Recombinant Mouse Kirrel2/NEPH3 Protein, CF

Kirrel2 (kin of irregular chiasm-1-like 2), also known as filtrin, NEPH3 (nephrin-like 3) or NLG1 (nephrin-like gene 1), is a 107 kDa type I transmembrane adhesion protein belonging to the immunoglobulin superfamily (1, 2). Kirrel2 is one of several proteins expressed both in pancreatic islet beta cells and kidney glomerulus, and is also found in brain and lymph nodes (1 - 9). Mouse Kirrel2 cDNA encodes a 700 amino acid (aa) protein that contains a 16 aa signal sequence, a 491 aa extracellular domain with five C2-type Ig-like domains, a 21 aa transmembrane sequence and a 172 aa intracellular domain with a nephrin-like, conserved podocin binding site (mouse aa 589 - 598) (4, 5). An extracellular RGD sequence allows for cell attachment (4). The extracellular domain of mouse Kirrel2 shares 96%, 86%, 85% and 85% aa identity with rat, human, equine and bovine Kirrel2, respectively. It shares 35 - 37% aa identity with other mouse Kirrel proteins. One mouse isoform that has been described is missing the transmembrane domain (aa 501 - 533), while another encodes only portions of Ig domains 1 - 4 (5). Human Kirrel2 is downregulated in glomeruli of patients with proteinuria, suggesting an involvement in the maintenance of the glomerular filtration barrier (6). Autoantibodies to Kirrel2 have been identified in a subset of humans with type I diabetes, indicating its involvement with islet beta cell function (7). In the brain, Kirrel2 is present in olfactory neurons; but only when they are active; homophilic adhesion of Kirrel2 is postulated to help correlate nerves identifying the same odorant (8). It is also a marker for mouse early postmitotic neural precursors in the ventricular zone of the developing mouse spinal cord (9).