Target Information

Target General Information

Target ID

T82297 (Former ID: TTDR00687)

Target Name

Folate receptor beta (FOLR2)

Synonyms

Placental folate-binding protein; Folate receptor, fetal/placental; Folate receptor type-beta; Folate receptor 2; FR-beta; FOLR2

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Gene Name

FOLR2

Target Type

Literature-reported target

[1]

Function

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.

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BioChemical Class

Folate receptor

UniProt ID

FOLR2_HUMAN

Sequence

MVWKWMPLLLLLVCVATMCSAQDRTDLLNVCMDAKHHKTKPGPEDKLHDQCSPWKKNACC
TASTSQELHKDTSRLYNFNWDHCGKMEPACKRHFIQDTCLYECSPNLGPWIQQVNQSWRK
ERFLDVPLCKEDCQRWWEDCHTSHTCKSNWHRGWDWTSGVNKCPAGALCRTFESYFPTPA
ALCEGLWSHSYKVSNYSRGSGRCIQMWFDSAQGNPNEEVARFYAAAMHVNAGEMLHGTGG
LLLSLALMLQLWLLG

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3D Structure

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PDB

HIT2.0 ID

T05SMP

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Methotrexate

Ligand Info

Structure Description

Human folate receptor beta (FOLR2) in complex with the antifolate methotrexate

PDB:4KN0

Method

X-ray diffraction

Resolution

2.10 Å

Mutation

[2]

PDB Sequence

RTDLLNVCMD

³³

AKHHKTKPGP

⁴³

EDKLHDQCSP

⁵³

WKKNACCTAS

⁶³

TSQELHKDTS

⁷³

RLYNFNWDHC

⁸³

GKMEPACKRH

⁹³

FIQDTCLYEC

¹⁰³

SPNLGPWIQQ

¹¹³

VNQSWRKERF

¹²³

LDVPLCKEDC

¹³³

QRWWEDCHTS

¹⁴³

HTCKSNWHRG

¹⁵³

WDWTSGVNKC

¹⁶³

PAGALCRTFE

¹⁷³

SYFPTPAALC

¹⁸³

EGLWSHSYKV

¹⁹³

SNYSRGSGRC

²⁰³

IQMWFDSAQG

²¹³

NPNEEVARFY

²²³

AAAMH

Residue

Distance (Å)

TYR76

3.359

PHE78

3.441

ASP97

3.079

THR98

4.183

TYR101

3.254

GLN116

2.712

SER117

4.930

TRP118

3.041

ARG119

3.323

Residue

Distance (Å)

PHE123

4.658

TRP150

3.703

HIS151

2.832

ARG152

3.494

GLY153

2.768

TRP154

3.029

TRP156

2.889

TRP187

3.128

SER190

2.991

Ligand Name: Folic acid

Ligand Info

Structure Description

Human folate receptor beta (FOLR2) in complex with the folate

PDB:4KMZ

Method

X-ray diffraction

Resolution

2.30 Å

Mutation

[2]

PDB Sequence

TDLLNVCMDA

³⁴

KHHKTKPGPE

⁴⁴

DKLHDQCSPW

⁵⁴

KKNACCTAST

⁶⁴

SQELHKDTSR

⁷⁴

LYNFNWDHCG

⁸⁴

KMEPACKRHF

⁹⁴

IQDTCLYECS

¹⁰⁴

PNLGPWIQQV

¹¹⁴

NQSWRKERFL

¹²⁴

DVPLCKEDCQ

¹³⁴

RWWEDCHTSH

¹⁴⁴

TCKSNWHRGW

¹⁵⁴

DWTSGVNKCP

¹⁶⁴

AGALCRTFES

¹⁷⁴

YFPTPAALCE

¹⁸⁴

GLWSHSYKVS

¹⁹⁴

NYSRGSGRCI

²⁰⁴

QMWFDSAQGN

²¹⁴

PNEEVARFYA

²²⁴

AAM

Residue

Distance (Å)

TYR76

3.517

PHE78

3.953

ASP97

2.797

THR98

4.368

TYR101

3.437

GLN116

3.797

SER117

3.556

TRP118

3.219

ARG119

2.905

ARG122

3.788

Residue

Distance (Å)

PHE123

3.823

TRP150

3.434

HIS151

2.758

ARG152

3.337

GLY153

2.941

TRP154

3.121

TRP156

2.626

TRP187

3.180

SER190

2.641

TYR191

3.474

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Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Endocytosis	hsa04144	Affiliated Target
Class: Cellular Processes => Transport and catabolism	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

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References

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REF 1

Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta-targeted liposomal doxorubicin combined with receptor induct... Blood. 2002 Jul 15;100(2):594-602.

REF 2

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15180-8.

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