GO:0004618 phosphoglycerate kinase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0004618 phosphoglycerate kinase activity describes the enzymatic function that transfers a phosphate group from 1,3-bisphosphoglycerate to ADP, producing 3-phosphoglycerate and ATP during glycolysis.
• PGK1 is the principal human gene encoding this activity, and its enzyme-dependent and enzyme-independent functions contribute to diabetic kidney disease, cardiac hypertrophy, autoimmune myocarditis, and multiple cancers.
• PGK1 activity is regulated by post-translational modifications including O-GlcNAcylation and succinylation, which link glycolytic flux to the TCA cycle and tumor growth.
• Loss or inhibition of phosphoglycerate kinase activity alters CD4+ T cell metabolism and attenuates autoimmune myocarditis, showing that this enzymatic step is immunometabolically relevant.
• PGK1 also participates in oxidative stress regulation through the estradiol-Keap1-Nrf2 pathway in gestational diabetes mellitus.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential for separating the catalytic activity of PGK1 from its non-enzymatic signaling roles.
Description
Phosphoglycerate kinase activity (GO:0004618) is a glycolytic enzymatic function that catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, yielding 3-phosphoglycerate and ATP. This reaction is one of the two ATP-generating steps of glycolysis and is therefore central to cellular energy production and metabolic reprogramming. In humans, the gene most commonly associated with this activity is PGK1, which is widely expressed and has been implicated in both normal metabolism and disease. Because the reaction sits at the intersection of glycolysis and biosynthetic metabolism, researchers study GO:0004618 to understand how cells balance ATP production, redox homeostasis, and anabolic precursor supply. Recent work has shown that PGK1 is not only a metabolic enzyme but also a signaling molecule whose post-translational modifications and subcellular localization influence tumor growth, immune cell function, and cardiac remodeling. Consequently, phosphoglycerate kinase activity is a high-value target for mechanistic studies and for therapeutic hypothesis testing in oncology, immunology, and metabolic disease.
phosphoglycerate kinase activity At A Glance
| GO ID | GO:0004618 |
|---|---|
| GO term | phosphoglycerate kinase activity |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Catalyzes phosphate transfer from 1,3-bisphosphoglycerate to ADP, producing 3-phosphoglycerate and ATP during glycolysis |
| Representative human gene | PGK1 |
| Pathway context | Glycolysis / gluconeogenesis and metabolic reprogramming in cancer and immune cells |
| Regulatory modifications | O-GlcNAcylation and succinylation of PGK1 modulate its activity and interactions |
| Disease relevance | Diabetic kidney disease, autoimmune myocarditis, cardiac hypertrophy, gestational diabetes mellitus, and multiple cancers |
What Is GO:0004618?
Phosphoglycerate kinase activity (GO:0004618) is the catalytic function that enables the transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, forming 3-phosphoglycerate and ATP. In the context of glycolysis, this activity represents the step that converts the high-energy acyl phosphate of 1,3-bisphosphoglycerate into ATP, thereby contributing to net ATP yield. The activity is reversible in vitro, but in cells it typically operates in the glycolytic direction when glucose is abundant. The official QuickGO definition was not retrieved for this term, so the description here is based on the canonical biochemical reaction and the published literature on PGK1.
Why Is phosphoglycerate kinase activity Important in Cell Biology?
Phosphoglycerate kinase activity is important because it is a core ATP-generating step of glycolysis and a node where metabolic flux, post-translational regulation, and disease signaling converge. In cancer, the Warburg effect and metabolic reprogramming depend on efficient glycolytic ATP production, and PGK1 supports tumor growth through both catalytic and non-catalytic mechanisms. In immune cells, inhibition of PGK1 alters CD4+ T cell metabolism and attenuates autoimmune myocarditis, indicating that this activity shapes inflammatory responses. In the kidney, PGK1 contributes to diabetic kidney disease through enzyme-dependent and enzyme-independent manners, highlighting the need to dissect its catalytic function from its scaffolding roles. In the heart, PGK1 drives cardiac hypertrophy by regulating the vimentin/PI3K/Akt pathway, further expanding its physiological reach. Finally, PGK1 regulates oxidative stress in gestational diabetes mellitus through the estradiol-Keap1-Nrf2 pathway, linking this enzymatic activity to redox biology.
• Provides one of the two ATP-generating reactions of glycolysis, making it essential for cellular energy homeostasis.
• Supports the Warburg effect and biosynthetic metabolism in proliferating cancer cells.
• Functions as an enzyme-dependent and enzyme-independent contributor to diabetic kidney disease.
• Modulates CD4+ T cell metabolism and autoimmune myocarditis severity.
• Is regulated by O-GlcNAcylation, which coordinates glycolysis with the TCA cycle to promote tumor growth.
• Undergoes succinylation that is controlled by HIF1α/ATF3 and P4HA1/succinate signaling in glioblastoma.
• Drives cardiac hypertrophy through the vimentin/PI3K/Akt pathway.
• Regulates oxidative stress in gestational diabetes mellitus via the estradiol-Keap1-Nrf2 axis.
• Is conserved across species, including filarial parasites, where its biochemical properties have been characterized.
• Serves as a tractable target for CRISPR knockout, point-mutation, and overexpression studies that separate catalysis from signaling.
What Happens During phosphoglycerate kinase activity?
Substrate binding and phosphate transfer
In simple terms: The enzyme grabs a high-energy phosphate from one molecule and hands it to ADP to make ATP.
Phosphoglycerate kinase activity catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, generating 3-phosphoglycerate and ATP. This reaction is a key ATP-yielding step of glycolysis and is conserved from parasites to humans. The catalytic cycle requires binding of both substrates and is dependent on the enzyme's conformational flexibility, which is a general feature of phosphoglycerate kinases.
Coupling to glycolytic flux
In simple terms: This step keeps glycolysis moving by regenerating ATP while consuming a high-energy intermediate.
Because 1,3-bisphosphoglycerate is produced by glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase activity is tightly coupled to upstream glycolytic flux. In cancer cells, increased glycolytic flux and the Warburg effect elevate demand for this activity to sustain ATP production and anabolic metabolism. PGK1, the main human enzyme for this activity, is therefore a marker of metabolic reprogramming in tumors.
Post-translational control of the enzyme
In simple terms: Sugar and succinate tags can be attached to the enzyme to change how it behaves.
PGK1 is modified by O-GlcNAcylation, which coordinates glycolysis and the TCA cycle to promote tumor growth. In glioblastoma, HIF1α/ATF3 signaling modulates PGK1 K191/K192 succinylation through P4HA1/succinate signaling, linking oxygen sensing and metabolite availability to PGK1 function. These modifications can alter enzymatic activity, protein interactions, or localization, thereby tuning phosphoglycerate kinase activity in response to the cellular environment.
Non-catalytic roles in signaling and disease
In simple terms: The protein can do jobs beyond making ATP, such as influencing signaling pathways.
PGK1 contributes to diabetic kidney disease through both enzyme-dependent and enzyme-independent manners, indicating that phosphoglycerate kinase activity is only part of its biological function. In the heart, PGK1 drives cardiac hypertrophy by regulating the vimentin/PI3K/Akt pathway, a non-glycolytic signaling role. In gestational diabetes mellitus, PGK1 regulates oxidative stress through the estradiol-Keap1-Nrf2 pathway, further demonstrating that the protein integrates metabolic and stress responses.
Immunometabolic consequences
In simple terms: Blocking this enzyme changes how immune T cells use fuel and can calm inflammation.
Inhibition of PGK1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism, showing that phosphoglycerate kinase activity influences immune cell fate and inflammatory disease. This finding positions the enzyme as a metabolic checkpoint in T cells and supports further investigation of GO:0004618 in immunometabolism.
Key Genes Involved in GO:0004618 phosphoglycerate kinase activity
The following genes and proteins are directly or functionally linked to phosphoglycerate kinase activity (GO:0004618) in the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PGK1 | Primary human phosphoglycerate kinase that catalyzes the ATP-generating glycolytic step | Central to studies of glycolysis, cancer metabolism, and diabetic kidney disease |
| PGK2 | Testis-specific phosphoglycerate kinase paralog | Relevant to germ cell metabolism and male fertility research |
| GAPDH | Upstream glycolytic enzyme producing 1,3-bisphosphoglycerate | Provides substrate for phosphoglycerate kinase activity and is a common metabolic control |
| HIF1A | Oxygen-sensitive transcription factor that modulates PGK1 succinylation | Links hypoxia signaling to PGK1 post-translational regulation in glioblastoma |
| ATF3 | Stress-responsive transcription factor involved in PGK1 succinylation | Studied with HIF1A in glioblastoma metabolic adaptation |
| P4HA1 | Prolyl hydroxylase that influences succinate signaling toward PGK1 | Connects collagen hydroxylation and succinate metabolism to PGK1 modification |
| O-GlcNAc transferase (OGT) | Adds O-GlcNAc to PGK1 | Key for understanding how nutrient sensing modifies glycolytic enzymes |
| O-GlcNAcase (OGA) | Removes O-GlcNAc from PGK1 | Counter-regulates PGK1 O-GlcNAcylation and metabolic flux |
| Vimentin (VIM) | Intermediate filament protein regulated by PGK1 in cardiac hypertrophy | Links PGK1 to cytoskeletal and PI3K/Akt signaling in the heart |
| PI3K/Akt pathway components | Signaling axis downstream of PGK1 in cardiac hypertrophy | Targets for dissecting PGK1-driven cardiac remodeling |
| Keap1 | Oxidative stress regulator in the estradiol-PGK1-Keap1-Nrf2 pathway | Relevant to gestational diabetes mellitus and redox biology |
| Nrf2 (NFE2L2) | Transcription factor downstream of Keap1 in PGK1-related oxidative stress | Studied in gestational diabetes mellitus models |
| Estradiol pathway genes | Hormonal regulators of PGK1-linked oxidative stress | Provide endocrine context for PGK1 function |
| CD4+ T cell metabolic genes | Effectors of PGK1 inhibition in autoimmune myocarditis | Used to study immunometabolic reprogramming |
| Filarial PGK | Parasite phosphoglycerate kinase with characterized biochemistry | Model for comparative enzymology and antiparasitic targeting |
How Is phosphoglycerate kinase activity Regulated?
Phosphoglycerate kinase activity is regulated at multiple levels. Post-translational modification by O-GlcNAcylation coordinates glycolysis with the TCA cycle and promotes tumor growth, indicating that nutrient-sensing pathways can tune PGK1 function. In glioblastoma, HIF1α/ATF3 signaling modulates PGK1 K191/K192 succinylation through P4HA1/succinate signaling, linking hypoxia and metabolite availability to enzyme modification. In gestational diabetes mellitus, PGK1 regulates oxidative stress through the estradiol-Keap1-Nrf2 pathway, showing hormonal and redox control. Inhibition of PGK1 reprograms CD4+ T cell metabolism, suggesting that immune signals and metabolic checkpoints influence this activity. In the heart, PGK1 drives cardiac hypertrophy via the vimentin/PI3K/Akt pathway, indicating that growth factor signaling intersects with PGK1 function. Finally, PGK1 contributes to diabetic kidney disease through enzyme-dependent and enzyme-independent manners, implying that its regulation is context-dependent.
phosphoglycerate kinase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PGK1 | Diabetic kidney disease | Knockout or point-mutation kidney cell models to separate enzyme-dependent and independent effects |
| PGK1 | Autoimmune myocarditis | CD4+ T cell-specific knockout or inhibitor-treated models |
| PGK1 | Glioblastoma and tumor growth | Knockout, succinylation-site point mutants, or O-GlcNAc-site mutants in glioma cells |
| PGK1 | Cardiac hypertrophy | Cardiomyocyte overexpression or knockout models with PI3K/Akt readouts |
| PGK1 | Gestational diabetes mellitus | Knockout or overexpression models with Keap1/Nrf2 and oxidative stress endpoints |
Cancer and metabolic reprogramming
PGK1 supports tumor growth through O-GlcNAcylation-dependent coordination of glycolysis and the TCA cycle, and its succinylation is modulated in glioblastoma by HIF1α/ATF3 and P4HA1/succinate signaling. The Warburg effect in tumor cells depends on efficient glycolytic ATP production, making phosphoglycerate kinase activity a key node in cancer metabolism. These findings support the study of GO:0004618 in oncology and the development of PGK1-targeted hypotheses.
Cardiovascular and metabolic disease
Inhibition of PGK1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism, linking phosphoglycerate kinase activity to immune-mediated heart disease. PGK1 also drives cardiac hypertrophy by regulating the vimentin/PI3K/Akt pathway, indicating a role in pathological cardiac remodeling. In diabetic kidney disease, PGK1 contributes through enzyme-dependent and enzyme-independent manners, highlighting the need to separate catalytic from non-catalytic functions.
Gestational diabetes mellitus and oxidative stress
PGK1 regulates oxidative stress in gestational diabetes mellitus through the estradiol-Keap1-Nrf2 pathway, connecting phosphoglycerate kinase activity to redox homeostasis during pregnancy. This suggests that PGK1 may influence maternal metabolic adaptation and fetal outcomes, although further studies are needed to define causal mechanisms.
From phosphoglycerate kinase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of phosphoglycerate kinase activity impair glycolysis and ATP production? | PGK1 knockout cell lines with metabolic flux assays |
| Does a specific post-translational modification site regulate PGK1 function? | Point-mutation knock-in of K191/K192 or O-GlcNAc sites |
| Can wild-type PGK1 rescue phenotypes caused by PGK1 loss? | Knock-in of tagged or untagged wild-type PGK1 |
| Does overexpression of PGK1 drive hypertrophy or tumor growth? | Overexpression models in cardiomyocytes or cancer cells |
| Which metabolic pathways depend on PGK1 catalytic activity? | Knockout plus metabolomics and bioinformatics analysis |
| Does PGK1 inhibition reprogram immune cell metabolism? | CD4+ T cell knockout or inhibitor-treated models |
How to Study the phosphoglycerate kinase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Coupled enzymatic assay | Phosphoglycerate kinase catalytic rate | Validating knockout or point-mutant effects on activity |
| Seahorse extracellular flux | Glycolytic and oxidative metabolism | Assessing metabolic reprogramming after PGK1 perturbation |
| Metabolomics | Levels of glycolytic and TCA cycle intermediates | Mapping pathway dependencies on PGK1 |
| Immunoprecipitation and western blot | O-GlcNAcylation or succinylation of PGK1 | Testing modification-site mutants |
| Mass spectrometry | Post-translational modification sites and protein interactions | Identifying regulatory residues on PGK1 |
| CRISPR knockout screening | Gene essentiality and pathway dependencies | Discovering context-specific roles of phosphoglycerate kinase activity |
| RNA-seq | Transcriptional consequences of PGK1 perturbation | Linking PGK1 to downstream signaling programs |
| Histology and imaging | Tissue pathology in heart or kidney models | Evaluating disease severity after PGK1 manipulation |
Enzymatic activity assays
Phosphoglycerate kinase activity can be measured by coupling the reaction to NADH oxidation or by monitoring ATP production from 1,3-bisphosphoglycerate and ADP. These assays are used to confirm that CRISPR-engineered mutations alter catalytic function rather than only protein abundance.
Metabolic flux and metabolomics
Glycolytic flux, extracellular acidification rate, and metabolite profiling can reveal how loss or inhibition of PGK1 reshapes central carbon metabolism. Such approaches are particularly useful for distinguishing enzyme-dependent from enzyme-independent phenotypes.
Post-translational modification analysis
O-GlcNAcylation and succinylation of PGK1 can be assessed by immunoprecipitation, western blotting with modification-specific reagents, and mass spectrometry. These methods help map how nutrient and oxygen signals modify phosphoglycerate kinase activity.
Disease model phenotyping
Animal and cell models of diabetic kidney disease, autoimmune myocarditis, cardiac hypertrophy, and gestational diabetes mellitus can be used to test whether PGK1 loss or inhibition changes disease endpoints. Combining these models with CRISPR engineering enables causal inference.
How CRISPR Can Be Used to Study GO:0004618 phosphoglycerate kinase activity
Knockout
CRISPR knockout of PGK1 eliminates phosphoglycerate kinase activity and is used to test whether glycolytic ATP production, tumor growth, or immune cell function depends on this enzyme. Knockout models are also valuable for separating catalytic from non-catalytic functions when combined with rescue experiments.
Point Mutation
Point mutations at catalytic residues or at regulatory modification sites such as K191/K192 can dissect which functions of PGK1 require enzymatic activity versus post-translational modification. These models are essential for attributing phenotypes to phosphoglycerate kinase activity specifically.
Knock-in
Knock-in of tagged or mutant PGK1 allows controlled expression and localization studies in disease-relevant cell types. Tagged knock-in can also facilitate interaction proteomics and live-cell imaging of PGK1.
Overexpression
Overexpression of PGK1 is used to test sufficiency in driving tumor growth, cardiac hypertrophy, or oxidative stress phenotypes. Combining overexpression with point mutants helps determine whether the observed effects require catalytic activity.
How EDITGENE Supports phosphoglycerate kinase activity Research
Researchers studying phosphoglycerate kinase activity-related genes often need to determine whether a candidate gene is causally involved in a metabolic or disease phenotype, and whether its catalytic activity or a non-enzymatic function is responsible. EDITGENE provides CRISPR-based cell models and screening services that enable such causal experiments with high precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for phosphoglycerate kinase activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PGK2 Knockout HEK293 Cell Line | EDJ-KQ1516 | Human | 5232 | Details Get a Quote |
| PGK2 Knockout HeLa Cell Line | EDJ-KQ54129 | Human | 5232 | Details Get a Quote |
| PGK2 Knockout A-549 Cell Line | EDJ-KQ62618 | Human | 5232 | Details Get a Quote |
| PGK2 Knockout HCT 116 Cell Line | EDJ-KQ71090 | Human | 5232 | Details Get a Quote |
| PGK1 Knockout HEK293T Cell Line | EDJ-KQ78143 | Human | 5230 | Details Get a Quote |
| PGK1 Knockout A-549 Cell Line | EDJ-KQ78144 | Human | 5230 | Details Get a Quote |
Displaying Records 1 To 6 Of 6 Records
Frequently Asked Questions About phosphoglycerate kinase activity
What is phosphoglycerate kinase activity?
Phosphoglycerate kinase activity (GO:0004618) is the enzymatic function that transfers a phosphate group from 1,3-bisphosphoglycerate to ADP, producing 3-phosphoglycerate and ATP during glycolysis.
What gene encodes phosphoglycerate kinase activity in humans?
PGK1 is the principal human gene encoding phosphoglycerate kinase activity, and it has been studied in cancer, kidney disease, and cardiac disease.
What does GO:0004618 mean?
GO:0004618 is the Gene Ontology identifier for phosphoglycerate kinase activity, classified under the biological_process aspect, and it describes the glycolytic ATP-generating reaction.
How is phosphoglycerate kinase activity regulated?
It is regulated by post-translational modifications such as O-GlcNAcylation and succinylation, as well as by signaling pathways including HIF1α/ATF3 and estradiol-Keap1-Nrf2.
Why is phosphoglycerate kinase activity important in cancer?
Cancer cells often rely on high glycolytic flux, and PGK1 supports tumor growth through O-GlcNAcylation-dependent coordination of glycolysis and the TCA cycle.
Is PGK1 involved in heart disease?
Yes, inhibition of PGK1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism, and PGK1 drives cardiac hypertrophy via the vimentin/PI3K/Akt pathway.
What diseases are linked to PGK1?
PGK1 has been linked to diabetic kidney disease, autoimmune myocarditis, glioblastoma, cardiac hypertrophy, and gestational diabetes mellitus.
How do researchers study phosphoglycerate kinase activity?
They use coupled enzymatic assays, metabolic flux analysis, metabolomics, post-translational modification analysis, and CRISPR knockout or point-mutation models.
Can CRISPR knockout be used to study PGK1?
Yes, CRISPR knockout of PGK1 is used to test loss-of-function phenotypes and to separate catalytic from non-catalytic roles in disease models.
What is the difference between PGK1 enzyme-dependent and enzyme-independent functions?
PGK1 can contribute to disease through its catalytic activity or through protein interactions and signaling, and knockout plus rescue or point-mutation experiments are needed to distinguish these mechanisms.
Conclusion
Phosphoglycerate kinase activity (GO:0004618) is a central glycolytic function that generates ATP and supports metabolic reprogramming in health and disease. The human enzyme PGK1 is regulated by O-GlcNAcylation and succinylation and contributes to cancer, diabetic kidney disease, autoimmune myocarditis, cardiac hypertrophy, and gestational diabetes mellitus through both catalytic and non-catalytic mechanisms. Because these functions are context-dependent, rigorous CRISPR-based models are essential for causal dissection. EDITGENE provides the knockout, point-mutation, knock-in, overexpression, and screening tools needed to study phosphoglycerate kinase activity in disease-relevant systems.
References
- 1. Sun HJ et al.. 2025. Phosphoglycerate kinase 1 contributes to diabetic kidney disease through enzyme-dependent and independent manners.. Cell Rep Med 6(8):102241 PMID: 40695289
- 2. Lu Y et al.. 2023. Inhibition of phosphoglycerate kinase 1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism.. Cardiovasc Res 119(6):1377-1389 PMID: 36726197
- 3. Yang S et al.. 2024. HIF1α/ATF3 partake in PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma.. Neuro Oncol 26(8):1405-1420 PMID: 38441561
- 4. Nie H et al.. 2020. O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth.. Nat Commun 11(1):36 PMID: 31911580
- 5. Fukushi A et al.. 2022. Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells.. Int J Mol Sci 23(17) PMID: 36077431
- 6. Zhu XX et al.. 2026. PGK1 Drives Cardiac Hypertrophy by Regulating the Vimentin/PI3K/Akt Pathway.. Circ Res 138(7):e327173 PMID: 41732856
- 7. Peng Y et al.. 2025. PGK1 Regulates Oxidative Stress in Gestational Diabetes Mellitus through the Estradiol-Keap1-Nrf2 Pathway.. Int J Biol Sci 21(12):5496-5513 PMID: 40959277
- 8. Kumar R et al.. 2019. Characterization of filarial phosphoglycerate kinase.. Biochimie 165:258-266 PMID: 31446011
