{PDOC00379}
{PS00479; ZF_DAG_PE_1}
{PS50081; ZF_DAG_PE_2}
{BEGIN}
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* Zinc finger phorbol-ester/DAG-type signature and profile *
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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.

-Consensus pattern: H-x-[LIVMFYW]-x(8,11)-C-x(2)-C-x(3)-[LIVMFC]-x(5,10)-
                    C-x(2)-C-x(4)-[HD]-x(2)-C-x(5,9)-C
                    [The 6 C's and the 2 H's are involved in binding Zinc]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 a few DGK's.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL,  except
 3.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: May 2004 / Text revised.

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

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