BSG (gen)
Basigin (BSG), znan i kao induktor vanćelijskog metaloproteinaznog matriksa (EMMPRIN) il i klaster diferencijacije 147 (CD147), je protein koji je kod ljudi kodiran genom BSG.[5][6][7] Ovaj protein je odrednica za OK sistem ljudskih krvnih grupa. U sistemu Ok poznata su tri antigena; najčešći su Oka (također se naziva i OK1), OK2 i OK3. Pokazalo se da je basigin važan receptor na crvenim krvnim zrncima za ljudski parazit malarije, Plasmodium falciparum.[8]
Aminokiselinska sekvanca:
- 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
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAAALFVLLG | FALLGTHGAS | GAAGFVQAPL | SQQRWVGGSV | ELHCEAVGSP | ||||
| VPEIQWWFEG | QGPNDTCSQL | WDGARLDRVH | IHATYHQHAA | STISIDTLVE | ||||
| EDTGTYECRA | SNDPDRNHLT | RAPRVKWVRA | QAVVLVLEPG | TVFTTVEDLG | ||||
| SKILLTCSLN | DSATEVTGHR | WLKGGVVLKE | DALPGQKTEF | KVDSDDQWGE | ||||
| YSCVFLPEPM | GTANIQLHGP | PRVKAVKSSE | HINEGETAML | VCKSESVPPV | ||||
| TDWAWYKITD | SEDKALMNGS | ESRFFVSSSQ | GRSELHIENL | NMEADPGQYR | ||||
| CNGTSSKGSD | QAIITLRVRS | HLAALWPFLG | IVAEVLVLVT | IIFIYEKRRK | ||||
| PEDVLDDDDA | GSAPLKSSGQ | HQNDKGKNVR | QRNSS |
Funkcija
urediBasigin je član i superporodice munoglobulina, sa strukturom koja se odnosi na navodni drevni oblik porodice. Kako članovi imunoglobulinske natporodice imaju temeljne uloge u međućelijskom prepoznavanju, uključeni u različite imunske pojave, diferencijaciju i razvoj; smatra se da basigin ima ulogu i u međućelijskom prepoznavanju (Miyauchi et al., 1991; Kanekura et al., 1991).[9][10]
Ima razne funkcije. Uz sposobnost induciranja metaloproteinaze, basigin također regulira nekoliko različitih funkcija, kao što su spermatogeneza, ekspresija monokarboksilatnog transportera i reaktivnost limfocita.[6]
Basigin je tip I integralnih membranskih receptora, koji ima mnogo liganada, uključujući proteine ciklofilin (CyP) Cyp-A i CyP-B i određene integrine.[11][12][13] Eksprimiraju ga mnogi tipovi ćelija, uključujući epitelne, endotelle i leukocite. Ljudski protein basigin sadrži 269 aminokiselina, koje formiraju dva jako glikozilirana tipa C2 imunoglobulinu sličnih domena na N-terminalnom vanćelijskom dijelu. Karakteriziran je i drugi oblik basigina koji sadrži jedan dodatni domen sličan imunoglobulinu u vanćelijskom dijelu.[6]
Interakcije
urediPokazano je da masigin ima interakcije sa ubikvitinom C.[14]
Pokazano je da basigin tvori kompleks sa monokarboksilatnim transporterima u mrežnjači miševa. Čini se da je potreban za pravilno postavljanje MCT-a u membranu. U basigin null miševa, neuspjeh MCT-a da se integriraju s membranom može biti izravno povezan s neuspjehom prijenosa hranjivih sastojaka u mrežnjčinom pigmentiranom epitelu (laktati koji se prenose MCT-ovima 1, 3 i 4 ključni su hranjivi sastojci za razvoj RPE) , što je rezultiralo gubitkom vida kod nultih životinja.[15]
Basigin stupa u interakciju sa četvrtim domenom C-tip lektina u receptoru Endo180[16] za formiranje molekulskog epitelno-mezenhimskog prijelaza supresorskog kompleksa, koji ako se poremeti rezultira indukcijom invazivnog ponašanja epitelnih ćelija prostate, povezanog sa lošim preživljavanjem njenog raka.[17]
Uloga u malariji
urediNedavno je (novembar 2011.) utvrđeno da je basigin receptor koji je bitan za invaziju većine sojeva Plasmodium falciparum na eritrocite, najvirulentnijih vrsta parazita plazmodija, koji uzrokuju ljudski malariju. Postoje nade da bi se razvojem antitijela na ligand parazita za basigin, Rh5 moglo naći bolje cjepivo za malariju.[8] Na površinu parazita malarije, sasigin se veže proteinom PfRh5 .
Uloga u infekciji SARS-CoV-2 (COVID-19)
urediBasigin koji se eksprimira u ćeliji domaćinu (CD147) može vezati protein proteina SARS-CoV-2 i možda biti uključen u invaziju ćelija domaćina.[18] Nakon toga, meplazumab, humanizirano antitelo na CD147, testirano je na pacijentima sa upalom pluća u SARS-CoV-2.[19] Neke od ovih tvrdnji osporila je druga grupa naučnika koja nije pronašla dokaze o direktnoj ulozi basigina u vezanju virusnog proteina spike ili promociji infekcije plućnih ćelija.[20]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000172270 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023175 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Kasinrerk W, Fiebiger E, Stefanová I, Baumruker T, Knapp W, Stockinger H (1992). "Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule". J Immunol. 149 (3): 847–54. PMID 1634773.
- ^ a b c Yurchenko V, Constant S, Bukrinsky M (2006). "Dealing with the family: CD147 interactions with cyclophilins". Immunology. 117 (3): 301–9. doi:10.1111/j.1365-2567.2005.02316.x. PMC 1782239. PMID 16476049.
- ^ Miyauchi T, Masuzawa Y, Muramatsu T (1992). "The basigin group of the immunoglobulin superfamily: complete conservation of a segment in and around transmembrane domains of human and mouse basigin and chicken HT7 antigen". J. Biochem. 110 (5): 770–4. doi:10.1093/oxfordjournals.jbchem.a123657. PMID 1783610.
- ^ a b Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Duraisingh MT, Rayner JC, Wright GJ (novembar 2011). "Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum". Nature. 480 (7378): 534–7. Bibcode:2011Natur.480..534C. doi:10.1038/nature10606. PMC 3245779. PMID 22080952.
- ^ "Entrez Gene: BSG basigin (Ok blood group)".
- ^ Kanekura T, Chen X, Kanzaki T (2002). "Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts". Int. J. Cancer. 99 (4): 520–8. doi:10.1002/ijc.10390. PMID 11992541. S2CID 37384660.
- ^ Yurchenko V, Zybarth G, O'Connor M, Dai W, Franchin G, Hao T, Guo H, Hung H, Toole B, Gallay P, Sherry B, Bukrinsky M (2002). "Active site residues of cyclophilin A are crucial for its signaling activity via CD147". J Biol Chem. 277 (25): 22959–65. doi:10.1074/jbc.M201593200. PMID 11943775.
- ^ Yurchenko V, O'Connor M, Dai W, Guo H, Toole B, Sherry B, Bukrinsky M (2001). "CD147 is a signaling receptor for cyclophilin B". Biochem Biophys Res Commun. 288 (4): 786–8. doi:10.1006/bbrc.2001.5847. PMID 11688976.
- ^ Berditchevski F, Chang S, Bodorova J, Hemler M (1997). "Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6". J Biol Chem. 272 (46): 29174–80. doi:10.1074/jbc.272.46.29174. PMID 9360995.
- ^ Wang WJ, Li QQ, Xu JD, Cao XX, Li HX, Tang F, Chen Q, Yang JM, Xu ZD, Liu XP (2008). "Interaction between CD147 and P-glycoprotein and their regulation by ubiquitination in breast cancer cells". Chemotherapy. 54 (4): 291–301. doi:10.1159/000151225. PMID 18689982. S2CID 7260048.
- ^ Philp NJ, Ochrietor JD, Rudoy C, Muramatsu T, Linser PJ (mart 2003). "Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse". Investigative Ophthalmology & Visual Science. 44 (3): 1305–11. doi:10.1167/iovs.02-0552. PMID 12601063.
- ^ "WikiGenes: MRC2 - mannose receptor C, type 2 Homo sapiens". Arhivirano s originala, 12. 5. 2021. Pristupljeno 30. 5. 2021.
- ^ Rodriguez-Teja M, Gronau JH, Minamidate A, Darby S, Gaughan L, Robson C, Mauri F, Waxman J, Sturge J (mart 2015). "Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147". Molecular Cancer Research (jezik: engleski). American Association for Cancer Research. 13 (3): 538–47. doi:10.1158/1541-7786.MCR-14-0344-T. PMID 25381222.
- ^ Wang K, Chen W, Zhang Z, Deng Y, Lian JQ, Du P, et al. (decembar 2020). "CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells". Signal Transduction and Targeted Therapy. 5 (1): 283. doi:10.1038/s41392-020-00426-x. PMC 7714896. PMID 33277466.
- ^ Bian H, Zheng ZH, Wei D, Zhang Z, Kang WZ, Hao CQ, et al. (2020). "Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial". bioRxiv. doi:10.1101/2020.03.21.20040691.
- ^ Shilts J, Crozier TW, Greenwood EJ, Lehner PJ, Wright GJ (11. 1. 2021). "No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor". Scientific Reports (jezik: engleski). 11 (1): 413. doi:10.1038/s41598-020-80464-1. ISSN 2045-2322. PMC 7801465. PMID 33432067.
Dopunska literatura
uredi- Muramatsu T, Miyauchi T (2004). "Basigin (CD147): a multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion". Histol. Histopathol. 18 (3): 981–7. PMID 12792908.
- Yan L, Zucker S, Toole BP (2005). "Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression". Thromb. Haemost. 93 (2): 199–204. doi:10.1160/TH04-08-0536. PMID 15711733.
- Kasinrerk W, Fiebiger E, Stefanová I, et al. (1992). "Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule". J. Immunol. 149 (3): 847–54. PMID 1634773.
- Nabeshima K, Lane WS, Biswas C (1991). "Partial sequencing and characterization of the tumor cell-derived collagenase stimulatory factor". Arch. Biochem. Biophys. 285 (1): 90–6. doi:10.1016/0003-9861(91)90332-D. PMID 1846736.
- Biswas C, Zhang Y, DeCastro R, et al. (1995). "The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily". Cancer Res. 55 (2): 434–9. PMID 7812975.
- Kaname T, Miyauchi T, Kuwano A, et al. (1993). "Mapping basigin (BSG), a member of the immunoglobulin superfamily, to 19p13.3". Cytogenet. Cell Genet. 64 (3–4): 195–7. doi:10.1159/000133573. PMID 8404035.
- DeCastro R, Zhang Y, Guo H, et al. (1996). "Human keratinocytes express EMMPRIN, an extracellular matrix metalloproteinase inducer". J. Invest. Dermatol. 106 (6): 1260–5. doi:10.1111/1523-1747.ep12348959. PMID 8752667.
- Spring FA, Holmes CH, Simpson KL, et al. (1997). "The Oka blood group antigen is a marker for the M6 leukocyte activation antigen, the human homolog of OX-47 antigen, basigin and neurothelin, an immunoglobulin superfamily molecule that is widely expressed in human cells and tissues". Eur. J. Immunol. 27 (4): 891–7. doi:10.1002/eji.1830270414. PMID 9130641. S2CID 23072979.
- Berditchevski F, Chang S, Bodorova J, Hemler ME (1997). "Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6". J. Biol. Chem. 272 (46): 29174–80. doi:10.1074/jbc.272.46.29174. PMID 9360995.
- Guo H, Majmudar G, Jensen TC, et al. (1998). "Characterization of the gene for human EMMPRIN, a tumor cell surface inducer of matrix metalloproteinases". Gene. 220 (1–2): 99–108. doi:10.1016/S0378-1119(98)00400-4. PMID 9767135.
- Guo H, Li R, Zucker S, Toole BP (2000). "EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface". Cancer Res. 60 (4): 888–91. PMID 10706100.
- Kirk P, Wilson MC, Heddle C, et al. (2000). "CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression". EMBO J. 19 (15): 3896–904. doi:10.1093/emboj/19.15.3896. PMC 306613. PMID 10921872.
- Yurchenko V, O'Connor M, Dai WW, et al. (2001). "CD147 is a signaling receptor for cyclophilin B". Biochem. Biophys. Res. Commun. 288 (4): 786–8. doi:10.1006/bbrc.2001.5847. PMID 11688976.
- Yurchenko V, Zybarth G, O'Connor M, et al. (2002). "Active site residues of cyclophilin A are crucial for its signaling activity via CD147". J. Biol. Chem. 277 (25): 22959–65. doi:10.1074/jbc.M201593200. PMID 11943775.
- Major TC, Liang L, Lu X, et al. (2002). "Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma". Arterioscler. Thromb. Vasc. Biol. 22 (7): 1200–7. doi:10.1161/01.ATV.0000021411.53577.1C. PMID 12117738.
- Taylor PM, Woodfield RJ, Hodgkin MN, et al. (2002). "Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathway". Oncogene. 21 (37): 5765–72. doi:10.1038/sj.onc.1205702. PMID 12173047.
- Thorns C, Feller AC, Merz H (2002). "EMMPRIN (CD 174) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases". Anticancer Res. 22 (4): 1983–6. PMID 12174874.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Vanjski linkovi
uredi
- Lokacija ljudskog genoma BSG i stranica sa detaljima o genu BSG u UCSC Genome Browseru.
- Ok blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Basigin