Vitamin D-binding protein
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | GC, DBP, DBP/GRD3, HEL-S-51, VDBG, VDBP, Gc-MAF, GcMAF, vitamin D binding protein, DBP-maf, VDB, GC vitamin D binding protein | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 139200; MGI: 95669; HomoloGene: 486; GeneCards: GC; OMA:GC - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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.[5][6]
Function
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.[6]
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.[7]
Production
It is synthesized by hepatic parenchymal cells and secreted into the [blood] circulation. [8]
Structure
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.[9]
Many genetic variants of the GC gene are known and they produce 6 main haplotypes and 3 main protein variants (Gc1S, Gc1F and Gc2).[8] The genetic variations have been found to correlate with the response to vitamin D supplementation.[8]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000145321 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035540 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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.
- ^ a b "Entrez Gene: GC group-specific component (vitamin D binding protein)".
- ^ 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 2510818. PMID 18633461.
- ^ 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 3613945. PMID 23427793.
- ^ 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
PDB gallery | |
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