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).[5][6] Kod ljudi, β2 mikroglobulinskz protein[7] kodiran je genom B2M.[6][8]

B2M
Dostupne strukture
PDBPretraga 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
AliasiB2M
Vanjski ID-jeviOMIM: 109700 MGI: 88127 HomoloGene: 2987 GeneCards: B2M
Lokacija gena (čovjek)
Hromosom 15 (čovjek)
Hrom.Hromosom 15 (čovjek)[1]
Hromosom 15 (čovjek)
Genomska lokacija za B2M
Genomska lokacija za B2M
Bend15q21.1Početak44,711,358 bp[1]
Kraj44,718,851 bp[1]
Lokacija gena (miš)
Hromosom 2 (miš)
Hrom.Hromosom 2 (miš)[2]
Hromosom 2 (miš)
Genomska lokacija za B2M
Genomska lokacija za B2M
Bend2 E5|2 60.55 cMPočetak121,978,167 bp[2]
Kraj121,983,564 bp[2]
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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_004048

NM_009735

RefSeq (bjelančevina)

NP_004039

NP_033865

Lokacija (UCSC)Chr 15: 44.71 – 44.72 MbChr 2: 121.98 – 121.98 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Struktura i funkcija

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Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 119 aminokiselina, a molekulska težina 13.715 Da.[9].

1020304050
MSRSVALAVLALLSLSGLEAIQRTPKIQVYSRHPAENGKSNFLNCYVSGF
HPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYAC
RVNHVTLSQPKIVKWDRDM
Simboli
 
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.[10]

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

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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.[11]

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.[12] Međutim, s obzirom na multipli mijelom, nivoi β2 mikroglobulina mogu biti i na drugom kraju spektra.[13] 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[14] β2 razine mikroglobulina ne mogu, međutim, razlikovati monoklonsku gamopatiju neodređenog značaja (MGUS) koja ima bolju prognozu i tinjajući (nizak stupanj) mijeloma.[15][16]

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

Reference

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  1. ^ a b c ENSG00000273686 GRCh38: Ensembl release 89: ENSG00000166710, ENSG00000273686 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060802 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: Beta-2-microglobulin".
  6. ^ a b Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL (novembar 1987). "The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit". Journal of Immunology. 139 (9): 3132–8. PMID 3312414.
  7. ^ Cunningham BA, Wang JL, Berggård I, Peterson PA (novembar 1973). "The complete amino acid sequence of beta 2-microglobulin". Biochemistry. 12 (24): 4811–22. doi:10.1021/bi00748a001. PMID 4586824.
  8. ^ Suggs SV, Wallace RB, Hirose T, Kawashima EH, Itakura K (novembar 1981). "Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin". Proceedings of the National Academy of Sciences of the United States of America. 78 (11): 6613–7. Bibcode:1981PNAS...78.6613S. doi:10.1073/pnas.78.11.6613. PMC 349099. PMID 6171820.
  9. ^ "UniProt, P61769". Pristupljeno 13. 7. 2021.
  10. ^ Hundall SD (2011). "Chapter 3: Iron, Heme, and Hemoglobin". Hematology: A Pathophysiologic Approach (1st izd.). str. 17–25. ISBN 978-0-323-04311-3.
  11. ^ Rao M, Sayal SK, Uppal SS, Gupta RM, Ohri VC, Banerjee S (oktobar 1997). "Beta-2-Microglobulin Levels in Human-Immunodeficiency Virus Infected Subjects". Medical Journal, Armed Forces India. 53 (4): 251–254. doi:10.1016/S0377-1237(17)30746-3. PMC 5531080. PMID 28769505.
  12. ^ Pignone M, Nicoll D; McPhee SJ (2004). Pocket guide to diagnostic tests (4th izd.). New York: McGraw-Hill. str. 191. ISBN 0-07-141184-4.
  13. ^ "Amyloidosis". The Lecturio Medical Concept Library. Pristupljeno 28. 6. 2021.
  14. ^ Munshi NC, Longo DL, Anderson KC (2011). "Chapter 111: Plasma Cell Disorders". u Loscalzo J, Longo DL, Fauci AS, Dennis LK, Hauser SL (ured.). Harrison's Principles of Internal Medicine (18th izd.). McGraw-Hill Professional. str. 936–44. ISBN 978-0-07-174889-6.
  15. ^ Rajkumar SV (2005). "MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management". Hematology. American Society of Hematology. Education Program. 2005: 340–5. doi:10.1182/asheducation-2005.1.340. PMID 16304401.
  16. ^ Bataille R, Klein B (novembar 1992). "Serum levels of beta 2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of undetermined significance". Blood. 80 (9): 2433–4. doi:10.1182/blood.V80.9.2433.2433. PMID 1421418.

Dopunska literatura

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Vanjski linkovi

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