Beta-2 microglobulin

Beta-2-microglobulin

PDB rendering based on 1a1m[1].
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbol B2M
External IDs OMIM: 109700 MGI: 88127 HomoloGene: 2987 ChEMBL: 1741302 GeneCards: B2M Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 567 12010
Ensembl ENSG00000166710 ENSMUSG00000060802
UniProt P61769 P01887
RefSeq (mRNA) NM_004048 NM_009735
RefSeq (protein) NP_004039 NP_033865
Location (UCSC) Chr 15:
44.71 – 44.72 Mb		 Chr 2:
122.15 – 122.15 Mb
PubMed search

β2 microglobulin also known as B2M is a component of MHC class I molecules, which are present on all nucleated cells (excludes red blood cells).[2][3] In humans, the β2 microglobulin protein[4] is encoded by the B2M gene.[3][5]

Structure and function

Schematic representation of MHC class I

β2 microglobulin lies beside the α3 chain on the cell surface. Unlike α3, β2 has no transmembrane region. Directly above β2 (that is, further away from the cell) lies the α1 chain, which itself is next to the α2.

β2 microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as CD1 and Qa.

An additional function is association with the HFE protein, together regulating the expression of hepcidin in the liver which targets the iron transporter ferroportin on the cytoplasmic membrane of enterocytes and macrophages for degradation resulting in decreased iron uptake from food and iron release from recycled red blood cells respectively. Loss of this function causes iron excess and hemochromatosis.

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.)

Clinical significance

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

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.[6] 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.[7] Beta-2 microglobulin levels cannot, however, distinguish between monoclonal gammopathy of uncertain significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.[8][9]

References

  1. ↑ Smith, K. J.; Reid, S. W.; Harlos, K.; McMichael, A. J.; Stuart, D. I.; Bell, J. I.; Jones, E. Y. (1996). "Bound water structure and polymorphic amino acids act together to allow the binding of different peptides to MHC class I HLA-B53". Immunity 4 (3): 215–228. doi:10.1016/S1074-7613(00)80430-6. PMID 8624812.
  2. ↑ "Entrez Gene: Beta-2-microglobulin".
  3. 1 2 Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL (1 November 1987). "The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit". J. Immunol. 139 (9): 3132–8. PMID 3312414.
  4. ↑ Cunningham BA, Wang JL, Berggård I, Peterson PA (November 1973). "The complete amino acid sequence of beta 2-microglobulin". Biochemistry 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID 4586824.
  5. ↑ Suggs SV, Wallace RB, Hirose T, Kawashima EH, Itakura K (November 1981). "Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin". Proc. Natl. Acad. Sci. U.S.A. 78 (11): 6613–7. doi:10.1073/pnas.78.11.6613. PMC 349099. PMID 6171820.
  6. ↑ Pignone M, Nicoll D; McPhee SJ (2004). Pocket guide to diagnostic tests (4th ed.). New York: McGraw-Hill. p. 191. ISBN 0-07-141184-4.
  7. ↑ Munshi NC, Longo DL, Anderson KC (2011). "Chapter 111: Plasma Cell Disorders". In Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL. Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill Professional. pp. 936–44. ISBN 0-07-174889-X.
  8. ↑ 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.
  9. ↑ 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.

Further reading

External links

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