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Protein

Folate receptor beta

Gene

FOLR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei97 – 971FolateCombined sources
Binding sitei101 – 1011FolateCombined sources
Binding sitei190 – 1901FolateCombined sources

GO - Molecular functioni

  • drug binding Source: BHF-UCL
  • folic acid binding Source: UniProtKB
  • folic acid receptor activity Source: BHF-UCL
  • folic acid transporter activity Source: UniProtKB
  • methotrexate binding Source: BHF-UCL

GO - Biological processi

  • cellular response to folic acid Source: GOC
  • folic acid transport Source: UniProtKB
  • inflammatory response Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • receptor-mediated endocytosis Source: BHF-UCL
  • regulation of thymidylate synthase biosynthetic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transport

Keywords - Ligandi

Folate-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Folate receptor beta
Short name:
FR-beta
Alternative name(s):
Folate receptor 2
Folate receptor, fetal/placental
Placental folate-binding protein
Short name:
FBP
Gene namesi
Name:FOLR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:3793. FOLR2.

Subcellular locationi

GO - Cellular componenti

  • anchored component of external side of plasma membrane Source: UniProtKB
  • cell surface Source: BHF-UCL
  • extracellular region Source: UniProtKB-SubCell
  • membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28209.

Chemistry

ChEMBLiCHEMBL5064.
DrugBankiDB00158. Folic Acid.

Polymorphism and mutation databases

BioMutaiFOLR2.
DMDMi116241366.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616Add
BLAST
Chaini17 – 230214Folate receptor betaPRO_0000008806Add
BLAST
Propeptidei231 – 25525Removed in mature formPRO_0000008807Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi31 ↔ 59Combined sources1 Publication
Disulfide bondi51 ↔ 99Combined sources1 Publication
Disulfide bondi60 ↔ 103Combined sources1 Publication
Disulfide bondi83 ↔ 169Combined sources1 Publication
Disulfide bondi90 ↔ 140Combined sources1 Publication
Glycosylationi115 – 1151N-linked (GlcNAc...)Combined sources
Disulfide bondi129 ↔ 203Combined sources1 Publication
Disulfide bondi133 ↔ 183Combined sources1 Publication
Disulfide bondi146 ↔ 163Combined sources1 Publication
Glycosylationi195 – 1951N-linked (GlcNAc...)Combined sources1 Publication
Lipidationi230 – 2301GPI-anchor amidated asparagine1 Publication

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiP14207.
PRIDEiP14207.

PTM databases

PhosphoSiteiP14207.

Expressioni

Tissue specificityi

Expressed in placenta and hematopoietic cells. Expression is increased in malignant tissues.2 Publications

Inductioni

Up-regulated by retinoic acid.1 Publication

Gene expression databases

BgeeiP14207.
CleanExiHS_FOLR2.
ExpressionAtlasiP14207. baseline and differential.
GenevisibleiP14207. HS.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000298223.

Chemistry

BindingDBiP14207.

Structurei

Secondary structure

1
255
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi24 – 274Combined sources
Beta strandi33 – 364Combined sources
Helixi49 – 546Combined sources
Beta strandi57 – 604Combined sources
Helixi62 – 687Combined sources
Beta strandi74 – 763Combined sources
Turni80 – 834Combined sources
Helixi88 – 10316Combined sources
Helixi108 – 1103Combined sources
Beta strandi111 – 1166Combined sources
Beta strandi119 – 1235Combined sources
Beta strandi126 – 1283Combined sources
Helixi130 – 14011Combined sources
Beta strandi144 – 1463Combined sources
Beta strandi150 – 1523Combined sources
Helixi172 – 1754Combined sources
Helixi179 – 1857Combined sources
Turni186 – 1883Combined sources
Beta strandi189 – 1913Combined sources
Beta strandi200 – 2045Combined sources
Helixi216 – 2238Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KMYX-ray1.80A24-228[»]
4KMZX-ray2.30A24-228[»]
4KN0X-ray2.10A24-228[»]
4KN1X-ray2.30A24-228[»]
4KN2X-ray2.60A/B/C24-227[»]
ProteinModelPortaliP14207.
SMRiP14207. Positions 24-228.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni118 – 1225Folate bindingCombined sources
Regioni151 – 1566Folate bindingCombined sources

Sequence similaritiesi

Belongs to the folate receptor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFFP. Eukaryota.
ENOG4111IU4. LUCA.
GeneTreeiENSGT00390000010470.
HOGENOMiHOG000006539.
HOVERGENiHBG039612.
InParanoidiP14207.
KOiK13649.
OMAiPVALCEG.
PhylomeDBiP14207.
TreeFamiTF328532.

Family and domain databases

InterProiIPR004269. Folate_rcpt.
IPR018143. Folate_rcpt-like.
IPR032937. FOLR2.
[Graphical view]
PANTHERiPTHR10517. PTHR10517. 1 hit.
PTHR10517:SF8. PTHR10517:SF8. 1 hit.
PfamiPF03024. Folate_rec. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P14207-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVWKWMPLLL LLVCVATMCS AQDRTDLLNV CMDAKHHKTK PGPEDKLHDQ
60 70 80 90 100
CSPWKKNACC TASTSQELHK DTSRLYNFNW DHCGKMEPAC KRHFIQDTCL
110 120 130 140 150
YECSPNLGPW IQQVNQSWRK ERFLDVPLCK EDCQRWWEDC HTSHTCKSNW
160 170 180 190 200
HRGWDWTSGV NKCPAGALCR TFESYFPTPA ALCEGLWSHS YKVSNYSRGS
210 220 230 240 250
GRCIQMWFDS AQGNPNEEVA RFYAAAMHVN AGEMLHGTGG LLLSLALMLQ

LWLLG
Length:255
Mass (Da):29,280
Last modified:October 17, 2006 - v4
Checksum:iF585715CF5631C98
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti103 – 1031C → V AA sequence (PubMed:2561247).Curated
Sequence conflicti111 – 1122IQ → VR AA sequence (PubMed:2561247).Curated
Sequence conflicti115 – 1151N → D AA sequence (PubMed:2561247).Curated
Sequence conflicti117 – 1171S → T in AAA35821 (PubMed:2605182).Curated
Sequence conflicti117 – 1171S → T in AAA17370 (PubMed:8106441).Curated
Sequence conflicti117 – 1171S → T AA sequence (PubMed:2561247).Curated
Sequence conflicti141 – 1411H → L in AAA17370 (PubMed:8106441).Curated
Sequence conflicti244 – 2441S → R in AAA17370 (PubMed:8106441).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti236 – 2361H → N in a breast cancer sample; somatic mutation. 1 Publication
VAR_036408

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X69516 Genomic DNA. Translation: CAA49267.1.
J02876 mRNA. Translation: AAA35821.1.
U02714, U02716 Genomic DNA. Translation: AAA17370.1.
AK222643 mRNA. Translation: BAD96363.1.
BC058036 mRNA. Translation: AAH58036.1.
BC027894 mRNA. Translation: AAH27894.1.
CCDSiCCDS8212.1.
PIRiA53315. A33417.
RefSeqiNP_000794.3. NM_000803.4.
NP_001107006.1. NM_001113534.1.
NP_001107007.1. NM_001113535.1.
NP_001107008.1. NM_001113536.1.
UniGeneiHs.433159.

Genome annotation databases

EnsembliENST00000298223; ENSP00000298223; ENSG00000165457.
GeneIDi2350.
KEGGihsa:2350.
UCSCiuc001ose.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X69516 Genomic DNA. Translation: CAA49267.1.
J02876 mRNA. Translation: AAA35821.1.
U02714, U02716 Genomic DNA. Translation: AAA17370.1.
AK222643 mRNA. Translation: BAD96363.1.
BC058036 mRNA. Translation: AAH58036.1.
BC027894 mRNA. Translation: AAH27894.1.
CCDSiCCDS8212.1.
PIRiA53315. A33417.
RefSeqiNP_000794.3. NM_000803.4.
NP_001107006.1. NM_001113534.1.
NP_001107007.1. NM_001113535.1.
NP_001107008.1. NM_001113536.1.
UniGeneiHs.433159.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KMYX-ray1.80A24-228[»]
4KMZX-ray2.30A24-228[»]
4KN0X-ray2.10A24-228[»]
4KN1X-ray2.30A24-228[»]
4KN2X-ray2.60A/B/C24-227[»]
ProteinModelPortaliP14207.
SMRiP14207. Positions 24-228.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000298223.

Chemistry

BindingDBiP14207.
ChEMBLiCHEMBL5064.
DrugBankiDB00158. Folic Acid.

PTM databases

PhosphoSiteiP14207.

Polymorphism and mutation databases

BioMutaiFOLR2.
DMDMi116241366.

Proteomic databases

PaxDbiP14207.
PRIDEiP14207.

Protocols and materials databases

DNASUi2350.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000298223; ENSP00000298223; ENSG00000165457.
GeneIDi2350.
KEGGihsa:2350.
UCSCiuc001ose.5. human.

Organism-specific databases

CTDi2350.
GeneCardsiFOLR2.
HGNCiHGNC:3793. FOLR2.
MIMi136425. gene.
neXtProtiNX_P14207.
PharmGKBiPA28209.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFFP. Eukaryota.
ENOG4111IU4. LUCA.
GeneTreeiENSGT00390000010470.
HOGENOMiHOG000006539.
HOVERGENiHBG039612.
InParanoidiP14207.
KOiK13649.
OMAiPVALCEG.
PhylomeDBiP14207.
TreeFamiTF328532.

Miscellaneous databases

GeneWikiiFOLR2.
GenomeRNAii2350.
PROiP14207.
SOURCEiSearch...

Gene expression databases

BgeeiP14207.
CleanExiHS_FOLR2.
ExpressionAtlasiP14207. baseline and differential.
GenevisibleiP14207. HS.

Family and domain databases

InterProiIPR004269. Folate_rcpt.
IPR018143. Folate_rcpt-like.
IPR032937. FOLR2.
[Graphical view]
PANTHERiPTHR10517. PTHR10517. 1 hit.
PTHR10517:SF8. PTHR10517:SF8. 1 hit.
PfamiPF03024. Folate_rec. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Expression of the human placental folate receptor transcript is regulated in human tissues. Organization and full nucleotide sequence of the gene."
    Page S.T., Owen W.C., Price K., Elwood P.C.
    J. Mol. Biol. 229:1175-1183(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
  2. "Homologous membrane folate binding proteins in human placenta: cloning and sequence of a cDNA."
    Ratnam M., Marquardt H., Duhring J.L., Freisheim J.H.
    Biochemistry 28:8249-8254(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, TISSUE SPECIFICITY, GLYCOSYLATION, SUBCELLULAR LOCATION.
    Tissue: Placenta.
  3. "Characterization of the gene encoding a folate-binding protein expressed in human placenta. Identification of promoter activity in a G-rich SP1 site linked with the tandemly repeated GGAAG motif for the ets encoded GA-binding protein."
    Sadasivan E., Cedeno M.M., Rothenberg S.P.
    J. Biol. Chem. 269:4725-4735(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  4. Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
    Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Cerebellum.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pancreas and Placenta.
  6. "Folate coenzyme and antifolate transport proteins in normal and neoplastic cells."
    Freisheim J.H., Price E.M., Ratnam M.
    Adv. Enzyme Regul. 29:13-26(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 68-86; 102-120 AND 173-184.
  7. "Studies of the role of a particulate folate-binding protein in the uptake of 5-methyltetrahydrofolate by cultured human KB cells."
    Antony A.C., Kane M.A., Portillo R.M., Elwood P.C., Kolhouse J.F.
    J. Biol. Chem. 260:14911-14917(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  8. "Preferred sites of glycosylphosphatidylinositol modification in folate receptors and constraints in the primary structure of the hydrophobic portion of the signal."
    Yan W., Ratnam M.
    Biochemistry 34:14594-14600(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: GPI-ANCHOR AT ASN-230.
  9. "Proteolysis of the carboxyl-terminal GPI signal independent of GPI modification as a mechanism for selective protein secretion."
    Wang J., Shen F., Yan W., Wu M., Ratnam M.
    Biochemistry 36:14583-14592(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING.
  10. "All-trans retinoic acid is capable of inducing folate receptor beta expression in KG-1 cells."
    Xu Y., Wang T., Tang R., Tang S.
    Tumor Biol. 31:589-595(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY RETINOIC ACID.
  11. "Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition."
    Wibowo A.S., Singh M., Reeder K.M., Carter J.J., Kovach A.R., Meng W., Ratnam M., Zhang F., Dann C.E. III
    Proc. Natl. Acad. Sci. U.S.A. 110:15180-15188(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 24-228 IN COMPLEXES WITH FOLATE AND THE ANTIFOLATES METHOTREXATE; AMINOPTERIN AND PEMETREXED, FUNCTION, GLYCOSYLATION AT ASN-195, DISULFIDE BONDS.
  12. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-236.

Entry informationi

Entry nameiFOLR2_HUMAN
AccessioniPrimary (citable) accession number: P14207
Secondary accession number(s): Q05CA5, Q6GTE8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: October 17, 2006
Last modified: June 8, 2016
This is version 145 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.