Vitamin D-binding protein

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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
External IDsMGI: 95669 HomoloGene: 486 GeneCards: GC
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for GC
Genomic location for GC
Band4q13.3Start71,741,693 bp[1]
End71,804,041 bp[1]
RNA expression pattern
PBB GE GC 204965 at fs.png
More reference expression data
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: 89.42 – 89.46 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Structure[edit]

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]

Function[edit]

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]

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]

Interactive pathway map[edit]

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

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VitaminDSynthesis_WP1531Go to articleGo to articleGo to articleGo to articlego to articleGo to articleGo to articleGo to articlego to articlego to articlego to articlego to articleGo to articleGo to articlego to articleGo to articlego to articlego to articlego to articleGo to articlego to article
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VitaminDSynthesis_WP1531Go to articleGo to articleGo to articleGo to articlego to articleGo to articleGo to articleGo to articlego to articlego to articlego to articlego to articleGo to articleGo to articlego to articleGo to articlego to articlego to articlego to articleGo to articlego to article
|{{{bSize}}}px|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". 

Production[edit]

It is synthesized by hepatic parenchymal cells and secreted into the [blood] circulation.[8]

Genetic variation[edit]

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]

References[edit]

  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:". 
  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. ^ 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. ^ 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 2510818Freely accessible. PMID 18633461. 
  10. ^ 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 3613945Freely accessible. 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 4030388Freely accessible. PMID 24256378. 

Further reading[edit]