InterPro domain: IPR020464

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) [ 1 , 2 , 3 ]; subtilin biosynthesis protein SpaC from Bacillus subtilis [ 4 , 5 ]; epidermin biosynthesis protein EpiC from Staphylococcus epidermidis [ 6 ]; nisin biosynthesis protein NisC from Lactococcus lactis [ 7 , 8 , 9 ]; GCR2 from Arabidopsis thaliana (Mouse-ear cress) [ 10 ]; and many others.

The 3D structure of the lantibiotic cyclase from L. lactis has been determined by X-ray crystallography to 2.5A resolution [ 11 ]. 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 [ 12 , 12 ]; some of these claims have since been corrected [ 13 , 13 , 14 ].

The eukaryotic lanthionine synthetase C-like proteins 1-3, are relatives of the bacterial lanthionine synthetase components C (LanC) [ 15 , 15 , 15 ]. 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 1 is a glutathione-binding protein [ 15 ]. 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 [ 16 ].

1. Organization and chromosomal localization of the human and mouse genes coding for LanC-like protein 1 (LANCL1). Cytogenet. Cell Genet. 93, 100-4
2. Characterization of p40/GPR69A as a peripheral membrane protein related to the lantibiotic synthetase component C. Biochem. Biophys. Res. Commun. 275, 69-74
3. Lanthionine synthetase components C-like 2 increases cellular sensitivity to adriamycin by decreasing the expression of P-glycoprotein through a transcription-mediated mechanism. Cancer Res. 63, 723-7
4. The subtilin gene of Bacillus subtilis ATCC 6633 is encoded in an operon that contains a homolog of the hemolysin B transport protein. J. Bacteriol. 174, 1417-22
5. Analysis of genes involved in biosynthesis of the lantibiotic subtilin. Appl. Environ. Microbiol. 58, 132-42
6. Analysis of genes involved in the biosynthesis of lantibiotic epidermin. Eur. J. Biochem. 204, 57-68
7. Regulation of nisin biosynthesis and immunity in Lactococcus lactis 6F3. Appl. Environ. Microbiol. 60, 814-25
8. Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis. Requirement of expression of the nisA and nisI genes for development of immunity. Eur. J. Biochem. 216, 281-91
9. Biosynthesis of the lantibiotic nisin: genomic organization and membrane localization of the NisB protein. Appl. Environ. Microbiol. 58, 3730-43
10. A G protein-coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid. Science 315, 1712-6
11. Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis. Science 311, 1464-7
12. Isolation, molecular characterization, and tissue-specific expression of a novel putative G protein-coupled receptor. Biochim. Biophys. Acta 1395, 301-8
13. Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR? Biophys. Chem. 133, 28-35
14. Genetic characterization reveals no role for the reported ABA receptor, GCR2, in ABA control of seed germination and early seedling development in Arabidopsis. Plant J. 52, 1001-13
15. Lanthionine synthetase C-like protein 1 interacts with and inhibits cystathionine β-synthase: a target for neuronal antioxidant defense. J. Biol. Chem. 287, 34189-201