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NameFolate receptor alpha
Synonyms
  • Adult folate-binding protein
  • FBP
  • Folate receptor 1
  • Folate receptor, adult
  • FOLR
  • FR-alpha
  • KB cells FBP
  • Ovarian tumor-associated antigen MOv18
Gene NameFOLR1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0012384|Folate receptor alpha
MAQRMTTQLLLLLVWVAVVGEAQTRIAWARTELLNVCMNAKHHKEKPGPEDKLHEQCRPW
RKNACCSTNTSQEAHKDVSYLYRFNWNHCGEMAPACKRHFIQDTCLYECSPNLGPWIQQV
DQSWRKERVLNVPLCKEDCEQWWEDCRTSYTCKSNWHKGWNWTSGFNKCAVGAACQPFHF
YFPTPTVLCNEIWTHSYKVSNYSRGSGRCIQMWFDPAQGNPNEEVARFYAAAMSGAGPWA
AWPFLLSLALMLLWLLS
Number of residues257
Molecular Weight29818.94
Theoretical pI8.02
GO Classification
Functions
  • drug binding
  • receptor activity
  • folic acid binding
  • folic acid transporter activity
  • methotrexate binding
Processes
  • COPII vesicle coating
  • anterior neural tube closure
  • ER to Golgi vesicle-mediated transport
  • cardiac neural crest cell migration involved in outflow tract morphogenesis
  • membrane organization
  • heart looping
  • post-translational protein modification
  • neural crest cell migration involved in heart formation
  • protein N-linked glycosylation via asparagine
  • pharyngeal arch artery morphogenesis
  • regulation of canonical Wnt signaling pathway
  • regulation of transforming growth factor beta receptor signaling pathway
  • cellular response to folic acid
  • receptor-mediated endocytosis
  • folic acid transport
  • cellular protein metabolic process
  • folic acid metabolic process
  • axon regeneration
Components
  • membrane
  • nucleus
  • basolateral plasma membrane
  • plasma membrane
  • endosome
  • endoplasmic reticulum membrane
  • apical plasma membrane
  • anchored component of external side of plasma membrane
  • cell surface
  • clathrin-coated vesicle
  • extracellular exosome
  • integral component of plasma membrane
  • endoplasmic reticulum-Golgi intermediate compartment membrane
  • Golgi membrane
  • ER to Golgi transport vesicle membrane
General FunctionReceptor activity
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. Required for normal embryonic development and normal cell proliferation.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP15328
UniProtKB Entry NameFOLR1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0012385|Folate receptor alpha (FOLR1)
ATGGCTCAGCGGATGACAACACAGCTGCTGCTCCTTCTAGTGTGGGTGGCTGTAGTAGGG
GAGGCTCAGACAAGGATTGCATGGGCCAGGACTGAGCTTCTCAATGTCTGCATGAACGCC
AAGCACCACAAGGAAAAGCCAGGCCCCGAGGACAAGTTGCATGAGCAGTGTCGACCCTGG
AGGAAGAATGCCTGCTGTTCTACCAACACCAGCCAGGAAGCCCATAAGGATGTTTCCTAC
CTATATAGATTCAACTGGAACCACTGTGGAGAGATGGCACCTGCCTGCAAACGGCATTTC
ATCCAGGACACCTGCCTCTACGAGTGCTCCCCCAACTTGGGGCCCTGGATCCAGCAGGTG
GATCAGAGCTGGCGCAAAGAGCGGGTACTGAACGTGCCCCTGTGCAAAGAGGACTGTGAG
CAATGGTGGGAAGATTGTCGCACCTCCTACACCTGCAAGAGCAACTGGCACAAGGGCTGG
AACTGGACTTCAGGGTTTAACAAGTGCGCAGTGGGAGCTGCCTGCCAACCTTTCCATTTC
TACTTCCCCACACCCACTGTTCTGTGCAATGAAATCTGGACTCACTCCTACAAGGTCAGC
AACTACAGCCGAGGGAGTGGCCGCTGCATCCAGATGTGGTTCGACCCAGCCCAGGGCAAC
CCCAATGAGGAGGTGGCGAGGTTCTATGCTGCAGCCATGAGTGGGGCTGGGCCCTGGGCA
GCCTGGCCTTTCCTGCTTAGCCTGGCCCTAATGCTGCTGTGGCTGCTCAGCTGA
GenBank Gene IDM28099
GeneCard IDNot Available
GenAtlas IDFOLR1
HGNC IDHGNC:3791
Chromosome Location11
Locus11q13.3-q14.1
References
  1. Elwood PC: Molecular cloning and characterization of the human folate-binding protein cDNA from placenta and malignant tissue culture (KB) cells. J Biol Chem. 1989 Sep 5;264(25):14893-901. 2768245
  2. Lacey SW, Sanders JM, Rothberg KG, Anderson RG, Kamen BA: Complementary DNA for the folate binding protein correctly predicts anchoring to the membrane by glycosyl-phosphatidylinositol. J Clin Invest. 1989 Aug;84(2):715-20. 2527252
  3. Campbell IG, Jones TA, Foulkes WD, Trowsdale J: Folate-binding protein is a marker for ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5329-38. 1717147
  4. Coney LR, Tomassetti A, Carayannopoulos L, Frasca V, Kamen BA, Colnaghi MI, Zurawski VR Jr: Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Res. 1991 Nov 15;51(22):6125-32. 1840502
  5. Sadasivan E, Cedeno M, Rothenberg SP: Genomic organization of the gene and a related pseudogene for a human folate binding protein. Biochim Biophys Acta. 1992 May 7;1131(1):91-4. 1581364
  6. Elwood PC, Nachmanoff K, Saikawa Y, Page ST, Pacheco P, Roberts S, Chung KN: The divergent 5' termini of the alpha human folate receptor (hFR) mRNAs originate from two tissue-specific promoters and alternative splicing: characterization of the alpha hFR gene structure. Biochemistry. 1997 Feb 11;36(6):1467-78. 9063895
  7. 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
  8. Sadasivan E, Rothenberg SP: The complete amino acid sequence of a human folate binding protein from KB cells determined from the cDNA. J Biol Chem. 1989 Apr 5;264(10):5806-11. 2538429
  9. Luhrs CA, Pitiranggon P, da Costa M, Rothenberg SP, Slomiany BL, Brink L, Tous GI, Stein S: Purified membrane and soluble folate binding proteins from cultured KB cells have similar amino acid compositions and molecular weights but differ in fatty acid acylation. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6546-9. 3476960
  10. Orr RB, Kamen BA: UMSCC38 cells amplified at 11q13 for the folate receptor synthesize a mutant nonfunctional folate receptor. Cancer Res. 1994 Jul 15;54(14):3905-11. 8033114
  11. 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
  12. Rijnboutt S, Jansen G, Posthuma G, Hynes JB, Schornagel JH, Strous GJ: Endocytosis of GPI-linked membrane folate receptor-alpha. J Cell Biol. 1996 Jan;132(1-2):35-47. 8567728
  13. Elortza F, Nuhse TS, Foster LJ, Stensballe A, Peck SC, Jensen ON: Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins. Mol Cell Proteomics. 2003 Dec;2(12):1261-70. Epub 2003 Sep 29. 14517339
  14. Elortza F, Mohammed S, Bunkenborg J, Foster LJ, Nuhse TS, Brodbeck U, Peck SC, Jensen ON: Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment. J Proteome Res. 2006 Apr;5(4):935-43. 16602701
  15. Omaetxebarria MJ, Elortza F, Rodriguez-Suarez E, Aloria K, Arizmendi JM, Jensen ON, Matthiesen R: Computational approach for identification and characterization of GPI-anchored peptides in proteomics experiments. Proteomics. 2007 Jun;7(12):1951-60. 17566972
  16. Picariello G, Ferranti P, Mamone G, Roepstorff P, Addeo F: Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry. Proteomics. 2008 Sep;8(18):3833-47. doi: 10.1002/pmic.200701057. 18780401
  17. Steinfeld R, Grapp M, Kraetzner R, Dreha-Kulaczewski S, Helms G, Dechent P, Wevers R, Grosso S, Gartner J: Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism. Am J Hum Genet. 2009 Sep;85(3):354-63. doi: 10.1016/j.ajhg.2009.08.005. 19732866
  18. Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong EL, Xu HE, Melcher K: Structural basis for molecular recognition of folic acid by folate receptors. Nature. 2013 Aug 22;500(7463):486-9. doi: 10.1038/nature12327. Epub 2013 Jul 14. 23851396
  19. 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