Beta-2 microglobulin

Beta-2-microglobulin
250px PDB rendering based on 1a1m.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1A1M, 1A1N, 1A1O, 1A6Z, 1A9B, 1A9E, 1AGB, 1AGC, 1AGD, 1AGE, 1AGF, 1AKJ, 1AO7, 1B0G, 1B0R, 1BD2, 1C16, 1CE6, 1CG9, 1DE4, 1DUY, 1DUZ, 1E27, 1E28, 1EEY, 1EEZ, 1EFX, 1EXU, 1GZP, 1GZQ, 1HHG, 1HHH, 1HHI, 1HHJ, 1HHK, 1HLA, 1HSA, 1HSB, 1I1F, 1I1Y, 1I4F, 1I7R, 1I7T, 1I7U, 1IM3, 1IM9, 1JF1, 1JGD, 1JGE, 1JHT, 1JNJ, 1K5N, 1KPR, 1KTL, 1LDS, 1LP9, 1M05, 1M6O, 1MHE, 1MI5, 1N2R, 1OF2, 1OGA, 1OGT, 1ONQ, 1P7Q, 1PY4, 1Q94, 1QEW, 1QLF, 1QQD, 1QR1, 1QRN, 1QSE, 1QSF, 1QVO, 1R3H, 1S8D, 1S9W, 1S9X, 1S9Y, 1SYS, 1SYV, 1T1W, 1T1X, 1T1Y, 1T1Z, 1T20, 1T21, 1T22, 1TMC, 1TVB, 1TVH, 1UQS, 1UR7, 1UXS, 1UXW, 1VGK, 1W0V, 1W0W, 1W72, 1X7Q, 1XH3, 1XR8, 1XR9, 1XZ0, 1YDP, 1YPZ, 1ZHK, 1ZHL, 1ZS8, 1ZSD, 1ZT4, 1ZVS, 2A83, 2AK4, 2AV1, 2AV7, 2AXF, 2AXG, 2BCK, 2BNQ, 2BNR, 2BSR, 2BSS, 2BST, 2BVO, 2BVP, 2BVQ, 2C7U, 2CII, 2CIK, 2CLR, 2D31, 2D4D, 2D4F, 2DYP, 2E8D, 2ESV, 2F53, 2F54, 2F74, 2F8O, 2FYY, 2FZ3, 2GIT, 2GJ6, 2GT9, 2GTW, 2GTZ, 2GUO, 2H26, 2H6P, 2HJK, 2HJL, 2HLA, 2HN7, 2J8U, 2JCC, 2NW3, 2NX5, 2P5E, 2P5W, 2PO6, 2PYE, 2RFX, 2UWE, 2V2W, 2V2X, 2VB5, 2VLJ, 2VLK, 2VLL, 2VLR, 2X4N, 2X4O, 2X4P, 2X4Q, 2X4R, 2X4S, 2X4T, 2X4U, 2X70, 2X89, 2XKS, 2XKU, 2XPG, 2YPK, 2YPL, 2YXF, 2Z9T, 3AM8, 3B3I, 3B6S, 3BGM, 3BH8, 3BH9, 3BHB, 3BO8, 3BP4, 3BP7, 3BVN, 3BW9, 3BWA, 3BXN, 3BZE, 3BZF, 3C9N, 3CDG, 3CII, 3CIQ, 3CZF, 3D18, 3D25, 3D2U, 3D39, 3D3V, 3DBX, 3DHJ, 3DHM, 3DTX, 3DX6, 3DX7, 3DX8, 3DXA, 3EKC, 3FFC, 3FQN, 3FQR, 3FQT, 3FQU, 3FQW, 3FQX, 3FT2, 3FT3, 3FT4, 3GIV, 3GJF, 3GSN, 3GSO, 3GSQ, 3GSR, 3GSU, 3GSV, 3GSW, 3GSX, 3H7B, 3H9H, 3H9S, 3HAE, 3HCV, 3HG1, 3HLA, 3HPJ, 3HUJ, 3I6G, 3I6K, 3I6L, 3IB4, 3IXA, 3JTS, 3KLA, 3KPL, 3KPM, 3KPN, 3KPO, 3KPP, 3KPQ, 3KPR, 3KPS, 3KWW, 3KXF, 3KYN, 3KYO, 3L3D, 3L3G, 3L3I, 3L3J, 3L3K, 3LKN, 3LKO, 3LKP, 3LKQ, 3LKR, 3LKS, 3LN4, 3LN5, 3LOW, 3LOZ, 3LV3, 3M17, 3M1B, 3MGO, 3MGT, 3MR9, 3MRB, 3MRC, 3MRD, 3MRE, 3MRF, 3MRG, 3MRH, 3MRI, 3MRJ, 3MRK, 3MRL, 3MRM, 3MRN, 3MRO, 3MRP, 3MRQ, 3MRR, 3MV7, 3MV8, 3MV9, 3MYJ, 3MYZ, 3MZT, 3NA4, 3NFN, 3O3A, 3O3B, 3O3D, 3O3E, 3O4L, 3OV6, 3OX8, 3OXR, 3OXS, 3PWJ, 3PWL, 3PWN, 3PWP, 3QDA, 3QDG, 3QDJ, 3QDM, 3QEQ, 3QFD, 3QFJ, 3QZW, 3REW, 3RL1, 3RL2, 3RWJ, 3S6C, 3SDX, 3SJV, 3SKM, 3SKO, 3SPV, 3T8X, 3TID, 3TIE, 3TLR, 3TM6, 3TO2, 3TZV, 3U0P, 3UPR, 3UTQ, 3UTS, 3UTT, 3V5D, 3V5H, 3V5K, 3VCL, 3VFM, 3VFN, 3VFO, 3VFP, 3VFR, 3VFS, 3VFT, 3VFU, 3VFV, 3VFW, 3VH8, 3VRI, 3VRJ, 3VWJ, 3VWK, 3VXM, 3VXN, 3VXO, 3VXP, 3VXR, 3VXS, 3VXU, 3W0W, 3W39, 3WL9, 3WLB, 3WUW, 3X11, 3X12, 3X13, 3X14, 4BEO, 4E0K, 4E0L, 4E5X, 4EN3, 4EUP, 4EUQ, 4F7M, 4F7P, 4F7T, 4FTV, 4FXL, 4G8G, 4G8I, 4G9D, 4G9F, 4GKN, 4GKS, 4GUP, 4HKJ, 4HWZ, 4HX1, 4I48, 4I4W, 4JFD, 4JFE, 4JFF, 4JFO, 4JFP, 4JFQ, 4JQV, 4JQX, 4JRX, 4JRY, 4K71, 4K7F, 4KDT, 4L29, 4L3C, 4L3E, 4L4T, 4L4V, 4LCW, 4LCY, 4LHU, 4LNR, 4M8V, 4MJ5, 4MJ6, 4MJI, 4MNQ, 4N0F, 4N0U, 4N8V, 4NNX, 4NNY, 4NO0, 4NO2, 4NO3, 4NO5, 4NQC, 4NQD, 4NQE, 4NQV, 4NQX, 4NT6, 4O2C, 4O2E, 4O2F, 4ONO, 4PJ5, 4PJ7, 4PJ8, 4PJ9, 4PJA, 4PJB, 4PJC, 4PJD, 4PJE, 4PJF, 4PJG, 4PJH, 4PJI, 4PJX, 4PR5, 4PRA, 4PRB, 4PRD, 4PRE, 4PRH, 4PRI, 4PRN, 4PRP, 4QOK, 4QRP, 4QRQ, 4QRR, 4QRS, 4QRT, 4QRU, 4U1H, 4U1I, 4U1J, 4U1K, 4U1L, 4U1M, 4U1N, 4U1S, 4U6X, 4U6Y, 4UQ2, 4UQ3, 4WJ5, 4WO4, 4WU5, 4WU7, 4X6C, 4X6D, 4X6E, 4X6F, 4XXC
Identifiers
Symbol	B2M
External IDs	OMIM: 109700 MGI: 88127 HomoloGene: 2987 ChEMBL: 1741302 GeneCards: B2M Gene
Gene ontology Molecular function • glycoprotein binding • protein binding • identical protein binding Cellular component • Golgi membrane • extracellular region • extracellular space • cytoplasm • endoplasmic reticulum lumen • Golgi apparatus • plasma membrane • focal adhesion • external side of plasma membrane • ER to Golgi transport vesicle membrane • membrane • phagocytic vesicle membrane • early endosome membrane • early endosome lumen • MHC class I protein complex • extracellular exosome • HFE-transferrin receptor complex Biological process • retina homeostasis • positive regulation of T cell mediated cytotoxicity • response to molecule of bacterial origin • antigen processing and presentation of peptide antigen via MHC class I • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent • antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent • positive regulation of T cell cytokine production • viral process • cytokine-mediated signaling pathway • antigen processing and presentation of endogenous peptide antigen via MHC class I • T cell differentiation in thymus • protein refolding • response to drug • antigen processing and presentation of exogenous peptide antigen via MHC class I • innate immune response • response to cadmium ion • regulation of defense response to virus by virus • regulation of immune response • iron ion homeostasis • interferon-gamma-mediated signaling pathway • negative regulation of receptor binding Sources: Amigo / QuickGO
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	[1]	[2]

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). In humans, the β₂ microglobulin protein is encoded by the B2M gene.

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.

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.

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

External links

• beta 2-Microglobulin at the US National Library of Medicine Medical Subject Headings (MeSH)