Summary: Diacylglycerol kinase catalytic domain
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Diacylglycerol kinase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Prokaryotic diacylglycerol kinase|
|Diacylglycerol kinase catalytic domain|
|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.
In bacteria, DGK is very small (13 to 15 kD) membrane protein which seems to contain three transmembrane domains. 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.
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. These are as follows:
- Type 1 - DGK-Î±, DGK-Î², DGK-Î³ - contain EF-hand motifs and a recoverin homology domain
- Type 2 - DGK-Î´, DGK-Î· - contain a pleckstrin homology domain
- Type 3 - DGK-Îµ - has specificity for arachidonate-containing DAG
- Type 4 - DGK-Î¶, DGK-Î¹ - contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localisation signal, and a PDZ-binding motif.
- Type 5 - DGK-Î¸ - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region
- MÃ©rida I, Avila-Flores A, Merino E (January 2008). "Diacylglycerol kinases: at the hub of cell signalling". The Biochemical Journal. 409 (1): 1â€“18. doi:10.1042/BJ20071040. PMIDÂ 18062770.
- Smith RL, O'Toole JF, Maguire ME, Sanders CR (September 1994). "Membrane topology of Escherichia coli diacylglycerol kinase". Journal of Bacteriology. 176 (17): 5459â€“65. doi:10.1128/jb.176.17.5459-5465.1994. PMCÂ 196734. PMIDÂ 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 diacylglycerol kinases". Structure. 16 (7): 1036â€“46. doi:10.1016/j.str.2008.03.019. PMCÂ 2847398. PMIDÂ 18611377.
- van Blitterswijk WJ, Houssa B (October 2000). "Properties and functions of diacylglycerol kinases". Cellular Signalling. 12 (9â€“10): 595â€“605. doi:10.1016/s0898-6568(00)00113-3. PMIDÂ 11080611.
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 catalytic domain Provide feedback
Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. The catalytic domain is assumed from the finding of bacterial homologues. YegS is the Escherichia coli protein in this family whose crystal structure reveals an active site in the inter-domain cleft formed by four conserved sequence motifs, revealing a novel metal-binding site. The residues of this site are conserved across the family .
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
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
Bakali HM, Herman MD, Johnson KA, Kelly AA, Wieslander A, Hallberg BM, Nordlund P; , J Biol Chem. 2007;282:19644-19652.: Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site. PUBMED:17351295 EPMC:17351295
Internal database links
|SCOOP:||NAD_kinase Neisseria_PilC Peripla_BP_6 PFK Tim54|
|Similarity to PfamA using HHSearch:||NAD_kinase|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001206
The DAG-kinase catalytic domain or DAGKc domain is present in mammalian lipid kinases, such as diacylglycerol (DAG), ceramide and sphingosine kinases, as well as in related bacterial proteins [ PUBMED:8626538 , PUBMED:17351295 ]. Eukaryotic DAG-kinase ( EC ) catalyses the phosphorylation of DAG to phosphatidic acid, thus modulating the balance between the two signaling lipids. At least ten different isoforms have been identified in mammals, which form 5 groups characterised by different functional domains, such as the calcium-binding EF hand (see PROSITEDOC ), PH (see PROSITEDOC ), SAM (see PROSITEDOC ) , DAG/PE-binding C1 domain (see PROSITEDOC ) and ankyrin repeats (see PROSITEDOC ) [ PUBMED:17512245 ].
In bacteria, an integral membrane DAG kinase forms a homotrimeric protein that lacks the DAGKc domain (see PROSITEDOC ). In contrast, the bacterial yegS protein is a soluble cytosolic protein that contains the DAGKc domain in the N-terminal part. YegS is a lipid kinase with two structural domains, wherein the active site is located in the interdomain cleft, C-terminal to the DAGKc domain which forms an alpha/beta fold [ PUBMED:17351295 ]. The tertiary structure resembles that of NAD kinases and contains a metal-binding site in the C-terminal region [ PUBMED:17351295 , PUBMED:19112175 ].
This domain is usually associated with an accessory domain (see INTERPRO ).
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||kinase activity (GO:0016301)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan includes two SCOP superfamilies. Strong similarities between NAD kinases, DAG kinase, sphingosine kinase and PFK have previously been shown.
The clan contains the following 4 members:DAGK_cat NAD_kinase PFK Pfk_N
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Seed source:||Alignment kindly provided by SMART|
|Author:||SMART, Coggill P|
|Number in seed:||105|
|Number in full:||27760|
|Average length of the domain:||124.00 aa|
|Average identity of full alignment:||25 %|
|Average coverage of the sequence by the domain:||22.72 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||27|
|Download:||download the raw HMM for this family|
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DAGK_cat domain has been found. There are 51 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.