ISOLATION AND CHARACTERIZATION OF LRP6, A NOVEL MEMBER OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE FAMILY

novel member of the low density lipoprotein receptor (LDLR) gene famil y has been identified and characterized. This gene, termed LDL recepto r-related protein 6 (LRP6), encodes a transmembrane protein which has 71% identity and is structurally similar to the protein encoded by LRP 5, a proposed candidate gene for type 1 diabetes located on human chro mosome 11q13, LRP6 maps to human chromosome 12p11-p13. Mouse Lrp6 enco des a protein that has 98% identity to human LRP6 and maps to chromoso me 6. Unlike other members of the LDLR family, LRP6 and LRP5 display a unique pattern of four epidermal growth factor (EGF) and three LDLR r epeats in the extracellular domain. The cytoplasmic domain of LRP6 is not similar to other members of the LDLR family, while comparison with LRP5 reveals proline-rich motifs that may mediate protein-protein int eractions. Thus, it is Likely that LRP6 and LRP5 comprise a new class of the LDLR family. 1998 Academic Press.