Vitamin D-binding protein

GC
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1J78, 1J7E, 1KW2, 1KXP, 1LOT, 1MA9
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
Gene location (Human)
Chr.	Chromosome 4 (human)
End	71,804,041 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	89,605,757 bp
RNA expression pattern
	Top expressed in
	liver; ; Right lobe of liver; ; gallbladder; ; pancreatic ductal cell; ; duodenum; ; Body of pancreas; ; jejunal mucosa; ; body of stomach; ; cardia; ; fundus;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	vitamin D binding ; calcidiol binding ; actin binding ; vitamin transmembrane transporter activity ;
Cellular component	blood microparticle ; extracellular region ; lysosomal lumen ; extracellular exosome ; extracellular space ; cytosol ;
Biological process	vitamin D metabolic process ; vitamin transport ; transport ; vitamin transmembrane transport ;
	Sources:Amigo / QuickGO
Orthologs
	2638
	14473
	ENSG00000145321
	ENSMUSG00000035540
	P02774
	P21614
	NM_000583 ; NM_001204306 ; NM_001204307
	NM_008096
	NP_000574 ; NP_001191235 ; NP_001191236
	NP_032122
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated June 12, 2022

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]

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.^[8]

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 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 map

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)

↑ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

Production

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

Regulation

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

Variation

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]

Related Research Articles

Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene. The AFP gene is located on the q arm of chromosome 4 (4q25). Maternal AFP serum level is used to screen for Down syndrome, neural tube defects, and other chromosomal abnormalities.

Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe³⁺ ions. Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.

α₂-Macroglobulin (α₂M), or alpha-2-macroglobulin, is a large plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the A2M gene.

Blood proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood proteins act as enzymes, complement components, protease inhibitors or kinin precursors. Contrary to popular belief, haemoglobin is not a blood protein, as it is carried within red blood cells, rather than in the blood serum.

Ceruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.

Serum albumin, often referred to simply as blood albumin, is an albumin found in vertebrate blood. Human serum albumin is encoded by the ALB gene. Other mammalian forms, such as bovine serum albumin, are chemically similar.

Vitamin D toxicity, or hypervitaminosis D is the toxic state of an excess of vitamin D. The normal range for blood concentration is 20 to 50 nanograms per milliliter (ng/mL). However, the toxic state is known to be a value of 100 ng/ml or more in a clinical setting.

Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric.

Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins are commonly found in blood plasma and differ from other blood proteins in that they are not glycosylated. Substances containing albumins are called albuminoids.

The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)₂vitamin D₃) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. VDR binding results in expression or transrepression of many specific gene products. VDR is also involved in microRNA-directed post transcriptional mechanisms. In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13.11.

Calcifediol, also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D₃ (abbreviated 25(OH)D₃), is a form of vitamin D produced in the liver by hydroxylation of vitamin D₃ (cholecalciferol) by the enzyme vitamin D 25-hydroxylase. Calcifediol can be further hydroxylated by the enzyme 25(OH)D-1α-hydroxylase, primarily in the kidney, to form calcitriol (1,25-(OH)₂D₃), which is the active hormonal form of vitamin D.

Actin, alpha skeletal muscle is a protein that in humans is encoded by the ACTA1 gene.

CEBPB Protein-coding gene in the species Homo sapiens

CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.

Nuclear transcription factor Y subunit beta is a protein that in humans is encoded by the NFYB gene.

Serum response factor, also known as SRF, is a transcription factor protein.

Afamin is a protein that in humans is encoded by the AFM gene.

D site of albumin promoter binding protein, also known as DBP, is a protein which in humans is encoded by the DBP gene.

DNA-binding protein A is a protein that in humans is encoded by the CSDA gene.

The liver plays the major role in producing proteins that are secreted into the blood, including major plasma proteins, factors in hemostasis and fibrinolysis, carrier proteins, hormones, prohormones and apolipoprotein:

In molecular biology, Vitamin D binding protein domain III protein domain is predominantly found in Vitamin D binding proteins (DBP). Vitamin D-binding protein (DBP)(also referred to as Gc-globulin) is synthesized primarily in the liver. This entry outlines the domain III of DBP. Domain III is G-actin binding region located in the C-terminal. Domain. This protein is found ubiquitously in vivo in significant quantities and can be detected in all fluid compartments. During acute phase inflammatory response, DBP levels tend to increase.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000145321 - Ensembl, May 2017
1 2 3 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". Human Heredity. 27 (2): 105–7. doi:10.1159/000152857. PMID 558959.
1 2 "Entrez Gene: GC group-specific component (vitamin D binding protein)".
↑ 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.
↑ 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.
1 2 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.
↑ 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.
↑ 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.
1 2 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.
↑ 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.
↑ 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.

External links

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

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[WikiPathways-11] The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000145321 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[pmid558959-5] 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.

[entrez-6] 1 2 "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.

[pmid11799400-8] 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.

[Norman2008-9] 1 2 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.

[Bouillon_2019-12] 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.

[Malik-2013-13] 1 2 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.

[14] 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.

[15] 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.

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