Vitamin D-binding protein (DBP), also/originally known as gc-globulin (group-specific component), is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''GC''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
DBP is genetically the oldest member of the
albuminoid family and appeared early in the evolution of vertebrates.
Structure
Human GC is a glycosylated
alpha-globulin
Alpha globulins are a group of globular proteins in blood plasma, plasma that are highly mobile in alkaline or electrically charged solutions. They inhibit certain blood proteases and show significant inhibitor activity.
The alpha globulins typic ...
, ~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.
Function
Vitamin D-binding protein belongs to the
albumin
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 ...
gene family, together with
human serum albumin
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 ...
and
alpha-fetoprotein
Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...
. It is a multifunctional protein found in plasma,
ascitic fluid,
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
and on the surface of many cell types.
It is able to bind the various forms of
vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
including
ergocalciferol
Ergocalciferol, also known as vitamin D2 and nonspecifically calciferol, is a type of vitamin D found in food and used as a dietary supplement. As a supplement it is used to prevent and treat vitamin D deficiency. This includes vitamin D defici ...
(vitamin D
2) and
cholecalciferol
Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement.
Cholecalciferol is made in the skin f ...
(vitamin D
3), the 25-hydroxylated forms (
calcifediol
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-hydroxylas ...
), and the active hormonal product, 1,25-dihydroxyvitamin D (
calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
). 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.
As
Gc protein-derived macrophage activating factor it is a
Macrophage Activating Factor
A macrophage-activating factor (MAF) is a lymphokine or other receptor based signal that primes macrophages towards cytotoxicity to tumors, cytokine secretion, or clearance of pathogens. Similar molecules may cause development of an inhibitory, ...
(MAF) that has been tested for use as a cancer treatment that would activate
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s against cancer cells.
Interactive pathway map
Production
It is synthesized by
hepatic parenchymal cell
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, ...
s and secreted into the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
circulation.
Regulation
The transcription factors
HFN1α is a positive regulator while
HFN1β is a dominant negative regulator of DBP expression.
Variation
Many genetic variants of the ''GC'' gene are known. They produce 6 main
haplotype
A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent.
Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...
s and 3 main protein variants (Gc1S, Gc1F and Gc2).
[ The genetic variations are associated with differences in circulating 25-hydroxyvitamin D levels. They have been proposed to account for some of the differences in vitamin D status in different ethnic groups,] and have been found to correlate with the response to vitamin D supplementation.
References
Further reading
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External links
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{{PDB Gallery, geneid=2638
Vitamin D