Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Automatic Gene Ontology annotation based on Rhea mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Epstein-Barr virus encoded nuclear protein EBNA-3 binds a novel human uridine kinase/uracil phosphoribosyltransferase.
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UCKL1/F538 specifically binds EBV EBNA3.
"We have shown that F538 interacts specifically with EBNA-3 in the yeast two-hybrid system and in GST pull down assays."
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Full-length UCKL1 is predominantly cytoplasmic and relocalizes to the nucleus with EBNA3.
"The predominantly cytoplasmic GFP-F538 translocates to the nucleus when EBNA-3 is expressed."
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The C-terminally truncated isoform does not undergo EBNA3-dependent nuclear targeting.
"GFP-F538ΔC is not targeted to the nucleus by EBNA-3."
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UPRT activity was proposed from sequence and structural modeling rather than measured.
"On the basis of the high homology to UK and UK/UPRT and the similar 3D structure of the C-terminal part of F538 to the T. gondii UPRT, we propose that F538 is a novel uridine kinas/uracil phosphoribosyltransferase (UK/UPRT) – an enzyme with double catalytic activity."
NK lytic-associated molecule, involved in NK cytotoxic function, is an E3 ligase.
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RNF19B/NKLAM and UCKL1 interact in mammalian cells.
"We confirmed that NKLAM and URKL-1 interact in mammalian cells by using both immunoprecipitation and confocal microscopy."
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RNF19B/NKLAM promotes UCKL1 ubiquitination and lowers its abundance.
"We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM."
Characterization of uridine-cytidine kinase like-1 nucleoside kinase activity and its role in tumor growth.
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Purified UCKL1 phosphorylates uridine and cytidine.
"Both enzymes efficiently phosphorylated uridine and cytidine (Figure 3)."
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ATP was used as the phosphate donor for both UCKL1 reactions.
"We analyzed the phosphorylation of both uridine and cytidine with ATP as the phosphate donor."
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UPRT activity remained under investigation and was not established.
"We are also examining whether UCKL-1 has UPRT activity."
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UCKL1 depletion in K562 tumor xenografts increased apoptosis and reduced tumor growth and dissemination.
"These results indicate that decreasing UCKL-1 expression in tumor cells induces apoptosis and inhibits tumor growth, dissemination, and metastasis."
Downregulation of uridine-cytidine kinase like-1 decreases proliferation and enhances tumor susceptibility to lysis by apoptotic agents and natural killer cells.
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UCKL1 RNAi in K562 cells induced apoptosis, slowed the cell cycle, and reduced growth.
"It was seen that downregulation of UCKL-1 initiated apoptosis and slowed the cell cycle, resulting in lower growth in the small interfering UCKL-1 RNA treated K562 cell culture."
Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells.
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UCKL1 expression partly contributes to EUrd cytotoxicity and positively regulates UMP synthesis in resistant glioblastoma-initiating cells.
"We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively."
Uridine Cytidine Kinase Like-1 Enhances Tumor Cell Proliferation and Mediates Protection from Natural Killer-Mediated Killing.
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UCKL1 overexpression increases proliferation and protects tumor cells from NK- and drug-induced apoptosis.
"We show that UCKL-1 over-expression protects tumor cells from NK-mediated and drug-induced apoptosis, enhances tumor survival in vitro and in vivo and increases the rate of tumor cell proliferation."
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UCKL1 abundance correlates with NF-kappaB activity in K562 cells.
"UCKL-1 transfected K562 cells had significantly higher NF-κB activity than control transfected cells; siUCKL-1 treated K562 cells had less NF-κB activity (Figure 7a)."
Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition.
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Deleting UCKL1 in UCK1/UCK2-deficient Jurkat cells eliminated residual uridine rescue, genetically supporting a contribution to uridine salvage.
"We therefore generated a cell line also lacking the predicted UCK, UCKL1 (UCK tKO), and observed that uridine was unable to rescue the effects of de novo pyrimidine synthesis inhibition on proliferation and Chk1 phosphorylation, confirming the absence of UCK activity (Fig. 3c and Extended Data Fig. 4d)."
Uridine-Cytidine Kinase 2 (UCK2)/Uridine-Cytidine Kinase Like 1 (UCKL1) complex exacerbates the differentiation of myocardial fibroblasts via TRIM21/Smurf2/Smad3 pathway after myocardial infarction.
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Endogenous UCK2 and UCKL1 associate in human cardiac fibroblasts and mouse myocardium.
"To experimentally validate this putative interaction, we conducted co-immunoprecipitation (Co-IP) assays, confirming that endogenous UCK2 physically associates with UCKL1 in both HCFs and myocardial tissues (Fig. 2b, c)."
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UCK2 and UCKL1 cooperatively promote TGF-beta-mediated cardiac fibroblast differentiation.
"Collectively, these results establish UCK2 and UCKL1 as critical, potentially cooperative drivers of TGF-β-mediated HCF differentiation."
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Kinase-dead UCK2/UCKL1 proteins retained the reported profibrotic activity.
"Strikingly, the loss of kinase activity did not abolish their pro-fibrotic potential, as indicated by the sustained upregulation of fibrogenic markers and HCFs proliferation (Fig. S3)."
Pyrimidine salvage
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Reactome defines the human pyrimidine-salvage pathway that contains the UCKL1 event.
"In pyrimidine salvage reactions, nucleosides and free bases generated by DNA and RNA breakdown are converted back to nucleotide monophosphates, allowing them to re-enter the pathways of pyrimidine biosynthesis and interconversion."
UCKL1 phosphorylates urindine, cytidine
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Reactome places UCKL1 in the cytosol and models uridine/cytidine phosphorylation.
"Based on sequence similarity, cytosolic uridine-cytidine kinase-like 1 (UCKL1 aka F538) is thought to function as a novel human uridine kinase/uracil phosphoribosyltransferase (Kashuba et al. 2002)."
UniProt record for human UCKL1 (Q9NWZ5)