PGK1

Existing Annotations Review

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

📄 View Raw YAML

id: P00558
gene_symbol: PGK1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
alternative_products:
- name: '1'
  id: P00558-1
- name: '2'
  id: P00558-2
  sequence_note: VSP_056159
existing_annotations:
- term:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: 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
- term:
    id: GO:0043531
    label: ADP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic annotation of ADP binding, reflecting the substrate/product
      nucleotide bound during catalysis (ADP is the phosphate acceptor in the
      glycolytic direction).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: Reaction=(2R)-3-phosphoglycerate + ATP = (2R)-3-phospho-glyceroyl
        phosphate + ADP
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic annotation placing PGK1 activity in the cytosol, the
      principal compartment where glycolysis occurs.
    action: ACCEPT
    reason: The cytosol is the true core cellular location of PGK1's glycolytic
      activity, consistent with direct experimental evidence.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic annotation of involvement in the glycolytic process, the
      central biological role of PGK1.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from
        D-glyceraldehyde 3-phosphate: step 2/5.'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic annotation of ATP binding, reflecting the nucleotide
      substrate/product of the phosphoglycerate kinase reaction.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: KM=0.56 mM for ATP
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic annotation of involvement in gluconeogenesis, the
      biosynthetic direction of the reversible PGK reaction.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14803
- term:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation (multiple IEA methods, incl. ARBA, InterPro, RHEA,
      EC 2.7.2.3) of the core phosphoglycerate kinase activity.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: EC=2.7.2.3
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: Mitochondrial PGK1, acting as a protein kinase, phosphorylates
        and activates PDHK1.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation (UniProt SubCell mapping) of mitochondrial matrix
      localization, matching the experimentally documented hypoxia/oncogene-induced
      mitochondrial translocation of PGK1.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: mitochondrial translocation of PGK1
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic annotation of cytosolic localization, consistent with the
      core glycolytic compartment.
    action: ACCEPT
    reason: The cytosol is the principal, core subcellular location of PGK1, agreeing
      with direct experimental evidence.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic annotation (InterPro/UniPathway) of involvement in glycolysis.
    action: ACCEPT
    reason: Consistent with the core glycolytic role of PGK1; the pathway mapping is
      correct.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'PATHWAY: Carbohydrate degradation; glycolysis'
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: Electronic (RHEA:17989) annotation of protein serine kinase activity,
      corresponding to the documented moonlighting phosphorylation of PDHK1.
    action: KEEP_AS_NON_CORE
    reason: This reflects a real but context-specific, non-core moonlighting activity
      of mitochondria-translocated PGK1, distinct from its principal glycolytic role.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: Mitochondrial PGK1, acting as a protein kinase, phosphorylates
        and activates PDHK1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20392205
  qualifier: enables
  review:
    summary: IntAct-curated interaction of PGK1 with GAPDH (P04406), captured only as
      the uninformative generic term protein binding.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:20392205
      supporting_text: Loose interaction between glyceraldehyde-3-phosphate
        dehydrogenase and phosphoglycerate kinase revealed by fluorescence resonance
        energy transfer-fluorescence lifetime imaging microscopy in living cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20849852
  qualifier: enables
  review:
    summary: IntAct-curated interaction of PGK1 with PCNA (P12004), captured only as
      the generic term protein binding.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:20849852
      supporting_text: Proliferating cell nuclear antigen in the cytoplasm interacts
        with components of glycolysis and cancer.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26030842
  qualifier: enables
  review:
    summary: IntAct-curated interaction of PGK1 with PCNA (P12004) from a bimolecular
      complementation screen, captured only as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding provides no informative molecular function for PGK1.
    supported_by:
    - reference_id: PMID:26030842
      supporting_text: A fluorescent bimolecular complementation screen reveals MAF1,
        RNF7 and SETD3 as PCNA-associated proteins in human cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26356530
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:26356530
      supporting_text: HDAC3 deacetylates and activates PGK1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: High-throughput interactome interaction with PGK2 (P07205), captured only
      as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative; PGK2 is the closely related testis
      paralog and this high-throughput interaction conveys no specific function.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: Architecture of the human interactome defines protein
        communities and disease networks.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  qualifier: enables
  review:
    summary: Kinase interaction-network interaction with NEK7 (Q8TDX7), captured only
      as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative for molecular function.
    supported_by:
    - reference_id: PMID:32707033
      supporting_text: Kinase Interaction Network Expands Functional and Disease Roles
        of Human Kinases.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Proteome-scale interactome interaction with PGK2 (P07205), captured only
      as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative; a high-throughput paralog
      interaction with no specified function.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of
        the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Endogenous-tagging (OpenCell) interaction with PGK2 (P07205), captured
      only as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative for molecular function.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: 'OpenCell: Endogenous tagging for the cartography of human
        cellular organization.'
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl orthology (from mouse P09411) electronic transfer of
      involvement in gluconeogenesis.
    action: ACCEPT
    reason: Consistent with the reversible PGK reaction being used in the
      gluconeogenic direction; the orthology transfer is appropriate.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14803
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ensembl orthology (from mouse P09411) electronic transfer of
      transmembrane transporter binding. There is no strong human evidence for a
      specific transporter-binding function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'SIMILARITY: Belongs to the phosphoglycerate kinase family.'
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic annotation (ARBA) of involvement in canonical glycolysis, a
      more specific child of glycolytic process.
    action: ACCEPT
    reason: Canonical glycolysis (Embden-Meyerhof-Parnas) is precisely the pathway in
      which PGK1 operates; this is a correct, appropriately specific core BP term.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from
        D-glyceraldehyde 3-phosphate: step 2/5.'
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70263
  qualifier: involved_in
  review:
    summary: Reactome traceable-author-statement annotation of involvement in
      gluconeogenesis.
    action: ACCEPT
    reason: PGK1 is a Reactome-curated participant in the gluconeogenesis pathway (the
      reverse glycolytic direction); a legitimate core biological role.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14803
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70171
  qualifier: involved_in
  review:
    summary: Reactome traceable-author-statement annotation of involvement in
      canonical glycolysis.
    action: ACCEPT
    reason: PGK1 is a Reactome-curated participant in the glycolysis pathway; an
      appropriately specific core biological process.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from
        D-glyceraldehyde 3-phosphate: step 2/5.'
- term:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  evidence_type: EXP
  original_reference_id: PMID:1278465
  qualifier: enables
  review:
    summary: Experimental characterization of phosphoglycerate kinase activity from
      human tissue (spermatozoa), confirming the core enzymatic function.
    action: ACCEPT
    reason: Direct experimental evidence for phosphoglycerate kinase activity; this is
      the core molecular function of PGK1.
    supported_by:
    - reference_id: PMID:1278465
      supporting_text: We have confirmed the presence of a unique electrophoretic
        isoenzyme of phosphoglycerate kinase (PGK) in homogenate extracts of human
        sperm.
- term:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  evidence_type: EXP
  original_reference_id: PMID:5009693
  qualifier: enables
  review:
    summary: Experimental crystallization and characterization of the normal human
      phosphoglycerate kinase enzyme, establishing the core catalytic function.
    action: ACCEPT
    reason: Direct experimental characterization of the purified enzyme supports the
      core phosphoglycerate kinase molecular function.
    supported_by:
    - reference_id: PMID:5009693
      supporting_text: Human phosphoglycerate kinase. I. Crystallization and
        characterization of normal enzyme.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9975250
  qualifier: enables
  review:
    summary: Reactome traceable-author-statement annotation of the moonlighting
      protein serine/threonine kinase activity (PGK1 phosphorylating AKT1S1/PRAS40).
    action: KEEP_AS_NON_CORE
    reason: Reflects the documented but context-specific moonlighting protein kinase
      activity of PGK1, not its core glycolytic function.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: Mitochondrial PGK1, acting as a protein kinase, phosphorylates
        and activates PDHK1.
- term:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  evidence_type: EXP
  original_reference_id: PMID:30323285
  qualifier: enables
  review:
    summary: Experimental study characterizing PGK1 as a glycolytic enzyme and
      identifying a small-molecule inhibitor (CBR-470-0), confirming its catalytic
      activity.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:30323285
      supporting_text: we identify a small-molecule inhibitor of the glycolytic enzyme
        PGK1, and reveal
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:26942675
  qualifier: enables
  review:
    summary: Experimental demonstration that mitochondria-translocated PGK1 acts as a
      protein kinase, phosphorylating PDHK1 on a serine/threonine residue.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: 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.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:26942675
  qualifier: enables
  review:
    summary: Direct assay demonstrating PGK1 protein serine/threonine kinase activity
      toward PDHK1 (T338).
    action: KEEP_AS_NON_CORE
    reason: Experimentally validated moonlighting protein kinase activity of
      mitochondrial PGK1; non-core relative to the principal glycolytic function.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: protein kinase to phosphorylate pyruvate dehydrogenase kinase 1
        (PDHK1) at T338
- term:
    id: GO:0160218
    label: negative regulation of pyruvate decarboxylation to acetyl-CoA
  evidence_type: IDA
  original_reference_id: PMID:26942675
  qualifier: involved_in
  review:
    summary: Direct evidence that PGK1-mediated phosphorylation/activation of PDHK1
      leads to inhibition of the pyruvate dehydrogenase complex, suppressing pyruvate
      decarboxylation to acetyl-CoA.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: which activates PDHK1 to phosphorylate and inhibit the pyruvate
        dehydrogenase (PDH) complex. This reduces mitochondrial pyruvate utilization
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26942675
  qualifier: enables
  review:
    summary: Curated interaction of PGK1 with MAPK1/ERK2 (P28482), captured only as
      generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: Interacts with kinase MAPK1/ERK2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26942675
  qualifier: enables
  review:
    summary: Curated interaction of PGK1 with peptidyl-prolyl isomerase PIN1
      (Q13526), captured only as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative for molecular function; the PIN1
      interaction is regulatory (targeting to mitochondrion) rather than a specific
      function term.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: peptidyl-prolyl cis-trans isomerase PIN1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26942675
  qualifier: enables
  review:
    summary: Curated interaction of PGK1 with pyruvate dehydrogenase kinase PDK1/PDHK1
      (Q15118), captured only as generic protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative; the functionally relevant content
      (PGK1 phosphorylating PDHK1) is already captured by the kinase and pyruvate
      regulation annotations.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: Interacts with pyruvate dehydrogenase kinase PDK1
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:26942675
  qualifier: located_in
  review:
    summary: Direct evidence that PGK1 is translocated to the mitochondrion under
      hypoxic/oncogenic conditions where it acts as a protein kinase.
    action: KEEP_AS_NON_CORE
    reason: Mitochondrial matrix localization is condition-dependent and tied to the
      moonlighting kinase role, not the core cytosolic glycolytic location.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: mitochondrial translocation of PGK1
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:36849569
  qualifier: located_in
  review:
    summary: Direct evidence that the mitochondrial circRNA mcPGK1 promotes import of
      PGK1 into mitochondria in liver tumour-initiating cells.
    action: KEEP_AS_NON_CORE
    reason: Confirms condition-dependent mitochondrial localization of PGK1, part of
      its moonlighting function; not the core cytosolic location.
    supported_by:
    - reference_id: PMID:36849569
      supporting_text: mcPGK1 promotes the mitochondrial localization of PGK1
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:36849569
  qualifier: located_in
  review:
    summary: Direct evidence that PGK1 is present in the cytosol (with a fraction
      redistributing to mitochondria).
    action: ACCEPT
    reason: The cytosol is the principal, core subcellular location of PGK1 where it
      performs glycolysis.
    supported_by:
    - reference_id: PMID:36849569
      supporting_text: mcPGK1 was predominantly localized in mitochondria and also
        detectable in cytoplasm
- term:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  evidence_type: IMP
  original_reference_id: PMID:7391028
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: A loss-of-function disease variant that reduces enzymatic activity
      provides genetic (IMP) support for the core phosphoglycerate kinase function.
    supported_by:
    - reference_id: PMID:7391028
      supporting_text: A single amino acid substitution (Asp leads to Asn) in a
        phosphoglycerate kinase variant (PGK München) associated with enzyme
        deficiency.
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IMP
  original_reference_id: PMID:7391028
  qualifier: involved_in
  review:
    summary: The PGK Munchen deficiency variant impairs glycolytic flux, supporting
      PGK1's involvement in the glycolytic process.
    action: ACCEPT
    reason: Genetic evidence from an enzyme-deficiency variant supports the core
      biological role of PGK1 in glycolysis.
    supported_by:
    - reference_id: PMID:7391028
      supporting_text: phosphoglycerate kinase variant (PGK München) associated with
        enzyme deficiency
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IDA
  original_reference_id: PMID:11130727
  qualifier: located_in
  review:
    summary: PGK1 is secreted by tumour cells into the extracellular milieu, where it
      acts as a plasmin/disulfide reductase.
    action: KEEP_AS_NON_CORE
    reason: A documented moonlighting extracellular localization tied to the secreted
      disulfide-reductase/angiogenesis function; not the core cytosolic glycolytic
      location.
    supported_by:
    - reference_id: PMID:11130727
      supporting_text: phosphoglycerate kinase not only functions in glycolysis but is
        secreted by tumour cells and participates in the angiogenic process as a
        disulphide reductase
- term:
    id: GO:0016525
    label: negative regulation of angiogenesis
  evidence_type: IMP
  original_reference_id: PMID:11130727
  qualifier: involved_in
  review:
    summary: Administration of PGK1 to tumour-bearing mice increased plasma
      angiostatin and reduced tumour vascularity, implicating secreted PGK1 in
      negative regulation of angiogenesis.
    action: KEEP_AS_NON_CORE
    reason: A moonlighting function of secreted PGK1 (via angiostatin release), not
      the core glycolytic role.
    supported_by:
    - reference_id: PMID:11130727
      supporting_text: 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.
- term:
    id: GO:0031639
    label: plasminogen activation
  evidence_type: IMP
  original_reference_id: PMID:11130727
  qualifier: involved_in
  review:
    summary: Secreted PGK1 reduces disulfide bonds in plasmin, initiating proteolytic
      cleavage and angiostatin release.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:11130727
      supporting_text: Reduction of plasmin initiates proteolytic cleavage in the
        kringle 5 domain and release of the tumour blood vessel inhibitor angiostatin.
- term:
    id: GO:0047134
    label: protein-disulfide reductase [NAD(P)H] activity
  evidence_type: IMP
  original_reference_id: PMID:11130727
  qualifier: enables
  review:
    summary: PGK1 secreted from fibrosarcoma cells was identified as the plasmin
      reductase, exhibiting protein-disulfide reductase activity in the extracellular
      space.
    action: KEEP_AS_NON_CORE
    reason: A well-documented moonlighting molecular function of secreted PGK1,
      distinct from its core phosphoglycerate kinase activity.
    supported_by:
    - reference_id: PMID:11130727
      supporting_text: the plasmin reductase isolated from conditioned medium of
        fibrosarcoma cells is the glycolytic enzyme phosphoglycerate kinase
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: IDA
  original_reference_id: PMID:11130727
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:26942675
      supporting_text: hypoxia, EGFR activation, and expression of K-Ras G12V and
        B-Raf V600E induce mitochondrial translocation of phosphoglycerate kinase 1
        (PGK1)
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:11487543
  qualifier: located_in
  review:
    summary: High-throughput proteomic detection of PGK1 in extracellular
      exosome-like vesicles.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:11487543
      supporting_text: Intestinal epithelial cells secrete exosome-like vesicles.
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: IDA
  original_reference_id: PMID:25204797
  qualifier: located_in
  review:
    summary: PGK1 was detected by SILAC mass spectrometry in the detergent-resistant
      (membrane raft) fraction of endothelial cells.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:25204797
      supporting_text: shRNA against flotillin-1 reduced the abundance of the
        structural caveolae proteins caveolin-1, cavin-1 and cavin-2 in the
        detergent-resistant fraction.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: High-throughput proteomic detection of PGK1 in exosomes from prostatic
      secretions.
    action: KEEP_AS_NON_CORE
    reason: Reflects incidental presence of an abundant cytosolic protein in exosome
      proteomes rather than the core function or location.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: In-depth proteomic analyses of exosomes isolated from expressed
        prostatic secretions in urine.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput proteomic detection of PGK1 in an NK-cell membrane
      proteome.
    action: MARK_AS_OVER_ANNOTATED
    reason: A generic membrane localization from a membrane-proteome dataset for an
      abundant cytosolic protein; uninformative and not part of the core function.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: Defining the membrane proteome of NK cells.
- term:
    id: GO:0030855
    label: epithelial cell differentiation
  evidence_type: IEP
  original_reference_id: PMID:21492153
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:21492153
      supporting_text: Analysis of proteomic changes induced upon cellular
        differentiation of the human intestinal cell line Caco-2.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19199708
  qualifier: located_in
  review:
    summary: High-throughput proteomic detection of PGK1 in parotid gland exosomes.
    action: KEEP_AS_NON_CORE
    reason: Reflects incidental exosomal presence of an abundant cytosolic protein,
      not the core function or location.
    supported_by:
    - reference_id: PMID:19199708
      supporting_text: Proteomic analysis of human parotid gland exosomes by
        multidimensional protein identification technology (MudPIT).
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: High-throughput proteomic detection of PGK1 in B-cell exosomes.
    action: KEEP_AS_NON_CORE
    reason: Reflects incidental exosomal presence of an abundant cytosolic protein,
      not the core function or location.
    supported_by:
    - reference_id: PMID:20458337
      supporting_text: MHC class II-associated proteins in B-cell exosomes and
        potential functional implications for exosome biogenesis.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70486
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement annotation of cytosolic localization
      (PGK complexes phosphorylating 3PG).
    action: ACCEPT
    reason: The cytosol is the core subcellular location where PGK1 performs
      glycolysis.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71850
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement annotation of cytosolic localization
      (PGK complexes dephosphorylating 1,3BPG, the gluconeogenic direction).
    action: ACCEPT
    reason: The cytosol is the core subcellular location of PGK1 activity.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9636658
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement annotation of cytosolic localization
      (in the context of EsxA binding PGK1).
    action: ACCEPT
    reason: The cytosol is the core subcellular location of PGK1.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9975250
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement annotation of cytosolic localization
      (in the context of PGK1 phosphorylating AKT1S1).
    action: ACCEPT
    reason: The cytosol is the core subcellular location of PGK1.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Sequence-similarity annotation (from UniProtKB:P41759) of the core
      phosphoglycerate kinase activity.
    action: ACCEPT
    reason: Consistent with, and redundant to, the strong experimental support for
      the core catalytic function.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: EC=2.7.2.3
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Sequence-similarity annotation (from UniProtKB:P00559) of ATP binding,
      the nucleotide substrate/product of the reaction.
    action: ACCEPT
    reason: ATP binding is intrinsic to the phosphoglycerate kinase reaction and is
      supported by kinetic and structural data; supports the core catalytic function.
    supported_by:
    - reference_id: file:human/PGK1/PGK1-uniprot.txt
      supporting_text: KM=0.56 mM for ATP
core_functions:
- description: Catalyzes the reversible, Mg2+-dependent transfer of a phosphate
    between 1,3-bisphosphoglycerate + ADP and 3-phosphoglycerate + ATP, the first
    ATP-generating step of the glycolytic payoff phase (and the reverse step in
    gluconeogenesis), acting in the cytosol.
  molecular_function:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  directly_involved_in:
  - id: GO:0006096
    label: glycolytic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:26942675
    supporting_text: 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
  - reference_id: file:human/PGK1/PGK1-uniprot.txt
    supporting_text: 'PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from
      D-glyceraldehyde 3-phosphate: step 2/5.'
- description: In the gluconeogenic direction, uses the reverse phosphoglycerate
    kinase reaction (3-phosphoglycerate + ATP -> 1,3-bisphosphoglycerate + ADP) to
    contribute to glucose biosynthesis in the cytosol.
  molecular_function:
    id: GO:0004618
    label: phosphoglycerate kinase activity
  directly_involved_in:
  - id: GO:0006094
    label: gluconeogenesis
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/PGK1/PGK1-uniprot.txt
    supporting_text: PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14803
references:
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/PGK1/PGK1-uniprot.txt
  title: UniProtKB entry P00558 (PGK1_HUMAN)
  findings: []
- id: PMID:11130727
  title: Phosphoglycerate kinase acts in tumour angiogenesis as a disulphide reductase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Establishes the secreted disulfide-reductase
      moonlighting function (plasmin reduction -> angiostatin -> anti-angiogenesis).
      Abstract fully supports the extracellular, disulfide reductase, angiogenesis
      and plasminogen annotations.
- id: PMID:11487543
  title: Intestinal epithelial cells secrete exosome-like vesicles.
  findings: []
- id: PMID:1278465
  title: Characterization of phosphoglycerate kinase from human spermatozoa.
  findings: []
- id: PMID:19199708
  title: Proteomic analysis of human parotid gland exosomes by multidimensional protein
    identification technology (MudPIT).
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:20392205
  title: Loose interaction between glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate
    kinase revealed by fluorescence resonance energy transfer-fluorescence lifetime
    imaging microscopy in living cells.
  findings: []
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
- id: PMID:20849852
  title: Proliferating cell nuclear antigen in the cytoplasm interacts with components
    of glycolysis and cancer.
  findings: []
- id: PMID:21492153
  title: Analysis of proteomic changes induced upon cellular differentiation of the
    human intestinal cell line Caco-2.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
- id: PMID:25204797
  title: Flotillin-1 facilitates toll-like receptor 3 signaling in human endothelial
    cells.
  findings: []
- id: PMID:26030842
  title: A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3
    as PCNA-associated proteins in human cells.
  findings: []
- id: PMID:26356530
  title: Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation
    of PGK1.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified. Full text shows HDAC3 directly deacetylates PGK1
      at K220 to activate it; supports a regulatory interaction but the GOA annotation
      only captures generic protein binding.
- id: PMID:26942675
  title: Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate
    Glycolysis and the TCA Cycle in Tumorigenesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Definitive study of the PGK1 moonlighting protein
      kinase activity (phosphorylates PDHK1 T338), mitochondrial translocation, and
      the resulting suppression of pyruvate oxidation. Full text also states the core
      glycolytic reaction verbatim.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:30323285
  title: A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2
    signalling.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Identifies a PGK1 small-molecule inhibitor and
      confirms PGK1 as the glycolytic enzyme (EC 2.7.2.3); supports the core catalytic
      activity annotation.
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human
    Kinases.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36849569
  title: mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming
    and self-renewal of liver TICs.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Shows mitochondrial circRNA mcPGK1 drives PGK1
      import into mitochondria in liver tumour-initiating cells; supports the
      condition-dependent mitochondrial and cytosolic localization annotations.
- id: PMID:5009693
  title: Human phosphoglycerate kinase. I. Crystallization and characterization of
    normal enzyme.
  findings: []
- id: PMID:7391028
  title: A single amino acid substitution (Asp leads to Asn) in a phosphoglycerate
    kinase variant (PGK München) associated with enzyme deficiency.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. PGK Munchen (Asp268Asn) deficiency variant with
      reduced enzyme activity; genetic (IMP) support for the core phosphoglycerate
      kinase function and glycolytic role.
- id: Reactome:R-HSA-70171
  title: Glycolysis
  findings: []
- id: Reactome:R-HSA-70263
  title: Gluconeogenesis
  findings: []
- id: Reactome:R-HSA-70486
  title: PGK complexes (PGK1,2) phosphorylate 3PG to form 1,3BPG
  findings: []
- id: Reactome:R-HSA-71850
  title: PGK complexes dephosphorylate 1,3BPG
  findings: []
- id: Reactome:R-HSA-9636658
  title: EsxA binds PGK1
  findings: []
- id: Reactome:R-HSA-9975250
  title: PGK1 phosphorylates AKT1S1
  findings: []

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the reversible, Mg2+-dependent transfer of a phosphate between 1,3-bisphosphoglycerate + ADP and 3-phosphoglycerate + ATP, the first ATP-generating step of the glycolytic payoff phase (and the reverse step in gluconeogenesis), acting in the cytosol.

In the gluconeogenic direction, uses the reverse phosphoglycerate kinase reaction (3-phosphoglycerate + ATP -> 1,3-bisphosphoglycerate + ADP) to contribute to glucose biosynthesis in the cytosol.

References

📚 Additional Documentation

Notes

PGK1 (human) review notes

Core function

Moonlighting / non-core functions

PPI / protein binding (bare GO:0005515)

Localization (proteomics / HDA)

Disease

Wrong / to-remove

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