Human R‑Spondin 1 Antibody

R-Spondin 1 (RSPO1, Roof plate-specific Spondin 1), also known as cysteine-rich and single thrombospondin domain containing protein 3 (Cristin 3), is a 27 kDa secreted protein that shares ~40% amino acid (aa) identity with three otherR-Spondin family members (1, 2). All R-Spondins regulate Wnt/ beta -catenin signaling, but have distinct expression patterns (1‑3). Like other R-Spondins, R-Spondin 1 contains two adjacent cysteine-rich furin-like domains (aa 34‑135) with one potential N‑glycosylation site, followed by a thrombospondin (TSP-1) motif (aa 147‑207) and a region rich in basic residues (aa 211‑263). Only the furin-like domains are needed for beta -catenin stabilization (2, 4). A putative nuclear localization signal at the C-terminus may allow some expression in the nucleus (5). Potential isoforms of 200 and 236 aa have an alternate, shorter N‑terminus or are missing aa 146‑208, respectively (6). Over aa 21‑263, human R-Spondin 1 shares 89%, 87%, 92%, 91%, 91% and 89% aa identity with mouse, rat, equine, canine, caprine and bovine R-Spondin 1, respectively. R-Spondin 1 is expressed in early development at the roof plate boundary and is thought to contribute to dorsal neural tube development (3, 5). In humans, rare disruptions of the R-Spondin 1 gene are associated with tendencies for XX sex reversal (phenotypic male) or hermaphroditism, indicating a role for R-Spondin 1 in gender-specific differentiation (7, 8). Disruption is also associated with palmoplantar keratosis (7, 8). Postnatally, R-Spondin 1 is expressed by neuroendocrine cells in the intestine, adrenal gland and pancreas, and by epithelia in kidney and prostate (9). Injection of recombinant R-Spondin 1 in mice causes activation of beta -catenin and proliferation of intestinal crypt epithelial cells, and ameliorates experimental colitis (9, 10). R-Spondin 1 regulates Wnt/ beta -catenin by competing with the Wnt antagonist DKK-1 for binding to the Wnt co-receptors, Kremen and LRP-6, reducing their DKK-1-mediated internalization (11). Reports differ on whether R-Spondin 1 binds LRP-6 directly (11‑13).