Phosphoglycerate kinase 1 is the enzyme that catalyzes the first ATP-generating (substrate-level phosphorylation) step of the glycolytic payoff phase, reversibly transferring a phosphate between 1,3-bisphosphoglycerate + ADP and 3-phosphoglycerate + ATP (EC 2.7.2.3); the reverse reaction operates in gluconeogenesis. It is a cytosolic, monomeric, Mg2+-dependent enzyme that is X-linked and ubiquitously expressed. Beyond glycolysis, PGK1 has documented moonlighting activities, including a secreted extracellular disulfide-reductase activity that liberates the angiogenesis inhibitor angiostatin from plasmin, and, under hypoxic or oncogenic conditions, a mitochondrially-translocated protein kinase activity that phosphorylates PDHK1 to suppress pyruvate oxidation and promote aerobic glycolysis (the Warburg effect). Loss-of-function variants cause phosphoglycerate kinase 1 deficiency, an X-linked disorder combining hemolytic anemia, myopathy (exercise intolerance and rhabdomyolysis) and central nervous system involvement.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004618 phosphoglycerate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation of the core catalytic molecular function, phosphoglycerate kinase activity, shared across the PGK family. This is the defining, well-supported function of PGK1. Reason: This is the core molecular function of PGK1, catalyzing the reversible 1,3-bisphosphoglycerate + ADP <-> 3-phosphoglycerate + ATP reaction, and is independently supported by direct experimental and structural evidence. Supporting Evidence: PMID:26942675 Phosphoglycerate kinase 1 (PGK1), the first ATP-generating enzyme in the glycolytic pathway, catalyzes the transfer of the high-energy phosphate from the 1-position of 1,3-diphosphoglycerate (1,3-BPG) to ADP, which leads to the generation of 3-phosphoglycerate (3-PG) and ATP |
| GO:0043531 ADP binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of ADP binding, reflecting the substrate/product nucleotide bound during catalysis (ADP is the phosphate acceptor in the glycolytic direction). Reason: ADP is a bona fide substrate of the phosphoglycerate kinase reaction, and structural studies confirm nucleotide binding in the C-terminal domain. This supports the core catalytic function. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt Reaction=(2R)-3-phosphoglycerate + ATP = (2R)-3-phospho-glyceroyl phosphate + ADP |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation placing PGK1 activity in the cytosol, the principal compartment where glycolysis occurs. Reason: The cytosol is the true core cellular location of PGK1's glycolytic activity, consistent with direct experimental evidence. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0006096 glycolytic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of involvement in the glycolytic process, the central biological role of PGK1. Reason: PGK1 catalyzes step 2/5 of the conversion of glyceraldehyde-3-phosphate to pyruvate and is one of only two ATP-generating enzymes in glycolysis. This is a core biological process for the gene. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 2/5. |
| GO:0005524 ATP binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of ATP binding, reflecting the nucleotide substrate/product of the phosphoglycerate kinase reaction. Reason: ATP is a direct substrate/product of the catalyzed reaction and its binding is documented by kinetic (KM for ATP) and structural analyses. Supports the core catalytic function. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt KM=0.56 mM for ATP |
| GO:0006094 gluconeogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of involvement in gluconeogenesis, the biosynthetic direction of the reversible PGK reaction. Reason: The phosphoglycerate kinase reaction is reversible, and the right-to-left (ATP-consuming) direction is used in gluconeogenesis. This is a legitimate core biological role. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14803 |
| GO:0004618 phosphoglycerate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (multiple IEA methods, incl. ARBA, InterPro, RHEA, EC 2.7.2.3) of the core phosphoglycerate kinase activity. Reason: Redundant with, and consistent with, experimental and phylogenetic support for the core catalytic function; the InterPro/EC/RHEA mapping is correct for this family. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt EC=2.7.2.3 |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | KEEP AS NON CORE | Summary: Electronic annotation derived from the EC 2.7.11.1 mapping, corresponding to the documented moonlighting protein kinase activity of PGK1 (phosphorylating PDHK1). The generic EC-to-GO mapping is broad but the underlying activity is real. Reason: PGK1 has an experimentally validated moonlighting protein kinase activity, but this is a context-specific (hypoxia/oncogenic, mitochondrial) function, distinct from its core cytosolic glycolytic role. Supporting Evidence: PMID:26942675 Mitochondrial PGK1, acting as a protein kinase, phosphorylates and activates PDHK1. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation (UniProt SubCell mapping) of mitochondrial matrix localization, matching the experimentally documented hypoxia/oncogene-induced mitochondrial translocation of PGK1. Reason: PGK1 is imported into the mitochondrial matrix only under specific conditions (hypoxia, oncogenic signalling) as part of its moonlighting protein kinase role; it is not the core cytosolic glycolytic location. Supporting Evidence: PMID:26942675 mitochondrial translocation of PGK1 |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of cytosolic localization, consistent with the core glycolytic compartment. Reason: The cytosol is the principal, core subcellular location of PGK1, agreeing with direct experimental evidence. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0006096 glycolytic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (InterPro/UniPathway) of involvement in glycolysis. Reason: Consistent with the core glycolytic role of PGK1; the pathway mapping is correct. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Electronic (RHEA:17989) annotation of protein serine kinase activity, corresponding to the documented moonlighting phosphorylation of PDHK1. Reason: This reflects a real but context-specific, non-core moonlighting activity of mitochondria-translocated PGK1, distinct from its principal glycolytic role. Supporting Evidence: PMID:26942675 Mitochondrial PGK1, acting as a protein kinase, phosphorylates and activates PDHK1. |
| GO:0005515 protein binding | IPI PMID:20392205 Loose interaction between glyceraldehyde-3-phosphate dehydro... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction of PGK1 with GAPDH (P04406), captured only as the uninformative generic term protein binding. Reason: Bare protein binding does not convey a specific molecular function. The GAPDH-PGK1 interaction reflects the physical proximity of consecutive glycolytic enzymes but is not annotated to an informative function term. Supporting Evidence: PMID:20392205 Loose interaction between glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase revealed by fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy in living cells. |
| GO:0005515 protein binding | IPI PMID:20849852 Proliferating cell nuclear antigen in the cytoplasm interact... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction of PGK1 with PCNA (P12004), captured only as the generic term protein binding. Reason: Bare protein binding is uninformative. The interaction with PCNA relates to cytoplasmic PCNA associating with glycolytic enzymes but is not tied to a specific molecular function. Supporting Evidence: PMID:20849852 Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer. |
| GO:0005515 protein binding | IPI PMID:26030842 A fluorescent bimolecular complementation screen reveals MAF... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction of PGK1 with PCNA (P12004) from a bimolecular complementation screen, captured only as generic protein binding. Reason: Bare protein binding provides no informative molecular function for PGK1. Supporting Evidence: PMID:26030842 A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells. |
| GO:0005515 protein binding | IPI PMID:26356530 Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylati... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction of PGK1 with HDAC3 (O15379). HDAC3 deacetylates PGK1 at K220 to activate it; a regulatory interaction, but here captured only as generic protein binding. Reason: Bare protein binding is uninformative. The functionally meaningful content (HDAC3-mediated deacetylation/activation of PGK1) is regulatory and is better described elsewhere; the term itself conveys no specific PGK1 molecular function. Supporting Evidence: PMID:26356530 HDAC3 deacetylates and activates PGK1. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: High-throughput interactome interaction with PGK2 (P07205), captured only as generic protein binding. Reason: Bare protein binding is uninformative; PGK2 is the closely related testis paralog and this high-throughput interaction conveys no specific function. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MARK AS OVER ANNOTATED | Summary: Kinase interaction-network interaction with NEK7 (Q8TDX7), captured only as generic protein binding. Reason: Bare protein binding is uninformative for molecular function. Supporting Evidence: PMID:32707033 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Proteome-scale interactome interaction with PGK2 (P07205), captured only as generic protein binding. Reason: Bare protein binding is uninformative; a high-throughput paralog interaction with no specified function. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Endogenous-tagging (OpenCell) interaction with PGK2 (P07205), captured only as generic protein binding. Reason: Bare protein binding is uninformative for molecular function. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0006094 gluconeogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology (from mouse P09411) electronic transfer of involvement in gluconeogenesis. Reason: Consistent with the reversible PGK reaction being used in the gluconeogenic direction; the orthology transfer is appropriate. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14803 |
| GO:0044325 transmembrane transporter binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology (from mouse P09411) electronic transfer of transmembrane transporter binding. There is no strong human evidence for a specific transporter-binding function. Reason: This is an orthology-transferred electronic annotation with no corroborating human experimental evidence and no specific transporter named; it is uninformative and not part of the core function of PGK1. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt SIMILARITY: Belongs to the phosphoglycerate kinase family. |
| GO:0061621 canonical glycolysis | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (ARBA) of involvement in canonical glycolysis, a more specific child of glycolytic process. Reason: Canonical glycolysis (Embden-Meyerhof-Parnas) is precisely the pathway in which PGK1 operates; this is a correct, appropriately specific core BP term. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 2/5. |
| GO:0006094 gluconeogenesis | TAS Reactome:R-HSA-70263 | ACCEPT | Summary: Reactome traceable-author-statement annotation of involvement in gluconeogenesis. Reason: PGK1 is a Reactome-curated participant in the gluconeogenesis pathway (the reverse glycolytic direction); a legitimate core biological role. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14803 |
| GO:0061621 canonical glycolysis | TAS Reactome:R-HSA-70171 | ACCEPT | Summary: Reactome traceable-author-statement annotation of involvement in canonical glycolysis. Reason: PGK1 is a Reactome-curated participant in the glycolysis pathway; an appropriately specific core biological process. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 2/5. |
| GO:0004618 phosphoglycerate kinase activity | EXP PMID:1278465 Characterization of phosphoglycerate kinase from human sperm... | ACCEPT | Summary: Experimental characterization of phosphoglycerate kinase activity from human tissue (spermatozoa), confirming the core enzymatic function. Reason: Direct experimental evidence for phosphoglycerate kinase activity; this is the core molecular function of PGK1. Supporting Evidence: PMID:1278465 We have confirmed the presence of a unique electrophoretic isoenzyme of phosphoglycerate kinase (PGK) in homogenate extracts of human sperm. |
| GO:0004618 phosphoglycerate kinase activity | EXP PMID:5009693 Human phosphoglycerate kinase. I. Crystallization and charac... | ACCEPT | Summary: Experimental crystallization and characterization of the normal human phosphoglycerate kinase enzyme, establishing the core catalytic function. Reason: Direct experimental characterization of the purified enzyme supports the core phosphoglycerate kinase molecular function. Supporting Evidence: PMID:5009693 Human phosphoglycerate kinase. I. Crystallization and characterization of normal enzyme. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-9975250 | KEEP AS NON CORE | Summary: Reactome traceable-author-statement annotation of the moonlighting protein serine/threonine kinase activity (PGK1 phosphorylating AKT1S1/PRAS40). Reason: Reflects the documented but context-specific moonlighting protein kinase activity of PGK1, not its core glycolytic function. Supporting Evidence: PMID:26942675 Mitochondrial PGK1, acting as a protein kinase, phosphorylates and activates PDHK1. |
| GO:0004618 phosphoglycerate kinase activity | EXP PMID:30323285 A metabolite-derived protein modification integrates glycoly... | ACCEPT | Summary: Experimental study characterizing PGK1 as a glycolytic enzyme and identifying a small-molecule inhibitor (CBR-470-0), confirming its catalytic activity. Reason: Direct experimental evidence for the core phosphoglycerate kinase activity (EC 2.7.2.3); the inhibitor study depends on and confirms the enzymatic function. Supporting Evidence: PMID:30323285 we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal |
| GO:0106310 protein serine kinase activity | EXP PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase... | KEEP AS NON CORE | Summary: Experimental demonstration that mitochondria-translocated PGK1 acts as a protein kinase, phosphorylating PDHK1 on a serine/threonine residue. Reason: This is a genuine, experimentally validated moonlighting activity, but it is context-specific (hypoxia/oncogenic, mitochondrial) and distinct from the core cytosolic glycolytic function. Supporting Evidence: PMID:26942675 The current study shows that highly purified PGK1 with no obvious protein kinase contamination phosphorylated highly purified PDHK1 supporting that glycolytic enzymes can possess dual enzymatic activities, functioning both as metabolic enzymes and protein kinases. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase... | KEEP AS NON CORE | Summary: Direct assay demonstrating PGK1 protein serine/threonine kinase activity toward PDHK1 (T338). Reason: Experimentally validated moonlighting protein kinase activity of mitochondrial PGK1; non-core relative to the principal glycolytic function. Supporting Evidence: PMID:26942675 protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1) at T338 |
| GO:0160218 negative regulation of pyruvate decarboxylation to acetyl-CoA | IDA PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase... | KEEP AS NON CORE | Summary: Direct evidence that PGK1-mediated phosphorylation/activation of PDHK1 leads to inhibition of the pyruvate dehydrogenase complex, suppressing pyruvate decarboxylation to acetyl-CoA. Reason: A biologically meaningful consequence of the moonlighting mitochondrial kinase activity; it is a context-specific regulatory role rather than the core glycolytic function of PGK1. Supporting Evidence: PMID:26942675 which activates PDHK1 to phosphorylate and inhibit the pyruvate dehydrogenase (PDH) complex. This reduces mitochondrial pyruvate utilization |
| GO:0005515 protein binding | IPI PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase... | MARK AS OVER ANNOTATED | Summary: Curated interaction of PGK1 with MAPK1/ERK2 (P28482), captured only as generic protein binding. Reason: Bare protein binding is uninformative. The MAPK1 interaction (which phosphorylates PGK1 at S203 to promote mitochondrial import) is regulatory, but the term itself conveys no specific PGK1 molecular function. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt Interacts with kinase MAPK1/ERK2 |
| GO:0005515 protein binding | IPI PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase... | MARK AS OVER ANNOTATED | Summary: Curated interaction of PGK1 with peptidyl-prolyl isomerase PIN1 (Q13526), captured only as generic protein binding. Reason: Bare protein binding is uninformative for molecular function; the PIN1 interaction is regulatory (targeting to mitochondrion) rather than a specific function term. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt peptidyl-prolyl cis-trans isomerase PIN1 |
| GO:0005515 protein binding | IPI PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase... | MARK AS OVER ANNOTATED | Summary: Curated interaction of PGK1 with pyruvate dehydrogenase kinase PDK1/PDHK1 (Q15118), captured only as generic protein binding. Reason: Bare protein binding is uninformative; the functionally relevant content (PGK1 phosphorylating PDHK1) is already captured by the kinase and pyruvate regulation annotations. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt Interacts with pyruvate dehydrogenase kinase PDK1 |
| GO:0005759 mitochondrial matrix | IDA PMID:26942675 Mitochondria-Translocated PGK1 Functions as a Protein Kinase... | KEEP AS NON CORE | Summary: Direct evidence that PGK1 is translocated to the mitochondrion under hypoxic/oncogenic conditions where it acts as a protein kinase. Reason: Mitochondrial matrix localization is condition-dependent and tied to the moonlighting kinase role, not the core cytosolic glycolytic location. Supporting Evidence: PMID:26942675 mitochondrial translocation of PGK1 |
| GO:0005759 mitochondrial matrix | IDA PMID:36849569 mcPGK1-dependent mitochondrial import of PGK1 promotes metab... | KEEP AS NON CORE | Summary: Direct evidence that the mitochondrial circRNA mcPGK1 promotes import of PGK1 into mitochondria in liver tumour-initiating cells. Reason: Confirms condition-dependent mitochondrial localization of PGK1, part of its moonlighting function; not the core cytosolic location. Supporting Evidence: PMID:36849569 mcPGK1 promotes the mitochondrial localization of PGK1 |
| GO:0005829 cytosol | IDA PMID:36849569 mcPGK1-dependent mitochondrial import of PGK1 promotes metab... | ACCEPT | Summary: Direct evidence that PGK1 is present in the cytosol (with a fraction redistributing to mitochondria). Reason: The cytosol is the principal, core subcellular location of PGK1 where it performs glycolysis. Supporting Evidence: PMID:36849569 mcPGK1 was predominantly localized in mitochondria and also detectable in cytoplasm |
| GO:0004618 phosphoglycerate kinase activity | IMP PMID:7391028 A single amino acid substitution (Asp leads to Asn) in a pho... | ACCEPT | Summary: Characterization of the PGK Munchen deficiency variant (Asp268Asn), linking a single amino acid substitution to reduced enzyme activity and thereby confirming the phosphoglycerate kinase molecular function. Reason: A loss-of-function disease variant that reduces enzymatic activity provides genetic (IMP) support for the core phosphoglycerate kinase function. Supporting Evidence: PMID:7391028 A single amino acid substitution (Asp leads to Asn) in a phosphoglycerate kinase variant (PGK München) associated with enzyme deficiency. |
| GO:0006096 glycolytic process | IMP PMID:7391028 A single amino acid substitution (Asp leads to Asn) in a pho... | ACCEPT | Summary: The PGK Munchen deficiency variant impairs glycolytic flux, supporting PGK1's involvement in the glycolytic process. Reason: Genetic evidence from an enzyme-deficiency variant supports the core biological role of PGK1 in glycolysis. Supporting Evidence: PMID:7391028 phosphoglycerate kinase variant (PGK München) associated with enzyme deficiency |
| GO:0005576 extracellular region | IDA PMID:11130727 Phosphoglycerate kinase acts in tumour angiogenesis as a dis... | KEEP AS NON CORE | Summary: PGK1 is secreted by tumour cells into the extracellular milieu, where it acts as a plasmin/disulfide reductase. Reason: A documented moonlighting extracellular localization tied to the secreted disulfide-reductase/angiogenesis function; not the core cytosolic glycolytic location. Supporting Evidence: PMID:11130727 phosphoglycerate kinase not only functions in glycolysis but is secreted by tumour cells and participates in the angiogenic process as a disulphide reductase |
| GO:0016525 negative regulation of angiogenesis | IMP PMID:11130727 Phosphoglycerate kinase acts in tumour angiogenesis as a dis... | KEEP AS NON CORE | Summary: Administration of PGK1 to tumour-bearing mice increased plasma angiostatin and reduced tumour vascularity, implicating secreted PGK1 in negative regulation of angiogenesis. Reason: A moonlighting function of secreted PGK1 (via angiostatin release), not the core glycolytic role. Supporting Evidence: PMID:11130727 Administration of phosphoglycerate kinase to tumour-bearing mice caused an increase in plasma levels of angiostatin, and a decrease in tumour vascularity and rate of tumour growth. |
| GO:0031639 plasminogen activation | IMP PMID:11130727 Phosphoglycerate kinase acts in tumour angiogenesis as a dis... | KEEP AS NON CORE | Summary: Secreted PGK1 reduces disulfide bonds in plasmin, initiating proteolytic cleavage and angiostatin release. Reason: Part of the secreted disulfide-reductase moonlighting function; not the core glycolytic role. The term captures PGK1's action on the plasmin(ogen) system. Supporting Evidence: PMID:11130727 Reduction of plasmin initiates proteolytic cleavage in the kringle 5 domain and release of the tumour blood vessel inhibitor angiostatin. |
| GO:0047134 protein-disulfide reductase [NAD(P)H] activity | IMP PMID:11130727 Phosphoglycerate kinase acts in tumour angiogenesis as a dis... | KEEP AS NON CORE | Summary: PGK1 secreted from fibrosarcoma cells was identified as the plasmin reductase, exhibiting protein-disulfide reductase activity in the extracellular space. Reason: A well-documented moonlighting molecular function of secreted PGK1, distinct from its core phosphoglycerate kinase activity. Supporting Evidence: PMID:11130727 the plasmin reductase isolated from conditioned medium of fibrosarcoma cells is the glycolytic enzyme phosphoglycerate kinase |
| GO:0071456 cellular response to hypoxia | IDA PMID:11130727 Phosphoglycerate kinase acts in tumour angiogenesis as a dis... | KEEP AS NON CORE | Summary: Annotation of PGK1 in the cellular response to hypoxia. PGK1 is a HIF-1 target gene, and hypoxia promotes its mitochondrial targeting and moonlighting functions. Reason: Hypoxia responsiveness is a physiologically relevant context for PGK1 (both as a HIF target and via hypoxia-induced mitochondrial translocation), but it is a regulatory/context annotation rather than the core molecular function. Supporting Evidence: PMID:26942675 hypoxia, EGFR activation, and expression of K-Ras G12V and B-Raf V600E induce mitochondrial translocation of phosphoglycerate kinase 1 (PGK1) |
| GO:0070062 extracellular exosome | HDA PMID:11487543 Intestinal epithelial cells secrete exosome-like vesicles. | KEEP AS NON CORE | Summary: High-throughput proteomic detection of PGK1 in extracellular exosome-like vesicles. Reason: PGK1 is an abundant cytosolic protein commonly detected in exosome proteomes; this reflects its secretion/exosomal presence rather than the core cytosolic glycolytic location. Supporting Evidence: PMID:11487543 Intestinal epithelial cells secrete exosome-like vesicles. |
| GO:0045121 membrane raft | IDA PMID:25204797 Flotillin-1 facilitates toll-like receptor 3 signaling in hu... | MARK AS OVER ANNOTATED | Summary: PGK1 was detected by SILAC mass spectrometry in the detergent-resistant (membrane raft) fraction of endothelial cells. Reason: This is a proteomic co-purification of an abundant cytosolic protein in a detergent-resistant membrane fraction, not evidence of a specific membrane-raft function; it over-represents an incidental localization. Supporting Evidence: PMID:25204797 shRNA against flotillin-1 reduced the abundance of the structural caveolae proteins caveolin-1, cavin-1 and cavin-2 in the detergent-resistant fraction. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of PGK1 in exosomes from prostatic secretions. Reason: Reflects incidental presence of an abundant cytosolic protein in exosome proteomes rather than the core function or location. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput proteomic detection of PGK1 in an NK-cell membrane proteome. Reason: A generic membrane localization from a membrane-proteome dataset for an abundant cytosolic protein; uninformative and not part of the core function. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells. |
| GO:0030855 epithelial cell differentiation | IEP PMID:21492153 Analysis of proteomic changes induced upon cellular differen... | MARK AS OVER ANNOTATED | Summary: Expression-based (IEP) annotation from a proteomic comparison of proliferating versus differentiated Caco-2 intestinal cells, where PGK1 was among the differentially regulated proteins. Reason: Differential abundance of PGK1 during Caco-2 differentiation reflects a general metabolic shift, not a specific role of PGK1 in epithelial cell differentiation; an over-annotation of a correlative expression change. Supporting Evidence: PMID:21492153 Analysis of proteomic changes induced upon cellular differentiation of the human intestinal cell line Caco-2. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of PGK1 in parotid gland exosomes. Reason: Reflects incidental exosomal presence of an abundant cytosolic protein, not the core function or location. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of PGK1 in B-cell exosomes. Reason: Reflects incidental exosomal presence of an abundant cytosolic protein, not the core function or location. Supporting Evidence: PMID:20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-70486 | ACCEPT | Summary: Reactome traceable-author-statement annotation of cytosolic localization (PGK complexes phosphorylating 3PG). Reason: The cytosol is the core subcellular location where PGK1 performs glycolysis. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71850 | ACCEPT | Summary: Reactome traceable-author-statement annotation of cytosolic localization (PGK complexes dephosphorylating 1,3BPG, the gluconeogenic direction). Reason: The cytosol is the core subcellular location of PGK1 activity. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9636658 | ACCEPT | Summary: Reactome traceable-author-statement annotation of cytosolic localization (in the context of EsxA binding PGK1). Reason: The cytosol is the core subcellular location of PGK1. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9975250 | ACCEPT | Summary: Reactome traceable-author-statement annotation of cytosolic localization (in the context of PGK1 phosphorylating AKT1S1). Reason: The cytosol is the core subcellular location of PGK1. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0004618 phosphoglycerate kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity annotation (from UniProtKB:P41759) of the core phosphoglycerate kinase activity. Reason: Consistent with, and redundant to, the strong experimental support for the core catalytic function. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt EC=2.7.2.3 |
| GO:0005524 ATP binding | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity annotation (from UniProtKB:P00559) of ATP binding, the nucleotide substrate/product of the reaction. Reason: ATP binding is intrinsic to the phosphoglycerate kinase reaction and is supported by kinetic and structural data; supports the core catalytic function. Supporting Evidence: file:human/PGK1/PGK1-uniprot.txt KM=0.56 mM for ATP |
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