GUT1

UniProt ID: P32190
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

Gut1p is the glycerol kinase (EC 2.7.1.30) of S. cerevisiae, an FGGY-family carbohydrate kinase that phosphorylates glycerol with ATP to sn-glycerol 3-phosphate. This is the first step of the phosphorylative glycerol utilisation pathway, in which mitochondrial Gut2p then oxidises glycerol 3-phosphate to DHAP. GUT1 is glucose-repressed and, on non-fermentable carbon sources, activated through promoter elements bound by Adr1 and by Ino2-Ino4, repressed by Opi1, and dependent on the respiration factor Rsf1; gut1 disruptants have no glycerol kinase activity and cannot grow on glycerol, but grow normally on glucose or ethanol. Gut1p is mainly cytosolic, with evidence for import of a fraction into mitochondria. Gut1p reproducibly co-purifies with the glycerol-3-phosphatase Gpp2p in proteome-wide interaction screens.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004370 glycerol kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000023392 (FGGY glycerol kinase clade incl. E. coli GlpK, human GK, Arabidopsis GLI1, yeast Gut1). Correct core activity.
Supporting Evidence:
PMID:8358828
No glycerol kinase activity was detected in the disruption mutant.
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
GO:0004370 glycerol kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined IEA (ARBA/IPR005999/RHEA:21644/EC 2.7.1.30). Correct.
Supporting Evidence:
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
GO:0004370 glycerol kinase activity
IMP
PMID:8358828
The glycerol kinase (GUT1) gene of Saccharomyces cerevisiae:...
ACCEPT
Summary: IMP (Pavlik 1993): no glycerol kinase activity in gut1 disruptants. Core MF.
Supporting Evidence:
PMID:8358828
No glycerol kinase activity was detected in the disruption mutant.
PMID:8358828
The GUT1 gene of Saccharomyces cerevisiae, encoding glycerol kinase, was cloned and sequenced.
GO:0004370 glycerol kinase activity
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways glycerol degradation (AERO-GLYCEROL-CAT-PWY), EC 2.7.1.30. Correct.
Supporting Evidence:
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
GO:0005515 protein binding
IPI
PMID:20489023
A global protein kinase and phosphatase interaction network ...
REMOVE
Summary: IPI from the Breitkreutz 2010 kinase/phosphatase AP-MS network (Gut1p with Gpp2p). Uninformative 'protein binding'; no functional consequence known. Removal does not mean the interaction is false.
Supporting Evidence:
PMID:20489023
We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes.
GO:0005515 protein binding
IPI
PMID:37968396
The social and structural architecture of the yeast protein ...
REMOVE
Summary: IPI from the Michaelis 2023 AE-MS interactome (Gut1p with Gpp2p). Uninformative 'protein binding'; the reproducible pair is noted as a suggested question.
Supporting Evidence:
PMID:37968396
The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions
GO:0005737 cytoplasm
HDA
PMID:14562095
Global analysis of protein localization in budding yeast.
ACCEPT
Summary: HDA (Huh 2003 GFP screen): cytoplasmic. Consistent with Gut1p being a soluble kinase.
Supporting Evidence:
PMID:14562095
Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins.
GO:0005737 cytoplasm
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA cytoplasm prediction; agrees with GFP data.
Supporting Evidence:
PMID:14562095
Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins.
GO:0005739 mitochondrion
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: IBA is_active_in mitochondrion from PTN000023394; in mammals glycerol kinase binds the outer mitochondrial membrane via porin. For yeast Gut1p there is in vitro mitochondrial import evidence (Perocchi 2006) but the GFP screen scores it cytoplasmic. Plausible minor pool; non-core.
Supporting Evidence:
PMID:17054397
we performed mitochondrial import experiments and confirmed import of both Gut1p and Gpd2p, implying a novel dual cytosolic and mitochondrial localization
PMID:14562095
Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins.
GO:0005739 mitochondrion
IDA
PMID:17054397
Assessing systems properties of yeast mitochondria through a...
KEEP AS NON CORE
Summary: IDA (Perocchi 2006): in vitro import assay confirmed mitochondrial import of Gut1p, predicted dual cytosolic/mitochondrial localization. Accepted as a minor location; the main pool is cytosolic.
Supporting Evidence:
PMID:17054397
we performed mitochondrial import experiments and confirmed import of both Gut1p and Gpd2p, implying a novel dual cytosolic and mitochondrial localization
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways glycerol degradation; cytosolic compartment. Correct.
Supporting Evidence:
PMID:14562095
Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins.
GO:0005975 carbohydrate metabolic process
IEA
GO_REF:0000002
MODIFY
Summary: InterPro2GO (FGGY carbohydrate kinase signatures) broad 'carbohydrate metabolic process'. Gut1p's process is glycerol catabolism (a descendant via glycerol metabolism).
Proposed replacements: glycerol catabolic process
Supporting Evidence:
PMID:8358828
Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media.
GO:0006071 glycerol metabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000023394 (glycerol kinases); correct though general - glycerol catabolism is the specific process.
Supporting Evidence:
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
GO:0006071 glycerol metabolic process
IMP
PMID:8358828
The glycerol kinase (GUT1) gene of Saccharomyces cerevisiae:...
ACCEPT
Summary: IMP (Pavlik 1993): gut1 mutants cannot grow on glycerol but grow on glucose/ethanol, i.e. Gut1p is required for glycerol utilisation. Correct; the more specific glycerol catabolic process is already annotated (UniPathway/RCA) and is the core process.
Supporting Evidence:
PMID:8358828
Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media.
GO:0006072 glycerol-3-phosphate metabolic process
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO (IPR005999 glycerol kinase): glycerol-3-phosphate metabolism; Gut1p produces sn-glycerol 3-phosphate. Correct, general.
Supporting Evidence:
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
GO:0006641 triglyceride metabolic process
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: IBA triglyceride metabolic process from PTN000023394, seeded by mammalian GK (glycerol phosphorylation feeding TAG synthesis in liver/adipose). In yeast GUT1 is glucose-repressed and specifically required for glycerol utilisation; any contribution of Gut1p-derived G3P to TAG is indirect (substrate supply) and undocumented.
Reason: Supplying a precursor is not participation in triglyceride metabolism; no yeast evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION
Sources checked:
PANTHER:PTN000023394 SUPPORTS SOURCE BUT NOT TARGET
Mammalian GK TAG-related annotations reflect tissue lipid physiology; not transferable to yeast Gut1p.
Supporting Evidence:
PMID:8358828
Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media.
GO:0016301 kinase activity
IEA
GO_REF:0000002
MODIFY
Summary: InterPro2GO (FGGY N/C domains) generic 'kinase activity'; replace with glycerol kinase.
Proposed replacements: glycerol kinase activity
Supporting Evidence:
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
GO:0016773 phosphotransferase activity, alcohol group as acceptor
IEA
GO_REF:0000002
MODIFY
Summary: InterPro2GO (FGGY signature) 'phosphotransferase activity, alcohol group as acceptor'; parent of glycerol kinase activity, replace with the specific term.
Proposed replacements: glycerol kinase activity
Supporting Evidence:
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
GO:0019563 glycerol catabolic process
IEA
GO_REF:0000041
ACCEPT
Summary: UniPathway mapping (UPA00618 glycerol degradation via glycerol kinase pathway). Correct core process.
Supporting Evidence:
PMID:8358828
Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media.
file:yeast/GUT1/GUT1-uniprot.txt
PATHWAY: Polyol metabolism; glycerol degradation via glycerol kinase
GO:0019563 glycerol catabolic process
RCA
GO_REF:0000123
ACCEPT
Summary: RCA from YeastPathways glycerol degradation (AERO-GLYCEROL-CAT-PWY). Correct.
Supporting Evidence:
PMID:8358828
Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media.
GO:0046167 glycerol-3-phosphate biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000023394: glycerol kinase forms sn-glycerol 3-phosphate, so G3P biosynthesis is literally what Gut1p catalyses; first step of glycerol catabolism.
Supporting Evidence:
file:yeast/GUT1/GUT1-uniprot.txt
Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);

Core Functions

ATP-dependent phosphorylation of glycerol to sn-glycerol 3-phosphate, the first step of glycerol utilisation as a carbon source.

Molecular Function:
glycerol kinase activity
Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:8358828
    Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media.
  • PMID:8358828
    No glycerol kinase activity was detected in the disruption mutant.
  • file:yeast/GUT1/GUT1-uniprot.txt
    Reaction=glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+);
  • PMID:14562095
    Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins.

References

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Suggested Questions for Experts

Q: Is the mitochondrial import of Gut1p seen in vitro physiologically significant, e.g. coupling glycerol phosphorylation to Gut2p at the inner membrane?

Q: What is the functional meaning of the Gut1p-Gpp2p association (prevention of a glycerol <-> G3P futile cycle)?

Suggested Experiments

Experiment: Quantify the cytosolic versus mitochondrial pools of endogenously tagged Gut1p on glycerol medium by fractionation with protease protection, and test growth on glycerol of a cytosol-restricted Gut1p.

Deep Research

SGD

(GUT1-deep-research-sgd.md)
SGD gene description for GUT1 (yeast) SGD

SGD gene description for GUT1 (yeast)

Glycerol kinase; converts glycerol to glycerol-3-phosphate; glucose repression of expression is mediated by Adr1p and Ino2p-Ino4p; derepression of expression on non-fermentable carbon sources is mediated by Opi1p and Rsf1p

πŸ“š Additional Documentation

Notes

(GUT1-notes.md)

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