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]
Quick Facts BSG, Available structures ...
| BSG |
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| Identifiers |
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| Aliases | BSG, 5F7, CD147, EMMPRIN, M6, OK, TCSF, basigin (Ok blood group), EMPRIN, SLC7A11, HAb18G |
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| External IDs | OMIM: 109480; MGI: 88208; HomoloGene: 1308; GeneCards: BSG; OMA:BSG - orthologs |
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| Bgee | | Human | Mouse (ortholog) |
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| Top expressed in | - apex of heart
- right testis
- left testis
- mucosa of transverse colon
- right auricle
- left ventricle
- right frontal lobe
- stromal cell of endometrium
- right adrenal cortex
- left adrenal gland
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| | Top expressed in | - choroid plexus of fourth ventricle
- molar
- interventricular septum
- myocardium of ventricle
- left lung lobe
- cardiac muscle tissue of left ventricle
- right ventricle
- tail of embryo
- spermatocyte
- muscle of thigh
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| | More reference expression data |
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| Wikidata |
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Close
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]
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]
It have been shown that Atorvastatin suppresses CD147 and MMP-3 expression.[20][21]
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]
Meplazumab, an anti-CD147 antibody, was tested in patients with SARS-CoV-2 pneumonia.[22]
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.[23]
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.[24]
Another study states that platelets challenged with SARS-CoV-2 undergo activation, dependent on the CD147 receptor.[25] Yet SARS-CoV-2 does not replicate in human platelets, but initiates cell death.[26]
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]
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. Yurchenko V, O'Connor M, Dai WW, Guo H, Toole B, Sherry B, et al. (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. 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. 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.
- Muramatsu T, Miyauchi T (July 2003). "Basigin (CD147): a multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion". Histology and Histopathology. 18 (3): 981–987. doi:10.14670/HH-18.981. PMID 12792908. S2CID 4635815.
- Yan L, Zucker S, Toole BP (February 2005). "Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression". Thrombosis and Haemostasis. 93 (2): 199–204. doi:10.1160/TH04-08-0536. PMID 15711733. S2CID 27979932.
- 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.
- Nabeshima K, Lane WS, Biswas C (February 1991). "Partial sequencing and characterization of the tumor cell-derived collagenase stimulatory factor". Archives of Biochemistry and Biophysics. 285 (1): 90–96. doi:10.1016/0003-9861(91)90332-D. PMID 1846736.
- Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, et al. (January 1995). "The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily". Cancer Research. 55 (2): 434–439. PMID 7812975.
- Kaname T, Miyauchi T, Kuwano A, Matsuda Y, Muramatsu T, Kajii T (1993). "Mapping basigin (BSG), a member of the immunoglobulin superfamily, to 19p13.3". Cytogenetics and Cell Genetics. 64 (3–4): 195–197. doi:10.1159/000133573. PMID 8404035.
- DeCastro R, Zhang Y, Guo H, Kataoka H, Gordon MK, Toole BP, et al. (June 1996). "Human keratinocytes express EMMPRIN, an extracellular matrix metalloproteinase inducer". The Journal of Investigative Dermatology. 106 (6): 1260–1265. doi:10.1111/1523-1747.ep12348959. PMID 8752667.
- Spring FA, Holmes CH, Simpson KL, Mawby WJ, Mattes MJ, Okubo Y, et al. (April 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". European Journal of Immunology. 27 (4): 891–897. doi:10.1002/eji.1830270414. PMID 9130641. S2CID 23072979.
- 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.
- Guo H, Majmudar G, Jensen TC, Biswas C, Toole BP, Gordon MK (October 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 (February 2000). "EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface". Cancer Research. 60 (4): 888–891. PMID 10706100.
- Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP (August 2000). "CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression". The EMBO Journal. 19 (15): 3896–3904. doi:10.1093/emboj/19.15.3896. PMC 306613. PMID 10921872.
- Yurchenko V, O'Connor M, Dai WW, Guo H, Toole B, Sherry B, et al. (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.
- 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.
- Major TC, Liang L, Lu X, Rosebury W, Bocan TM (July 2002). "Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (7): 1200–1207. doi:10.1161/01.ATV.0000021411.53577.1C. PMID 12117738.
- Taylor PM, Woodfield RJ, Hodgkin MN, Pettitt TR, Martin A, Kerr DJ, et al. (August 2002). "Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathway". Oncogene. 21 (37): 5765–5772. doi:10.1038/sj.onc.1205702. PMID 12173047.
- Thorns C, Feller AC, Merz H (2002). "EMMPRIN (CD 147) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases". Anticancer Research. 22 (4): 1983–1986. PMID 12174874. INIST 14501263 NAID 10020332737.
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