The Phospholipase D (PLD) domain

A duplicated sequence motif occuring in phospholipases D and related phosphatidyltransferases, as well as in several other proteins using a ping-pong phosphotransferase mechanism.

This page is based on unpublished observations

Description and biological implications

After observing a short duplication in the plant phospholipase D sequences, we used generalize profiles to find related sequence motifs in several other proteins. Interestingly, all the proteins found initially seemed to catalyze phospholipase D-related hydrolysis or phosphatidyl-transferase reactions. Among these proteins were a bacterial PLD from streptomyces, bacterial phosphatidylserine-synthases and a yeast homolog (yeast normally uses a different, unrelated phosphatidylserine synthase), and bacterial cardiolipin synthases. We also found this motif in an uncharacterized yeast protein and a human EST sequence, both of which were later shown to encode phospholipase D enzymes [1,2].
Interestingly, the PLD motif was also found in two proteins from vaccinia virus and their human homologs. One of these proteins (F13L) seems to be involved in the fusion of the outermost layer of the intracellular enveloped virus with the host cell membrane [3]. On that basis, we suggest the participation of a phosphatidyl-transfer reaction (or hydrolysis) in this process. In this respect it should be noted that vaccinia virus membranes accumulate large amounts of an unusual lipid, acyl-bis(monoacylglycero)phosphate [4], which is also a likely product of a PLD-type phosphatidyltransferase reaction.
By using a less stringent definition of the motif, several other proteins were shown to contain two copies of the PLD-motif, including bacterial endonucleases and polyphosphate-kinases.
A common feature of all characterized enzyme of this family is a ping-pong type phosphotransfer mechanism. First, the enzyme forms a covalent bond to the phosphate of the transfered unit (like e.g. phosphatidic acid). In a second step, this intermediate is either hydrolyzed, resulting in a PLD-type cleavage, or the phosphate is transfered onto another target.

Proteins found to contain PLD-motifs include

Many members of this family contain a second repeated motif which is less well conserved. At the bottom of this page is an alignment of some representative examples of this motif (PLDA-motif).

[1] Hammond S.M., Altshuller Y.M., Sung T.C., Rudge S.A., Rose K., Engebrecht J., Morris A.J. and Frohman M.A., J. Biol. Chem. 270:29640-29643 (1995).
[2] Waksman M., Eli Y., Liscovitch M., Gerst JE., J. Biol. Chem. 271:2361-2364 (1996).
[3] Blasco R., Moss B., J. Virol. 65:5910-5920 (1991).
[4] Sodeik B., Doms R.W., Ericsson M., Hiller G., Machamer C.E., van't Hof W., van Meer G., Moss B., Griffiths G., J. Cell Biol. 121:521-541 (1993).

PROSITE

The PLD domain will be included in PROSITE under the accession numbers PS50035 for the data entry, and PDOC50035 for the documentation entry. The alignment used for construction of the profile is available in MSF format. There is also an updated list of database sequences containing PLD domains.

Domain cartoons

[gif] [Postscript]

Abbreviations: D: PLD-domain; PH: PH-domain; C2: C2-domain. The small gray boxes are another motif conserved in this family.
Links to WWW-pages describing some of these domains can be found near the bottom of this page.

PLD-motif alignment of representative sequences

[gif] [Postscript]

PLDA-motif alignment of representative sequences

[gif] [Postscript]

Note: You can check your sequence for the occurence of this and other domains by using the ProfileScan server.
This document was last modified on

Go back to the protein domains page or to the ISREC-bioinformatics home page