Pck2 encodes the mitochondrial isoform of GTP-dependent phosphoenolpyruvate carboxykinase (PEPCK-M), a manganese-activated enzyme of the mitochondrial matrix that converts oxaloacetate and GTP into phosphoenolpyruvate (PEP), GDP and CO2. Unlike the cytosolic isoform (Pck1), it is expressed in many tissues, including liver, kidney and pancreatic beta cells, where it is the only PEPCK. In liver it supplies PEP for gluconeogenesis from lactate, alanine and glutamine; in beta cells it couples mitochondrial GTP made by succinyl-CoA synthetase to an anaplerotic PEP cycle required for glucose-stimulated insulin secretion. Human PCK2 has also been reported to act as a protein kinase that phosphorylates ACSL4 and promotes ferroptosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004611 phosphoenolpyruvate carboxykinase activity | IDA PMID:11440903 Mechanism of fat-induced hepatic gluconeogenesis: effect of ... | MODIFY | Summary: PEPCK activity measured in rat liver in a high-fat-feeding/metformin study (abstract only). Reason: PEPCK activity is a true function of Pck2, but the generic parent term should be refined to the GTP-specific child GO:0004613, which Pck2 already carries (rat IDA PMID:6049928). The cited abstract measures total hepatic gluconeogenic enzyme activity and does not say the mitochondrial isoform was assayed; because adult rat liver PEPCK is >90% cytosolic, the activity is probably mostly Pck1. We cannot read the full text, so the row is not overruled; the possible gene-product mix-up is recorded as a suspected source defect. Proposed replacements: phosphoenolpyruvate carboxykinase (GTP) activity Supporting Evidence: PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. PMID:6049928 more than 90% of the activity is in the cytoplasm |
| GO:0004611 phosphoenolpyruvate carboxykinase activity | IDA PMID:4353083 Induction and suppression of the key enzymes of glycolysis a... | MODIFY | Summary: PEPCK activity changes in isolated perfused rat liver (abstract only). Reason: As for the other whole-liver IDA row: the function is true of Pck2, but GO:0004611 should be refined to GO:0004613 (GTP-dependent), already on the gene. The abstract measures total hepatic PEPCK and does not distinguish the mitochondrial isoform; recorded as a suspected source defect pending full-text check. Proposed replacements: phosphoenolpyruvate carboxykinase (GTP) activity Supporting Evidence: PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. PMID:6049928 more than 90% of the activity is in the cytoplasm |
| GO:0004611 phosphoenolpyruvate carboxykinase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from GTP-dependent PEPCK domains to the generic PEPCK activity term. Reason: Correct but general. Pck2 is a GTP-dependent PEPCK (HAMAP MF_00452, PROSITE PS00505), so the specific child GO:0004613, already carried by the gene, is the right term. Proposed replacements: phosphoenolpyruvate carboxykinase (GTP) activity Supporting Evidence: file:rat/Pck2/Pck2-uniprot.txt HAMAP; MF_00452; PEPCK_GTP; 1. file:rat/Pck2/Pck2-uniprot.txt PROSITE; PS00505; PEPCK_GTP; 1. PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. |
| GO:0004613 phosphoenolpyruvate carboxykinase (GTP) activity | IDA PMID:6049928 Phosphoenolpyruvate carboxykinase and pyruvate carboxylase i... | ACCEPT | Summary: Mitochondrial PEPCK activity measured in fractionated foetal, newborn and adult rat liver. Reason: Ballard and Hanson assayed PEPCK in rat liver mitochondrial fractions and showed the mitochondrial enzyme is kinetically indistinguishable from the cytosolic one; the mitochondrial activity is the Pck2 product. Core catalytic activity, also confirmed in rat islets and INS-1 cells (PMID:19635791). Supporting Evidence: PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. PMID:6049928 Kinetic and other studies on the properties of phosphoenolpyruvate carboxykinase have shown no differences between the soluble and mitochondrial enzymes. PMID:19635791 Virtually all of the PEPCK activity from cells and islets was localized to the mitochondrial fraction when adjusted for leakage of mitochondrial contents into the cytosol fraction by parallel measurements of glutamate dehydrogenase activity from the same samples |
| GO:0004613 phosphoenolpyruvate carboxykinase (GTP) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA/orthologs/InterPro/EC) for GTP-dependent PEPCK activity. Reason: Consistent with family membership and with rat experimental data; core function. Supporting Evidence: file:rat/Pck2/Pck2-uniprot.txt HAMAP; MF_00452; PEPCK_GTP; 1. PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. |
| GO:0004613 phosphoenolpyruvate carboxykinase (GTP) activity | ISO GO_REF:0000121 | ACCEPT | Summary: ISO from human PCK2 for GTP-dependent PEPCK activity. Reason: Ortholog transfer of the core catalytic activity, independently established for rat PEPCK-M. Supporting Evidence: PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. |
| GO:0004613 phosphoenolpyruvate carboxykinase (GTP) activity | ISO GO_REF:0000121 | ACCEPT | Summary: ISO from mouse Pck2 for GTP-dependent PEPCK activity. Reason: Ortholog transfer of the core catalytic activity, independently established for rat PEPCK-M. Supporting Evidence: PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from human PCK2 of protein serine/threonine kinase activity. Reason: Human PCK2 was shown in one study to phosphorylate ACSL4 Thr679 in an in vitro kinase assay using GTP as phosphate donor (PMID:38720107). Rat Pck2 is the 1:1 ortholog with conserved active site, so the transfer is reasonable, but this moonlighting activity rests on a single report in human cancer cells and is peripheral to the metabolic role. Supporting Evidence: PMID:38720107 in vitro kinase assays showed that PCK2 could directly phosphorylate ACSL4 |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: RGD ISO from human PCK2 of protein serine/threonine kinase activity. Reason: Same claim as the Ensembl row; single human study (PMID:38720107), peripheral to the metabolic function. Supporting Evidence: PMID:38720107 in vitro kinase assays showed that PCK2 could directly phosphorylate ACSL4 |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO GTP binding from the GTP-dependent PEPCK family signature. Reason: GTP is the phosphoryl donor substrate of the enzyme, so GTP binding is true; it is a component of the catalytic activity rather than a separate function. Supporting Evidence: PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. file:rat/Pck2/Pck2-uniprot.txt HAMAP; MF_00452; PEPCK_GTP; 1. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (UniProt subcellular location, orthologs) to mitochondrion. Reason: Root organelle term; the claim holds: rat PEPCK-M activity is in the mitochondrial fraction (GDH-controlled fractionation in rat islets/INS-1 cells; rat liver mitochondria). The matrix sub-compartment is already carried by other rows. Supporting Evidence: PMID:19635791 Virtually all of the PEPCK activity from cells and islets was localized to the mitochondrial fraction when adjusted for leakage of mitochondrial contents into the cytosol fraction by parallel measurements of glutamate dehydrogenase activity from the same samples PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | ACCEPT | Summary: RGD ISO from human PCK2 to mitochondrion (is_active_in). Reason: Root organelle term with sound support; rat PEPCK-M activity is mitochondrial (PMID:19635791, PMID:6049928). Supporting Evidence: PMID:19635791 Virtually all of the PEPCK activity from cells and islets was localized to the mitochondrial fraction when adjusted for leakage of mitochondrial contents into the cytosol fraction by parallel measurements of glutamate dehydrogenase activity from the same samples |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | ACCEPT | Summary: RGD ISO from human PCK2 to mitochondrion (located_in). Reason: Root organelle term with sound support; rat PEPCK-M activity is mitochondrial (PMID:19635791, PMID:6049928). Supporting Evidence: PMID:19635791 Virtually all of the PEPCK activity from cells and islets was localized to the mitochondrial fraction when adjusted for leakage of mitochondrial contents into the cytosol fraction by parallel measurements of glutamate dehydrogenase activity from the same samples |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse Pck2 to mitochondrial matrix. Reason: Two independent lines agree on the matrix: an Arg-rich amphipathic N-terminal presequence (rat Met28 "MAAMYLPGLRLSWHRLRPW..." aligns with the human/mouse start) with no transmembrane segment, and co-fractionation with the matrix marker glutamate dehydrogenase; the enzyme uses matrix mtGTP made by SCS-GTP. Core location. Supporting Evidence: PMID:24177027 PEPCK that can either take place in the cytosol (PEPCK-C) or the mitochondrial matrix (PEPCK-M) PMID:19635791 Virtually all of the PEPCK activity from cells and islets was localized to the mitochondrial fraction when adjusted for leakage of mitochondrial contents into the cytosol fraction by parallel measurements of glutamate dehydrogenase activity from the same samples file:rat/Pck2/Pck2-deep-research-manual.md the human PCK2 start (MAAL...) aligns to rat Met28 ("MAAMYLPGLRL..."), so residues 1-27 of the Ensembl model are probably 5' UTR translation. |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000121 | ACCEPT | Summary: RGD ISO from mouse Pck2 to mitochondrial matrix. Reason: Same as the Ensembl matrix row; core location. Supporting Evidence: PMID:24177027 PEPCK that can either take place in the cytosol (PEPCK-C) or the mitochondrial matrix (PEPCK-M) PMID:19635791 Virtually all of the PEPCK activity from cells and islets was localized to the mitochondrial fraction when adjusted for leakage of mitochondrial contents into the cytosol fraction by parallel measurements of glutamate dehydrogenase activity from the same samples |
| GO:0006094 gluconeogenesis | IDA PMID:11440903 Mechanism of fat-induced hepatic gluconeogenesis: effect of ... | ACCEPT | Summary: Hepatic gluconeogenesis measured in rats (abstract only). Reason: Gluconeogenesis is a core process of Pck2: PEPCK-M catalyses the OAA to PEP step, and ASO knockdown of PEPCK-M in rat liver and hepatocytes reduces gluconeogenesis from lactate, alanine and glutamine (PMID:24497630). This abstract-only paper measured whole-animal gluconeogenesis and total enzyme activities, so it is weak support for Pck2 specifically, but the process is independently established and the curator read the full text; accepted with the same suspected gene-product caveat as the companion MF row. Supporting Evidence: PMID:24497630 Consistent with its predicted role, gluconeogenesis rates from hepatocytes lacking PEPCK-M are severely reduced for lactate, alanine, and glutamine, but not for pyruvate and glycerol. PMID:24497630 Synthesis of phosphoenolpyruvate (PEP) from oxaloacetate is an absolute requirement for gluconeogenesis from mitochondrial substrates. |
| GO:0006094 gluconeogenesis | IDA PMID:4353083 Induction and suppression of the key enzymes of glycolysis a... | ACCEPT | Summary: Gluconeogenic enzyme induction in perfused rat liver (abstract only). Reason: Gluconeogenesis is a core process of Pck2: PEPCK-M catalyses the OAA to PEP step, and ASO knockdown of PEPCK-M in rat liver and hepatocytes reduces gluconeogenesis from lactate, alanine and glutamine (PMID:24497630). This abstract-only paper measured total hepatic PEPCK; accepted because the process is independently established for Pck2, with a suspected gene-product caveat. Supporting Evidence: PMID:24497630 Consistent with its predicted role, gluconeogenesis rates from hepatocytes lacking PEPCK-M are severely reduced for lactate, alanine, and glutamine, but not for pyruvate and glycerol. PMID:24497630 Synthesis of phosphoenolpyruvate (PEP) from oxaloacetate is an absolute requirement for gluconeogenesis from mitochondrial substrates. |
| GO:0006094 gluconeogenesis | IDA PMID:6049928 Phosphoenolpyruvate carboxykinase and pyruvate carboxylase i... | ACCEPT | Summary: Mitochondrial PEPCK in developing rat liver. Reason: Gluconeogenesis is a core process of Pck2: PEPCK-M catalyses the OAA to PEP step, and ASO knockdown of PEPCK-M in rat liver and hepatocytes reduces gluconeogenesis from lactate, alanine and glutamine (PMID:24497630). This paper measured mitochondrial PEPCK activity in rat liver. Supporting Evidence: PMID:24497630 Consistent with its predicted role, gluconeogenesis rates from hepatocytes lacking PEPCK-M are severely reduced for lactate, alanine, and glutamine, but not for pyruvate and glycerol. PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. |
| GO:0006094 gluconeogenesis | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (UniPathway, orthologs, InterPro) to gluconeogenesis. Reason: Gluconeogenesis is a core process of Pck2: PEPCK-M catalyses the OAA to PEP step, and ASO knockdown of PEPCK-M in rat liver and hepatocytes reduces gluconeogenesis from lactate, alanine and glutamine (PMID:24497630). Supporting Evidence: PMID:24497630 Consistent with its predicted role, gluconeogenesis rates from hepatocytes lacking PEPCK-M are severely reduced for lactate, alanine, and glutamine, but not for pyruvate and glycerol. PMID:24497630 Synthesis of phosphoenolpyruvate (PEP) from oxaloacetate is an absolute requirement for gluconeogenesis from mitochondrial substrates. |
| GO:0006094 gluconeogenesis | ISO GO_REF:0000121 | ACCEPT | Summary: RGD ISO from mouse Pck2 to gluconeogenesis. Reason: Gluconeogenesis is a core process of Pck2: PEPCK-M catalyses the OAA to PEP step, and ASO knockdown of PEPCK-M in rat liver and hepatocytes reduces gluconeogenesis from lactate, alanine and glutamine (PMID:24497630). Supporting Evidence: PMID:24497630 Consistent with its predicted role, gluconeogenesis rates from hepatocytes lacking PEPCK-M are severely reduced for lactate, alanine, and glutamine, but not for pyruvate and glycerol. |
| GO:0006107 oxaloacetate metabolic process | IDA PMID:6049928 Phosphoenolpyruvate carboxykinase and pyruvate carboxylase i... | KEEP AS NON CORE | Summary: Oxaloacetate metabolism by mitochondrial PEPCK in rat liver. Reason: True: PEPCK-M decarboxylates/phosphorylates oxaloacetate to PEP. The term has no more specific descendant that fits (its only is_a child is a microbial protocatechuate pathway), and the metabolic context is better captured by gluconeogenesis, so it is retained as non-core. Supporting Evidence: PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. PMID:6049928 This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. |
| GO:0017076 purine nucleotide binding | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO purine nucleotide binding. Reason: Correct but general: GTP binding (GO:0005525), already on the gene, is an is_a descendant of purine nucleotide binding (via guanyl nucleotide binding) and is what the evidence supports, GTP being the phosphoryl donor. Proposed replacements: GTP binding Supporting Evidence: PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. |
| GO:0030145 manganese ion binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from human PCK2 of manganese ion binding. Reason: Mn2+ is the activating divalent cation of PEPCK-M; binding is true and part of the catalytic mechanism, not a separate function. Supporting Evidence: PMID:24177027 PEPCK-M binds a single divalent cation in tetrahedral coordination in the absence of substrates with Mn2+ being the most activating cation PMID:19635791 Mg2+ reduces PEPCK-M activity, whereas Mn2+ is the preferred divalent |
| GO:0030145 manganese ion binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: RGD ISO from human PCK2 of manganese ion binding. Reason: As for the Ensembl row: cofactor binding, true, non-core. Supporting Evidence: PMID:24177027 PEPCK-M binds a single divalent cation in tetrahedral coordination in the absence of substrates with Mn2+ being the most activating cation PMID:19635791 Mg2+ reduces PEPCK-M activity, whereas Mn2+ is the preferred divalent |
| GO:0032024 positive regulation of insulin secretion | IMP PMID:19635791 Phosphoenolpyruvate cycling via mitochondrial phosphoenolpyr... | ACCEPT | Summary: siRNA knockdown of PEPCK-M in rat INS-1 832/13 cells abolishes glucose-stimulated insulin secretion. Reason: Full text read. Two independent siRNAs that reduced PEPCK-M activity by 75% lowered PEP and completely blocked GSIS. PEPCK-M does work in this process: it is the enzyme of the beta-cell PEP cycle that hydrolyses mtGTP and exports anaplerotic carbon as PEP, the proposed metabolic coupling signal (it is the only PEPCK in these cells). This is the best-characterised rat-specific role and is recorded as a core function alongside gluconeogenesis. Supporting Evidence: PMID:19635791 Silencing the PEPCK-M gene completely inhibited GSIS underscoring its central role in mitochondrial metabolism-mediated insulin secretion. PMID:19635791 As high as 30% of PEP in INS-1 832/13 cells and 41% of PEP in rat islets came from PEPCK-M. |
| GO:0032496 response to lipopolysaccharide | IEP PMID:19268478 Endotoxin induced hyperlactatemia and hypoglycemia is linked... | KEEP AS NON CORE | Summary: Hepatic Pck2 mRNA and PEPCK-M activity fall in LPS-induced endotoxaemia in rats. Reason: Expression-pattern (IEP) evidence: the rat Pck2 transcript and activity respond to LPS. Accurate but describes regulation of the gene, not a function it performs. Supporting Evidence: PMID:19268478 In rat endotoxemia, hepatic PCK2 mRNA and PEPCK-M enzyme activity decreased by 53% and 38%, compared to sham controls. |
| GO:0042866 pyruvate biosynthetic process | IMP PMID:19635791 Phosphoenolpyruvate cycling via mitochondrial phosphoenolpyr... | MARK AS OVER ANNOTATED | Summary: Knockdown of PEPCK-M lowers PEP in rat INS-1 cells (IMP to pyruvate biosynthetic process). Reason: PEPCK-M produces phosphoenolpyruvate, not pyruvate; in the PEP cycle described in the paper, pyruvate kinase converts PEPCK-M-derived PEP to pyruvate. The knockdown result shown is reduced PEP. PCK2 is upstream of, rather than a catalyst of, pyruvate formation; GO has no phosphoenolpyruvate biosynthetic process term, so the existing gluconeogenesis/OAA metabolism rows plus the core MF capture the activity. Recorded as a WRONG_TERM query to RGD. Supporting Evidence: PMID:19635791 PEPCK-M will then consume oxaloacetate and GTP to produce PEP, GDP, and CO2. PMID:19635791 both total and 13C-labeled PEP concentrations were significantly reduced, confirming the impact of silencing on metabolism |
| GO:0046167 glycerol-3-phosphate biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from mouse Pck2 to glycerol-3-phosphate biosynthetic process (glyceroneogenesis). Reason: PEP made by PEPCK is the entry point of glyceroneogenesis, so a PEPCK does perform a step of this process; however glyceroneogenesis is mainly attributed to cytosolic PEPCK-C (Pck1) in adipose and liver, and the contribution of the mitochondrial isoform is shown only indirectly. Retained as non-core, peripheral. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8BH04 · mouse Pck2 SOURCE WEAK OR INFERRED Mouse source not inspected in full; PEPCK-M role in glyceroneogenesis is less established than PEPCK-C. Supporting Evidence: PMID:24177027 reversed flux (in the direction of OAA synthesis) by PEPCK-C would be counterproductive for gluconeogenesis and glyceroneogenesis |
| GO:0046167 glycerol-3-phosphate biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: RGD ISO from mouse Pck2 to glycerol-3-phosphate biosynthetic process. Reason: Same claim as the Ensembl row; PEPCK performs the PEP-forming step of glyceroneogenesis, but the mitochondrial isoform contribution is peripheral. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:1860456 · mouse Pck2 SOURCE WEAK OR INFERRED Donor evidence not inspected in full. Supporting Evidence: PMID:24177027 reversed flux (in the direction of OAA synthesis) by PEPCK-C would be counterproductive for gluconeogenesis and glyceroneogenesis |
| GO:0071333 cellular response to glucose stimulus | IEP PMID:19635791 Phosphoenolpyruvate cycling via mitochondrial phosphoenolpyr... | KEEP AS NON CORE | Summary: Glucose increases the contribution of PEPCK-M to PEP synthesis in rat INS-1 cells. Reason: Full text read: glucose stimulation more than tripled the PEPCK-M share of PEP synthesis, and PEPCK-M is required for the secretory response to glucose. The response is real but is a context-specific aspect of the beta-cell role; non-core. Supporting Evidence: PMID:19635791 The contribution of PEPCK-M to overall PEP synthesis more than tripled with glucose stimulation. PMID:19635791 Silencing the PEPCK-M gene completely inhibited GSIS underscoring its central role in mitochondrial metabolism-mediated insulin secretion. |
| GO:0071356 cellular response to tumor necrosis factor | IEP PMID:19268478 Endotoxin induced hyperlactatemia and hypoglycemia is linked... | KEEP AS NON CORE | Summary: TNF-alpha suppresses lactate-induced Pck2 mRNA and PEPCK-M activity in cultured hepatocytes. Reason: Expression-pattern evidence; accurate but describes regulation of the gene rather than a function it performs. Supporting Evidence: PMID:19268478 Incubation of cultured hepatocytes with TNF-alpha inhibited lactate-induced increases in glucose production, PCK2 mRNA levels and PEPCK-M enzyme activity |
| GO:0071548 response to dexamethasone | IEP PMID:16570165 Prenatal programming of hepatocyte nuclear factor 4alpha in ... | KEEP AS NON CORE | Summary: Prenatal dexamethasone exposure raises hepatic Pck2 expression in rat offspring. Reason: Expression-pattern evidence of glucocorticoid programming of Pck2 (abstract only); accurate as an expression response, not a function of the protein. Supporting Evidence: PMID:16570165 Prenatal glucocorticoid exposure causes lifelong hyperglycaemia in rat offspring, associated with permanently increased hepatic phosphoenolpyruvate carboxykinase 2 (PCK2) |
| GO:0160020 positive regulation of ferroptosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from human PCK2 to positive regulation of ferroptosis. Reason: Human PCK2 phosphorylates and activates ACSL4, promoting ferroptosis-associated phospholipid remodelling in cancer cells (PMID:38720107). Plausible for the rat ortholog but rests on a single study and is peripheral to the metabolic role. Supporting Evidence: PMID:38720107 mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling |
| GO:0160020 positive regulation of ferroptosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: RGD ISO from human PCK2 to positive regulation of ferroptosis. Reason: Same claim as the Ensembl row; single human study, non-core. Supporting Evidence: PMID:38720107 mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling |
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Download this section (compressed HTML)Q: Did the whole-liver PEPCK activity measurements in PMID:11440903 and PMID:4353083 distinguish the mitochondrial isoform, or should those IDA rows move to Pck1?
Q: Is the protein kinase activity reported for human PCK2 on ACSL4 (PMID:38720107) conserved in rodent Pck2, and does it occur in the mitochondrial matrix or on a cytosolic pool?
Q: Should GO add a phosphoenolpyruvate biosynthetic process term so that PEP-forming enzymes are not annotated to pyruvate biosynthesis?
Q: The Ensembl-derived F1LQJ7 model begins without an initiator methionine (TLLPSPP...); is the correct start Met28, as in human and mouse PCK2?
Experiment: Isoform-specific (Pck1 vs Pck2 knockdown or fractionated) PEPCK activity assays in rat liver under the dietary conditions of PMID:11440903 to apportion activity to each isoform.
Experiment: In vitro kinase assay of recombinant rat Pck2 on ACSL4 with catalytic-site mutants to test whether the protein kinase activity uses the PEPCK active site.
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