Group-specific component (Gc) proteins bind vitamin D and 25-hydroxyvitamin D.
Group-specific component (Gc) proteins are human plasma proteins for which a worldwide polymorphism exists. As yet no functional role has been assigned this protein. We show that the products of both Gc alleles, proteins Gc 1 and Gc 2 (distinguished electrophoretically), bind substantial quantities of vitamin D and 25-hydroxyvitamin D. Three lines of evidence are reported: (1) Polyacrylamide gel electrophoresis and autoradiography of serum labeled with (14-C)vitamin D3 revealed patterns of radioactive bands identical to those expected of the two Gc alleles. Population gene frequencies for these proteins binding vitamin D were in the range of those reported for Gc, and individuals of known Gc phenotype were found to have the corresponding vitamin-D-binding phenotype. (2) Immunoelectrophoresis and autoradiography of labeled serum reacted against antiserum to human Gc revealed labeling by (14-C)vitamin D3 of Gc-antibody precipitation ares. (3) (14-C)vitamin D3 or 25-hydroxy(3-H)vitamin D3 was found to coprecipitate specifically with Gc in serum incubated with Gc antiserum. Use of these techniques demonstrated further that plasma proteins that bind vitamin D and that are immunologically similar to human Gc are found in mouse, rat, cow, horse, dog, rhesus monkey, and chimpanzee. We propose that Gc and "vitamin-D-binding alpha-globulin" are in fact the same portein, and that the ability of Gc to bind vitamin D may be directly related to the action of selection on this locus. These techniques may also find application in the study of other plasms transport proteins.
D000483:Alleles; D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001798:Blood Proteins / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002417:Cattle; D002762:Cholecalciferol / Q000378:metabolism*; D003429:Cross Reactions; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006168:Guinea Pigs; D006736:Horses; D006801:Humans; D006887:Hydroxycholecalciferols / Q000378:metabolism*; D007122:Immunoelectrophoresis; D008251:Macaca; D008297:Male; D051379:Mice; D002679:Pan troglodytes; D010641:Phenotype; D011233:Precipitin Tests; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D014807:Vitamin D / Q000378:metabolism*
D000510:Alpha-Globulins; D001798:Blood Proteins; D002250:Carbon Radioisotopes; D006887:Hydroxycholecalciferols; D014807:Vitamin D; D002762:Cholecalciferol