PCK1
Description
The PCK1 (phosphoenolpyruvate carboxykinase 1) is a protein-coding gene located on chromosome 20.
Phosphoenolpyruvate carboxykinase 1 (soluble), also known as PCK1, is an enzyme which in humans is encoded by the PCK1 gene.
== Function == This enzyme is a main control point for the regulation of gluconeogenesis. The cytosolic enzyme encoded by this gene, along with GTP, catalyzes the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP. The expression of this gene can be regulated by insulin, glucocorticoids, glucagon, cAMP, and diet. A mitochondrial isozyme of the encoded protein also has been characterized.
== Interactive pathway map == Click on genes, proteins and metabolites below to link to respective articles.
PCK1 is a cytosolic enzyme that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:30193097, PubMed:24863970, PubMed:26971250, PubMed:28216384). It regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle (PubMed:30193097, PubMed:24863970, PubMed:26971250, PubMed:28216384). At low glucose levels, PCK1 catalyzes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle (PubMed:30193097). At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate (PubMed:30193097). PCK1 also acts as a regulator of formation and maintenance of memory CD8(+) T-cells: it is up-regulated in these cells, where it generates phosphoenolpyruvate, via gluconeogenesis (By similarity). The resultant phosphoenolpyruvate flows to glycogen and pentose phosphate pathway, which is essential for memory CD8(+) T-cells homeostasis (By similarity). In addition to its phosphoenolpyruvate carboxykinase activity, PCK1 also acts as a protein kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes an atypical serine protein kinase activity using GTP as donor (PubMed:32322062). The protein kinase activity regulates lipogenesis: upon phosphorylation at Ser-90, PCK1 translocates to the endoplasmic reticulum and catalyzes phosphorylation of INSIG proteins (INSIG1 and INSIG2), thereby disrupting the interaction between INSIG proteins and SCAP and promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes (PubMed:32322062). {ECO:0000250|UniProtKB:Q9Z2V4, ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250, ECO:0000269|PubMed:28216384, ECO:0000269|PubMed:30193097, ECO:0000269|PubMed:32322062}
PCK1 is also known as PCKDC, PEPCK-C, PEPCK1, PEPCKC.
