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0  structures 629  species 0  interactions 5573  sequences 161  architectures

Family: DAGK_acc (PF00609)

Summary: Diacylglycerol kinase accessory domain

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This is the Wikipedia entry entitled "Diacylglycerol kinase". More...

Diacylglycerol kinase Edit Wikipedia article

Diacylglycerol kinase
Soluble diacylglycerol kinase DgkB from Staphylococcus aureus.png
DgkB, soluble DAGK from Staphylococcus aureus. α-helices in red, β-strands in yellow, coils in green.
EC number2.7.1.107
CAS number60382-71-0
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Prokaryotic diacylglycerol kinase
OPM superfamily196
OPM protein4d2e
Diacylglycerol kinase catalytic domain
Pfam clanCL0240
Diacylglycerol kinase accessory domain

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

Clinical significance

Mutations in the genes for deoxyguanosine kinase along with myophosphorylase have been associated with muscle glycogenosis and mitochondrial hepatopathy. The duplication in exon 6 of dGK that results in a truncated protein and the G456A PYGM mutation have been associated with phosphorylase deficiency in muscle, cytochrome c oxidase deficiency in liver, severe congenital hypotonia, hepatomegaly, and liver failure. This expands on the current understanding of McArdle disease and suggests that this combination of mutations could result in a complex disease with severe phenotypes.[5]


  1. ^ Mérida I, Avila-Flores A, Merino E (January 2008). "Diacylglycerol kinases: at the hub of cell signalling". The Biochemical Journal. 409 (1): 1–18. doi:10.1042/BJ20071040. PMID 18062770.
  2. ^ Smith RL, O'Toole JF, Maguire ME, Sanders CR (September 1994). "Membrane topology of Escherichia coli diacylglycerol kinase". Journal of Bacteriology. 176 (17): 5459–65. doi:10.1128/jb.176.17.5459-5465.1994. PMC 196734. PMID 8071224.
  3. ^ 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 diacylglycerol kinases". Structure. 16 (7): 1036–46. doi:10.1016/j.str.2008.03.019. PMC 2847398. PMID 18611377.
  4. ^ van Blitterswijk WJ, Houssa B (October 2000). "Properties and functions of diacylglycerol kinases". Cellular Signalling. 12 (9–10): 595–605. doi:10.1016/s0898-6568(00)00113-3. PMID 11080611.
  5. ^ Mancuso M, Filosto M, Tsujino S, Lamperti C, Shanske S, Coquet M, Desnuelle C, DiMauro S (October 2003). "Muscle glycogenosis and mitochondrial hepatopathy in an infant with mutations in both the myophosphorylase and deoxyguanosine kinase genes". Archives of Neurology. 60 (10): 1445–7. doi:10.1001/archneur.60.10.1445. PMID 14568816.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Diacylglycerol kinase accessory domain Provide feedback

Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. This domain is assumed to be an accessory domain: its function is unknown.

Literature references

  1. Sakane F, Yamada K, Kanoh H, Yokoyama C, Tanabe T; , Nature 1990;344:345-348.: Porcine diacylglycerol kinase sequence has zinc finger and E-F hand motifs. PUBMED:2156169 EPMC:2156169

  2. Sakane F, Imai S, Kai M, Wada I, Kanoh H; , J Biol Chem 1996;271:8394-8401.: Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases. PUBMED:8626538 EPMC:8626538

  3. Schaap D, de Widt J, van der Wal J, Vandekerckhove J, van Damme J, Gussow D, Ploegh HL, van Blitterswijk WJ, van der Bend RL; , FEBS Lett 1990;275:151-158.: Purification, cDNA-cloning and expression of human diacylglycerol kinase. PUBMED:2175712 EPMC:2175712

  4. Kanoh H, Yamada K, Sakane F; , Trends Biochem Sci 1990;15:47-50.: Diacylglycerol kinase: a key modulator of signal transduction? PUBMED:2159661 EPMC:2159661

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000756

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [PUBMED:3291115]:

  • Serine/threonine-protein kinases
  • Tyrosine-protein kinases
  • Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human [PUBMED:12471243]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [PUBMED:12368087]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [PUBMED:15078142], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [PUBMED:15320712].

Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. The DAG kinase domain is assumed to be an accessory domain. Upon cell stimulation, DAG kinase converts DAG into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. It catalyses the reaction: ATP + 1,2-diacylglycerol = ADP + 1,2-diacylglycerol 3-phosphate. The enzyme is stimulated by calcium and phosphatidylserine and phosphorylated by protein kinase C. This domain is always associated with INTERPRO.

Gene Ontology

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Domain organisation

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Seed source: SMART
Previous IDs: DAGKa;
Type: Family
Sequence Ontology: SO:0100021
Author: Ponting CP , Schultz J, Bork P
Number in seed: 37
Number in full: 5573
Average length of the domain: 153.60 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 19.55 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.3 21.3
Trusted cut-off 21.3 21.3
Noise cut-off 21.2 21.2
Model length: 159
Family (HMM) version: 20
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