Folate receptor alpha

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
  • anterior neural tube closure
  • COPII vesicle coating
  • cardiac neural crest cell migration involved in outflow tract morphogenesis
  • ER to Golgi vesicle-mediated transport
  • heart looping
  • membrane organization
  • neural crest cell migration involved in heart formation
  • post-translational protein modification
  • pharyngeal arch artery morphogenesis
  • protein N-linked glycosylation via asparagine
  • 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
  • plasma membrane
  • basolateral plasma membrane
  • endoplasmic reticulum membrane
  • endosome
  • apical plasma membrane
  • cell surface
  • anchored component of external side of plasma membrane
  • clathrin-coated vesicle
  • extracellular exosome
  • integral component of plasma membrane
  • endoplasmic reticulum-Golgi intermediate compartment membrane
  • ER to Golgi transport vesicle membrane
  • Golgi 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
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  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
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  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
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