Alternative titles; symbols
HGNC Approved Gene Symbol: FOLR3
Cytogenetic location: 11q13.4 Genomic coordinates (GRCh38) : 11:72,135,725-72,139,892 (from NCBI)
Levels of cell membrane-associated folate receptors (FOLR) are elevated in a variety of malignant tissues compared to their normal counterparts. FOLR1 (136430) and FOLR2 (136425), 2 isoforms of the human high-affinity folate receptor, are homologous N-glycosylated polypeptides attached to the membrane by a glycosylphosphatidylinositol (GPI) anchor. They have opposite stereospecificities and different affinities for folate coenzymes and antifolates, and are differentially regulated in various tissues. Neither of these isoforms, identified by polyclonal antibodies raised against purified placental FOLR, was detected in chronic myelogenous leukemia (CML; 608232) spleen tissue with high levels of membrane-associated tritiated folic acid-binding protein (Sadasivan et al., 1986; Sadasivan et al., 1987). Shen et al. (1994) found that spleen and bone marrow samples from patients with CML, acute myelogenous leukemia (AML), and other hematopoietic malignancies had significantly elevated levels of membrane-associated FOLR. They also found that this FOLR is GPI membrane-anchored. Contrary to the previous findings, antibodies against human placental FOLR crossreacted quantitatively with tritiated folic acid-bound membrane protein in CML and AML. To identify the FOLR in normal and pathologic specimens of spleen and bone marrow, the authors performed degenerate PCR with primers corresponding to a conserved region in FOLR1, FOLR2, and 2 murine FOLR sequences on RNA from tissue samples. Using a cDNA fragment from mouse FOLR, they also screened a cDNA library from a CML spleen sample. Shen et al. (1994) isolated 2 types of folate receptors, FOLR2 and a novel isoform called FOLR3, as well as a deletion variant of FOLR3. The cDNA for FOLR3 predicts a 243-amino acid protein with 71% and 79% amino acid sequence homology to FOLR1 and FOLR2, respectively, a 23-residue amino-terminal signal peptide, 16 conserved cysteine residues, and 3 potential N-linked glycosylation sites. The authors found that the FOLR3 cDNA encodes a GPI membrane-anchored protein. Using PCR, Shen et al. (1994) detected FOLR3 mRNA in certain carcinomas and in tissues that are sources for hematopoietic cells such as normal or malignant spleen, bone marrow, and thymus. They also detected FOLR2 mRNA in samples of spleen, bone marrow, and thymus.
Sadasivan, E., da Costa, M., Rothenberg, S. P., Brink, L. Purification, properties, and immunological characterization of folate-binding proteins from human leukemia cells. Biochim. Biophys. Acta 925: 36-47, 1987. [PubMed: 3474029] [Full Text: https://doi.org/10.1016/0304-4165(87)90145-0]
Sadasivan, E., Rothenberg, S. P., da Costa, M., Brink, L. Characterization of multiple forms of folate-binding protein from human leukemia cells. Biochim. Biophys. Acta 882: 311-321, 1986. [PubMed: 3460637] [Full Text: https://doi.org/10.1016/0304-4165(86)90253-9]
Shen, F., Ross, J. F., Wang, X., Ratnam, M. Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry 33: 1209-1215, 1994. [PubMed: 8110752] [Full Text: https://doi.org/10.1021/bi00171a021]