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) . Phorbol esters can directly stimulate PKC. The N-terminal region of PKC, known as C1, has been shown  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 188.8.131.52) (DGK) , 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 .
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.
May 2004 / Text revised.
PROSITE methods (with tools and information) covered by this documentation:
Ahmed S., Kozma R., Lee J., Monfries C., Harden N., Lim L.
The cysteine-rich domain of human proteins, neuronal chimaerin, protein kinase C and diacylglycerol kinase binds zinc. Evidence for the involvement of a zinc-dependent structure in phorbol ester binding.
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