Proteína que se une á vitamina D
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| Locus | Cr. 4 q13.3 | ||
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A proteína que se une á vitamina D (abreviada DBP, do inglés vitamin D-binding protein), coñecida orixinalmente como globulina gc (globulina de compoñente específico de grupo) é unha proteína que en humanos está codificada no xene GC do cromosoma 4.[1][2] Pode unirse a diversas formas da vitamina D. A DBP é xeneticamente o membro máis antigo da familia do albuminoide e apareceu moi cedo na evolución dos vertebrados.[3]
Estrutura[editar | editar a fonte]
A DBP humana é unha alfa-globulina glicosilada de ~58 kDa. Os seus 458 aminoácidos están codificados en 1690 nucleótidos no cromosoma 4 (4q11–q13). A súa estrutura primaria contén 28 residuos de cisteína formando moitos enlaces dislfuro. Contén 3 dominios. O dominio 1 está composto de 10 hélices alfa, o dominios 2 de 9, e o dominio 3 de 4.[4]
Función[editar | editar a fonte]
A proteína que se une á vitamina D pertence á familia xénica da albumina, xunto coa albumina sérica humana e a alfa-fetoproteína. É unha proteína multifuncional que se atopa no plasma, fluído ascítico, líquido cefalorraquídeo e na superficie de moitos tipos celulares.
Pode unirse a varias formas de vitamina D incluíndo o ergocalciferol (vitamina D2) e colecalciferol (vitamina D3), as formas hidroxiladas (calcifediol), e o produto hormonal activo, 1,25-dihidroxivitamina D (calcitriol). A maior proporción de vitamina D no sangue está unida a esta proteína. Transporta metabolitos de vitamina D entre a pel, fígado e riles, e a varios tecidos diana.[2][5]
Igual que o factor activador de macrófagos derivado da proteína Gc, é un factor activador dos macrófagos (MAF) que foi testado para usalo no tratamento do cancro, que activaría os macrófagos contra as células do cancro.[6]
Produción[editar | editar a fonte]
Sintetízana as células parenquimais hepáticas e segrégana na circulación sanguínea.[5]
Regulación[editar | editar a fonte]
Os factores de transcrición HFN1α é un regulador positivo, mentres que HFN1β é un regulador negativo dominante da expresión da DBP.[7]
Variación[editar | editar a fonte]
Coñécense moitas variantes xenéticas do xene GC. Producen 6 haplotipos principais e 3 variantes proteicas principais (Gc1S, Gc1F e Gc2).[8] As variacións xenéticas están asociadas con diferenzas nos niveis circulantes de 25-hidroxivitamina D.[9] Propúxose que serven para explicar algunhas das diferenzas no status da vitamina D en diferentes grupos étnicos,[10] e correlaciónanse coa resposta á suplementaciónn con vitamina D.[8]
Notas[editar | editar a fonte]
- ↑ Mikkelsen M, Jacobsen P, Henningsen K (xullo de 1977). "Possible localization of Gc-System on chromosome 4. Loss of long arm 4 material associated with father-child incompatibility within the Gc-System". Human Heredity 27 (2): 105–7. PMID 558959. doi:10.1159/000152857.
- ↑ 2,0 2,1 "Entrez Gene: GC group-specific component (vitamin D binding protein)".
- ↑ Bouillon, R.; Schuit, F.; Antonio, L.; Rastinejad, F. (2020). "Vitamin D Binding Protein: A Historic Overview". Frontiers in Endocrinology 10: 910. PMC 6965021. PMID 31998239. doi:10.3389/fendo.2019.00910.
- ↑ Verboven C, Rabijns A, De Maeyer M, Van Baelen H, Bouillon R, De Ranter C (febreiro de 2002). "A structural basis for the unique binding features of the human vitamin D-binding protein". Nature Structural Biology 9 (2): 131–6. PMID 11799400. doi:10.1038/nsb754.
- ↑ 5,0 5,1 Norman AW (agosto de 2008). "From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health". The American Journal of Clinical Nutrition 88 (2): 491S–499S. PMID 18689389. doi:10.1093/ajcn/88.2.491S.
- ↑ Yamamoto N, Suyama H, Yamamoto N (xullo de 2008). "Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF" ([PDF]). Translational Oncology 1 (2): 65–72. PMC 2510818. PMID 18633461. doi:10.1593/tlo.08106.
- ↑ Bouillon R, Schuit F, Antonio L, Rastinejad F (2019). "Vitamin D Binding Protein: A Historic Overview". Frontiers in Endocrinology 10: 910. PMC 6965021. PMID 31998239. doi:10.3389/fendo.2019.00910.
- ↑ 8,0 8,1 Malik S, Fu L, Juras DJ, Karmali M, Wong BY, Gozdzik A, Cole DE (xaneiro–febreiro de 2013). "Common variants of the vitamin D binding protein gene and adverse health outcomes". Critical Reviews in Clinical Laboratory Sciences 50 (1): 1–22. PMC 3613945. PMID 23427793. doi:10.3109/10408363.2012.750262.
- ↑ McGrath JJ, Saha S, Burne TH, Eyles DW (xullo de 2010). "A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations". The Journal of Steroid Biochemistry and Molecular Biology 121 (1–2): 471–7. PMID 20363324. doi:10.1016/j.jsbmb.2010.03.073.
- ↑ Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R (novembro de 2013). "Vitamin D-binding protein and vitamin D status of black Americans and white Americans". The New England Journal of Medicine 369 (21): 1991–2000. PMC 4030388. PMID 24256378. doi:10.1056/NEJMoa1306357.
Véxase tamén[editar | editar a fonte]
Bibliografía[editar | editar a fonte]
- Svasti J, Kurosky A, Bennett A, Bowman BH (abril de 1979). "Molecular basis for the three major forms of human serum vitamin D binding protein (group-specific component)". Biochemistry 18 (8): 1611–7. PMID 218624. doi:10.1021/bi00575a036.
- Braun A, Bichlmaier R, Cleve H (xuño de 1992). "Molecular analysis of the gene for the human vitamin-D-binding protein (group-specific component): allelic differences of the common genetic GC types". Human Genetics 89 (4): 401–6. PMID 1352271. doi:10.1007/BF00194311.
- Esteban C, Geuskens M, Ena JM, Mishal Z, Macho A, Torres JM, Uriel J (maio de 1992). "Receptor-mediated uptake and processing of vitamin D-binding protein in human B-lymphoid cells". The Journal of Biological Chemistry 267 (14): 10177–83. PMID 1374401. doi:10.1016/S0021-9258(19)50216-2.
- Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J (xuño d 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. PMID 1535333. doi:10.1016/0888-7543(92)90245-N.
- Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection 24 (3): 317–20. PMID 1602151. doi:10.1016/S0163-4453(05)80037-4.
- Yang F, Bergeron JM, Linehan LA, Lalley PA, Sakaguchi AY, Bowman BH (agosto de 1990). "Mapping and conservation of the group-specific component gene in mouse". Genomics 7 (4): 509–16. PMID 1696927. doi:10.1016/0888-7543(90)90193-X.
- Yang F, Luna VJ, McAnelly RD, Naberhaus KH, Cupples RL, Bowman BH (novembro de 1985). "Evolutionary and structural relationships among the group-specific component, albumin and alpha-fetoprotein". Nucleic Acids Research 13 (22): 8007–17. PMC 322106. PMID 2415926. doi:10.1093/nar/13.22.8007.
- Yang F, Brune JL, Naylor SL, Cupples RL, Naberhaus KH, Bowman BH (decembro de 1985). "Human group-specific component (Gc) is a member of the albumin family". Proceedings of the National Academy of Sciences of the United States of America 82 (23): 7994–8. Bibcode:1985PNAS...82.7994Y. PMC 391428. PMID 2415977. doi:10.1073/pnas.82.23.7994.
- Cooke NE, David EV (decembro de 1985). "Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family". The Journal of Clinical Investigation 76 (6): 2420–4. PMC 424397. PMID 2416779. doi:10.1172/JCI112256.
- Schoentgen F, Metz-Boutigue MH, Jollès J, Constans J, Jollès P (xuño de 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". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 871 (2): 189–98. PMID 2423133. doi:10.1016/0167-4838(86)90173-1.
- McNearney TA, Odell C, Holers VM, Spear PG, Atkinson JP (novembro de 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". The Journal of Experimental Medicine 166 (5): 1525–35. PMC 2189652. PMID 2824652. doi:10.1084/jem.166.5.1525.
- Yang F, Naberhaus KH, Adrian GS, Gardella JM, Brissenden JE, Bowman BH (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. PMID 2958390. doi:10.1016/0378-1119(87)90499-9.
- Cooke NE, Willard HF, David EV, George DL (xullo de 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". Human Genetics 73 (3): 225–9. PMID 3015768. doi:10.1007/BF00401232.
- Nestler JE, McLeod JF, Kowalski MA, Strauss JF, Haddad JG (maio de 1987). "Detection of vitamin D binding protein on the surface of cytotrophoblasts isolated from human placentae". Endocrinology 120 (5): 1996–2002. PMID 3552627. doi:10.1210/endo-120-5-1996.
- Pierce EA, Dame MC, Bouillon R, Van Baelen H, DeLuca HF (decembro de 1985). "Monoclonal antibodies to human vitamin D-binding protein". Proceedings of the National Academy of Sciences of the United States of America 82 (24): 8429–33. Bibcode:1985PNAS...82.8429P. PMC 390929. PMID 3936035. doi:10.1073/pnas.82.24.8429.
- Wooten MW, Nel AE, Goldschmidt-Clermont PJ, Galbraith RM, Wrenn RW (outubro de 1985). "Identification of a major endogenous substrate for phospholipid/Ca2+-dependent kinase in pancreatic acini as Gc (vitamin D-binding protein)". FEBS Letters 191 (1): 97–101. PMID 4054306. doi:10.1016/0014-5793(85)81001-2.
- Constans J, Oksman F, Viau M (agosto de 1981). "Binding of the apo and holo forms of the serum vitamin D-binding protein to human lymphocyte cytoplasm and membrane by indirect immunofluorescence". Immunology Letters 3 (3): 159–62. PMID 7026425. doi:10.1016/0165-2478(81)90120-6.
- Braun A, Kofler A, Morawietz S, Cleve H (decembro de 1993). "Sequence and organization of the human vitamin D-binding protein gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1216 (3): 385–94. PMID 7505619. doi:10.1016/0167-4781(93)90005-x.
- Swamy N, Roy A, Chang R, Brisson M, Ray R (abril de1995). "Affinity purification of human plasma vitamin D-binding protein". Protein Expression and Purification 6 (2): 185–8. PMID 7606167. doi:10.1006/prep.1995.1023.
