Figure 4.

Structure of lactase and the location of the identified CLD mutations. The genomic size of the LCT gene is ∼55 kb and is composed of 17 exons (Boll et al. 1991). The size of messenger RNA (mRNA) is 6,274 bases, and the primary translation product (prolactase) is 1,927 amino acids. The prolactase contains a cleavable signal sequence from Met₁ to Gly₁₉ that guides the polypeptide to the endoplasmic reticulum (von Heijne 1986; Mantei et al. 1988). The region from Ser₂₀ to Thr₁₈₈₂ consists of four homologous domains (I–IV). The prolactase is processed by two proteolytic cleavages. The first, an intracellular cleavage, occurs between Arg₇₃₄ and Leu₇₃₅. The second cleavage in the intestinal lumen between Arg₈₆₈ and Ala₈₆₉ generates lactaseβ_final, the mature enzyme (Jacob et al. 1996; Wüthrich et al. 1996). The figure is modified from Naim (2001).