Klotho b, a divergent structural member of the glycosidase I superfamily, is expressed primarily in the liver and pancreas, with lower expression in adipose tissue.1 Like Klotho, Klotho b facilitates binding between FGF19 subfamily members and their receptors via formation of a ternary complex.2 The Klotho b mediated interaction of FGF15 (human FGF19) 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-a hydroxylase (Cyp7a1) and sterol 12-a hydroxylase (Cyp8b1).2-4 Klotho b is also a cofactor for the interaction of FGF21 with FGF Receptor 1c in adipocytes, which allows FGF21 to stimulate GLUT1 expression, upregulating adipocyte insulin-dependent glucose uptake.2-3, 5 The 1043 amino acid (aa) type I transmembrane protein is composed of a 51 aa signal sequence, a 943 aa extracellular domain (ECD) containing two glycosidase-like regions, a 21 aa transmembrane domain, and 28 aa intracellular tail. Since Klotho-related proteins lack critical active site Glu residues present in b-glycosidases, it was initially unclear whether they were functional enzymes.1, 6 However, glucuronidase activity has since been demonstrated for Klotho, indicating that physiologically relevant enzymatic activity for Klotho b is also possible.7 The extracellular domain shares 79%, 79%, 80% and 67% identity with human, bovine, canine and rat Klotho b, respectively. The low identity with rat reflects aa discordance within rodent ECD.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.