Basigin

BSG
Available structures PDB Ortholog search: A0A087X2B5 PDBe A0A087X2B5 RCSB List of PDB id codes 4U0Q, 3B5H, 3I84, 3I85, 3QQN, 3QR2
Identifiers
Aliases	BSG, 5F7, CD147, EMMPRIN, M6, OK, TCSF, basigin (Ok blood group), EMPRIN, SLC7A11, HAb18G
External IDs	OMIM: 109480 MGI: 88208 HomoloGene: 1308 GeneCards: BSG
Gene location (Human) Chr. Chromosome 19 (human) Band 19p13.3 Start 571,277 bp End 583,494 bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10 C1|10 39.72 cM Start 79,540,325 bp End 79,547,803 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left ventricle stromal cell of endometrium left adrenal gland body of stomach anterior pituitary right uterine tube left lobe of thyroid gland ascending aorta right lobe of thyroid gland canal of the cervix Top expressed in molar interventricular septum myocardium of ventricle left lung lobe right ventricle spermatocyte spermatid calvaria extensor digitorum longus muscle triceps brachii muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding mannose binding carbohydrate binding monocarboxylic acid transmembrane transporter activity cadherin binding cell-cell adhesion mediator activity Cellular component integral component of membrane membrane focal adhesion melanosome Golgi membrane plasma membrane integral component of plasma membrane acrosomal membrane mitochondrion membrane raft sarcolemma extracellular exosome intracellular membrane-bounded organelle axon Biological process response to peptide hormone extracellular matrix disassembly extracellular matrix organization odontogenesis of dentin-containing tooth cell surface receptor signaling pathway decidualization pyruvate metabolic process response to mercury ion response to cAMP embryo implantation leukocyte migration monocarboxylic acid transport protein localization to plasma membrane homophilic cell adhesion via plasma membrane adhesion molecules axon guidance dendrite self-avoidance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 682 12215 Ensembl ENSG00000172270 ENSMUSG00000023175 UniProt P35613 P18572 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 Mb Chr 10: 79.54 – 79.55 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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. This protein is a determinant for the Ok blood group system. There are three known antigens in the Ok system; the most common being Ok^a (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. The common isoform of basigin (basigin-2) has two immunoglobulin domains, and the extended form basigin-1 has three.

Function

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).

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. 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 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.

Interactions

Basigin has been shown to interact with Ubiquitin C.

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.

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

Modulators

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

Role in malaria

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

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

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

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.

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.

Another study states that platelets challenged with SARS-CoV-2 undergo activation, dependent on the CD147 receptor. 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.

Further reading

• 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, Nabeshima K (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, Biswas G (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, Parsons SF (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, 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.
• 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, Wakelam MJ (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.

External links

• Human BSG genome location and BSG gene details page in the UCSC Genome Browser.
• 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