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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)DescriptionActionsGraphical viewLength
Binding sitei97FolateCombined sources1
Binding sitei101FolateCombined sources1
Binding sitei190FolateCombined sources1

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

  • 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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165457-MONOMER.

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

DisGeNETi2350.
OpenTargetsiENSG00000165457.
PharmGKBiPA28209.

Chemistry databases

ChEMBLiCHEMBL5064.
DrugBankiDB00158. Folic Acid.

Polymorphism and mutation databases

BioMutaiFOLR2.
DMDMi116241366.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Add BLAST16
ChainiPRO_000000880617 – 230Folate receptor betaAdd BLAST214
PropeptideiPRO_0000008807231 – 255Removed in mature formAdd BLAST25

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
Glycosylationi115N-linked (GlcNAc...)Combined sources1
Disulfide bondi129 ↔ 203Combined sources1 Publication
Disulfide bondi133 ↔ 183Combined sources1 Publication
Disulfide bondi146 ↔ 163Combined sources1 Publication
Glycosylationi195N-linked (GlcNAc...)Combined sources1 Publication1
Lipidationi230GPI-anchor amidated asparagine1 Publication1

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiP14207.
PeptideAtlasiP14207.
PRIDEiP14207.

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

BgeeiENSG00000165457.
CleanExiHS_FOLR2.
ExpressionAtlasiP14207. baseline and differential.
GenevisibleiP14207. HS.

Organism-specific databases

HPAiCAB022164.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000298223.

Chemistry databases

BindingDBiP14207.

Structurei

Secondary structure

1255
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 27Combined sources4
Beta strandi33 – 36Combined sources4
Helixi49 – 54Combined sources6
Beta strandi57 – 60Combined sources4
Helixi62 – 68Combined sources7
Beta strandi74 – 76Combined sources3
Turni80 – 83Combined sources4
Helixi88 – 103Combined sources16
Helixi108 – 110Combined sources3
Beta strandi111 – 116Combined sources6
Beta strandi119 – 123Combined sources5
Beta strandi126 – 128Combined sources3
Helixi130 – 140Combined sources11
Beta strandi144 – 146Combined sources3
Beta strandi150 – 152Combined sources3
Helixi172 – 175Combined sources4
Helixi179 – 185Combined sources7
Turni186 – 188Combined sources3
Beta strandi189 – 191Combined sources3
Beta strandi200 – 204Combined sources5
Helixi216 – 223Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni118 – 122Folate bindingCombined sources5
Regioni151 – 156Folate bindingCombined sources6

Sequence similaritiesi

Belongs to the folate receptor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFFP. Eukaryota.
ENOG4111IU4. LUCA.
GeneTreeiENSGT00390000010470.
HOGENOMiHOG000006539.
HOVERGENiHBG039612.
InParanoidiP14207.
KOiK13649.
OMAiPVALCEG.
OrthoDBiEOG091G0GIA.
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)DescriptionActionsGraphical viewLength
Sequence conflicti103C → V AA sequence (PubMed:2561247).Curated1
Sequence conflicti111 – 112IQ → VR AA sequence (PubMed:2561247).Curated2
Sequence conflicti115N → D AA sequence (PubMed:2561247).Curated1
Sequence conflicti117S → T in AAA35821 (PubMed:2605182).Curated1
Sequence conflicti117S → T in AAA17370 (PubMed:8106441).Curated1
Sequence conflicti117S → T AA sequence (PubMed:2561247).Curated1
Sequence conflicti141H → L in AAA17370 (PubMed:8106441).Curated1
Sequence conflicti244S → R in AAA17370 (PubMed:8106441).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036408236H → N in a breast cancer sample; somatic mutation. 1 Publication1

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
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000298223.

Chemistry databases

BindingDBiP14207.
ChEMBLiCHEMBL5064.
DrugBankiDB00158. Folic Acid.

Polymorphism and mutation databases

BioMutaiFOLR2.
DMDMi116241366.

Proteomic databases

PaxDbiP14207.
PeptideAtlasiP14207.
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.
DisGeNETi2350.
GeneCardsiFOLR2.
HGNCiHGNC:3793. FOLR2.
HPAiCAB022164.
MIMi136425. gene.
neXtProtiNX_P14207.
OpenTargetsiENSG00000165457.
PharmGKBiPA28209.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFFP. Eukaryota.
ENOG4111IU4. LUCA.
GeneTreeiENSGT00390000010470.
HOGENOMiHOG000006539.
HOVERGENiHBG039612.
InParanoidiP14207.
KOiK13649.
OMAiPVALCEG.
OrthoDBiEOG091G0GIA.
PhylomeDBiP14207.
TreeFamiTF328532.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165457-MONOMER.

Miscellaneous databases

GeneWikiiFOLR2.
GenomeRNAii2350.
PROiP14207.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165457.
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...

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: November 2, 2016
This is version 148 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.