Recombinant Human Phosphoglycerate kinase 1 (PGK1)

Function

Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines (PubMed:18463139). In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis (PubMed:26942675, PubMed:36849569). May play a role in sperm motility (PubMed:26677959)

Subcellular Location

Cytoplasm, cytosol; Mitochondrion matrix

Disease Association

Phosphoglycerate kinase 1 deficiency (PGK1D) : A condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations, and some affected individuals develop parkinsonian symptoms. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Mainly expressed in spermatogonia. Localized on the principle piece in the sperm (at protein level). Expression significantly decreased in the testis of elderly men

Subunit

Monomer (PubMed:18463139). Interacts with kinase MAPK1/ERK2; the interaction is direct, occurs under hypoxic conditions, and promotes its interaction with PIN1 (PubMed:26942675). Interacts with peptidyl-prolyl cis-trans isomerase PIN1; the interaction is direct, occurs under hypoxic conditions, and targets the protein to the mitochondrion by promoting interactions with the TOM complex (PubMed:26942675). Interacts with mitochondrial circRNA mcPGK1 (via its 2nd stem-loop); the interaction is direct and targets the protein to the mitochondrion by promoting interactions with the TOM complex (PubMed:36849569). Interacts with pyruvate dehydrogenase kinase PDK1; the interaction is direct, occurs under hypoxic conditions and leads to PDK1-mediated inhibition of pyruvate dehydrogenase complex activity (PubMed:26942675)

Pathway

Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 2/5

• Michelson A.M. et al. Isolation and DNA sequence of a full-length cDNA clone for human X chromosome-encoded phosphoglycerate kinase. — Proc. Natl. Acad. Sci. U.S.A. (1983)
• Michelson A.M. et al. Structure of the human phosphoglycerate kinase gene and the intron-mediated evolution and dispersal of the nucleotide-binding domain. — Proc. Natl. Acad. Sci. U.S.A. (1985)
• Kim J.W. et al. Identification of a human migration-inducing gene 10 (MIG10). (SEP-)
• Shichijo S. et al. Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients. (MAY-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Ebert L. et al. Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201). (JUN-)
• Ross M.T. et al. The DNA sequence of the human X chromosome. — Nature (2005)
• Mural R.J. et al. PubMed: CI-56FTJV1JKRRTT (SEP-)