Vitamin D-binding protein

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Group-specific component (vitamin D binding protein)
Protein GC PDB 1j78.png
Crystallographic structure of the human vitamin D-binding protein.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GC ; DBP; DBP/GC; GRD3; VDBG; VDBP
External IDs OMIM139200 MGI95669 HomoloGene486 ChEMBL: 2259 GeneCards: GC Gene
EC number 6.4.-.-
RNA expression pattern
PBB GE GC 204965 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2638 14473
Ensembl ENSG00000145321 ENSMUSG00000035540
UniProt P02774 P21614
RefSeq (mRNA) NM_000583 NM_008096
RefSeq (protein) NP_000574 NP_032122
Location (UCSC) Chr 4:
72.61 – 72.67 Mb
Chr 5:
89.42 – 89.46 Mb
PubMed search [1] [2]

Vitamin D-binding protein, also known as gc-globulin (group-specific component), is a protein that in humans is encoded by the GC gene.[2][3]

Function[edit]

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.[3] 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.[4]

Structure[edit]

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.[1]

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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VitaminDSynthesis_WP1531 Go to article Go to article Go to article Go to article go to article Go to article Go to article Go to article go to article go to article go to article go to article Go to article Go to article go to article Go to article go to article go to article go to article Go to article go to article
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Vitamin D Synthesis Pathway edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531". 

References[edit]

  1. ^ a b PDB 1J78; 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. 
  2. ^ 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. 
  3. ^ a b "Entrez Gene: GC group-specific component (vitamin D binding protein)". 
  4. ^ 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. 

Further reading[edit]

  • Svasti J, Kurosky A, Bennett A, Bowman BH (1979). "Molecular basis for the three major forms of human serum vitamin D binding protein (group-specific component).". Biochemistry 18 (8): 1611–7. doi:10.1021/bi00575a036. PMID 218624. 
  • Braun A, Bichlmaier R, Cleve H (1992). "Molecular analysis of the gene for the human vitamin-D-binding protein (group-specific component): allelic differences of the common genetic GC types.". Hum. Genet. 89 (4): 401–6. doi:10.1007/BF00194311. PMID 1352271. 
  • Esteban C, Geuskens M, Ena JM, et al. (1992). "Receptor-mediated uptake and processing of vitamin D-binding protein in human B-lymphoid cells.". J. Biol. Chem. 267 (14): 10177–83. PMID 1374401. 
  • Szpirer C, Riviere M, Cortese R, et al. (1992). "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).". Genomics 13 (2): 293–300. doi:10.1016/0888-7543(92)90245-N. PMID 1535333. 
  • Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151. 
  • Yang F, Bergeron JM, Linehan LA, et al. (1990). "Mapping and conservation of the group-specific component gene in mouse.". Genomics 7 (4): 509–16. doi:10.1016/0888-7543(90)90193-X. PMID 1696927. 
  • Yang F, Luna VJ, McAnelly RD, et al. (1986). "Evolutionary and structural relationships among the group-specific component, albumin and alpha-fetoprotein.". Nucleic Acids Res. 13 (22): 8007–17. doi:10.1093/nar/13.22.8007. PMID 2415926. 
  • Yang F, Brune JL, Naylor SL, et al. (1986). "Human group-specific component (Gc) is a member of the albumin family.". Proc. Natl. Acad. Sci. U.S.A. 82 (23): 7994–8. doi:10.1073/pnas.82.23.7994. PMID 2415977. 
  • Cooke NE, David EV (1986). "Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family.". J. Clin. Invest. 76 (6): 2420–4. doi:10.1172/JCI112256. PMID 2416779. 
  • Schoentgen F, Metz-Boutigue MH, Jollès J, et al. (1986). "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.". Biochim. Biophys. Acta 871 (2): 189–98. doi:10.1016/0167-4838(86)90173-1. PMID 2423133. 
  • McNearney TA, Odell C, Holers VM, et al. (1987). "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.". J. Exp. Med. 166 (5): 1525–35. doi:10.1084/jem.166.5.1525. PMID 2824652. 
  • Yang F, Naberhaus KH, Adrian GS, et al. (1987). "The vitamin D-binding protein gene contains conserved nucleotide sequences that respond to heavy metal, adipocyte and mitotic signals.". Gene 54 (2-3): 285–90. doi:10.1016/0378-1119(87)90499-9. PMID 2958390. 
  • Cooke NE, Willard HF, David EV, George DL (1986). "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.". Hum. Genet. 73 (3): 225–9. doi:10.1007/BF00401232. PMID 3015768. 
  • Nestler JE, McLeod JF, Kowalski MA, et al. (1987). "Detection of vitamin D binding protein on the surface of cytotrophoblasts isolated from human placentae.". Endocrinology 120 (5): 1996–2002. doi:10.1210/endo-120-5-1996. PMID 3552627. 
  • Pierce EA, Dame MC, Bouillon R, et al. (1986). "Monoclonal antibodies to human vitamin D-binding protein.". Proc. Natl. Acad. Sci. U.S.A. 82 (24): 8429–33. doi:10.1073/pnas.82.24.8429. PMID 3936035. 
  • Wooten MW, Nel AE, Goldschmidt-Clermont PJ, et al. (1985). "Identification of a major endogenous substrate for phospholipid/Ca2+-dependent kinase in pancreatic acini as Gc (vitamin D-binding protein).". FEBS Lett. 191 (1): 97–101. doi:10.1016/0014-5793(85)81001-2. PMID 4054306. 
  • Constans J, Oksman F, Viau M (1981). "Binding of the apo and holo forms of the serum vitamin D-binding protein to human lymphocyte cytoplasm and membrane by indirect immunofluorescence.". Immunol. Lett. 3 (3): 159–62. doi:10.1016/0165-2478(81)90120-6. PMID 7026425. 
  • Braun A, Kofler A, Morawietz S, Cleve H (1994). "Sequence and organization of the human vitamin D-binding protein gene.". Biochim. Biophys. Acta 1216 (3): 385–94. doi:10.1016/0167-4781(93)90005-x. PMID 7505619. 
  • Swamy N, Roy A, Chang R, et al. (1995). "Affinity purification of human plasma vitamin D-binding protein.". Protein Expr. Purif. 6 (2): 185–8. doi:10.1006/prep.1995.1023. PMID 7606167.