basigin

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.{{cite web | title = Entrez Gene: BSG basigin (Ok blood group)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=682}}{{cite journal | vauthors = Kanekura T, Chen X, Kanzaki T | title = Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts | journal = International Journal of Cancer | volume = 99 | issue = 4 | pages = 520–528 | date = June 2002 | pmid = 11992541 | doi = 10.1002/ijc.10390 | s2cid = 37384660 | doi-access = free }}

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.

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.{{cite journal | vauthors = Yurchenko V, Zybarth G, O'Connor M, Dai WW, Franchin G, Hao T, Guo H, Hung HC, Toole B, Gallay P, Sherry B, Bukrinsky M | title = Active site residues of cyclophilin A are crucial for its signaling activity via CD147 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 25 | pages = 22959–22965 | date = June 2002 | pmid = 11943775 | doi = 10.1074/jbc.M201593200 | doi-access = free }}{{cite journal | vauthors = Yurchenko V, O'Connor M, Dai WW, Guo H, Toole B, Sherry B, Bukrinsky M | title = CD147 is a signaling receptor for cyclophilin B | journal = Biochemical and Biophysical Research Communications | volume = 288 | issue = 4 | pages = 786–788 | date = November 2001 | pmid = 11688976 | doi = 10.1006/bbrc.2001.5847 }}{{cite journal | vauthors = Berditchevski F, Chang S, Bodorova J, Hemler ME | title = Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 46 | pages = 29174–29180 | date = November 1997 | pmid = 9360995 | doi = 10.1074/jbc.272.46.29174 | doi-access = free }} 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. It is expressed by many cell types, including epithelial cells, endothelial cells, neural progenitor cells{{cite journal | vauthors = Kanemitsu M, Tsupykov O, Potter G, Boitard M, Salmon P, Zgraggen E, Gascon E, Skibo G, Dayer AG, Kiss JZ | title = EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex | journal = Experimental Neurology | volume = 297 | pages = 14–24 | date = November 2017 | pmid = 28716558 | doi = 10.1016/j.expneurol.2017.07.009 | s2cid = 4587600 }} 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.

Basigin has been shown to interact with Ubiquitin C.{{cite journal | vauthors = Wang WJ, Li QQ, Xu JD, Cao XX, Li HX, Tang F, Chen Q, Yang JM, Xu ZD, Liu XP | title = Interaction between CD147 and P-glycoprotein and their regulation by ubiquitination in breast cancer cells | journal = Chemotherapy | volume = 54 | issue = 4 | pages = 291–301 | year = 2008 | pmid = 18689982 | doi = 10.1159/000151225 | s2cid = 7260048 }}

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.{{cite journal | vauthors = Philp NJ, Ochrietor JD, Rudoy C, Muramatsu T, Linser PJ | title = Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse | journal = Investigative Ophthalmology & Visual Science | volume = 44 | issue = 3 | pages = 1305–1311 | date = March 2003 | pmid = 12601063 | doi = 10.1167/iovs.02-0552 | doi-access = free }}

Basigin interacts with the fourth C-type lectin{{Circular reference|date=January 2018}} domain in the receptor Endo180{{cite web | title = WikiGenes: MRC2 - mannose receptor C, type 2 Homo sapiens | url = https://www.wikigenes.org/e/gene/e/9902.html}} to form a molecular epithelial-mesenchymal transition{{citation needed|date=March 2020}} suppressor complex that if disrupted results in the induction of invasive prostate epithelial cell behavior associated with poor prostate cancer survival.{{cite journal | vauthors = Rodriguez-Teja M, Gronau JH, Minamidate A, Darby S, Gaughan L, Robson C, Mauri F, Waxman J, Sturge J | title = Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147 | journal = Molecular Cancer Research | volume = 13 | issue = 3 | pages = 538–547 | date = March 2015 | pmid = 25381222 | doi = 10.1158/1541-7786.MCR-14-0344-T | s2cid = 9946106 | doi-access = free }}

It have been shown that atorvastatin suppresses CD147 and MMP-3 expression.{{cite journal | vauthors = Yi F, Jiang L, Xu H, Dai F, Zhou L |title=Atorvastatin suppresses CD147 and MMP-3 expression and improves histological and neurological outcomes in an animal model of intracerebral hemorrhage |journal=International Journal of Clinical and Experimental Medicine |volume=11 |issue=9 |pages=9301–9311 |url=http://www.ijcem.com/files/ijcem0067243.pdf }}{{cite journal | vauthors = Sasidhar MV, Chevooru SK, Eickelberg O, Hartung HP, Neuhaus O | title = Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors | journal = PLOS ONE | volume = 12 | issue = 12 | pages = e0189701 | date = 18 December 2017 | pmid = 29253870 | pmc = 5734787 | doi = 10.1371/journal.pone.0189701 | doi-access = free | bibcode = 2017PLoSO..1289701S }}

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.{{cite journal | vauthors = Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Duraisingh MT, Rayner JC, Wright GJ | title = Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum | journal = Nature | volume = 480 | issue = 7378 | pages = 534–537 | date = November 2011 | pmid = 22080952 | pmc = 3245779 | doi = 10.1038/nature10606 | bibcode = 2011Natur.480..534C }} Basigin is bound by the PfRh5 protein on the surface of the malaria parasite.{{citation needed|date=November 2021}}

Meplazumab, an anti-CD147 antibody, was tested in patients with SARS-CoV-2 pneumonia.{{cite journal | vauthors = Bian H, Zheng ZH, Wei D, Zhang Z, Kang WZ, Hao CQ, Dong K, Kang W, Xia JL, Miao JL, Xie RH | date = 2020 | title = Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial | journal = bioRxiv | doi = 10.1101/2020.03.21.20040691 | doi-access = free }}

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.{{cite journal | vauthors = Shilts J, Crozier TW, Greenwood EJ, Lehner PJ, Wright GJ | title = No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 413 | date = January 2021 | pmid = 33432067 | pmc = 7801465 | doi = 10.1038/s41598-020-80464-1 | doi-access = free }}

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.{{cite journal | vauthors = Barrett TJ, Bilaloglu S, Cornwell M, Burgess HM, Virginio VW, Drenkova K, Ibrahim H, Yuriditsky E, Aphinyanaphongs Y, Lifshitz M, Xia Liang F, Alejo J, Smith G, Pittaluga S, Rapkiewicz AV, Wang J, Iancu-Rubin C, Mohr I, Ruggles K, Stapleford KA, Hochman J, Berger JS | title = Platelets contribute to disease severity in COVID-19 | journal = Journal of Thrombosis and Haemostasis | volume = 19 | issue = 12 | pages = 3139–3153 | date = December 2021 | pmid = 34538015 | pmc = 8646651 | doi = 10.1111/jth.15534 }}

Another study states that platelets challenged with SARS-CoV-2 undergo activation, dependent on the CD147 receptor.{{cite journal | vauthors = Maugeri N, De Lorenzo R, Clementi N, Antonia Diotti R, Criscuolo E, Godino C, Tresoldi C, Angels For Covid-BioB Study Group B, Bonini C, Clementi M, Mancini N, Ciceri F, Rovere-Querini P, Manfredi AA | title = Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19 | journal = Journal of Thrombosis and Haemostasis | pages = 434–448 | date = October 2021 | volume = 20 | issue = 2 | pmid = 34710269 | pmc = 8646617 | doi = 10.1111/jth.15575 }} Yet SARS-CoV-2 does not replicate in human platelets, but initiates cell death.{{cite journal | vauthors = Koupenova-Zamor M, Corkrey HA, Vitseva O, Tanriverdi K, Somasundaran M, Liu P, Soofi S, Parsi KM, Cousineau A, Maehr R, Wang JP | title = SARS-CoV-2 Initiates Programmed Cell Death in Platelets | date = September 2021 | journal = Circulation Research | volume = 129 | issue = 6 | pages = 631–646 | doi = 10.1161/CIRCRESAHA.121.319117 | pmid = 34293929 | pmc = 8409903 }}

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.{{cite journal | vauthors = Ximeno-Rodríguez I, Blanco-delRío I, Astigarraga E, Barreda-Gómez G | title = Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes | journal = Biomedical Journal | volume = 47 | issue = 3 | pages = 100650 | date = June 2024 | pmid = 37604249 | doi = 10.1016/j.bj.2023.100650 | s2cid = 261042891 | doi-access = free | pmc = 11332989 }}

{{reflist}}

{{refbegin | 2}}

• {{cite journal | vauthors = Muramatsu T, Miyauchi T | title = Basigin (CD147): a multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion | journal = Histology and Histopathology | volume = 18 | issue = 3 | pages = 981–987 | date = July 2003 | pmid = 12792908 | doi = 10.14670/HH-18.981 | s2cid = 4635815 }}
• {{cite journal | vauthors = Yan L, Zucker S, Toole BP | title = Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression | journal = Thrombosis and Haemostasis | volume = 93 | issue = 2 | pages = 199–204 | date = February 2005 | pmid = 15711733 | doi = 10.1160/TH04-08-0536 | s2cid = 27979932 | url = https://zenodo.org/record/896853 }}
• {{cite journal | vauthors = Kasinrerk W, Fiebiger E, Stefanová I, Baumruker T, Knapp W, Stockinger H | title = 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 = Journal of Immunology | volume = 149 | issue = 3 | pages = 847–854 | date = August 1992 | doi = 10.4049/jimmunol.149.3.847 | pmid = 1634773 | s2cid = 24602674 | doi-access = free }}
• {{cite journal | vauthors = Nabeshima K, Lane WS, Biswas C | title = Partial sequencing and characterization of the tumor cell-derived collagenase stimulatory factor | journal = Archives of Biochemistry and Biophysics | volume = 285 | issue = 1 | pages = 90–96 | date = February 1991 | pmid = 1846736 | doi = 10.1016/0003-9861(91)90332-D }}
• {{cite journal | vauthors = Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, Nabeshima K | title = The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily | journal = Cancer Research | volume = 55 | issue = 2 | pages = 434–439 | date = January 1995 | pmid = 7812975 | url = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7812975 }}
• {{cite journal | vauthors = Kaname T, Miyauchi T, Kuwano A, Matsuda Y, Muramatsu T, Kajii T | title = Mapping basigin (BSG), a member of the immunoglobulin superfamily, to 19p13.3 | journal = Cytogenetics and Cell Genetics | volume = 64 | issue = 3–4 | pages = 195–197 | year = 1993 | pmid = 8404035 | doi = 10.1159/000133573 }}
• {{cite journal | vauthors = DeCastro R, Zhang Y, Guo H, Kataoka H, Gordon MK, Toole BP, Biswas G | title = Human keratinocytes express EMMPRIN, an extracellular matrix metalloproteinase inducer | journal = The Journal of Investigative Dermatology | volume = 106 | issue = 6 | pages = 1260–1265 | date = June 1996 | pmid = 8752667 | doi = 10.1111/1523-1747.ep12348959 | doi-access = free }}
• {{cite journal | vauthors = Spring FA, Holmes CH, Simpson KL, Mawby WJ, Mattes MJ, Okubo Y, Parsons SF | title = 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 | journal = European Journal of Immunology | volume = 27 | issue = 4 | pages = 891–897 | date = April 1997 | pmid = 9130641 | doi = 10.1002/eji.1830270414 | s2cid = 23072979 }}
• {{cite journal | vauthors = Berditchevski F, Chang S, Bodorova J, Hemler ME | title = Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 46 | pages = 29174–29180 | date = November 1997 | pmid = 9360995 | doi = 10.1074/jbc.272.46.29174 | doi-access = free }}
• {{cite journal | vauthors = Guo H, Majmudar G, Jensen TC, Biswas C, Toole BP, Gordon MK | title = Characterization of the gene for human EMMPRIN, a tumor cell surface inducer of matrix metalloproteinases | journal = Gene | volume = 220 | issue = 1–2 | pages = 99–108 | date = October 1998 | pmid = 9767135 | doi = 10.1016/S0378-1119(98)00400-4 }}
• {{cite journal | vauthors = Guo H, Li R, Zucker S, Toole BP | title = EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface | journal = Cancer Research | volume = 60 | issue = 4 | pages = 888–891 | date = February 2000 | pmid = 10706100 | url = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10706100 }}
• {{cite journal | vauthors = Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP | title = CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression | journal = The EMBO Journal | volume = 19 | issue = 15 | pages = 3896–3904 | date = August 2000 | pmid = 10921872 | pmc = 306613 | doi = 10.1093/emboj/19.15.3896 }}
• {{cite journal | vauthors = Yurchenko V, O'Connor M, Dai WW, Guo H, Toole B, Sherry B, Bukrinsky M | title = CD147 is a signaling receptor for cyclophilin B | journal = Biochemical and Biophysical Research Communications | volume = 288 | issue = 4 | pages = 786–788 | date = November 2001 | pmid = 11688976 | doi = 10.1006/bbrc.2001.5847 }}
• {{cite journal | vauthors = Yurchenko V, Zybarth G, O'Connor M, Dai WW, Franchin G, Hao T, Guo H, Hung HC, Toole B, Gallay P, Sherry B, Bukrinsky M | title = Active site residues of cyclophilin A are crucial for its signaling activity via CD147 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 25 | pages = 22959–22965 | date = June 2002 | pmid = 11943775 | doi = 10.1074/jbc.M201593200 | doi-access = free }}
• {{cite journal | vauthors = Major TC, Liang L, Lu X, Rosebury W, Bocan TM | title = Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 22 | issue = 7 | pages = 1200–1207 | date = July 2002 | pmid = 12117738 | doi = 10.1161/01.ATV.0000021411.53577.1C | doi-access = free }}
• {{cite journal | vauthors = Taylor PM, Woodfield RJ, Hodgkin MN, Pettitt TR, Martin A, Kerr DJ, Wakelam MJ | title = Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathway | journal = Oncogene | volume = 21 | issue = 37 | pages = 5765–5772 | date = August 2002 | pmid = 12173047 | doi = 10.1038/sj.onc.1205702 | doi-access = free }}
• {{cite journal | vauthors = Thorns C, Feller AC, Merz H | title = EMMPRIN (CD 147) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases | journal = Anticancer Research | volume = 22 | issue = 4 | pages = 1983–1986 | year = 2002 | pmid = 12174874 | id = {{INIST|14501263}} {{NAID|10020332737}} }}

{{refend}}

{{Commons category}}

• {{UCSC gene info|BSG}}
• [https://www.ncbi.nlm.nih.gov/projects/mhc/xslcgi.fcgi?cmd=bgmut/systems_info&system=ok Ok blood group system] at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
• [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P35613 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Basigin

{{Clusters of differentiation}}

{{Complement_system}}

Category:Complement system

Category:Clusters of differentiation

Category:Blood

Category:Transfusion medicine

Category:Hematology

Category:Blood antigen systems