Table 2.

Major characteristics of the human vitamin D binding protein.

Gene	- Located on chromosome 4q11–q13, close to albumin, α-fetoprotein, and afamin genes and in syntheny with its two neighboring genes, SLC4A4 and the neuropeptide receptor 2, NPFFR2 - Autosomal co-dominant gene transmission - Highly polymorphic gene/protein with more than 120 variants in human populations around the world. Polymorphisms also found in several other species including rodents
Protein	- 458 amino acids−58 kD–preceded by 16 amino acid signal propeptide - Three domains: a highly evolutionary conserved A domain with a cleft able to bind all vitamin D metabolites. The B and C domains can bind actin with high affinity - Single binding site at the surface of the A domain, creating a cleft for all vitamin D metabolites - Isoelectric point 4.6–5.0 depending on gene polymorphism or posttranslational modifications - Pool size: 2.8 g - T½: 1.7 days - Daily production: 10 mg/kg
Serum concentrations	- μmolar concentration (~200–600 mg/l) in normal adults - Mainly apoprotein configuration and <5% as holoprotein
Biological functions	- Binding/transport of all vitamin D metabolites with high affinity (25OHD lactone > 25OHD = 24,25(OH)2D = 25,26(OH)2D > 1,25(OH)2D > vitamin D, and vitamin D3 metabolites > vitamin D2 metabolites) - Binding of actin monomers and enhanced clearance of fibrillar actin - Binding of fatty acids and especially unsaturated fatty acids - Binding to megalin-cubilin receptor complex - Binding to membrane of leucocytes and activation of complement C5 system
Clinical implications	- DBP concentration and affinity define the free concentration of all vitamin D metabolites - Low concentration in fetus and neonates - Increased serum concentration when exposed to estrogens - Decreased serum concentration in case of liver diseases, nephrotic syndrome, malnutrition, severe acute trauma, or disease - Complete genetic absence leads to very low serum concentrations of all vitamin D metabolites without a clinical phenotype