Β2微球蛋白

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β2微球蛋白

Beta-2-microglobulin
β-2-微球蛋白

β2微球蛋白在I類MHC中的位置
有效結構
PDB 直系同源檢索:PDBe, RCSB
標識
代號 B2M
擴展標識 遺傳學109700 鼠基因88127 同源基因2987 ChEMBL: 1741302 GeneCards: B2M Gene
RNA表達模式
PBB GE B2M 201891 s at tn.png
PBB GE B2M 216231 s at tn.png
更多表達數據
直系同源體
物種 人類 鼠類
Entrez 567 12010
Ensembl ENSG00000166710 ENSMUSG00000060802
UniProt P61769 P01887
mRNA序列 NM_004048 NM_009735
蛋白序列 NP_004039 NP_033865
基因位置 Chr 15:
45 – 45.01 Mb
Chr 2:
122.15 – 122.15 Mb
PubMed查詢 [1] [2]

β2微球蛋白英語:β2 microglobulin,縮寫B2M)是第一類主要組織相容性抗原分子的組成部分之一,在所有有核的細胞中(即不包括紅細胞)都有表達[1][2]。在人類基因組中,β2微球蛋白[3]B2M 基因所編碼[2][4]

目錄

結構功能

β2微球蛋白位於細胞表面的α3鏈旁,但與α鏈不同的是,β2並沒有跨膜區域,且為非共價結合。在β2的「上方」(指遠離細胞膜的一端)為α鏈的α1區和α2區,構成了MHC的肽結合區。

β2微球蛋白不止參與形成第一類MHC分子,還能組成與之類似的表面受體,如CD1等。

β2微球蛋白還有一個功能,就是能與HFE (基因)結合,來調控鐵調素肝臟中的表達,which targets the iron transporter 膜鐵轉運蛋白 on the cytoplasmic membrane of 腸上皮細胞巨噬細胞 for degradation resulting in decreased iron uptake from food and iron release from recycled red blood cells respectively. 該功能的喪失會導致鐵過量和血色沉著病

臨床意義

In patients on long-term hemodialysis, it can aggregate into amyloid fibers that deposit in joint spaces, a disease known as dialysis-related amyloidosis.

Mice models deficient for the β2 microglobulin gene have been engineered. These mice demonstrate that β2 microglobulin is necessary for cell surface expression of MHC class I and stability of the peptide binding groove. In fact, in the absence of β2 microglobulin, very limited amounts of MHC class I (classical and non-classical) molecules can be detected on the surface. In the absence of MHC class I, CD8 T cells cannot develop. (CD8 T cells are a subset of T cells involved in the development of acquired immunity.) Low levels of β2 microglobulin can indicate non-progression of HIV.

Levels of beta-2 microglobulin can be elevated in multiple myeloma and lymphoma, though in these cases primary amyloidosis (amyloid light chain) and secondary amyloidosis (amyloid associated protein) are more common. The normal value of beta-2 microglobulin is <2 mg/L.[5] However, with respect to multiple myeloma, the levels of beta2-microglobulin may also be at the other end of the spectrum. Diagnostic testing for multiple myeloma includes obtaining the beta2-microglobulin level, for this level is an important prognostic indicator. A patient with a level <4 mg/L is expected to have a median survival of 43 months, while one with a level >4 mg/L has a median survival of only 12 months.[6] Beta-2 microglobulin levels cannot, however, distinguish between monoclonal gammopathy of uncertain significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.[7][8]

參考文獻

  1. Entrez Gene: Beta-2-microglobulin. 
  2. 2.0 2.1 Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. J. Immunol.. 1 November 1987, 139 (9): 3132–8. PMID 3312414. 
  3. Cunningham BA, Wang JL, Berggård I, Peterson PA. The complete amino acid sequence of beta 2-microglobulin. Biochemistry. November 1973, 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID 4586824. 
  4. Suggs SV, Wallace RB, Hirose T, Kawashima EH, Itakura K. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC349099/ Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin]. Proc. Natl. Acad. Sci. U.S.A.. November 1981, 78 (11): 6613–7. doi:10.1073/pnas.78.11.6613. PMID 6171820. PMC 349099. 
  5. Pignone M, Nicoll D; McPhee SJ. Pocket guide to diagnostic tests. 4th. New York: McGraw-Hill. 2004: pp. 191. ISBN 0-07-141184-4. 
  6. Munshi NC, Longo DL, Anderson KC. Chapter 111: Plasma Cell Disorders//Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL. Harrison's Principles of Internal Medicine. 18th. McGraw-Hill Professional. 2011: pp. 936–44. ISBN 0-07-174889-X. 
  7. Rajkumar S. V. "MGUS and Smoldering Multiple Myeloma: Update on Pathogenesis, Natural History, and Management." Hematology, American Society of Hematology Education Program. doi: 10.1182/asheducation-2005.1.340 (ASH Education Book January 1, 2005 vol. 2005 no. 1 340-345) Accessed 23 May 2014.
  8. Bataille R. and Klein B. "Serum levels of beta-2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of uncertain significance." Blood 1992 80(9) p2433 Accessed 23 May 2014.

延伸閱讀


  • Huang WC, Havel JJ, Zhau HE, Qian WP, Lue HW, Chu CY, Nomura T, Chung LW.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC3032570/ β2-Microglobulin Signaling Blockade Inhibited Androgen Receptor Axis and Caused Apoptosis in Human Prostate Cancer Cells]. Clin. Cancer Res.. 2008, 14 (17): 5341–7. doi:10.1158/1078-0432.CCR-08-0793. PMID 18765525. PMC 3032570. 
  • Huang WC, Wu D, Xie Z, Zhau HE, Nomura T, Zayzafoon M, Pohl J, Hsieh CL, Weitzmann MN, Farach-Carson MC, Chung LW.. Beta2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Res.. 2006, 66 (18): 9108–16. doi:10.1158/0008-5472.CAN-06-1996. PMID 16982753. 
  • Winchester JF, Salsberg JA, Levin NW. Beta-2 microglobulin in ESRD: an in-depth review. Advances in renal replacement therapy. 2004, 10 (4): 279–309. doi:10.1053/j.arrt.2003.11.003. PMID 14681859. 
  • Krangel MS, Orr HT, Strominger JL. Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell. 1980, 18 (4): 979–91. doi:10.1016/0092-8674(79)90210-1. PMID 93026. 
  • Okon M, Bray P, Vucelić D. 1H NMR assignments and secondary structure of human beta 2-microglobulin in solution. Biochemistry. 1992, 31 (37): 8906–15. doi:10.1021/bi00152a030. PMID 1390678. 
  • Guo HC, Jardetzky TS, Garrett TP et al.. Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature. 1992, 360 (6402): 364–6. doi:10.1038/360364a0. PMID 1448153. 
  • Gattoni-Celli S, Kirsch K, Timpane R, Isselbacher KJ. Beta 2-microglobulin gene is mutated in a human colon cancer cell line (HCT) deficient in the expression of HLA class I antigens on the cell surface. Cancer Res.. 1992, 52 (5): 1201–4. PMID 1737380. 
  • Saper MA, Bjorkman PJ, Wiley DC. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J. Mol. Biol.. 1991, 219 (2): 277–319. doi:10.1016/0022-2836(91)90567-P. PMID 2038058. 
  • Caruana RJ, Lobel SA, Leffell MS et al.. Tumor necrosis factor, interleukin-1 and beta 2-microglobulin levels in chronic hemodialysis patients. The International journal of artificial organs. 1991, 13 (12): 794–8. PMID 2289831. 
  • Connors LH, Shirahama T, Skinner M et al.. In vitro formation of amyloid fibrils from intact beta 2-microglobulin. Biochem. Biophys. Res. Commun.. 1985, 131 (3): 1063–8. doi:10.1016/0006-291X(85)90198-6. PMID 2413854. 
  • Hochman JH, Shimizu Y, DeMars R, Edidin M. Specific associations of fluorescent beta-2-microglobulin with cell surfaces. The affinity of different H-2 and HLA antigens for beta-2-microglobulin. J. Immunol.. 1988, 140 (7): 2322–9. PMID 2450918. 
  • Homma N, Gejyo F, Isemura M, Arakawa M. Collagen-binding affinity of beta-2-microglobulin, a preprotein of hemodialysis-associated amyloidosis. Nephron. 1989, 53 (1): 37–40. doi:10.1159/000185699. PMID 2674742. 
  • Bataille R, Grenier J, Commes T. In vitro production of beta 2 microglobulin by human myeloma cells. Cancer Invest.. 1988, 6 (3): 271–7. doi:10.3109/07357908809080649. PMID 3048575. 
  • Hönig R, Marsen T, Schad S et al.. Correlation of beta-2-microglobulin concentration changes to changes of distribution volume. The International journal of artificial organs. 1989, 11 (6): 459–64. PMID 3060434. 
  • Bjorkman PJ, Saper MA, Samraoui B et al.. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987, 329 (6139): 506–12. doi:10.1038/329506a0. PMID 3309677. 
  • Güssow D, Rein R, Ginjaar I et al.. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. J. Immunol.. 1987, 139 (9): 3132–8. PMID 3312414. 
  • Cunningham BA, Wang JL, Berggård I, Peterson PA. The complete amino acid sequence of beta 2-microglobulin. Biochemistry. 1974, 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID 4586824. 
  • Suggs SV, Wallace RB, Hirose T et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC349099/ Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin]. Proc. Natl. Acad. Sci. U.S.A.. 1982, 78 (11): 6613–7. doi:10.1073/pnas.78.11.6613. PMID 6171820. PMC 349099. 
  • Momoi T, Suzuki M, Titani K et al.. Amino acid sequence of a modified beta 2-microglobulin in renal failure patient urine and long-term dialysis patient blood. Clin. Chim. Acta. 1995, 236 (2): 135–44. doi:10.1016/0009-8981(95)06039-G. PMID 7554280. 
  • Collins EJ, Garboczi DN, Karpusas MN, Wiley DC. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC42670/ The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain]. Proc. Natl. Acad. Sci. U.S.A.. 1995, 92 (4): 1218–21. doi:10.1073/pnas.92.4.1218. PMID 7862664. PMC 42670. 
  • Matoba R, Okubo K, Hori N et al.. The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression. Gene. 1994, 146 (2): 199–207. doi:10.1016/0378-1119(94)90293-3. PMID 8076819. 
  • Wang Z, Cao Y, Albino AP et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC288010/ Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA]. J. Clin. Invest.. 1993, 91 (2): 684–92. doi:10.1172/JCI116249. PMID 8432869. PMC 288010. 

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