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类MHC中的位置
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 B2M
扩展标识 遗传学：109700 鼠基因：88127 同源基因：2987 ChEMBL: 1741302 GeneCards: B2M Gene
RNA表达模式
PBB GE B2M 201891 s at tn.png
PBB GE B2M 216231 s at tn.png
更多表达数据
直系同源体
物种 人类 鼠类
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查询 [1] [2]
This box:

β2微球蛋白（英语：β2 microglobulin，缩写B2M）是第一类主要组织相容性抗原分子的组成部分之一，在所有有核的细胞中（即不包括红细胞）都有表达[1][2]。在人类基因组中，β2微球蛋白[3]由B2M 基因所编码[2][4]。

目录

结构功能

β2微球蛋白位于细胞表面的α3链旁，但与α链不同的是，β2并没有跨膜区域，且为非共价结合。在β2的“上方”（指远离细胞膜的一端）为α链的α1区和α2区，构成了MHC的肽结合区。

β2微球蛋白不止参与形成第一类MHC分子，还能组成与之类似的表面受体，如CD1等。

β2微球蛋白还有一个功能，就是能与HFE (基因)结合，来调控铁调素在肝脏中的表达，which targets the iron transporter 膜铁转运蛋白 on the cytoplasmic membrane of 肠上皮细胞和巨噬细胞 for degradation resulting in decreased iron uptake from food and iron release from recycled red blood cells respectively. 该功能的丧失会导致铁过量和血色沉着病。

临床意义

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]

参考文献

  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.

延伸阅读


  • 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. 

外部链接

血清球蛋白
其他
其他球蛋白
清蛋白
其他

参考来源

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