Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme
J. Clin. Invest. Ralf Jacob, et al. 106:281 doi:10.1172/JCI9677 [Go to this article.]

Figure 1
Structure and membrane orientation of pro-SI. (a) Structural features of pro-SI deduced from biosynthetic studies (8) and cDNA cloning (6). Pro-SI is a type II membrane glycoprotein (N_in/C_out) that is synthesized with an uncleavable signal sequence, which also serves as a membrane anchoring domain (6). The cytoplasmic tail contains 12 amino acid residues and is followed by a membrane anchor of 20 amino acids and a Ser/Thr-rich stalk domain of 28 amino acids that is considered to be part of the isomaltase subunit. Isomaltase ends with amino acid residue Arg₁₀₀₇ and sucrase starts immediately thereafter with Ile₁₀₀₈. The location of the L340P mutation in the CSID patient and the putative cleavage site are indicated. The Arg/Ile peptide sequence between isomaltase and sucrase is a trypsin site where the mature large precursor pro-SI is cleaved in the intestinal lumen by pancreatic trypsin (16). (b) Schematic drawing of the membrane orientation of pro-SI. The NH₂-terminus on the cytosolic side of the membrane (N), the luminal COOH-terminus (C), the stalk domain, and the putative cleavage region are indicated. I, isomaltase; S, sucrase.