PCK1

Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:24863970, PubMed:26971250, PubMed:28216384, PubMed:30193097). Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle (PubMed:24863970, PubMed:26971250, PubMed:28216384, PubMed:30193097). At low glucose levels, it 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). Acts as a regulator of formation and maintenance of memory CD8(+) T-cells: 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 the phosphoenolpyruvate carboxykinase activity, 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, 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).

Phosphoenolpyruvate carboxykinase deficiency, cytosolic

PCKDC

An autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, hypoglycemia, hypotonia, hepatomegaly, hepatic dysfunction, failure to thrive, lactic acidosis, and elevated tricarboxylic acid intermediates, particularly fumarate, in urine.

None

The disease is caused by variants affecting the gene represented in this entry.

Carbohydrate biosynthesis; gluconeogenesis.

Acetylated. Lysine acetylation by p300/EP300 is increased on high glucose conditions (PubMed:20167786, PubMed:21726808, PubMed:30193097). Lysine acetylation promotes ubiquitination by UBR5 (PubMed:21726808). Acetylation is enhanced in the presence of BAG6. Deacetylated by SIRT2. Deacetylation of Lys-91 is carried out by SIRT1 and depends on PCK1 phosphorylation levels (PubMed:30193097).

Phosphorylated in a GSK3B-mediated pathway; phosphorylation affects the efficiency of SIRT1-mediated deacetylation, and regulates PCK1 ubiquitination and degradation (PubMed:30193097). Phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes the protein kinase activity: phosphorylated PCK1 translocates to the endoplasmic reticulum, where it phosphorylates INSIG1 and INSIG2 (PubMed:32322062).

Ubiquitination by UBR5 leads to proteasomal degradation.

Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.

Major sites of expression are liver, kidney and adipocytes.

• Cytoplasm
• Cytosol
• Endoplasmic reticulum
• Phosphorylation at Ser-90 promotes translocation to the endoplasmic reticulum.

PEPCK1, PCK1, PEPCK-C, Serine-protein kinase PCK1

• entrezGene:5105
• omim:614168
• swissprot:P35558

Proteins

Immunology & Infectious Disease

69195Da