Beta-2 microglobulin

B2M
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, 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, 1OF2, 1OGA, 1OGT, 1ONQ, 1PY4, 1Q94, 1QEW, 1QLF, 1QQD, 1QR1, 1QRN, 1QSE, 1QSF, 1QVO, 1R3H, 1S9W, 1S9X, 1S9Y, 1SYS, 1SYV, 1TMC, 1TVB, 1TVH, 1UQS, 1UXS, 1UXW, 1VGK, 1W0V, 1W0W, 1W72, 1X7Q, 1XH3, 1XR8, 1XR9, 1XZ0, 1YDP, 1YPZ, 1ZHK, 1ZHL, 1ZS8, 1ZSD, 1ZT4, 1ZVS, 2A83, 2AK4, 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, 2GIT, 2GJ6, 2GT9, 2GTW, 2GTZ, 2GUO, 2H26, 2H6P, 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, 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, 3KPO, 3KPR, 3KPS, 3KWW, 3KXF, 3KYN, 3KYO, 3L3D, 3L3G, 3L3I, 3L3J, 3L3K, 3LKN, 3LKO, 3LKP, 3LKQ, 3LKR, 3LKS, 3LN4, 3LN5, 3LOW, 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, 3OX8, 3OXR, 3OXS, 3PWJ, 3PWL, 3PWN, 3PWP, 3QDA, 3QDG, 3QDJ, 3QDM, 3QEQ, 3QFD, 3QFJ, 3QZW, 3RL1, 3RWJ, 3S6C, 3SDX, 3SJV, 3SKM, 3SKO, 3SPV, 3T8X, 3TID, 3TIE, 3TLR, 3TM6, 3TO2, 3TZV, 3U0P, 3UPR, 3UTQ, 3UTS, 3UTT, 3V5D, 3V5H, 3V5K, 3VCL, 3VFR, 3VFS, 3VFT, 3VFU, 3VFV, 3VFW, 3VH8, 3VRI, 3VRJ, 3VWJ, 3VWK, 3W39, 4E0K, 4E0L, 4E5X, 4EN3, 4EUP, 4F7M, 4F7P, 4F7T, 4FTV, 4FXL, 4G8G, 4G8I, 4G9D, 4G9F, 4GKS, 4GUP, 4HKJ, 4I4W, 4JFD, 4JFE, 4JFF, 4JFO, 4JFP, 4JFQ, 4JQX, 4JRX, 4JRY, 4K7F, 4KDT, 4L4T, 4L4V, 1CG9, 1N2R, 1P7Q, 1S8D, 1T1W, 1T1X, 1T1Y, 1T1Z, 1T20, 1T21, 1T22, 2AV1, 2FYY, 2FZ3, 2HJK, 3DX6, 3DX7, 3DX8, 3KPL, 3KPM, 3KPN, 3KPP, 3KPQ, 3LOZ, 3OV6, 3REW, 3RL2, 3VXM, 3VXN, 3VXO, 3VXP, 3VXR, 3VXS, 3VXU, 3W0W, 3WL9, 3WLB, 3WUW, 3X11, 3X12, 3X13, 3X14, 4GKN, 4HWZ, 4HX1, 4I48, 4K71, 4L29, 4L3C, 4L3E, 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, 4WDI, 4Z76, 4Z77, 4Z78, 4R9H, 4RA3, 4RAH, 5D2L, 5D2N, 4WW2, 5DEG, 4RMT, 5DEF, 4RMW, 4RMV, 4RMR, 5D7J, 4RMQ, 4RMS, 4WWK, 5BXF, 5D5M, 5D7L, 4RMU, 4WUU, 5D7I, 5EU5, 5EO0, 5EO1, 5EU4, 5BRZ, 5EU6, 5BS0, 5EU3, 5C9J, 5D9S, 5HGA, 5C0D, 5C0B, 5C0I, 5C0A, 5B38, 5E9D, 5B39, 5C0H, 5HHN, 5HGD, 5C08, 5CFH, 5CKG, 4ZEZ, 5C0C, 5HGH, 5C0J, 5HHQ, 5DDH, 5HHM, 5HGB, 5C09, 5HYJ, 5CKA, 5C07, 5HHP, 5C0G, 5C0F, 5HHO, 5C0E
Identifiers
Aliases	B2M, entrez:567, IMD43, beta-2-microglobulin, Β2 microglobulin
External IDs	OMIM: 109700 MGI: 88127 HomoloGene: 2987 GeneCards: B2M
Gene location (Human) Chr. Chromosome 15 (human) Band 15q21.1 Start 44,711,358 bp End 44,718,851 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 E5|2 60.55 cM Start 121,978,167 bp End 121,983,564 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte gallbladder appendix lymph node right lung spleen upper lobe of left lung rectum stromal cell of endometrium Achilles tendon Top expressed in seminal vesicula lymph node submandibular gland right lung white adipose tissue right lung lobe spleen subcutaneous adipose tissue thymus calvaria More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding identical protein binding Cellular component HFE-transferrin receptor complex Golgi apparatus phagocytic vesicle membrane early endosome membrane endoplasmic reticulum lumen membrane focal adhesion Golgi membrane plasma membrane extracellular region MHC class I protein complex ER to Golgi transport vesicle membrane early endosome lumen extracellular exosome external side of plasma membrane extracellular space cytosol cell surface specific granule lumen recycling endosome membrane tertiary granule lumen MHC class I peptide loading complex Biological process positive regulation of receptor-mediated endocytosis cellular response to iron ion response to cadmium ion negative regulation of receptor binding negative regulation of neuron projection development antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent T cell differentiation in thymus immune system process interferon-gamma-mediated signaling pathway antigen processing and presentation of peptide antigen via MHC class I iron ion homeostasis positive regulation of T cell mediated cytotoxicity mitigation of host defenses by virus antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent regulation of membrane depolarization antigen processing and presentation of endogenous peptide antigen via MHC class I positive regulation of ferrous iron binding positive regulation of transferrin receptor binding retina homeostasis positive regulation of T cell cytokine production protein refolding immune response regulation of immune response positive regulation of receptor binding positive regulation of protein binding innate immune response cellular response to lipopolysaccharide response to molecule of bacterial origin antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent iron ion transport neutrophil degranulation regulation of erythrocyte differentiation cellular response to iron(III) ion antimicrobial humoral immune response mediated by antimicrobial peptide positive regulation of iron ion import across plasma membrane regulation of iron ion transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 567 12010 Ensembl ENSG00000166710 ENSG00000273686 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: 121.98 – 121.98 Mb PubMed search
Wikidata
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β₂ microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α₁, α₂, and α₃ proteins which are present on all nucleated cells (excluding 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 (5 genes in humans), MR1, the neonatal Fc receptor (FcRn), and Qa-1 (a form of alloantigen). Nevertheless, the β₂ microglobulin gene is outside of the MHC (HLA) locus, on a different chromosome.

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 basolateral membrane of enterocytes and cell membrane of macrophages for degradation resulting in decreased iron uptake from food and decreased iron release from recycled red blood cells in the MPS (mononuclear phagocyte system) respectively. Loss of this function causes iron excess and hemochromatosis.

In a cytomegalovirus infection, a viral protein binds to β₂ microglobulin, preventing assembly of MHC class I molecules and their transport to the plasma membrane.

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 (bare lymphocyte syndrome or BLS). 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 β₂ 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 β₂ microglobulin is < 2 mg/L. However, with respect to multiple myeloma, the levels of β₂ microglobulin may also be at the other end of the spectrum. Diagnostic testing for multiple myeloma includes obtaining the β₂ microglobulin level, for this level is an important prognostic indicator. As of 2011, 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. β₂ microglobulin levels cannot, however, distinguish between monoclonal gammopathy of undetermined significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.

Loss-of-function mutations in this gene have been reported in cancer patients unresponsive to immunotherapies.

Virus relevance

β₂ microglobulin has been shown to be of high relevance for viral entry of Coxsackievirus A9 and Vaccinia virus (a Poxvirus). For Coxsackievirus A9, it is likely that β₂ microglobulin is required for the transport to plasma membrane of the identified receptor, the Human Neonatal Fc Receptor (FcRn). However, the specific function for Vaccinia virus has not yet been elucidated.

Further reading

External links

• beta+2-Microglobulin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human B2M genome location and B2M gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P61769 (Beta-2 microglobulin) at the PDBe-KB.