Recombinant Cynomolgus Monkey Klotho beta His Protein, CF

Klotho beta (KLB), a divergent structural member of the glycosidase I superfamily, is a type I transmembrane protein expressed primarily in the liver and pancreas, with lower expression in adipose tissue (1). Klotho beta, along with the closely related Klotho, consists of a large extracellular domain (ECD) containing two glycosidase-like regions, a transmembrane domain, and a short intracellular tail. The two glycosidase-like regions of Klotho beta share high homology to the one beta-glycosidase family yet lack the critical active site Glu residues present in beta-glycosidases necessary for catalytic activity, though physiologically relevant enzymatic activity for Klotho beta has been suggested (2, 3). The ECD of mature cynomologus Klotho beta shares 97% and 80% amino acid sequence identity with the ECD of human and mouse Klotho beta, respectively. Similar to Klotho, Klotho beta helps to regulate multiple metabolic processes in mammals by acting as a co-receptor that facilitates binding between FGF19 subfamily members and their receptors (4). The Klotho beta mediated interaction of FGF19 (FGF15 in mouse) with FGF Receptor 4 in the liver negatively regulates bile acid synthesis by controlling the secretion of two key bile acid synthase genes, cholesterol 7- alpha hydroxylase (Cyp7a1) and sterol 12- alpha hydroxylase (Cyp8b1) (5-7). Klotho beta is also a cofactor for the interaction of FGF21 with FGF Receptor 1c in adipocytes, which allows FGF21 to stimulate GLUT1 expression, up-regulating adipocyte insulin-dependent glucose uptake (5 - 8). Regulation of Klotho beta function has been suggested as a therapy for several cardiometabolic diseases (9).