Pgam2

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining phosphoglycerate mutase activity as a direct annotation (IBA, GO_REF:0000033).

Reason: phosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: cytosol is retained as useful context for Pgam2, but it is not the defining core function (IBA, GO_REF:0000033).

Reason: cytosol records where Pgam2 has been observed, but localization does not define the gene product's primary activity.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining canonical glycolysis as a direct annotation (IBA, GO_REF:0000033).

Reason: canonical glycolysis is a direct metabolic process expected from Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: catalytic activity captures part of Pgam2 biology, but a more specific replacement better represents the direct role (IEA, GO_REF:0000002).

Reason: catalytic activity is directionally correct but less specific than the curated replacement term for Pgam2's role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Proposed replacements: phosphoglycerate mutase activity

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining bisphosphoglycerate mutase activity as a direct annotation (IEA, GO_REF:0000120).

Reason: bisphosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining phosphoglycerate mutase activity as a direct annotation (IEA, GO_REF:0000120).

Reason: phosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining glycolytic process as a direct annotation (IEA, GO_REF:0000120).

Reason: glycolytic process is a direct metabolic process expected from Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: intramolecular phosphotransferase activity captures part of Pgam2 biology, but a more specific replacement better represents the direct role (IEA, GO_REF:0000002).

Reason: intramolecular phosphotransferase activity is directionally correct but less specific than the curated replacement term for Pgam2's role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Proposed replacements: phosphoglycerate mutase activity

Summary: nucleoplasm is retained as useful context for Pgam2, but it is not the defining core function (IEA, GO_REF:0000107). The supporting evidence for a nuclear pool of PGAM is the immunocytochemical and biochemical study PMID:2158448, which found the enzyme in both cytosol and nucleus of rat skeletal muscle and confirmed the nuclear localization biochemically.

Reason: nucleoplasm is biologically compatible with Pgam2 (a nuclear pool of PGAM was demonstrated in rat skeletal muscle), but it is contextual rather than the direct catalytic core function in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: cytosol is retained as useful context for Pgam2, but it is not the defining core function (IEA, GO_REF:0000107).

Reason: cytosol records where Pgam2 has been observed, but localization does not define the gene product's primary activity.

Summary: striated muscle contraction is treated as over-annotation because it reflects context or consequence rather than Pgam2's direct role (IEA, GO_REF:0000107).

Reason: striated muscle contraction reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Pgam2 role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: identical protein binding is retained as useful context for Pgam2, but it is not the defining core function (IEA, GO_REF:0000107).

Reason: identical protein binding records substrate, cofactor, or quaternary-structure context for Pgam2, but the curated core function is phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining canonical glycolysis as a direct annotation (IEA, GO_REF:0000107).

Reason: canonical glycolysis is a direct metabolic process expected from Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: identical protein binding is retained as useful context for Pgam2, but it is not the defining core function (ISO, GO_REF:0000121).

Reason: identical protein binding records substrate, cofactor, or quaternary-structure context for Pgam2, but the curated core function is phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: nucleoplasm is retained as useful context for Pgam2, but it is not the defining core function (ISO, GO_REF:0000121). The supporting evidence for a nuclear pool of PGAM is the immunocytochemical and biochemical study PMID:2158448, which found the enzyme in both cytosol and nucleus of rat skeletal muscle and confirmed the nuclear localization biochemically.

Reason: nucleoplasm is biologically compatible with Pgam2 (a nuclear pool of PGAM was demonstrated in rat skeletal muscle), but it is contextual rather than the direct catalytic core function in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: nucleus is retained as useful context for Pgam2, but it is not the defining core function (IDA, PMID:2158448).

Reason: nucleus records where Pgam2 has been observed, but localization does not define the gene product's primary activity.

Summary: The cited reference (PMID:2158448) is an immunogold study of rat skeletal muscle that localized the enzyme to cytosol and nucleus; it does not provide evidence for an oocyte/ooplasm localization. The experimental observation (a cytoplasmic, non-organellar pool) is sound, but the term chosen does not match the tissue studied. Falcon deep research finds no support for non-cytosolic localization of mammalian PGAM2 beyond the intracellular carbohydrate-metabolism context.

Reason: Ooplasm is defined as the cytoplasm of an ovum, whereas the title and abstract of PMID:2158448 state explicitly that the study was done on rat skeletal muscle and that the enzyme was found in the cytosol (the nuclear pool from the same paper is captured by the separate nucleus IDA row). The localization finding is retained but re-expressed as GO:0005829 cytosol, the compartment the abstract names. GO:0016528 sarcoplasm (the cytoplasm of a muscle cell) would be an acceptable tissue-specific alternative and is the likely intended term; cytosol is preferred because it is what the abstract reports and matches the other Pgam2 cytosol rows.

Proposed replacements: cytosol

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining bisphosphoglycerate mutase activity as a direct annotation (ISS, GO_REF:0000024).

Reason: bisphosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining phosphoglycerate mutase activity as a direct annotation (ISS, GO_REF:0000024).

Reason: phosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: cytosol is retained as useful context for Pgam2, but it is not the defining core function (ISO, GO_REF:0000121).

Reason: cytosol records where Pgam2 has been observed, but localization does not define the gene product's primary activity.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining canonical glycolysis as a direct annotation (ISO, GO_REF:0000121).

Reason: canonical glycolysis is a direct metabolic process expected from Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Notch signaling pathway is treated as over-annotation because it reflects context or consequence rather than Pgam2's direct role (ISO, GO_REF:0000121).

Reason: Notch signaling pathway reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Pgam2 role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining glycolytic process as a direct annotation (ISO, GO_REF:0000121).

Reason: glycolytic process is a direct metabolic process expected from Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: phosphoglycerate mutase activity is a specific catalytic activity consistent with Pgam2's core role. Note that in PMID:15720133 (Sakai et al. 2005) phosphoglycerate mutase activity was measured as a negative control and shown NOT to be inactivated by MCA (in contrast to GAPDH); the measurement nonetheless demonstrates assayable PGAM activity, so the activity annotation is retained as a correct molecular function term.

Reason: phosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role; PMID:15720133 directly measured this activity (as an MCA-insensitive negative control).

Summary: The cited reference (PMID:15720133, Sakai et al. 2005) does not provide IDA support for a direct PGAM role in gluconeogenesis. The paper concludes that MCA-induced inhibition of liver gluconeogenesis is caused by inactivation of GAPDH, and explicitly shows that phosphoglycerate mutase (along with enolase and phosphoglycerate kinase) was NOT inactivated; PGAM was measured only as a negative control. While PGAM2 catalyzes a reversible reaction and can in principle participate in gluconeogenesis, this reference actively argues that PGAM is not the operative enzyme in the studied effect, so the IDA annotation to gluconeogenesis from this paper is an over-annotation.

Reason: PMID:15720133 implicates GAPDH (not PGAM) in MCA-induced inhibition of liver gluconeogenesis and shows phosphoglycerate mutase was not inactivated, so it does not support a direct IDA annotation of PGAM2 to gluconeogenesis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining phosphoglycerate mutase activity as a direct annotation (IDA, PMID:2158448).

Reason: phosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: spermatogenesis is treated as over-annotation. PMID:7867621 shows that the muscle-specific PGAM-M gene is developmentally expressed in testis during spermatogenesis, where the paper frames PGAM as "an essential glycolytic enzyme for the spermatozoa energy supply". This testis expression reflects the same core glycolytic mutase function operating in a germ-cell context (an IEP expression-pattern observation) rather than a distinct, direct involvement of PGAM2 in the spermatogenesis differentiation program itself.

Reason: The evidence is an IEP expression-pattern observation; although PMID:7867621 frames PGAM-M as essential for spermatozoa energy supply, this is the same glycolytic mutase activity deployed in germ cells, not a direct PGAM2 role in the spermatogenesis developmental process, so annotating Pgam2 to spermatogenesis over-states its function.

Summary: response to mercury ion is treated as over-annotation because it reflects context or consequence rather than Pgam2's direct role (IMP, PMID:2850701).

Reason: response to mercury ion reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Pgam2 role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining phosphoglycerate mutase activity as a direct annotation (ISO, GO_REF:0000121).

Reason: phosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: striated muscle contraction is treated as over-annotation because it reflects context or consequence rather than Pgam2's direct role (ISO, GO_REF:0000121).

Reason: striated muscle contraction reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Pgam2 role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: Pgam2's phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis supports retaining phosphoglycerate mutase activity as a direct annotation (IDA, PMID:2850701).

Reason: phosphoglycerate mutase activity is a specific catalytic activity matching Pgam2's documented role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.

Summary: ISO transfer of phosphoglycerate mutase activity from human PGAM2 (UniProtKB:P15259), the muscle-type phosphoglycerate mutase ortholog; donor-split companion of the accepted ISO row from mouse Pgam2 (MGI:1933118).

Reason: Human PGAM2 is the direct muscle-isoform ortholog, and rat Pgam2 phosphoglycerate mutase activity is independently supported by IDA rows (PMID:2158448, PMID:2850701). The transferred activity is the core catalytic function.

Summary: ISO transfer of glycolysis (GO:0006096, now labelled "glycolysis" in GO) from human PGAM2 (UniProtKB:P15259); donor-split companion of the accepted mouse-donor (MGI:1933118) ISO row for the same term.

Reason: Phosphoglycerate mutase catalyses the 3-phosphoglycerate to 2-phosphoglycerate step of glycolysis, so Pgam2 directly performs a step of the process; human PGAM2 is an appropriate ortholog donor.

Summary: Electronic (ARBA:ARBA00093730) ooplasm localization; companion of the ooplasm IDA row (PMID:2158448), which this rule most likely echoes. The only cellular localization data for rat Pgam2 come from skeletal muscle.

Reason: Ooplasm is defined as the cytoplasm of an ovum. The experimental localization study cited for the IDA ooplasm row examined rat skeletal muscle and found the enzyme in cytosol and nucleus; no evidence places Pgam2, the muscle/heart glycolytic isozyme, in oocyte cytoplasm. This rule-based electronic transfer is therefore demonstrably inapplicable rather than merely over-general, and it should be removed; the correct cytosolic localization is already carried by the cytosol rows and by the MODIFY proposed for the IDA sibling.