CLONING OF A NOVEL MEMBER OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR FAMILY

A gene encoding a novel transmembrane protein was identified by DNA se quence analysis within the insulin-dependent diabetes mellitus (IDDM) locus IDDM4 on chromosome 11q13. Based on its chromosomal position, th is gene is a candidate for conferring susceptibility to diabetes. The gene, termed low-density lipoprotein receptor related protein 5 (LRP5) , encodes a protein of 1615 amino acids that contains conserved module s which are characteristic of the low-density lipoprotein (LDL) recept or family. These modules include a putative signal peptide for protein export, four epidermal growth factor (EGF) repeats with associated sp acer domains, three LDL-receptor (LDLR) repeats, a single transmembran e spanning domain, and a cytoplasmic domain. The encoded protein has a unique organization of EGF and LDLR repeats; therefore, LRP5 likely r epresents a new category of the LDLR family. Both human and mouse LRP5 cDNAs have been isolated and the encoded mature proteins are 95% iden tical, indicating a high degree of evolutionary conservation. (C) 1998 Elsevier Science B.V. All rights reserved.