Diacylglycerol kinase

Diacylglycerol kinase (DGK or DAGK) is a family of enzymes that catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low allowing DAG to be used for glycerophospholipid biosynthesis but on receptor activation of the phosphoinositide pathway, DGK activity increases driving the conversion of DAG to PA. As both lipids are thought to function as bioactive lipid signaling molecules with distinct cellular targets, DGK therefore occupies an important position, effectively serving as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another.^[1]

In bacteria, DGK is very small (13 to 15 kD) membrane protein which seems to contain three transmembrane domains.^[2] The best conserved region is a stretch of 12 residues which are located in a cytoplasmic loop between the second and third transmembrane domains. Some Gram-positive bacteria also encode a soluble diacylglycerol kinase capable of reintroducing DAG into the phospholipid biosynthesis pathway. DAG accumulates in Gram-positive bacteria as a result of the transfer of glycerol-1-phosphate moieties from phosphatidylglycerol to lipotechoic acid.^[3]

Mammalian DGK Isoforms

Currently, nine members of the DGK family have been cloned and identified. Although all family members have conserved catalytic domains and two cysteine rich domains, they are further classified into five groups according to the presence of additional functional domains and substrate specificity.^[4] These are as follows:

Type 1 - DGK-α, DGK-β, DGK-γ - contain EF-hand motifs and a recoverin homology domain
Type 2 - DGK-δ, DGK-η - contain a pleckstrin homology domain
Type 3 - DGK-ε - has specificity for arachidonate-containing DAG
Type 4 - DGK-ζ, DGK-ι - contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localisation signal, and a PDZ-binding motif.
Type 5 - DGK-θ - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region

References

↑ Merida I, Avila-Flores A, Merino E (2008). "Diacylglycerol kinases: at the hub of cell signalling.". Biochem. J. 409 (1): 1–18. doi:10.1042/BJ20071040. PMID 18062770.
↑ Smith RL, O'Toole JF, Maguire ME, Sanders CR (September 1994). "Membrane topology of Escherichia coli diacylglycerol kinase". J. Bacteriol. 176 (17): 5459–65. PMC 196734. PMID 8071224.
↑ Miller DJ, Jerga A, Rock CO, White SW (July 2008). "Analysis of the Staphylococcus aureus DgkB structure reveals a common catalytic mechanism for the soluble diacylglycol kinases". Structure. 16 (7): 1036–46. doi:10.1016/j.str.2008.03.019. PMC 2847398. PMID 18611377.
↑ Van Blitterswijk, WJ; Houssa, B (2000). "Properties and functions of diacylglycerol kinases.". Cellular Signaling. 1 (9-10): 595–605. PMID 11080611.

External links

Diacylglycerol Kinase at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 2.7.1.107

Anabolism

to diacylglycerol: Acyltransferase Phosphatidate phosphatase 2C

Choline kinase CHKA CHKB Choline-phosphate cytidylyltransferase

phosphatidylinositol glycan anchor biosynthesis: PIGA PIGB PIGC PIGF PIGG PIGH PIGK PIGL PIGM PIGN PIGO PIGP PIGQ PIGS PIGT PIGU PIGV PIGW PIGX PIGY PIGZ

cardiolipin: Tafazzin

Catabolism

Phospholipase C

Diacylglycerol kinase DGKA DGKB DGKD DGKE DGKG DGKH DGKI DGKK DGKQ DGKZ

Phosphoric monoester hydrolases Inositol-phosphate phosphatase

Transferases: phosphorus-containing groups (EC 2.7)

2.7.1-2.7.4:
phosphotransferase/kinase
(PO₄)

2.7.1: OH acceptor	Hexo- Gluco- Fructo- Hepatic Galacto- Phosphofructo- 1 Liver Muscle Platelet 2 Riboflavin Shikimate Thymidine ADP-thymidine NAD⁺ Glycerol Pantothenate Mevalonate Pyruvate Deoxycytidine PFP Diacylglycerol Phosphoinositide 3 Class I PI 3 Class II PI 3 Sphingosine Glucose-1,6-bisphosphate synthase

2.7.2: COOH acceptor	Phosphoglycerate Aspartate kinase

2.7.3: N acceptor	Creatine

2.7.4: PO₄ acceptor	Phosphomevalonate Adenylate Nucleoside-diphosphate Uridylate Guanylate Thiamine-diphosphate

2.7.6: diphosphotransferase
(P₂O₇)

2.7.7: nucleotidyltransferase
(PO₄-nucleoside)

Polymerase

DNA polymerase	DNA-directed DNA polymerase I II III IV V RNA-directed DNA polymerase Reverse transcriptase Telomerase DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase

RNA nucleotidyltransferase	RNA polymerase/DNA-directed RNA polymerase RNA polymerase I RNA polymerase II RNA polymerase III RNA polymerase IV Primase RNA-dependent RNA polymerase PNPase

Phosphorolytic
3' to 5' exoribonuclease

Nucleotidyltransferase

Guanylyltransferase

mRNA capping enzyme

Other

2.7.8: miscellaneous

Phosphatidyltransferases	CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase CDP-diacylglycerol—serine O-phosphatidyltransferase CDP-diacylglycerol—inositol 3-phosphatidyltransferase CDP-diacylglycerol—choline O-phosphatidyltransferase

Glycosyl-1-phosphotransferase	N-acetylglucosamine-1-phosphate transferase

2.7.10-2.7.13: protein kinase
(PO₄; protein acceptor)

2.7.10: protein-tyrosine	see tyrosine kinases

2.7.11: protein-serine/threonine	see serine/threonine-specific protein kinases

2.7.12: protein-dual-specificity	see serine/threonine-specific protein kinases

2.7.13: protein-histidine	Protein-histidine pros-kinase Protein-histidine tele-kinase Histidine kinase

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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