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FLASH GENE

Symbol

PCK1

contributors: mct - updated : 15-05-2020

HGNC name	phosphoenolpyruvate carboxykinase 1 (soluble)
HGNC id	8724

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies	homolog to murine Pck1
	homolog to C.elegans r11a5.4

Homologene

FAMILY

phosphoenolpyruvate carboxykinase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic

basic FUNCTION	main control point for the regulation of gluconeogenesis
	catalyzing the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP
	functions in the pathway for the conversion of gluconeogenic precursors to glucose and contributes to glycerol-3-phosphate synthesis through glyceroneogenesis
	PCK1 plays an important role in both the mammary gland adipocytes and epithelial cells during lactation
	acid-induced PCK1 provides glucose for acid-base homeostasis at an individual level, which is supported by rapid pumping of H(+) via V-ATPase at the cellular level
	PCK1 plays a regulatory role in gluconeogenesis and glyceroneogenesis
	PCK1 activity contributes to metabolic reprogramming and polarization in macrophages
	importance of the protein kinase activity of PCK1 in the activation of SREBPs, lipogenesis and the development of hepatocellular carcinoma (HCC)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

carbohydrate , energetic

signaling

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	GTP

protein	PCK1 is acetylated by the EP300 acetyltransferase, and this acetylation stimulates the interaction between PCK1 and UBR5, a HECT domain containing E3 ubiquitin ligase, therefore promoting PCK1 ubiquitinylation and degradation
	overexpression of ESRRG induced PCK1 and G6PC gene expression and glucose production in primary hepatocytes
	thyroid hormone (TH), a regulator of hepatic gluconeogenesis acts through its nuclear receptor (THRA, THRB) to induce the expression of PCK1 and G6PC
	mechanistically, LAMTOR5 inhibited the expression of PCK1 through down-regulating transcription factor FOXO1 in hepatoma cells
	CREB3L3 regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including PYGL, PCK1, and G6PC
	PCK1 reduces the stability of LDHA through posttranslational regulation and the effects of PCK1 on glucose metabolism, cell proliferation and metastasis are mediated via the inhibition of LDHA
	gluconeogenic enzyme PCK1 phosphorylates INSIG1/INSIG2 for lipogenesis

cell & other

REGULATION

induced by	thyroid hormone T3 and CAMP
		glucagon

repressed by

insulin

Other

acetylation regulates the stability of the gluconeogenic rate-limiting enzyme PCK1, thereby modulating cellular response to glucose

ASSOCIATED DISORDERS

corresponding disease(s)

PCKDC

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   lower in clinical hepatocellular carcinoma (HCC) tissues than that in normal tissues

Susceptibility

to type 2 diabetes mellitus to late-onset Alzheimer's disease

Variant & Polymorphism SNP	promoter SNP associated with type 2 diabetes mellitus

Candidate gene
Marker	PCK1 may serve as a candidate prognostic biomarker in clear cell renal cell carcinoma (ccRCC)
Therapy target
	System Type Disorder Pubmed cancer urinary   targeting the PCK1/LDHA pathway might be a new strategy to selectively inhibit tumor metabolism in in clear cell renal cell carcinoma cancer digestive colon DHODH and PCK1 are metabolic therapeutic targets in Colorectal metastatic progression

ANIMAL & CELL MODELS