Beta-2 mikroglobulin

β₂ mikroglobulin, znan i kao B2M je komponenta molekula MHC klase I. Molekule MHC-klase imaju α₁, α₂ i α₃ proteine koji su prisutni u svim jedarnim ćelijama (isključujući crvene krvne ćelije). Kod ljudi, β₂ mikroglobulinskz protein kodiran je genom B2M.

B2M
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 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
Identifikatori
Aliasi	B2M
Vanjski ID-jevi	OMIM: 109700 MGI: 88127 HomoloGene: 2987 GeneCards: B2M
Lokacija gena (čovjek) Hrom. Hromosom 15 (čovjek) Bend 15q21.1 Početak 44,711,358 bp Kraj 44,718,851 bp
Lokacija gena (miš) Hrom. Hromosom 2 (miš) Bend 2 E5|2 60.55 cM Početak 121,978,167 bp Kraj 121,983,564 bp
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • vezivanje identičnih proteina Ćelijska komponenta • HFE-transferrin receptor complex • Golđijev aparat • phagocytic vesicle membrane • early endosome membrane • endoplasmic reticulum lumen • membrana • focal adhesion • Golđijeva membrana • ćelijska membrana • extracellular region • MHC class I protein complex • ER to Golgi transport vesicle membrane • early endosome lumen • Egzosom • external side of plasma membrane • Vanćelijsko • citosol • cell surface • specific granule lumen • recycling endosome membrane • tertiary granule lumen • MHC class I peptide loading complex Biološki proces • 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 • GO:0019049, GO:0030683 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 • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor • regulation of immune response • positive regulation of receptor binding • positive regulation of protein binding • Urođeni imunski sistem • 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 • GO:1900400 regulation of iron ion transport Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	567	12010
Ensembl	ENSG00000166710 ENSG00000273686	ENSMUSG00000060802
UniProt	P61769	P01887
RefSeq (mRNK)	NM_004048	NM_009735
RefSeq (bjelančevina)	NP_004039	NP_033865
Lokacija (UCSC)	Chr 15: 44.71 – 44.72 Mb	Chr 2: 121.98 – 121.98 Mb
PubMed pretraga
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Struktura i funkcija

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 119 aminokiselina, a molekulska težina 13.715 Da..

10		20		30		40		50
MSRSVALAVL		ALLSLSGLEA		IQRTPKIQVY		SRHPAENGKS		NFLNCYVSGF
HPSDIEVDLL		KNGERIEKVE		HSDLSFSKDW		SFYLLYYTEF		TPTEKDEYAC
RVNHVTLSQP		KIVKWDRDM

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Shema MHC klase I

β₂ microglobulin mikroglobulin leži pored lanca α₃ na površini ćelije. Za razliku od α₃, β₂ nema transmembransku regiju. Neposredno iznad β₂ (tj. dalje od ćelije) nalazi se lanac α₁, koji je sam pored α₂.

β₂ mikroglobulin pridružuje se ne samo na alfa lanac molekula MHC klase I, već i na molekule slične klasi I kao što je CD1 (kod ljudi pet gena), glavni kompleks histokompatibilnosti , MR1, neonatusni Fc receptor (FcRn) i Qa-1 (oblik aloantigena). Ipak, gen β₂ mikroglobulina nalazi se izvan lokusa MHC (HLA), na drugom hromosomu.

Dodatna funkcija je povezanost sa HFE protein, zajedno regulišući ekspresiju hepcidina u jetri koji cilja transporter gvožđa feroportin na bazolateralnoj membrani enterocita i ćelijskoj membrani makrofaga za razgradnju, što rezultira smanjenim unosom gvožđa iz hrane i smanjenim oslobađanjem gvožđa iz recikliranih crvenih krvnih zrnaca u MPS (monojedarni sistem fagocita). Gubitak ove funkcije uzrokuje višak gvožđa i hemohromatozu.

Kod infekcija citomegalovirusom, a virusni protein veže se za β₂ mikroglobulin, sprečavajući skupljanje molekula MHC klase I i njihov transport do plazmamembrane.

Konstruirani su modeli miševa kojima nedostaje gen β₂ mikroglobulina. Ovi miševi pokazuju da je β₂ mikroglobulin neophodan za ekspresiju površinsloćelijske MHC klase I i stabilnost brazde koja veže peptide. U stvari, u nedostatku β₂ mikroglobulina, na površini se mogu otkriti vrlo ograničene količine molekula MHC klase I (klasični i neklasični) (sindrom golih limfocita ili BLS) . U nedostatku MHC klase I, ne mogu se razviti CD8⁺ T-ćelija. (CD8⁺ T-ćelije su podskup T-ćelija uključenih u razvoj stečenog imuniteta.)

Klinički značaj

U pacijenata na dugotrajnoj hemodijalizi, može se agregirati u amiloidna vlakna koja se talože u zglobovima, bolest poznata kao amiloidoza povezana s dijalizom.

Niski nivoi β₂ mikroglobulina mogu ukazivati na neprogresivnost HIV-a.

Nivoi β₂ mikroglobulin može biti povišen kod multiplog mijeloma i limfoma, iako su u ovim slučajevima primarna amiloidoza (lahki lanac amiloida) i sekundarna amiloidoza (protein povezan sa amiloidima) češći. Normalna vrijednost β₂ mikroglobulina je < 2 mg/L. Međutim, s obzirom na multipli mijelom, nivoi β₂ mikroglobulina mogu biti i na drugom kraju spektra. Dijagnostičko ispitivanje multiplog mijeloma uključuje dobivanje nivoa β₂ mikroglobulina, jer je ovaj nivo važan prognostički pokazatelj. Od 2011., očekuje se da će pacijent sa razinom od < 4  mg/L imati medijanu preživljavanja 43 mjeseca, dok će pacijent sa nivoom > 4  mg/ imati medijanu preživljavanja od samo 12 mjeseci β₂ razine mikroglobulina ne mogu, međutim, razlikovati monoklonsku gamopatiju neodređenog značaja (MGUS) koja ima bolju prognozu i tinjajući (nizak stupanj) mijeloma.

Zabilježene su mutacije gubitka funkcije ovog gena kod pacijenata sa karcinomom, koji nisu reagirali na imunoterapije

Dopunska literatura

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• Winchester JF, Salsberg JA, Levin NW (oktobar 2003). "Beta-2 microglobulin in ESRD: an in-depth review". Advances in Renal Replacement Therapy. 10 (4): 279–309. doi:10.1053/j.arrt.2003.11.003. PMID 14681859.
• Krangel MS, Orr HT, Strominger JL (decembar 1979). "Assembly and maturation of HLA-A and HLA-B antigens in vivo". Cell. 18 (4): 979–91. doi:10.1016/0092-8674(79)90210-1. PMID 93026.
• Okon M, Bray P, Vucelić D (septembar 1992). "1H NMR assignments and secondary structure of human beta 2-microglobulin in solution". Biochemistry. 31 (37): 8906–15. doi:10.1021/bi00152a030. PMID 1390678.
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Vanjski linkovi

• beta 2-Microglobulin na US National Library of Medicine Medical Subject Headings (MeSH)
• Lokacija ljudskog genoma B2M i stranica sa detaljima o genu B2M u UCSC Genome Browseru.
• https://www.ebi.ac.uk/pdbe P61769