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Gene Review

GC  -  group-specific component (vitamin D...

Homo sapiens

Synonyms: DBP, DBP/GC, GRD3, Gc-globulin, Group-specific component, ...
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Disease relevance of GC


Psychiatry related information on GC

  • The proportion of alcoholic patients considered hypertensive on the basis of 24-hour BP criteria (daytime SBP >/=135 mm Hg or daytime DBP >/=85 mm Hg) fell from 42% during alcohol drinking to 12% after 1 month of complete abstinence [6].
  • In the present study we aimed at determining for the first time whether metabolic changes would also occur in vascular dementia (VD) patients in the supraoptic (SON), infundibular (INF), tuberomamillary (TMN), medial mamillary nuclei, vertical limb of the diagonal band of Broca (VDB), and nucleus basalis of Meynert [7].
  • The association between DBP and SBP by tertiles, and spatial functions (Block Design and Benton Visual Retention test) remained after controlling for education, marital status, smoking, alcohol and physical activity, and intermediates such as arteriosclerotic manifestations (block design, beta = 0.17; = 0.029) in multiple regression models [8].
  • The slopes of the relationship between MSNA and DBP were more negative (steeper) in the panic disorder group compared with the control subjects (-5.97 +/- 0.45 versus -3.06 +/- 0.43 bursts/100 heart beats per mmHg, P < 0.001) [9].
  • Among pain-free normotensives, elevated resting systolic (SBP) and diastolic (DBP) blood pressure were associated with significantly higher ISC pain thresholds (P values <0.05) [10].

High impact information on GC


Chemical compound and disease context of GC


Biological context of GC

  • The GC gene, and the tandemly linked ALB and AFP genes, have been previously localized to human chromosome 4q11-13 [20].
  • It appears that GC is very close (and may be the gene proximal) to the centromere [20].
  • Statistically significant linkage disequilibrium between the AluVpA and the GC iso-electric focusing (IEF) phenotypes was found in a sample of 188 unrelated individuals and delta values were calculated from the observed haplotype distribution [21].
  • The GC polymorphism revealed by Southern blot analysis of StyI-digests provides an informative DNA marker system for chromosome 4q11-q13 [22].
  • In a single case, the observed result of the StyI-digest differed from the result expected after IEF classification: homozygous GC 1F-1F by IEF and heterozygous by StyI RFLP analysis [22].

Anatomical context of GC

  • Radioiodinated DBP (125I-DBP) was used to follow the uptake of the protein by Raji cells, a human pre-B-lymphoma cell line [23].
  • In this work, we demonstrate that normal and malignant human B-lymphocytes specifically bind and internalize DBP [23].
  • Accordingly, most DBP molecules accumulated in endosomes should be degraded in lysosomes, instead of being recycled back to the surface, as in the case of AFP [23].
  • Their binding affinity was examined with calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP) [24].
  • The human serum vitamin D-binding protein (DBP) has many physiologically important functions, ranging from transporting vitamin D3 metabolites, binding and sequestering globular actin and binding fatty acids to functioning in the immune system [25].

Associations of GC with chemical compounds


Physical interactions of GC

  • Platelet-derived thrombospondin-1 is necessary for the vitamin D-binding protein (Gc-globulin) to function as a chemotactic cofactor for C5a [27].
  • BACKGROUND: The vitamin D receptor (VDR) and binding protein (DBP) mediate the cellular transport, activity, and anti-tumor action of 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D3] [5].
  • DBP binds to CD44 on the cell surface as evidenced by coimmunoprecipitation, confocal microscopy, and cell binding studies [28].
  • Genetic polymorphism was detected in the red deer (Cervus elaphus L.), plasma proteins, plasminogen (PLG) and vitamin D binding protein (GC) using antiserum to human proteins [29].
  • The RNase-gold complex does not bind to the FC but to the DFC and the GC, suggesting that rDNA transcription does not occur in the FC although both fluorescence in situ hybridization (FISH) and electron microscopic in situ hybridization reveal that the rDNA is specifically localized in the FCs [30].

Regulatory relationships of GC


Other interactions of GC

  • The results suggest that, unlike the corresponding sequences in the ALB and AFP genes, chromosomal sequences encoding the first domain and the leader sequence of the GC gene have specifically been conserved throughout vertebrate evolution [32].
  • Serum protein polymorphisms (GC, TF, and PI subtypes) in the Basque population of Alava [33].
  • The levels of certain other proteins, like haptoglobin, fibrinogen, complement component 3, and Gc-globulin, were altered in the disease group as well, however, the changes did not reach a statistical significance [34].
  • The more extensive interactions of DBP give an affinity for actin some 3 orders of magnitude higher than that for profilin [35].
  • These results provide clear evidence that CD44 and annexin A2 mediate the C5a chemotactic cofactor function of DBP [28].

Analytical, diagnostic and therapeutic context of GC


  1. Megalin-mediated endocytosis of vitamin d binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells. Rowling, M.J., Kemmis, C.M., Taffany, D.A., Welsh, J. J. Nutr. (2006) [Pubmed]
  2. Progress toward resolving the possible linkage of multiple endocrine neoplasia type 2A to haptoglobin and group-specific loci: use of restriction fragment length polymorphisms extends exclusion region. Kidd, K.K., Kidd, J.R., Castiglione, C.M., Pakstis, A.J., Sparkes, R.S. Genet. Epidemiol. (1986) [Pubmed]
  3. Identification of a region in the vitamin D-binding protein that mediates its C5a chemotactic cofactor function. Zhang, J., Kew, R.R. J. Biol. Chem. (2004) [Pubmed]
  4. A polymorphism within the vitamin D-binding protein gene is associated with Graves' disease but not with Hashimoto's thyroiditis. Pani, M.A., Regulla, K., Segni, M., Hofmann, S., Hüfner, M., Pasquino, A.M., Usadel, K.H., Badenhoop, K. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  5. Sequence variation within the 5' regulatory regions of the vitamin D binding protein and receptor genes and prostate cancer risk. Kidd, L.C., Paltoo, D.N., Wang, S., Chen, W., Akereyeni, F., Isaacs, W., Ahaghotu, C., Kittles, R. Prostate (2005) [Pubmed]
  6. Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring. Aguilera, M.T., de la Sierra, A., Coca, A., Estruch, R., Fernández-Solá, J., Urbano-Márquez, A. Hypertension (1999) [Pubmed]
  7. Metabolic alterations in the hypothalamus and basal forebrain in vascular dementia. Ishunina, T.A., Kamphorst, W., Swaab, D.F. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  8. Hypertension and changes of cognitive function in 81-year-old men: a 13-year follow-up of the population study "Men born in 1914", Sweden. Reinprecht, F., Elmståhl, S., Janzon, L., André-Petersson, L. J. Hypertens. (2003) [Pubmed]
  9. Sympathetic and cardiac baroreflex function in panic disorder. Lambert, E.A., Thompson, J., Schlaich, M., Laude, D., Elghozi, J.L., Esler, M.D., Lambert, G.W. J. Hypertens. (2002) [Pubmed]
  10. The relationship between resting blood pressure and acute pain sensitivity in healthy normotensives and chronic back pain sufferers: the effects of opioid blockade. Bruehl, S., Chung, O.Y., Ward, P., Johnson, B., McCubbin, J.A. Pain (2002) [Pubmed]
  11. A Rac-cGMP Signaling Pathway. Guo, D., Tan, Y.C., Wang, D., Madhusoodanan, K.S., Zheng, Y., Maack, T., Zhang, J.J., Huang, X.Y. Cell (2007) [Pubmed]
  12. Vitamin D binding protein (Gc-globulin). Cooke, N.E., Haddad, J.G. Endocr. Rev. (1989) [Pubmed]
  13. Liver-enriched transcription factors in liver function and development. Part II: the C/EBPs and D site-binding protein in cell cycle control, carcinogenesis, circadian gene regulation, liver regeneration, apoptosis, and liver-specific gene regulation. Schrem, H., Klempnauer, J., Borlak, J. Pharmacol. Rev. (2004) [Pubmed]
  14. Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Vasconcellos, C.A., Allen, P.G., Wohl, M.E., Drazen, J.M., Janmey, P.A., Stossel, T.P. Science (1994) [Pubmed]
  15. Regulation of the human vitamin D3 receptor promoter in breast cancer cells is mediated through Sp1 sites. Wietzke, J.A., Ward, E.C., Schneider, J., Welsh, J. Mol. Cell. Endocrinol. (2005) [Pubmed]
  16. Total plasma homocysteine and related amino acids in end-stage renal disease (ESRD) patients measured by gas chromatography-mass spectrometry--comparison with the Abbott IMx homocysteine assay and the HPLC method. Sigit, J.I., Hages, M., Brensing, K.A., Frotscher, U., Pietrzik, K., von Bergmann, K., Lütjohann, D. Clin. Chem. Lab. Med. (2001) [Pubmed]
  17. Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride: a meta-analysis. Graudal, N.A., Galløe, A.M., Garred, P. JAMA (1998) [Pubmed]
  18. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. Bikle, D.D., Gee, E., Halloran, B., Haddad, J.G. J. Clin. Invest. (1984) [Pubmed]
  19. Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance. Hirai, M., Suzuki, S., Hinokio, Y., Hirai, A., Chiba, M., Akai, H., Suzuki, C., Toyota, T. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  20. Tandem arrangement of the human serum albumin multigene family in the sub-centromeric region of 4q: evolution and chromosomal direction of transcription. Nishio, H., Heiskanen, M., Palotie, A., Bélanger, L., Dugaiczyk, A. J. Mol. Biol. (1996) [Pubmed]
  21. Molecular evaluation of an Alu repeat including a polymorphic variable poly(dA) (AluVpA) in the vitamin D binding protein (DBP) gene. Braun, A., Bichlmaier, R., Müller, B., Cleve, H. Hum. Genet. (1993) [Pubmed]
  22. Molecular analysis of the gene for the human vitamin-D-binding protein (group-specific component): allelic differences of the common genetic GC types. Braun, A., Bichlmaier, R., Cleve, H. Hum. Genet. (1992) [Pubmed]
  23. Receptor-mediated uptake and processing of vitamin D-binding protein in human B-lymphoid cells. Esteban, C., Geuskens, M., Ena, J.M., Mishal, Z., Macho, A., Torres, J.M., Uriel, J. J. Biol. Chem. (1992) [Pubmed]
  24. Biological Activities of 2alpha-Substituted Analogues of 1alpha,25-Dihydroxyvitamin D(3) in Transcriptional Regulation and Human Promyelocytic Leukemia (HL-60) Cell Proliferation and Differentiation. Takahashi, E., Nakagawa, K., Suhara, Y., Kittaka, A., Nihei, K., Konno, K., Takayama, H., Ozono, K., Okano, T. Biol. Pharm. Bull. (2006) [Pubmed]
  25. A structural basis for the unique binding features of the human vitamin D-binding protein. Verboven, C., Rabijns, A., De Maeyer, M., Van Baelen, H., Bouillon, R., De Ranter, C. Nat. Struct. Biol. (2002) [Pubmed]
  26. Specific uptake of alpha-fetoprotein by malignant human lymphoid cells. Laborda, J., Naval, J., Allouche, M., Calvo, M., Georgoulias, V., Mishal, Z., Uriel, J. Int. J. Cancer (1987) [Pubmed]
  27. Platelet-derived thrombospondin-1 is necessary for the vitamin D-binding protein (Gc-globulin) to function as a chemotactic cofactor for C5a. Trujillo, G., Kew, R.R. J. Immunol. (2004) [Pubmed]
  28. CD44 and annexin A2 mediate the C5a chemotactic cofactor function of the vitamin D binding protein. McVoy, L.A., Kew, R.R. J. Immunol. (2005) [Pubmed]
  29. Genetic polymorphism of plasminogen and vitamin D binding protein in red deer (Cervus elaphus L.). Tate, M.L., Dodds, K.G., Thomas, K.J., McEwan, K.M. Anim. Genet. (1992) [Pubmed]
  30. Nucleolonema as a fundamental substructure of the nucleolus. Sato, S., Yano, H., Makimoto, Y., Kaneta, T., Sato, Y. J. Plant Res. (2005) [Pubmed]
  31. Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor. Raymond, M.A., Désormeaux, A., Labelle, A., Soulez, M., Soulez, G., Langelier, Y., Pshezhetsky, A.V., Hébert, M.J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  32. Mapping and conservation of the group-specific component gene in mouse. Yang, F., Bergeron, J.M., Linehan, L.A., Lalley, P.A., Sakaguchi, A.Y., Bowman, B.H. Genomics (1990) [Pubmed]
  33. Serum protein polymorphisms (GC, TF, and PI subtypes) in the Basque population of Alava. Manzano, C., Moral, P., De la Rúa, C., Moreno, P. Hum. Hered. (1993) [Pubmed]
  34. Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia. Jiang, L., Lindpaintner, K., Li, H.F., Gu, N.F., Langen, H., He, L., Fountoulakis, M. Amino Acids (2003) [Pubmed]
  35. Crystal structure of the complex between actin and human vitamin D-binding protein at 2.5 A resolution. Head, J.F., Swamy, N., Ray, R. Biochemistry (2002) [Pubmed]
  36. The evaluation of five electrophoretic phenotyping systems for routine screening of bloodstains. Thomas, A.S. Journal - Forensic Science Society. (1989) [Pubmed]
  37. Localization and quantitation of the vitamin D binding protein (Gc-globulin) in human neutrophils. Kew, R.R., Sibug, M.A., Liuzzo, J.P., Webster, R.O. Blood (1993) [Pubmed]
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