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BSG

Official Full Name
basigin (Ok blood group)
Organism
Homo sapiens
GeneID
682
Background
The protein encoded by this gene, basigin, is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. Basigin is also a member of the immunoglobulin superfamily, ubiquitously expressed in various tissues. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]
Synonyms
OK; 5F7; TCSF; CD147; EMPRIN; HAb18G; EMMPRIN;
Bio Chemical Class
Basigin protein
Protein Sequence
MAAALFVLLGFALLGTHGASGAAGFVQAPLSQQRWVGGSVELHCEAVGSPVPEIQWWFEGQGPNDTCSQLWDGARLDRVHIHATYHQHAASTISIDTLVEEDTGTYECRASNDPDRNHLTRAPRVKWVRAQAVVLVLEPGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQKTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWYKITDSEDKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALWPFLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS
Open
Disease
Graft-versus-host disease, Liver cancer
Approved Drug
0
Clinical Trial Drug
2 +
Discontinued Drug
0

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Detailed Information

Encoding the protein basigin, the gene BSG also known as CD147 or EMMPRIN has a prominent place in the immunoglobulin superfamily. Its fundamental involvement in several physiological processes—including spermatogenesis, embryo implantation, brain network development, and tumor progression—is well known. Common in many tissues, basigin has many transcript variations coding for distinct isoforms, hence contributing to its functional variety. With a molecular weight between 50 and 60 kDa, this protein is described as a highly glycosylated single transmembrane protein, therefore stressing its intricacy and relevance in cellular interactions.

Structural Characteristics of CD147

Two main isoforms constitute the basis: Basigin-1 (BSG1) and Basigin-2 (BSG2). Mostly expressed in the retina and essential for appropriate retinal development, BSG1 is unique in its three immunoglobulin domains. Crucially for the survival of retinal cone photoreceptors, especially by improving aerobic glycolysis, it serves as a cell surface receptor for NXNL1. By contrast, the more often occurring isoform, BSG2, is expressed more broadly across different organs and has two immunoglobulin domains.

The many glycosylation patterns of CD147, which vary depending on tissue type and developmental stage, also show its structural complexity. This structural variation helps to explain the numerous physiological activities connected to CD147 in various biological environments. The wide expression range of the gene points to its participation in many physiological processes, therefore stressing its relevance in both diseases and in normal cellular function.

Role of Basigin in Tumorigenesis

One very interesting feature of Basigin's action is its connection to cancer. Many cancers, including breast cancer, lung cancer, kidney cancer, and lymphomas, show raised levels of CD147. Using fibroblasts, CD147 induces matrix metalloproteinases (MMPs) including MMP-1, MMP-2, MMP-3, and MMP-9 in tumor cells. Tumor progression depends on these MMPs, which also help processes like invasion, metastases, and neoangiogenesis. Particularly important is CD147's capacity to induce angiogenesis as it controls the production of Vascular endothelial growth factor (VEGF) and its receptor, VEGFR2, therefore improving tumor blood supply and development.

CD147 modulates the extracellular matrix and interacts with signaling pathways connected to cell adhesion and migration, therefore contributing to cancer. CD147 increases the breakdown of extracellular matrix components by inducing MMP synthesis, therefore encouraging the invading potential of tumor cells.

Figure 1 illustrates the multifaceted role of CD147 in cancer pathogenesis.Figure 1. Chart representing the multifunctional role of CD147 in the pathogenesis of cancer. (Kumar D, et al., 2019)

CD147 in Neural Development and Function

Beyond its part in tumor biology, CD147 is crucial for brain growth and function. Retinal pigment epithelial cells, choroidal epithelial cells, and endothelial cells of the blood-brain barrier (BBB) all express CD147 inside the central nervous system (CNS). Its expression is intimately related to the development of central nervous system endothelial cells, which are essential for preserving BBB integrity. Studies show that CD147 is essential for the connections between glial cells and neurons, therefore influencing synaptic plasticity and neural survival.

In the framework of neurodegenerative illnesses, including Alzheimer's disease, research has shown that CD147 is linked with dopaminergic neuron regeneration. Suggesting that CD147 may affect neuronal health and plasticity in the aging brain, mice with CD147 gene deletion show behavioral characteristics similar to those seen in Alzheimer's transgenic animal models.

CD147 and Visual Function

Visual function depends critically on interactions between CD147 and monocarboxylate transporters (MCTs). Particularly, CD147 helps lactate and other metabolites be transported in retinal cells—necessary for the survival and operation of photoreceptor cells. Research using CD147-deficient mice has shown that the lack of CD147 causes notable visual impairment, therefore highlighting its significance in preserving photoreceptor integrity and proper visual processing.

Dependent on glycolysis, Müller glial cells in the retina exude lactate, which is subsequently used for energy generation by photoreceptor cells. This interaction of glycolytic activity with CD147-mediated transport emphasizes the significance of the protein in retinal metabolism and phototransduction.

Involvement in Immune Response and Inflammation

In immunological responses and inflammation, CD147 also is rather important. It serves as a receptor for cyclophilin A (CyPA), a protein produced in inflammatory reactions that may attract T lymphocytes and neutrophils among other immune cells. Expression of CD147 is much higher in activated T cells; its function in promoting T cell responses emphasizes its significance in both natural and adaptive immunity.

Moreover, CD147 has been linked to the entrance of several infections, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the human immunodeficiency virus (HIV). Its interactions with viral proteins let these viruses enter host cells, therefore defining CD147 as a possible treatment target in infectious illnesses.

Studies show that CD147 interacts with viral proteins linked with immune evasion and replication to improve the entrance of HIV-1. Similarly, while CD147 is a SARS-CoV-1 receptor, it is not necessary for SARS-CoV-2 infection, suggesting complex functions of CD147 in viral pathogenesis.

References:

  1. Muramatsu T. Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners. J Biochem. 2016;159(5):481-490.
  2. Kumar D, Vetrivel U, Parameswaran S, et al. Structural insights on druggable hotspots in CD147: A bull's eye view. Life Sci. 2019;224:76-87.
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