Human Crossveinless-2/CV-2 Antibody

Crossveinless-2 (CV-2), also known as bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER), is a secreted chordin-like protein that modulates the BMP signaling pathway (1‑3). Human CV-2 is synthesized as a 685 amino acid (aa) residue precursor protein with a putative 39 aa signal peptide, five tandem chordin-like cysteine-rich (CR) domains, a partial von Willebrand factor type D domain (vWD), and a carboxyl trypsin inhibitor-like cysteine-rich domain (TIL) (1, 4). Secreted CV-2 is reported to be proteolytically cleaved to generate two fragments that are disulfide-linked (1, 2). The GDPH sequence is conserved in CV-2 from other species. It is also found in multiple proteins that undergo a similar type of cleavage (5). Human CV-2 message is detected in many tissues, with the highest expression detected in adult brain and adult and fetal lung (1). It is also expressed in flk-1⁺ endothelial cell precursors and in primary chondrocytes (2). During embryonic development, CV-2 is expressed in regions of high BMP signaling, such as the posterior primitive streak and the ventral tail bud (4). Human CV-2 shares 92% and 34% aa sequence identity with the mouse and Drosophila homologs, respectively (1, 4). Results from biochemical experiments using recombinant CV-2 show that CV-2 directly interacts with BMP-2, -4, and -6 to antagonize BMP signaling, which can regulate a wide range of differentiation processes (1, 2). In contrast, genetic data from Drosophila suggest that CV-2 potentiates BMP-signaling (6). It is possible that like TSG, CV-2 can positively and negatively modulate BMP signal transduction depending on the cell context (7).