosine 5'-diphosphate (ADP) and CMP [9].
• UCK2 catalyzes the phosphorylation of the natural ribonucleosides cytidine and uridine to cytidine 5'-monophosphate (CMP) and uridine 5'-monophosphate (UMP), respectively, and activates several important frontline antimetabolite drugs [9].

Other interactions of UCK2

• It was unclear, however, whether UCK1 or UCK2 is responsible for the phosphorylation of the 3'-ethynyl nucleosides [8].

Analytical, diagnostic and therapeutic context of UCK2

• Crystallization and preliminary X-ray analysis of human uridine-cytidine kinase 2 [13].
• Increased intranuclear levels of UK/UPRT may contribute to the metabolic build-up that is needed for blast transformation and rapid proliferation [14].
• Simultaneous determination of uridine monophosphate kinase (UMPK) and aminolevulinate dehydrase (ALAD) has been carried out after discontinuous starch gel electrophoresis in the Galician population (NW Spain), including 129 families with a total of 291 descendents [15].
• Three genetic markers, red-cell UMPK, PGP and serum AMY2 were investigated in Malaysians of Malay, Chinese and Indian ancestries using starch-gel and agarose-gel electrophoresis [16].
• UK gene therapy gets go-ahead [17].

References