“Vitamin D-binding protein”的意思、由来-开放百科全书

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.^[3]

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.^[2]^[4]

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.^[5]

Interactive pathway map

Production

It is synthesized by hepatic parenchymal cells and secreted into the blood circulation.^[4]

Genetic variation

Many genetic variants of the GC gene are known. They produce 6 main haplotypes and 3 main protein variants (Gc1S, Gc1F and Gc2).^[8] The genetic variations are associated with differences in circulating 25-hydroxyvitamin D levels.^[6] They have been proposed to account for some of the differences in vitamin D status in different ethnic groups,^[7] and have been found to correlate with the response to vitamin D supplementation.^[8]

References

1. ^{{cite journal | vauthors = Mikkelsen M, Jacobsen P, Henningsen K | title = Possible localization of Gc-System on chromosome 4. Loss of long arm 4 material associated with father-child incompatibility within the Gc-System | journal = Human Heredity | volume = 27 | issue = 2 | pages = 105–7 | date = Jul 1977 | pmid = 558959 | pmc = | doi = 10.1159/000152857 }}
2. ^¹{{cite web | title = Entrez Gene: GC group-specific component (vitamin D binding protein)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2638| accessdate = }}
3. ^{{cite journal | vauthors = Verboven C, Rabijns A, De Maeyer M, Van Baelen H, Bouillon R, De Ranter C | title = A structural basis for the unique binding features of the human vitamin D-binding protein | journal = Nature Structural Biology | volume = 9 | issue = 2 | pages = 131–6 | date = February 2002 | pmid = 11799400 | doi = 10.1038/nsb754 }}
4. ^¹{{cite journal | vauthors = Norman AW | title = From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health | journal = The American Journal of Clinical Nutrition | volume = 88 | issue = 2 | pages = 491S-499S | date = August 2008 | pmid = 18689389 }}
5. ^{{cite journal | vauthors = Yamamoto N, Suyama H, Yamamoto N | title = Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF | journal = Translational Oncology | volume = 1 | issue = 2 | pages = 65–72 | date = July 2008 | pmid = 18633461 | pmc = 2510818 | url = http://www.transonc.com/pdf/manuscript/v01i02/neo08106.pdf | format = [PDF] | doi=10.1593/tlo.08106}}
6. ^{{cite journal | vauthors = McGrath JJ, Saha S, Burne TH, Eyles DW | title = A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 121 | issue = 1–2 | pages = 471–7 | date = July 2010 | pmid = 20363324 | doi = 10.1016/j.jsbmb.2010.03.073 }}
7. ^{{cite journal | vauthors = Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R | title = Vitamin D-binding protein and vitamin D status of black Americans and white Americans | journal = The New England Journal of Medicine | volume = 369 | issue = 21 | pages = 1991–2000 | date = November 2013 | pmid = 24256378 | doi = 10.1056/NEJMoa1306357 | pmc=4030388}}
8. ^¹{{cite journal | vauthors = Malik S, Fu L, Juras DJ, Karmali M, Wong BY, Gozdzik A, Cole DE | title = Common variants of the vitamin D binding protein gene and adverse health outcomes | journal = Critical Reviews in Clinical Laboratory Sciences | volume = 50 | issue = 1 | pages = 1–22 | date = January–February 2013 | pmid = 23427793 | pmc = 3613945 | doi = 10.3109/10408363.2012.750262 }}

Further reading

{{cite journal | vauthors = Svasti J, Kurosky A, Bennett A, Bowman BH | title = Molecular basis for the three major forms of human serum vitamin D binding protein (group-specific component) | journal = Biochemistry | volume = 18 | issue = 8 | pages = 1611–7 | date = April 1979 | pmid = 218624 | doi = 10.1021/bi00575a036 }}

{{cite journal | vauthors = Braun A, Bichlmaier R, Cleve H | title = Molecular analysis of the gene for the human vitamin-D-binding protein (group-specific component): allelic differences of the common genetic GC types | journal = Human Genetics | volume = 89 | issue = 4 | pages = 401–6 | date = June 1992 | pmid = 1352271 | doi = 10.1007/BF00194311 }}

{{cite journal | vauthors = Esteban C, Geuskens M, Ena JM, Mishal Z, Macho A, Torres JM, Uriel J | title = Receptor-mediated uptake and processing of vitamin D-binding protein in human B-lymphoid cells | journal = The Journal of Biological Chemistry | volume = 267 | issue = 14 | pages = 10177–83 | date = May 1992 | pmid = 1374401 | doi = }}

{{cite journal | vauthors = Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J | title = Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF) | journal = Genomics | volume = 13 | issue = 2 | pages = 293–300 | date = June 1992 | pmid = 1535333 | doi = 10.1016/0888-7543(92)90245-N }}

{{cite journal | vauthors = Dawson SJ, White LA | title = Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin | journal = The Journal of Infection | volume = 24 | issue = 3 | pages = 317–20 | date = May 1992 | pmid = 1602151 | doi = 10.1016/S0163-4453(05)80037-4 }}

{{cite journal | vauthors = Yang F, Bergeron JM, Linehan LA, Lalley PA, Sakaguchi AY, Bowman BH | title = Mapping and conservation of the group-specific component gene in mouse | journal = Genomics | volume = 7 | issue = 4 | pages = 509–16 | date = August 1990 | pmid = 1696927 | doi = 10.1016/0888-7543(90)90193-X }}

{{cite journal | vauthors = Yang F, Luna VJ, McAnelly RD, Naberhaus KH, Cupples RL, Bowman BH | title = Evolutionary and structural relationships among the group-specific component, albumin and alpha-fetoprotein | journal = Nucleic Acids Research | volume = 13 | issue = 22 | pages = 8007–17 | date = November 1985 | pmid = 2415926 | pmc = 322106 | doi = 10.1093/nar/13.22.8007 }}

{{cite journal | vauthors = Yang F, Brune JL, Naylor SL, Cupples RL, Naberhaus KH, Bowman BH | title = Human group-specific component (Gc) is a member of the albumin family | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 23 | pages = 7994–8 | date = December 1985 | pmid = 2415977 | pmc = 391428 | doi = 10.1073/pnas.82.23.7994 }}

{{cite journal | vauthors = Cooke NE, David EV | title = Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family | journal = The Journal of Clinical Investigation | volume = 76 | issue = 6 | pages = 2420–4 | date = December 1985 | pmid = 2416779 | pmc = 424397 | doi = 10.1172/JCI112256 }}

{{cite journal | vauthors = Schoentgen F, Metz-Boutigue MH, Jollès J, Constans J, Jollès P | title = Complete amino acid sequence of human vitamin D-binding protein (group-specific component): evidence of a three-fold internal homology as in serum albumin and alpha-fetoprotein | journal = Biochimica et Biophysica Acta | volume = 871 | issue = 2 | pages = 189–98 | date = June 1986 | pmid = 2423133 | doi = 10.1016/0167-4838(86)90173-1 }}

{{cite journal | vauthors = McNearney TA, Odell C, Holers VM, Spear PG, Atkinson JP | title = Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity | journal = The Journal of Experimental Medicine | volume = 166 | issue = 5 | pages = 1525–35 | date = November 1987 | pmid = 2824652 | pmc = 2189652 | doi = 10.1084/jem.166.5.1525 }}

{{cite journal | vauthors = Yang F, Naberhaus KH, Adrian GS, Gardella JM, Brissenden JE, Bowman BH | title = The vitamin D-binding protein gene contains conserved nucleotide sequences that respond to heavy metal, adipocyte and mitotic signals | journal = Gene | volume = 54 | issue = 2–3 | pages = 285–90 | year = 1987 | pmid = 2958390 | doi = 10.1016/0378-1119(87)90499-9 }}

{{cite journal | vauthors = Cooke NE, Willard HF, David EV, George DL | title = Direct regional assignment of the gene for vitamin D binding protein (Gc-globulin) to human chromosome 4q11-q13 and identification of an associated DNA polymorphism | journal = Human Genetics | volume = 73 | issue = 3 | pages = 225–9 | date = July 1986 | pmid = 3015768 | doi = 10.1007/BF00401232 }}

{{cite journal | vauthors = Nestler JE, McLeod JF, Kowalski MA, Strauss JF, Haddad JG | title = Detection of vitamin D binding protein on the surface of cytotrophoblasts isolated from human placentae | journal = Endocrinology | volume = 120 | issue = 5 | pages = 1996–2002 | date = May 1987 | pmid = 3552627 | doi = 10.1210/endo-120-5-1996 }}

{{cite journal | vauthors = Pierce EA, Dame MC, Bouillon R, Van Baelen H, DeLuca HF | title = Monoclonal antibodies to human vitamin D-binding protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 24 | pages = 8429–33 | date = December 1985 | pmid = 3936035 | pmc = 390929 | doi = 10.1073/pnas.82.24.8429 }}

{{cite journal | vauthors = Wooten MW, Nel AE, Goldschmidt-Clermont PJ, Galbraith RM, Wrenn RW | title = Identification of a major endogenous substrate for phospholipid/Ca2+-dependent kinase in pancreatic acini as Gc (vitamin D-binding protein) | journal = FEBS Letters | volume = 191 | issue = 1 | pages = 97–101 | date = October 1985 | pmid = 4054306 | doi = 10.1016/0014-5793(85)81001-2 }}

{{cite journal | vauthors = Constans J, Oksman F, Viau M | title = Binding of the apo and holo forms of the serum vitamin D-binding protein to human lymphocyte cytoplasm and membrane by indirect immunofluorescence | journal = Immunology Letters | volume = 3 | issue = 3 | pages = 159–62 | date = August 1981 | pmid = 7026425 | doi = 10.1016/0165-2478(81)90120-6 }}

{{cite journal | vauthors = Braun A, Kofler A, Morawietz S, Cleve H | title = Sequence and organization of the human vitamin D-binding protein gene | journal = Biochimica et Biophysica Acta | volume = 1216 | issue = 3 | pages = 385–94 | date = December 1993 | pmid = 7505619 | doi = 10.1016/0167-4781(93)90005-x }}

{{cite journal | vauthors = Swamy N, Roy A, Chang R, Brisson M, Ray R | title = Affinity purification of human plasma vitamin D-binding protein | journal = Protein Expression and Purification | volume = 6 | issue = 2 | pages = 185–8 | date = April 1995 | pmid = 7606167 | doi = 10.1006/prep.1995.1023 }}

1 : Vitamin D