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PROSITE documentation PDOC00379Zinc finger phorbol-ester/DAG-type signature and profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC00379
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.
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PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Azzi A. Boscoboinik D. Hensey C. |
| Title | The protein kinase C family. | |
| Source | Eur. J. Biochem. 208:547-557(1992). | |
| PubMed ID | 1396661 |
| 2 | Authors | Ono Y. Fujii T. Igarashi K. Kuno T. Tanaka C. Kikkawa U. Nishizuka Y. |
| Title | Phorbol ester binding to protein kinase C requires a cysteine-rich zinc-finger-like sequence. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 86:4868-4871(1989). | |
| PubMed ID | 2500657 |
| 3 | Authors | Sakane F. Yamada K. Kanoh H. Yokoyama C. Tanabe T. |
| Title | Porcine diacylglycerol kinase sequence has zinc finger and E-F hand motifs. | |
| Source | Nature 344:345-348(1990). | |
| PubMed ID | 2156169 |
| 4 | Authors | Ahmed S. Kozma R. Monfries C. Hall C. Lim H.H. Smith P. Lim L. |
| Title | Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor. | |
| Source | Biochem. J. 272:767-773(1990). | |
| PubMed ID | 2268301 |
| 5 | Authors | Ahmed S. Kozma R. Lee J. Monfries C. Harden N. Lim L. |
| Title | 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. | |
| Source | Biochem. J. 280:233-241(1991). | |
| PubMed ID | 1660266 |
| 6 | Authors | Ahmed S. Maruyama I.N. Kozma R. Lee J. Brenner S. Lim L. |
| Title | The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high-affinity phorbol ester receptor. | |
| Source | Biochem. J. 287:995-999(1992). | |
| PubMed ID | 1445255 |
| 7 | Authors | Boguski M.S. Bairoch A. Attwood T.K. Michaels G.S. |
| Title | Proto-vav and gene expression. | |
| Source | Nature 358:113-113(1992). | |
| PubMed ID | 1614545 | |
| DOI | 10.1038/358113a0 |
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