GUK1 (YDR454C) encodes guanylate kinase (EC 2.7.4.8), the essential cytoplasmic monomeric enzyme that transfers the gamma-phosphate of ATP to GMP to form GDP, the obligatory step linking GMP (from de novo synthesis via Imd/Gua1 or from guanine salvage via Hpt1) to GDP/GTP and dGTP. GUK1 disruption is lethal. Hypomorphic alleles (bra3/pur5) accumulate GMP, which feedback-inhibits hypoxanthine-guanine phosphoribosyltransferase (Hpt1), deregulating ADE gene expression, causing purine excretion and purine-analogue resistance. A hypomorphic guk1 allele (nes25) lowers GDP-mannose to about a quarter of normal and impairs mannose outer chain elongation of N-linked cell wall glycoproteins, increasing cell wall porosity and neomycin sensitivity; this reflects the dependence of GDP-mannose synthesis on GTP supply.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004385 GMP kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PANTHER PTN000563396 (guanylate kinase). Correct; core MF. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP file:yeast/GUK1/GUK1-uniprot.txt Belongs to the guanylate kinase family. |
| GO:0004385 GMP kinase activity | IDA PMID:1334480 Cloning and expression of the essential gene for guanylate k... | ACCEPT | Summary: IDA (Konrad 1992): cloned GUK1 was overexpressed in yeast and E. coli as active guanylate kinase. Core MF. Supporting Evidence: PMID:1334480 Guanylate kinase catalyzes the reversible transfer of the terminal phosphoryl group of ATP to the acceptor molecule GMP PMID:1334480 guanylate kinase was produced in large amounts both in S. cerevisiae and in Escherichia coli |
| GO:0004385 GMP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:20780 / EC 2.7.4.8 and InterPro IPR017665. Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0004385 GMP kinase activity | IMP PMID:11063676 Yeast GMP kinase mutants constitutively express AMP biosynth... | ACCEPT | Summary: IMP (Lecoq et al. 2000): bra3/pur5 alleles of GUK1 have low GMP kinase activity, accumulate GMP and deregulate ADE genes. Core MF. Supporting Evidence: PMID:11063676 We show that bra3 mutations are alleles of the GUK1 gene, which encodes GMP kinase PMID:11063676 The bra3 mutants have a low GMP kinase activity |
| GO:0004385 GMP kinase activity | IMP PMID:1334480 Cloning and expression of the essential gene for guanylate k... | ACCEPT | Summary: IMP (Konrad 1992): GUK1 disruption is recessive lethal, consistent with an essential GMP kinase. Core MF. Supporting Evidence: PMID:1334480 Insertional mutagenesis of the GUK1 locus caused recessive lethality PMID:1334480 Guanylate kinase catalyzes the reversible transfer of the terminal phosphoryl group of ATP to the acceptor molecule GMP |
| GO:0004385 GMP kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from human GUK1 (Q16774). Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP file:yeast/GUK1/GUK1-uniprot.txt Belongs to the guanylate kinase family. |
| GO:0004385 GMP kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II), assigning Guk1 to GMP + ATP <-> GDP + ADP (EC 2.7.4.8). Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0004385 GMP kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides), assigning Guk1 to GMP + ATP <-> GDP + ADP (EC 2.7.4.8). Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0004385 GMP kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis), assigning Guk1 to GMP + ATP <-> GDP + ADP (EC 2.7.4.8). Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0004385 GMP kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-6125 (superpathway of guanosine nucleotides de novo biosynthesis II), assigning Guk1 to GMP + ATP <-> GDP + ADP (EC 2.7.4.8). Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0004385 GMP kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-7221 (guanosine ribonucleotides de novo biosynthesis), assigning Guk1 to GMP + ATP <-> GDP + ADP (EC 2.7.4.8). Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0004385 GMP kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways), assigning Guk1 to GMP + ATP <-> GDP + ADP (EC 2.7.4.8). Correct. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0005634 nucleus | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | KEEP AS NON CORE | Summary: HDA from the Huh et al. 2003 GFP screen scoring Guk1 in nucleus and cytoplasm. A small soluble monomeric kinase can diffuse into the nucleus; no nuclear role is described. Reason: High-throughput GFP observation; no nuclear function known. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the Huh et al. 2003 GFP screen: Guk1-GFP is cytoplasmic. Correct. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in cytoplasm) from PTN000563396. Correct. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories file:yeast/GUK1/GUK1-uniprot.txt Belongs to the guanylate kinase family. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II). Guk1 is a soluble cytoplasmic kinase; cytosol is appropriate. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides). Guk1 is a soluble cytoplasmic kinase; cytosol is appropriate. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis). Guk1 is a soluble cytoplasmic kinase; cytosol is appropriate. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PWY-6125 (superpathway of guanosine nucleotides de novo biosynthesis II). Guk1 is a soluble cytoplasmic kinase; cytosol is appropriate. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PWY-7221 (guanosine ribonucleotides de novo biosynthesis). Guk1 is a soluble cytoplasmic kinase; cytosol is appropriate. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways). Guk1 is a soluble cytoplasmic kinase; cytosol is appropriate. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0006163 purine nucleotide metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: IEA (InterPro IPR017665). True but less specific than GDP biosynthetic process. Reason: Correct but general parent. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Catalyzes the reversible transfer of the terminal phosphoryl group of ATP to the acceptor molecule GMP |
| GO:0006163 purine nucleotide metabolic process | ISS GO_REF:0000024 | TOO GENERAL | Summary: ISS (from human GUK1 Q16774). True but less specific than GDP biosynthetic process. Reason: Correct but general parent. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Catalyzes the reversible transfer of the terminal phosphoryl group of ATP to the acceptor molecule GMP |
| GO:0006164 purine nucleotide biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II). GMP -> GDP is required to make GTP/dGTP from GMP produced de novo or by salvage; Guk1 is essential. Correct, with GDP biosynthetic process as the precise term. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP PMID:1334480 Insertional mutagenesis of the GUK1 locus caused recessive lethality |
| GO:0006164 purine nucleotide biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides). GMP -> GDP is required to make GTP/dGTP from GMP produced de novo or by salvage; Guk1 is essential. Correct, with GDP biosynthetic process as the precise term. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP PMID:1334480 Insertional mutagenesis of the GUK1 locus caused recessive lethality |
| GO:0009165 nucleotide biosynthetic process | RCA GO_REF:0000123 | TOO GENERAL | Summary: RCA from YeastPathways superpathway PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis). True but uninformative. Reason: True but very general parent from a superpathway. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0043101 purine-containing compound salvage | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: RCA from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways). GMP formed by Hpt1 guanine salvage must be phosphorylated by Guk1, and guk1 hypomorphs phenocopy hpt1 by feedback-inhibiting Hpt1 with accumulated GMP. Guk1 acts downstream of salvage rather than performing it; keep as non-core. Reason: Guk1 converts salvage-derived GMP to GDP, but it is not a salvage enzyme as such. Supporting Evidence: PMID:11063676 the decrease in GMP kinase activity in the bra3 mutants results in GMP accumulation and feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase |
| GO:0046037 GMP metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA00027112. Guk1 consumes GMP; true but general. Reason: Correct but general. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0046711 GDP biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000563396. GDP is the direct product of the GMP kinase reaction. Core BP. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0046711 GDP biosynthetic process | IMP PMID:11063676 Yeast GMP kinase mutants constitutively express AMP biosynth... | ACCEPT | Summary: IMP (Lecoq et al. 2000): low GMP kinase activity in bra3/guk1 mutants causes GMP accumulation, i.e. reduced conversion of GMP to GDP. Core BP. Supporting Evidence: PMID:11063676 the decrease in GMP kinase activity in the bra3 mutants results in GMP accumulation and feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase PMID:11063676 The bra3 mutants have a low GMP kinase activity |
| GO:0046711 GDP biosynthetic process | IMP PMID:1334480 Cloning and expression of the essential gene for guanylate k... | ACCEPT | Summary: IMP (Konrad 1992): GUK1 is essential for vegetative growth, reflecting the requirement for GDP (and hence GTP) synthesis from GMP. Core BP. Supporting Evidence: PMID:1334480 Insertional mutagenesis of the GUK1 locus caused recessive lethality |
| GO:0106387 'de novo' GMP biosynthetic process | RCA GO_REF:0000123 | REMOVE | Summary: RCA from YeastPathways PWY-6125 (superpathway of guanosine nucleotides de novo biosynthesis II). That pathway runs IMP -> XMP -> GMP -> GDP -> GTP, and the GO-CAM conversion mapped the whole pathway to 'de novo GMP biosynthetic process' (GMP formation via IMP). Guk1 phosphorylates GMP to GDP, downstream of GMP formation; its role is captured by GDP biosynthetic process. Reason: Guk1 consumes GMP; it does not participate in making it. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
| GO:0106387 'de novo' GMP biosynthetic process | RCA GO_REF:0000123 | REMOVE | Summary: RCA from YeastPathways PWY-7221 (guanosine ribonucleotides de novo biosynthesis). That pathway runs IMP -> XMP -> GMP -> GDP -> GTP, and the GO-CAM conversion mapped the whole pathway to 'de novo GMP biosynthetic process' (GMP formation via IMP). Guk1 phosphorylates GMP to GDP, downstream of GMP formation; its role is captured by GDP biosynthetic process. Reason: Guk1 consumes GMP; it does not participate in making it. Supporting Evidence: file:yeast/GUK1/GUK1-uniprot.txt Reaction=GMP + ATP = GDP + ADP |
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Download this section (compressed HTML)Q: Does Guk1 also phosphorylate dGMP efficiently in vivo, and is it the sole route to dGDP for DNA synthesis in yeast?
Experiment: Determine kinetic parameters of purified Guk1 for GMP versus dGMP and measure dGTP pools in hypomorphic guk1 (bra3) mutants.
Guanylate kinase; converts GMP to GDP; required for growth and mannose outer chain elongation of cell wall N-linked glycoproteins
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