FOLR1_HUMAN
ID FOLR1_HUMAN Reviewed; 257 AA.
AC P15328; Q53EW2; Q6FGT8; Q6LC90; Q9UCT2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Folate receptor alpha;
DE Short=FR-alpha;
DE AltName: Full=Adult folate-binding protein;
DE Short=FBP;
DE AltName: Full=Folate receptor 1;
DE AltName: Full=Folate receptor, adult;
DE AltName: Full=KB cells FBP;
DE AltName: Full=Ovarian tumor-associated antigen MOv18;
DE Flags: Precursor;
GN Name=FOLR1; Synonyms=FOLR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=2768245; DOI=10.1016/s0021-9258(18)63786-x;
RA Elwood P.C.;
RT "Molecular cloning and characterization of the human folate-binding protein
RT cDNA from placenta and malignant tissue culture (KB) cells.";
RL J. Biol. Chem. 264:14893-14901(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=2527252; DOI=10.1172/jci114220;
RA Lacey S.W., Sanders J.M., Rothberg K.G., Anderson R.G.W., Kamen B.A.;
RT "Complementary DNA for the folate binding protein correctly predicts
RT anchoring to the membrane by glycosyl-phosphatidylinositol.";
RL J. Clin. Invest. 84:715-720(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=1717147;
RA Campbell I.G., Jones T.A., Foulkes W.D., Trowsdale J.;
RT "Folate-binding protein is a marker for ovarian cancer.";
RL Cancer Res. 51:5329-5338(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 31-56.
RC TISSUE=Ovarian carcinoma;
RX PubMed=1840502;
RA Coney L.R., Tomassetti A., Carayannopoulos L., Frasca V., Kamen B.A.,
RA Colnaghi M.I., Zurawski V.R. Jr.;
RT "Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies
RT recognize a folate-binding protein.";
RL Cancer Res. 51:6125-6132(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1581364; DOI=10.1016/0167-4781(92)90103-7;
RA Sadasivan E., Cedeno M., Rothenberg S.P.;
RT "Genomic organization of the gene and a related pseudogene for a human
RT folate binding protein.";
RL Biochim. Biophys. Acta 1131:91-94(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 1-56, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Lymphocyte;
RX PubMed=9063895; DOI=10.1021/bi962070h;
RA Elwood P.C., Nachmanoff K., Saikawa Y., Page S.T., Pacheco P., Roberts S.,
RA Chung K.-N.;
RT "The divergent 5' termini of the alpha human folate receptor (hFR) mRNAs
RT originate from two tissue-specific promoters and alternative splicing:
RT characterization of the alpha hFR gene structure.";
RL Biochemistry 36:1467-1478(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney proximal tubule;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-249.
RX PubMed=2538429; DOI=10.1016/s0021-9258(18)83621-3;
RA Sadasivan E., Rothenberg S.P.;
RT "The complete amino acid sequence of a human folate binding protein from KB
RT cells determined from the cDNA.";
RL J. Biol. Chem. 264:5806-5811(1989).
RN [13]
RP PROTEIN SEQUENCE OF 26-43, AND SUBCELLULAR LOCATION.
RX PubMed=3476960; DOI=10.1073/pnas.84.18.6546;
RA Luhrs C.A., Pitiranggon P., da Costa M., Rothenberg S.P., Slomiany B.L.,
RA Brink L., Tous G.I., Stein S.;
RT "Purified membrane and soluble folate binding proteins from cultured KB
RT cells have similar amino acid compositions and molecular weights but differ
RT in fatty acid acylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6546-6549(1987).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8033114;
RA Orr R.B., Kamen B.A.;
RT "UMSCC38 cells amplified at 11q13 for the folate receptor synthesize a
RT mutant nonfunctional folate receptor.";
RL Cancer Res. 54:3905-3911(1994).
RN [15]
RP GPI-ANCHOR AT SER-234, AND SUBCELLULAR LOCATION.
RX PubMed=7578066; DOI=10.1021/bi00044a039;
RA Yan W., Ratnam M.;
RT "Preferred sites of glycosylphosphatidylinositol modification in folate
RT receptors and constraints in the primary structure of the hydrophobic
RT portion of the signal.";
RL Biochemistry 34:14594-14600(1995).
RN [16]
RP FUNCTION, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=8567728; DOI=10.1083/jcb.132.1.35;
RA Rijnboutt S., Jansen G., Posthuma G., Hynes J.B., Schornagel J.H.,
RA Strous G.J.;
RT "Endocytosis of GPI-linked membrane folate receptor-alpha.";
RL J. Cell Biol. 132:35-47(1996).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=10787414; DOI=10.1074/jbc.m002328200;
RA Chancy C.D., Kekuda R., Huang W., Prasad P.D., Kuhnel J.M., Sirotnak F.M.,
RA Roon P., Ganapathy V., Smith S.B.;
RT "Expression and differential polarization of the reduced-folate
RT transporter-1 and the folate receptor alpha in mammalian retinal pigment
RT epithelium.";
RL J. Biol. Chem. 275:20676-20684(2000).
RN [18]
RP GPI-ANCHOR AT SER-234, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17566972; DOI=10.1002/pmic.200700068;
RA Omaetxebarria M.J., Elortza F., Rodriguez-Suarez E., Aloria K.,
RA Arizmendi J.M., Jensen O.N., Matthiesen R.;
RT "Computational approach for identification and characterization of GPI-
RT anchored peptides in proteomics experiments.";
RL Proteomics 7:1951-1960(2007).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-161 AND ASN-201.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
RN [20]
RP INVOLVEMENT IN NEURODEGENERATION DUE TO CEREBRAL FOLATE TRANSPORT
RP DEFICIENCY.
RX PubMed=19732866; DOI=10.1016/j.ajhg.2009.08.005;
RA Steinfeld R., Grapp M., Kraetzner R., Dreha-Kulaczewski S., Helms G.,
RA Dechent P., Wevers R., Grosso S., Gaertner J.;
RT "Folate receptor alpha defect causes cerebral folate transport deficiency:
RT a treatable neurodegenerative disorder associated with disturbed myelin
RT metabolism.";
RL Am. J. Hum. Genet. 85:354-363(2009).
RN [21]
RP FUNCTION.
RX PubMed=19074442; DOI=10.1074/jbc.m807665200;
RA Zhao R., Min S.H., Wang Y., Campanella E., Low P.S., Goldman I.D.;
RT "A role for the proton-coupled folate transporter (PCFT-SLC46A1) in folate
RT receptor-mediated endocytosis.";
RL J. Biol. Chem. 284:4267-4274(2009).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-235 IN COMPLEX WITH FOLATE,
RP FUNCTION, MUTAGENESIS OF TYR-82; ASP-103; TYR-107; TRP-124; ARG-125;
RP ARG-128; HIS-157; TRP-162 AND SER-196, DISULFIDE BONDS, AND GLYCOSYLATION
RP AT ASN-69; ASN-161 AND ASN-201.
RX PubMed=23851396; DOI=10.1038/nature12327;
RA Chen C., Ke J., Zhou X.E., Yi W., Brunzelle J.S., Li J., Yong E.L.,
RA Xu H.E., Melcher K.;
RT "Structural basis for molecular recognition of folic acid by folate
RT receptors.";
RL Nature 500:486-489(2013).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 30-234, FUNCTION, GLYCOSYLATION
RP AT ASN-69; ASN-161 AND ASN-201, AND DISULFIDE BONDS.
RX PubMed=23934049; DOI=10.1073/pnas.1308827110;
RA Wibowo A.S., Singh M., Reeder K.M., Carter J.J., Kovach A.R., Meng W.,
RA Ratnam M., Zhang F., Dann C.E. III;
RT "Structures of human folate receptors reveal biological trafficking states
RT and diversity in folate and antifolate recognition.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:15180-15188(2013).
CC -!- FUNCTION: Binds to folate and reduced folic acid derivatives and
CC mediates delivery of 5-methyltetrahydrofolate and folate analogs into
CC the interior of cells (PubMed:23851396, PubMed:23934049,
CC PubMed:2527252, PubMed:8033114, PubMed:8567728, PubMed:19074442). Has
CC high affinity for folate and folic acid analogs at neutral pH
CC (PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114,
CC PubMed:8567728). Exposure to slightly acidic pH after receptor
CC endocytosis triggers a conformation change that strongly reduces its
CC affinity for folates and mediates their release (PubMed:8567728).
CC Required for normal embryonic development and normal cell proliferation
CC (By similarity). {ECO:0000250|UniProtKB:P35846,
CC ECO:0000269|PubMed:19074442, ECO:0000269|PubMed:23851396,
CC ECO:0000269|PubMed:23934049, ECO:0000269|PubMed:2527252,
CC ECO:0000269|PubMed:8033114, ECO:0000269|PubMed:8567728}.
CC -!- INTERACTION:
CC P15328; Q8N357: SLC35F6; NbExp=3; IntAct=EBI-2556557, EBI-713484;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2527252,
CC ECO:0000269|PubMed:8033114, ECO:0000269|PubMed:8567728}; Lipid-anchor,
CC GPI-anchor {ECO:0000269|PubMed:17566972, ECO:0000269|PubMed:7578066}.
CC Apical cell membrane {ECO:0000269|PubMed:10787414}; Lipid-anchor, GPI-
CC anchor {ECO:0000269|PubMed:17566972, ECO:0000269|PubMed:7578066}.
CC Basolateral cell membrane {ECO:0000269|PubMed:10787414}; Lipid-anchor,
CC GPI-like-anchor {ECO:0000269|PubMed:17566972,
CC ECO:0000269|PubMed:7578066}. Secreted {ECO:0000305|PubMed:3476960}.
CC Cytoplasmic vesicle {ECO:0000269|PubMed:8567728}. Cytoplasmic vesicle,
CC clathrin-coated vesicle {ECO:0000269|PubMed:8567728}. Endosome
CC {ECO:0000269|PubMed:8567728}. Note=Endocytosed into cytoplasmic
CC vesicles and then recycled to the cell membrane.
CC {ECO:0000269|PubMed:8567728}.
CC -!- TISSUE SPECIFICITY: Primarily expressed in tissues of epithelial
CC origin. Expression is increased in malignant tissues. Expressed in
CC kidney, lung and cerebellum. Detected in placenta and thymus
CC epithelium. {ECO:0000269|PubMed:2527252, ECO:0000269|PubMed:2768245,
CC ECO:0000269|PubMed:9063895}.
CC -!- PTM: The secreted form is derived from the membrane-bound form either
CC by cleavage of the GPI anchor, or/and by proteolysis catalyzed by a
CC metalloprotease. {ECO:0000305|PubMed:3476960}.
CC -!- DISEASE: Neurodegeneration due to cerebral folate transport deficiency
CC (NCFTD) [MIM:613068]: An autosomal recessive neurodegenerative disorder
CC resulting from brain-specific folate deficiency early in life. Onset is
CC apparent in late infancy with severe developmental regression, movement
CC disturbances, epilepsy and leukodystrophy.
CC {ECO:0000269|PubMed:19732866}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the folate receptor family. {ECO:0000305}.
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DR EMBL; J05013; AAA35823.1; -; mRNA.
DR EMBL; M28099; AAA35822.1; -; mRNA.
DR EMBL; X62753; CAA44610.1; -; mRNA.
DR EMBL; U20391; AAB05827.1; -; Genomic_DNA.
DR EMBL; U78793; AAB39751.1; -; mRNA.
DR EMBL; U78794; AAB39752.1; -; mRNA.
DR EMBL; BT007158; AAP35822.1; -; mRNA.
DR EMBL; CR542019; CAG46816.1; -; mRNA.
DR EMBL; AK223527; BAD97247.1; -; mRNA.
DR EMBL; CH471076; EAW74848.1; -; Genomic_DNA.
DR EMBL; BC002947; AAH02947.1; -; mRNA.
DR EMBL; M25317; AAA74896.1; -; mRNA.
DR CCDS; CCDS8211.1; -.
DR PIR; A44904; A45753.
DR RefSeq; NP_000793.1; NM_000802.3.
DR RefSeq; NP_057936.1; NM_016724.2.
DR RefSeq; NP_057937.1; NM_016725.2.
DR RefSeq; NP_057941.1; NM_016729.2.
DR PDB; 4KM6; X-ray; 1.55 A; A=30-234.
DR PDB; 4KM7; X-ray; 1.80 A; A/B=28-234.
DR PDB; 4KMX; X-ray; 2.20 A; A=28-234.
DR PDB; 4LRH; X-ray; 2.80 A; A/B/C/D/E/F/G/H=23-235.
DR PDB; 5IZQ; X-ray; 3.60 A; A/B/C/D/E/F/G/H=1-235.
DR PDBsum; 4KM6; -.
DR PDBsum; 4KM7; -.
DR PDBsum; 4KMX; -.
DR PDBsum; 4LRH; -.
DR PDBsum; 5IZQ; -.
DR AlphaFoldDB; P15328; -.
DR SMR; P15328; -.
DR BioGRID; 108631; 27.
DR IntAct; P15328; 14.
DR MINT; P15328; -.
DR STRING; 9606.ENSP00000377284; -.
DR BindingDB; P15328; -.
DR ChEMBL; CHEMBL2121; -.
DR DrugBank; DB05595; Farletuzumab.
DR DrugBank; DB00158; Folic acid.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB15413; Pafolacianine.
DR DrugBank; DB05168; Vintafolide.
DR DrugCentral; P15328; -.
DR TCDB; 9.B.92.1.1; the folate receptor (fr) family.
DR GlyConnect; 1248; 24 N-Linked glycans (3 sites).
DR GlyGen; P15328; 4 sites, 23 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P15328; -.
DR PhosphoSitePlus; P15328; -.
DR SwissPalm; P15328; -.
DR BioMuta; FOLR1; -.
DR DMDM; 544337; -.
DR EPD; P15328; -.
DR jPOST; P15328; -.
DR MassIVE; P15328; -.
DR MaxQB; P15328; -.
DR PaxDb; P15328; -.
DR PeptideAtlas; P15328; -.
DR PRIDE; P15328; -.
DR ProteomicsDB; 53130; -.
DR ABCD; P15328; 7 sequenced antibodies.
DR Antibodypedia; 16919; 433 antibodies from 37 providers.
DR DNASU; 2348; -.
DR Ensembl; ENST00000312293.9; ENSP00000308137.4; ENSG00000110195.14.
DR Ensembl; ENST00000393676.5; ENSP00000377281.3; ENSG00000110195.14.
DR Ensembl; ENST00000393679.5; ENSP00000377284.1; ENSG00000110195.14.
DR Ensembl; ENST00000393681.6; ENSP00000377286.2; ENSG00000110195.14.
DR Ensembl; ENST00000675784.1; ENSP00000502440.1; ENSG00000110195.14.
DR GeneID; 2348; -.
DR KEGG; hsa:2348; -.
DR MANE-Select; ENST00000393676.5; ENSP00000377281.3; NM_016729.3; NP_057941.1.
DR UCSC; uc001orz.3; human.
DR CTD; 2348; -.
DR DisGeNET; 2348; -.
DR GeneCards; FOLR1; -.
DR HGNC; HGNC:3791; FOLR1.
DR HPA; ENSG00000110195; Tissue enhanced (choroid plexus, fallopian tube, lung, salivary gland).
DR MalaCards; FOLR1; -.
DR MIM; 136430; gene.
DR MIM; 613068; phenotype.
DR neXtProt; NX_P15328; -.
DR OpenTargets; ENSG00000110195; -.
DR Orphanet; 217382; Neurodegenerative syndrome due to cerebral folate transport deficiency.
DR PharmGKB; PA28207; -.
DR VEuPathDB; HostDB:ENSG00000110195; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00950000183144; -.
DR HOGENOM; CLU_070826_1_1_1; -.
DR InParanoid; P15328; -.
DR OMA; HKQCSPW; -.
DR OrthoDB; 1224404at2759; -.
DR PhylomeDB; P15328; -.
DR TreeFam; TF328532; -.
DR PathwayCommons; P15328; -.
DR Reactome; R-HSA-204005; COPII-mediated vesicle transport.
DR Reactome; R-HSA-5694530; Cargo concentration in the ER.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR SignaLink; P15328; -.
DR SIGNOR; P15328; -.
DR BioGRID-ORCS; 2348; 17 hits in 1074 CRISPR screens.
DR GeneWiki; Folate_receptor_1; -.
DR GenomeRNAi; 2348; -.
DR Pharos; P15328; Tchem.
DR PRO; PR:P15328; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P15328; protein.
DR Bgee; ENSG00000110195; Expressed in right uterine tube and 132 other tissues.
DR ExpressionAtlas; P15328; baseline and differential.
DR Genevisible; P15328; HS.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:BHF-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; HDA:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:CACAO.
DR GO; GO:0005886; C:plasma membrane; NAS:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; TAS:Reactome.
DR GO; GO:0005542; F:folic acid binding; IDA:UniProtKB.
DR GO; GO:0061714; F:folic acid receptor activity; IMP:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0061713; P:anterior neural tube closure; ISS:BHF-UCL.
DR GO; GO:0031103; P:axon regeneration; ISS:BHF-UCL.
DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0071231; P:cellular response to folic acid; IDA:BHF-UCL.
DR GO; GO:1904447; P:folate import across plasma membrane; IEA:InterPro.
DR GO; GO:0046655; P:folic acid metabolic process; IEA:Ensembl.
DR GO; GO:0015884; P:folic acid transport; IMP:UniProtKB.
DR GO; GO:0007342; P:fusion of sperm to egg plasma membrane involved in single fertilization; IBA:GO_Central.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0003147; P:neural crest cell migration involved in heart formation; ISS:BHF-UCL.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISS:BHF-UCL.
DR GO; GO:0006898; P:receptor-mediated endocytosis; TAS:ProtInc.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:BHF-UCL.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0035036; P:sperm-egg recognition; IBA:GO_Central.
DR InterPro; IPR004269; Folate_rcpt.
DR InterPro; IPR018143; Folate_rcpt-like.
DR InterPro; IPR032935; FOLR1.
DR PANTHER; PTHR10517; PTHR10517; 1.
DR PANTHER; PTHR10517:SF15; PTHR10517:SF15; 1.
DR Pfam; PF03024; Folate_rec; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Endosome; Folate-binding;
KW Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Neurodegeneration;
KW Receptor; Reference proteome; Secreted; Signal; Transport.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..234
FT /note="Folate receptor alpha"
FT /id="PRO_0000008802"
FT PROPEP 235..257
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:17566972,
FT ECO:0000305|PubMed:7578066"
FT /id="PRO_0000008803"
FT BINDING 103
FT /ligand="folate"
FT /ligand_id="ChEBI:CHEBI:62501"
FT /evidence="ECO:0000269|PubMed:23851396"
FT BINDING 107
FT /ligand="folate"
FT /ligand_id="ChEBI:CHEBI:62501"
FT /evidence="ECO:0000269|PubMed:23851396"
FT BINDING 124..128
FT /ligand="folate"
FT /ligand_id="ChEBI:CHEBI:62501"
FT /evidence="ECO:0000269|PubMed:23851396"
FT BINDING 157..162
FT /ligand="folate"
FT /ligand_id="ChEBI:CHEBI:62501"
FT /evidence="ECO:0000269|PubMed:23851396"
FT BINDING 196
FT /ligand="folate"
FT /ligand_id="ChEBI:CHEBI:62501"
FT /evidence="ECO:0000269|PubMed:23851396"
FT LIPID 234
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000269|PubMed:17566972,
FT ECO:0000269|PubMed:7578066"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18780401,
FT ECO:0000269|PubMed:23851396, ECO:0000269|PubMed:23934049"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18780401,
FT ECO:0000269|PubMed:23851396, ECO:0000269|PubMed:23934049"
FT DISULFID 37..65
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT DISULFID 57..105
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT DISULFID 66..109
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT DISULFID 89..175
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT DISULFID 96..146
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT DISULFID 135..209
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT DISULFID 139..189
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT DISULFID 152..169
FT /evidence="ECO:0000269|PubMed:23851396,
FT ECO:0000269|PubMed:23934049, ECO:0007744|PDB:4KM6,
FT ECO:0007744|PDB:4KM7, ECO:0007744|PDB:4KMX,
FT ECO:0007744|PDB:4LRH"
FT VARIANT 28
FT /note="W -> R (in dbSNP:rs7928649)"
FT /id="VAR_059284"
FT VARIANT 160
FT /note="W -> C (in dbSNP:rs1801932)"
FT /id="VAR_011963"
FT MUTAGEN 82
FT /note="Y->A: Slightly reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 103
FT /note="D->A: Strongly reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 107
FT /note="Y->A: Moderately reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 124
FT /note="W->A: Moderately reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 125
FT /note="R->A: Moderately reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 128
FT /note="R->A: Moderately reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 157
FT /note="H->A: Moderately reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 162
FT /note="W->A: Moderately reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT MUTAGEN 196
FT /note="S->A: Moderately reduced affinity for folate."
FT /evidence="ECO:0000269|PubMed:23851396"
FT CONFLICT 180
FT /note="F -> L (in Ref. 9; BAD97247)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="T -> S (in Ref. 12; AAA74896)"
FT /evidence="ECO:0000305"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:4KMX"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:4KM6"
FT TURN 53..56
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:4KM6"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 68..73
FT /evidence="ECO:0007829|PDB:4LRH"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:4KM6"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 94..109
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:4KM6"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:4LRH"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 136..145
FT /evidence="ECO:0007829|PDB:4KM6"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:4KM6"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:4KM6"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:4LRH"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:4LRH"
FT HELIX 178..181
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 185..191
FT /evidence="ECO:0007829|PDB:4KM6"
FT TURN 192..195
FT /evidence="ECO:0007829|PDB:4KM6"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:4KM6"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:4KM6"
SQ SEQUENCE 257 AA; 29819 MW; D458D8BB047C96A6 CRC64;
MAQRMTTQLL LLLVWVAVVG EAQTRIAWAR TELLNVCMNA KHHKEKPGPE DKLHEQCRPW
RKNACCSTNT SQEAHKDVSY LYRFNWNHCG EMAPACKRHF IQDTCLYECS PNLGPWIQQV
DQSWRKERVL NVPLCKEDCE QWWEDCRTSY TCKSNWHKGW NWTSGFNKCA VGAACQPFHF
YFPTPTVLCN EIWTHSYKVS NYSRGSGRCI QMWFDPAQGN PNEEVARFYA AAMSGAGPWA
AWPFLLSLAL MLLWLLS
