GLYCTK encodes glycerate kinase, an ATP-dependent enzyme that phosphorylates D-glycerate; curated UniProt and Reactome records describe the product as (2R)-3-phosphoglycerate/3-phospho-D-glycerate. This activity supports metabolism of D-glycerate produced during serine catabolism and minor fructose metabolism and is the affected activity in D-glyceric aciduria. Isoform 1 is cytoplasmic, while isoform 2 has both cytoplasmic and mitochondrial localization; the core gene-level function is glycerate kinase activity rather than protein phosphorylation or generic protein binding.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm localization is consistent with the UniProt isoform annotation and with GLYCTK acting as a soluble metabolic enzyme. Reason: Cytoplasmic/cytosolic localization is directly supported for isoform 1 and also applies to isoform 2, so this is a valid cellular component annotation. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. [Isoform 2]: Cytoplasm. Mitochondrion. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report summarizes that GLYCTK1 and GLYCTK2 were reported as cytosolic, with GLYCTK2 additionally localized to mitochondria. |
| GO:0008887 glycerate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: glycerate kinase activity is the specific core molecular function of GLYCTK. The UniProt catalytic activity describes ATP-dependent phosphorylation of (R)-glycerate to (2R)-3-phosphoglycerate, and human disease reports support loss of this enzyme activity in D-glyceric aciduria. Reason: This term is specific, aspect-correct, and directly matches the characterized enzyme activity of GLYCTK. Experimental, phylogenetic, computational, and mutant-phenotype evidence all converge on glycerate kinase activity as the primary molecular function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+); EC=2.7.1.31. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report confirms GLYCTK as human glycerate kinase / D-glycerate 2-kinase (EC 2.7.1.31) and links GLYCTK deficiency to D-glyceric aciduria. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: nucleotide binding is technically compatible with an ATP-dependent kinase but is too broad to add useful information when glycerate kinase activity is already annotated. Reason: The annotation should be interpreted through the specific GO:0008887 glycerate kinase activity term. Broad parent terms such as nucleotide binding, kinase activity, and transferase activity blur the actual function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt GLYCTK is annotated with the specific catalytic reaction for glycerate kinase activity, EC=2.7.1.31. |
| GO:0005524 ATP binding | IEA GO_REF:0000043 | ACCEPT | Summary: ATP binding is required for the glycerate kinase reaction because ATP is the phosphate donor for conversion of (R)-glycerate to (2R)-3-phosphoglycerate. Reason: Although less informative than glycerate kinase activity, ATP binding is mechanistically relevant and supported by the catalytic reaction. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+). |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: cytoplasm localization is consistent with the UniProt isoform annotation and with GLYCTK acting as a soluble metabolic enzyme. Reason: Cytoplasmic/cytosolic localization is directly supported for isoform 1 and also applies to isoform 2, so this is a valid cellular component annotation. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. [Isoform 2]: Cytoplasm. Mitochondrion. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report summarizes that GLYCTK1 and GLYCTK2 were reported as cytosolic, with GLYCTK2 additionally localized to mitochondria. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mitochondrial localization is supported for GLYCTK isoform 2 and by high-throughput mitochondrial proteomics, but it is isoform/context-specific rather than the universal location of all GLYCTK products. Reason: Keep this cellular component as a valid non-core localization. The core gene-level location remains cytoplasm/cytosol, with mitochondrion applying to isoform 2 and proteomic detections. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Mitochondrion. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report summarizes that GLYCTK1 and GLYCTK2 were reported as cytosolic, with GLYCTK2 additionally localized to mitochondria. |
| GO:0008887 glycerate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: glycerate kinase activity is the specific core molecular function of GLYCTK. The UniProt catalytic activity describes ATP-dependent phosphorylation of (R)-glycerate to (2R)-3-phosphoglycerate, and human disease reports support loss of this enzyme activity in D-glyceric aciduria. Reason: This term is specific, aspect-correct, and directly matches the characterized enzyme activity of GLYCTK. Experimental, phylogenetic, computational, and mutant-phenotype evidence all converge on glycerate kinase activity as the primary molecular function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+); EC=2.7.1.31. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report confirms GLYCTK as human glycerate kinase / D-glycerate 2-kinase (EC 2.7.1.31) and links GLYCTK deficiency to D-glyceric aciduria. |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: kinase activity is technically compatible with an ATP-dependent kinase but is too broad to add useful information when glycerate kinase activity is already annotated. Reason: The annotation should be interpreted through the specific GO:0008887 glycerate kinase activity term. Broad parent terms such as nucleotide binding, kinase activity, and transferase activity blur the actual function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt GLYCTK is annotated with the specific catalytic reaction for glycerate kinase activity, EC=2.7.1.31. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: transferase activity is technically compatible with an ATP-dependent kinase but is too broad to add useful information when glycerate kinase activity is already annotated. Reason: The annotation should be interpreted through the specific GO:0008887 glycerate kinase activity term. Broad parent terms such as nucleotide binding, kinase activity, and transferase activity blur the actual function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt GLYCTK is annotated with the specific catalytic reaction for glycerate kinase activity, EC=2.7.1.31. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: This generic protein binding row comes from high-throughput interactome evidence and does not describe the biochemical function of GLYCTK. Reason: Protein binding is uninformative here and is not the core molecular role of this metabolic enzyme. The useful GO annotation is glycerate kinase activity. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt The curated functional annotation describes glycerate kinase catalytic activity, while many listed interactions are high-throughput IntAct records. |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | MARK AS OVER ANNOTATED | Summary: This generic protein binding row comes from high-throughput interactome evidence and does not describe the biochemical function of GLYCTK. Reason: Protein binding is uninformative here and is not the core molecular role of this metabolic enzyme. The useful GO annotation is glycerate kinase activity. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt The curated functional annotation describes glycerate kinase catalytic activity, while many listed interactions are high-throughput IntAct records. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: This generic protein binding row comes from high-throughput interactome evidence and does not describe the biochemical function of GLYCTK. Reason: Protein binding is uninformative here and is not the core molecular role of this metabolic enzyme. The useful GO annotation is glycerate kinase activity. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt The curated functional annotation describes glycerate kinase catalytic activity, while many listed interactions are high-throughput IntAct records. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: This generic protein binding row comes from high-throughput interactome evidence and does not describe the biochemical function of GLYCTK. Reason: Protein binding is uninformative here and is not the core molecular role of this metabolic enzyme. The useful GO annotation is glycerate kinase activity. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt The curated functional annotation describes glycerate kinase catalytic activity, while many listed interactions are high-throughput IntAct records. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: cytosol localization is consistent with the UniProt isoform annotation and with GLYCTK acting as a soluble metabolic enzyme. Reason: Cytoplasmic/cytosolic localization is directly supported for isoform 1 and also applies to isoform 2, so this is a valid cellular component annotation. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. [Isoform 2]: Cytoplasm. Mitochondrion. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report summarizes that GLYCTK1 and GLYCTK2 were reported as cytosolic, with GLYCTK2 additionally localized to mitochondria. |
| GO:0061624 fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate | TAS Reactome:R-HSA-70350 | MODIFY | Summary: GLYCTK participates in fructose catabolism by phosphorylating D-glycerate, a metabolite generated downstream of fructose metabolism, to 3-phosphoglycerate. Reason: The Reactome pathway context is appropriate for GLYCTK. The direct molecular function remains glycerate kinase activity, but the biological-process placement in fructose catabolism is supported. GO:0061624 is obsolete in the GO release 2026-07-26 as a pathway variant (replaced_by GO:0006001, its former is_a parent), so the annotation moves to fructose catabolic process. Proposed replacements: fructose catabolic process Supporting Evidence: Reactome:R-HSA-6799495 GLYCTK phosphorylates DGA to 3PDGA |
| GO:0008887 glycerate kinase activity | EXP PMID:2537226 D-glycerate kinase deficiency as a cause of D-glyceric acidu... | ACCEPT | Summary: glycerate kinase activity is the specific core molecular function of GLYCTK. The UniProt catalytic activity describes ATP-dependent phosphorylation of (R)-glycerate to (2R)-3-phosphoglycerate, and human disease reports support loss of this enzyme activity in D-glyceric aciduria. Reason: This term is specific, aspect-correct, and directly matches the characterized enzyme activity of GLYCTK. Experimental, phylogenetic, computational, and mutant-phenotype evidence all converge on glycerate kinase activity as the primary molecular function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+); EC=2.7.1.31. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report confirms GLYCTK as human glycerate kinase / D-glycerate 2-kinase (EC 2.7.1.31) and links GLYCTK deficiency to D-glyceric aciduria. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: Mitochondrial localization is supported for GLYCTK isoform 2 and by high-throughput mitochondrial proteomics, but it is isoform/context-specific rather than the universal location of all GLYCTK products. Reason: Keep this cellular component as a valid non-core localization. The core gene-level location remains cytoplasm/cytosol, with mitochondrion applying to isoform 2 and proteomic detections. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Mitochondrion. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report summarizes that GLYCTK1 and GLYCTK2 were reported as cytosolic, with GLYCTK2 additionally localized to mitochondria. |
| GO:0008887 glycerate kinase activity | IDA PMID:31837836 d-Glycerate kinase deficiency in a neuropediatric patient. | ACCEPT | Summary: glycerate kinase activity is the specific core molecular function of GLYCTK. The UniProt catalytic activity describes ATP-dependent phosphorylation of (R)-glycerate to (2R)-3-phosphoglycerate, and human disease reports support loss of this enzyme activity in D-glyceric aciduria. Reason: This term is specific, aspect-correct, and directly matches the characterized enzyme activity of GLYCTK. Experimental, phylogenetic, computational, and mutant-phenotype evidence all converge on glycerate kinase activity as the primary molecular function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+); EC=2.7.1.31. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report confirms GLYCTK as human glycerate kinase / D-glycerate 2-kinase (EC 2.7.1.31) and links GLYCTK deficiency to D-glyceric aciduria. |
| GO:0008887 glycerate kinase activity | IMP PMID:31837836 d-Glycerate kinase deficiency in a neuropediatric patient. | ACCEPT | Summary: glycerate kinase activity is the specific core molecular function of GLYCTK. The UniProt catalytic activity describes ATP-dependent phosphorylation of (R)-glycerate to (2R)-3-phosphoglycerate, and human disease reports support loss of this enzyme activity in D-glyceric aciduria. Reason: This term is specific, aspect-correct, and directly matches the characterized enzyme activity of GLYCTK. Experimental, phylogenetic, computational, and mutant-phenotype evidence all converge on glycerate kinase activity as the primary molecular function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+); EC=2.7.1.31. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report confirms GLYCTK as human glycerate kinase / D-glycerate 2-kinase (EC 2.7.1.31) and links GLYCTK deficiency to D-glyceric aciduria. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6799495 | ACCEPT | Summary: cytosol localization is consistent with the UniProt isoform annotation and with GLYCTK acting as a soluble metabolic enzyme. Reason: Cytoplasmic/cytosolic localization is directly supported for isoform 1 and also applies to isoform 2, so this is a valid cellular component annotation. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. [Isoform 2]: Cytoplasm. Mitochondrion. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report summarizes that GLYCTK1 and GLYCTK2 were reported as cytosolic, with GLYCTK2 additionally localized to mitochondria. |
| GO:0005737 cytoplasm | IDA PMID:16753811 Isolation and characterization of the human D-glyceric acide... | ACCEPT | Summary: cytoplasm localization is consistent with the UniProt isoform annotation and with GLYCTK acting as a soluble metabolic enzyme. Reason: Cytoplasmic/cytosolic localization is directly supported for isoform 1 and also applies to isoform 2, so this is a valid cellular component annotation. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. [Isoform 2]: Cytoplasm. Mitochondrion. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report summarizes that GLYCTK1 and GLYCTK2 were reported as cytosolic, with GLYCTK2 additionally localized to mitochondria. |
| GO:0006468 protein phosphorylation | IDA PMID:16753811 Isolation and characterization of the human D-glyceric acide... | REMOVE | Summary: GLYCTK is a small-molecule glycerate kinase, not a protein kinase. Its catalytic activity phosphorylates (R)-glycerate to (2R)-3-phosphoglycerate and does not support protein phosphorylation. Reason: This is an aspect-correct BP term for protein kinases but a wrong biological-process annotation for GLYCTK. The evidence supports glycerate phosphorylation in metabolism, not phosphorylation of protein substrates. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+); EC=2.7.1.31. |
| GO:0008887 glycerate kinase activity | IDA PMID:16753811 Isolation and characterization of the human D-glyceric acide... | ACCEPT | Summary: glycerate kinase activity is the specific core molecular function of GLYCTK. The UniProt catalytic activity describes ATP-dependent phosphorylation of (R)-glycerate to (2R)-3-phosphoglycerate, and human disease reports support loss of this enzyme activity in D-glyceric aciduria. Reason: This term is specific, aspect-correct, and directly matches the characterized enzyme activity of GLYCTK. Experimental, phylogenetic, computational, and mutant-phenotype evidence all converge on glycerate kinase activity as the primary molecular function. Supporting Evidence: file:human/GLYCTK/GLYCTK-uniprot.txt Reaction=(R)-glycerate + ATP = (2R)-3-phosphoglycerate + ADP + H(+); EC=2.7.1.31. file:human/GLYCTK/GLYCTK-deep-research-falcon.md Falcon report confirms GLYCTK as human glycerate kinase / D-glycerate 2-kinase (EC 2.7.1.31) and links GLYCTK deficiency to D-glyceric aciduria. |
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Download this section (compressed HTML)Q: With the pathway-variant fructolysis term obsolete, the only core process term is the broad fructose catabolic process; should GLYCTK's role in D-glycerate disposal from serine and glycolate/glyoxylate metabolism (the context of D-glyceric aciduria) also be captured by a process term?
Suggested experts: metabolic biochemists
Q: Which GLYCTK isoforms account for mitochondrial glycerate kinase activity in human tissues?
Suggested experts: metabolic biochemists, mitochondrial proteomics experts
Q: How does GLYCTK deficiency produce variable neurological phenotypes in D-glyceric aciduria?
Suggested experts: clinical geneticists, inborn errors of metabolism specialists
Experiment: Quantitatively compare endogenous GLYCTK isoform 1 and isoform 2 localization in tissues with high fructose or glycerate flux.
Hypothesis: Isoform 2 provides a mitochondrial pool of glycerate kinase activity whereas isoform 1 supports cytosolic glycerate metabolism.
Type: Isoform localization
Experiment: Trace labeled D-glycerate in GLYCTK-null and rescue cells expressing individual isoforms.
Hypothesis: Loss of GLYCTK blocks conversion of D-glycerate into 3-phosphoglycerate and isoform-specific rescue distinguishes cytosolic and mitochondrial contributions.
Type: Metabolic flux analysis
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