Brown S D, Twells R C, Hey P J, Cox R D, Levy E R, Soderman A R, Metzker M L, Caskey C T, Todd J A, Hess J F
Department of Human Genetics, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Biochem Biophys Res Commun. 1998 Jul 30;248(3):879-88. doi: 10.1006/bbrc.1998.9061.
A novel member of the low density lipoprotein receptor (LDLR) gene family has been identified and characterized. This gene, termed LDL receptor-related protein 6 (LRP6), encodes a transmembrane protein which has 71% identity and is structurally similar to the protein encoded by LRP5, a proposed candidate gene for type 1 diabetes located on human chromosome 11q13. LRP6 maps to human chromosome 12p11-p13. Mouse Lrp6 encodes a protein that has 98% identity to human LRP6 and maps to chromosome 6. Unlike other members of the LDLR family, LRP6 and LRP5 display a unique pattern of four epidermal growth factor (EGF) and three LDLR repeats 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 interactions. Thus, it is likely that LRP6 and LRP5 comprise a new class of the LDLR family.
低密度脂蛋白受体(LDLR)基因家族的一个新成员已被鉴定和表征。这个基因被称为低密度脂蛋白受体相关蛋白6(LRP6),编码一种跨膜蛋白,该蛋白与LRP5编码的蛋白有71%的同源性,且在结构上相似,LRP5是位于人类染色体11q13上的1型糖尿病候选基因。LRP6定位于人类染色体12p11 - p13。小鼠Lrp6编码的蛋白与人类LRP6有98%的同源性,定位于染色体6。与LDLR家族的其他成员不同,LRP6和LRP5在细胞外结构域呈现出独特的模式,即有四个表皮生长因子(EGF)和三个LDLR重复序列。LRP6的细胞质结构域与LDLR家族的其他成员不同,而与LRP5比较则发现富含脯氨酸的基序,可能介导蛋白质 - 蛋白质相互作用。因此,LRP6和LRP5可能构成LDLR家族的一个新类别。