Target Information

Target General Information

Target ID

T89458 (Former ID: TTDR00963)

Target Name

HepG2 glucose transporter (SLC2A1)

Synonyms

Solute carrier family 2, facilitated glucose transporter member 1; HepG2 glucosetransporter; Glucose transporter type 1, erythrocyte/brain; GLUT1; GLUT-1

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Gene Name

SLC2A1

Target Type

Preclinical target

[1]

Disease

[+] 1 Target-related Diseases

Skin disease [ICD-11: EA00-EM0Z]

Function

Facilitative glucose transporter. This isoform may be responsible for constitutive or basal glucose uptake. Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses.

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BioChemical Class

Major facilitator

UniProt ID

GTR1_HUMAN

Sequence

MEPSSKKLTGRLMLAVGGAVLGSLQFGYNTGVINAPQKVIEEFYNQTWVHRYGESILPTT
LTTLWSLSVAIFSVGGMIGSFSVGLFVNRFGRRNSMLMMNLLAFVSAVLMGFSKLGKSFE
MLILGRFIIGVYCGLTTGFVPMYVGEVSPTALRGALGTLHQLGIVVGILIAQVFGLDSIM
GNKDLWPLLLSIIFIPALLQCIVLPFCPESPRFLLINRNEENRAKSVLKKLRGTADVTHD
LQEMKEESRQMMREKKVTILELFRSPAYRQPILIAVVLQLSQQLSGINAVFYYSTSIFEK
AGVQQPVYATIGSGIVNTAFTVVSLFVVERAGRRTLHLIGLAGMAGCAILMTIALALLEQ
LPWMSYLSIVAIFGFVAFFEVGPGPIPWFIVAELFSQGPRPAAIAVAGFSNWTSNFIVGM
CFQYVEQLCGPYVFIIFTVLLVLFFIFTYFKVPETKGRTFDEIASGFRQGGASQSDKTPE
ELFHPLGADSQV

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3D Structure

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PDB

ADReCS ID

BADD_A01328 ; BADD_A05962

HIT2.0 ID

T42PUG

Drugs and Modes of Action

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Preclinical Drug(s)

[+] 1 Preclinical Drugs

WZB-117

Drug Info

Preclinical

Skin fibrosis

[2]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

WZB-117

Drug Info

[3]

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: Preverex

Ligand Info

Structure Description

Human GLUT1 in complex with Cytochalasin B

PDB:5EQI

Method

X-ray diffraction

Resolution

3.00 Å

Mutation

[4]

PDB Sequence

TGRLMLAVGG

¹⁸

AVLGSLQFGY

²⁸

NTGVINAPQK

³⁸

VIEEFYNQTW

⁴⁸

VHRYGESILP

⁵⁸

TTLTTLWSLS

⁶⁸

VAIFSVGGMI

⁷⁸

GSFSVGLFVN

⁸⁸

RFGRRNSMLM

⁹⁸

MNLLAFVSAV

¹⁰⁸

LMGFSKLGKS

¹¹⁸

FEMLILGRFI

¹²⁸

IGVYCGLTTG

¹³⁸

FVPMYVGEVS

¹⁴⁸

PTALRGALGT

¹⁵⁸

LHQLGIVVGI

¹⁶⁸

LIAQVFGLDS

¹⁷⁸

IMGNKDLWPL

¹⁸⁸

LLSIIFIPAL

¹⁹⁸

LQCIVLPFCP

²⁰⁸

ESPRFLLINR

²¹⁸

NEENRAKSVL

²²⁸

KKLRGTADVT

²³⁸

HDLQEMKEES

²⁴⁸

RQMMREKKVT

²⁵⁸

ILELFRSPAY

²⁶⁸

RQPILIAVVL

²⁷⁸

QLSQQLSGIN

²⁸⁸

AVFYYSTSIF

²⁹⁸

EKAGVQQPVY

³⁰⁸

ATIGSGIVNT

³¹⁸

AFTVVSLFVV

³²⁸

ERAGRRTLHL

³³⁸

IGLAGMAGCA

³⁴⁸

ILMTIALALL

³⁵⁸

EQLPWMSYLS

³⁶⁸

IVAIFGFVAF

³⁷⁸

FEVGPGPIPW

³⁸⁸

FIVAELFSQG

³⁹⁸

PRPAAIAVAG

⁴⁰⁸

FSNWTSNFIV

⁴¹⁸

GMCFQYVEQL

⁴²⁸

CGPYVFIIFT

⁴³⁸

VLLVLFFIFT

⁴⁴⁸

YFKVPET

Residue

Distance (Å)

PHE26

2.986

THR30

4.736

SER80

2.728

GLY134

4.435

THR137

2.099

GLY138

4.505

PRO141

3.068

HIS160

3.015

GLN161

2.123

ILE164

2.530

VAL165

4.188

ILE168

3.740

GLN279

4.948

GLN282

2.039

GLN283

2.669

ILE287

3.044

ASN288

2.463

PHE291

3.195

Residue

Distance (Å)

TYR292

4.983

ASN317

4.790

THR321

4.080

PHE379

2.472

GLU380

3.226

PRO383

4.359

GLY384

2.306

PRO385

3.155

PRO387

4.889

TRP388

1.774

ILE404

4.789

ALA407

4.949

GLY408

2.416

PHE409

4.852

ASN411

2.528

TRP412

2.306

ASN415

2.526

Ligand Name: B-Nonylglucoside

Ligand Info

Structure Description

Crystal structure of human sugar transporter GLUT1 (SLC2A1) in the inward conformation

PDB:6THA

Method

X-ray diffraction

Resolution

2.40 Å

Mutation

[5]

PDB Sequence

LTGRLMLAVG

¹⁷

GAVLGSLQFG

²⁷

YNTGVINAPQ

³⁷

KVIEEFYNQT

⁴⁷

WVHRYGESIL

⁵⁷

PTTLTTLWSL

⁶⁷

SVAIFSVGGM

⁷⁷

IGSFSVGLFV

⁸⁷

NRFGRRNSML

⁹⁷

MMNLLAFVSA

¹⁰⁷

VLMGFSKLGK

¹¹⁷

SFEMLILGRF

¹²⁷

IIGVYCGLTT

¹³⁷

GFVPMYVGEV

¹⁴⁷

SPTALRGALG

¹⁵⁷

TLHQLGIVVG

¹⁶⁷

ILIAQVFGLD

¹⁷⁷

SIMGNKDLWP

¹⁸⁷

LLLSIIFIPA

¹⁹⁷

LLQCIVLPFC

²⁰⁷

PESPRFLLIN

²¹⁷

RNEENRAKSV

²²⁷

LKKLRGTADV

²³⁷

THDLQEMKEE

²⁴⁷

SRQMMREKKV

²⁵⁷

TILELFRSPA

²⁶⁷

YRQPILIAVV

²⁷⁷

LQLSQQLSGI

²⁸⁷

NAVFYYSTSI

²⁹⁷

FEKAGVQQPV

³⁰⁷

YATIGSGIVN

³¹⁷

TAFTVVSLFV

³²⁷

VERAGRRTLH

³³⁷

LIGLAGMAGC

³⁴⁷

AILMTIALAL

³⁵⁷

LEQLPWMSYL

³⁶⁷

SIVAIFGFVA

³⁷⁷

FFEVGPGPIP

³⁸⁷

WFIVAELFSQ

³⁹⁷

GPRPAAIAVA

⁴⁰⁷

GFSNWTSNFI

⁴¹⁷

VGMCFQYVEQ

⁴²⁷

LCGPYVFIIF

⁴³⁷

TVLLVLFFIF

⁴⁴⁷

TYFKVPET

Residue

Distance (Å)

THR30

3.546

ARG93

3.152

ASN94

3.162

LEU97

4.234

MET98

4.160

PRO141

3.821

GLY157

4.438

HIS160

4.032

GLN161

3.295

ILE164

4.681

VAL165

3.720

ILE168

3.738

GLU209

2.574

LEU214

4.590

ARG218

2.773

Residue

Distance (Å)

ARG223

2.605

GLN282

3.198

GLN283

3.059

ILE287

4.724

ASN288

2.740

PHE291

3.609

ASN317

2.903

PHE379

3.607

GLU380

2.851

GLY384

3.717

PRO385

3.636

TRP388

4.181

ASN411

4.370

ASN415

3.887

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Click to View More Binding Site Information of This Target with Different Ligands

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). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

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).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Organic cation transporter 3 (OCT3)	PF07690	23.744 (104/438)	1.33E-08
Solute carrier family 22 member 7 (SLC22A7)	PF07690	24.021 (92/383)	1.45E-06


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
HIF-1 signaling pathway	hsa04066	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Insulin secretion	hsa04911	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Thyroid hormone signaling pathway	hsa04919	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Adipocytokine signaling pathway	hsa04920	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Glucagon signaling pathway	hsa04922	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Bile secretion	hsa04976	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	2.02E-04
Closeness centrality	1.70E-01	Radiality	1.27E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	3.50E+00	Topological coefficient	5.00E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

References

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REF 1

GLUT1 messenger RNA and protein induction relates to the malignant transformation of cervical cancer. Am J Clin Pathol. 2003 Nov;120(5):691-8.

REF 2

Targeting metabolic dysregulation for fibrosis therapy. Nat Rev Drug Discov. 2020 Jan;19(1):57-75.

REF 3

Quercetin inhibits glucose transport by binding to an exofacial site on GLUT1. Biochimie. 2018 Aug;151:107-114.

REF 4

Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides. Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4711-6.

REF 5

Structural comparison of GLUT1 to GLUT3 reveal transport regulation mechanism in sugar porter family. Life Sci Alliance. 2021 Feb 3;4(4):e202000858.

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