VonWillebrand cDNA and prepropeptide

Von Willebrand factor is formed in endothelial
cells, in megakaryocytes, and possibly in some
other tissues and is coded for by a large (178 kb)
gene with 52 exons of various sizes on chromosome
12 (12p12-pter). Several polymorphic restriction
sites (red arrows) exist. The cDNA of
vWF is about 8.7 kb long. The corresponding
mRNA codes for a primary peptide (preprovWF)
of 2813 amino acids, including a signal
peptide of 22 amino acids, a segment of 741
amino acids (vW antigen II), and a subunit of
four different domains (A–D), which together
make up more than 90% of the sequence. The
three A domains (A1–A3) in the middle contain
binding sites for collagen, heparin, and thrombocytes.
Three small B domains are on the carboxy
side of the D4 domain, before the two C
domains. vWF contains 8.3% cysteine (234 of
2813 amino acids), concentrated at the amino
and carboxy ends, whereas the three A domains
are cysteine-poor. After posttranslational modification,
the mature plasma vWF contains 12
oligosaccharide side chains (19% of the total
weight is carbohydrate).