Basigin

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.[4][5][6] 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.[7]

BSG
Protein BSG PDB 3B5H.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBSG, 5F7, CD147, EMMPRIN, M6, OK, TCSF, basigin (Ok blood group), EMPRIN, SLC7A11
External IDsOMIM: 109480 MGI: 88208 HomoloGene: 1308 GeneCards: BSG
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for BSG
Genomic location for BSG
Band19p13.3Start571,277 bp[1]
End583,493 bp[1]
RNA expression pattern
PBB GE BSG 208677 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001728
NM_198589
NM_198590
NM_198591
NM_001322243

NM_001077184
NM_009768

RefSeq (protein)

NP_001309172
NP_001719
NP_940991
NP_940992
NP_940993

NP_001070652
NP_033898

Location (UCSC)Chr 19: 0.57 – 0.58 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

FunctionEdit

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).[8][9]

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.[5] 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.[10][11][12] It is expressed by many cell types, including epithelial cells, endothelial cells 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.[5]

InteractionsEdit

Basigin has been shown to interact with Ubiquitin C.[13]

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.[14]

Basigin interacts with the fourth C-type lectin[circular reference] domain in the receptor Endo180[15] 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.[16]

Role in malariaEdit

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.[7] Basigin is bound by the PfRh5 protein on the surface of the malaria parasite.

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.[17] Subsequently, meplazumab, a humanized anti-CD147 antibody, was tested in patients with SARS-CoV-2 pneumonia.[18] 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.[19]

ReferencesEdit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000172270 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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 (November 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.
  8. ^ "Entrez Gene: BSG basigin (Ok blood group)".
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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): 1305–11. doi:10.1167/iovs.02-0552. PMID 12601063.
  15. ^ "WikiGenes: MRC2 - mannose receptor C, type 2 Homo sapiens".
  16. ^ Rodriguez-Teja M, Gronau JH, Minamidate A, Darby S, Gaughan L, Robson C, Mauri F, Waxman J, Sturge J (March 2015). "Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147". Molecular Cancer Research. American Association for Cancer Research. 13 (3): 538–47. doi:10.1158/1541-7786.MCR-14-0344-T. PMID 25381222.
  17. ^ 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.
  18. ^ 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.
  19. ^ Shilts J, Crozier TW, Greenwood EJ, Lehner PJ, Wright GJ (11 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. ISSN 2045-2322.

Further readingEdit

External linksEdit