Vitamin D-binding protein

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] DBP is genetically the oldest member of the albuminoid family and appeared early in the evolution of vertebrates.[7]

GC
Protein GC PDB 1j78.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGC, DBP, DBP/GRD3, HEL-S-51, VDBG, VDBP, Gc-MAF, GcMAF, vitamin D binding protein, DBP-maf, VDB, GC vitamin D binding protein
External IDsOMIM: 139200 MGI: 95669 HomoloGene: 486 GeneCards: GC
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000583
NM_001204306
NM_001204307

NM_008096

RefSeq (protein)

NP_000574
NP_001191235
NP_001191236

NP_032122

Location (UCSC)Chr 4: 71.74 – 71.8 MbChr 5: 89.57 – 89.61 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

StructureEdit

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.[8]

FunctionEdit

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][9]

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.[10]

Interactive pathway mapEdit

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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|alt=Vitamin D Synthesis Pathway (view / edit)]]
Vitamin D Synthesis Pathway (view / edit)
  1. ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

ProductionEdit

It is synthesized by hepatic parenchymal cells and secreted into the blood circulation.[9]

RegulationEdit

The transcription factors HFN1α is a positive regulator while HFN1β is a dominant negative regulator of DBP expression.[11]

VariationEdit

Many genetic variants of the GC gene are known. They produce 6 main haplotypes and 3 main protein variants (Gc1S, Gc1F and Gc2).[12] The genetic variations are associated with differences in circulating 25-hydroxyvitamin D levels.[13] They have been proposed to account for some of the differences in vitamin D status in different ethnic groups,[14] and have been found to correlate with the response to vitamin D supplementation.[12]

ReferencesEdit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145321 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035540 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. ^ a b "Entrez Gene: GC group-specific component (vitamin D binding protein)".
  7. ^ Bouillon, R.; Schuit, F.; Antonio, L.; Rastinejad, F. (2020). "Vitamin D Binding Protein: A Historic Overview". Frontiers in Endocrinology. 10: 910. doi:10.3389/fendo.2019.00910. PMC 6965021. PMID 31998239.
  8. ^ 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. S2CID 38990672.
  9. ^ 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. doi:10.1093/ajcn/88.2.491S. PMID 18689389.
  10. ^ 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.
  11. ^ Bouillon R, Schuit F, Antonio L, Rastinejad F (2019). "Vitamin D Binding Protein: A Historic Overview". Frontiers in Endocrinology. 10: 910. doi:10.3389/fendo.2019.00910. PMC 6965021. PMID 31998239.
  12. ^ 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.
  13. ^ 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. S2CID 20057294.
  14. ^ 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.

Further readingEdit

External linksEdit

  • Overview of all the structural information available in the PDB for UniProt: P02774 (Vitamin D-binding protein) at the PDBe-KB.