Diacylglycerol (DAG) is an important second messenger. Phorbol esters (PE) are analogues of DAG and potent tumor promoters that cause a variety of physiological changes when administered to both cells and tissues. DAG activates a family of serine/threonine protein kinases, collectively known as protein kinase C (PKC) [1]. Phorbol esters can directly stimulate PKC. The N-terminal region of PKC, known as C1, has been shown [2] to bind PE and DAG in a phospholipid and zinc-dependent fashion. The C1 region contains one or two copies (depending on the isozyme of PKC) of a cysteine-rich domain about 50 amino-acid residues long and essential for DAG/PE-binding. Such a domain has also been found in the following proteins:

• Diacylglycerol kinase (EC 2.7.1.107) (DGK) [3], the enzyme that converts DAG into phosphatidate. It contains two copies of the DAG/PE-binding domain in its N-terminal section. At least five different forms of DGK are known in mammals.
• N-chimaerin. A brain specific protein which shows sequence similarities with the BCR protein at its C-terminal part and contains a single copy of the DAG/PE-binding domain at its N-terminal part. It has been shown [4,5] to be able to bind phorbol esters.
• The raf/mil family of serine/threonine protein kinases. These protein kinases contain a single N-terminal copy of the DAG/PE-binding domain.
• The unc-13 protein from Caenorhabditis elegans. Its function is not known but it contains a copy of the DAG/PE-binding domain in its central section and has been shown to bind specifically to a phorbol ester in the presence of calcium [6].
• The vav oncogene. Vav was generated by a genetic rearrangement during gene transfer assays. Its expression seems to be restricted to cells of hematopoeitic origin. Vav seems [5,7] to contain a DAG/PE-binding domain in the central part of the protein.
• The Drosophila GTPase activating protein rotund.

The DAG/PE-binding domain binds two zinc ions; the ligands of these metal ions are probably the six cysteines and two histidines that are conserved in this domain. We have developed both a signature pattern and a profile that span completely the DAG/PE domain.