Recombinant Human USAG1 Protein, CF

USAG1 (uterine sensitization‑associated gene 1), also called WISE (Wnt modulator in surface ectoderm) or Ectodin, gene name SOSTDC1, is a secreted, monomeric 26 ‑ 32 kDa glycoprotein of the sclerostin family of BMP antagonists (1 ‑ 3). Human USAG1 cDNA encodes 206 amino acids (aa), including a 23 aa signal sequence and a 183 aa mature protein with a cystine knot domain (2, 3). Mature human USAG1 shares 96 ‑ 98% aa identity with mouse, rat, canine, equine, porcine and bovine USAG1. USAG1 co‑localizes with BMP7 in the developing and adult kidney, especially in renal distal tubule cells postnatally (2, 4). It is also found in ectodermal tissues such as ameloblasts of teeth (for enamel formation), and cells of the dermal papilla (1, 2). USAG1 binds BMP‑2, ‑4, ‑6, and ‑7, sequestering BMPs and making them unavailable for BMP receptor binding (1 ‑ 5). USAG1 also binds LRPs such as LRP6, blocking LRP6 engagement of Wnt (3, 6). In dental mesenchymal cells, USAG1 is proposed to coordinate BMP, Wnt, FGF and SHH signals that regulate apoptosis during tooth development (1, 6, 7). Deletion of USAG1 results in mice with supernumerary teeth, while concurrent decreased expression of LRP5 and LRP6 restores normal tooth configurations (4 ‑ 6, 8).  USAG1^-/- mice show decreased susceptibility to kidney injury which is reversed by administration of a neutralizing antibody to BMP7 (4). In a mouse model of Alport syndrome, deletion of USAG1 alternates disease progression (7). These results support a proposed USAG1/WISE antagonism of BMP and Wnt signaling pathways in kidney and tooth development. USAG1 expression by uterine luminal epithelium is also associated with the timing and positioning of blastocyst implantation (9).