Folate receptor 1: Difference between revisions
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{{PBB_Summary | {{PBB_Summary | ||
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| summary_text = The protein encoded by this gene is a member of the folate receptor (FOLR) family. Members of this | | summary_text = The protein encoded by this gene is a member of the [[folate receptor]] (FOLR) family. Members of this family have a high affinity for [[folic acid]] and for several reduced folic acid derivatives, and mediate delivery of [[Levomefolic acid|5-methyltetrahydrofolate]] to the interior of cells. | ||
This gene is composed of 7 [[exon]]s; exons 1 through 4 encode the 5' [[Untranslated region|UTR]] and exons 4 through 7 encode the [[open reading frame]]. Due to the presence of 2 [[Promoter (genetics)|promoters]], multiple [[Transcription (genetics)|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.<ref name="entrez" /> | This gene is composed of 7 [[exon]]s; exons 1 through 4 encode the 5' [[Untranslated region|UTR]] and exons 4 through 7 encode the [[open reading frame]]. Due to the presence of 2 [[Promoter (genetics)|promoters]], multiple [[Transcription (genetics)|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.<ref name="entrez" /> | ||
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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 [[Folate targeting|targeted therapies]] and diagnostic tests, e.g. [[farletuzumab]] in phase III trial for [[ovarian cancer]]. | 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 [[Folate targeting|targeted therapies]] and diagnostic tests, e.g. [[farletuzumab]] in phase III trial for [[ovarian cancer]]. | ||
Autoantibodies to the FRA have been linked to neurodevelopmental diseases,<ref>{{cite journal|last1=Frye|first1=RE|last2=Slattery|first2=JC|last3=Quadros|first3=EV|title=Folate metabolism abnormalities in autism: potential biomarkers.|journal=Biomarkers in | Autoantibodies to the FRA have been linked to neurodevelopmental diseases,<ref>{{cite journal|last1=Frye|first1=RE|last2=Slattery|first2=JC|last3=Quadros|first3=EV|title=Folate metabolism abnormalities in autism: potential biomarkers.|journal=[[Biomarkers in Medicine]]|date=3 August 2017|doi=10.2217/bmm-2017-0109|pmid=28770615}}</ref> particularly [[cerebral folate deficiency]]<ref name = "Ramaekers_2005">{{cite journal | vauthors = Ramaekers VT, Rothenberg SP, Sequeira JM, Opladen T, Blau N, Quadros EV, Selhub J | title = Autoantibodies to folate receptors in the cerebral folate deficiency syndrome | journal = The New England Journal of Medicine | volume = 352 | issue = 19 | pages = 1985–91 | date = May 2005 | pmid = 15888699 | doi = 10.1056/NEJMoa043160 }}</ref> [[schizophrenia]]<ref name = "Ramaekers_2005" /> and [[autism spectrum disorder]].<ref name = "Frye_2013">{{cite journal | vauthors = Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA | title = Cerebral folate receptor autoantibodies in autism spectrum disorder | journal = Molecular Psychiatry | volume = 18 | issue = 3 | pages = 369–81 | date = March 2013 | pmid = 22230883 | pmc = 3578948 | doi = 10.1038/mp.2011.175 }}</ref> Recent studies have shown that these neurodevelopmental disorders can be treated with [[folinic acid]].<ref name = "Frye_2013" /><ref>{{cite journal | vauthors = Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV | title = Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial | journal = Molecular Psychiatry | date = October 2016 | pmid = 27752075 | doi = 10.1038/mp.2016.168 }}</ref> | ||
==See also== | ==See also== | ||
Latest revision as of 12:16, 2 January 2019
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Folate receptor alpha is a protein that in humans is encoded by the FOLR1 gene.[1][2]
The protein encoded by this gene is a member of the folate receptor (FOLR) family. Members of this 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.[2]
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.
Autoantibodies to the FRA have been linked to neurodevelopmental diseases,[3] particularly cerebral folate deficiency[4] schizophrenia[4] and autism spectrum disorder.[5] Recent studies have shown that these neurodevelopmental disorders can be treated with folinic acid.[5][6]
See also
References
- ↑ 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.
- ↑ 2.0 2.1 "Entrez Gene: FOLR1 folate receptor 1 (adult)".
- ↑ Frye, RE; Slattery, JC; Quadros, EV (3 August 2017). "Folate metabolism abnormalities in autism: potential biomarkers". Biomarkers in Medicine. doi:10.2217/bmm-2017-0109. PMID 28770615.
- ↑ 4.0 4.1 Ramaekers VT, Rothenberg SP, Sequeira JM, Opladen T, Blau N, Quadros EV, Selhub J (May 2005). "Autoantibodies to folate receptors in the cerebral folate deficiency syndrome". The New England Journal of Medicine. 352 (19): 1985–91. doi:10.1056/NEJMoa043160. PMID 15888699.
- ↑ 5.0 5.1 Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA (March 2013). "Cerebral folate receptor autoantibodies in autism spectrum disorder". Molecular Psychiatry. 18 (3): 369–81. doi:10.1038/mp.2011.175. PMC 3578948. PMID 22230883.
- ↑ Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV (October 2016). "Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial". Molecular Psychiatry. doi:10.1038/mp.2016.168. PMID 27752075.
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.