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	PROSITE documentation PDOC50146 [for PROSITE entry PS50146]

DAG-kinase catalytic (DAGKc) domain profile

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 [1,2]. Eukaryotic DAG-kinase (EC 2.7.1.107) catalyzes 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 characterized by different functional domains, such as the calcium-binding EF hand (see <PDOC00018>), PH (see <PDOC50003>), SAM (see <PDOC50105>), DAG/PE-binding C1 domain (see <PDOC00379>) and ankyrin repeats (see <PDOC50088>) [3].

In bacteria, an integral membrane DAG kinase forms a homotrimeric protein that lacks the DAGKc domain (see <PDOC00820>). 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 α/β fold (see <PDB: 2BON; A>) [2]. The tertiary structure resembles that of NAD kinases and contains a metal-binding site in the C-terminal region [2,4].

Some proteins known to contain a DAGKc domain are listed below:

• Mammalian diacylglycerol kinase (DGK/DAGK, EC 2.7.1.107), which upon cell stimulation converts the second messenger DAG into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity.
• Mammalian sphingosine kinase (EC 2.7.1.91), which catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions.
• Mammalian mitochondrial acylglycerol kinase (mulK, EC 2.7.1.94), a lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid and phosphatidic acid, respectively.
• Mammalian ceramide kinase (EC 2.7.1.138), which catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate.
• Bacterial lipid kinase yegS (EC 2.7.1.-), which in vitro phosphorylates phosphatidylglycerol but not diacylglycerol; probably phosphorylates lipids.
• Fruit fly diacylglycerol kinases (EC 2.7.1.107).
• Caenorhabditis elegans putative diacylglycerol kinase K06A1.6 and protein F52C9.3
• Plant sphingoid long-chain bases kinase.
• Yeast sphingoid long-chain bases kinase.

The profile we developed covers the entire DAGKc domain.

Last update:

June 2009 / First entry.

PROSITE method (with tools and information) covered by this documentation:

DAGK, PS50146; DAG-kinase catalytic (DAGKc) domain profile  (MATRIX)

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 193
  • detected by PS50146: 193 (true positives)
  • undetected by PS50146: 0 (false negative or 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS50146:
  NONE.
• Domain architecture view of Swiss-Prot proteins matching PS50146
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50146
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50146
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS50146
• View ligand binding statistics of PS50146
• Matching PDB structures: 2BON 2JGR 2P1R 2QV7 ... [ALL]

1	Authors	Sakane F., Imai S., Kai M., Wada I., Kanoh H.
	Title	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.
	Source	J. Biol. Chem. 271:8394-8401(1996).
	PubMed ID	8626538

2	Authors	Bakali H.M., Herman M.D., Johnson K.A., Kelly A.A., Wieslander A., Hallberg B.M., Nordlund P.
	Title	Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site.
	Source	J. Biol. Chem. 282:19644-19652(2007).
	PubMed ID	17351295
	DOI	10.1074/jbc.M604852200

3	Authors	Sakane F., Imai S., Kai M., Yasuda S., Kanoh H.
	Title	Diacylglycerol kinases: why so many of them?
	Source	Biochim. Biophys. Acta 1771:793-806(2007).
	PubMed ID	17512245
	DOI	10.1016/j.bbalip.2007.04.006

4	Authors	Jerga A., Miller D.J., White S.W., Rock C.O.
	Title	Molecular determinants for interfacial binding and conformational change in a soluble diacylglycerol kinase.
	Source	J. Biol. Chem. 284:7246-7254(2009).
	PubMed ID	19112175
	DOI	10.1074/jbc.M805962200

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