Function: Sodium-dependent transporter selective for purine nucleosides (e.g., adenosine, inosine) and uridine. Facilitates nucleoside salvage and uptake of nucleoside-derived drugs (e.g., cladribine) .
Structure: Integral plasma membrane protein with 12 predicted transmembrane domains .
Tissue Expression: Highest in kidney, liver, small intestine, and pancreas; lower in brain and lung .
Repression Mechanism: CNT2 expression is suppressed in CRC due to histone hypoacetylation at promoter regions (H3K9Ac, H3K18Ac, and H4Ac sites), driven by elevated histone deacetylase 7 (HDAC7) .
Therapeutic Implications: HDAC inhibitors (e.g., trichostatin A) restore CNT2 expression, enhancing cellular uptake of nucleoside drugs like cladribine and improving chemotherapeutic efficacy .
Drug Transport: CNT2 mediates uptake of antiviral/anticancer nucleoside analogs (e.g., ribavirin, gemcitabine) .
Energy Metabolism: Facilitates adenosine uptake, influencing glycogenolysis and gluconeogenesis pathways .
Cancer Studies: Used to investigate nucleoside drug resistance mechanisms .
Tissue Localization: Localizes CNT2 in apicolateral membranes of Sertoli cells (testis) and vascular endothelia .
Drug Development: Serves as a biomarker for optimizing nucleoside-based therapies .