P15328 (FOLR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	FOLR1
Synonyms:	FOLR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	257 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Secreted Probable Ref.14 Ref.17.
Tissue specificity	Exclusively expressed in tissues of epithelial origin. Expression is increased in malignant tissues. Expressed in kidney, lung and cerebellum. Ref.6
Post-translational modification	Eight disulfide bonds are present Probable. 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.
Involvement in disease	Neurodegeneration due to cerebral folate transport deficiency (NCFTD) [MIM:613068]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the folate receptor family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Disease	Neurodegeneration
Domain	Signal
Ligand	Folate-binding
Molecular function	Receptor
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW folic acid metabolic process Inferred from electronic annotation. Source: Compara folic acid transport Traceable author statement PubMed 9545095. Source: ProtInc receptor-mediated endocytosis Traceable author statement PubMed 9545095. Source: ProtInc
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement PubMed 10633085. Source: ProtInc
Molecular_function	folic acid binding Non-traceable author statement Ref.4. Source: UniProtKB receptor activity Traceable author statement PubMed 10633085. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 234	210	Folate receptor alpha		PRO_0000008802
	Propeptide	235 – 257	23	Removed in mature form		PRO_0000008803
Amino acid modifications
	Lipidation	234	1	GPI-anchor amidated serine Ref.14 Ref.15 Ref.16 Ref.17
	Glycosylation	69	1	N-linked (GlcNAc...) By similarity
	Glycosylation	161	1	N-linked (GlcNAc...) Ref.18
	Glycosylation	201	1	N-linked (GlcNAc...) Ref.18
Natural variations
	Natural variant	28	1	W → R. Corresponds to variant rs7928649 [ dbSNP | Ensembl ].		VAR_059284
	Natural variant	160	1	W → C. Corresponds to variant rs1801932 [ dbSNP | Ensembl ].		VAR_011963
Experimental info
	Sequence conflict	180	1	F → L in BAD97247. Ref.9
	Sequence conflict	184	1	T → S in AAA74896. Ref.12

Sequences

	Sequence		Length	Mass (Da)
	P15328 [UniParc]. Last modified June 1, 1994. Version 3. Checksum: D458D8BB047C96A6	FASTA	257	29,819
	10 20 30 40 50 60 MAQRMTTQLL LLLVWVAVVG EAQTRIAWAR TELLNVCMNA KHHKEKPGPE DKLHEQCRPW 70 80 90 100 110 120 RKNACCSTNT SQEAHKDVSY LYRFNWNHCG EMAPACKRHF IQDTCLYECS PNLGPWIQQV 130 140 150 160 170 180 DQSWRKERVL NVPLCKEDCE QWWEDCRTSY TCKSNWHKGW NWTSGFNKCA VGAACQPFHF 190 200 210 220 230 240 YFPTPTVLCN EIWTHSYKVS NYSRGSGRCI QMWFDPAQGN PNEEVARFYA AAMSGAGPWA 250 AWPFLLSLAL MLLWLLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of the human folate-binding protein cDNA from placenta and malignant tissue culture (KB) cells." Elwood P.C. J. Biol. Chem. 264:14893-14901(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complementary DNA for the folate binding protein correctly predicts anchoring to the membrane by glycosyl-phosphatidylinositol." Lacey S.W., Sanders J.M., Rothberg K.G., Anderson R.G.W., Kamen B.A. J. Clin. Invest. 84:715-720(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Folate-binding protein is a marker for ovarian cancer." Campbell I.G., Jones T.A., Foulkes W.D., Trowsdale J. Cancer Res. 51:5329-5338(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovary.
[4]	"Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein." Coney L.R., Tomassetti A., Carayannopoulos L., Frasca V., Kamen B.A., Colnaghi M.I., Zurawski V.R. Jr. Cancer Res. 51:6125-6132(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-56. Tissue: Ovarian carcinoma.
[5]	"Genomic organization of the gene and a related pseudogene for a human folate binding protein." Sadasivan E., Cedeno M., Rothenberg S.P. Biochim. Biophys. Acta 1131:91-94(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"The divergent 5' termini of the alpha human folate receptor (hFR) mRNAs originate from two tissue-specific promoters and alternative splicing: characterization of the alpha hFR gene structure." Elwood P.C., Nachmanoff K., Saikawa Y., Page S.T., Pacheco P., Roberts S., Chung K.-N. Biochemistry 36:1467-1478(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 1-56, TISSUE SPECIFICITY. Tissue: Lymphocyte.
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	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: Kidney proximal tubule.
[10]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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: Placenta.
[12]	"The complete amino acid sequence of a human folate binding protein from KB cells determined from the cDNA." Sadasivan E., Rothenberg S.P. J. Biol. Chem. 264:5806-5811(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 24-249.
[13]	"Purified membrane and soluble folate binding proteins from cultured KB cells have similar amino acid compositions and molecular weights but differ in fatty acid acylation." Luhrs C.A., Pitiranggon P., da Costa M., Rothenberg S.P., Slomiany B.L., Brink L., Tous G.I., Stein S. Proc. Natl. Acad. Sci. U.S.A. 84:6546-6549(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-43.
[14]	"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 SER-234.
[15]	"Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins." Elortza F., Nuehse T.S., Foster L.J., Stensballe A., Peck S.C., Jensen O.N. Mol. Cell. Proteomics 2:1261-1270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment." Elortza F., Mohammed S., Bunkenborg J., Foster L.J., Nuehse T.S., Brodbeck U., Peck S.C., Jensen O.N. J. Proteome Res. 5:935-943(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Computational approach for identification and characterization of GPI-anchored peptides in proteomics experiments." Omaetxebarria M.J., Elortza F., Rodriguez-Suarez E., Aloria K., Arizmendi J.M., Jensen O.N., Matthiesen R. Proteomics 7:1951-1960(2007) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR AT SER-234, MASS SPECTROMETRY.
[18]	"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry." Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F. Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-161 AND ASN-201, MASS SPECTROMETRY. Tissue: Milk.
[19]	"Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism." Steinfeld R., Grapp M., Kraetzner R., Dreha-Kulaczewski S., Helms G., Dechent P., Wevers R., Grosso S., Gaertner J. Am. J. Hum. Genet. 85:354-363(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN NEURODEGENERATION DUE TO CEREBRAL FOLATE TRANSPORT DEFICIENCY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00441498.
PIR	A45753. A44904.
RefSeq	NP_000793.1. NM_000802.3. NP_057936.1. NM_016724.2. NP_057937.1. NM_016725.2. NP_057941.1. NM_016729.2.
UniGene	Hs.73769.
3D structure databases
ProteinModelPortal	P15328.
ModBase	Search...
Protein-protein interaction databases
IntAct	P15328. 11 interactions.
STRING	9606.ENSP00000308137.
Protein family/group databases
TCDB	9.B.92.1.1. folate receptor (FR) family.
Polymorphism databases
DMDM	544337.
Proteomic databases
PaxDb	P15328.
PeptideAtlas	P15328.
PRIDE	P15328.
Protocols and materials databases
DNASU	2348.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000312293; ENSP00000308137; ENSG00000110195. ENST00000393676; ENSP00000377281; ENSG00000110195. ENST00000393679; ENSP00000377284; ENSG00000110195. ENST00000393681; ENSP00000377286; ENSG00000110195.
GeneID	2348.
KEGG	hsa:2348.
UCSC	uc001orz.2. human.
Organism-specific databases
CTD	2348.
GeneCards	GC11P071900.
HGNC	HGNC:3791. FOLR1.
MIM	136430. gene. 613068. phenotype.
neXtProt	NX_P15328.
Orphanet	217382. Neurodegenerative syndrome due to cerebral folate transport deficiency.
PharmGKB	PA28207.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG26606.
HOGENOM	HOG000006539.
HOVERGEN	HBG039612.
InParanoid	P15328.
KO	K13649.
OMA	NWTSGFN.
OrthoDB	EOG4HDSV6.
PhylomeDB	P15328.
Gene expression databases
ArrayExpress	P15328.
Bgee	P15328.
CleanEx	HS_FOLR1.
Genevestigator	P15328.
GermOnline	ENSG00000110195. Homo sapiens.
Family and domain databases
InterPro	IPR004269. Folate_rcpt. IPR018143. Folate_rcpt-like. [Graphical view]
PANTHER	PTHR10517. PTHR10517. 1 hit.
Pfam	PF03024. Folate_rec. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P15328.
ChEMBL	CHEMBL2121.
GenomeRNAi	2348.
NextBio	9519.
SOURCE	Search...

Entry information

Entry name

FOLR1_HUMAN

Accession

Primary (citable) accession number: P15328
Secondary accession number(s): Q53EW2 , Q6FGT8, Q6LC90, Q9UCT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	June 1, 1994
Last modified:	May 1, 2013
This is version 127 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.