URA6 encodes the essential UMP kinase (uridylate kinase, EC 2.7.4.14) of Saccharomyces cerevisiae, a monomeric short-form member of the adenylate kinase family (UMP-CMP kinase subfamily). It phosphorylates UMP to UDP using ATP (or dATP), linking de novo UMP synthesis and uracil/uridine salvage to UTP and CTP production; dUMP is used with similar efficiency, and lower activity has been reported with other monophosphates (CMP, dCMP, AMP, GMP, dTMP), although reports on the secondary substrates conflict. Ura6 has measurable AMP kinase activity, enough to suppress loss of the major adenylate kinase Aky2/Adk1 when overexpressed, and at high copy it suppresses cdc8 (thymidylate kinase) mutants. The enzyme is about 80% cytoplasmic and 20% nuclear and is absent from mitochondria.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004017 AMP kinase activity | IDA PMID:1333436 The adenylate kinase family in yeast: identification of URA6... | KEEP AS NON CORE | Summary: Schricker et al. showed yeast UMP kinase has significant AMP kinase activity that allows multicopy URA6 to suppress aky2 (IDA). A genuine but secondary activity; Adk1/Aky2 is the main AMP kinase. Reason: Real side activity revealed by overexpression; not the physiological role of Ura6. Supporting Evidence: PMID:1333436 We show that yeast UK exerts significant AK activity which is responsible for the complementation PMID:1333436 The gene URA6 encoding uridylate kinase (UK) from Saccharomyces cerevisiae was isolated as a multicopy suppressor of the respiratory-deficient phenotype |
| GO:0004017 AMP kinase activity | IGI PMID:1333436 The adenylate kinase family in yeast: identification of URA6... | KEEP AS NON CORE | Summary: Schricker et al. showed yeast UMP kinase has significant AMP kinase activity that allows multicopy URA6 to suppress aky2 (IGI). A genuine but secondary activity; Adk1/Aky2 is the main AMP kinase. Reason: Real side activity revealed by overexpression; not the physiological role of Ura6. Supporting Evidence: PMID:1333436 We show that yeast UK exerts significant AK activity which is responsible for the complementation PMID:1333436 The gene URA6 encoding uridylate kinase (UK) from Saccharomyces cerevisiae was isolated as a multicopy suppressor of the respiratory-deficient phenotype |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro adenylate kinase domain (IPR000850) to ATP binding; ATP is the phosphate donor, so true but uninformative. Reason: Substrate binding implied by the kinase activity. Supporting Evidence: PMID:8391780 ATP and dATP are the best phosphate donors |
| GO:0005634 nucleus | EXP PMID:1333436 The adenylate kinase family in yeast: identification of URA6... | ACCEPT | Summary: EXP nucleus; Jong et al. found ~20% of UMP kinase in the nucleus, proposed to support nuclear nucleotide supply. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA nucleus; Jong et al. found ~20% of UMP kinase in the nucleus, proposed to support nuclear nucleotide supply. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005634 nucleus | IDA PMID:8391780 Characteristics, substrate analysis, and intracellular locat... | ACCEPT | Summary: IDA nucleus; Jong et al. found ~20% of UMP kinase in the nucleus, proposed to support nuclear nucleotide supply. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA nucleus; Jong et al. found ~20% of UMP kinase in the nucleus, proposed to support nuclear nucleotide supply. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005737 cytoplasm | EXP PMID:1333436 The adenylate kinase family in yeast: identification of URA6... | ACCEPT | Summary: EXP cytoplasm; Ura6 is predominantly cytoplasmic (~80%). Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytoplasm; Ura6 is predominantly cytoplasmic (~80%). Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005737 cytoplasm | IDA PMID:8391780 Characteristics, substrate analysis, and intracellular locat... | ACCEPT | Summary: IDA cytoplasm; Ura6 is predominantly cytoplasmic (~80%). Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA cytoplasm; Ura6 is predominantly cytoplasmic (~80%). Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways superpathway of histidine, purine, and pyrimidine biosynthesis default cytosol compartment; correct here, Ura6 is ~80% cytoplasmic and not mitochondrial. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways UTP and CTP de novo biosynthesis default cytosol compartment; correct here, Ura6 is ~80% cytoplasmic and not mitochondrial. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways superpathway of pyrimidine ribonucleotides de novo biosynthesis default cytosol compartment; correct here, Ura6 is ~80% cytoplasmic and not mitochondrial. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways de novo biosynthesis of pyrimidine ribonucleotides default cytosol compartment; correct here, Ura6 is ~80% cytoplasmic and not mitochondrial. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways de novo biosynthesis of pyrimidine deoxyribonucleotides default cytosol compartment; correct here, Ura6 is ~80% cytoplasmic and not mitochondrial. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways salvage pathways of pyrimidine ribonucleotides default cytosol compartment; correct here, Ura6 is ~80% cytoplasmic and not mitochondrial. Supporting Evidence: PMID:8391780 Subcellular localization studies indicate that the UMP kinase locates primarily in the cytoplasm (approximately 80%) and also in the nucleus (approximately 20%), but not in the mitochondria |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | IDA PMID:8391780 Characteristics, substrate analysis, and intracellular locat... | MODIFY | Summary: Curated from Jong et al. 1993 enzymology to 'de novo' pyrimidine nucleobase biosynthetic process. Ura6 phosphorylates UMP after the ring-forming steps; the correct process is UDP biosynthesis (towards UTP/CTP). Reason: GO:0006207 covers synthesis of the pyrimidine ring; UMP kinase acts downstream on a nucleotide. Proposed replacements: UDP biosynthetic process Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR006266 mapping to 'de novo' pyrimidine nucleobase biosynthetic process. Ura6 phosphorylates UMP after the ring-forming steps; the correct process is UDP biosynthesis (towards UTP/CTP). Reason: GO:0006207 covers synthesis of the pyrimidine ring; UMP kinase acts downstream on a nucleotide. Proposed replacements: UDP biosynthetic process Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways UTP and CTP de novo biosynthesis to 'de novo' pyrimidine nucleobase biosynthetic process. Ura6 phosphorylates UMP after the ring-forming steps; the correct process is UDP biosynthesis (towards UTP/CTP). Reason: GO:0006207 covers synthesis of the pyrimidine ring; UMP kinase acts downstream on a nucleotide. Proposed replacements: UDP biosynthetic process Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways de novo biosynthesis of pyrimidine ribonucleotides to 'de novo' pyrimidine nucleobase biosynthetic process. Ura6 phosphorylates UMP after the ring-forming steps; the correct process is UDP biosynthesis (towards UTP/CTP). Reason: GO:0006207 covers synthesis of the pyrimidine ring; UMP kinase acts downstream on a nucleotide. Proposed replacements: UDP biosynthetic process Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity |
| GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways pyrimidine deoxyribonucleotide de novo pathway maps to 'de novo' pyrimidine nucleobase biosynthetic process. Ura6 acts on dUMP (and reportedly dCMP), downstream of ring synthesis; the nucleobase term is wrong for a nucleotide kinase. Reason: Nucleotide kinases do not build the pyrimidine ring; the deoxy pathway context is deoxyribonucleotide synthesis. Proposed replacements: deoxyribonucleotide biosynthetic process Supporting Evidence: PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity PMID:16240436 URA6 for deoxycytidylate monophosphate kinase (CK) |
| GO:0006221 pyrimidine nucleotide biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/UniRule mapping to pyrimidine nucleotide biosynthetic process; correct (UDP formation). Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt FUNCTION: Catalyzes the phosphorylation of pyrimidine nucleoside |
| GO:0006225 UDP biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; UMP to UDP phosphorylation is the core metabolic role of Ura6. Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity |
| GO:0009165 nucleotide biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: Inherited from YeastCyc PRPP-PWY-1 superpathway as generic 'nucleotide biosynthetic process'; true but uninformative. Reason: Superpathway-level term. Proposed replacements: UDP biosynthetic process Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, |
| GO:0009220 pyrimidine ribonucleotide biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: From superpathway of pyrimidine ribonucleotides de novo biosynthesis; UDP is a pyrimidine ribonucleotide. Correct, less specific than UDP biosynthesis. Reason: Broad specificity. No single child term covers this activity, which acts on UMP and CMP. This term is the lowest common ancestor of the child terms asserted here, so it states the range of the activity rather than repeating one of them. Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, |
| GO:0010138 pyrimidine ribonucleotide salvage | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways salvage pathway assigns Ura6 to CMP + ATP -> CDP + ADP (RXN-11832). CMP kinase activity of Ura6 is reported (Schricker et al.) but disputed; Ura6 also phosphorylates salvaged UMP. Plausible secondary role. Reason: Salvage role via secondary/disputed CMP kinase activity. Supporting Evidence: PMID:1333436 Since UK also significantly phosphorylates CMP (but not GMP), it must be considered an unspecific short-form nucleoside monophosphate kinase file:yeast/URA6/URA6-uniprot.txt CAUTION: There is controversy about the substrate specificity of the |
| GO:0016776 phosphotransferase activity, phosphate group as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: InterPro UMP_CMP_kinase (IPR006266) mapped to the grouping term 'phosphotransferase activity, phosphate group as acceptor'; uninformative parent. Reason: Replace with UMP kinase activity. Proposed replacements: UMP kinase activity Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, |
| GO:0019205 nucleobase-containing compound kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR000850 mapped to 'nucleobase-containing compound kinase activity'; uninformative parent. Reason: Replace with UMP kinase activity. Proposed replacements: UMP kinase activity Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, |
| GO:0033862 UMP kinase activity | EXP PMID:1333436 The adenylate kinase family in yeast: identification of URA6... | ACCEPT | Summary: URA6 encodes uridylate kinase; activity shown for the cloned gene product. Correct. Supporting Evidence: PMID:1333436 The gene URA6 encoding uridylate kinase (UK) from Saccharomyces cerevisiae was isolated as a multicopy suppressor of the respiratory-deficient phenotype file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, |
| GO:0033862 UMP kinase activity | EXP PMID:16240436 Cloning of deoxynucleoside monophosphate kinase genes and bi... | ACCEPT | Summary: Recombinant URA6 kinase was purified and characterised (abstract emphasises its dCMP kinase use); the curator recorded UMP kinase from the full text. Defer. Supporting Evidence: PMID:16240436 URA6 for deoxycytidylate monophosphate kinase (CK) file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, |
| GO:0033862 UMP kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN000599579 (eukaryotic UMP-CMP kinases incl. human CMPK1 P30085) assigns UMP kinase activity; correct. Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity |
| GO:0033862 UMP kinase activity | IDA PMID:1655742 Molecular characterization of Saccharomyces cerevisiae URA6 ... | ACCEPT | Summary: UMP kinase activity of the URA6/SOC8 product, abolished by mutation of the P-loop lysine; direct evidence. Supporting Evidence: PMID:1655742 Mutagenesis analysis of its putative nucleotide-binding site, altering essential lysine to glutamic acid, resulted in loss of its uridine monophosphate kinase activity PMID:1655742 Thus, both molecular genetic and biochemical evidence supports a notion that the URA6 is SOC8 encoding a yeast uridine monophosphate kinase |
| GO:0033862 UMP kinase activity | IDA PMID:2549068 The Saccharomyces cerevisiae SOC8-1 gene and its relationshi... | ACCEPT | Summary: Overexpression of SOC8-1 (= URA6) raises UMP phosphorylation in extracts; supports UMP kinase activity. Supporting Evidence: PMID:2549068 cells bearing a high copy number plasmid containing SOC8-1 gene were tested for the ability to phosphorylate several nucleoside monophosphates, including UMP, GMP and dTMP |
| GO:0033862 UMP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniRule UR000111469 / RHEA:24400 mapping; correct. Supporting Evidence: file:yeast/URA6/URA6-uniprot.txt Reaction=UMP + ATP = UDP + ADP; Xref=Rhea:RHEA:24400, PMID:8391780 The enzyme can use UMP and dUMP as phosphate acceptors with high activity |
| GO:0033862 UMP kinase activity | IMP PMID:1655742 Molecular characterization of Saccharomyces cerevisiae URA6 ... | ACCEPT | Summary: P-loop lysine-to-glutamate mutation abolishes UMP kinase activity and complementation of ura6; direct genetic evidence. Supporting Evidence: PMID:1655742 Mutagenesis analysis of its putative nucleotide-binding site, altering essential lysine to glutamic acid, resulted in loss of its uridine monophosphate kinase activity PMID:1655742 Thus, both molecular genetic and biochemical evidence supports a notion that the URA6 is SOC8 encoding a yeast uridine monophosphate kinase |
| GO:0046705 CDP biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference (seeded only by Dictyostelium) to CDP biosynthesis. Yeast Ura6 phosphorylates CMP in some studies but not others (UniProt caution); plausible salvage-side role. Reason: CMP kinase is a secondary, disputed activity of Ura6. Supporting Evidence: PMID:1333436 Since UK also significantly phosphorylates CMP (but not GMP), it must be considered an unspecific short-form nucleoside monophosphate kinase file:yeast/URA6/URA6-uniprot.txt CAUTION: There is controversy about the substrate specificity of the |
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Download this section (compressed HTML)Q: Which of the conflicting secondary substrates (CMP/dCMP versus GMP/dTMP) does Ura6 phosphorylate in vivo, and is Ura6 the only CMP kinase of yeast?
Experiment: Determine kcat/Km of purified Ura6 for UMP, dUMP, CMP, dCMP, AMP, GMP and dTMP side by side, and measure CDP/dCDP pools in a hypomorphic ura6 allele.
Uridylate kinase; catalyzes the seventh enzymatic step in the de novo biosynthesis of pyrimidines, converting uridine monophosphate (UMP) into uridine-5'-diphosphate (UDP)
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