id: P15259
gene_symbol: PGAM2
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PGAM2 is the muscle (M) isoform of phosphoglycerate mutase, a cytosolic enzyme
  of the cofactor-dependent phosphoglycerate mutase (histidine-phosphatase)
  superfamily. It catalyzes the reversible interconversion of 3-phosphoglycerate
  and 2-phosphoglycerate, the eighth step of the glycolytic payoff phase (and the
  corresponding reverse step in gluconeogenesis). Catalysis proceeds through a
  phospho-histidine enzyme intermediate and requires 2,3-bisphosphoglycerate as a
  cofactor/primer; the enzyme also displays a minor bisphosphoglycerate
  mutase/phosphatase side activity. Active human phosphoglycerate mutase is a
  dimer assembled from muscle (PGAM2/M) and brain (PGAM1/B) subunits; skeletal
  muscle expresses essentially the PGAM2 homodimer, whereas erythrocytes express
  PGAM1. PGAM2 is expressed predominantly in heart and skeletal muscle.
  Loss-of-function variants cause glycogen storage disease type X (muscle
  phosphoglycerate mutase deficiency), manifesting as exercise intolerance,
  muscle cramps, and myoglobinuria/rhabdomyolysis.
existing_annotations:
- term:
    id: GO:0004619
    label: phosphoglycerate mutase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic assignment of the cytosol as the site of action. Phosphoglycerate
      mutase is a soluble cytosolic glycolytic enzyme, consistent with Reactome and
      UniProt.
    action: ACCEPT
    reason: >-
      Correct subcellular location for a soluble glycolytic enzyme; agrees with
      Reactome TAS cytosol annotations and with the entire glycolytic pathway being
      cytosolic.
    supported_by:
    - reference_id: Reactome:R-HSA-71445
      supporting_text: "Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate"
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-70171
      supporting_text: "The reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert"
- term:
    id: GO:0003824
    label: catalytic activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Root-level InterPro2GO mapping asserting generic catalytic activity. Not
      incorrect but entirely uninformative given the specific mutase activity is
      already annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "catalytic activity" is a top-level MF placeholder subsumed by the specific
      phosphoglycerate mutase activity annotation; it adds no functional information.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate"
- term:
    id: GO:0004082
    label: bisphosphoglycerate mutase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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."
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC       3-phospho-glyceroyl phosphate, but with a reduced activity."
- term:
    id: GO:0004619
    label: phosphoglycerate mutase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Correct core molecular function; the automated EC/RHEA mapping agrees with the
      experimental and phylogenetic annotations.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate"
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic assignment to the glycolytic process. Correct core pathway for
      PGAM2, also supported experimentally by the deficiency phenotype (IMP).
    action: ACCEPT
    reason: >-
      Core biological process; consistent with the IMP annotation from the muscle
      PGAM deficiency case and with the canonical-glycolysis annotations.
    supported_by:
    - reference_id: PMID:6262916
      supporting_text: "Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest"
- term:
    id: GO:0016868
    label: intramolecular phosphotransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      High-throughput AP-MS interactome (BioPlex 2.0) reporting a PGAM2-BPGM
      (P07738) co-complex. Bare "protein binding" is uninformative about molecular
      function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: "BioPlex 2.0 is the largest collection of human co-complex data assembled from a single pipeline to date"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Binary interactome map (HuRI, yeast two-hybrid) reporting PGAM2 interactions
      (e.g. BPGM, CLVS2, DYNC1LI1, KATNAL1). Bare "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic "protein binding" from a systematic binary-interactome
      screen; retained as an experimental IPI but not treated as a defining function.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: "A reference map of the human binary protein interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      High-throughput AP-MS interactome (BioPlex 3.0) again reporting a PGAM2-BPGM
      (P07738) association. Bare "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic "protein binding" from an interactome screen; consistent with the
      other BioPlex/HuRI evidence but non-specific; retained as an experimental IPI.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: "Dual proteome-scale networks reveal cell-specific remodeling of the human"
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Self-interaction of PGAM2 (P15259-P15259) detected in the binary interactome
      map, consistent with the established homodimeric quaternary structure of
      phosphoglycerate mutase.
    action: ACCEPT
    reason: >-
      Informative self-association annotation that matches the documented homodimer;
      UniProt SUBUNIT states "Homodimer" and Reactome describes the active enzyme as
      a dimer.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- SUBUNIT: Homodimer. Interacts with ENO1. {ECO:0000250|UniProtKB:O70250,"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- SUBUNIT: Homodimer. Interacts with ENO1. {ECO:0000250|UniProtKB:O70250,"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: >-
      Orthology-based (Ensembl Compara, from mouse O70250) assignment of the cytosol
      as site of action. Correct core location for a glycolytic enzyme.
    action: ACCEPT
    reason: >-
      Agrees with the IBA and Reactome TAS cytosol annotations; correct compartment
      for phosphoglycerate mutase activity.
    supported_by:
    - reference_id: Reactome:R-HSA-71445
      supporting_text: "Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate"
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-70263
      supporting_text: "Gluconeogenesis is confined to cells of the liver and kidney"
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- TISSUE SPECIFICITY: Expressed in the heart and muscle. Not found in the"
- term:
    id: GO:0046689
    label: response to mercury ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:6262916
      supporting_text: "Electrophoretic, "
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-based (Ensembl Compara, from mouse O70250) assignment to canonical
      glycolysis. Correct core process; duplicate of the IBA/TAS glycolysis
      annotations.
    action: ACCEPT
    reason: >-
      Core glycolytic process for the muscle isoform, consistent with all other
      glycolysis evidence lines.
    supported_by:
    - reference_id: Reactome:R-HSA-70171
      supporting_text: "The reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert"
- term:
    id: GO:1990917
    label: ooplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-71445
      supporting_text: "Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate"
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70263
  qualifier: involved_in
  review:
    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).
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-70263
      supporting_text: "Gluconeogenesis is confined to cells of the liver and kidney"
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70171
  qualifier: involved_in
  review:
    summary: >-
      Reactome pathway annotation placing PGAM within canonical glycolysis (the
      cytosolic glucose-to-pyruvate route). Core process for PGAM2.
    action: ACCEPT
    reason: >-
      Authoritative pathway (TAS) annotation for the core glycolytic role; consistent
      with all other glycolysis evidence.
    supported_by:
    - reference_id: Reactome:R-HSA-70171
      supporting_text: "The reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert"
- term:
    id: GO:0004619
    label: phosphoglycerate mutase activity
  evidence_type: EXP
  original_reference_id: PMID:4827367
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Experimental support for the core catalytic activity of the muscle
      phosphoglycerate mutase isozyme; foundational isozyme-characterization work.
    supported_by:
    - reference_id: PMID:4827367
      supporting_text: "Phosphoglycerate mutase isozyme marker for tissue differentiation in man."
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- SUBUNIT: Homodimer. Interacts with ENO1. {ECO:0000250|UniProtKB:O70250,"
- term:
    id: GO:0004082
    label: bisphosphoglycerate mutase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC       3-phospho-glyceroyl phosphate, but with a reduced activity."
- term:
    id: GO:0004619
    label: phosphoglycerate mutase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      Sequence-similarity transfer (from PGAM1, P18669) of the core phosphoglycerate
      mutase activity. Duplicate of the well-supported core MF.
    action: ACCEPT
    reason: >-
      Correct core molecular function; the ISS inference agrees with experimental,
      phylogenetic, and automated evidence.
    supported_by:
    - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
      supporting_text: "CC   -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate"
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: "In-depth proteomic analyses of exosomes isolated from expressed prostatic"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:21630459
      supporting_text: "sperm nuclei were obtained "
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71445
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS annotation of the cytosol as the location where PGAM dimers
      isomerise 2PG to 3PG. Core, correct location.
    action: ACCEPT
    reason: >-
      Authoritative pathway annotation of the correct compartment for a cytosolic
      glycolytic enzyme.
    supported_by:
    - reference_id: Reactome:R-HSA-71445
      supporting_text: "Cytosolic phosphoglycerate mutase dimers (PGAM1,2) catalyze the reversible isomerisation of 2- and 3-phosphoglycerate"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71654
  qualifier: located_in
  review:
    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).
    action: ACCEPT
    reason: >-
      Authoritative pathway annotation of the correct cytosolic compartment.
    supported_by:
    - reference_id: Reactome:R-HSA-71654
      supporting_text: "Cytosolic phosphoglycerate mutase catalyzes the reversible isomerisation"
- term:
    id: GO:0004619
    label: phosphoglycerate mutase activity
  evidence_type: IMP
  original_reference_id: PMID:6262916
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:6262916
      supporting_text: "Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest"
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IMP
  original_reference_id: PMID:6262916
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Human loss-of-function evidence directly linking PGAM2 to the glycolytic
      process; the specific enzymatic block defines its glycolytic role.
    supported_by:
    - reference_id: PMID:6262916
      supporting_text: "All of the other enzymes of glycolysis "
- term:
    id: GO:0006941
    label: striated muscle contraction
  evidence_type: IMP
  original_reference_id: PMID:6262916
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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).
    supported_by:
    - reference_id: PMID:6262916
      supporting_text: "intolerance for strenuous exercise and "
core_functions:
- description: >-
    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.
  molecular_function:
    id: GO:0004619
    label: phosphoglycerate mutase activity
  directly_involved_in:
  - id: GO:0006096
    label: glycolytic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/PGAM2/PGAM2-uniprot.txt
    supporting_text: "CC   -!- FUNCTION: Catalyzes the interconversion of 3- and 2-phosphoglycerate"
  - reference_id: PMID:6262916
    supporting_text: "Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  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:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Sperm-nucleus proteome; PGAM detected as one of 403 proteins. Supports the
      nucleus HDA localization but is a high-throughput co-detection with no
      functional nuclear role; over-annotation for a cytosolic enzyme.
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Exosome proteome from prostatic secretions; PGAM detected as a high-throughput
      co-purifying protein. Supports the exosome HDA localization only; over-annotation.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 2.0 AP-MS interactome; source of a PGAM2-BPGM protein-binding IPI.
      Supports only generic protein binding, not a specific molecular function.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      HuRI binary (Y2H) interactome; source of protein-binding IPIs and the PGAM2
      self-interaction (identical protein binding), consistent with the homodimer.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 3.0 AP-MS interactome; source of a PGAM2-BPGM protein-binding IPI.
      Generic protein binding only.
- id: PMID:4827367
  title: Phosphoglycerate mutase isozyme marker for tissue differentiation in man.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Foundational characterization of human PGAM isozymes (M vs B subunits) as
      tissue-differentiation markers; underpins the EXP phosphoglycerate mutase
      activity annotation.
- id: PMID:6262916
  title: 'Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic
    myopathy.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      First description of human muscle PGAM deficiency (GSD X): muscle PGAM activity
      5.7% of control, residual activity is BB isozyme, implicating the M subunit.
      Directly supports the core catalytic and glycolytic roles of PGAM2; the
      muscle-contraction annotation from this paper is a downstream phenotype.
- id: Reactome:R-HSA-70171
  title: Glycolysis
  findings: []
- id: Reactome:R-HSA-70263
  title: Gluconeogenesis
  findings: []
- id: Reactome:R-HSA-71445
  title: PGAM dimers isomerise 2PG to 3PG
  findings: []
- id: Reactome:R-HSA-71654
  title: PGAM dimers isomerise 3PG to 2PG
  findings: []
- id: file:human/PGAM2/PGAM2-uniprot.txt
  title: UniProt entry P15259 (PGAM2_HUMAN)
  findings: []