Phosphoglucomutase-1 (PGM1; EC 5.4.2.2) is the major human phosphoglucomutase, a cytosolic Mg2+-dependent enzyme that catalyzes the reversible interconversion of alpha-D-glucose 1-phosphate and alpha-D-glucose 6-phosphate. Catalysis proceeds via an alpha-D-glucose 1,6-bisphosphate intermediate and a catalytic phosphoserine (Ser117), with the bound Mg2+ ion coordinated by Ser117 and three active-site aspartates. PGM1 sits at the junction of glycogen metabolism and glycolysis/gluconeogenesis. During glycogenolysis it converts the glucose-1-phosphate released by glycogen phosphorylase into glucose-6-phosphate for glycolysis (or, in liver after glucose-6-phosphatase, for blood glucose), and it runs in reverse to supply glucose-1-phosphate for glycogen synthesis. Its products also feed the nucleotide-sugar (UDP-glucose/UDP-galactose, Leloir), galactose, and pentose-phosphate pathways. The enzyme is a monomer of 562 residues belonging to the alpha-D-phosphohexomutase superfamily. Loss-of-function variants cause PGM1 deficiency (PGM1-CDG; congenital disorder of glycosylation type It / glycogen storage disease type XIV), a mixed glycogenosis and glycosylation disorder featuring cleft palate, hepatopathy, hypoglycemia, dilated cardiomyopathy, exercise intolerance, and abnormal transferrin glycosylation, and it is notably responsive to galactose supplementation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004614 phosphoglucomutase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the diagnostic phosphoglucomutase molecular function to PGM1. This is the well-established, experimentally confirmed core catalytic activity of the enzyme and is at the correct level of specificity. Reason: The core molecular function is directly demonstrated experimentally (IDA/EXP, PMID:25288802, PMID:15378030) and the IBA call is consistent with the entire phosphohexomutase family. This is a core function of PGM1. Supporting Evidence: PMID:26972339 It catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic assignment of PGM1 activity to the cytosol, consistent with the cytoplasmic localization of the enzyme. Reason: PGM1 is a soluble cytoplasmic enzyme; the cytosol is where its metabolic reaction takes place. Supported by direct immunofluorescence (IDA, HPA) and the UniProt subcellular location. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm |
| GO:0005975 carbohydrate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic assignment placing PGM1 in carbohydrate metabolism, the broad process encompassing its role in interconverting glucose phosphates. Reason: Correct but general. It accurately captures PGM1's participation in carbohydrate metabolism; more specific processes (glucose metabolic process, glycogen metabolism, glycolysis/gluconeogenesis) are separately annotated. Retained as a broad, non-core parent term. Supporting Evidence: PMID:26972339 It catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic assignment of magnesium ion binding, the catalytic cofactor of PGM1. Reason: PGM1 binds one Mg2+ per subunit as an essential catalytic cofactor; this is directly confirmed by crystallography (IDA, PMID:26972339) and the IEA mapping is correct. Supporting Evidence: PMID:26972339 Mg2+ serves as an electron-withdrawing group to facilitate phosphoryl transfer from phosphoserine 117 |
| GO:0004614 phosphoglucomutase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (multi-method IEA, incl. RHEA:23536/EC:5.4.2.2 mapping) assignment of phosphoglucomutase activity to PGM1. Reason: Redundant with, and confirmed by, the experimental IDA/EXP annotations for the same term. The RHEA/EC mapping is correct for this enzyme. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt Catalyzes the reversible isomerization of alpha-D-glucose 1- |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic assignment of cytoplasmic localization from the UniProt subcellular-location vocabulary. Reason: Consistent with the well-supported cytosolic localization of PGM1; a broader parent of cytosol. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic assignment of carbohydrate metabolic process. Reason: Redundant with the IBA annotation for the same term; correct but general parent process. Retained as non-core broad context. Supporting Evidence: PMID:26972339 It catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate |
| GO:0016868 intramolecular phosphotransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic assignment of the parent molecular-function class (intramolecular phosphotransferase) that subsumes phosphoglucomutase activity. Reason: This is the correct broad parent of GO:0004614 phosphoglucomutase activity (the reaction proceeds via intramolecular phosphoryl transfer through a glucose-1,6-bisphosphate intermediate). Accurate but redundant with the more specific phosphoglucomutase term; kept as a non-core general term. Supporting Evidence: PMID:26972339 The reaction entails two consecutive phosphoryl transfers and proceeds via a bisphosphorylated intermediate |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | MARK AS OVER ANNOTATED | Summary: IntAct-curated protein-protein interaction (with TINF2, UniProtKB:Q9BSI4) captured by a genome-wide split-YFP fluorescence-complementation screen for telomere-signaling regulators. Reason: Bare "protein binding" (GO:0005515) is uninformative about PGM1's molecular function. The interaction derives from a large-scale telomere-interactome screen that identified ~300 candidate binders and is not established as a functional partnership relevant to PGM1's enzymatic role; per curation policy this is marked as over-annotated rather than removed (it reflects a real IPI experiment). Supporting Evidence: PMID:21044950 we identified over 300 proteins that associated with the six core telomeric proteins |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence (Human Protein Atlas) localization of PGM1 to the cytosol. Reason: Direct experimental evidence for the primary subcellular location of this soluble metabolic enzyme; a core cellular-component annotation. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm |
| GO:0004614 phosphoglucomutase activity | EXP PMID:15378030 Regulation of phosphoglucomutase 1 phosphorylation and activ... | ACCEPT | Summary: Experimental demonstration of PGM1 catalytic (phosphoglucomutase) activity, whose regulation by PAK1-mediated phosphorylation is characterized in this study. Reason: Direct experimental support for the core catalytic function; PAK1 phosphorylation of PGM1 was shown to enhance its enzymatic activity, confirming the activity being measured. Supporting Evidence: PMID:15378030 selectively on threonine 466 significantly increased PGM enzymatic |
| GO:0004614 phosphoglucomutase activity | IDA PMID:30982613 The Metabolic Map into the Pathomechanism and Treatment of P... | ACCEPT | Summary: Direct assignment of phosphoglucomutase activity in the study mapping the metabolic pathomechanism and galactose treatment of PGM1-CDG. Reason: Reinforces the core catalytic function; the paper explicitly describes PGM1 as the enzyme that interconverts glucose-6-P and glucose-1-P and studies the metabolic consequences of its deficiency. Supporting Evidence: PMID:30982613 encodes the metabolic enzyme that interconverts |
| GO:0033499 beta-D-galactose catabolic process via UDP-galactose, Leloir pathway | IMP PMID:30982613 The Metabolic Map into the Pathomechanism and Treatment of P... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence linking PGM1 to the Leloir/UDP-galactose route, based on the galactose-responsive metabolic rewiring seen in PGM1-CDG fibroblasts. Reason: PGM1's products (glucose-1-P/glucose-6-P) connect to the nucleotide-sugar and galactose (Leloir) pathways, and galactose treatment replenishes galactose-1-P, UDP-glucose, and UDP-galactose in PGM1-CDG. This is a real, pathway-adjacent role but peripheral to PGM1's core glucose-phosphate interconversion function, so it is retained as non-core. Supporting Evidence: PMID:30982613 UDP-glucose and UDP-galactose, the nucleotide sugars |
| GO:0005980 glycogen catabolic process | IMP PMID:28882528 Impaired glycogen breakdown and synthesis in phosphoglucomut... | ACCEPT | Summary: Mutant-phenotype evidence that PGM1 deficiency blocks muscle glycogenolysis, placing PGM1 within glycogen catabolism. Reason: Well supported and biologically central; in glycogenolysis PGM1 converts the glucose-1-phosphate released by glycogen phosphorylase into glucose-6-phosphate. Severe PGM1 loss causes blocked muscle glycogenolysis mimicking McArdle disease, directly demonstrating this role. Supporting Evidence: PMID:28882528 severe loss of PGM1 activity causes blocked muscle |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798745 | KEEP AS NON CORE | Summary: Reactome-derived localization arising from PGM1's presence in neutrophil tertiary (secretory) granules that are exocytosed during degranulation. Reason: A secondary/extracellular localization reflecting the release of granule contents during neutrophil degranulation; not the site of PGM1's cytosolic catalytic function. Retained as non-core rather than removed because it derives from curated Reactome pathway data. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: Reactome-derived extracellular localization from exocytosis of ficolin-rich (granule) lumen proteins during neutrophil degranulation. Reason: As above, a secondary localization tied to neutrophil granule exocytosis rather than PGM1's core cytosolic metabolic role; kept as non-core. |
| GO:1904724 tertiary granule lumen | TAS Reactome:R-HSA-6798745 | KEEP AS NON CORE | Summary: Reactome localization of PGM1 to the tertiary (secretory) granule lumen of neutrophils. Reason: Reflects PGM1's presence in neutrophil secretory granules (degranulation pathway), a peripheral localization distinct from its principal cytosolic metabolic function; retained as non-core. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: Reactome localization of PGM1 to the ficolin-1-rich granule lumen of neutrophils. Reason: Peripheral granule localization from the neutrophil-degranulation pathway, not PGM1's core cytosolic site of action; retained as non-core. |
| GO:0000287 magnesium ion binding | IDA PMID:26972339 Induced Structural Disorder as a Molecular Mechanism for Enz... | ACCEPT | Summary: Direct (crystallographic) evidence that PGM1 binds one Mg2+ ion per subunit as an essential catalytic cofactor. Reason: Crystal structures show the Mg2+ ion coordinated in octahedral geometry by Ser117 and three aspartates, functioning as an electron-withdrawing group to facilitate phosphoryl transfer. Core cofactor of the enzyme. Supporting Evidence: PMID:26972339 Mg2+ serves as an electron-withdrawing group to facilitate phosphoryl transfer from phosphoserine 117 |
| GO:0004614 phosphoglucomutase activity | IDA PMID:25288802 Compromised catalysis and potential folding defects in in vi... | ACCEPT | Summary: Direct enzymatic characterization of recombinant wild-type PGM1 (and disease variants), confirming phosphoglucomutase catalytic activity and its kinetic parameters. Reason: In vitro biochemical characterization provides direct experimental support for the core catalytic function, with variants showing reduced kcat/Km; a defining core function of PGM1. Supporting Evidence: PMID:25288802 central role of the enzyme in glucose metabolism |
| GO:0006006 glucose metabolic process | IDA PMID:25288802 Compromised catalysis and potential folding defects in in vi... | ACCEPT | Summary: Direct evidence placing PGM1 within glucose metabolism, reflecting its central role in interconverting glucose phosphates. Reason: PGM1's reaction is a central node of glucose metabolism (breakdown and synthesis of glucose); this is a core biological-process annotation supported by the biochemical characterization of the enzyme and its deficiency phenotypes. Supporting Evidence: PMID:25288802 central role of the enzyme in glucose metabolism |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5609939 | ACCEPT | Summary: Reactome (curated) cytosolic localization of PGM1, in the reaction where defective PGM1 fails to isomerise G6P to G1P. Reason: Consistent with the well-established cytosolic localization; the reaction it participates in is cytosolic. A core cellular-component annotation. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: High-throughput mass-spectrometry detection of PGM1 in exosomes isolated from expressed prostatic secretions in urine. Reason: A proteomic detection of the abundant cytosolic enzyme in secreted exosomes; represents a secondary localization rather than PGM1's functional site. Retained as non-core. Supporting Evidence: PMID:23533145 exosome preparations were characterized by a shotgun proteomics procedure |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of PGM1 among proteins profiled in human urinary exosomes. Reason: As above, a mass-spectrometry-based detection in exosomes; a common finding for abundant cytosolic enzymes and peripheral to PGM1's core function. Retained as non-core. Supporting Evidence: PMID:19056867 profile the proteome of human urinary exosomes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9638125 | ACCEPT | Summary: Reactome (curated) cytosolic localization of PGM1 in the reaction where PGM1:Mg2+ isomerises G1P to G6P. Reason: Correct core localization; the phosphoglucomutase reaction (G1P to G6P) is cytosolic and requires the bound Mg2+ cofactor. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9638127 | ACCEPT | Summary: Reactome (curated) cytosolic localization of PGM1 in the reaction where PGM1:Mg2+ isomerises G6P to G1P (reverse direction). Reason: Correct core localization; the reverse phosphoglucomutase reaction (G6P to G1P) is likewise cytosolic and Mg2+-dependent. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm |
| GO:0004614 phosphoglucomutase activity | IDA PMID:1530890 Phosphoglucomutase 1: complete human and rabbit mRNA sequenc... | ACCEPT | Summary: Direct assignment of phosphoglucomutase activity to the human PGM1 gene product characterized in the cDNA cloning study. Reason: Establishes the identity of the cloned human PGM1 as the polymorphic phosphoglucomutase (EC 5.4.2.2); supports the core catalytic function. Supporting Evidence: PMID:1530890 highly polymorphic human enzyme |
| GO:0005737 cytoplasm | NAS PMID:1530890 Phosphoglucomutase 1: complete human and rabbit mRNA sequenc... | ACCEPT | Summary: Non-traceable author statement assigning cytoplasmic localization to PGM1 in the cloning/mapping study. Reason: Consistent with the well-established cytoplasmic/cytosolic localization of PGM1 (corroborated by IDA immunofluorescence and UniProt); accepted as a broad, correct localization. Supporting Evidence: file:human/PGM1/PGM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm |
| GO:0006006 glucose metabolic process | NAS PMID:1530890 Phosphoglucomutase 1: complete human and rabbit mRNA sequenc... | ACCEPT | Summary: Non-traceable author statement placing PGM1 in glucose metabolism. Reason: Redundant with the IDA glucose-metabolic-process annotation and consistent with PGM1's central metabolic role; a correct core biological process. Supporting Evidence: PMID:25288802 central role of the enzyme in glucose metabolism |
| GO:0004614 phosphoglucomutase activity | TAS PMID:8257433 Phosphoglucomutase 1: a gene with two promoters and a duplic... | ACCEPT | Summary: Traceable author statement (gene-structure study) affirming PGM1 as the phosphoglucomutase enzyme. Reason: The study explicitly notes PGM1's central role in glycolysis and gluconeogenesis; supports the core catalytic function. Supporting Evidence: PMID:8257433 central role in glycolysis and gluconeogenesis |
| GO:0006094 gluconeogenesis | TAS PMID:8257433 Phosphoglucomutase 1: a gene with two promoters and a duplic... | ACCEPT | Summary: Traceable author statement placing PGM1 in gluconeogenesis. Reason: In gluconeogenesis/glycogen synthesis PGM1 runs in the G6P to G1P direction; the enzyme participates in glucose synthesis. A genuine biological role supported by the literature, retained as a core metabolic process. Supporting Evidence: PMID:8257433 central role in glycolysis and gluconeogenesis |
| GO:0006096 glycolytic process | TAS PMID:8257433 Phosphoglucomutase 1: a gene with two promoters and a duplic... | KEEP AS NON CORE | Summary: Traceable author statement placing PGM1 in glycolysis. Reason: PGM1 feeds glycolysis by producing glucose-6-phosphate from the glucose-1-phosphate liberated during glycogenolysis, but it is not a core enzyme of the canonical glycolytic pathway itself (glucose to pyruvate). It is best regarded as an upstream/adjacent contributor, so it is kept as non-core. Supporting Evidence: PMID:8257433 central role in glycolysis and gluconeogenesis |
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