Vitamin D-binding protein (DBP), also/originally known as gc-globulin (group-specific component), is a protein that in humans is encoded by the GCgene. DBP is genetically the oldest member of the albuminoid family and appeared early in the evolution of vertebrates.
Human GC is a glycosylated alpha-globulin, ~58 kDa in size. Its 458 amino acids are coded for by 1690 nucleotides on chromosome 4 (4q11–q13). The primary structure contains 28 cysteine residues forming multiple disulfide bonds. GC contains 3 domains. Domain 1 is composed of 10 alpha helices, domain 2 of 9, and domain 3 of 4.
It is able to bind the various forms of vitamin D including ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), the 25-hydroxylated forms (calcifediol), and the active hormonal product, 1,25-dihydroxyvitamin D (calcitriol). The major proportion of vitamin D in blood is bound to this protein. It transports vitamin D metabolites between skin, liver and kidney, and then on to the various target tissues.
Many genetic variants of the GC gene are known. They produce 6 main haplotypes and 3 main protein variants (Gc1S, Gc1F and Gc2). The genetic variations are associated with differences in circulating 25-hydroxyvitamin D levels. They have been proposed to account for some of the differences in vitamin D status in different ethnic groups, and have been found to correlate with the response to vitamin D supplementation.
^Mikkelsen M, Jacobsen P, Henningsen K (Jul 1977). "Possible localization of Gc-System on chromosome 4. Loss of long arm 4 material associated with father-child incompatibility within the Gc-System". Human Heredity. 27 (2): 105–7. doi:10.1159/000152857. PMID558959.
^Verboven C, Rabijns A, De Maeyer M, Van Baelen H, Bouillon R, De Ranter C (February 2002). "A structural basis for the unique binding features of the human vitamin D-binding protein". Nature Structural Biology. 9 (2): 131–6. doi:10.1038/nsb754. PMID11799400. S2CID38990672.
^McGrath JJ, Saha S, Burne TH, Eyles DW (July 2010). "A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations". The Journal of Steroid Biochemistry and Molecular Biology. 121 (1–2): 471–7. doi:10.1016/j.jsbmb.2010.03.073. PMID20363324. S2CID20057294.
Svasti J, Kurosky A, Bennett A, Bowman BH (April 1979). "Molecular basis for the three major forms of human serum vitamin D binding protein (group-specific component)". Biochemistry. 18 (8): 1611–7. doi:10.1021/bi00575a036. PMID218624.
Braun A, Bichlmaier R, Cleve H (June 1992). "Molecular analysis of the gene for the human vitamin-D-binding protein (group-specific component): allelic differences of the common genetic GC types". Human Genetics. 89 (4): 401–6. doi:10.1007/BF00194311. PMID1352271. S2CID1913655.
Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J (June 1992). "Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF)". Genomics. 13 (2): 293–300. doi:10.1016/0888-7543(92)90245-N. PMID1535333.
Schoentgen F, Metz-Boutigue MH, Jollès J, Constans J, Jollès P (June 1986). "Complete amino acid sequence of human vitamin D-binding protein (group-specific component): evidence of a three-fold internal homology as in serum albumin and alpha-fetoprotein". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 871 (2): 189–98. doi:10.1016/0167-4838(86)90173-1. PMID2423133.
Yang F, Naberhaus KH, Adrian GS, Gardella JM, Brissenden JE, Bowman BH (1987). "The vitamin D-binding protein gene contains conserved nucleotide sequences that respond to heavy metal, adipocyte and mitotic signals". Gene. 54 (2–3): 285–90. doi:10.1016/0378-1119(87)90499-9. PMID2958390.
Cooke NE, Willard HF, David EV, George DL (July 1986). "Direct regional assignment of the gene for vitamin D binding protein (Gc-globulin) to human chromosome 4q11-q13 and identification of an associated DNA polymorphism". Human Genetics. 73 (3): 225–9. doi:10.1007/BF00401232. PMID3015768. S2CID38816588.
Nestler JE, McLeod JF, Kowalski MA, Strauss JF, Haddad JG (May 1987). "Detection of vitamin D binding protein on the surface of cytotrophoblasts isolated from human placentae". Endocrinology. 120 (5): 1996–2002. doi:10.1210/endo-120-5-1996. PMID3552627.
Constans J, Oksman F, Viau M (August 1981). "Binding of the apo and holo forms of the serum vitamin D-binding protein to human lymphocyte cytoplasm and membrane by indirect immunofluorescence". Immunology Letters. 3 (3): 159–62. doi:10.1016/0165-2478(81)90120-6. PMID7026425.
Braun A, Kofler A, Morawietz S, Cleve H (December 1993). "Sequence and organization of the human vitamin D-binding protein gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1216 (3): 385–94. doi:10.1016/0167-4781(93)90005-x. PMID7505619.
Swamy N, Roy A, Chang R, Brisson M, Ray R (April 1995). "Affinity purification of human plasma vitamin D-binding protein". Protein Expression and Purification. 6 (2): 185–8. doi:10.1006/prep.1995.1023. PMID7606167.