Pck2 (rat) — manual literature research

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Identity

• Gene: Pck2, phosphoenolpyruvate carboxykinase 2, mitochondrial (PEPCK-M); RGD:1311112; NCBI GeneID 361042.
• UniProt: GOA is keyed to the unreviewed TrEMBL entry F1LQJ7 (667 aa, Ensembl ENSRNOP00000025260).
  The accession requested for this review, B2RYG2 (663 aa, MGC cDNA, flagged "Fragment"), is the same
  gene (same symbol, RGD:1311112, GeneID 361042) but carries no GOA rows; the review is on F1LQJ7.
• F1LQJ7 begins "TLLPSPPSLT..." with no initiator methionine; the human PCK2 start (MAAL...) aligns to
  rat Met28 ("MAAMYLPGLRL..."), so residues 1-27 of the Ensembl model are probably 5' UTR translation.
• Family: GTP-dependent PEPCK (Pfam PF00821/PF17297, HAMAP MF_00452, PROSITE PS00505, PANTHER
  PTHR11561:SF11 "PHOSPHOENOLPYRUVATE CARBOXYKINASE [GTP], MITOCHONDRIAL").

Enzyme activity and location

• Mammals have two PEPCK genes: PCK1 (cytosolic, PEPCK-C) and PCK2 (mitochondrial, PEPCK-M)
  PMID:24177027.
• PEPCK-M acts in the matrix PMID:24177027.
• Mn2+ is the most activating cation PMID:24177027.
• Rat liver: mitochondrial PEPCK activity measured in foetal, newborn and adult rat liver and
  indistinguishable kinetically from the soluble enzyme PMID:6049928.
  In adult rat liver >90% of PEPCK activity is cytosolic (PCK1) PMID:6049928,
  so whole-liver PEPCK activity measurements (PMID:11440903, PMID:4353083; abstract-only) mostly report PCK1.
• Rat INS-1 832/13 cells and rat islets: PEPCK activity is mitochondrial, verified with glutamate
  dehydrogenase as a matrix marker PMID:19635791.

Biological roles (rat evidence)

• Insulin secretion (rat beta-cell line, rat islets): PEPCK-M consumes OAA and mtGTP to make PEP
  PMID:19635791;
  up to 41% of islet PEP comes from PEPCK-M, and knockdown abolishes GSIS
  PMID:19635791.
• Hepatic gluconeogenesis (rat, ASO knockdown in vivo and in hepatocytes)
  PMID:24497630.
• Endotoxaemia/TNF lower hepatic Pck2 mRNA and PEPCK-M activity PMID:19268478.
• Prenatal dexamethasone programming of hepatic Pck2 expression PMID:16570165.

Non-canonical protein kinase activity (human)

• Human PCK2 phosphorylates ACSL4 Thr679 and promotes ferroptosis in cancer cells (single study)
  PMID:38720107.
  Not tested in rat; the paralog PCK1 has a reported analogous protein-kinase activity.