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NameFolate receptor beta
  • FBP
  • Folate receptor 2
  • Folate receptor, fetal/placental
  • FR-beta
  • Placental folate-binding protein
Gene NameFOLR2
Amino acid sequence
>lcl|BSEQ0016050|Folate receptor beta
Number of residues255
Molecular Weight29279.31
Theoretical pI7.56
GO Classification
  • drug binding
  • folic acid binding
  • folic acid receptor activity
  • folic acid transporter activity
  • methotrexate binding
  • inflammatory response
  • receptor-mediated endocytosis
  • positive regulation of cell proliferation
  • cellular response to folic acid
  • folic acid transport
  • regulation of thymidylate synthase biosynthetic process
  • membrane
  • extracellular region
  • cell surface
  • anchored component of external side of plasma membrane
General FunctionMethotrexate binding
Specific FunctionBinds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1655592
UniProtKB IDP14207
UniProtKB Entry NameFOLR2_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0016051|Folate receptor beta (FOLR2)
GenBank Gene IDX69516
GeneCard IDNot Available
GenAtlas IDFOLR2
Chromosome Location11
  1. Page ST, Owen WC, Price K, Elwood PC: Expression of the human placental folate receptor transcript is regulated in human tissues. Organization and full nucleotide sequence of the gene. J Mol Biol. 1993 Feb 20;229(4):1175-83. 8445646
  2. Ratnam M, Marquardt H, Duhring JL, Freisheim JH: Homologous membrane folate binding proteins in human placenta: cloning and sequence of a cDNA. Biochemistry. 1989 Oct 3;28(20):8249-54. 2605182
  3. Sadasivan E, Cedeno MM, Rothenberg SP: Characterization of the gene encoding a folate-binding protein expressed in human placenta. Identification of promoter activity in a G-rich SP1 site linked with the tandemly repeated GGAAG motif for the ets encoded GA-binding protein. J Biol Chem. 1994 Feb 18;269(7):4725-35. 8106441
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. Freisheim JH, Price EM, Ratnam M: Folate coenzyme and antifolate transport proteins in normal and neoplastic cells. Adv Enzyme Regul. 1989;29:13-26. 2561247
  6. Antony AC, Kane MA, Portillo RM, Elwood PC, Kolhouse JF: Studies of the role of a particulate folate-binding protein in the uptake of 5-methyltetrahydrofolate by cultured human KB cells. J Biol Chem. 1985 Dec 5;260(28):14911-7. 4066659
  7. Yan W, Ratnam M: Preferred sites of glycosylphosphatidylinositol modification in folate receptors and constraints in the primary structure of the hydrophobic portion of the signal. Biochemistry. 1995 Nov 7;34(44):14594-600. 7578066
  8. Wang J, Shen F, Yan W, Wu M, Ratnam M: Proteolysis of the carboxyl-terminal GPI signal independent of GPI modification as a mechanism for selective protein secretion. Biochemistry. 1997 Nov 25;36(47):14583-92. 9398177
  9. Xu Y, Wang T, Tang R, Tang S: All-trans retinoic acid is capable of inducing folate receptor beta expression in KG-1 cells. Tumour Biol. 2010 Dec;31(6):589-95. doi: 10.1007/s13277-010-0074-0. Epub 2010 Jul 15. 20632143
  10. Wibowo AS, Singh M, Reeder KM, Carter JJ, Kovach AR, Meng W, Ratnam M, Zhang F, Dann CE 3rd: Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15180-8. doi: 10.1073/pnas.1308827110. Epub 2013 Aug 9. 23934049
  11. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. 16959974