Vitamin D-binding protein (DBP)

Vitamin D-binding protein (DBP), also/originally known as gc-globulin (group-specific component), is a protein that in humans is encoded by the GC gene.[5][6]

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.[7]

Vitamin D-binding protein belongs to the albumin gene family, together with human serum albumin and alpha-fetoprotein. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types.

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.[6][8]

Gc MAF & Cancer

As Gc protein-derived macrophage activating factor it is a Macrophage Activating Factor (MAF) that has been tested for use as a cancer treatment that would activate macrophages against cancer cells.[9] It is synthesized by hepatic parenchymal cells and secreted into the [blood] circulation.[8]

Notwithstanding some interesting cancer results, this therapy is still controversial and experimental, pending better evidence-based experimentation and clinical success. (See file)

Many genetic variants of the GC gene are known. They produce 6 main haplotypes and 3 main protein variants (Gc1S, Gc1F and Gc2).[10] The genetic variations are associated with differences in circulating 25-hydroxyvitamin D levels.[11] They have been proposed to account for some of the differences in vitamin D status in different ethnic groups,[12] and have been found to correlate with the response to vitamin D supplementation.[10]

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 References

  1.  GRCh38: Ensembl release 89: ENSG00000145321Ensembl, May 2017
  2.  GRCm38: Ensembl release 89: ENSMUSG00000035540Ensembl, May 2017
  3. ^ “Human PubMed Reference:”.
  4. ^ “Mouse PubMed Reference:”.
  5. ^ 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. PMID 558959.
  6. ^ Jump up to: a b “Entrez Gene: GC group-specific component (vitamin D binding protein)”.
  7. ^ 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. PMID 11799400.
  8. ^ Jump up to: a b Norman AW (August 2008). “From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health”. The American Journal of Clinical Nutrition. 88 (2): 491S–499S. PMID 18689389.
  9. ^ Yamamoto N, Suyama H, Yamamoto N (July 2008). “Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF” ([PDF]). Translational Oncology. 1 (2): 65–72. doi:10.1593/tlo.08106. PMC 2510818. PMID 18633461.
  10. ^ Jump up to: a b Malik S, Fu L, Juras DJ, Karmali M, Wong BY, Gozdzik A, Cole DE (January–February 2013). “Common variants of the vitamin D binding protein gene and adverse health outcomes”. Critical Reviews in Clinical Laboratory Sciences. 50(1): 1–22. doi:10.3109/10408363.2012.750262. PMC 3613945. PMID 23427793.
  11. ^ 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. PMID 20363324.
  12. ^ Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R (November 2013). “Vitamin D-binding protein and vitamin D status of black Americans and white Americans”. The New England Journal of Medicine. 369 (21): 1991–2000. doi:10.1056/NEJMoa1306357. PMC 4030388. PMID 24256378.

 Extra Readings

 

Open Access: This article incorporates public domain material from the U.S. National Cancer Institute and other public domain Governmental institutions.  This article is also distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this C.C. article which has been modified and improved by the ACR Institute for the benefit of the People’s fundamental right to benefit from equal  access to relevant knowledge that can significantly improve their chances of avoiding serious chronic diseases.
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