Figure 1.

Mucin-1 structural domains and recurrent MUC1 dupC variation hotspot

(A) Mucin-1 is a transmembrane glycoprotein widely expressed in different segments of the nephron in the kidney. Protein domains of the full-length mucin-1 protein are shown: N-terminus signal sequence, VNTR regions (variable repetition of 20aa blocks), SEA cleavage domain (is a highly conserved domain that undergoes an autocatalytic cleavage during folding in the endoplasmic reticulum), transmembrane domain (TM), and cytoplasmic domain.

(B and C) The frameshift caused by the insertion of a C in the VNTR motifs (blue boxes) with stretch of seven C (GCCCCCCCAGC) creates a new stop codon shortly (85aa) beyond the VNTR domain. This variation could be studied by the SNaPshot method using MwoI restriction enzyme. The 20 amino acid (aa) repeat blocks for wild-type (WT) and mutant (MT) protein are shown. The mutant protein harbors novel aa repeats (yellow boxes) and lacks the C-terminal domain.