Recombinant Mouse Kirrel1/NEPH1 Protein, CF

Kirrel1, also called neph1, is a 90 - 110 kDa type I transmembrane glycoprotein that belongs to the NEPH family of the immunoglobulin superfamily (1 - 4). The 789 amino acid (aa) mouse Kirrel1 contains a 47 aa signal sequence, a 484 aa extracellular domain (ECD) with five C2-type Ig-like domains, a 21 aa transmembrane sequence and a 237 aa cytoplasmic domain (5). An isoform diverges in the cytoplasmic domain and ends at aa 634, prior to four tyrosine phosphorylation sites, a podocin interaction motif, and a C-terminal PDZ motif that are all important for the signaling functions of Kirrel1 (1, 6). If expressed, this isoform would be expected to block homo- and hetero-multimer formation, thus acting as an inhibitor. The ECD also contains a site for FGF/FGF R interaction, and an RGD site that may allow integrin-mediated cell attachment (5). Mouse Kirrel1 shares 99% and 97% aa identity with rat and human Kirrel1, respectively, within the ECD. Kirrel1 expression has been mainly studied in the kidney glomerular slit diaphragm, but its expression with nephrin or other family members has also been reported in central nervous system neurons, pancreas and placenta (3, 4, 7 - 9). Kirrel1 forms cis hetero-oligomers with nephrin, which brings together signaling molecules that direct actin polymerization (3, 4, 10). This interaction is essential for barrier function in the slit diaphragm, and mice deleted for Kirrel1 die perinatally due to proteinuria and failure to thrive (2, 3).