ID FOLR1_MOUSE Reviewed; 255 AA. AC P35846; Q9R222; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 11-DEC-2013, sequence version 2. DT 27-MAR-2024, entry version 155. DE RecName: Full=Folate receptor alpha; DE Short=FR-alpha; DE AltName: Full=Folate receptor 1; DE AltName: Full=Folate-binding protein 1; DE Flags: Precursor; GN Name=Folr1; Synonyms=Fbp1, Folbp1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=1894617; DOI=10.1016/s0021-9258(19)47365-1; RA Brigle K.E., Westin E.H., Houghton M.T., Goldman I.D.; RT "Characterization of two cDNAs encoding folate-binding proteins from L1210 RT murine leukemia cells. Increased expression associated with a genomic RT rearrangement."; RL J. Biol. Chem. 266:17243-17249(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION. RX PubMed=10216260; DOI=10.1016/s0378-1119(99)00081-5; RA Bolton J.A., Wood S.A., Kennedy D., Don R.H., Mattick J.S.; RT "Retinoic acid-dependent upregulation of mouse folate receptor-alpha RT expression in embryonic stem cells, and conservation of alternative RT splicing patterns."; RL Gene 230:215-224(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54. RX PubMed=1429588; DOI=10.1016/s0021-9258(18)41678-x; RA Brigle K.E., Westin E.H., Houghton M.T., Goldman I.D.; RT "Insertion of an intracisternal A particle within the 5'-regulatory region RT of a gene encoding folate-binding protein in L1210 leukemia cells in RT response to low folate selection. Association with increased protein RT expression."; RL J. Biol. Chem. 267:22351-22355(1992). RN [7] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=10508523; DOI=10.1038/13861; RA Piedrahita J.A., Oetama B., Bennett G.D., van Waes J., Kamen B.A., RA Richardson J., Lacey S.W., Anderson R.G., Finnell R.H.; RT "Mice lacking the folic acid-binding protein Folbp1 are defective in early RT embryonic development."; RL Nat. Genet. 23:228-232(1999). RN [8] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=12854656; DOI=10.1002/bdra.10045; RA Tang L.S., Finnell R.H.; RT "Neural and orofacial defects in Folp1 knockout mice."; RL Birth Defects Res. A Clin. Mol. Teratol. 67:209-218(2003). RN [9] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=15259034; DOI=10.1002/bdra.20043; RA Tang L.S., Wlodarczyk B.J., Santillano D.R., Miranda R.C., Finnell R.H.; RT "Developmental consequences of abnormal folate transport during murine RT heart morphogenesis."; RL Birth Defects Res. A Clin. Mol. Teratol. 70:449-458(2004). RN [10] RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=15703271; DOI=10.1681/asn.2004080711; RA Birn H., Spiegelstein O., Christensen E.I., Finnell R.H.; RT "Renal tubular reabsorption of folate mediated by folate binding protein RT 1."; RL J. Am. Soc. Nephrol. 16:608-615(2005). RN [11] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=17286298; DOI=10.1002/bdra.20347; RA Zhu H., Wlodarczyk B.J., Scott M., Yu W., Merriweather M., RA Gelineau-van Waes J., Schwartz R.J., Finnell R.H.; RT "Cardiovascular abnormalities in Folr1 knockout mice and folate rescue."; RL Birth Defects Res. A Clin. Mol. Teratol. 79:257-268(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). 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:1894617). Has high affinity for folate CC and folic acid analogs at neutral pH (By similarity). Exposure to CC slightly acidic pH after receptor endocytosis triggers a conformation CC change that strongly reduces its affinity for folates and mediates CC their release (By similarity). Required for normal embryonic CC development and normal cell proliferation (PubMed:10508523, CC PubMed:12854656, PubMed:15259034, PubMed:17286298). Required for renal CC folate reabsorption (PubMed:15703271). {ECO:0000250|UniProtKB:P15328, CC ECO:0000269|PubMed:10508523, ECO:0000269|PubMed:12854656, CC ECO:0000269|PubMed:15259034, ECO:0000269|PubMed:15703271, CC ECO:0000269|PubMed:17286298, ECO:0000269|PubMed:1894617}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15328}; CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P15328}. Apical cell CC membrane {ECO:0000250|UniProtKB:P15328}; Lipid-anchor, GPI-anchor CC {ECO:0000250|UniProtKB:P15328}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:P15328}; Lipid-anchor, GPI-like-anchor CC {ECO:0000250|UniProtKB:P15328}. Secreted CC {ECO:0000250|UniProtKB:P15328}. Cytoplasmic vesicle CC {ECO:0000250|UniProtKB:P15328}. Cytoplasmic vesicle, clathrin-coated CC vesicle {ECO:0000250|UniProtKB:P15328}. Endosome CC {ECO:0000250|UniProtKB:P15328}. Note=Endocytosed into cytoplasmic CC vesicles and then recycled to the cell membrane. CC {ECO:0000250|UniProtKB:P15328}. CC -!- TISSUE SPECIFICITY: Detected in kidney proximal tubules (at protein CC level). {ECO:0000269|PubMed:15703271}. 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:0000250|UniProtKB:P15328}. CC -!- DISRUPTION PHENOTYPE: Embryonic lethality at about 10.5 dpc, due to CC gross developmental defects, including defects of neural tube closure, CC craniofacial defects and defects in heart development. Embryos can be CC rescued by maternal folate supplementation. CC {ECO:0000269|PubMed:10508523, ECO:0000269|PubMed:12854656, CC ECO:0000269|PubMed:15259034, ECO:0000269|PubMed:15703271, CC ECO:0000269|PubMed:17286298}. CC -!- SIMILARITY: Belongs to the folate receptor family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M64782; AAA37595.1; -; mRNA. DR EMBL; AF096319; AAD19353.1; -; mRNA. DR EMBL; AC167240; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466531; EDL16530.1; -; Genomic_DNA. DR EMBL; CH466531; EDL16532.1; -; Genomic_DNA. DR EMBL; CH466531; EDL16533.1; -; Genomic_DNA. DR EMBL; CH466531; EDL16534.1; -; Genomic_DNA. DR EMBL; CH466531; EDL16535.1; -; Genomic_DNA. DR EMBL; CH466531; EDL16536.1; -; Genomic_DNA. DR EMBL; CH466531; EDL16537.1; -; Genomic_DNA. DR EMBL; CH466531; EDL16538.1; -; Genomic_DNA. DR EMBL; BC138781; AAI38782.1; -; mRNA. DR EMBL; BC138795; AAI38796.1; -; mRNA. DR EMBL; BC145414; AAI45415.1; -; mRNA. DR EMBL; M97700; AAA37596.1; -; Genomic_DNA. DR EMBL; M97701; AAA37598.1; -; Genomic_DNA. DR CCDS; CCDS21517.1; -. DR PIR; A40969; A40969. DR RefSeq; NP_001239481.1; NM_001252552.1. DR RefSeq; NP_001239482.1; NM_001252553.1. DR RefSeq; NP_001239483.1; NM_001252554.1. DR RefSeq; NP_032060.2; NM_008034.3. DR RefSeq; XP_006507423.1; XM_006507360.3. DR RefSeq; XP_006507424.1; XM_006507361.2. DR RefSeq; XP_006507426.1; XM_006507363.3. DR RefSeq; XP_006507427.1; XM_006507364.2. DR RefSeq; XP_006507428.1; XM_006507365.3. DR RefSeq; XP_006507429.1; XM_006507366.2. DR RefSeq; XP_006507430.1; XM_006507367.3. DR RefSeq; XP_006507431.1; XM_006507368.3. DR RefSeq; XP_006507432.1; XM_006507369.3. DR RefSeq; XP_006507433.1; XM_006507370.3. DR AlphaFoldDB; P35846; -. DR SMR; P35846; -. DR STRING; 10090.ENSMUSP00000102598; -. DR MoonProt; P35846; -. DR GlyCosmos; P35846; 4 sites, 10 glycans. DR GlyGen; P35846; 3 sites. DR PhosphoSitePlus; P35846; -. DR SwissPalm; P35846; -. DR jPOST; P35846; -. DR PaxDb; 10090-ENSMUSP00000102598; -. DR PeptideAtlas; P35846; -. DR ProteomicsDB; 267613; -. DR Antibodypedia; 16919; 547 antibodies from 38 providers. DR DNASU; 14275; -. DR Ensembl; ENSMUST00000106981.8; ENSMUSP00000102594.2; ENSMUSG00000001827.13. DR Ensembl; ENSMUST00000106982.8; ENSMUSP00000102595.2; ENSMUSG00000001827.13. DR Ensembl; ENSMUST00000106983.8; ENSMUSP00000102596.2; ENSMUSG00000001827.13. DR Ensembl; ENSMUST00000106985.8; ENSMUSP00000102598.2; ENSMUSG00000001827.13. DR Ensembl; ENSMUST00000106986.9; ENSMUSP00000102599.3; ENSMUSG00000001827.13. DR GeneID; 14275; -. DR KEGG; mmu:14275; -. DR UCSC; uc009ipm.1; mouse. DR AGR; MGI:95568; -. DR CTD; 2348; -. DR MGI; MGI:95568; Folr1. DR VEuPathDB; HostDB:ENSMUSG00000001827; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00950000183144; -. DR HOGENOM; CLU_070826_1_1_1; -. DR InParanoid; P35846; -. DR OMA; HKQCSPW; -. DR OrthoDB; 2905009at2759; -. DR PhylomeDB; P35846; -. DR TreeFam; TF328532; -. DR Reactome; R-MMU-204005; COPII-mediated vesicle transport. DR Reactome; R-MMU-5694530; Cargo concentration in the ER. DR Reactome; R-MMU-6807878; COPI-mediated anterograde transport. DR BioGRID-ORCS; 14275; 3 hits in 79 CRISPR screens. DR ChiTaRS; Folr1; mouse. DR PRO; PR:P35846; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; P35846; Protein. DR Bgee; ENSMUSG00000001827; Expressed in choroid plexus of fourth ventricle and 153 other cell types or tissues. DR ExpressionAtlas; P35846; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI. DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI. DR GO; GO:0031526; C:brush border membrane; ISO:MGI. DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; TAS:MGI. DR GO; GO:0005634; C:nucleus; ISO:MGI. DR GO; GO:0005542; F:folic acid binding; ISS:UniProtKB. DR GO; GO:0061714; F:folic acid receptor activity; ISS:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central. DR GO; GO:0061713; P:anterior neural tube closure; IMP:BHF-UCL. DR GO; GO:0031103; P:axon regeneration; IMP:BHF-UCL. DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IMP:BHF-UCL. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0071231; P:cellular response to folic acid; ISO:MGI. DR GO; GO:0046655; P:folic acid metabolic process; IMP:MGI. DR GO; GO:0015884; P:folic acid transport; ISS: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; IMP:BHF-UCL. DR GO; GO:0003147; P:neural crest cell migration involved in heart formation; IMP:BHF-UCL. DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IMP:BHF-UCL. DR GO; GO:0006620; P:post-translational protein targeting to endoplasmic reticulum membrane; TAS:MGI. DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IMP:BHF-UCL. DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0048678; P:response to axon injury; IMP: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 PANTHER; PTHR10517; FOLATE RECEPTOR; 1. DR PANTHER; PTHR10517:SF15; FOLATE RECEPTOR ALPHA; 1. DR Pfam; PF03024; Folate_rec; 1. DR Genevisible; P35846; MM. PE 1: Evidence at protein level; KW Cell membrane; Cytoplasmic vesicle; Disulfide bond; Endosome; KW Folate-binding; Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Receptor; KW Reference proteome; Secreted; Signal; Transport. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..232 FT /note="Folate receptor alpha" FT /id="PRO_0000008804" FT PROPEP 233..255 FT /note="Removed in mature form" FT /evidence="ECO:0000250|UniProtKB:P15328" FT /id="PRO_0000008805" FT BINDING 101 FT /ligand="folate" FT /ligand_id="ChEBI:CHEBI:62501" FT /evidence="ECO:0000250|UniProtKB:P15328" FT BINDING 105 FT /ligand="folate" FT /ligand_id="ChEBI:CHEBI:62501" FT /evidence="ECO:0000250|UniProtKB:P15328" FT BINDING 122..126 FT /ligand="folate" FT /ligand_id="ChEBI:CHEBI:62501" FT /evidence="ECO:0000250|UniProtKB:P15328" FT BINDING 155..160 FT /ligand="folate" FT /ligand_id="ChEBI:CHEBI:62501" FT /evidence="ECO:0000250|UniProtKB:P15328" FT BINDING 194 FT /ligand="folate" FT /ligand_id="ChEBI:CHEBI:62501" FT /evidence="ECO:0000250|UniProtKB:P15328" FT LIPID 232 FT /note="GPI-anchor amidated serine" FT /evidence="ECO:0000250|UniProtKB:P15328" FT CARBOHYD 67 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 159 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 199 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 35..63 FT /evidence="ECO:0000250|UniProtKB:P15328" FT DISULFID 55..103 FT /evidence="ECO:0000250|UniProtKB:P15328" FT DISULFID 64..107 FT /evidence="ECO:0000250|UniProtKB:P15328" FT DISULFID 87..173 FT /evidence="ECO:0000250|UniProtKB:P15328" FT DISULFID 94..144 FT /evidence="ECO:0000250|UniProtKB:P15328" FT DISULFID 133..207 FT /evidence="ECO:0000250|UniProtKB:P15328" FT DISULFID 137..187 FT /evidence="ECO:0000250|UniProtKB:P15328" FT DISULFID 150..167 FT /evidence="ECO:0000250|UniProtKB:P15328" FT CONFLICT 236 FT /note="F -> L (in Ref. 1; AAA37595)" FT /evidence="ECO:0000305" SQ SEQUENCE 255 AA; 29449 MW; A12ACA978BC8E134 CRC64; MAHLMTVQLL LLVMWMAECA QSRATRARTE LLNVCMDAKH HKEKPGPEDN LHDQCSPWKT NSCCSTNTSQ EAHKDISYLY RFNWNHCGTM TSECKRHFIQ DTCLYECSPN LGPWIQQVDQ SWRKERILDV PLCKEDCQQW WEDCQSSFTC KSNWHKGWNW SSGHNECPVG ASCHPFTFYF PTSAALCEEI WSHSYKLSNY SRGSGRCIQM WFDPAQGNPN EEVARFYAEA MSGAGFHGTW PLLCSLSLVL LWVIS //