GAL1 encodes galactokinase (EC 2.7.1.6) of Saccharomyces cerevisiae, a monomeric ~58 kDa GHMP-family kinase that phosphorylates alpha-D-galactose at C1 using ATP to give galactose 1-phosphate, the first step of the Leloir pathway of galactose catabolism. The enzyme is highly specific for galactose and follows an ordered ternary-complex mechanism. GAL1 is strongly induced by galactose through the Gal4/Gal80/Gal3 switch. Gal1 is also bifunctional: like its catalytically inactive paralog Gal3, it can bind the Gal80 repressor in a galactose- and ATP-dependent manner and thereby contribute to induction of the GAL genes, an activity separable from its kinase function. Gal1 is a soluble cytosolic enzyme.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000411 positive regulation of transcription by galactose | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine-learning rule assigning galactose-induced transcriptional activation. For Gal1 this is correct: Gal1 has a GAL3-like inducer activity (galactose/ATP-dependent binding of the Gal80 repressor). It is a genuine but secondary role relative to its galactokinase activity and to Gal3, the principal inducer. Supporting Evidence: PMID:2199310 the results indicate that GAL1 encodes a bifunctional protein PMID:12106903 Yeast galactokinase, Gal1p, and the closely related but catalytically inactive Gal3p, also function as ligand sensors in the GAL genetic switch. |
| GO:0000411 positive regulation of transcription by galactose | IGI PMID:2199310 Analysis of the GAL3 signal transduction pathway activating ... | KEEP AS NON CORE | Summary: Bhat et al. 1990 showed multicopy GAL1 complements the gal3 long-term-adaptation induction defect independently of galactokinase activity (E. coli GalK does not complement gal3). Supports a direct GAL3-like inducer role for Gal1; secondary to the Leloir kinase function in wild-type cells. Supporting Evidence: PMID:2199310 Thus, the complementation activity provided by GAL1 is not likely due to galactokinase activity, but rather due to a distinct GAL3-like activity. PMID:2199310 the results indicate that GAL1 encodes a bifunctional protein PMID:2199310 gal3 mutants exhibit a 3-5-day induction lag |
| GO:0000435 obsolete positive regulation of transcription from RNA polymerase II promoter by galactose | NAS PMID:1317007 Overproduction of the GAL1 or GAL3 protein causes galactose-... | MODIFY | Summary: NAS from Bhat & Hopper 1992 (Gal1 overproduction causes galactose-independent GAL4 activation) to an obsolete term. The biology (Gal1 contributes to galactose induction of GAL genes) is sound; the current term is positive regulation of transcription by galactose (GO:0000411). Proposed replacements: positive regulation of transcription by galactose Supporting Evidence: PMID:1317007 Overproduction of the GAL1 protein (galactokinase) also causes constitutivity |
| GO:0004335 galactokinase activity | EXP PMID:12106903 Kinetic analysis of yeast galactokinase: implications for tr... | ACCEPT | Summary: Timson & Reece 2002 kinetic analysis of purified Gal1 galactokinase (ordered ternary-complex mechanism). Direct experimental support for the core activity. Supporting Evidence: PMID:12106903 Galactokinase (EC 2.7.1.6) catalyses the first step in the catabolism of galactose. PMID:12106903 Galactose-1-phosphate, a product of the reaction, is a mixed inhibitor both with respect to galactose and to ATP suggesting that the reaction proceeds via a compulsory, ordered, ternary complex mechanism. |
| GO:0004335 galactokinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from GalK node PTN000048421 (GHMP kinase, GalK subfamily); Gal1 is a bona fide member with its own experimental annotation among the descendant evidence. Correct. Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt Belongs to the GHMP kinase family. GalK subfamily. file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
| GO:0004335 galactokinase activity | IDA PMID:14144 Purification and properties of galactokinase from Saccharomy... | ACCEPT | Summary: Schell & Wilson 1977 purified yeast galactokinase to homogeneity and measured Km for galactose and ATP; highly galactose-specific. Core MF. Supporting Evidence: PMID:14144 Galactokinase (EC 2.7.1.6; ATP:D-galactose-1-phosphotransferase) was purified to homogeneity with a 50% yield from cells of Saccharomyces cerevisiae which were fully induced for the production of the galactose metabolizing enzymes. PMID:14144 The enzyme is highly specific for galactose since galactokinase did not appear to phosphorylate any of the other sugars tested at a rate greater than 0.5% of the rate of galactose phosphorylation. |
| GO:0004335 galactokinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from InterPro GalK (IPR000705), RHEA:13553 and EC 2.7.1.6; matches the experimentally characterised reaction. Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
| GO:0004335 galactokinase activity | IMP PMID:13495476 Induction of enzymes of the galactose pathway in mutants of ... | ACCEPT | Summary: IMP from de Robichon-Szulmajster 1958 (galactose pathway mutants lacking galactokinase); abstract not available, but the UniProt entry cites this paper as experimental evidence for EC 2.7.1.6. Deferring to the curator. Supporting Evidence: PMID:13495476 Induction of enzymes of the galactose pathway in mutants of Saccharomyces cerevisiae. file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
| GO:0004335 galactokinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (YEAST-GALACT-METAB-PWY, galactose kinase step EC 2.7.1.6); correct assignment. Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
| GO:0005515 protein binding | IPI PMID:11964151 Gal3p and Gal1p interact with the transcriptional repressor ... | MODIFY | Summary: IPI with Gal80 (P04387): gel filtration shows Gal1 binds the Gal80 repressor in a 1:1 complex in the presence of galactose and ATP. 'protein binding' is uninformative; Gal80 is a transcriptional corepressor of Gal4, so transcription corepressor binding is the informative term. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:11964151 Gel-filtration experiments indicate that Gal3p, or the galactokinase Gal1p, interact directly with Gal80p to form a complex with 1:1 stoichiometry. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro GHMP kinase-domain mapping to ATP binding; ATP is a co-substrate of Gal1 (Km for ATP measured) and ATP is also required for Gal1-Gal80 interaction. Correct. Supporting Evidence: PMID:14144 The purified enzyme preparation was used to determine the Km values for the two substrates, galactose and ATP |
| GO:0005667 transcription regulator complex | IPI PMID:11964151 Gal3p and Gal1p interact with the transcriptional repressor ... | KEEP AS NON CORE | Summary: IPI from Timson et al. 2002: Gal1 forms a 1:1 complex with the Gal80 repressor, which itself controls Gal4. Gal1 can thus be part of a Gal80-containing regulatory complex; this is a secondary regulatory role, not the core metabolic function. Supporting Evidence: PMID:11964151 Gel-filtration experiments indicate that Gal3p, or the galactokinase Gal1p, interact directly with Gal80p to form a complex with 1:1 stoichiometry. |
| GO:0005737 cytoplasm | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (IPR006206, GHMP kinase/galactokinase) mapping to cytoplasm; galactokinase is a soluble cytosolic enzyme. Correct, though cytosol is more precise. Reason: Kept ACCEPT for consistency with the IGI row for the same term; cytosol refines rather than replaces it. Supporting Evidence: PMID:14144 Galactokinase (EC 2.7.1.6; ATP:D-galactose-1-phosphotransferase) was purified to homogeneity with a 50% yield from cells of Saccharomyces cerevisiae which were fully induced for the production of the galactose metabolizing enzymes. |
| GO:0005737 cytoplasm | IGI PMID:2199310 Analysis of the GAL3 signal transduction pathway activating ... | ACCEPT | Summary: IGI with GAL3 (Bhat et al. 1990) for cytoplasm; unusual evidence type for location but consistent with the soluble cytosolic location of Gal1 and Gal3; full text not seen, deferring to curator. Supporting Evidence: PMID:2199310 the results indicate that GAL1 encodes a bifunctional protein |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for cytosol from GalK node PTN000048421 (E. coli GalK, Arabidopsis); Gal1 is a soluble enzyme purified from cell extracts. Correct. Supporting Evidence: PMID:14144 Galactokinase (EC 2.7.1.6; ATP:D-galactose-1-phosphotransferase) was purified to homogeneity with a 50% yield from cells of Saccharomyces cerevisiae which were fully induced for the production of the galactose metabolizing enzymes. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA placing the galactokinase reaction in the cytosol; correct. Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
| GO:0006012 galactose metabolic process | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT IBA for galactose metabolic process from GalK node PTN000048421; correct but general (Leloir pathway GO:0033499 is the precise process, also annotated). Supporting Evidence: PMID:12106903 Galactokinase (EC 2.7.1.6) catalyses the first step in the catabolism of galactose. |
| GO:0006012 galactose metabolic process | IEA GO_REF:0000120 | TOO GENERAL | Summary: Combined IEA (ARBA, InterPro GalK, UniPathway UPA00214 galactose metabolism); correct general process. Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt PATHWAY: Carbohydrate metabolism; galactose metabolism. |
| GO:0006012 galactose metabolic process | NAS PMID:1317007 Overproduction of the GAL1 or GAL3 protein causes galactose-... | TOO GENERAL | Summary: NAS from Bhat & Hopper 1992; Gal1 is the galactokinase of galactose metabolism. Correct, general. Supporting Evidence: PMID:1317007 Overproduction of the GAL1 protein (galactokinase) also causes constitutivity |
| GO:0016301 kinase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro GHMP kinase mapping to kinase activity; correct but uninformative parent of galactokinase activity. Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
| GO:0016773 phosphotransferase activity, alcohol group as acceptor | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to phosphotransferase activity, alcohol group as acceptor; correct parent of galactokinase activity (phosphorylation of the C1 hydroxyl of galactose). Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
| GO:0019388 galactose catabolic process | RCA GO_REF:0000123 | TOO GENERAL | Summary: YeastPathways RCA for galactose catabolic process; correct parent of the Leloir pathway term. Supporting Evidence: PMID:12106903 Galactokinase (EC 2.7.1.6) catalyses the first step in the catabolism of galactose. |
| GO:0033499 D-galactose catabolic process, Leloir pathway | IDA PMID:14144 Purification and properties of galactokinase from Saccharomy... | ACCEPT | Summary: IDA from Schell & Wilson 1977 (purified galactokinase from galactose-induced cells). Gal1 catalyses the first committed step of the Leloir pathway. Core BP. Supporting Evidence: PMID:14144 Galactokinase (EC 2.7.1.6; ATP:D-galactose-1-phosphotransferase) was purified to homogeneity with a 50% yield from cells of Saccharomyces cerevisiae which were fully induced for the production of the galactose metabolizing enzymes. |
| GO:0033499 D-galactose catabolic process, Leloir pathway | IMP PMID:13495476 Induction of enzymes of the galactose pathway in mutants of ... | ACCEPT | Summary: IMP from de Robichon-Szulmajster 1958 galactose-pathway mutants (abstract not available); consistent with Gal1 being required for galactose utilisation. Deferring to curator; core BP. Supporting Evidence: PMID:13495476 Induction of enzymes of the galactose pathway in mutants of Saccharomyces cerevisiae. PMID:12106903 Galactokinase (EC 2.7.1.6) catalyses the first step in the catabolism of galactose. |
| GO:0046835 carbohydrate phosphorylation | IDA PMID:14144 Purification and properties of galactokinase from Saccharomy... | KEEP AS NON CORE | Summary: IDA from Schell & Wilson 1977; Gal1 phosphorylates galactose, a carbohydrate phosphorylation. Correct, general. Supporting Evidence: PMID:14144 The enzyme is highly specific for galactose since galactokinase did not appear to phosphorylate any of the other sugars tested at a rate greater than 0.5% of the rate of galactose phosphorylation. |
| GO:0046835 carbohydrate phosphorylation | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro GalK (IPR000705) mapping to carbohydrate phosphorylation; correct, general. Supporting Evidence: file:yeast/GAL1/GAL1-uniprot.txt Reaction=alpha-D-galactose + ATP = alpha-D-galactose 1-phosphate + ADP |
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Galactokinase; phosphorylates alpha-D-galactose to alpha-D-galactose-1-phosphate in the first step of galactose catabolism; expression regulated by Gal4p; human homolog GALK2 complements yeast null mutant; GAL1 has a paralog, GAL3, that arose from the whole genome duplication
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