Folate Receptor 2 (FOLR2), also known as Folate Receptor beta, is a 38kD protein that mediates the cellular uptake of folic acid and reduced folates. Dietary folates are required for many key metabolic processes including nucleotide and methionine synthesis, the interconversion of glycine and serine, and histidine breakdown. Mature FOLR2 is an N-glycosylated protein that is anchored to the cell surface by a GPI linkage. Mouse FOLR2 shares 82% and 91% aa sequence identity with human and rat FOLR2, respectively. FOLR2 is predominantly expressed in placenta, cells of the neutrophilic lineage, and some CD34+ hematopoietic progenitor cells. It is up-regulated on myeloid leukemias, head and neck squamous cell carcinomas, and several nonepithelial cancers. It is also up-regulated on immunosuppressive tumor-associated macrophages as well as on macrophages and monocytes at chronic inflammatory sites including rheumatoid arthritis synovium and glioblastoma. FOLR2 knockout mice do not show gross morphological defects, but they exhibit increased sensitivity to arsenate-induced teratogenicity.
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