SHMT2 protein, or serine hydroxymethyltransferase 2, is a mitochondrial enzyme that plays a pivotal role in one-carbon metabolism by catalyzing the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction is crucial for the synthesis of glycine and the provision of one-carbon units necessary for DNA synthesis, particularly through the production of thymidine and pyrimidine nucleotides. SHMT2 is expressed ubiquitously, with particularly high levels in the liver, and its activity is suggested to be the primary source of intracellular glycine. It is also associated with maintaining normal cellular methylation patterns, DNA stability, and genetic mutations. Abnormal expression of SHMT2 has been linked to various cancers, including colorectal, renal cell, head and neck, hepatocellular carcinoma, non-small cell lung cancer, breast cancer, and prostate cancer, where it contributes to cancer cell proliferation and survival by supporting metabolic reprogramming. Therefore, SHMT2 is not only a key player in cellular metabolism but also a potential therapeutic target in cancer treatment.
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