QBRICK/FREM1: Products

QBRICK, also known as Frem1 (Fras1-related extracellular matrix gene1) is a 244 kDa (predicted), secreted, extracellular matrix glycoprotein and member of the Fras1 family of proteins. Human QBRICK is synthesized as a 2179 amino acid (aa) precursor that has a 21 aa signal sequence and a 2158 aa mature chain. The mature chain is made up of an N-terminal variable region domain containing an Arg-Gly-Asp (RGD) cell adhesive motif, 12 consecutive chondroitin sulfate proteoglycan (CSPG) repeats of approximately 120 aa, a Calx-beta domain, a second RGD sequence, and a C-terminal C-type lectin-like domain, respectively. In addition, there are five potential sites of N-linked glycosylation. Multiple splicing variants produce four isoforms for human QBRICK. Because of the characteristic feature of the 12 CSPG repeats, the protein was named QBRICK: "Q" stands for queen and is taken from the queen being the twelfth in a suit of playing cards, and "BRICK" stands for the repeating unit. Human QBRICK shares 78% aa sequence identity with mouse QBRICK. QBRICK is localized to the basement membrane in mesenchymal tissue. QBRICK plays a role in epidermal differentiation and is required for epidermal adhesion during embryonic development. QBRICK mediates cell-substratum adhesion through alpha V or alpha 8 integrins. Mutations in QBRICK and other Fras1 family proteins (i.e. Fras1 and Frem2) are associated with Fraser syndrome, a recessive multiorgan disorder characterized by crypthophthalmos, syndactyly, renal agenesis, and a variety of morphogenetic defects. It is postulated that QBRICK, Fras1 and Frem2 make up a ternary complex that act together to ensure adhesion between the epidermal basement membrane and the underlying mesenchyme in embryonic skin.