Folate receptor 1

FOLR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4KM6, 4KM7, 4KMX, 4LRH
Identifiers
Aliases	FOLR1, FBP, FOLR, Folate receptor 1, folate receptor 1 (adult)
External IDs	MGI: 95568 HomoloGene: 7322 GeneCards: FOLR1
Gene ontology Molecular function • methotrexate binding • drug binding • receptor activity • folic acid receptor activity • folic acid transporter activity • folic acid binding Cellular component • anchored component of external side of plasma membrane • extracellular region • brush border • clathrin-coated vesicle • ER to Golgi transport vesicle membrane • anchored component of membrane • Golgi membrane • nucleus • integral component of plasma membrane • cytoplasmic, membrane-bounded vesicle • apical plasma membrane • membrane • cell surface • endoplasmic reticulum membrane • brush border membrane • basolateral plasma membrane • plasma membrane • cytoplasmic vesicle • endosome • endoplasmic reticulum-Golgi intermediate compartment membrane • anchored component of plasma membrane • extracellular exosome Biological process • receptor-mediated endocytosis • cellular response to folic acid • neural crest cell migration involved in heart formation • axon regeneration • COPII vesicle coating • ER to Golgi vesicle-mediated transport • heart looping • cardiac neural crest cell migration involved in outflow tract morphogenesis • pharyngeal arch artery morphogenesis • folic acid metabolic process • transport • regulation of transforming growth factor beta receptor signaling pathway • response to axon injury • regulation of canonical Wnt signaling pathway • anterior neural tube closure • folic acid transport Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2348	14275
Ensembl	ENSG00000110195	ENSMUSG00000001827
UniProt	P15328	P35846
RefSeq (mRNA)	NM_016730 NM_000802 NM_016724 NM_016725 NM_016729	NM_001252552 NM_001252553 NM_001252554 NM_008034
RefSeq (protein)	NP_000793.1 NP_057936.1 NP_057937.1 NP_057941.1	NP_001239481.1 NP_001239482.1 NP_001239483.1 NP_032060.2
Location (UCSC)	Chr 11: 72.19 – 72.2 Mb	Chr 7: 101.86 – 101.87 Mb
PubMed search	[1]	[2]
Wikidata

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Folate receptor alpha is a protein that in humans is encoded by the FOLR1 gene.^[3][4]

The protein encoded by this gene is a member of the folate receptor (FOLR) family. Members of this gene family have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells.

This gene is composed of 7 exons; exons 1 through 4 encode the 5' UTR and exons 4 through 7 encode the open reading frame. Due to the presence of 2 promoters, multiple transcription start sites, and alternative splicing of exons, several transcript variants are derived from this gene. These variants differ in the lengths of 5' and 3' UTR, but they encode an identical amino acid sequence.^[4]

Clinical significance

FRA can be overexpressed by a number of epithelial-derived tumors including ovarian, breast, renal, lung, colorectal, and brain. Hence antibodies to it are used in targeted therapies and diagnostic tests, e.g. farletuzumab in phase III trial for ovarian cancer.

See also

• SLC19A1

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Campbell IG, Jones TA, Foulkes WD, Trowsdale J (Oct 1991). "Folate-binding protein is a marker for ovarian cancer". Cancer Res. 51 (19): 5329–38. PMID 1717147.
4. "Entrez Gene: FOLR1 folate receptor 1 (adult)".

Further reading

• Henderson GB (1990). "Folate-binding proteins". Annu. Rev. Nutr. 10: 319–35. doi:10.1146/annurev.nu.10.070190.001535. PMID 2166548.
• Kelemen LE (2006). "The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander?". Int. J. Cancer. 119 (2): 243–50. doi:10.1002/ijc.21712. PMID 16453285.
• Ragoussis J, Senger G, Trowsdale J, Campbell IG (1992). "Genomic organization of the human folate receptor genes on chromosome 11q13". Genomics. 14 (2): 423–30. doi:10.1016/S0888-7543(05)80236-8. PMID 1330883.
• Sadasivan E, Cedeno M, Rothenberg SP (1992). "Genomic organization of the gene and a related pseudogene for a human folate binding protein". Biochim. Biophys. Acta. 1131 (1): 91–4. doi:10.1016/0167-4781(92)90103-7. PMID 1581364.
• Coney LR, Tomassetti A, Carayannopoulos L, et al. (1991). "Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein". Cancer Res. 51 (22): 6125–32. PMID 1840502.
• Lacey SW, Sanders JM, Rothberg KG, et al. (1989). "Complementary DNA for the folate binding protein correctly predicts anchoring to the membrane by glycosyl-phosphatidylinositol". J. Clin. Invest. 84 (2): 715–20. doi:10.1172/JCI114220. PMC 548937. PMID 2527252.
• Sadasivan E, Rothenberg SP (1989). "The complete amino acid sequence of a human folate binding protein from KB cells determined from the cDNA". J. Biol. Chem. 264 (10): 5806–11. PMID 2538429.
• Elwood PC (1989). "Molecular cloning and characterization of the human folate-binding protein cDNA from placenta and malignant tissue culture (KB) cells". J. Biol. Chem. 264 (25): 14893–901. PMID 2768245.
• Sadasivan E, Rothenberg SP (1989). "Molecular cloning of the complementary DNA for a human folate binding protein". Proc. Soc. Exp. Biol. Med. 189 (2): 240–4. doi:10.3181/00379727-189-42804. PMID 3194438.
• Luhrs CA, Pitiranggon P, da Costa M, et al. (1987). "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. 84 (18): 6546–9. doi:10.1073/pnas.84.18.6546. PMC 299115. PMID 3476960.
• Yan W, Ratnam M (1995). "Preferred sites of glycosylphosphatidylinositol modification in folate receptors and constraints in the primary structure of the hydrophobic portion of the signal". Biochemistry. 34 (44): 14594–600. doi:10.1021/bi00044a039. PMID 7578066.
• Saikawa Y, Price K, Hance KW, et al. (1995). "Structural and functional analysis of the human KB cell folate receptor gene P4 promoter: cooperation of three clustered Sp1-binding sites with initiator region for basal promoter activity". Biochemistry. 34 (31): 9951–61. doi:10.1021/bi00031a018. PMID 7632694.
• Prasad PD, Ramamoorthy S, Moe AJ, et al. (1994). "Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytiotrophoblast and choriocarcinoma cells". Biochim. Biophys. Acta. 1223 (1): 71–5. doi:10.1016/0167-4889(94)90074-4. PMID 8061055.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Elwood PC, Nachmanoff K, Saikawa Y, et al. (1997). "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. 36 (6): 1467–78. doi:10.1021/bi962070h. PMID 9063895.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Barber RC, Shaw GM, Lammer EJ, et al. (1998). "Lack of association between mutations in the folate receptor-alpha gene and spina bifida". Am. J. Med. Genet. 76 (4): 310–7. doi:10.1002/(SICI)1096-8628(19980401)76:4<310::AID-AJMG6>3.0.CO;2-T. PMID 9545095.
• Tomassetti A, Bottero F, Mazzi M, et al. (1999). "Molecular requirements for attachment of the glycosylphosphatidylinositol anchor to the human alpha folate receptor". J. Cell. Biochem. 72 (1): 111–8. doi:10.1002/(SICI)1097-4644(19990101)72:1<111::AID-JCB12>3.0.CO;2-1. PMID 10025672.