PGAM2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004619 phosphoglycerate mutase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the core catalytic activity of PGAM2: reversible interconversion of 3- and 2-phosphoglycerate. This is the defining molecular function of the muscle phosphoglycerate mutase subunit and is strongly corroborated by experimental and UniProt evidence. Reason: Core molecular function, correct at the right level of specificity, and consistent across independent evidence lines (IBA, EXP, IMP, ISS, IEA) and the UniProt catalytic-activity record (EC 5.4.2.11). Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment of the cytosol as the site of action. Phosphoglycerate mutase is a soluble cytosolic glycolytic enzyme, consistent with Reactome and UniProt. Reason: Correct subcellular location for a soluble glycolytic enzyme; agrees with Reactome TAS cytosol annotations and with the entire glycolytic pathway being cytosolic. Supporting Evidence: Reactome:R-HSA-71445 Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate
GO:0061621 canonical glycolysis	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment of PGAM2 to canonical glycolysis (the ATP-generating glucose-to-pyruvate route). PGAM catalyzes step 8 (3-PG to 2-PG) of the glycolytic payoff phase. Reason: Core biological process for the muscle glycolytic isoform, at an appropriate level of specificity; corroborated by the Reactome Glycolysis pathway and by the IMP glycolytic-process annotation. Supporting Evidence: Reactome:R-HSA-70171 The reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Root-level InterPro2GO mapping asserting generic catalytic activity. Not incorrect but entirely uninformative given the specific mutase activity is already annotated. Reason: "catalytic activity" is a top-level MF placeholder subsumed by the specific phosphoglycerate mutase activity annotation; it adds no functional information. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate
GO:0004082 bisphosphoglycerate mutase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic mapping (EC 5.4.2.4 / RHEA:17765) of the minor bisphosphoglycerate mutase side activity. UniProt records that the enzyme "can also catalyze the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate, but with a reduced activity." Reason: Genuine, documented secondary catalytic activity of the BPG-dependent PGAM subfamily; correctly captured, though it is the reduced-activity side reaction rather than the primary physiological function. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC 3-phospho-glyceroyl phosphate, but with a reduced activity.
GO:0004619 phosphoglycerate mutase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic mapping (EC 5.4.2.11 / RHEA:15901 / ARBA) of the core phosphoglycerate mutase activity. Duplicate of the core MF from an automated pipeline. Reason: Correct core molecular function; the automated EC/RHEA mapping agrees with the experimental and phylogenetic annotations. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate
GO:0006096 glycolytic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment to the glycolytic process. Correct core pathway for PGAM2, also supported experimentally by the deficiency phenotype (IMP). Reason: Core biological process; consistent with the IMP annotation from the muscle PGAM deficiency case and with the canonical-glycolysis annotations. Supporting Evidence: PMID:6262916 Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest
GO:0016868 intramolecular phosphotransferase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping to intramolecular phosphotransferase activity, the isomerase parent class (EC 5.4.2.-) that includes phosphoglycerate mutase. Correct but more general than the specific mutase term already annotated. Reason: Accurate parent-level molecular function; an IEA term is permitted to be broader than the specific mutase activity, and it correctly reflects the isomerase reaction chemistry (intramolecular phospho group transfer). Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: High-throughput AP-MS interactome (BioPlex 2.0) reporting a PGAM2-BPGM (P07738) co-complex. Bare "protein binding" is uninformative about molecular function. Reason: Per curation guidance, bare "protein binding" is not an informative molecular function and this is an interactome-screen IPI. The recurrent BPGM partner is biologically plausible (both enzymes act on 2,3-bisphosphoglycerate) but does not itself define a specific molecular function; retained (not removed) as an experimental IPI. Supporting Evidence: PMID:28514442 BioPlex 2.0 is the largest collection of human co-complex data assembled from a single pipeline to date
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Binary interactome map (HuRI, yeast two-hybrid) reporting PGAM2 interactions (e.g. BPGM, CLVS2, DYNC1LI1, KATNAL1). Bare "protein binding" is uninformative. Reason: Uninformative generic "protein binding" from a systematic binary-interactome screen; retained as an experimental IPI but not treated as a defining function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: High-throughput AP-MS interactome (BioPlex 3.0) again reporting a PGAM2-BPGM (P07738) association. Bare "protein binding" is uninformative. Reason: Generic "protein binding" from an interactome screen; consistent with the other BioPlex/HuRI evidence but non-specific; retained as an experimental IPI. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	ACCEPT	Summary: Self-interaction of PGAM2 (P15259-P15259) detected in the binary interactome map, consistent with the established homodimeric quaternary structure of phosphoglycerate mutase. Reason: Informative self-association annotation that matches the documented homodimer; UniProt SUBUNIT states "Homodimer" and Reactome describes the active enzyme as a dimer. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- SUBUNIT: Homodimer. Interacts with ENO1. {ECO:0000250\|UniProtKB:O70250,
GO:0005634 nucleus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Orthology-based (Ensembl Compara, from rat P16290) transfer of a nuclear localization. PGAM2 is a soluble cytosolic glycolytic enzyme; a nuclear location is not associated with any established nuclear function. Reason: Nuclear localization is not part of the core biology of this cytosolic enzyme; it derives from orthology transfer plus proteomic detection in sperm nuclei and likely reflects contamination/moonlighting rather than a functional nuclear role. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- SUBUNIT: Homodimer. Interacts with ENO1. {ECO:0000250\|UniProtKB:O70250,
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Orthology-based (Ensembl Compara, from mouse O70250) assignment of the cytosol as site of action. Correct core location for a glycolytic enzyme. Reason: Agrees with the IBA and Reactome TAS cytosol annotations; correct compartment for phosphoglycerate mutase activity. Supporting Evidence: Reactome:R-HSA-71445 Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate
GO:0006094 gluconeogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-based (Ensembl Compara) assignment to gluconeogenesis. The phosphoglycerate mutase reaction is reversible and is shared with the gluconeogenic direction, but physiological gluconeogenesis is confined to liver and kidney, which express PGAM1 rather than the muscle PGAM2 isoform. Reason: The reaction chemistry participates in gluconeogenesis, but the muscle isoform's core in-vivo role is glycolytic; muscle does not perform gluconeogenesis, so this is retained as a non-core, reaction-shared process rather than PGAM2's primary physiological function. Supporting Evidence: Reactome:R-HSA-70263 Gluconeogenesis is confined to cells of the liver and kidney
GO:0007283 spermatogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-based (Ensembl Compara, from rat P16290) transfer of a spermatogenesis role. Sperm rely heavily on glycolysis, but a direct role of the muscle PGAM2 isoform in spermatogenesis is not established in human. Reason: Speculative context transferred by orthology; not a core molecular/biological function of the human muscle isoform. Retained as non-core rather than removed, since it is a plausible tissue context for a glycolytic enzyme. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- TISSUE SPECIFICITY: Expressed in the heart and muscle. Not found in the
GO:0046689 response to mercury ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Orthology-based (Ensembl Compara, from rat P16290) transfer of a "response to mercury ion" process. The M subunit is mercury-inhibitable in vitro (historically used to distinguish M from BB isozymes), but this is an enzyme-property observation, not a biological response process of human PGAM2. Reason: "response to mercury ion" as a biological process is an orthology artifact and does not represent a core biological role of PGAM2; in-vitro Hg sensitivity of the catalytic His does not constitute a cellular mercury-response pathway. Supporting Evidence: PMID:6262916 Electrophoretic,
GO:0061621 canonical glycolysis	IEA GO_REF:0000107	ACCEPT	Summary: Orthology-based (Ensembl Compara, from mouse O70250) assignment to canonical glycolysis. Correct core process; duplicate of the IBA/TAS glycolysis annotations. Reason: Core glycolytic process for the muscle isoform, consistent with all other glycolysis evidence lines. Supporting Evidence: Reactome:R-HSA-70171 The reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert
GO:1990917 ooplasm	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-based (Ensembl Compara, from rat P16290) transfer of an ooplasm (oocyte cytoplasm) location. This is a tissue-context transfer; the compartment (cytoplasm) is consistent with a cytosolic enzyme, but the specific ooplasmic localization is not established for the human muscle isoform. Reason: Cytoplasmic location is consistent with PGAM2 biology, but "ooplasm" is an orthology-derived tissue-specific location not relevant to the muscle isoform's core role; retained as non-core rather than removed. Supporting Evidence: Reactome:R-HSA-71445 Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate
GO:0006094 gluconeogenesis	TAS Reactome:R-HSA-70263	KEEP AS NON CORE	Summary: Reactome pathway annotation placing the reversible phosphoglycerate mutase reaction within gluconeogenesis. The reaction is genuinely part of the gluconeogenic sequence (a reverse-of-glycolysis step). Reason: The PGAM reaction participates in the gluconeogenesis pathway as modeled by Reactome, so the annotation is not wrong; however gluconeogenesis is a liver/kidney process (PGAM1), so it is not the core physiological role of the muscle PGAM2 isoform. Retained as non-core. Supporting Evidence: Reactome:R-HSA-70263 Gluconeogenesis is confined to cells of the liver and kidney
GO:0061621 canonical glycolysis	TAS Reactome:R-HSA-70171	ACCEPT	Summary: Reactome pathway annotation placing PGAM within canonical glycolysis (the cytosolic glucose-to-pyruvate route). Core process for PGAM2. Reason: Authoritative pathway (TAS) annotation for the core glycolytic role; consistent with all other glycolysis evidence. Supporting Evidence: Reactome:R-HSA-70171 The reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert
GO:0004619 phosphoglycerate mutase activity	EXP PMID:4827367 Phosphoglycerate mutase isozyme marker for tissue differenti...	ACCEPT	Summary: Experimental annotation of phosphoglycerate mutase activity based on characterization of the human PGAM isozymes as tissue-differentiation markers (Omenn & Cheung 1974), which established the muscle (M) versus brain (B) subunit isozyme system. Reason: Experimental support for the core catalytic activity of the muscle phosphoglycerate mutase isozyme; foundational isozyme-characterization work. Supporting Evidence: PMID:4827367 Phosphoglycerate mutase isozyme marker for tissue differentiation in man.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: Human Protein Atlas immunofluorescence (IDA) reporting nucleoplasmic signal. PGAM2 is an abundant soluble cytosolic enzyme; nucleoplasmic staining is not linked to any established nuclear function. Reason: A single-technique IF localization for an abundant cytosolic glycolytic enzyme, without a corresponding nuclear function; likely reflects the diffuse distribution/permeabilization artifacts common for soluble enzymes rather than a core nucleoplasmic role. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- SUBUNIT: Homodimer. Interacts with ENO1. {ECO:0000250\|UniProtKB:O70250,
GO:0004082 bisphosphoglycerate mutase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer (from PGAM1, P18669) of the minor bisphosphoglycerate mutase activity. Consistent with the UniProt-documented reduced-activity side reaction of the BPG-dependent PGAM subfamily. Reason: Genuine secondary catalytic activity supported by family membership and the UniProt catalytic-activity record (EC 5.4.2.4); appropriately marked as a similarity-based inference. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC 3-phospho-glyceroyl phosphate, but with a reduced activity.
GO:0004619 phosphoglycerate mutase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer (from PGAM1, P18669) of the core phosphoglycerate mutase activity. Duplicate of the well-supported core MF. Reason: Correct core molecular function; the ISS inference agrees with experimental, phylogenetic, and automated evidence. Supporting Evidence: file:human/PGAM2/PGAM2-uniprot.txt CC -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: High-throughput proteomic detection in exosomes from expressed prostatic secretions in urine. PGAM2 is a ubiquitous soluble cytosolic enzyme that commonly co-purifies in exosome/secretome proteomes. Reason: A single high-throughput exosome-proteome detection does not establish extracellular exosome as a functional location for this cytosolic glycolytic enzyme; frequent contaminant in such datasets. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: High-throughput proteomic detection of PGAM in isolated human sperm nuclei. Nuclear detection of an abundant soluble glycolytic enzyme in a whole-organelle proteome does not establish a functional nuclear role. Reason: Proteomic co-detection in a sperm-nucleus preparation is prone to soluble-enzyme carryover; there is no established nuclear function for PGAM2, so this is an over-annotation of its core cytosolic biology. Supporting Evidence: PMID:21630459 sperm nuclei were obtained
GO:0005829 cytosol	TAS Reactome:R-HSA-71445	ACCEPT	Summary: Reactome TAS annotation of the cytosol as the location where PGAM dimers isomerise 2PG to 3PG. Core, correct location. Reason: Authoritative pathway annotation of the correct compartment for a cytosolic glycolytic enzyme. Supporting Evidence: Reactome:R-HSA-71445 Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate
GO:0005829 cytosol	TAS Reactome:R-HSA-71654	ACCEPT	Summary: Reactome TAS annotation of the cytosol as the location where PGAM dimers isomerise 3PG to 2PG. Core, correct location (duplicate direction of the same reversible reaction). Reason: Authoritative pathway annotation of the correct cytosolic compartment. Supporting Evidence: Reactome:R-HSA-71654 Cytosolic phosphoglycerate mutase catalyzes the reversible isomerisation
GO:0004619 phosphoglycerate mutase activity	IMP PMID:6262916 Human muscle phosphoglycerate mutase deficiency: newly disco...	ACCEPT	Summary: Experimental (IMP) support from the first described human muscle phosphoglycerate mutase deficiency: muscle PGAM activity was reduced to 5.7% of the lowest control value, with the residual activity being the brain (BB) isoenzyme, implicating loss of the M subunit encoded by PGAM2. Reason: Direct genetic/biochemical evidence in humans that PGAM2 provides phosphoglycerate mutase activity in muscle; the disease phenotype tracks the loss of M-subunit activity. Supporting Evidence: PMID:6262916 Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest
GO:0006096 glycolytic process	IMP PMID:6262916 Human muscle phosphoglycerate mutase deficiency: newly disco...	ACCEPT	Summary: Experimental (IMP) support that PGAM2 functions in glycolysis: the muscle PGAM deficiency produces a block at the phosphoglycerate mutase step of glycolysis while all other glycolytic enzymes had normal activities. Reason: Human loss-of-function evidence directly linking PGAM2 to the glycolytic process; the specific enzymatic block defines its glycolytic role. Supporting Evidence: PMID:6262916 All of the other enzymes of glycolysis
GO:0006941 striated muscle contraction	IMP PMID:6262916 Human muscle phosphoglycerate mutase deficiency: newly disco...	MARK AS OVER ANNOTATED	Summary: Annotation to striated muscle contraction derived from the muscle PGAM deficiency phenotype (exercise intolerance, cramps, pigmenturia). PGAM2 is a glycolytic enzyme, not a component of the contractile apparatus. Reason: Exercise intolerance and cramps in PGAM deficiency are downstream consequences of impaired muscle glycolytic ATP supply, not evidence that PGAM2 participates directly in the muscle-contraction process; the causal role is glycolysis. This is an over-annotation of a phenotype (retained rather than removed as it derives from an experimental report). Supporting Evidence: PMID:6262916 intolerance for strenuous exercise and

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the reversible, 2,3-bisphosphoglycerate-dependent interconversion of 3-phosphoglycerate and 2-phosphoglycerate via a phospho-histidine intermediate, the eighth step of glycolysis, in the cytosol of skeletal and cardiac muscle.

References

📚 Additional Documentation

Notes

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