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PROSITE documentation PDOC00379 [for PROSITE entry PS50081]

Zinc finger phorbol-ester/DAG-type signature and profile





Description

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.

Last update:

May 2004 / Text revised.

Technical section

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

ZF_DAG_PE_2, PS50081; Zinc finger phorbol-ester/DAG-type profile  (MATRIX)

ZF_DAG_PE_1, PS00479; Zinc finger phorbol-ester/DAG-type signature  (PATTERN)


References

1AuthorsAzzi A., Boscoboinik D., Hensey C.
TitleThe protein kinase C family.
SourceEur. J. Biochem. 208:547-557(1992).
PubMed ID1396661

2AuthorsOno Y., Fujii T., Igarashi K., Kuno T., Tanaka C., Kikkawa U., Nishizuka Y.
TitlePhorbol ester binding to protein kinase C requires a cysteine-rich zinc-finger-like sequence.
SourceProc. Natl. Acad. Sci. U.S.A. 86:4868-4871(1989).
PubMed ID2500657

3AuthorsSakane F., Yamada K., Kanoh H., Yokoyama C., Tanabe T.
TitlePorcine diacylglycerol kinase sequence has zinc finger and E-F hand motifs.
SourceNature 344:345-348(1990).
PubMed ID2156169

4AuthorsAhmed S., Kozma R., Monfries C., Hall C., Lim H.H., Smith P., Lim L.
TitleHuman brain n-chimaerin cDNA encodes a novel phorbol ester receptor.
SourceBiochem. J. 272:767-773(1990).
PubMed ID2268301

5AuthorsAhmed S., Kozma R., Lee J., Monfries C., Harden N., Lim L.
TitleThe 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.
SourceBiochem. J. 280:233-241(1991).
PubMed ID1660266

6AuthorsAhmed S., Maruyama I.N., Kozma R., Lee J., Brenner S., Lim L.
TitleThe Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high-affinity phorbol ester receptor.
SourceBiochem. J. 287:995-999(1992).
PubMed ID1445255

7AuthorsBoguski M.S., Bairoch A., Attwood T.K., Michaels G.S.
TitleProto-vav and gene expression.
SourceNature 358:113-113(1992).
PubMed ID1614545
DOI10.1038/358113a0



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