Basigin (BSG) also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) is a protein that in humans is encoded by the BSG gene.[5][6][7] This protein is a determinant for the Ok blood group system. There are three known antigens in the Ok system; the most common being Oka (also called OK1), OK2 and OK3. Basigin has been shown to be an essential receptor on red blood cells for the human malaria parasite, Plasmodium falciparum.[8] The common isoform of basigin (basigin-2) has two immunoglobulin domains, and the extended form basigin-1 has three.[9]

Available structures
PDBOrtholog search: A0A087X2B5 PDBe A0A087X2B5 RCSB
AliasesBSG, 5F7, CD147, EMMPRIN, M6, OK, TCSF, basigin (Ok blood group), EMPRIN, SLC7A11, HAb18G
External IDsOMIM: 109480 MGI: 88208 HomoloGene: 1308 GeneCards: BSG
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 19: 0.57 – 0.58 MbChr 10: 79.54 – 79.55 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Function edit

Basigin is a member of the immunoglobulin superfamily, with a structure related to the putative primordial form of the family. As members of the immunoglobulin superfamily play fundamental roles in intercellular recognition involved in various immunologic phenomena, differentiation, and development, basigin is thought also to play a role in intercellular recognition (Miyauchi et al., 1991; Kanekura et al., 1991).[10][11]

It has a variety of functions. In addition to its metalloproteinase-inducing ability, basigin also regulates several distinct functions, such as spermatogenesis, expression of the monocarboxylate transporter and the responsiveness of lymphocytes.[6] Basigin is a type I integral membrane receptor that has many ligands, including the cyclophilin (CyP) proteins Cyp-A and CyP-B and certain integrins.[12][13][14] Basigin also serves as a receptor for S100A9 and platelet glycoprotein VI, and basigin-1 acts as a receptor for the rod-derived cone viability factor.[9] It is expressed by many cell types, including epithelial cells, endothelial cells, neural progenitor cells[15] and leukocytes. The human basigin protein contains 269 amino acids that form two heavily glycosylated C2 type immunoglobulin-like domains at the N-terminal extracellular portion. A second form of basigin has also been characterized that contains one additional immunoglobulin-like domain in its extracellular portion.[6]

Interactions edit

Basigin has been shown to interact with Ubiquitin C.[16]

Basigin has been shown to form a complex with monocarboxylate transporters in the retina of mice. Basigin appears to be required for proper placement of MCTs in the membrane. In the Basigin null mouse, the failure of MCTs to integrate with the membrane may be directly linked to a failure of nutrient transfer in the retinal pigmented epithelium (the lactates transported by MCTs 1, 3, and 4 are essential nutrients for the developing RPE), resulting in loss of sight in the null animal.[17]

Basigin interacts with the fourth C-type lectin[circular reference] domain in the receptor Endo180[18] to form a molecular epithelial-mesenchymal transition[citation needed] suppressor complex that if disrupted results in the induction of invasive prostate epithelial cell behavior associated with poor prostate cancer survival.[19]

Modulators edit

It have been shown that Atorvastatin suppresses CD147 and MMP-3 expression.[20] Statins altered CD147 expression, structure and function.[21]

Role in malaria edit

It has recently (November 2011) been found that basigin is a receptor that is essential to erythrocyte invasion by most strains of Plasmodium falciparum, the most virulent species of the plasmodium parasites that cause human malaria. It is hoped that by developing antibodies to the parasite ligand for Basigin, Rh5, a better vaccine for malaria might be found.[8] Basigin is bound by the PfRh5 protein on the surface of the malaria parasite.[citation needed]

Role in SARS-CoV-2 infection (COVID-19) edit

The host-cell-expressed basigin (CD147) may bind spike protein of SARS-CoV-2 and possibly be involved in host cell invasion.[22] Subsequently, meplazumab, a humanized anti-CD147 antibody, was tested in patients with SARS-CoV-2 pneumonia.[23]

Some of these claims have been challenged by another group of scientists who found no evidence of a direct role for basigin in either binding the viral spike protein or promoting lung cell infection.[24]

More recent studies suggests CD147 as SARS-CoV-2 entry receptor of platelets and megakaryocytes, leading to hyperactivation and thrombosis, that differs from common cold coronavirus CoV-OC43. Incubation of megakaryocyte cells with SARS-CoV-2 resulted in a significant increase in the proinflammatory transcripts LGALS3BP and S100A9. Notably, CD147 antibody-mediated blocking significantly reduced the expression of S100A9, and S100A8 on megakaryocytes following incubation with SARS-CoV-2. These data indicate that megakaryocytes and platelets actively take up SARS-CoV-2 virions, likely via an ACE-2-independent mechanism.[25]

Another study states that platelets challenged with SARS-CoV-2 undergo activation, dependent on the CD147 receptor.[26] Yet SARS-CoV-2 does not replicate in human platelets.

Yet another study describes high-interaction coupling of N-RBD of SARS-CoV-2 and CD147 as the main way of infecting lymphocytes allegedly leading to Acquired Immune Deficiency Syndrome.[27]

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000172270 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023175 - Ensembl, May 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. ^ Kasinrerk W, Fiebiger E, Stefanová I, Baumruker T, Knapp W, Stockinger H (August 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". Journal of Immunology. 149 (3): 847–854. doi:10.4049/jimmunol.149.3.847. PMID 1634773. S2CID 24602674.
  6. ^ a b c Yurchenko V, Constant S, Bukrinsky M (March 2006). "Dealing with the family: CD147 interactions with cyclophilins". Immunology. 117 (3): 301–309. doi:10.1111/j.1365-2567.2005.02316.x. PMC 1782239. PMID 16476049.
  7. ^ Miyauchi T, Masuzawa Y, Muramatsu T (November 1991). "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". Journal of Biochemistry. 110 (5): 770–774. doi:10.1093/oxfordjournals.jbchem.a123657. PMID 1783610.
  8. ^ a b Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, et al. (November 2011). "Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum". Nature. 480 (7378): 534–537. Bibcode:2011Natur.480..534C. doi:10.1038/nature10606. PMC 3245779. PMID 22080952.
  9. ^ a b Muramatsu T (May 2016). "Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners". Journal of Biochemistry. 159 (5): 481–490. doi:10.1093/jb/mvv127. PMC 4846773. PMID 26684586. Retrieved 13 February 2023.
  10. ^ "Entrez Gene: BSG basigin (Ok blood group)".
  11. ^ Kanekura T, Chen X, Kanzaki T (June 2002). "Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts". International Journal of Cancer. 99 (4): 520–528. doi:10.1002/ijc.10390. PMID 11992541. S2CID 37384660.
  12. ^ Yurchenko V, Zybarth G, O'Connor M, Dai WW, Franchin G, Hao T, et al. (June 2002). "Active site residues of cyclophilin A are crucial for its signaling activity via CD147". The Journal of Biological Chemistry. 277 (25): 22959–22965. doi:10.1074/jbc.M201593200. PMID 11943775.
  13. ^ Yurchenko V, O'Connor M, Dai WW, Guo H, Toole B, Sherry B, Bukrinsky M (November 2001). "CD147 is a signaling receptor for cyclophilin B". Biochemical and Biophysical Research Communications. 288 (4): 786–788. doi:10.1006/bbrc.2001.5847. PMID 11688976.
  14. ^ Berditchevski F, Chang S, Bodorova J, Hemler ME (November 1997). "Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6". The Journal of Biological Chemistry. 272 (46): 29174–29180. doi:10.1074/jbc.272.46.29174. PMID 9360995.
  15. ^ Kanemitsu M, Tsupykov O, Potter G, Boitard M, Salmon P, Zgraggen E, et al. (November 2017). "EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex". Experimental Neurology. 297: 14–24. doi:10.1016/j.expneurol.2017.07.009. PMID 28716558. S2CID 4587600.
  16. ^ Wang WJ, Li QQ, Xu JD, Cao XX, Li HX, Tang F, et al. (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.
  17. ^ Philp NJ, Ochrietor JD, Rudoy C, Muramatsu T, Linser PJ (March 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): 1305–1311. doi:10.1167/iovs.02-0552. PMID 12601063.
  18. ^ "WikiGenes: MRC2 - mannose receptor C, type 2 Homo sapiens".
  19. ^ Rodriguez-Teja M, Gronau JH, Minamidate A, Darby S, Gaughan L, Robson C, et al. (March 2015). "Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147". Molecular Cancer Research. 13 (3): 538–547. doi:10.1158/1541-7786.MCR-14-0344-T. PMID 25381222. S2CID 9946106.
  20. ^ Yi F, Jiang L, Xu H, Dai F, Zhou L. "Atorvastatin suppresses CD147 and MMP-3 expression and improves histological and neurological outcomes in an animal model of intracerebral hemorrhage" (PDF). International Journal of Clinical and Experimental Medicine. 11 (9): 9301–9311.
  21. ^ Sasidhar MV, Chevooru SK, Eickelberg O, Hartung HP, Neuhaus O (18 December 2017). "Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors". PLOS ONE. 12 (12): e0189701. Bibcode:2017PLoSO..1289701S. doi:10.1371/journal.pone.0189701. PMC 5734787. PMID 29253870.
  22. ^ Wang K, Chen W, Zhang Z, Deng Y, Lian JQ, Du P, et al. (December 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.
  23. ^ 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.
  24. ^ Shilts J, Crozier TW, Greenwood EJ, Lehner PJ, Wright GJ (January 2021). "No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor". Scientific Reports. 11 (1): 413. doi:10.1038/s41598-020-80464-1. PMC 7801465. PMID 33432067.
  25. ^ Barrett TJ, Bilaloglu S, Cornwell M, Burgess HM, Virginio VW, Drenkova K, et al. (December 2021). "Platelets contribute to disease severity in COVID-19". Journal of Thrombosis and Haemostasis. 19 (12): 3139–3153. doi:10.1111/jth.15534. PMC 8646651. PMID 34538015.
  26. ^ Maugeri N, De Lorenzo R, Clementi N, Antonia Diotti R, Criscuolo E, Godino C, et al. (October 2021). "Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19". Journal of Thrombosis and Haemostasis. 20 (2): 434–448. doi:10.1111/jth.15575. PMC 8646617. PMID 34710269.
  27. ^ Ximeno-Rodríguez I, Blanco-Delrío I, Astigarraga E, Barreda-Gómez G (2023). "Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes". Biomedical Journal. doi:10.1016/ PMID 37604249. S2CID 261042891.

Further reading edit

External links edit