<p>The LanC-like protein superfamily encompasses a highly divergent group of peptide-modifying enzymes, including the eukaryotic and bacterial lanthionine synthetase C-like proteins (LanC) [<cite idref="PUB00046016"/>, <cite idref="PUB00046017"/>, <cite idref="PUB00046018"/>]; subtilin biosynthesis protein SpaC from <taxon tax_id="1423">Bacillus subtilis</taxon> [<cite idref="PUB00002161"/>, <cite idref="PUB00008599"/>]; epidermin biosynthesis protein EpiC from <taxon tax_id="1282">Staphylococcus epidermidis</taxon> [<cite idref="PUB00018966"/>]; nisin biosynthesis protein NisC from <taxon tax_id="1358">Lactococcus lactis</taxon> [<cite idref="PUB00011680"/>, <cite idref="PUB00046051"/>, <cite idref="PUB00046021"/>]; GCR2 from <taxon tax_id="3702">Arabidopsis thaliana</taxon> (Mouse-ear cress) [<cite idref="PUB00035552"/>]; and many others. </p> <p> The 3D structure of the lantibiotic cyclase from L. lactis has been determined by X-ray crystallography to 2.5A resolution [<cite idref="PUB00040886"/>]. The globular structure is characterised by an all-alpha fold, in which an outer ring of helices envelops an inner toroid composed of 7 shorter, hydrophobic helices. This 7-fold hydrophobic periodicity has led several authors to claim various members of the family, including eukaryotic LanC-1 and GCR2, to be novel G protein-coupled receptors [<cite idref="PUB00035552"/>, <cite idref="PUB00046022"/>]; some of these claims have since been corrected [<cite idref="PUB00046017"/>, <cite idref="PUB00046023"/>, <cite idref="PUB00046024"/>]. </p> <p> The eukaryotic lanthionine synthetase C-like proteins 1-3, are relatives of the bacterial lanthionine synthetase components C (LanC) [<cite idref="PUB00046016"/>, <cite idref="PUB00046017"/>, <cite idref="PUB00046018"/>]. They are ubiquitous in nature, being variously expressed in brain, spinal chord, pituitary gland, kidney, heart, skeletal muscle, pancreas, ovary and testis. LanC-like protein 2 is a bystander gene co-amplified and over- expressed with epidermal growth factor receptor (EGFR) in 20% of glioblastomas; its exogenous expression in a sarcoma cell line decreases the expression of ABCB1 (P-glycoprotein 1) and increases cellular sensitivity to the anticancer drug adriamycin [<cite idref="PUB00046018"/>]. </p> LanC-like protein, eukaryotic