# BSG

## Overview
The BSG gene encodes the protein Basigin, also known as CD147 or EMMPRIN, which is a multifunctional transmembrane glycoprotein belonging to the immunoglobulin superfamily. Basigin is involved in a variety of biological processes, including cellular metabolism, signal transduction, and intercellular interactions. It is highly glycosylated, which enhances its function in mediating the translocation and activity of various transporters and receptors on the cell surface. The protein is particularly notable for its role in disease pathogenesis, including cancer progression and infectious diseases like malaria, where it serves as a critical receptor for the invasion of pathogens (Muramatsu2015Basigin; Crosnier2011Basigin). The gene's expression and the activity of the protein have significant implications for cell adhesion, tumor metastasis, and metabolic regulation, making it a key subject of medical research and therapeutic targeting (Łacina2022BSG; Yang2021FOXO3-induced).

## Structure
The molecular structure of the BSG protein, also known as CD147 or basigin, includes several immunoglobulin-like domains which are crucial for its function. Specifically, the BSG protein contains two immunoglobulin domains in its primary isoform, BSG-001, while other isoforms such as BSG-010 and BSG-011 lack these domains (Fu2022Impact). The presence of these domains suggests a specific structural feature that is essential for interactions with other proteins, such as PfRH5, a parasite protein necessary for malaria pathogenesis. Both Ig-like domains of human BSG are necessary for binding to PfRH5, indicating their functional significance in the protein's interaction surface (Wanaguru2013RH5–Basigin).

BSG is also characterized by a high level of glycosylation, particularly N-glycans, which are significant for its function and interactions. This post-translational modification is notably rich in the protein and is crucial for maintaining interactions within the testes and for the protein's role in reproductive processes (Bi2013Basigin).

However, detailed information on the primary, secondary, tertiary, and quaternary structures of BSG is not provided in the available literature excerpts. Similarly, while the existence of multiple splice variant isoforms is noted, specific details on their structural differences and biological roles are not elaborated (Fu2022Impact).

## Function
The BSG gene encodes the Basigin protein, also known as CD147 or EMMPRIN, which is a multifunctional transmembrane glycoprotein part of the immunoglobulin superfamily. Basigin plays a critical role in various cellular processes by facilitating molecular interactions both within the same cell (cis-recognition) and with external molecules (trans-recognition), enhancing intercellular communication. This protein is highly glycosylated and is involved in the translocation and function of monocarboxylate transporters on the cell surface, crucial for nutrient transport (Muramatsu2015Basigin).

In the context of metabolism, Basigin forms tight associations with monocarboxylate transporters (MCTs), which are essential for the transport of metabolites like lactate, pyruvate, and ketone bodies across the plasma membrane. It acts as an ancillary protein for MCT1, MCT3, and MCT4, facilitating their proper localization and function at the plasma membrane, which is vital for the expression of MCT activities necessary for energy metabolism in metabolically active cells, including tumor cells and activated lymphocytes (Muramatsu2015Basigin).

Additionally, Basigin interacts with other proteins such as GLUT1, enhancing glucose uptake in cone photoreceptors, and forms complexes with CD44 and the epidermal growth factor receptor, which are involved in cellular signaling and tumor cell invasiveness. It also interacts with integrins, influencing cell adhesion and signaling pathways (Muramatsu2015Basigin). These interactions underline the role of Basigin in cellular adhesion, metabolism, and signaling, contributing to its multifunctional nature in healthy human cells.

## Clinical Significance
BSG (basigin) is implicated in a range of diseases primarily due to its role in cancer progression and metastasis. In hepatocellular carcinoma (HCC), BSG is one of the top 50 overexpressed genes and its high expression correlates with advanced stages, tumor metastasis, and shorter survival rates (Yang2021FOXO3-induced). Similarly, in acute myeloid leukemia (AML), overexpression of BSG is associated with poor prognosis and disease progression (Łacina2022BSG). The gene also plays a significant role in cardiovascular diseases; for instance, variations in BSG expression are linked to chronic heart failure, with certain genetic polymorphisms like rs8259 associated with decreased risk and lower mRNA expression levels (Li2017Basigin).

In non-cancerous conditions, BSG contributes to the pathogenesis of multiple sclerosis and cardiovascular diseases such as atherosclerosis and myocardial infarction (Xiong2014The). Its role extends to infectious diseases, where it acts as a critical receptor for the invasion of Plasmodium parasites, including those causing malaria (Xiong2014The). Furthermore, alterations in BSG expression influence the severity and treatment responses in metabolic regulation and infectious diseases, highlighting its clinical significance across a broad spectrum of human health conditions.

## Interactions
Basigin (BSG), also known as CD147 or EMMPRIN, is a transmembrane glycoprotein that interacts with several proteins, playing a crucial role in physiological and pathological processes. One of the key interactions of BSG is with the Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5), which is essential for the malaria parasite's invasion of erythrocytes. This interaction is mediated primarily through the N-terminal domain of BSG and is critical for the parasite's ability to invade human red blood cells (Wanaguru2013RH5–Basigin; Wright2014Structure; Crosnier2011Basigin).

BSG also interacts with Tumor necrosis factor receptor-associated factor 6 (TRAF6) in the context of melanoma. This interaction involves the transmembrane domain of BSG and is significant for the expression of matrix metalloproteinases (MMPs), which are key in cancer progression and metastasis (Biswas2017A).

Additionally, BSG forms various dimeric interactions, as evidenced in its crystal structure. These include homophilic interactions between two BSG molecules and potential heterophilic interactions with other IgSF cell surface molecules (Yu2008Crystal). These interactions highlight the multifunctional role of BSG in cell adhesion, signaling, and protein-protein interactions crucial for various biological processes.


## References


[1. (Yu2008Crystal) Xiao-Ling Yu, Tiancen Hu, Jia-Mu Du, Jian-Ping Ding, Xiang-Min Yang, Jian Zhang, Bin Yang, Xu Shen, Zheng Zhang, Wei-De Zhong, Ning Wen, Hualiang Jiang, Ping Zhu, and Zhi-Nan Chen. Crystal structure of hab18g/cd147. Journal of Biological Chemistry, 283(26):18056–18065, June 2008. URL: http://dx.doi.org/10.1074/jbc.m802694200, doi:10.1074/jbc.m802694200. (108 citations) 10.1074/jbc.m802694200](https://doi.org/10.1074/jbc.m802694200)

[2. (Li2017Basigin) Mu-Peng Li, Xiao-Lei Hu, Yong-Long Yang, Yan-Jiao Zhang, Ji-Peng Zhou, Li-Ming Peng, Jie Tang, and Xiao-Ping Chen. Basigin rs8259 polymorphism confers decreased risk of chronic heart failure in a chinese population. International Journal of Environmental Research and Public Health, 14(2):211, February 2017. URL: http://dx.doi.org/10.3390/ijerph14020211, doi:10.3390/ijerph14020211. (10 citations) 10.3390/ijerph14020211](https://doi.org/10.3390/ijerph14020211)

[3. (Biswas2017A) Ria Biswas, Semanti Ghosh, and Angshuman Bagchi. A structural perspective on the interactions of traf6 and <scp>b</scp>asigin during the onset of melanoma: a molecular dynamics simulation study. Journal of Molecular Recognition, June 2017. URL: http://dx.doi.org/10.1002/jmr.2643, doi:10.1002/jmr.2643. (9 citations) 10.1002/jmr.2643](https://doi.org/10.1002/jmr.2643)

[4. (Wanaguru2013RH5–Basigin) Madushi Wanaguru, Weimin Liu, Beatrice H. Hahn, Julian C. Rayner, and Gavin J. Wright. Rh5–basigin interaction plays a major role in the host tropism of plasmodium falciparum. Proceedings of the National Academy of Sciences, 110(51):20735–20740, December 2013. URL: http://dx.doi.org/10.1073/pnas.1320771110, doi:10.1073/pnas.1320771110. (121 citations) 10.1073/pnas.1320771110](https://doi.org/10.1073/pnas.1320771110)

[5. (Wright2014Structure) Katherine E. Wright, Kathryn A. Hjerrild, Jonathan Bartlett, Alexander D. Douglas, Jing Jin, Rebecca E. Brown, Joseph J. Illingworth, Rebecca Ashfield, Stine B. Clemmensen, Willem A. de Jongh, Simon J. Draper, and Matthew K. Higgins. Structure of malaria invasion protein rh5 with erythrocyte basigin and blocking antibodies. Nature, 515(7527):427–430, August 2014. URL: http://dx.doi.org/10.1038/nature13715, doi:10.1038/nature13715. (171 citations) 10.1038/nature13715](https://doi.org/10.1038/nature13715)

[6. (Fu2022Impact) Jiewen Fu, Binghui Song, Jiaman Du, Shuguang Liu, Jiayue He, Ting Xiao, Baixu Zhou, Dabing Li, Xiaoyan Liu, Tao He, Jingliang Cheng, and Junjiang Fu. Impact of bsg/cd147 gene expression on diagnostic, prognostic and therapeutic strategies towards malignant cancers and possible susceptibility to sars-cov-2. Molecular Biology Reports, 50(3):2269–2281, December 2022. URL: http://dx.doi.org/10.1007/s11033-022-08231-1, doi:10.1007/s11033-022-08231-1. (7 citations) 10.1007/s11033-022-08231-1](https://doi.org/10.1007/s11033-022-08231-1)

[7. (Bi2013Basigin) Jiajia Bi, Yanfen Li, Fengyun Sun, Anja Saalbach, Claudia Klein, David J. Miller, Rex Hess, and Romana A. Nowak. Basigin null mutant male mice are sterile and exhibit impaired interactions between germ cells and sertoli cells. Developmental Biology, 380(2):145–156, August 2013. URL: http://dx.doi.org/10.1016/j.ydbio.2013.05.023, doi:10.1016/j.ydbio.2013.05.023. (56 citations) 10.1016/j.ydbio.2013.05.023](https://doi.org/10.1016/j.ydbio.2013.05.023)

[8. (Xiong2014The) Lijuan Xiong, Carl Edwards, and Lijun Zhou. The biological function and clinical utilization of cd147 in human diseases: a review of the current scientific literature. International Journal of Molecular Sciences, 15(10):17411–17441, September 2014. URL: http://dx.doi.org/10.3390/ijms151017411, doi:10.3390/ijms151017411. (151 citations) 10.3390/ijms151017411](https://doi.org/10.3390/ijms151017411)

[9. (Muramatsu2015Basigin) Takashi Muramatsu. Basigin (cd147), a multifunctional transmembrane glycoprotein with various binding partners. Journal of Biochemistry, 159(5):481–490, December 2015. URL: http://dx.doi.org/10.1093/jb/mvv127, doi:10.1093/jb/mvv127. (290 citations) 10.1093/jb/mvv127](https://doi.org/10.1093/jb/mvv127)

[10. (Łacina2022BSG) Piotr Łacina, Aleksandra Butrym, Eliza Turlej, Martyna Stachowicz-Suhs, Joanna Wietrzyk, Grzegorz Mazur, and Katarzyna Bogunia-Kubik. Bsg (cd147) serum level and genetic variants are associated with overall survival in acute myeloid leukaemia. Journal of Clinical Medicine, 11(2):332, January 2022. URL: http://dx.doi.org/10.3390/jcm11020332, doi:10.3390/jcm11020332. (11 citations) 10.3390/jcm11020332](https://doi.org/10.3390/jcm11020332)

[11. (Crosnier2011Basigin) Cécile Crosnier, Leyla Y. Bustamante, S. Josefin Bartholdson, Amy K. Bei, Michel Theron, Makoto Uchikawa, Souleymane Mboup, Omar Ndir, Dominic P. Kwiatkowski, Manoj T. Duraisingh, Julian C. Rayner, and Gavin J. Wright. Basigin is a receptor essential for erythrocyte invasion by plasmodium falciparum. Nature, 480(7378):534–537, November 2011. URL: http://dx.doi.org/10.1038/nature10606, doi:10.1038/nature10606. (770 citations) 10.1038/nature10606](https://doi.org/10.1038/nature10606)

[12. (Yang2021FOXO3-induced) Lin Yang, Wan-li Deng, Bao-guo Zhao, Yao Xu, Xiao-wen Wang, Yu Fang, and Hai-juan Xiao. Foxo3-induced lncrna loc554202 contributes to hepatocellular carcinoma progression via the mir-485-5p/bsg axis. Cancer Gene Therapy, 29(3–4):326–340, March 2021. URL: http://dx.doi.org/10.1038/s41417-021-00312-w, doi:10.1038/s41417-021-00312-w. (28 citations) 10.1038/s41417-021-00312-w](https://doi.org/10.1038/s41417-021-00312-w)