Vitamin D-binding protein

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GC
Protein GC PDB 1j78.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GC, DBP, DBP/GRD3, HEL-S-51, VDBG, VDBP, Gc-MAF, GcMAF, vitamin D binding protein
External IDs MGI: 95669 HomoloGene: 486 GeneCards: GC
Genetically Related Diseases
vitamin metabolic disorder[1]
RNA expression pattern
PBB GE GC 204965 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000583
NM_001204306
NM_001204307

NM_008096

RefSeq (protein)

NP_000574
NP_001191235
NP_001191236

NP_032122.1
NP_032122

Location (UCSC) Chr 4: 71.74 – 71.8 Mb Chr 5: 89.42 – 89.46 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Vitamin D-binding protein, also/originally known as gc-globulin (group-specific component), is a protein that in humans is encoded by the GC gene.[4][5]

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 binds to vitamin D and its plasma metabolites and transports them to target tissues.[5]

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.[6]

Production[edit]

It is synthesized by hepatic parenchymal cells and secreted into the [blood] circulation. [7]

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.[8]

Many genetic variants of the GC gene are known and they produce 6 main haplotypes and 3 main protein variants (Gc1S, Gc1F and Gc2).[7] The genetic variations have been found to correlate with the response to vitamin D supplementation.[7]

Interactive pathway map[edit]

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

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VitaminDSynthesis_WP1531 Go to article Go to article Go to article Go to article go to article Go to article Go to article Go to article go to article go to article go to article go to article Go to article Go to article go to article Go to article go to article go to article go to article Go to article go to article
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VitaminDSynthesis_WP1531 Go to article Go to article Go to article Go to article go to article Go to article Go to article Go to article go to article go to article go to article go to article Go to article Go to article go to article Go to article go to article go to article go to article Go to article go 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". 

References[edit]

  1. ^ "Diseases that are genetically associated with GC view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ 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". Hum Hered. 27 (2): 105–7. doi:10.1159/000152857. PMID 558959. 
  5. ^ a b "Entrez Gene: GC group-specific component (vitamin D binding protein)". 
  6. ^ Yamamoto N, Suyama H, Yamamoto N (2008). "Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF" ([PDF]). TRANSLATIONAL ONCOLOGY. 1 (2): 65–72. PMC 2510818Freely accessible. PMID 18633461. 
  7. ^ a b c Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y. L.; Gozdzik, Agnes; Cole, David E. C. (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. 
  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". Nat. Struct. Biol. 9 (2): 131–6. doi:10.1038/nsb754. PMID 11799400. 

Further reading[edit]