InterPro domain: IPR036610

The PEBP (PhosphatidylEthanolamine-Binding Protein) superfamily is a highly conserved group of proteins that have been identified in numerous tissues in a wide variety of organisms, including bacteria, yeast, nematodes, plants, drosophila and mammals. The various functions described for members of this family include lipid binding, neuronal development [ 1 ], serine protease inhibition [ 2 ], the control of the morphological switch between shoot growth and flower structures [ 3 ], and the regulation of several signalling pathways such as the MAP kinase pathway [ 4 ], and the NF-kappaB pathway [ 5 ]. The control of the latter two pathways involves the PEBP protein RKIP, which interacts with MEK and Raf-1 to inhibit the MAP kinase pathway, and with TAK1, NIK, IKKalpha and IKKbeta to inhibit the NF-kappaB pathway. Other PEBP-like proteins that show strong structural homology to PEBP include Escherichia coli YBHB and YBCL, the Rattus norvegicus (Rat) neuropeptide HCNP, and Antirrhinum majus (Garden snapdragon) protein centroradialis (CEN).

Structures have been determined for several members of the PEBP-like family, all of which show extensive fold conservation. The structure consists of a large central beta-sheet flanked by a smaller beta-sheet on one side, and an alpha helix on the other. Sequence alignments show two conserved central regions, CR1 and CR2, that form a consensus signature for the PEBP family. These two regions form part of the ligand-binding site, which can accommodate various anionic groups. The N- and C-terminal regions are the least conserved, and may be involved in interactions with different protein partners. The N-terminal residues 2-12 form the natural cleavage peptide HCNP involved in neuronal development. The C-terminal region is deleted in plant and bacterial PEBP homologues, and may help control accessibility to the active site.

1. Peptides corresponding to the N- and C-terminal parts of PEBP are well-structured in solution: new insights into their possible interaction with partners in vivo. J. Pept. Res. 61, 47-57
2. The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors. J. Biol. Chem. 276, 535-40
3. The structure of Antirrhinum centroradialis protein (CEN) suggests a role as a kinase regulator. J. Mol. Biol. 297, 1159-70
4. Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. J. Biol. Chem. 278, 13061-8
5. Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation. Mol. Cell. Biol. 21, 7207-17