THE MOUSE INSULIN-LIKE GROWTH-FACTOR-II CATION-INDEPENDENT MANNOSE 6-PHOSPHATE (IGF-II MPR) RECEPTOR GENE - MOLECULAR-CLONING AND GENOMIC ORGANIZATION/

The mammalian insulin-like growth factor II/cation-independent mannose 6-phosphate receptor (IGF-II/MPR) is a multifunctional protein that b inds both IGF-II and ligands containing a mannose 6-phosphate recognit ion marker through distinct high-affinity sites. This receptor plays a n integral part in lysosomal enzyme transport, has a potential role in growth factor maturation and clearance, and may mediate IGF-II-activa ted signal transduction through a G-protein-coupled mechanism. Recent studies have shown that production of IGF-II/MPR mRNA and protein begi ns in the mouse embryo soon after fertilization and have demonstrated that the receptor gene is on mouse chromosome 17 and is maternally imp rinted. In this paper, we report the cloning and characterization of t he mouse IGF-II/MPR gene. The gene is 93 kb long, is composed of 48 ex ons, and codes for a predicted protein of 2482 amino acids. The extrac ellular part of the receptor is encoded by exons 1-46, with each of 15 related repeating motifs being determined by parts of 3-5 exons. A si ngle fibronectin type II-like element is found in exon 39. The transme mbrane portion of the receptor also is encoded by exon 46, and the cyt oplasmic region by exons 46-48. The positions of exon-intron splice ju nctions are conserved between several of the repeats in the IGF-II/MPR and the homologous extracellular region of the gene for the other kno wn lysosomal sorting receptor, the cation-dependent mannose 6-phosphat e receptor. The gene duplications that gave rise to the modern IGF-II/ MPR probably occurred before the divergence of mammals, since there is more extensive protein sequence conservation between receptors from d ifferent species than between any pair or repeating motifs within a si ngle receptor. (C) 1994 Academic Press, Inc.