2.7.1.30	evolution	although there are two African human pathogenic Trypanosoma subspecies: Trypanosoma brucei gambiense (Tbg) and Trypanosoma brucei rhodesiense (Tbr), it is reported in that the amino acid sequences of their GKs are exactly identical. Hence, TbgGK represents the glycerol kinase of both subspecies	
2.7.1.30	evolution	Bacteria and Eukarya have cell membranes with sn-glycerol-3-phosphate (G3P), whereas archaeal membranes contain sn-glycerol-1-phosphate (G1P). Determining the time at which cells with either G3P-lipid membranes or G1P-lipid membranes appeared is important for understanding the early evolution of terrestrial life. Reconstructed molecular phylogenetic trees of G1PDH (G1P dehydrogenase, EgsA/AraM), which is responsible for G1P synthesis and G3PDHs (G3P dehydrogenase, GpsA and GlpA/GlpD), and glycerol kinase (GlpK), which is responsible for G3P synthesis. Together with the distribution of these protein-encoding genes among archaeal and bacterial groups, phylogenetic analyses suggest that GlpA/GlpD in the Commonote (the last universal common ancestor of all extant life with a cellular form, Commonote commonote) acquired EgsA (G1PDH) from the archaeal common ancestor (Commonote archaea) and acquired GpsA and GlpK from a bacterial common ancestor (Commonote bacteria). The Commonote probably possessed a G3P-lipid membrane synthesized enzymatically, after which the archaeal lineage acquires G1PDH followed by the replacement of a G3P-lipid membrane with a G1P-lipid membrane. Detailed overview	
2.7.1.30	evolution	both Gykl1 and Gk2 are thought to have arisen by the transposition of Gk located on the X chromosome, and have high homology with Gk. But both Gykl1 and Gk2 show testis-specific expression, and the proteins have no glycerol kinase activity in vitro, unlike GK and GK5	
2.7.1.30	evolution	glycerol kinase is a member of the ATPase superfamily, which includes hexokinase, actin, and heat shock protein. These share a common betabetabetaalphabetaalphabetaalpha folding motif and markedly change conformation upon substrate binding because of interdomain motion	
2.7.1.30	malfunction	a glycerol kinase knockout strain is incapable to grow on glycerol and shows higher NADPH-dependent xylitol production compared to the wild type strain	
2.7.1.30	malfunction	frequently observed variation in the glpK coding sequence produces a drug-tolerant phenotype that can reduce antibiotic efficacy and may contribute to the evolution of resistance. Common variation in a homopolymeric region in the glpK gene is associated with drug resistance in clinical isolates. Glycerol catabolic defects are associated with extensive drug resistance in Korea. A panel of Korean Mycobacterium tuberculosis isolates that vary in drug sensitivity profiles, from fully sensitive strains to extensively evolved clones that are phenotypically resistant to more than ten different antibiotics. GlpK frameshift mutations are common in Mycobacterium tuberculosis isolates and associated with drug resistance in Peru	
2.7.1.30	malfunction	Gk2-deficient mice show male infertility with disordered mitochondrial sheath formation. Gk2 disrupted mice are male infertile because their spermatozoa cannot pass through the uterotubal junction (UTJ) due to reduced motility. Disorganization of the mitochondrial sheath occurs in glycerol kinase 2 (Gk2) disrupted mice	
2.7.1.30	malfunction	overexpression of glycerol kinase GlcA bypasses the requirement of glycerol-3-phosphate dehydrogenase (EC 1.1.1.8), encoded by gene gfdA, in glucose media for colony growth. The DELTAgfdADELTAglcA double mutant shows an exacerbation of colony defects in both glucose and glycerol media	
2.7.1.30	malfunction	overexpression of glycerol kinase under oxidative stress with glycerol supplementation leads to enhancement of lipid production in Synechocystis sp. PCC 6803	
2.7.1.30	malfunction	silencing GK5 in PC9R cells induces mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via SREBP1/SCD1 signaling pathway. The exosomal mRNA of GK5 in the plasma of patients with gefitinib-resistant adenocarcinoma is significantly higher compared with that of gefitinib-sensitive patients. GK5 knockdown induces PC9R cell apoptosis and cell cycle arrest in the presence of gefitinib, as well as PC9R cell mitochondrial dysfunction and caspase activation. GK5 knockdown suppresses tumor proliferation in vivo	
2.7.1.30	metabolism	the enzyme plays an essential role in central and lipid metabolism	
2.7.1.30	metabolism	an EIIA homologue in the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS or KPN00353, UniProt ID A6T5D4), negatively regulates the 1,3-propanediol (1,3-PD) production in Klebsiella pneumoniae, mutational analysis, overview. Residue His65 of KPN00353 is important for binding to GlpK, weak binding to enzyme GlpK mutant H65Q	
2.7.1.30	metabolism	glycerol 3-phosphate (G3P) can be synthesized by two classical pathways. The first pathway is catalyzed by an NAD-dependent glycerol 3-phosphate dehydrogenase converting dihydroxyacetone phosphate (DHAP) into G3P The second pathway is catalyzed by a glycerol kinase encoded by glcA converting glycerol to G3P	
2.7.1.30	metabolism	glycerol kinase (GK) is a key enzyme of glycerol metabolism. It participates in glycolysis and lipid membrane biosynthesis	
2.7.1.30	metabolism	glycerol kinase interacts with nuclear receptor NR4A1 and regulates glucose metabolism in the liver, Gyk interacts with NR4A1 in the nucleus	
2.7.1.30	metabolism	lipase, glycerol kinase, and glycerol-3-phosphate oxidase are required for lipid analysis in a cascade reaction	
2.7.1.30	metabolism	Mycobacterium tuberculosis genes that alter the rate of bacterial clearance in drug-treated mice. Several functionally distinct bacterial genes are found to alter bacterial clearance, and prominent among these is the glpK gene that encodes the glycerol-3-kinase enzyme that is necessary for glycerol catabolism. Growth on glycerol generally increases the sensitivity of Mycobacterium tuberculosis to antibiotics in vitro, and glpK-deficient bacteria persist during antibiotic treatment in vivo, particularly during exposure to pyrazinamide-containing regimens. Reversible high-frequency variation in carbon metabolic pathways can produce phenotypically drug-tolerant clones and have a role in the development of resistance. The glycerol metabolism increases drug efficacy in vitro and during murine infection, overview	
2.7.1.30	metabolism	overview of the stereospecific biosynthetic pathways of glycerol 1-phosphate (G1P) and glycerol 3-phosphate (G3P)	
2.7.1.30	additional information	detailed kinetic analysis of glycerol kinase as a function of Mg2+ to ATP molar ratio, and multinuclear NMR study of the Mg-ATP complex formation is described in order to elucidate the effect of Mg2+ in modifying the physical and chemical features of ATP, and mechanistic elucidation of the effect of Mg-ATP interaction on the catalytic properties of glycerol kinase, overview	
2.7.1.30	additional information	NR4A1-Gyk b interaction analysis using protein fragments	
2.7.1.30	additional information	the enzyme uses a common catalytic site for both activities, phosphatase and kinase	
2.7.1.30	physiological function	glycerol kinase expression leads to increased fat storage in H4IIE rat hepatoma cells	
2.7.1.30	physiological function	the enzyme is essential for energy metabolism	
2.7.1.30	physiological function	enzyme glycerol kinase 2 (GK2) is essential for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during mouse spermatogenesis	
2.7.1.30	physiological function	GK5 confers gefitinib resistance in lung cancer by inhibiting apoptosis and cell cycle arrest. Role of glycerol kinase 5 (GK5) in mediating gefitinib resistance in non-small cell lung cancer (NSCLC), overview. GK5 confers gefitinib resistance through upregulating SCD1 expression, molecular mechanism underlying GK5-mediated gefitinib resistance	
2.7.1.30	physiological function	glycerol kinase (GK) catalyzes the Mg/ATP-dependent phosphorylation of glycerol to produce glycerol-3-phosphate which is an important metabolic intermediate in glycolysis. In the absence of glycerol, Tk-GK was a dimer in solution. In the presence of its glycerol substrate, it becomes a hexamer consisting of three symmetrical dimers about the threefold axis. Through glycerol binding, all Tk-GK molecules in the hexamer are in closed form as a result of domain-motion. The closed form of Tk-GK has 10fold higher ATP affinity than the open form of enzyme Tk-GK. The hexamer structure stabilizes the closed conformation and enhances ATP binding affinity when the glycerol kinase is bound to glycerol	
2.7.1.30	physiological function	glycerol kinase (GlpK) is responsible for sn-glycerol 3-phosphate (G3P) synthesis	
2.7.1.30	physiological function	glycerol kinase (Gyk), consisting of 4 isoforms, plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP-dependent reaction. The nuclear orphan receptor subfamily 4 group A member (NR4A)-1 (also known as Nur77, NGFI-B, NAK-1, or TR3is) an important regulator of hepatic glucose homeostasis and lipid metabolism in adipose tissue. Nuclear Gyk isoform b is a corepressor of NR4A1 in the liver. This recruitment is dependent on the C-terminal ligand-binding domain instead of the N-terminal activation function 1 domain, which interacts with other NR4A1 coregulators. NR4A1 transcriptional activity is inhibited by Gyk via protein-protein interaction but not enzymatic activity. Moreover, Gyk overexpression suppresses NR4A1 ability to regulate the expression of target genes involved in hepatic gluconeogenesis in vitro and in vivo as well as blood glucose regulation, which is observed in both unfed and diabetic transfected mice. Moonlighting function of nuclear Gyk isozyme b, which acts as a coregulator of NR4A1, participating in the regulation of hepatic glucose homeostasis in the unfed state and diabetes. The Gyk activity does not affect the interaction between Gyk and NR4A1, Gyk antagonizes the effects of NR4A1 on hepatic gluconeogenesis in vitro and in vivo	
2.7.1.30	physiological function	glycerol plays an important role in the adaptation of fungi to various microenvironments and stressors, including heat shock, anoxic conditions and osmotic stress. Glycerol kinase GlcA coordinately adapts to various carbon sources and osmotic stress in Aspergillus fumigatus. It is suggested that glcA is required when glycerol is the sole carbon source, and gfdA is required when glucose is the sole carbon source, functional relationship between gfdA and glcA, overview