Folate receptor alpha
Also known as: FOLR, FOLR1
Function
Binds 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 (By similarity).
Classification
- Family (Pfam)
- PF03024 Folate_rec
- InterPro
- Folate_rcpt, Folate_rcpt-like
- Functional cluster
- Secreted Growth Factors & Cytokines
Experimental structures · PDB · 5
A predicted model is available from AlphaFold.
Gene Ontology · 34
- GO:0016324 apical plasma membrane
- GO:0016323 basolateral plasma membrane
- GO:0031526 brush border membrane
- GO:0009986 cell surface
- GO:0030136 clathrin-coated vesicle
- GO:0005789 endoplasmic reticulum membrane
- GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane
- GO:0005768 endosome
- GO:0012507 ER to Golgi transport vesicle membrane
- GO:0009897 external side of plasma membrane
- GO:0070062 extracellular exosome
- GO:0000139 Golgi membrane
- GO:0016020 membrane
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0030133 transport vesicle
- GO:0005542 folic acid binding
- GO:0061714 folic acid receptor activity
- GO:0038023 signaling receptor activity
- GO:0061713 anterior neural tube closure
- GO:0031103 axon regeneration
- GO:0003253 cardiac neural crest cell migration involved in outflow tract morphogenesis
- GO:0007155 cell adhesion
- GO:0071231 cellular response to folic acid
- GO:0015884 folic acid transport
- GO:0007342 fusion of sperm to egg plasma membrane involved in single fertilization
- GO:0001947 heart looping
- GO:0003147 neural crest cell migration involved in heart formation
- GO:0061626 pharyngeal arch artery morphogenesis
- GO:0006898 receptor-mediated endocytosis
- GO:0060828 regulation of canonical Wnt signaling pathway
- GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
- GO:0035036 sperm-egg recognition
- GO:0046654 tetrahydrofolate biosynthetic process
Disease associations
Drugs targeting this protein · 1
- VINTAFOLIDE binding agent
Related proteins · sequence + function similarity
- Folate receptor beta 0.98
- Folate receptor alpha 0.96
- Folate receptor alpha 0.96
- Folate receptor gamma 0.95
- Folate receptor beta 0.94
- Sperm-egg fusion protein Juno 0.92
- Sperm-egg fusion protein Juno 0.90
- Sperm-egg fusion protein Juno 0.89
- Riboflavin-binding protein 0.71
- Riboflavin-binding protein 0.71
- Retbindin 0.68
- NALCN channel auxiliary factor 2 0.65
Co-cited proteins · studied together in the literature
- Folate receptor beta 2 shared papers
- Proton-coupled folate transporter 1 shared papers
- Reduced folate transporter 1 shared papers
- Reduced folate transporter 1 shared papers
- Proton-coupled folate transporter 1 shared papers
- Neuronal growth regulator 1 1 shared papers
- CD59 glycoprotein 2 shared papers
- Lymphocyte function-associated antigen 3 1 shared papers
- Alkaline phosphatase, tissue-nonspecific isozyme 1 shared papers
- Cadherin-13 1 shared papers
- Bone marrow stromal antigen 2 1 shared papers
- Butyrophilin subfamily 1 member A1 1 shared papers
Literature · 19 cited papers
- Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. Proc. Natl. Acad. Sci. U.S.A. · 2013
- Structural basis for molecular recognition of folic acid by folate receptors. Nature · 2013
- Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism. Am. J. Hum. Genet. · 2009
- A role for the proton-coupled folate transporter (PCFT-SLC46A1) in folate receptor-mediated endocytosis. J. Biol. Chem. · 2009
- Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry. Proteomics · 2008
- Computational approach for identification and characterization of GPI-anchored peptides in proteomics experiments. Proteomics · 2007
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Expression and differential polarization of the reduced-folate transporter-1 and the folate receptor alpha in mammalian retinal pigment epithelium. J. Biol. Chem. · 2000
- 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
- Endocytosis of GPI-linked membrane folate receptor-alpha. J. Cell Biol. · 1996
- UMSCC38 cells amplified at 11q13 for the folate receptor synthesize a mutant nonfunctional folate receptor. Cancer Res. · 1994
- Preferred sites of glycosylphosphatidylinositol modification in folate receptors and constraints in the primary structure of the hydrophobic portion of the signal. Biochemistry · 1995
- … and 7 more in the literature graph
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