FOLR1_MOUSE
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 03-AUG-2022, entry version 146.
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}.
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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 GlyGen; P35846; 3 sites.
DR PhosphoSitePlus; P35846; -.
DR jPOST; P35846; -.
DR PaxDb; P35846; -.
DR PeptideAtlas; P35846; -.
DR PRIDE; P35846; -.
DR ProteomicsDB; 267613; -.
DR Antibodypedia; 16919; 433 antibodies from 37 providers.
DR DNASU; 14275; -.
DR Ensembl; ENSMUST00000106981; ENSMUSP00000102594; ENSMUSG00000001827.
DR Ensembl; ENSMUST00000106982; ENSMUSP00000102595; ENSMUSG00000001827.
DR Ensembl; ENSMUST00000106983; ENSMUSP00000102596; ENSMUSG00000001827.
DR Ensembl; ENSMUST00000106985; ENSMUSP00000102598; ENSMUSG00000001827.
DR Ensembl; ENSMUST00000106986; ENSMUSP00000102599; ENSMUSG00000001827.
DR GeneID; 14275; -.
DR KEGG; mmu:14275; -.
DR UCSC; uc009ipm.1; mouse.
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; 1224404at2759; -.
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; 2 hits in 74 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 150 other tissues.
DR ExpressionAtlas; P35846; baseline and differential.
DR Genevisible; P35846; MM.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISO:MGI.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005903; C:brush border; 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: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:1904447; P:folate import across plasma membrane; IEA:InterPro.
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 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 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
