Vitamin D-binding protein

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]

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; OMA:GC - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q13.3 Start 71,741,696 bp[1] End 71,804,041 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 E1|5 44.32 cM Start 89,565,381 bp[2] End 89,605,757 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in liver right lobe of liver gallbladder pancreatic ductal cell beta cell duodenum body of pancreas jejunal mucosa testicle gonad Top expressed in left lobe of liver gallbladder islet of Langerhans fetal liver hematopoietic progenitor cell human fetus right kidney human kidney sexually immature organism morula stomach More reference expression data BioGPS 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 Species Human Mouse Entrez 2638 14473 Ensembl ENSG00000145321 ENSMUSG00000035540 UniProt P02774 P21614 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 Mb Chr 5: 89.57 – 89.61 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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)

1. 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]