Recombinant Human 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 (Ig) superfamily (1, 2). Kirrel2 is expressed both in pancreatic islet beta cells and kidney glomerulus, and is also found in brain and lymph nodes (1 - 9). Human Kirrel2 cDNA encodes a 708 amino acid (aa) protein that contains a 19 aa signal sequence, a 491 aa extracellular domain with five C2-type Ig-like domains, a 21 aa transmembrane sequence and a 177 aa intracellular domain with a nephrin-like podocin binding site (aa 597 - 606) (4, 5). An extracellular RGD sequence allows for cell attachment (4). The extracellular domain of human Kirrel2 shares 86%, 84%, 89% and 87% aa identity with mouse, rat, equine and bovine Kirrel2, respectively. Alternately spliced human Kirrel2 isoforms of 688, 633 and 583 aa have been described (6). These are, respectively, either missing aa 192 - 211, or have a 23 aa alternate C-terminus in place of aa 611 - 708, with or without aa 22 - 71 at the N-terminus. Human Kirrel2 is downregulated in glomeruli of patients with proteinuria, suggesting an involvement in the maintenance of the glomerular filtration barrier (7). Autoantibodies to Kirrel2 have been identified in a subset of humans with type I diabetes, indicating its involvement with islet  beta cell function (8). 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 (9). It is also a marker for mouse early postmitotic neural precursors in the ventricular zone of the developing mouse spinal cord (10).