Pyruvate kinase PKLR

Function

Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis. Also produces the side product 2-phospholactate which can inhibit fructose-2,6-bisphosphate production. 2-phospholactate can be dephosphorylated by PGP which prevents the inhibition of fructose-2,6-bisphosphate production and allows glycolysis to occur.

Classification

Family (Pfam)

PF00224 PK, PF02887 PK_C

InterPro

Pyr_Knase, Pyrv/PenolPyrv_kinase-like_dom, Pyrv_kinase-like_dom_sf, Pyrv_Knase-like_insert_dom_sf, Pyrv_Knase_AS, Pyrv_Knase_brl, Pyrv_Knase_C, Pyrv_Knase_C_sf, Pyrv_Knase_insert_dom_sf

Functional cluster

Tubulins & Mitochondrial Metabolic Enzymes

Experimental structures · PDB · 55

• 2VGB X-ray 2.73A
• 2VGF X-ray 2.75A
• 2VGG X-ray 2.74A
• 2VGI X-ray 2.87A
• 4IMA X-ray 1.95A
• 4IP7 X-ray 1.80A
• 5SC8 X-ray 1.77A
• 5SC9 X-ray 1.69A
• 5SCA X-ray 1.92A
• 5SCB X-ray 1.80A
• 5SCC X-ray 1.89A
• 5SCD X-ray 2.04A
• … and 43 more

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0005524 ATP binding
• GO:0016301 kinase activity
• GO:0000287 magnesium ion binding
• GO:0048029 monosaccharide binding
• GO:0030955 potassium ion binding
• GO:0004743 pyruvate kinase activity
• GO:0071872 cellular response to epinephrine stimulus
• GO:0032869 cellular response to insulin stimulus
• GO:0006096 glycolytic process
• GO:0042866 pyruvate biosynthetic process
• GO:0033198 response to ATP
• GO:0051591 response to cAMP
• GO:0009749 response to glucose
• GO:0001666 response to hypoxia
• GO:0010038 response to metal ion
• GO:0007584 response to nutrient

Disease associations

• pyruvate kinase hyperactivity MONDO:0007067
• pyruvate kinase deficiency of red cells MONDO:0009950

Drugs targeting this protein · 3

• MITAPIVAT SULFATE activator
• MITAPIVAT activator
• ETAVOPIVAT activator

Related proteins · sequence + function similarity

• Pyruvate kinase PKLR 0.97
• Pyruvate kinase PKLR 0.95
• Pyruvate kinase PKLR 0.93
• Pyruvate kinase PKM 0.83
• Pyruvate kinase PKM 0.82
• Pyruvate kinase PKM 0.81
• Pyruvate kinase PKM 0.81
• Pyruvate kinase PKM 0.80
• Pyruvate kinase PKM 0.79
• Pyruvate kinase PKM 0.79
• Pyruvate kinase 0.78
• Pyruvate kinase PKM 0.76

Co-cited proteins · studied together in the literature

• Phosphoglycolate phosphatase 1 shared papers
• Phosphoglycolate phosphatase 1 shared papers
• Phosphoglycolate phosphatase 1 shared papers

Literature · 29 cited papers

• A conserved phosphatase destroys toxic glycolytic side products in mammals and yeast. Nat. Chem. Biol. · 2016
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Exome sequencing and unrelated findings in the context of complex disease research: ethical and clinical implications. Discov. Med. · 2011
• Fifteen novel mutations in PKLR associated with pyruvate kinase (PK) deficiency: structural implications of amino acid substitutions in PK. Hum. Mutat. · 2009
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia. J. Biol. Chem. · 2002
• Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients. Br. J. Haematol. · 2001
• Hematologically important mutations: red cell pyruvate kinase (third update). Blood Cells Mol. Dis. · 2000
• Hematologically important mutations: red cell pyruvate kinase (2nd update). Blood Cells Mol. Dis. · 1998
• A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha-2 globin gene variant (Hb Conakry). Br. J. Haematol. · 1998
• Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. Br. J. Haematol. · 1998
• … and 17 more in the literature graph