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Protein

Folate receptor alpha

Gene

FOLR1

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. Required for normal embryonic development and normal cell proliferation.5 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei103 – 1031Folate1 Publication
Binding sitei107 – 1071Folate1 Publication
Binding sitei196 – 1961Folate1 Publication

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
  • receptor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transport

Keywords - Ligandi

Folate-binding

Enzyme and pathway databases

ReactomeiR-HSA-204005. COPII (Coat Protein 2) Mediated Vesicle Transport.
R-HSA-5694530. Cargo concentration in the ER.
R-HSA-6807878. COPI-mediated anterograde transport.

Protein family/group databases

TCDBi9.B.92.1.1. the folate receptor (fr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Folate receptor alpha
Short name:
FR-alpha
Alternative name(s):
Adult folate-binding protein
Short name:
FBP
Folate receptor 1
Folate receptor, adult
KB cells FBP
Ovarian tumor-associated antigen MOv18
Gene namesi
Name:FOLR1
Synonyms:FOLR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:3791. FOLR1.

Subcellular locationi

GO - Cellular componenti

  • anchored component of external side of plasma membrane Source: UniProtKB
  • apical plasma membrane Source: BHF-UCL
  • basolateral plasma membrane Source: BHF-UCL
  • brush border membrane Source: Ensembl
  • cell surface Source: UniProtKB
  • clathrin-coated vesicle Source: UniProtKB-SubCell
  • endoplasmic reticulum-Golgi intermediate compartment membrane Source: Reactome
  • endoplasmic reticulum membrane Source: Reactome
  • endosome Source: UniProtKB-SubCell
  • ER to Golgi transport vesicle membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • Golgi membrane Source: Reactome
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: ProtInc
  • nucleus Source: CACAO
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endosome, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Neurodegeneration due to cerebral folate transport deficiency (NCFTD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy and leukodystrophy.
See also OMIM:613068

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi82 – 821Y → A: Slightly reduced affinity for folate. 1 Publication
Mutagenesisi103 – 1031D → A: Strongly reduced affinity for folate. 1 Publication
Mutagenesisi107 – 1071Y → A: Moderately reduced affinity for folate. 1 Publication
Mutagenesisi124 – 1241W → A: Moderately reduced affinity for folate. 1 Publication
Mutagenesisi125 – 1251R → A: Moderately reduced affinity for folate. 1 Publication
Mutagenesisi128 – 1281R → A: Moderately reduced affinity for folate. 1 Publication
Mutagenesisi157 – 1571H → A: Moderately reduced affinity for folate. 1 Publication
Mutagenesisi162 – 1621W → A: Moderately reduced affinity for folate. 1 Publication
Mutagenesisi196 – 1961S → A: Moderately reduced affinity for folate. 1 Publication

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

MalaCardsiFOLR1.
MIMi613068. phenotype.
Orphaneti217382. Neurodegenerative syndrome due to cerebral folate transport deficiency.
PharmGKBiPA28207.

Chemistry

ChEMBLiCHEMBL2121.
DrugBankiDB00563. Methotrexate.

Polymorphism and mutation databases

BioMutaiFOLR1.
DMDMi544337.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 234210Folate receptor alphaPRO_0000008802Add
BLAST
Propeptidei235 – 25723Removed in mature formPRO_0000008803Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi37 ↔ 65Combined sources2 Publications
Disulfide bondi57 ↔ 105Combined sources2 Publications
Disulfide bondi66 ↔ 109Combined sources2 Publications
Glycosylationi69 – 691N-linked (GlcNAc...)2 Publications
Disulfide bondi89 ↔ 175Combined sources2 Publications
Disulfide bondi96 ↔ 146Combined sources2 Publications
Disulfide bondi135 ↔ 209Combined sources2 Publications
Disulfide bondi139 ↔ 189Combined sources2 Publications
Disulfide bondi152 ↔ 169Combined sources2 Publications
Glycosylationi161 – 1611N-linked (GlcNAc...)3 Publications
Glycosylationi201 – 2011N-linked (GlcNAc...)3 Publications
Lipidationi234 – 2341GPI-anchor amidated serine2 Publications

Post-translational modificationi

The secreted form is derived from the membrane-bound form either by cleavage of the GPI anchor, or/and by proteolysis catalyzed by a metalloprotease.

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

EPDiP15328.
MaxQBiP15328.
PaxDbiP15328.
PeptideAtlasiP15328.
PRIDEiP15328.

Expressioni

Tissue specificityi

Primarily expressed in tissues of epithelial origin. Expression is increased in malignant tissues. Expressed in kidney, lung and cerebellum. Detected in placenta and thymus epithelium.3 Publications

Gene expression databases

BgeeiENSG00000110195.
CleanExiHS_FOLR1.
ExpressionAtlasiP15328. baseline and differential.
GenevisibleiP15328. HS.

Interactioni

Protein-protein interaction databases

BioGridi108631. 13 interactions.
IntActiP15328. 11 interactions.
STRINGi9606.ENSP00000308137.

Chemistry

BindingDBiP15328.

Structurei

Secondary structure

1
257
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi31 – 333Combined sources
Beta strandi48 – 503Combined sources
Turni53 – 564Combined sources
Helixi58 – 603Combined sources
Beta strandi63 – 675Combined sources
Helixi68 – 736Combined sources
Turni81 – 833Combined sources
Turni86 – 894Combined sources
Helixi94 – 10916Combined sources
Helixi114 – 1163Combined sources
Beta strandi117 – 1226Combined sources
Beta strandi124 – 1263Combined sources
Helixi136 – 14510Combined sources
Turni146 – 1483Combined sources
Beta strandi150 – 1523Combined sources
Beta strandi156 – 1583Combined sources
Helixi172 – 1743Combined sources
Helixi178 – 1814Combined sources
Helixi185 – 1917Combined sources
Turni192 – 1954Combined sources
Beta strandi206 – 2105Combined sources
Helixi216 – 2183Combined sources
Helixi222 – 23211Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KM6X-ray1.55A30-234[»]
4KM7X-ray1.80A/B28-234[»]
4KMXX-ray2.20A28-234[»]
4LRHX-ray2.80A/B/C/D/E/F/G/H23-235[»]
ProteinModelPortaliP15328.
SMRiP15328. Positions 30-233.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni124 – 1285Folate binding1 Publication
Regioni157 – 1626Folate binding1 Publication

Sequence similaritiesi

Belongs to the folate receptor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFFP. Eukaryota.
ENOG4111IU4. LUCA.
GeneTreeiENSGT00390000010470.
HOGENOMiHOG000006539.
HOVERGENiHBG039612.
InParanoidiP15328.
KOiK13649.
OMAiNWTSGFN.
OrthoDBiEOG091G0GIA.
PhylomeDBiP15328.
TreeFamiTF328532.

Family and domain databases

InterProiIPR004269. Folate_rcpt.
IPR018143. Folate_rcpt-like.
IPR032935. FOLR1.
[Graphical view]
PANTHERiPTHR10517. PTHR10517. 1 hit.
PTHR10517:SF15. PTHR10517:SF15. 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.

P15328-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQRMTTQLL LLLVWVAVVG EAQTRIAWAR TELLNVCMNA KHHKEKPGPE
60 70 80 90 100
DKLHEQCRPW RKNACCSTNT SQEAHKDVSY LYRFNWNHCG EMAPACKRHF
110 120 130 140 150
IQDTCLYECS PNLGPWIQQV DQSWRKERVL NVPLCKEDCE QWWEDCRTSY
160 170 180 190 200
TCKSNWHKGW NWTSGFNKCA VGAACQPFHF YFPTPTVLCN EIWTHSYKVS
210 220 230 240 250
NYSRGSGRCI QMWFDPAQGN PNEEVARFYA AAMSGAGPWA AWPFLLSLAL

MLLWLLS
Length:257
Mass (Da):29,819
Last modified:June 1, 1994 - v3
Checksum:iD458D8BB047C96A6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti180 – 1801F → L in BAD97247 (Ref. 9) Curated
Sequence conflicti184 – 1841T → S in AAA74896 (PubMed:2538429).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti28 – 281W → R.
Corresponds to variant rs7928649 [ dbSNP | Ensembl ].
VAR_059284
Natural varianti160 – 1601W → C.
Corresponds to variant rs1801932 [ dbSNP | Ensembl ].
VAR_011963

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05013 mRNA. Translation: AAA35823.1.
M28099 mRNA. Translation: AAA35822.1.
X62753 mRNA. Translation: CAA44610.1.
U20391 Genomic DNA. Translation: AAB05827.1.
U78793 mRNA. Translation: AAB39751.1.
U78794 mRNA. Translation: AAB39752.1.
BT007158 mRNA. Translation: AAP35822.1.
CR542019 mRNA. Translation: CAG46816.1.
AK223527 mRNA. Translation: BAD97247.1.
CH471076 Genomic DNA. Translation: EAW74848.1.
BC002947 mRNA. Translation: AAH02947.1.
M25317 mRNA. Translation: AAA74896.1.
CCDSiCCDS8211.1.
PIRiA44904. A45753.
RefSeqiNP_000793.1. NM_000802.3.
NP_057936.1. NM_016724.2.
NP_057937.1. NM_016725.2.
NP_057941.1. NM_016729.2.
UniGeneiHs.73769.

Genome annotation databases

EnsembliENST00000312293; ENSP00000308137; ENSG00000110195.
ENST00000393676; ENSP00000377281; ENSG00000110195.
ENST00000393679; ENSP00000377284; ENSG00000110195.
ENST00000393681; ENSP00000377286; ENSG00000110195.
GeneIDi2348.
KEGGihsa:2348.
UCSCiuc001orz.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05013 mRNA. Translation: AAA35823.1.
M28099 mRNA. Translation: AAA35822.1.
X62753 mRNA. Translation: CAA44610.1.
U20391 Genomic DNA. Translation: AAB05827.1.
U78793 mRNA. Translation: AAB39751.1.
U78794 mRNA. Translation: AAB39752.1.
BT007158 mRNA. Translation: AAP35822.1.
CR542019 mRNA. Translation: CAG46816.1.
AK223527 mRNA. Translation: BAD97247.1.
CH471076 Genomic DNA. Translation: EAW74848.1.
BC002947 mRNA. Translation: AAH02947.1.
M25317 mRNA. Translation: AAA74896.1.
CCDSiCCDS8211.1.
PIRiA44904. A45753.
RefSeqiNP_000793.1. NM_000802.3.
NP_057936.1. NM_016724.2.
NP_057937.1. NM_016725.2.
NP_057941.1. NM_016729.2.
UniGeneiHs.73769.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KM6X-ray1.55A30-234[»]
4KM7X-ray1.80A/B28-234[»]
4KMXX-ray2.20A28-234[»]
4LRHX-ray2.80A/B/C/D/E/F/G/H23-235[»]
ProteinModelPortaliP15328.
SMRiP15328. Positions 30-233.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108631. 13 interactions.
IntActiP15328. 11 interactions.
STRINGi9606.ENSP00000308137.

Chemistry

BindingDBiP15328.
ChEMBLiCHEMBL2121.
DrugBankiDB00563. Methotrexate.

Protein family/group databases

TCDBi9.B.92.1.1. the folate receptor (fr) family.

Polymorphism and mutation databases

BioMutaiFOLR1.
DMDMi544337.

Proteomic databases

EPDiP15328.
MaxQBiP15328.
PaxDbiP15328.
PeptideAtlasiP15328.
PRIDEiP15328.

Protocols and materials databases

DNASUi2348.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312293; ENSP00000308137; ENSG00000110195.
ENST00000393676; ENSP00000377281; ENSG00000110195.
ENST00000393679; ENSP00000377284; ENSG00000110195.
ENST00000393681; ENSP00000377286; ENSG00000110195.
GeneIDi2348.
KEGGihsa:2348.
UCSCiuc001orz.3. human.

Organism-specific databases

CTDi2348.
GeneCardsiFOLR1.
HGNCiHGNC:3791. FOLR1.
MalaCardsiFOLR1.
MIMi136430. gene.
613068. phenotype.
neXtProtiNX_P15328.
Orphaneti217382. Neurodegenerative syndrome due to cerebral folate transport deficiency.
PharmGKBiPA28207.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFFP. Eukaryota.
ENOG4111IU4. LUCA.
GeneTreeiENSGT00390000010470.
HOGENOMiHOG000006539.
HOVERGENiHBG039612.
InParanoidiP15328.
KOiK13649.
OMAiNWTSGFN.
OrthoDBiEOG091G0GIA.
PhylomeDBiP15328.
TreeFamiTF328532.

Enzyme and pathway databases

ReactomeiR-HSA-204005. COPII (Coat Protein 2) Mediated Vesicle Transport.
R-HSA-5694530. Cargo concentration in the ER.
R-HSA-6807878. COPI-mediated anterograde transport.

Miscellaneous databases

GeneWikiiFolate_receptor_1.
GenomeRNAii2348.
PROiP15328.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110195.
CleanExiHS_FOLR1.
ExpressionAtlasiP15328. baseline and differential.
GenevisibleiP15328. HS.

Family and domain databases

InterProiIPR004269. Folate_rcpt.
IPR018143. Folate_rcpt-like.
IPR032935. FOLR1.
[Graphical view]
PANTHERiPTHR10517. PTHR10517. 1 hit.
PTHR10517:SF15. PTHR10517:SF15. 1 hit.
PfamiPF03024. Folate_rec. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFOLR1_HUMAN
AccessioniPrimary (citable) accession number: P15328
Secondary accession number(s): Q53EW2
, Q6FGT8, Q6LC90, Q9UCT2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: June 1, 1994
Last modified: September 7, 2016
This is version 155 of the entry and version 3 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.