Human KIRREL1, C-His, Flag Tag (ECD) Protein

Kirrel1, also called NEPH1, is a 90-110 kDa type I transmembrane glycoprotein that belongs to the NEPH family of the immunoglobulin superfamily. The 757 amino acid (aa) human Kirrel1 contains a 16 aa signal sequence, a 483 aa extracellular domain (ECD) with five C2-type Ig-like domains, a 21 aa transmembrane sequence and a 237 aa cytoplasmic domain. The ECD also contains a site for FGF/FGF R interaction, and an RGD site that may allow integrin-mediated cell attachment. Five IgG-like repeats characterize the extracellular domain. The interaction of these five IgG-like motifs with the eight IgG-like motifs in Nephrin form a zipper-like meshwork around the glomerular capillaries in podocytes. This interaction is what forms the structural basis of the slit diaphragm regulating macromolecule movement from the blood. Human Kirrel1 shares 98% aa identity with mouse and rat homologs, 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. Kirrel1 forms cis hetero-oligomers with Nephrin, which brings together signaling molecules that direct actin polymerization. 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.