YWHAE: Human protein 14-3-3 epsilon isoform
PDB Code: 2BR9
Phosphorylation of a target protein by a specific kinase alters the characteristics of the protein in a number of ways. One alteration is that the attached phosphate group presents a handle to which other molecules can bind thus forming a complex. Gnerally, this is how the14-3-3 molecules interact with their target proteins.
14-3-3 proteins are highly conserved eukaryotic proteins that bind to phosphorylated Ser (pS) residues via the two consensus sequences of RXXXpSXP and R(S/X)XpSXP. The functional unit is a dimer and their interaction with the phosphorylated target can result in stabilisation of the protein, alteration of enzyme activity, localisation within the cell, prevention of dephosphorylation and either blockage or mediation of protein interactions.
Among the known targets of 14-3-3epsilon are the human ether-a-go-go (HERG) K+ channel and poly(A) polymerase. It can mudulate the activity of Ca(2+)-activated Cl(-) channels and DNA topoisomerase IIalpha and plays a central role in neuronal development. It is also likely to have the ability to interact with the Kinesin-like motor protein KIF1C as YWHAEA was co-crystallised with a KIF1C peptide during the structure determination presented here. In mice KIF1C is a determinant of the lethality of anthrax. Certain KIF1C polymorphs protect the mice macrophages against anthrax. The protective effect of KIF1C appears to be as part of the intoxication pathway. Hence 14-3-3 proteins are likely to play key roles in a variety of signalling processes.

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