Nuclear vitamin K2 binding protein in human osteoblasts: homologue to glyceraldehyde-3-phosphate dehydrogenase.

The importance of vitamin K in bone metabolism has been suggested previously. The binding protein of vitamin K2 (menatetrenone, 2-methyl-3-all-trans-tetraphenyl-1,4-naphthoquinone, menaquinone-4), found in nuclear extract of human osteoblasts, binds to vitamin K1 and K2, but not K3. Since the binding protein does not bind to other steroids or vitamins, such as hydrocortisone, vitamin A, 1,25(OH)2vitamin D3, trolox (a derivative of vitamin E), and warfarin, a specific binding protein to vitamin K1 and vitamin K2 in osteoblasts was suggested. The size of the specific binding protein was revealed to be 6S by sucrose density gradient and about 40,000 daltons by SDS-PAGE. Twenty amino acid residues from the N-terminal were the same as human glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but the 21st residue, alanine, was replaced with serine. The binding protein was precipitated with anti-human GAPDH antibody, and authentic human GAPDH could bind vitamin K2. We propose that the nuclear binding protein for vitamin K2 exists in nuclei similarly to other vitamin receptors and that the molecular structure is very close to human GAPDH.