Target Information

Target General Information

Target ID

T99189

Target Name

Sodium/bile acid cotransporter (SLC10A1)

Synonyms

Solute carrier family 10 member 1; Sodium/taurocholate cotransporting polypeptide; Na(+)/taurocholate transport protein; Na(+)/bile acid cotransporter; Cell growth-inhibiting gene 29 protein

Click to Show/Hide

Gene Name

SLC10A1

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Hepatitis virus infection [ICD-11: 1E50-1E51]

Function

The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium.

Click to Show/Hide

BioChemical Class

Bile acid:sodium symporter (BASS) (TC 2.A.28) family

UniProt ID

NTCP_HUMAN

Sequence

MEAHNASAPFNFTLPPNFGKRPTDLALSVILVFMLFFIMLSLGCTMEFSKIKAHLWKPKG
LAIALVAQYGIMPLTAFVLGKVFRLKNIEALAILVCGCSPGGNLSNVFSLAMKGDMNLSI
VMTTCSTFCALGMMPLLLYIYSRGIYDGDLKDKVPYKGIVISLVLVLIPCTIGIVLKSKR
PQYMRYVIKGGMIIILLCSVAVTVLSAINVGKSIMFAMTPLLIATSSLMPFIGFLLGYVL
SALFCLNGRCRRTVSMETGCQNVQLCSTILNVAFPPEVIGPLFFFPLLYMIFQLGEGLLL
IAIFWCYEKFKTPKDKTKMIYTAATTEETIPGALGNGTYKGEDCSPCTA

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

AlphaFold

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 1 Approved Drugs

Bulevirtide

Drug Info

Approved

Hepatitis D virus infection

[2]

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

LUM001

Drug Info

Phase 2

Primary biliary cirrhosis

[3]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 2 Inhibitor drugs

Bulevirtide

Drug Info

[4]

LUM001

Drug Info

[1]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

Top

Ligand Name: Cholesterol

Ligand Info

Structure Description

Structure of the human sodium/bile acid cotransporter (NTCP) in complex with Fab and nanobody

PDB:7ZYI

Method

Electron microscopy

Resolution

2.88 Å

Mutation

[5]

PDB Sequence

GKRPTDLALS

²⁸

VILVFMLFFI

³⁸

MLSLGCTMEF

⁴⁸

SKIKAHLWKP

⁵⁸

KGLAIALVAQ

⁶⁸

YGIMPLTAFV

⁷⁸

LGKVFRLKNI

⁸⁸

EALAILVCGC

⁹⁸

SPGGNLSNVF

¹⁰⁸

SLAMKGDMNL

¹¹⁸

SIVMTTCSTF

¹²⁸

CALGMMPLLL

¹³⁸

YIYSRGIYDG

¹⁴⁸

DLKDKVPYKG

¹⁵⁸

IVISLVLVLI

¹⁶⁸

PCTIGIVLKS

¹⁷⁸

KRPQYMRYVI

¹⁸⁸

KGGMIIILLC

¹⁹⁸

SVAVTVLSAI

²⁰⁸

NVGKSIMFAM

²¹⁸

TPLLIATSSL

²²⁸

MPFIGFLLGY

²³⁸

VLSALFCLNG

²⁴⁸

RCRRTVSMET

²⁵⁸

GCQNVQLCST

²⁶⁸

ILNVAFPPEV

²⁷⁸

IGPLFFFPLL

²⁸⁸

YMIFQLGEGL

²⁹⁸

LLIAIFWCYE

³⁰⁸

KFK

Residue

Distance (Å)

THR203

4.791

SER206

3.446

ALA207

3.708

VAL210

3.547

MET215

3.550

PHE216

3.225

ALA217

3.926

MET218

3.524

PHE231

3.810

LEU235

3.605

TYR238

2.376

Residue

Distance (Å)

GLY248

3.325

ARG251

3.403

ARG252

3.024

PHE284

3.804

LEU287

3.849

LEU288

3.650

ILE291

4.351

LEU300

3.807

ILE303

4.570

PHE304

4.330

TYR307

4.158

Ligand Name: glycochenodeoxycholic acid

Ligand Info

Structure Description

Structure of the human sodium/bile acid cotransporter (NTCP) in complex with Fab and nanobody

PDB:7ZYI

Method

Electron microscopy

Resolution

2.88 Å

Mutation

[5]

PDB Sequence

GKRPTDLALS

²⁸

VILVFMLFFI

³⁸

MLSLGCTMEF

⁴⁸

SKIKAHLWKP

⁵⁸

KGLAIALVAQ

⁶⁸

YGIMPLTAFV

⁷⁸

LGKVFRLKNI

⁸⁸

EALAILVCGC

⁹⁸

SPGGNLSNVF

¹⁰⁸

SLAMKGDMNL

¹¹⁸

SIVMTTCSTF

¹²⁸

CALGMMPLLL

¹³⁸

YIYSRGIYDG

¹⁴⁸

DLKDKVPYKG

¹⁵⁸

IVISLVLVLI

¹⁶⁸

PCTIGIVLKS

¹⁷⁸

KRPQYMRYVI

¹⁸⁸

KGGMIIILLC

¹⁹⁸

SVAVTVLSAI

²⁰⁸

NVGKSIMFAM

²¹⁸

TPLLIATSSL

²²⁸

MPFIGFLLGY

²³⁸

VLSALFCLNG

²⁴⁸

RCRRTVSMET

²⁵⁸

GCQNVQLCST

²⁶⁸

ILNVAFPPEV

²⁷⁸

IGPLFFFPLL

²⁸⁸

YMIFQLGEGL

²⁹⁸

LLIAIFWCYE

³⁰⁸

KFK

Residue

Distance (Å)

LEU27

4.614

SER28

4.948

LEU31

3.768

VAL32

4.124

MET34

3.964

LEU35

3.543

ILE38

3.532

GLY102

4.529

ASN103

3.692

LEU104

3.688

VAL107

4.545

SER162

4.842

ILE195

4.340

SER199

4.233

Residue

Distance (Å)

VAL202

3.051

THR203

3.397

SER206

4.404

ASN262

3.153

VAL263

4.154

GLN264

3.037

SER267

3.308

THR268

4.212

PRO286

4.557

LEU287

3.680

MET290

3.500

ILE291

3.985

LEU294

4.080

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 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 Pathway Affiliation

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 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 Pathway Affiliation

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

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Bile secretion	hsa04976	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

Top

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 2 KEGG Pathways

Bile secretion

Hepatitis B

References

Top

REF 1

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 2

ClinicalTrials.gov (NCT03852719) Phase 3 Study of Bulevirtide in Patients With CHD. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT02321306) An Open-label Study to Evaluate the Long-term Safety and Tolerability of LUM001 in Patients With Primary Biliary Cirrhosis. U.S. National Institutes of Health.

REF 4

Bulevirtide: First Approval. Drugs. 2020 Oct;80(15):1601-1605.

REF 5

Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver. Cell Res. 2022 Aug;32(8):773-776.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Feng ZHU

Prof. Yuzong CHEN